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Electrical devices |
An electrical device such as a portable communications device, domestic or personal care appliance has a main body adapted to couple to an accessory which may be in the form of a tool attachable to the main body or a housing portion. The accessory carries a passive data storage device having a memory (59) storing control data for controlling an operation or affecting a function of the device. The passive data storage device is arranged to derive a power supply from the main body when a first coupler carried by the main body is placed in proximity to a second coupler carried by the accessory (3). Where the electrical device is a portable communications device, then the accessory may be, for example, a fascia The coupling between the first and second couplers may be inductive or capacitive. |
1-99. (cancelled). 100. A device comprising a main body having a housing portion; a controller operable to control operation of the device; and a signal supplier operable to supply a carrier signal; the main body and the housing portion having respective first and second couplers arranged in close proximity to one another to enable coupling of the carrier signal from the first coupler to the second coupler; the housing portion carrying a data storage device having a memory storing data; a power supply deriver operable to derive a power supply from a carrier signal coupled to the second coupler; a data controller operable to read data from the memory in response to derivation of a power supply by the power supply deriver; and a modulator operable to modulate the carrier signal in accordance with data read from the memory; the main body having a data extractor operable to extract data from the modulation of the carrier signal and a data supplier operable to supply the data to the controller of the main body to affect the operation of the device. 101. A device according to claim 100, wherein the signal supplier comprises a radio frequency carrier signal supplier comprising a carrier signal generator of a transceiver. 102. A device according to claim 100, wherein the signal supplier includes a signal interrupter operable to periodically vary the signal and the data storage device has a clock signal deriver operable to derive a clock signal for the data storage device on the basis of the periodic variations. 103. A device according to claim 100, having at least one of the following features: the housing portion is removable; the housing portion is non-removable; the main body has a transceiver operable to enable transmission and reception of communications over a mobile telecommunications network; the coupling between the first and second couplers is inductive or capacitive; the device is an electrical device; the device is a portable communications device; the data storage device has a clock signal generator operable to generate a clock signal for the data storage device in response to derivation of a power supply by the power supply deriver. 104. A device according to claim 100, wherein the memory is a writable memory, the signal supplier includes a data supplier operable to modulate the carrier signal in accordance with data to be written to the memory and the data storage device has a writer operable to derive the data from the modulated carrier signal and to write the derived data into the memory. 105. A device according to claim 104, wherein the controller has a use information deriver operable to obtain information regarding use of the device and is operable to cause the carrier signal to be modulated in accordance with the use data so as to enable the writer to write the use data into the memory. 106. A device according to claim 104, wherein a user operator is associated with the housing portion. 107. A device according to claim 100, wherein a user operator is carried by the housing portion and the data storage device comprises a user operation controller operable to supply data regarding user operation of the user operator to the main body. 108. A device according to claim 107, wherein the user operation controller is operable to supply instructions to the controller to configure a display of the device for use in one of a number different orientations. 109. A device according to claim 106, wherein the user operator comprises at least one of a keyboard, a key pad, a touch screen, a joystick, a digitizing table or other input. 110. A device according to claim 106, further comprising an additional user interface device having a different form of configuration of user operator, the user interface device also having a passive control device, a power deriver operable to derive a power supply when a coupler of the user interface device is coupled to a coupler of the device and a data supplier operable to supply, in response to operation by a user of the user input device, user input data to the controller when the user interface device is coupled to the device. 111. A device according to claim 100, wherein the data stored in the memory comprises data enabling the controller to identify the housing portion and the controller is operable to inhibit at least one function or operating characteristic of the device if the controller does not receive identification data or does not receive correct identification data. 112. A device according to claim 100, wherein the housing portion carries an orientation sensor and a data storage controller of the data storage device is operable, in response to an orientation signal from the orientation sensor, to communicate to the controller data regarding the orientation of the device to cause the controller to control the orientation of a display screen accordingly. 113. A device according to claim 100, wherein the housing portion carries a display. 114. A device according to claim 100, wherein the housing portion carries, instead of or in addition to the data storage device, at least one environmental sensor responsive, to at least one of temperature, pressure, orientation, position, height, humidity, light, sound, a chemical, a fluid, water, magnetic field, an odour, and the data storage device is operable to communicate to the controller data relating to an output of the sensor to affect an operation of the device. 115. A portable communications device comprising a main body having a removable housing portion; the main body having a transceiver operable to enable transmission and reception of communications over a mobile telecommunications network; a controller operable to control operation of the device; and a radio frequency signal supplier operable to supply a radio frequency carrier signal; the housing having a radio frequency signal affecter and the main body having a detector operable to detect the effect of the radio frequency signal affecter to affect the operation of the portable communications device. 116. A portable communications device having: a transceiver operable to enable transmission and reception of communications over a mobile telecommunications network and a controller operable to control operation of the device, the portable communications device having a radio frequency signal supplier that, when the portable communications device is in close proximity to an article carrying a data storage device responsive to the radio frequency signal, causes the data storage device to derive a power supply from the radio frequency signal and to modulate the radio frequency signal in accordance with data stored by the data storage device, the portable communications device having a data extractor operable to extract the data from the modulated radio frequency signal to affect the operation of the portable communications device. 117. An electrical device comprising a main body and an accessory in the form of a tool or part of a tool; the main body having a controller operable to control operation of the tool and a signal supplier operable to supply a carrier signal; the main body and the tool having respective first and second couplers arranged in close proximity to one another when the tool is attached to or in the proximity of the main body to enable coupling of the carrier signal from the first coupler to the second coupler; the accessory carrying a data storage device having a memory storing data, a power supply deriver operable to derive a power supply from a carrier signal coupled to the second coupler, a controller operable to read data from the memory in response to derivation of a power supply by the power supply deriver, and a modulator operable to modulate the carrier signal in accordance with data read from the memory, the main body having a data extractor operable to extract data from the modulation of the carrier signal and a data supplier operable to supply the data to the controller of the main body to affect the operation of or to affect the function of at least one of the electrical device and the accessory. 118. An electrical device comprising a main body and an accessory in the form of a tool or a part of a tool; the main body having a controller operable to control operation of the tool and a signal supplier operable to supply a signal; the tool carrying a component that, when the tool is in the close vicinity of or attached to the main body, affects the signal supplied by the signal supplier, and the main body having a detector operable to detect such an affect on the signal supplied by the signal supplier, the controller of the main body being arranged to affect an operation of or a function of at least one of the electrical device and the tool in accordance with such a detection by the detector. 119. A product information providing system having a user interface wherein different products are associated with corresponding passive data storage devices each of which, in response to receipt of a radio frequency signal from a mobile communications device located in the vicinity of the data storage device, causes the mobile communications device to communicate with a source of data relating to the product or information associated with that passive data storage device. 120. A device according to claim 117, wherein the accessory is a separable or movable component and the controller is operable to inhibit activation of the device when the accessory is moved away form the main body. 121. A portable communications device having a transceiver configured to enable transmission and reception of communications over a mobile telecommunications network and a controller operable to control operation of the device, the portable communications device having a reader having a radio frequency signal supplier operable to, when the portable communications device is in close proximity to an article carrying a data storage device responsive to the radio frequency signal, cause the data storage device to modulate the radio frequency signal in accordance with data stored by the data storage device, and the portable communications device having a data extractor operable to extract the data from the modulated radio frequency signal to affect an operation or service of the portable communications device. 122. A portable communications device according to claim 121, wherein the reader is arranged to couple inductively to the data storage device. 123. A portable communication device according to claim 121, wherein the controller is arranged to cause transmission of a communication over the mobile telecommunications network to a location on the network determined in accordance with the data received from the data storage device. 124. A portable communications device according to claim 121, wherein the radio frequency signal supplier comprises the transceiver. 125. A portable communications device according to claim 121, wherein the radio frequency signal supplier is independent of the transceiver. 126. A portable communications device according to claim 121, wherein the reader is provided in a reader unit on part of the device. 127. A portable communications device according to claim 121, having a removable and/or exchangeable portion. 128. A portable communications device according to claim 127, wherein the portion comprises a fascia of the device. 129. A portable communications device according to claim 121, further comprising a data storage device having a memory storing data, wherein the portable communications device is operable to communicate data from the memory to the article. 130. A portable communications device according to claim 129, wherein the data storage device forms part of the reader. 131. A portable communications device according to claim 129, wherein the memory is a read-writable memory. 132. A portable communications device according to claim 121, wherein the device is arranged to communication with an article having a read-writable memory and comprises a signal supplier operable to modulate the radio frequency signal in accordance with data to be written to the memory. 133. A portable communication device according to claim 121 in the form of a mobile telephone or cell phone or PDA. 134. A data transmission system comprising a portable communications device according to claim 121 and the article. 135. A system according to claim 134, wherein the article has a power supply deriver operable to derive a power supply from the radio frequency signal supplied by the portable communications device when the portable communications device is in close proximity to the article, a controller operable to read data from the memory in response to derivation of a power supply by the power supply deriver, and a modulator operable to modulate the radio frequency signal in accordance with the data stored by the data storage device. |
Method of producing biperiden I |
The invention relates to a method for producing biperiden which is characterised in that an exo/endo mixture of 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone is reacted with an isomer ratio of the exo form to the endo form of at least 2.5:1 with diphenyl magnesium, an isomer mixture containing biperiden is obtained therefrom and biperiden is produced therefrom. |
1. A method for producing biperiden, characterized in that an exo/endo mixture of 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone with a ratio of the exo-form to the endo-form isomers of at least 2.5:1 is reacted with diphenylmagnesium, resulting in a biperiden-containing mixture of isomers from which biperiden is isolated. 2. The method of claim 1, characterized in that diphenyl magnesium and 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone are employed in a molar ratio of from 0.8:1 to 3:1. 3. The method of claim 1, characterized in that the reaction of diphenylmagnesium with 1-(bicyclo[2.2.1]-hept-5-en-2-yl)-3-piperidino-1-propanone is carried out at a temperature of from −20° C. to the boiling point of the reaction mixture. 4. The method of claim 3, characterized in that the reaction of diphenylmagnesium with 1-(bicyclo[2.2.1]-hept-5-en-2-yl)-3-piperidino-1-propanone is carried out at a temperature of from −10° C. to 90° C. 5. The method of claim 1, characterized in that the reaction of diphenylmagnesium with 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone is carried out in the presence of a cyclic ether. 6. The method of claim 1 characterized in that 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone is added to a solution of diphenylmagnesium. 7. The method of claim 1 characterized in that to isolate biperiden the mixture of isomers of 1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-phenyl-3-piperidino-1-propanol obtained in the reaction of the exo/endo mixture of 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone with diphenyl magnesium is converted into the hydrochloride at elevated temperature in aqueous isopropanol, the precipitated hydrochloride is isolated, suspended in aqueous isopropanol at elevated temperature and again isolated after cooling, the hydrochloride obtained in this way is converted into the corresponding free base at elevated temperature in a C1-C2-alkanol or in a mixture thereof with a base after cooling, the base which has formed is isolated and washed with water, and the base obtained in this way is suspended at elevated temperature in a C1-C2-alkanol or in a mixture thereof and, after cooling, biperiden is isolated by removing the solid from the mother liquor. 8. The method of claim 1, characterized in that 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone is prepared by a) reacting cyclopentadiene and methyl vinyl ketone together and obtaining an exo/endo mixture of 1-(bicyclo[2.2.1]hept-5-en-2-yl)ethanone, b) heating this mixture of isomers with an alkali metal C1-C4-alcoholate, and obtaining exo-1-(bicyclo[2.2.1]hept-5-en-2-yl)ethanone by fractional distillation, and c) reacting this exo-1-(bicyclo[2.2.1]hept-5-en 2-yl)ethanone in the presence of an acid with piperidine and of a formaldehyde source, and obtaining an exo/endo mixture of 1-(bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone. 9. The method of claim 8, characterized in that from 0.1 to 5% by weight of alkali metal alcoholate, based on the total weight of the mixture, is employed in step b). 10. The method of claim 8, characterized in that in step b) there is heating to reflux under a pressure of from I to 100 mbar for from 10 minutes to 5 hours. 11. The method of claim 8, characterized in that exo-1-(bicyclo[2.2.1]hept-5-en-2-yl)ethanone is obtained in step b) by distillation through a column under a pressure of from 1 to 100 mbar and at a temperature of from 30 to 110° C. 12. The method of claim 8, characterized in that sodium methanolate is used in step b). 13. The method of claim 8, characterized in that paraformaldehyde is used as the formaldehyde source in step c). 14. The method of claim 13, characterized in that piperidine hydrochloride is used in step c). 15. The method of claim 8, characterized in that formaldehyde is employed in excess in step c). 16. 1-(Bicyclo[2.2.1]hept-5-en-2-yl)-3-piperidino-1-propanone with an exo/endo ratio of from 2.5:1 to 4.0:1. |
Closing banding |
A closing banding (1) for a bobbin (2), in particular for a bobbin (2) of cigarette paper, comprising a) a paper carrier (3) which is coated with a self-adhesive compound (6) on its underside (4) in the region of the upper transverse edge (5), and b) has a non-adhesive tab (8) in the region of the lower transverse edge (7), opposite the upper transverse edge (5), characterized by c) a double-sided adhesive tape (9) which is arranged on the underside (4) of the paper carrier (3), between the self-adhesive compound (6) and the tab (8), d) the double-sided adhesive tape (9) having a cleavable paper carrier (10) which is coated on both sides with self-adhesive compound (11). |
1. A closing banding for a bobbin comprising a) a paper carrier having an upper transverse edge and a lower transverse edge opposite said upper transverse edge, and which is coated with a self-adhesive compound on its underside in the region of the upper transverse edges, and has a non-adhesive tab in the region of the lower transverse edge, wherein b) a double-sided adhesive tape is arranged on the underside of the paper carrier, between the self-adhesive compound and the tab, the double-sided adhesive tape having a cleavable paper carrier which is coated on both sides with self-adhesive compound. 2. The closing banding as claimed in claim 1, wherein the self-adhesive compound is one for permanent (irreversible) bonding. 3. The closing banding as claimed in claim 1, wherein the self-adhesive compound coated on the underside of the paper carrier in the region of the upper transverse edge comprises a double-sided adhesive tape laminated on or the self-adhesive compound consists of a carrier-less self-adhesive compound. 4. The closing banding as claimed in claim 1, wherein the self-adhesive compounds are contact adhesive compounds based on acrylates or rubber. 5. The closing banding as claimed in claim 1, wherein the length of the tab is 10-25 mm, measured from the lower transverse edge. 6. The closing banding as claimed in claim 1, which is present in the form of an adhesive tape, optionally wound up into a roll. 7. The closing banding as claimed in claim 1, wherein the width of the self-adhesive compound measured from a transverse edge_is 20-100 mm and the width of the double-sided adhesive tapes measured from a transverse edge is 10-100 mm. 8. The closing banding as claimed in claim 1, wherein the cleavage strength of the cleavable paper carrier is 20-70 cN/cm. 9. The closing banding as claimed in claim 1, which is present in the form of individual labels which, optionally, are arranged on an auxiliary carrier, the label width corresponding to the width of the bobbin to be bonded. 10. A method of closing and unclosing a bobbin said method comprising providing a closing banding as claimed in claim 1 on a bobbin, and closing the bobbin by fixing an end of an uppermost layer of the bobbin to a second layer located underneath by bonding the closing banding to an end of the uppermost layer of the bobbin by means of the self-adhesive compound in the region of the upper transverse edge of the closing banding, in such a way that the closing banding projects beyond this end; and fixing the closing banding, to the second layer of the bobbin by means of the self-adhesive compound on the cleavable paper carrier of the closing banding, and in order to unclose the bobbin then pulling on the projecting tab, causing the cleavable paper carrier to cleave so that liberated end of the bobbin is now capable of being inserted into a machine. 11. The closing banding as claimed in claim 1, which is for a bobbin of cigarette paper. 12. The closing banding as claimed in claim 3, wherein the double-sided adhesive tape comprises a tear-resistant paper carrier coated on both sides with a self-adhesive compound. 13. The closing banding as claimed in claim 4, wherein the self-adhesive compounds are water-soluble. 14. The closing banding as claimed in claim 5, wherein the length of the tab is 12-18 mm as measured from the lower transverse edge. 15. The closing banding as claimed in claim 6, which is in the form of an adhesive tape having a width of 20-2000 mm. 16. The closing banding as claimed in claim 15, which is in the form of an adhesive tape having a width of 22-1500 mm, which adhesive tape is aligned with a width of a parent reel to be secured before the parent reel is cut up into bobbins. 17. The closing banding as claimed in claim 7, wherein the width of the self-adhesive compound measured from a transverse edge is 25-60 mm and the width of the double-sided adhesive tape measured from a transverse edge is 15-50 mm. 18. The closing banding as claimed in claim 8, wherein the cleavage strength of the cleavable paper carrier is 22-60 cN/cm. 19. The closing banding as claimed in claim 18, wherein the cleavage strength of the cleavable paper carrier is 25-50 cN/cm. 20. The method according to claim 10, wherein the bobbin is a bobbin of cigarette paper, and the machine is a cigarette machine. |
Pyrimidine derivatives as selective inhibitors of cox-2 |
The invention thus provides the compounds of formula (I) and pharmaceutically acceptable salts thereof, in which: R1 and R2 are independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C3-4alkynyl, C3-10cycloalkylC0-6alkyl and C4-12bridged cycloalkyl; R3 is selected from the group consisting of C1-6alkyl, NH2 and R5CONH; R4 is selected from the group consisting of CH2F, CHF2, CF3CH2, CF3CHF and CF3CF2; and R5 is selected from the group consisting of H, C1-6alkyl, C1-6alkoxy, C1-6alkylOC1-6alkyl, phenyl, HO 2cc1-6?alkyl, C1-6alkylOCOC1-6alkyl, C1-4alkylOCO, H2NC1-6alkyl, C1-6alkylOCONHC1-6alkyl and C1-6alkylCONHC1-6alkyl. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of the pain, fever, inflammation of a variety of conditions and diseases. |
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof, in which: R1 and R2 are independently selected from the group consisting of H, C1-6alkyl, C2-6alkenyl, C3-6alkynyl, C3-10cycloalkylC0-6alkyl and C4-12bridged cycloalkyl; R3 is selected from the group consisting of C1-6alkyl, NH2 and R5CONH; R4 is selected from the group consisting of CH2F, CHF2, CF3CH2, CF3CHF and CF3CF2; and R5 is selected from the group consisting of H, C1-6alkyl, C1-6alkoxy, C1-6alkylOC1-6alkyl, phenyl, HO2CC1-6alkyl, C1-6alkylOCOC1-6alkyl, C1-6alkylOCO, H2NC1-6alkyl, C1-6alkylOCONHC1-6alkyl and C1-6alkylCONHC1-6alkyl. 2. The compound as claimed in claim 1 wherein R1 is H. 3. A compound as claimed in claim 1 wherein R2 is C1-6alkyl. 4. A compound as claimed in claim 1 wherein R3 is C1-6alkyl. 5. A compound as claimed in claim 1 wherein R4 is CH2F or CHF2. 6. A compound as claimed in claim 1 wherein R5 is selected from the group consisting of C1-6alkyl, phenyl and aminomethyl. 7. (Canceled.) 8. A process for the preparation of a compound as defined in claim 1, which comprises: (A), reacting an amine HNR1R2 of formula (II) or a protected derivative thereof with a compound of formula (III) and thereafter and if necessary, (B), interconverting a compound of formula (I) into another compound of formula (I); and/or (C), deprotecting a protected derivative of compound of formula (I). 9. A pharmaceutical composition comprising a compound as defined in claim 1 in admixture with one or more physiologically acceptable carriers or exciplents. 10. (Canceled.) 11. A method of treating a subject suffering from a condition which is mediated by COX-2 which comprises administering to said subject an effective amount of a compound as defined in claim 1. 12. A method of treating a subject suffering from an inflammatory disorder, which method comprises administering to said subject an effective amount of a compound as defined in claim 1. 13-14. (Canceled.) 15. The method according to claim 11, wherein said subject is a human. 16. The method according to claim 12, wherein said subject is a human. 17. A compound selected from: N-butyl-4-(fluoromethyl)-6-[4-(methylsulfonyl)phenyl]pyrimidin-2-amine; N-butyl-4-(difluoromethyl)-6-[4-(methylsulfonyl)phenyl]pyrimidin-2-amine; and pharmaceutically acceptable salts thereof. 18. A compound as claimed in claim 1 wherein R2 is straight chain C1-6alkyl or branched chain C3-6alkyl. |
Adhesive dressings |
An adhesive film or membrane (1) is disclosed which is dismensioned for application to, and conformable to, the skin of a patient. The film or membrane (1) has an adhesive surface and carries, on that adhesive surface, a release liner (2) to mask the adhesive prior to use. The release liner (2) is formed with a generally central portion (6) which is releasable from the adhesive surface of the film or membrane (1) to permit application of dressing material (7) to the region of the adhesive surface so exposed, prior to complete removal of the release liner (2). |
1. A method for the preparation of a dressing for application to the skin of a patient, which method comprises: providing an adhesive film or membrane, said film or membrane being dimensioned for application to, and conformable to, the skin of the patient, the film or membrane having an adhesive surface and carrying, on that adhesive surface, a release liner to mask the adhesive prior to use, wherein the release liner is formed with a generally central portion which is releasable from the adhesive surface of said film or membrane; releasing said generally central portion of the release liner from the adhesive surface of said film or membrane to expose a region of said adhesive surface; applying dressing material to the region of said adhesive surface so exposed; and completely removing said release liner. 2. A method according to claim 1, wherein the central portion of the release liner is generally square or rectangular in form. 3. A method according to claim 2, wherein the central portion is defined by cuts formed in at least three sides of the square or rectangle. 4. A method according to claim 3, wherein the cuts are perforated or interrupted by bridges to preserve the integrity of the release liner and prevent premature release of the central portion. 5. A method according to claim 1, wherein the film or membrane is substantially straight-edged. 6. A method according to claim 5, wherein the corners of the film or membrane are rounded. 7. A method according to claim 1, wherein the release liner is formed of paper. 8. A method according to claim 7, wherein the release liner comprises white paper coated on both sides with a polymer for dimensional stability. 9. A method according to claim 7, wherein the release liner comprises a glassine or clay coated paper. 10. A method according to claim 1, wherein the side of the release liner that is applied to the adhesive surface of the film or membrane film is overcoated with a release coating to facilitate separation of the liner from the adhesive surface of the membrane of film. 11. A method according to claim 10, wherein the release coating is silicon. 12. A method according to claim 1, wherein the release liner is formed in two parts, both parts having portions that are free of the adhesive surface of the membrane or film such that those portions can be grasped and the respective part thereby removed. 13. A method according to claim 12, wherein the two parts of the release liner are of differing sizes, the first part of the release liner masking a minor part of the adhesive surface of the membrane or film and the second part of the release liner masking a major part of the adhesive surface of the membrane or film. 14. A method according to claim 13, wherein the first part is applied to a strip of the adhesive surface that extends across one edge of the assembly. 15. A method according to claim 14, wherein the part of the adhesive surface exposed by removal of the first part has a width of between 3 mm and 15 mm. 16. A method according to claim 13, wherein the second part is overlapped by the first part. 17. A method according claim 16, wherein the portion of the second part that is overlapped by the first part is folded over such that when the first part is removed, the folded-over part of the second part is freed and serves as a tab by which the second part can be grasped. 18. A method according claim 17, wherein the first part overlies and extends a short distance beyond the folded over portion of the second part. 19. A method according to claim 1, wherein the membrane or film is supported by a carrier layer of greater rigidity. 20. A method according to claim 19, wherein the carrier layer is adhered to the membrane or film by physical bonding. 21. A method according to claim 19, wherein the carrier layer extends beyond the membrane or film at least one of its edges to form a tab by which the carrier layer can be grasped for removal from the membrane or film. 22. A method according to claim 21, wherein the carrier layer projects across the full extent of one of its edges. 23. A method according to claim 21, wherein the tab has a width of between 3 mm and 15 mm. 24. A method according to claim 19, wherein the carrier layer and the release liner are co-extensive. 25. A method according to claim 24, wherein the release liner projects beyond the membrane or film. 26. A method according to claim 21, wherein the adhesive film or membrane is provided with a non-adhesive tab by which it can be held in contact with the skin during removal of the carrier layer, the non-adhesive tab extending across substantially the whole width of the adhesive film or membrane at the edge at which the carrier layer projects beyond the membrane or film. 27. A method according to claim 26, wherein the non-adhesive tab is a strip of material that overlaps with, and is attached to, the adhesive side of the film or membrane. 28. A method according to claim 27, wherein the film or membrane is formed with a line of weakness adjacent to the non-adhesive tab so that the film or membrane may be easily broken at that line and the non-adhesive tab thereby removed. 29. A method according to claim 19, wherein the membrane film and the carrier layer are transparent or substantially transparent. 30. A method according to claim 1, wherein the membrane or film with its adhesive lower surface is moisture-permeable. 31. A method according to claim 30, wherein the membrane or film has a moisture vapor transmission rate of at least 300/m2/24 h at 37° C. at 100% to 10% relative humidity difference. 32. A method according to claim 31, wherein the membrane or film has a moisture vapor transmission rate of at least 700g/m2/24 h at 37° C. at 100% to 10% relative humidity difference. 33. A method according to claim 30, wherein the membrane of film comprises apertures to render it permeable to liquids such as water. 34. A method according to claim 30, wherein the membrane or film is formed from polyether-polyurethane or polyester-polyether copolymers. 35. A method according to claim 1, wherein the thickness of the membrane of film is in the range 9 to 80 um. 36. A method according to claim 35, wherein the thickness of the membrane or film is in the range 20 to 40 um. 37. A method according to claim 1, wherein the lower surface of the membrane or film is rendered adhesive by having applied to it an adhesive coating. 38. A method according to claim 37, wherein the adhesive coating has a thickness in the range 15 to 65 um. 39. A method according to claim 38, wherein the adhesive coating has a thickness in the range 20 to 40 um. 40. A method according to claim 37, wherein the adhesive coating has a weight per unit area in the range 10 to 75 g/m2. 41. A method according to claim 40, wherein the adhesive coating has a weight per unit area in the range 20 to 40 g/m2. 42. A method according to claim 37, wherein the adhesive coating is of a polyvinyl ether adhesive or acrylic adhesive. 43. A method according to claim 19, wherein the carrier layer is a film of polyethylene, polypropylene or unplasticised polyvinyl chloride. 44. A method according to claim 19, wherein the carrier layer is a paper sheet. 45. A method according to claim 43, wherein the carrier layer is of polypropylene. 46. A method according to claim 45, wherein the carrier layer is of bi-oriented polypropylene. 47. A method according to claim 19, wherein the carrier layer has a thickness in the range 30 to 100 um. 48. A method according to claim 47, wherein the carrier layer has a thickness in the range 40 to 70 um. |
Hevein-binding monoclonal antibodies |
This invention relates to antibody engineering technology. More particularly, the present invention relates to human IgE antibodies and derivatives thereof, which bind allergenic hevein with high affinity and specificity. The present invention also relates to processes for makings and engineering such hevein-binding monoclonal antibodies and to methods for using these antibodies and derivatives thereof in the field of immunodiagnostics, enabling qualitative and quantitative determination of allergenic hevein in biological and raw material samples, as well as in immunotherapy, enabling blocking of allergenic hevein in allergic patients. |
1. A monoclonal antibody belonging to an IgE subclass and having binding specificity to allergenic hevein, or a functional fragment or derivative thereof. 2. The monoclonal antibody according to claim 1, wherein the fragment is a scFv fragment or a Fab fragment. 3. The monoclonal antibody according to claim 2, wherein the scFv fragment is 1A4 or 1C2. 4. An isolated DNA molecule encoding the monoclonal antibody or a fragment or derivative thereof according to any one of the preceding claims, and fragments of such DNA, which encode at least one antibody chain of said antibody or antibody derivative. 5. The isolated DNA molecule according to claim 4, wherein the antibody chain is the Complementarity Determining Region (CDR) of the VL and/or VH region. 6. The isolated DNA molecule according to claim 4 cloned into a vector. 7. The isolated DNA molecule according to claim 6, wherein said vector is an expression vector capable of expressing antibodies, as well as fragments and derivatives thereof as claimed in any one of claims 1 to 3. 8. A host cell containing a DNA according to claim 4. 9. The host cell according to claim 8, capable of expressing a monoclonal antibody or a fragment or derivative thereof as claimed in any one of claims 1 to 3 or at least one antibody chain of said antibody or antibody derivative. 10. The host cell according to claim 9, wherein the antibody chain is the scFv fragment as claimed in claim 2 or 3. 11. A method of preparing a monoclonal antibody or a fragment or derivative thereof according to any one of claims 1 to 3, comprising the steps of culturing a host cell according to claim 8 capable of expressing at least one of the required antibody chains, and recovering said antibody or antibody fragment or derivative. 12. The method according to claim 11, further comprising the steps of combining component chains after the recovery step, introducing combined component chains into a second host cell, and recovering said combined component chains. 13. The method according to claim 11, further comprising the step of labelling said antibody or antibody derivative. 14. A method of preparing a monoclonal antibody or a fragment or derivative thereof according to any one of claims 1 to 3, comprising the step of synthetically producing at least a portion of said antibody or antibody derivative. 15. A phage or microbial cell, which presents an antibody fragment according to claim 2 as a fusion protein with a surface protein. 16. A method of selecting an antibody fragment according to claim 2 or 3, comprising the steps selecting said antibody fragment from a display library of antibody fragments containing a phage or cell according to claim 15. 17. A method of assaying hevein in a sample, comprising the steps of obtaining said sample, and assaying for hevein by employing a monoclonal antibody or a fragment or derivative thereof according to any one of claims 1 to 3. 18. A test kit comprising an antibody or a fragment or derivative thereof according to any one of claims 1 to 3 in a suitable container for transport and storage. 19. A monoclonal antibody or a fragment or derivative thereof according to any one of claims 1 to 3 for use in immunodiagnostics. 20. A monoclonal antibody or a fragment or derivative thereof according to any one of claims 1 to 3 for use in immunotherapy. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Almost 20% of the population world-wide are suffering from allergy. Consequently, it is a health problem of increasing seriousness. Allergy is a hypersensitivity reaction against substances in air, food or water, which are normally harmless (Corry and Kheradmand, 1999). A new and foreign external agent triggers an allergic reaction, which aims at disposal of that agent from the body. In IgE-mediated allergic reactions, also called immediate or type I hypersensitivity reactions, under the first exposure of a foreign substance, allergen, to the body, IgE-bearing B-cells begin to produce soluble IgE molecules which will then bind to high-affinity IgE receptors present on the surface of a wide variety of cells, most importantly to mast cells. If the same foreign substance is encountered again, the cross-linking of the receptor-bound IgE molecules by the allergen occurs, resulting in cellular activation followed by the release of toxic products such as histamines, which will elicit the signs and symptoms of an allergic reaction. Latex allergy is a serious medical problem with an increasing number of patients (Slater, 1994, Turjanmaa et al., 1996). Latex is a complex intracellular product, a milky sap, produced by the laticiferous cells of the rubber tree, Hevea brasiliensis , which is used in a variety of everyday articles, e.g. for the production of gloves, balloons, and condoms, and in manufacturing of medical devices. Latex allergy is a serious problem especially with health-care workers, rubber industry workers and patients having undergone several surgical procedures. Latex allergy has also been reported to be associated with pollen allergies and food allergies (Nel and Gujuluva, 1998). The cross-reactivity between latex and food allergens is established as the latex-fruit syndrome that might be the consequence of hevein-like protein domains or similar epitopes (Brehler et al., 1997, Chen et al., 1998, Mikkola et al., 1998). Many latex proteins have been identified as allergens (Breiteneder and Scheiner, 1998). One of the major latex allergens is hevein, which is a defence protein involved in, for instance, the inhibition of several chitin-containing fungi (Lee et al., 1991, Alenius et al., 1996, Chen et al., 1997). Hevein is a small chitin-binding protein of 43 amino acids with four disulphide bonds. Its three-dimensional structure has been determined by X-ray diffraction and NMR (Rodriguez-Romero et al., 1991; Andersen et al., 1993). IgE antibodies distinctively recognise allergenic epitopes, which would be useful in clinics or immunodiagnostics for detecting and determining allergen concentrations of complex materials. Further, allergenic epitopes are usually different from the immunogenic epitopes of proteins. This fact has hampered the production of monoclonal antibodies capable of specific binding of allergenic epitopes by conventional methodology such as hybridoma technology. It has been recently shown that the development of allergen-specific IgE antibodies is possible by the phage display technology (Steinberger et al., 1996). This methodology is giving new tools to produce allergen-specific recombinant antibodies that can be produced in consistent quality for clinical and diagnostic applications. |
<SOH> SUMMARY OF THE INVENTION <EOH>We describe in this application the development and characterisation of human IgE antibody fragments that bind allergenic hevein with affinity and specificity high enough to be utilised as reagents in immunoassays designed for the qualitative and quantitative measurement of hevein in biological samples and, in immunotherapy of allergic patients. Specifically, the present invention describes selection of human IgE antibodies specific to hevein by the phage display technique, and the characterisation of the binding properties of the engineered antibody fragments produced in E.coli. This invention thus provides new reagents to be utilised in different kinds of immunoassay protocols, as well as human immunotherapy. The invention also permits guaranteed continuous supply of these specific reagents of uniform quality, eliminating inherent batch-to-batch variation of polyclonal antisera. These advantageous effects permit the manufacture of new, specific and economical immunodiagnostic assays of uniform quality. Consequently, one specific object of the present invention is to provide human IgE mono-clonal antibodies, fragments thereof, or other-derivatives of such antibodies, which bind hevein with affinity and specificity high enough to allow qualitative and quantitative measurement of hevein in biological samples, as well as their use in immunotherapy. The monovalent antibodies of the present invention demonstrate a specific binding to allergenic hevein. Another object of the present invention is to provide cDNA clones encoding hevein-specific antibody chains, as well as constructs and methods for expression of such clones to produce hevein-binding antibodies, fragments thereof or other derivatives of such antibodies. A further object of this invention is to provide methods of using such hevein-binding antibodies, fragments thereof or other derivatives of such antibodies, or combinations of them for qualitative and quantitative measurement of hevein in biological samples. Additionally, this invention provides hevein-binding antibodies, fragments thereof or other derivatives of such antibodies, or combinations of them for immunotherapy in allergic patients. Other objects, features and advantages of the present invention will be become apparent from the following drawings and detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given for illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. |
Mullite bodies and methods of forming mullite bodies |
A method of forming a porous mullite composition of acicular mullite grains having improved properties is described, where the mullite is formed at some time in the presence of a fluorine containing gas. For example, it has been discovered that improved properties may result from heating the mullite to a high temperature in an atmosphere selected from the group consisting of water vapor, oxygen, an inert gas or mixtures thereof or forming the mullite composition from precursors having an AL/Si ratio of at most 2.95. |
1. A method for preparing an acicular mullite composition, the method comprising, a) forming a mixture of one or more precursor compounds having the elements present in mullite wherein one of the precursor compounds is clay, b) shaping the mixture into a porous green shape c) heating the porous green shape of step (b) under an atmosphere having a fluorine containing gas and to a temperature sufficient to form an untreated mullite composition comprised substantially of acicular mullite grains that are essentially chemically bound and d) subsequently heating the untreated mullite composition to a heat treatment temperature of at least 950° C. under a heat treatment atmosphere selected from the group consisting of water vapor, oxygen, air, an inert gas or mixtures thereof for a time sufficient to form the mullite composition; 2. The method of claim 1 wherein the precursor compounds are clay and another compound selected from the group consisting of alumina, silica, fluorotopaz, zeolite, AlF3 and mixtures thereof. 3. The method of claim 2 wherein the other precursor compounds are selected from the group consisting of alumina, silica, fluorotopaz, zeolite, and mixtures thereof. 4. The method of claim 1 wherein the precursor compounds are alumina, silica and clay. 5. The method of claim 1 wherein the fluorine containing gas is SiF4 separately provided. 6. The method of claim 1 wherein the heat treatment temperature is at least 1000° C. 7. The method of claim 1 wherein the heat treatment temperature is at least 1050° C. 8. The method of claim 1 wherein the heat treatment temperature is at least 1100° C. 9. The method of claim 1 wherein the heat treatment temperature is at least 1200° C. 10. The method of claim 1 wherein the heat treatment atmosphere is selected from the group consisting of air, an inert gas, water vapor and a mixture thereof. 11. The method of claim 10 wherein the heat treatment atmosphere is air or nitrogen. 12. The method of claim 1 wherein the heat treatment time is at least 2 hours. 13. The method of claim 1 wherein the precursors have an Al/Si bulk stoichiometry of at most 3.3. 14. The method of claim 13 wherein the precursors have an Al/Si bulk stoichiometric ratio of at most 2.95. 15. The method of claim 14 wherein the Al/Si bulk stoichiometric ratio is at most 2.9. 16. The method of claim 15 wherein the Al/Si bulk stoichiometric ratio is at least 2. 17. A porous mullite composition of any one of the preceding claims. 18. A porous mullite composition comprised substantially of acicular mullite grains that are essentially chemically bound, wherein the mullite composition has a bulk Al/Si stoichiometry of at most 3.3 to at least 2 and the acicular mullite grains have an Al/Si ratio of at least 2.95 and the mullite composition has at most 2 percent by volume of a crystalline silica phase and a glassy phase distributed on at least a portion of the mullite grains wherein the glassy phase is comprised of silica, magnesium and iron, wherein the magnesium and iron are incorporated in the glassy phase such that at most a trace amount of precipitates of magnesium and iron are present and the mullite composition has an amount of fluorine of at most 1 percent by weight of the mullite composition. 19. The mullite composition of claim 18 wherein the mullite composition has a retained strength, after heating to 800° C. for 2 hours in air, of at least 15 MPa and a porosity of at least 55 percent to at most 85 percent. 20. The mullite composition of claim 19 wherein the porosity is at most 75 percent. 21. The mullite composition of claim 20 wherein the retained strength is at least 17 MPa. 22. The mullite composition of claim 21 wherein the retained strength is at least 19 MPa. 23. The mullite composition of claim 22 wherein the retained strength is at least 25 MPa. 24. The mullite composition of claim 19 wherein the mullite composition has essentially zero crystalline silica phases. 25. The mullite composition of claim 18 wherein the amount of fluorine is at most 0.5 percent. 26. The mullite composition of claim 25 wherein the amount of fluorine is at most 0.1 percent. 27. The mullite composition of claim 26 wherein there is at most trace amounts of fluorine. 28. A diesel particulate trap comprised of the mullite composition of claim 17. 29. A diesel particulate trap comprised of the mullite composition of any one of claims 18-28. 30. An automotive catalytic converter comprised of the mullite composition of claim 17. 31. An automotive catalytic converter comprised of the mullite composition of any one of claims 18-28. |
Process for precooking grains and an equipment for precooking grains |
A process of precooking grains is described, which comprises the steps of: a) Charging the grains into a reactor (4) in a controlled manner; b) Applying a first negative pressure to the reactor (4); c) Heating the grains contained in the reactor (4); d) Applying a second negative pressure to the reactor (4); and e) Cooling the grains. An equipment for precooking grains is also described, which comprises at least one reactor (4), which is associable with means (9) for applying negative pressure. |
1.-25. (Canceled) 26. A method of precooking grains comprising the steps of: charging the grains into a reactor in a controlled manner; applying a first negative pressure to the reactor; heating the grains contained in the reactor; applying a second negative pressure to the reactor; and cooling the grains. 27. The method according to claim 26, wherein during the step of applying the first negative pressure to the reactor the internal pressure of the latter ranges from about an absolute pressure of 6 mmHg to about a relative pressure of 4 Kg/cm2. 28. The method according to claim 27, wherein air is evacuated from inside the reactor during applying of the first negative pressure. 29. The method according to claim 26, wherein, in the step of heating the grains contained in the reactor, a direct injection of vapor onto the grains and an indirect heating takes place, the dry saturated vapor passing through a sleeve that transfers heat to the grains. 30. The method according to claim 29, wherein the temperature ranges from 100° C. to 125° C. at the end of the step of heating the grains. 31. The method according to claim 26, further comprising a cooking step before applying the second negative pressure. 32. The method according to claim 31, wherein the temperature ranges from about 100° C. to 125° C. and the pressure ranges from 0.5 to 1.5 Kg/cm2 during the cooking step. 33. The method according to claim 26, wherein the pressure inside the container is about negative 0.9 Kg/cm2 in the step of applying the second negative pressure. 34. The method according to claim 33, wherein in the step of applying the second negative pressure, the temperature ranges between 60° C. and 150° C., and the humidity of the grains ranges between 12 and 12.5%. 35. The method according to claim 34, wherein during the step of applying the second negative pressure, a lyophilization process occurs, which comprises evaporating water from the grains. 36. The method according to claim 35, wherein the lyophilization process consumes heat from the grains and reduces mycotoxins by about 99% and pesticides by about 75-99%. 37. The method according to claim 26 wherein the cooling occurs partially in the reactor and partially in a cooler subsequently. 38. The method according to claim 26, wherein the cooling takes place in the reactor. 39. The method according to claim 37, wherein the internal pressure of the reactor is negative and is about 0.9 Kg/cm2 during the cooling step. 40. The method according to claim 39, wherein the temperature is within a maximum limit of about 70° C. and a minimum of about 10° C. during the cooling step. 41. An apparatus for precooking grains, comprising at least one reactor wherein the reactor is associable with means for applying negative pressure. 42. The apparatus according to claim 41, further comprising a feeder associated with a dosing means the dosing means being associated with the reactor to enable selectively charging grains into the reactor. 43. The apparatus according to claim 41, wherein the means for applying negative pressure comprises a vacuum pump. 44. The apparatus according to claim 41, wherein the means for applying negative pressure corresponds to at least one ejector and one thermocompressor-type ejector. 45. The apparatus according to claim 43, wherein the vacuum pump is associated with a barometric tank and a barometric condenser. 46. The apparatus according to claim 44, wherein the ejector is associated with a barometric tank and with a barometric condenser. 47. The apparatus according to claim 45, wherein the apparatus comprises an indirect-heating system and a tangential vapor-injection system dipped together with the grains. 48. The apparatus according to claim 41, wherein the reactor comprises homogenizing and substantially inclined flaps, arranged in an internal portion of the reactor. 49. The apparatus according to claims 41, further comprising at least one moistener associated with the reactor. 50. The apparatus according to claim 49, wherein the apparatus is controlled and monitored by an automation system. 51. The method according to claim 38, wherein the internal pressure of the reactor is negative and is about 0.9 Kg/cm2 during the cooling step. 52. The apparatus according to claim 44, wherein the apparatus comprises an indirect-heating system and a tangential vapor-injection system dipped together with the grains. 53. The apparatus according to claims 48, further comprising at least one moistener associated with the reactor. |
<SOH> BRIEF DESCRIPTION OF THE INVENTION <EOH>The objectives of the present invention are achieved by means of a process of precooking grains that comprises the steps of: a) Charging the grains into a reactor in a controlled manner; b) Applying a first negative pressure to the reactor; c) Heating the grains contained in the reactor; d) Applying a second negative pressure to the reactor; and e) Cooling the grains. The present invention has also the objective of providing an equipment for precooking grains, which comprises at least one reactor that is associable with means for applying negative pressure. |
Manufacture of materials from graphite particles |
A method of manufacturing flexible sheets of expanded graphite material from recycled materials, comprising providing source materials in the form of flexible sheets of expanded graphite; comminuting the source materials into particles; re-expending the particles; and preparing a mat from the re-expanded particles. Also described herein is a process of manufacturing a graphite material comprising grinding a cured resin impregnated graphite material into particles; removing at least part of the resin from the particles; and expanding the resin removed particles. |
1. A method of manufacturing flexible sheets of expanded graphite material from recycled materials, comprising: (a) providing source materials in the form of flexible sheets of expanded graphite; (b) comminuting the source materials into particles; (c) re-expanding the particles; and (d) preparing a mat from the re-expanded particles. 2. The method of claim 1, further comprising: compressing the mat into a flexible sheet of expanded graphite material. 3. The method of claim 1, wherein: in step (a) the source materials are selected from the group consisting of unimpregnated expanded graphite sheets, uncured resin impregnated expanded graphite sheets and cured resin impregnated graphite sheets. 4. The method of claim 1, wherein: in step (a) the source materials include resin impregnated expanded graphite sheets. 5. The method of claim 4, further comprising: between steps (b) and (c), removing at least part of the resin from the particles. 6. The method of claim 5, wherein: the removing step includes heating the particles, while avoiding flashing of the resin decomposition products from the particles. 7. The method of claim 5, wherein: the removing step includes heating the particles at less than about 600° C. 8. The method of claim 5, wherein: the removing step includes heating the particles to a temperature in a range of from about 250° C. to about 600° C. 9. The method of claim 5, wherein: the removing step includes heating the particles at about 500° C. for about 150 minutes. 10. The method of claim 5, further comprising: compressing the mat into a flexible sheet of expanded graphite material; and wherein the removing step results in increased tensile strength of the sheet created in the compressing step, as compared to a similar method in which the resin is not removed. 11. The method of claim 5, wherein the removing step further comprises: removing greater than 75% of the resin. 12. The method of claim 1, wherein: step (c) includes steps of intercalating the particles and heating the intercalated particles. 13. The method of claim 12, wherein: in step (c), the particles are expanded to have a specific volume of at least about 100 cc/g. 14. The method of claim 1, wherein: in step (b), the particles have a particle size of no greater than about 20 mesh. 15. The method of claim 1, further comprising: impregnating the mat with resin; compressing the impregnated mat into a flexible sheet of expanded graphite material; and embossing and curing the sheet. 16. The method of claim 1, further comprising: blending the particles with expandable natural graphite flakes. 17. The method of claim 16, wherein: step (c) includes steps of intercalating the particles and exfoliating the intercalated particles by heating the intercalated particles in a furnace; and the blending step occurs in the furnace during the exfoliation process. 18. A material suitable for the construction of a component of a fuel cell, manufactured by the process of claim 1. 19. A process of manufacturing a graphite material comprising: (a) grinding a resin impregnated graphite material into particles; (b) removing at least part of the resin from the particles; and (c) expanding the resin removed particles. 20. The process of claim 19, further comprising: after step (c), forming the expanded resin removed particles, into a flexible sheet of graphite material. 21. The process of claim 19, wherein: step (c) includes an intercalation process followed by exfoliation of the intercalated particles in a furnace. 22. The process of claim 21, further comprising: blending expandable natural graphite flake material with the intercalated particles in the furnace during the exfoliation process. 23. The method of claim 19, wherein step (b), further comprises: heating the particles, while avoiding flashing of theresin decomposition products from the particles. 24. The method of claim 19, wherein: the removing step includes heating the particles at less than about 600° C. 25. The method of claim 19, wherein: the removing step includes heating the particles to a temperature in a range of from about 300° C. to about 600° C. 26. The method of claim 19, wherein: the removing step includes heating the particles in the range of from about 400° C. to about 800° C. for a time in the range of from about 10 to about 150 minutes. 27. The method of claim 19, wherein: in step (a), the particles have a particle size of no greater than about 20 mesh. 28. The method of claim 19, wherein: in step (b), greater than 75% of the resin is removed. |
<SOH> BACKGROUND ART <EOH>An ion exchange membrane fuel cell, more specifically a proton exchange membrane (PEM) fuel cell, produces electricity through the chemical reaction of hydrogen and oxygen in the air. Within the fuel cell, electrodes denoted as anode and cathode surround a polymer electrolyte to form what is generally referred to as a membrane electrode assembly, or MEA. Oftentimes, the electrodes also function as the gas diffusion layer (or GDL) of the fuel cell. A catalyst material stimulates hydrogen molecules to split into hydrogen atoms and then, at the membrane, the atoms each split into a proton and an electron. The electrons are utilized as electrical energy. The protons migrate through the electrolyte and combine with oxygen and electrons to form water. A PEM fuel cell includes a membrane electrode assembly sandwiched between two graphite flow field plates. Conventionally, the membrane electrode assembly consists of random-oriented carbon fiber paper electrodes (anode and cathode) with a thin layer of a catalyst material, particularly platinum or a platinum group metal coated on isotropic carbon particles, such as lamp black, bonded to either side of a proton exchange membrane disposed between the electrodes. In operation, hydrogen flows through channels in one of the flow field plates to the anode, where the catalyst promotes its separation into hydrogen atoms and thereafter into protons that pass through the membrane and electrons that flow through an external load. Air flows through the channels in the other flow field plate to the cathode, where the oxygen in the air is separated into oxygen atoms, which joins with the protons through the proton exchange membrane and the electrons through the circuit, and combine to form water. Since the membrane is an insulator, the electrons travel through an external circuit in which the electricity is utilized, and join with protons at the cathode. An air stream on the cathode side is one mechanism by which the water formed by combination of the hydrogen and oxygen is removed. Combinations of such fuel cells are used in a fuel cell stack to provide the desired voltage. The flow field plates may be flexible graphite sheets as described herein that are deformed into a shape (e.g., by embossing, stamping, molding, or a calender roll) that has a continuous reactant flow channel with an inlet and an outlet. The inlet is connected to a source of fuel in the case of an anode flow field plate, or a source of oxidant in the case of a cathode flow field plate. When assembled in a fuel cell stack, each flow field plate functions as a current collector. Electrodes may be formed by providing a graphite sheet as described herein and providing the sheet with channels, which are preferably smooth-sided, and which pass between the parallel, opposed surfaces of the flexible graphite sheet and are separated by walls of compressed expandable graphite. It is the walls of the flexible graphite sheet that actually abut the ion exchange membrane, when the inventive flexible graphite sheet functions as an electrode in an electrochemical fuel cell. The channels are formed in the flexible graphite sheet at a plurality of locations by mechanical impact. Thus, a pattern of channels is formed in the flexible graphite sheet. That pattern can be devised in order to control, optimize or maximize fluid flow through the channels, as desired. For instance, the pattern formed in the flexible graphite sheet can comprise selective placement of the channels, as described, or it can comprise variations in channel density or channel shape in order to, for instance, equalize fluid pressure along the surface of the electrode when in use, as well as for other purposes which would be apparent to the skilled artisan. The impact force is preferably delivered using a patterned roller, suitably controlled to provide well-formed perforations in the graphite sheet. In the course of impacting the flexible graphite sheet to form channels, graphite is displaced within the sheet to disrupt and deform the parallel orientation of the expanded graphite particles. In effect the displaced graphite is being “die-molded” by the sides of adjacent protrusions and the smooth surface of the roller. This can reduce the anisotropy in the flexible graphite sheet and thus increase the electrical and thermal conductivity of the sheet in the direction transverse to the opposed surfaces. A similar effect is achieved with frusto-conical and parallel-sided peg-shaped flat-ended protrusions. Graphites are made up of layer planes of hexagonal arrays or networks of carbon atoms. These layer planes of hexagonally arranged carbon atoms are substantially flat and are oriented or ordered so as to be substantially parallel and equidistant to one another. The substantially flat, parallel equidistant sheets or layers of carbon atoms, usually referred to as graphene layers or basal planes, are linked or bonded together and groups thereof are arranged in crystallites. Highly ordered graphites consist of crystallites of considerable size: the crystallites being highly aligned or oriented with respect to each other and having well ordered carbon layers. In other words, highly ordered graphites have a high degree of preferred crystallite orientation. It should be noted that graphites possess anisotropic structures and thus exhibit or possess many properties that are highly directional e.g. thermal and electrical conductivity and fluid diffusion. Briefly, graphites may be characterized as laminated structures of carbon, that is, structures consisting of superposed layers or laminae of carbon atoms joined together by weak van der Waals forces. In considering the graphite structure, two axes or directions are usually noted, to wit, the “c” axis or direction and the “a” axes or directions. For simplicity, the “c” axis or direction may be considered as the direction perpendicular to the carbon layers. The “a” axes or directions may be considered as the directions parallel to the carbon layers or the directions perpendicular to the “c” direction. The graphites suitable for manufacturing flexible graphite sheets possess a very high degree of orientation. As noted above, the bonding forces holding the parallel layers of carbon atoms together are only weak van der Waals forces. Natural graphites can be treated so that the spacing between the superposed carbon layers or laminae can be appreciably opened up so as to provide a marked expansion in the direction perpendicular to the layers, that is, in the “c” direction, and thus form an expanded or intumesced graphite structure in which the laminar character of the carbon layers is substantially retained. Graphite flake which has been greatly expanded and more particularly expanded so as to have a final thickness or “c” direction dimension which is as much as about 80 or more times the original “c” direction dimension can be formed without the use of a binder into cohesive or integrated sheets of expanded graphite, e.g. webs, papers, strips, tapes, foils, mats or the like (typically referred to as “flexible graphite”). The formation of graphite particles which have been expanded to have a final thickness or “c” dimension which is as much as about 80 times or more the original “c” direction dimension into integrated flexible sheets by compression, without the use of any binding material, is believed to be possible due to the mechanical interlocking, or cohesion, which is achieved between the voluminously expanded graphite particles. In addition to flexibility, the sheet material, as noted above, has also been found to possess a high degree of anisotropy with respect to thermal and electrical conductivity and fluid diffusion, comparable to the natural graphite starting material due to orientation of the expanded graphite particles and graphite layers substantially parallel to the opposed faces of the sheet resulting from very high compression, e.g. roll pressing. Sheet material thus produced has excellent flexibility, good strength and a very high degree of orientation. Briefly, the process of producing flexible, binderless anisotropic graphite sheet material, e.g. web, paper, strip, tape, foil, mat, or the like, comprises compressing or compacting under a predetermined load and in the absence of a binder, expanded graphite particles which have a “c” direction dimension which is as much as about 80 or more times that of the original particles so as to form a substantially flat, flexible, integrated graphite sheet. The expanded graphite particles that generally are worm-like or vermiform in appearance, once compressed, will maintain the compression set and alignment with the opposed major surfaces of the sheet. The density and thickness of the sheet material can be varied by controlling the degree of compression. The density of the sheet material can be within the range of from about 0.04 g/cc to about 2.0 g/cc. The flexible graphite sheet material exhibits an appreciable degree of anisotropy due to the alignment of graphite particles parallel to the major opposed, parallel surfaces of the sheet, with the degree of anisotropy increasing upon roll pressing of the sheet material to increased density. In roll pressed anisotropic sheet material, the thickness, i.e. the direction perpendicular to the opposed, parallel sheet surfaces comprises the “c” direction and the directions ranging along the length and width, i.e. along or parallel to the opposed, major surfaces comprises the “a” directions and the thermal and electrical properties of the sheet are very different, by orders of magnitude, for the “c” and “a” directions. Methods of manufacturing articles from graphite particles have been proposed. For example, U.S. Pat. No. 5,882,570 to Hayward discloses a method of grinding flexible unimpregnated graphite foil to a small particle size, thermally shocking the particles to expand them, mixing the expanded graphite with a thermoset phenolic resin, injection molding the mixture to form low density blocks or other shapes, then heat treating the blocks to thermoset the material. The resulting blocks may be used as insulating material in a furnace or the like. WO 00/54953 and U.S. Pat. No. 6,217,800, both to Hayward further describe processes related to those of U.S. Pat. No. 5,882,570. The Hayward processes are very limited in the scope of the source materials they use, and the type of end products they can produce. Hayward uses only unimpregnated graphite source materials, and his finished products are only formed by mixing the graphite powder with large proportions of resin and injection molding the mixture to form articles which are then thermoset. Accordingly, there is a continuing need in the art for improved processes for producing flexible graphite sheets or products from various types of graphite materials, including those which are already resin impregnated, and for manufacture of more broadly useful products from those materials. Such improved processes are provided by the present invention. |
Method, microprocessor system for critical safety regulations and the use of the same |
In a method of operating a microprocessor system provided with safety functions, which comprises two or more processor cores (1, 2) and periphery elements (5, 7) on a common chip carrier, to which the cores can have access for write or read operations, a distinction is made between algorithms for safety-critical functions and algorithms for comfort functions. Further, a microprocessor system appropriate for implementing the method, and the use of the same, has process cores connected to periphery elements (5,6,7,8,9,10) by way of bus systems (3, 4), and bus driver circuits (19) can transmit bus information from one bus to another with the provision of at least one address comparator (18). |
1-16. (canceled) 17. A method of operating a microprocessor system provided with safety functions, which comprises two or more processor cores (1, 2) on a joint chip carrier, the microprocessor system comprising periphery elements (5, 7) to which the cores can have access for write or read operations, including the step of making a distinction between algorithms for safety-critical functions and algorithms for comfort functions. 18. The method as claimed in claim 17, wherein access to address ranges of the periphery elements allocated to the safety algorithms is possible only when a safety algorithm controls the system program run, and access to ranges of the periphery allocated to the comfort algorithms are allowed only when comfort algorithms control the system program run. 19. The method as claimed in claim 17, wherein the periphery elements comprise read-only memories (5, 7, 8, 9) in which algorithms for function,s that mainly serve comfort, are stored in addition to algorithms for safety-critical functions. 20. The method as claimed in claim 17, wherein the periphery elements comprise at least two read-write memories (6, 10) in which exclusively safety-critical data is stored in critical data ranges (11) and comfort data is stored in uncritical ranges (12). 21. The method as claimed in claim 17, wherein exclusively critical algorithms are stored in two or more first separate chip ranges or components (20) of two or more read-only memories (5 and 8) or corresponding partial ranges of respectively contiguous joint read-only memories (5, 7 and 8, 9), and exclusively comfort algorithms are stored in two or more other separate chip ranges or components (21) of the read-only memory (7 and 9) or in corresponding other partial ranges of respectively contiguous joint read-only memories (5, 7 and 8, 9). 22. The method as claimed in claim 17, wherein the safety-critical functions generate input/output operations for a first type of devices intended for safety functions, and the comfort functions generate input/output operations for a second type of devices intended for comfort functions. 23. The method as claimed in claim 17, wherein upon occurrence of an erroneous write access of a comfort algorithm, an erroneous memory access is identified and the incorrect data value corrected. 24. The method as claimed in claim 17, wherein a comparison of data lying on data buses (3, 4) is not made in a read operation in at least one predetermined address range. 25. A microprocessor system for at least partly safety-critical regulations, comprising at least two processor cores (1, 2) which are connected to periphery elements (5,6,7,8,9,10) by way of at least two bus systems (3, 4) associated with the cores, and at least two bus driver circuits (19) able to transmit bus information from one bus to the other bus, wherein the microprocessor comprises at least one address comparator (18) comparing the addresses of at least one processor core with at least one established address range. 26. The microprocessor system as claimed in claim 25, wherein the microprocessor comprises at least one data comparator (16, 17) which detects a writing error in the periphery elements by comparing data of the first bus with data of another bus. 27. The microprocessor system as claimed in claim 26, wherein a bridging device (19) is provided that can be actuated by the address comparator (18) by way of a connection (13), said bridging device deactivating or bridging one or more data comparators (16, 17) in dependence on the result of the comparison of addresses. 28. The microprocessor system as claimed in claim 25, wherein the bus systems have substantially the same design. 29. The microprocessor system as claimed in claim 25, wherein the periphery elements comprise at least read-write memories (10), read-only memories (5,7,8,9) and input/output elements (10). 30. The microprocessor system as claimed in claim 25, wherein the comparator of addresses comprises logical components, in particular binary comparators. 31. The microprocessor system as claimed in claim 25, wherein at least one element of the group consisting of address comparator (18), comparator (16, 17) and driver (19) is designed redundantly. 32. A motor vehicle control/regulation system comrising a microprocessor system for at least partly safety-critical regulations with at least two processor cores (1, 2), which are connected to periphery elements (5,6,7,8,9,10) by way of at least two bus systems (3, 4) associated with the cores, and with at least two bus driver circuits (19) able to transmit bus information from one bus to the other bus, capable of performing joint brake control/regulation and/or also driving dynamics and of comfort functions of the motor vehicle, which are not critical under safety aspects. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to a method of operating a microprocessor system provided with safety functions, which comprises two or more processor cores on a joint chip carrier, a microprocessor system for at least partly safety-critical regulations, comprising at least two processor cores which are connected to periphery elements ( 5 , 6 , 7 , 8 , 9 , 10 ) by way of at least two bus systems associated with the cores, and at least two bus driver circuits able to transmit bus information from one bus to the other bus, and a motor vehicle control/regulation system comrising such a microprocessor system. EP 0 843 853 A1 discloses a microprocessor system for safety-critical control systems comprising two synchronously operated central units or CPU cores which can have access to periphery elements integrated on the same chip such as memory and input/output components by way of two separate bus systems. The microprocessor system described is especially used for safety-critical control and regulation systems in vehicles, for example, for the active control, or a control activated by the brake function, of the brake pressure applied to the wheels, such as in yaw rate control systems (ESP, TCS), lock control or anti-lock systems (ABS) and traction slip control systems (TCS, etc.). By doubling the processor core, the bus system and at least partly also the periphery elements it is possible to monitor processing errors in one of the two processors either by the respectively second processor or by a device checking whether the result of a working step is identical in both processors. This method permits a drastic increase of the error detection rate because errors that occur simultaneously in both processor branches are comparatively unlikely. Once an error is detected, appropriate measures can be taken such as deactivation of the control system or implementation of an emergency program (trap/interrupt) or a reset, thereby enhancing the reliability of operation of a brake system. The periphery elements, which are connected to the two bus systems, generally comprise permanent stores (ROM, OTP, Flash) and read-write memories (RAM), and input and output units or further bus systems connected by way of bus driver circuits. The bus systems are connected or coupled to each other by drive stages so that the processor cores can also write data into the respectively other bus system, or read the data. The design of the microprocessor system described in EP 0 843 853 A1 is not fully redundant with respect to the memory. At least part of the memory, which is connected to one of the two buses, is reproduced virtually by a hardware comparator. The reproduced memory in this case does not contain the same data word as the first memory at the same address but parity information linked to the complete data word that was calculated or produced from the data word written in the storage. The advantage involved hereby is that a major part of the memory existing for redundancy reasons can be saved practically without any loss of safety. An object of the present invention is to further improve upon the above-mentioned microprocessor system in that way that a distinction can be made between data and/or programs being uncritical with respect to safety and critical data and/or programs. Another objective of the invention is to provide a microprocessor system, which now as before reaches a high rate of error detection as in prior-art systems with respect to the critical data and/or programs so that the reliability of operation mandatory for safety-critical applications is complied with, and which additionally offers the opportunity of executing programs which do not meet the high safety requirements of the safety-critical programs without disturbing the run of the safety-critical programs by any additional programs. In addition, it is desired that the microprocessor system involve comparatively low effort in manufacture. |
<SOH> SUMMARY OF THE INVENTION <EOH>This object is achieved by a method including the step of making a distinction between algorithms for safety-critical functions and algorithms for comfort functions and a microprocessor system that comprises at least one address comparator ( 18 ) comparing the addresses of at least one processor core with at least one established address range. The microprocessor system comprises two or more microcomputers. At least one of these microcomputers is a complete unit made up of central unit and periphery elements comprised of read-only memory, read-write memory and input/output unit. The term ‘complete unit’ implies that the microcomputer includes the components necessary for its basic functions, which does not exclude that part of the periphery such as additional memory components is arranged outside the chip or the chip casing. These externally arranged chips can then be actuated by way of further external bus systems or by way of local buses extending to the outside. The periphery elements, the processor cores and the bus systems of the existing at least two microcomputers are integrated on a joint chip carrier which is preferably a semiconductor dice. As mentioned before, it is possible and hence preferred that the chip carrier on which the processor cores are integrated, comprises integrated periphery elements. It can be expedient that the microcomputer connected to a second bus system does not coincide exactly with the first microcomputer in defined address ranges, e.g. in that defined memory components are not provided in a microcomputer. Also, a memory with memory locations for test data may be provided in one of the two microcomputers instead of a read-only and/or read-write memory. Among others, the two bus systems are interconnected by way of coupling drive stages for the exchange of data in the above-noted address ranges. A high degree of redundancy may be achieved by the mainly complete double or manifold design of the periphery, in particular the memory. Especially preferred is, however, a microprocessor system wherein the memory, in particular the read-write memory and the read-only memory, has a fully redundant design at least in defined address ranges. Further preferred embodiments can be taken from the sub claims and the following description of the Figures. |
Screening methods for pathogen virulence factors under low oxygen conditions |
In general, the invention relates to screening methods for identifying pathogen virulence factors expressed under conditions of low oxygen and for identifying drugs that inhibit a pathogen. The method includes the steps of: (a) exposing a nematode to a mutagenized pathogen cultured under a low oxygen condition; (b) determining whether the mutant pathogen infects the nematode, a reduction of disease in the nematode relative to that caused by the non-mutagenized pathogen indicating a mutation in a pathogenic virulence factor; and (c) using the mutation as a marker for identifying the pathogenic virulence factor. |
1. A method for identifying a pathogenic virulence factor, comprising the steps of: (a) exposing a nematode to a mutagenized pathogen cultured under a low oxygen condition; (b) determining whether said mutant pathogen infects said nematode, a reduction of disease in said nematode relative to that caused by the non-mutagenized pathogen indicating a mutation in a pathogenic virulence factor; and (c) using said mutation as a marker for identifying said pathogenic virulence factor. 2. The method of claim 1, wherein said nematode and said mutant pathogen are cultured together under a low oxygen condition. 3. The method of claim 1, wherein said pathogen is a bacterium. 4. The method of claim 1, wherein said pathogen is in the form of a spore. 5. The method of claim 1, wherein said pathogen is a member of the genus of Enterococcus. 6. The method of claim 1, wherein said pathogen is a member of the genus of Bacteroides. 7. The method of claim 1, wherein said pathogen is a member of the genus of Propionibacterium. 8. The method of claim 1, wherein said pathogen is a member of the genus of Clostridium. 9. The method of claim 1, wherein said nematode is Caenorhabditis elegans. 10. The method of claim 1, wherein said method utilizes a bacterial/C. elegans killing assay. 11. The method of claim 10, wherein said bacterial pathogen causes less C. elegans killing than the non-mutagenized bacterial pathogen. 12. A method of identifying a compound that inhibits pathogenicity of a bacterial pathogen, comprising the steps of: (a) providing a nematode comprising a pathogen cultured under a low oxygen condition; (b) contacting said nematode with a test compound; and (c) determining whether the test compound inhibits the pathogenicity of said pathogen in said nematode. 13. The method of claim 12, wherein said nematode and said mutant pathogen are cultured together under a low oxygen condition. 14. The method of claim 12, wherein said pathogen is a bacterium. 15. The method of claim 12, wherein said pathogen is in the form of a spore. 16. The method of claim 12, wherein said pathogen is a bacterium belonging to the genus of Enterococcus. 17. The method of claim 12, wherein said pathogen is a bacterium belonging to the genus of Bacteroides. 18. The method of claim 12, wherein said pathogen is a member of the genus of Bacteroides. 19. The method of claim 12, wherein said pathogen is a member of the genus of Clostridium. 20. The method of claim 12, wherein said nematode is Caenorhabditis elegans. 21. The method of claim 12, wherein said test compound is provided in a compound library. 22. The method of claim 12, wherein said test compound is a small organic compound. 23. The method of claim 12, wherein said test compound is a peptide, peptidomimetic, or antibody or fragment thereof. 24. The method of claim 12, wherein said inhibition of pathogenicity is measured by a bacteria/C. elegans killing assay. 25. The method of claim 24, wherein said bacterial pathogen causes less C. elegans killing in the presence of said test compound than in the absence of said test compound. |
<SOH> BACKGROUND OF THE INVENTION <EOH>The invention relates to screening methods for identifying pathogen virulence factors expressed under conditions of low oxygen and for identifying drugs that inhibit a pathogen. Microbial pathogens use a variety of complex strategies to subvert host cellular functions, ensuring their multiplication and survival. To this end, some pathogens require low oxygen conditions for their proliferation, and utilize finely tuned host-specific strategies to establish a pathogenic relationship. During infection, pathogens encounter different conditions, and respond by expressing virulence factors that are appropriate for the particular environment, host, or both. Although antibiotics have been effective tools in treating infectious disease, the emergence of drug resistant pathogens is becoming problematic in the clinical setting. New antibiotic or antipathogenic molecules are therefore needed to combat such drug resistant pathogens. Accordingly, there is a need in the art for screening methods aimed not only at identifying and characterizing potential antipathogenic agents, but also for identifying and characterizing the virulence factors that enable pathogens to infect and debilitate their hosts, especially those virulence factors expressed under conditions of low oxygen. |
<SOH> SUMMARY OF THE INVENTION <EOH>In general, the invention features a method for identifying a pathogenic virulence factor. The method includes the steps of: (a) exposing a nematode to a mutagenized pathogen cultured under a low oxygen condition; (b) determining whether the mutant pathogen infects the nematode, a reduction of disease in the nematode relative to that caused by the non-mutagenized pathogen indicating a mutation in a pathogenic virulence factor; and (c) using the mutation as a marker for identifying the pathogenic virulence factor. In preferred embodiments, the nematode (for example, Caenorhabditis elegans ) and the mutant pathogen (for example, a member of the genus of Enterococcus, Bacteroides, Propionibacterium, or Clostridium ) are cultured together under a low oxygen condition. In other preferred embodiments, the method utilizes a bacterial/ C. elegans killing assay, wherein the bacterial pathogen causes less C. elegans killing than the non-mutagenized bacterial pathogen. In another aspect, the invention features a method of identifying a compound that inhibits pathogenicity of a bacterial pathogen. The method includes the steps of: (a) providing a nematode including a pathogen cultured under a low oxygen condition; (b) contacting the nematode with a test compound; and (c) determining whether the test compound inhibits the pathogenicity of the pathogen in the nematode. In preferred embodiments, the nematode and the mutant pathogen are cultured together under a low oxygen condition. Preferably, the test compound is provided in a compound library; is a small organic compound; is an inorganic compound; or is a peptide, peptidomimetic, or antibody or fragment thereof. In other preferred embodiments, inhibition of pathogenicity is measured by a bacterial/ C. elegans killing assay, wherein the bacterial pathogen causes less C. elegans killing in the presence of the test compound than in the absence of the test compound. By “virulence factor” is meant a cellular component (for example, a protein such as a transcription factor or a molecule without which the pathogen is incapable of causing disease) that gives an advantage to a microorganism to cause disease or to colonize a host (for example, a eukaryotic host organism such as a nematode or mammal). Such cellular components are involved in the adaptation of the pathogen to a host (for example, a nematode host), establishment and maintenance of an infection, and generation of the damaging effects of the infection to the host organism. Further, the phrase includes cellular components that act directly on host tissue, as well as components that regulate the activity or production of other pathogenic factors. By “infection” or “infected” is meant an invasion or colonization of a host animal (e.g., nematode) by a pathogen that is damaging to the host or to others. By “pathogen” is meant a causative agent of disease. Exemplary pathogens include bacteria, fungi, protists, and viruses, especially pathogens that thrive under conditions of low oxygen. Such pathogens may also be in a variety of developmental forms or stages including, without limitation, spores and biofilms. By “inhibits pathogenicity of a pathogen” is meant the ability of a test compound to decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a pathogen-mediated disease or infection in a eukaryotic host organism. Preferably, such inhibition decreases pathogenicity by at least 5%, more preferably by at least 25%, and most preferably by at least 50% or more, as compared to symptoms in the absence of the test compound in any appropriate pathogenicity assay (for example, those assays described herein). In one particular example, inhibition may be measured by monitoring pathogenic symptoms in a nematode infected with a pathogen exposed to a test compound or extract, a decrease in the level of pathogenic symptoms relative to the level of symptoms in the host organism not exposed to the compound indicating compound-mediated inhibition of the pathogen. By “low oxygen conditions” or “under a condition of low oxygen” is meant an environment having less than twenty percent (20%) oxygen, preferably less than 15%, more preferably less than ten percent (10%), and most preferably less than five percent (5%) oxygen. The present invention provides a number of advantages. For example, the invention facilitates the identification of novel targets and therapeutic approaches for identifying or preparing agents active on pathogenic virulence factors and genes expressed under conditions of low oxygen. The invention also provides long awaited advantages over a wide variety of standard screening methods used for distinguishing and evaluating the efficacy of a compound against a variety of pathogens that live and thrive under varying conditions of low oxygen. In one particular example, the screening methods described herein allow for the simultaneous evaluation of host toxicity as well as anti-pathogenic potency in a simple in vivo screen. Moreover, the methods of the invention allow one to evaluate the ability of a compound to inhibit pathogenesis and infection of a pathogen (for example, a bacterium), and, at the same time, to evaluate the ability of the compound to stimulate and strengthen a host's response to pathogenic attack. Accordingly, the methods of the invention provide a straightforward means to identify compounds that are both safe for use in eukaryotic host organisms (i.e., compounds which do not adversely affect the normal development and physiology of the organism) and efficacious against a variety of pathogenic microbes. In addition, the methods of the invention provide a route for analyzing virtually any number of compounds for an anti-pathogenic effect with high-volume throughput, high sensitivity, and low complexity. The methods are also relatively inexpensive to perform and enable the analysis of small quantities of active substances found in either purified or crude extract form. Furthermore, the methods disclosed herein provide a means for identifying anti-pathogenic compounds that cross eukaryotic cell membranes and which maintain therapeutic efficacy in an in vivo method of administration. In addition, the above-described methods of screening are suitable for both known and unknown compounds and compound libraries, including synthetic combinatorial chemical libraries. Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims. |
Treatment of neuropathic pain with n-methyl-d-aspartate (nmda) receptor antagonists |
Central neuropathic pain is treated with an analgesic composition that consists essentially of an N-methyl-D-aspartate (NMDA) receptor antagonist. In one embodiment, the invention includes chronic administration of the (NMDA) receptor antagonist. In another embodiment, the invention is use of an NMDA receptor antagonist or component thereof for the manufacture of a medicament than includes an analgesic component that consists essentially of an NMDA receptor antagonist for the chronic treatment of central neuropathic pain. |
1-32. canceled. 33. A method for treatment in a human of central neuropathic pain resulting from injury, trauma, lesion or other disorder in the spinal cord or brain, comprising administering to the human an effective amount of an N-methyl-D-aspartate receptor antagonist, or component thereof. 34. The method of claim 1 wherein the N-methyl-D-aspartate receptor antagonist does not include a high-affinity N-methyl-D-aspartate receptor antagonist. 35. The method of claim 1 wherein the N-methyl-D-aspartate receptor antagonist does not include ketamine. 36. The method of claim 1, wherein the central neuropathic pain occurs acutely or wherein the central neuropathic pain is chronic. 37. The method of claim 1, wherein the central neuropathic pain results from compression or disruption of the spinal cord. 38. The method of claim 5, wherein the compression or disruption of the spinal cord is intrinsic or extrinsic to the spinal cord. 39. The method of claim 6 wherein the compression or disruption of the spinal cord is due to trauma, surgery or lesion. 40. The method of claim 7 wherein the lesion is a plaque, a cyst, a tumor or a vascular malformation. 41. The method of claim 1, wherein the N-methyl-D-aspartate receptor antagonist is a low-affinity N-methyl-D-aspartate receptor antagonist. 42. The method of claim 9, wherein the N-methyl-D-aspartate receptor antagonist is at least one member selected for the group consisting of dextromethorphan hydrobromide, amantadine, memantine, remacemide and riluzole. 43. The method of claim 10, wherein the N-methyl-D-aspartate receptor antagonist consists essentially of dextromethorphan hydrobromide. 44. The method of claim 1, wherein the effective amount of the N-methyl-D-aspartate receptor antagonist is in the range of about 120 mg to about 1200 mg per day. 45. A method of treating central neuropathic pain in a human resulting from injury, trauma, lesion or other disorder in the spinal cord or brain, comprising administering to the human an effective amount of a composition comprising an N-methyl-D-aspartate receptor antagonist and gabapentin at a ratio of 1:5 by weight. 46. The method of claim 13, wherein the N-methyl-D-aspartate receptor antagonist comprises a low-affinity N-methyl-D-aspartate receptor antagonist. 47. The method of claim 14, wherein the low-affinity N-methyl-D-aspartate receptor antagonist is a member selected from the group consisting of dextromethorphan hydrobromide, amantadine, memantine, remacemide and riluzole. 48. The method of claim 13, wherein the central neuropathic pain occurs acutely or wherein the central neuropathic pain is chronic. 49. The method of claim 13, wherein the central neuropathic pain results from compression or disruption of the spinal cord. 50. The method of claim 17, wherein the compression or disruption of the spinal cord is intrinsic or extrinsic to the spinal cord. 51. The method of claim 18, wherein the compression or disruption of the spinal cord is due to trauma, surgery or lesion. 52. The method of claim 19, wherein the lesion is a plaque, a cyst, a tumor or a vascular malformation. 53. An analgesic composition for the treating central neuropathic pain in a human resulting from injury, trauma, lesion or other disorder in the spinal cord or brain, comprising an N-methyl-D-aspartate receptor antagonist, comprising an N-methyl-D-aspartate receptor antagonist and gabapentin at a ratio of 1:5 by weight and a pharmaceutically acceptable carrier. 54. The composition of claim 21, wherein the N-methyl-D-aspartate receptor antagonist is a low-affinity N-methyl-D-aspartate receptor antagonist. 55. The composition of claim 22 wherein the low-affinity N-methyl-D-aspartate receptor antagonist is selected from the group consisting of dextromethorphan hydrobromide, amantadine, memantine, remacemide and riluzole. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Humans with injury to the central nervous system (e.g., brain and spinal cord) can suffer from chronic central neuropathic pain. However, standard analgesics, such as nonsteroidal anti-inflammatory drugs, opioids, tricyclic antidepressants, anticonvulsants and antispasmodics, are ineffective in relieving the chronic central neuropathic pain, in particular pain associated with spinal cord injury. Further, relief of pain by certain analgesics can result in adverse side effects such as fatigue, confusion, dizziness, somnolence and speech difficulty thereby diminishing the attractiveness of the analgesic to the human. Thus, there is a need to develop new, improved and effective methods of treatments for pain in humans with central nervous system injury which alleviate pain without adverse side effects. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a method of treating chronic central neuropathic pain in humans suffering from spinal cord injury by administering an N-methyl-D-aspartate (NMDA) receptor antagonist. In one embodiment, the method is treatment of central neuropathic pain in a human, the method including administering to the human an analgesic composition, wherein the improvement comprises chronic administration to the human an analgesic composition that consists essentially of an N-methyl-D-aspartate receptor antagonist and wherein there is essentially no high affinity N-methyl-D-aspartate receptor antagonist in the analgesic composition. In another embodiment, the method is for treating central neuropathic pain in a human, the method including administering to the human an analgesic composition, wherein the improvement comprises administering to the human an analgesic composition that consists essentially of an N-methyl-D-aspartate receptor antagonist, and wherein the N-methyl-D-aspartate receptor antagonist essentially does not include ketamine or a subtype selective N-methyl-D-aspartate receptor antagonist. In an additional embodiment, the invention is the use of an N-methyl-D-aspartate receptor antagonist, or component thereof for the manufacture of a medicament that includes an analgesic component that consists essentially of the N-methyl-D-aspartate receptor antagonist, for the chronic treatment of central neuropathic pain. In still another embodiment, the method is treating central neuropathic pain in a human, comprising the step of acutely administering to the human an analgesic composition that consists essentially of an N-methyl-D-aspartate receptor antagonist, and wherein the N-methyl-D-aspartate receptor antagonist essentially does not include ketamine. In yet another embodiment, the method is treating central neuropathic pain in a human, comprising chronically administering to the human an analgesic composition that consists essentially of an N-methyl-D-aspartate receptor antagonist and wherein there is essentially no high affinity N-methyl-D-aspartate receptor antagonist in the analgesic composition. In a further embodiment, the method is treating central neuropathic pain in a human, comprising the step of administering to the human an analgesic composition that consists essentially of an N-methyl-D-aspartate receptor antagonist, and wherein the N-methyl-D-aspartate receptor antagonist essentially does not include ketamine or a subtype selective N-methyl-D-aspartate receptor antagonist. The invention described herein provides a method of treating chronic neuropathic pain in a human suffering from a spinal cord injury by administering NMDA receptor antagonists. Advantages of the method of the invention include, for example, augmented pain relief with no or significantly reduced side effects (e.g., fatigue, confusion, dizziness, somnolence and speech difficulty) particularly in humans where pain management strategies are difficult to implement. The methods of the invention provide an efficient way to treat and reduce the severity of central neuropathic pain in a human suffering from a spinal cord injury. Thus, treatment of humans with a spinal cord injury who have central neuropathic pain with NMDA receptor antagonists can diminish their pain without intolerable side effects. |
Supression of allergic reactions by transdermal administration of allergens conjugated to cholera toxin or fragments thereof |
The present invention discloses the use of the non-toxic cell-binding B subunit of CT (CTB), and holotoxin CT that is devoid of ADP-ribosylating activity, as adjuvants for enhancing transcutaneous immune response to a co-administered protein allergen. It was found that topical administration of CTB to mice induced serum antibody response against itself comparable to those evoked by CT, but was inefficient at promoting systemic antibody responses against an admixed prototype protein allergen. To the contrary co-administration of either CT or CTB with allergen led to vigorous antigen-specific T cell proliferative responses in lymph nodes draining the cutaneous site of administration and at distant systemic sites. Consistent with these observations, it was found that CTB selectively potentiated Th1-driven responses without affecting Th2-dependent responses. Cutaneously applied CT enhanced serum IgE responses to a co-administered allergen, while CTB partially suppressed epicutaneously induced IgE responses to the same allergen. |
1. A method for suppressing an IgE-mediated hypersensitivity allergic reaction in a mammal comprising the steps of: transdermally administering to a mammal in need of such treatment a composition comprising: a) at least one allergen; and b) a non-ADP ribosylating toxin or subunit thereof, wherein the amounts of a) and b) together are effective to suppress said allergic reaction. 2. The method of claim 1 wherein said allergen is a protein. 3. The method of claim 1 wherein said allergen is a peptide. 4. The method of claim 1 wherein said non-ADP-ribosylating toxin subunit is selected from cholera toxin B subunit, E. coli heat-labile toxin B subunit, mutants and derivatives thereof. 5. The method of claim 1 wherein said allergen and said non-ADP-ribosylating toxin or subunit are chemically linked. 6. The method of claim 1 wherein said allergen and said non-ADP-ribosylating toxin or subunit are genetically fused. 7. The method of claim 1 wherein said allergen and said non-ADP-ribosylating toxin subunit are mixed together. 8. The method of claim 1 wherein said allergen and said non-ADP-ribosylating toxin or subunit are administered using a patch. 9. The method of claim 1, further comprising administering an adjuvant with said composition. 10. The method of claim 1 further comprising administering a plurality of allergens. 11. The method of claim 4 wherein said non-ADP-ribosylating toxin subunit is CTB. 12. The method according to claim 1, wherein said allergen is selected from the group consisting of food allergens, plant allergens, pollen allergens, tree allergens, animal allergens, parasitic allergens, mite allergens, bacterial allergens, viral allergens, mycoplasma allergens, fungal allergens, drug allergens and occupational allergens. 13. The method according to claim 1, wherein said hypersensitivity reaction comprises an immediate hypersensitivity reaction. 14. The method of claim 1 wherein said allergen is a derivative, analog or mutant of an allergen. 15. The method of claim 14 wherein said derivative is a fragment comprising one or more than one T cell epitope. 16. The method of claim 14 wherein said derivative or analog comprises one or more epitope capable of eliciting an IgE response. 17. The method claim 14 wherein said derivative comprise at least one epitope capable of interacting with specific IgE antibodies. 18. The method of claim 17 wherein said derivative is chemically linked to cholera toxin B subunit. 19. The method of claim 17 wherein said derivative is chemically linked to E. coli heat-labile toxin B subunit. 20. The method of claim 1 wherein said non-ribosylating toxin comprises and aldehyde-treated toxin. 21. The method of claim 20 wherein said allergen and said non-ADP ribosylating toxin subunit are administered in a formulation containing an aldehyde. 22. The method of claim 20, wherein said non-ribosylating toxin is cholera toxin. 23. The method of claim 20, wherein said non-ribosylating toxin is heat-labile toxin from E. coli. |
<SOH> BACKGROUND OF THE INVENTION <EOH> |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides a method for suppression an IgE-mediated allergic reaction in a mammal by transdermal administration of an allergen in conduction with a non-ADP ribosylating toxin or toxin subunit in amounts effective to suppress the allergic reaction. In one embodiment, the allergen is admixed with the non-ADP ribosylating toxin or toxin subunit. In another embodiment, the allergen is chemically conjugated to the non-ADP ribosylating toxin or toxin subunit. In yet a further embodiment, the allergen is genetically fused to the non-ADP ribosylating toxin or toxin subunit. In another embodiment, the allergen and non-ADP-ribosylating toxin or subunit are comprised in a formulation suitable for topical or transcutaneous administration. In yet another embodiment, the allergen and holotoxin comprising both A and B subunits are comprised in a formulation along with an aldehyde. These and other aspects of the present invention will be apparent to those of ordinary skill in the art in light of the present specification, claims and drawings. |
Printed biodegradable plastic film |
A biodegradable plastic film 1 has at least one surface formed with a printed region 5. Within the region 5, non-printed sub-regions 7 are rather evenly distributed. |
1. A biodegradable plastic film having at least one surface formed with a printed region, said plastic film further comprises non-printed sub-regions distributed rather evenly within said printed region formed on said plastic film, and totally occupying 10-20% of said printed region. 2. The plastic film according to claim 1, wherein said non-printed sub-regions comprise a plurality of individual non-printed sub-regions each enclosed with printing ink defining said printed region and dimensioned to be in a range of 15-30 μm in two directions orthogonal to each other. 3. The plastic film according to claim 2, wherein each of said individual non-printed sub-regions has at least one of adjacent said individual non-printed sub-regions with a distance shorter than twice as long as a thickness of said plastic film. 4. The plastic film according to claim 1, wherein said printed region is formed on an outer surface of said plastic film in form of an envelope. 5. The plastic film according to claim 4, wherein said envelope is used as a package for a disposable diaper, disposable training pants or a sanitary napkin. 6. The plastic film according to claim 1, wherein said biodegradable plastic film is made of polyethylene succinate, polybutylene succinate or polylactic acid. |
<SOH> TECHNICAL FIELD OF THE INVENTION <EOH>This invention relates to a printed biodegradable plastic film and more particularly, to such a film, for example, a stock material for a disposable sanitary article and the like. |
<SOH> BRIEF DESCRIPTION OF THE DRAWINGS <EOH>FIG. 1 is a perspective view showing an exemplary application of a printed biodegradable plastic film; FIG. 2 is a scale-enlarged diagram showing important parts in FIG. 1 ; and FIG. 3 is a cross-sectional view taken along a line III-III in FIG. 2 . detailed-description description="Detailed Description" end="lead"? |
Financial market trading system |
According to the present invention, there is provided a computer system for providing a centralized trading service to one or more trading party sites, the system comprising: a) a service data centre comprising: i) a trading computer arranged to process and communicate trading data and to generate trading ticket data in respect of confirmed trades on the basis of trading data: ii) a data store accessible to the trading computer for temporarily storing trading ticket data records; and b) one or more trading party sites each comprising at least one user terminal running a hypermedia browser application, each trading party site being located remotely from the data centre, and being arranged to communicate with the trading computer over a packet-switched communications network: the system being arranged to present, to users of the terminals, hypermedia user interface components comprising trading data received from the trading computer. |
1. A computer system for providing a centralized trading service to one or more trading party sites, the system comprising: a) a service data centre comprising: i) a trading computer arranged to process and communicate trading data and to generate trading ticket data in respect of confirmed trades on the basis of trading data; ii) a data store accessible to the trading computer for temporarily storing trading ticket data records; and b) one or more trading party sites each comprising at least one user terminal running a hypermedia browser application, each trading party site being located remotely from the data centre, and being arranged to communicate with the trading computer over a packet-switched communications network; the system being arranged to present, to users of the terminals, hypermedia user interface components comprising trading data received from the trading computer. 2. A system according to claim 1, wherein trading data for communication from the trading computer to a user terminal of one of the trading party sites is published using a publish and subscribe protocol to an information channel identifying the trading party site. 3. A system according to any preceding claim, wherein the trading party sites each comprise a trading ticket data receiving computer arranged to receive trading ticket data from the data store. 4. A system according to claim 3, wherein trading ticket data for communication from the data store to the trading ticket data receiving computer of one of the trading party sites is published using a publish and subscribe protocol to an information channel identifying the trading party site. 5. A system according to claim 3, wherein the data store is arranged to delete trading ticket data records sent to the data record receiving computer upon confirmation of receipt. 6. A system according to claim 1, wherein the trading data comprises conversational trading data or matching trading data. 7. A service data centre for use in the computer system according to claim 1. 8. A trading party site for use in the computer system according to claim 1. 9. A method of providing a centralised trading service to one or more trading party sites, the method comprising the steps of: a) processing trading data at a trading computer of a service data centre; b) generating, at the trading computer, trading ticket data in respect of confirmed trades on the basis of the trading ticket data; c) temporarily storing generated trading ticket data at a data store of the service data centre; d) transmitting trading data over a packet-switched communications network to one or more trading party sites remote to the data centre, each trading party site comprising at least one user terminal running a hypermedia browser application; and e) presenting, to users of the terminals, hypermedia user interface components comprising trading data received from the trading computer. 10. A method according to claim 9, comprising publishing trading data, for communication from the trading computer to a user terminal of one of the trading party sites, to an information channel identifying the trading party site using a publish and subscribe protocol. 11. A system according to claim 9, comprising transmitting trading ticket data from the data store to one or more trading ticket data receiving computers at the trading party sites. 12. A method according to claim 11, comprising publishing trading ticket data, for communication from the data store to the trading ticket data receiving computer of one of the trading party sites, to an information channel identifying the trading party site using a publish and subscribe protocol. 13. A method according to claim 11, comprising deleting, at the data store, trading ticket data records sent to the data record receiving computer upon confirmation of receipt. 14. A system according to claim 1, wherein the trading data comprises conversational trading data or matching trading data. 15. A service data centre for communicating and presenting trading data for trading financial instruments, the data centre comprising: a) a trading computer arranged to process trading data and to generate trading ticket data in respect of confirmed trades on the basis of trading data; b) a hypermedia server arranged to communicate with the trading server, the hypermedia server comprising a hypermedia user interface generation component for generating hypermedia content for presenting trading data to a user; and c) a data store accessible to the trading server for temporarily storing trading ticket data records; wherein the hypermedia server is arranged to publish trading data and trading ticket data, for communication from the trading computer to one of one or more trading party sites remote to the data centre, to an information channel identifying the trading party site using a publish and subscribe protocol. 16. A trading party site for processing and communicating trading data for trading financial instruments, the trading party site comprising: a) a computer for receiving trading data and trading ticket data from a remote service data centre; and b) at least one user terminal running a hypermedia browser application, the terminal being arranged to present to a user hypermedia user interface components comprising received trading data; wherein the computer is arranged to subscribe to an information channel identifying the trading party site, to receive trading data and trading ticket data from the remote service data centre, using a publish and subscribe protocol. 17. A system for communicating real-time conversational trading data for trading financial instruments, the system comprising a) a first user terminal associated with a trading party and comprising: i) a real-time conversational trading data communication component; and ii) a hypermedia user interface component for receiving from a user real-time conversational trading data for transmission to a user terminal associated with a counterparty using the conversational trading data communication component and for presenting to a user real-time conversational trading data received by the real-time conversational trading data communication component from the user terminal associated with the counterparty. b) a second user terminal associated with a trading counterparty and comprising: i) a real-time conversational trading data communication component; and ii) a hypermedia user interface component for receiving from a user real-time conversational trading data for transmission to a user terminal associated with a trading party using the conversational trading data communication component and for presenting to a user real-time conversational trading data received by the real-time conversational trading data communication component from the user terminal associated with the trading party; and c) a communications network connecting the first and second user terminals for communicating real-time conversational trading data. 18. A system according to claim 17 wherein the first and second user terminals are arranged to be in a first state in which conversational trading data may be transmitted from the user terminal associated with the trading party to the user terminal associated with the counterparty or in a second state in which conversational trading data may be transmitted from the user terminal associated with the counterparty to the user terminal associated with the trading party but not in a state in which conversational trading data may be both transmitted and received between the user terminal associated with the trading party and the user terminal associated with the counterparty. 19. A method of communicating real-time conversational trading data for trading financial instruments, the method comprising the steps of: a) communicating real-time conversational trading data between a user terminal associated with a trading party and a user terminal associated with a counterparty; and b) presenting, at one of the user terminals, a hypermedia user interface component comprising real-time conversational trading data received from the other user terminal or for transmission to the other user terminal. 20. A method according to claim 19, wherein in a first time period, conversational trading data may only be transmitted from the user terminal associated with the trading party to the user terminal associated with a counterparty and not received by the user terminal associated with the trading party from the user terminal associated with a counterparty, and in a second time period, conversational trading data may only be transmitted from the user terminal associated with the counterparty to the user terminal associated with a trading party and not received by the user terminal associated with the from the user terminal associated with a trading party. 21. A user terminal associated with a trading party, the terminal being for communicating trading data for trading financial instruments, the user terminal comprising: a) a trading data communication component for communicating trading data with a user terminal associated with a counterparty; and b) a hypermedia user interface component for presenting to a user graphical user interface elements received from a remote hypermedia server, the graphical user interface elements comprising trading data received by the trading data communication component; wherein the trading data is communicated over a secure communications channel different the channel over which the graphical user interface elements are communicated. 22. One or more computer programs for performing the method of claim 9. 23. Apparatus for performing the method of claim 9. |
<SOH> BACKGROUND OF THE PRESENT INVENTION <EOH>In the major financial markets of today, trading of financial instruments is largely performed using communications and data processing systems. For example, in the Interbank foreign exchange market, products such as Reuters Dealing 3000 (which includes versions providing conversational and anonymous matching functions) are used by banks to trade currencies between themselves. Conversational trading involves a party initiating contact with a known counter party and negotiating trading terms between the parties using a conversational communications capability such as text-based messaging. To enable creation of contracts and to avoid the crossing of offer, counter offer or acceptance messages, the conversational capability may be half-duplex in the sense that only one of the party or counter party is allowed to transmit a message at any one time. Trading using a matching capability involves parties unilaterally placing trading bids or offers or other trading requirements on a central database. Parties also generally maintain credit limits in respect of potential counter parties which are stored on a distributed database. Matching is performed independently of the parties and if a match between a party and counter party is identified, and if sufficient credit exists between the parties, the trade is executed automatically and the parties notified. With conversational trading, it is essential for each party to maintain a record of all completed conversations, whether resulting in agreed trades or not, for evidential purposes. These conversational records may be used by the parties' back office computer systems for settlement and other purposes. Often, a summary of the terms of agreed trades is also maintained for future reference and for processing by back office systems of the parties. This summary is generally referred to as a trading or deal ticket and generally contains at least the information required to settle an agreed trade—for example, the name of the counter party, the financial instrument traded, the price and volume agreed and any other terms such as the type of instrument or settlement period. Optionally, there may be stored within a ticket a further record of the corresponding conversation. Although conversations do not occur with matched trading, data for the ticket and the confirmation of the trade still needs to be maintained by the parties as a record of the trade agreed. Reuters Dealing 3000 provides facilities for recording ticket data at client-sited data storage devices when a trade has been confirmed by the user. Furthermore, Dealing 3000 has a facility for automatically generating ticket data on the basis of conversational data exchange performed using the product. FIG. 1 shows in simplified form the computer systems architecture used in the conversational features of Dealing 3000. Data processing devices for implementing the product are located at a client site 10 . The client, for example, is a bank which trades on the Interbank foreign exchange market. At client site 10 , traders use the product by operating a keystation 12 which implements business logic elements of the product and is a local client of dealing server 14 to which it is connected over a local area network (LAN) 16 . Keystation 12 comprises several components including a graphical user interface, a local service manager, local network communication components, and dealing business logic components which implement the main functionality of the product such as managing outgoing and incoming calls with other traders, and analysing conversation data to generate ticket data. Dealing server 14 comprises several components such as local area network communications components and a data store for storing conversational data and ticket data generated by keystation 12 . Dealing server 14 also acts as an aggregator of keystations so that a plurality of keystations identical to keystation 12 may be connected over LAN 16 and may communicate over dealing network 20 . Dealing server 14 also comprises a wide area network communication component for sending conversational data to Dealing network 20 via a dealing network access function 18 which acts as an aggregator of connections to dealing network 20 and will typically have a plurality of dealing servers from different client sites connected to it. Typically, there will be a plurality of dealing network access functions identical to dealing network access function 18 each connected to dealing network 20 . The individual dealing servers connected to dealing network 20 are administered by an administration server 22 . Thus, it can be seen that the business logic components and data store for storing conversational data and ticket data are wholly implemented at the client site. The client/server components implemented at client site 10 are proprietary to Reuters. For example, keystation 12 and dealing server 14 comprise proprietary applications for implementing the Dealing 3000 product. Keystation 12 may further comprise standard client applications such as a Web browser for accessing network resources over the internet, for example. However, this access is not enabled over local area network 16 or via dealing server 14 , but rather over other conventional network access arrangements. FIG. 1 a shows in simplified form the computer systems architecture used in both the conversational and the matching features of Dealing 3000. Keystation 12 , dealing server 14 , LAN 16 , dealing network access function 18 , dealing network 20 and administration server 22 are as described above and provide the infrastructure for implementing a conversational dealing capability. Keystation 13 and matching concentrator 15 , both at client site 10 , are also connected to LAN 16 which in turn is connected to central matching server 19 via several further matching concentrators 17 which are remote from client site 10 . Matching concentrators 15 and 17 are part of an fan-like arrangement of matching concentrators such that central matching server 19 is connected to a plurality of level 0 matching concentrators which are in turn each connected to a plurality of level 1 matching concentrators and so on through a plurality of levels of matching concentrators until the connection to a client-sited matching concentrator is made. Thus, the fan-like architecture of matching concentrators provides communication capabilities between a plurality of keystations, such as keystation 13 , and central matching server 19 whereby bids, offers and other trading requirements may be communicated by users of keystations to central matching server 19 which performs the matching service and may execute trades between parties in real time and notify the parties of the trade. Central matching server 19 is also connected to administration server 22 for administration purposes. Keystations 12 and 13 may be implemented in a single terminal device thus providing both conversational dealing and matching capabilities from a single terminal. Various aspects of the Dealing 3000 product are shown in simplified form in FIGS. 1 and 1 a . Previous dealing products as well as aspects of the dealing network operated by Reuters are described in detail in the Applicant's granted patents U.S. Pat. No. 4,388,489; U.S. Pat. No. 4,525,779; U.S. Pat. No. 4,531,184; U.S. Pat. No. 5,003,473; U.S. Pat. No. 5,034,916 and U.S. Pat. No. 5,195,031 which documents are incorporated herein by reference. For ease of understanding, some of the main technical aspects described in these documents are summarized below. The documents describe a data communications network for conducting conversational video textual data communications—i.e. text typed at a keystation which may be displayed on a computer screen and sent over the network to be displayed on other computer screens. The system comprises a central message switching node connected to one or more terminal controllers at one or more subscriber premises via data communications links. Each terminal controller at subscriber premises may be connected to one or more keystations comprising a keyboard and a screen so that a trader may type in messages for sending to other traders at other subscribers premises and also receive messages from other traders. The conversation is locally stored at the subscriber premises by the terminal controller connected to the keystation and a hard copy of conversations may be printed out. Keystation screens may be split to display at least two different video conversations and also to display a conversation in one split screen and supplementary data retrieved from a database connected to the central message switching nodes of the central system. Conversational text is sent in packets which may be less than the total displayable data content. Messages are addressed to particular keystations by unique identifiers and the central system has a packet switching network for routing received messages to the appropriate destination. The communication is half-duplex in that a keystation cannot both transmit and receive at the same time, but messages may be prepared prior to transmission while receiving a transmission from another party. Messages received by a keystation are displayed with the unique identifier of the sender as well as an optional interest message indicating the reason for the communication. Additional functionality available at keystations includes i) the ability to create a contact list as well as an inhibit list to accelerate and screen contacts made throughout the network; ii) a “deal key” function that may be employed to immediately confirm receipt of a sent message on the screen of the sender; the use of a mouse and screen pointer used with a window display—by pointing to a contact and performing a single click an interest message is inserted into a command line ready for transmission, by double clicking, the interest message is automatically transmitted to the appropriate contact; iii) using a conversation analysing component connected to keystations to parse a trading conversation and automatically provide context-sensitive trading data messages in real-time—for example, the analysis may recognise the type of transaction occurring, and the details of the transaction; error messages may be provided highlighting inconsistencies in the data analysed; furthermore, tickets are created dynamically on the basis of the analysis. U.S. Pat. No. 5,003,473 describes a communication system for transferring ticket data stored at a local database at a client site to a remote back office database thus back office records of tickets may be made without the back office computer continually polling the trading system. The matching aspect of Reuters Dealing 3000 employ a similar computer systems architecture as has been described above in relation to the conversational aspect of Reuters Dealing 3000. The business logic components will of course implement matching capabilities rather than conversational trading capabilities and, likewise, data communicated from client site 10 over matching network 20 will be trading bids, offers or other requirements rather than conversational data. Furthermore, one or more central servers will be connected to a matching network 20 for implementing the anonymous matching process. Various matching aspects of the Dealing 3000 Matching™ product, and previous matching products, are described in greater detail in granted U.S. Pat. No. 5,136,501 which is incorporated herein by reference. In the Dealing 3000 product, other data may be sent to client site 10 over dealing network 20 such as real time data feeds of financial information and other news. It is important to realize that in the prior art described above, the business logic components which process trading data, for example to automatically generate trading tickets for confirmed trades, are executed using dedicated computer systems of each trading party at a trading party site. One object of the present invention is to provide a centralised trading service which may be delivered from a central service data centre but which provides the functionality of the products described above, including the real-time conversational or matching trading facility and the automatic generation of trading tickets for confirmed trades. International patent application publication no. WO 00/39719 and WO 00/55775 disclose computer-based matching systems for party and counterparty exchanges. Parties and counterparties may post their requirements with a central server over the Internet using a Web browser at a client terminal. The system enables consumers to obtain foreign exchange transactions directly with other consumers thereby cutting out the Interbank foreign exchange market. A trade can be identified which is at the mid-point of the Interbank bid/offer spread. The invention disclosed in these two documents cannot be used by the banks themselves to trade on the Interbank foreign exchange market. Furthermore the invention is not capable of providing a conversational trading facility or of generating or storing conversational trading data or trading ticket data. |
<SOH> SUMMARY OF THE PRESENT INVENTION <EOH>According to a first aspect of the present invention, there is provided a computer system for providing a centralized trading service to one or more trading party sites, the system comprising: a) a service data centre comprising: i) a trading computer arranged to process and communicate trading data and to generate trading ticket data in respect of confirmed trades on the basis of trading data; ii) a data store accessible to the trading computer for temporarily storing trading ticket data records; and b) one or more trading party sites each comprising at least one user terminal running a hypermedia browser application, each trading party site being located remotely from the data centre, and being arranged to communicate with the trading computer over a packet-switched communications network; the system being arranged to present, to users of the terminals, hypermedia user interface components comprising trading data received from the trading computer. Preferably, trading data for communication from the trading computer to a user terminal of one of the trading party sites is published using a publish and subscribe protocol to an information channel identifying the trading party site. In one embodiment the trading party sites each comprise a trading ticket data receiving computer arranged to receive trading ticket data from the data store. Preferably, trading ticket data for communication from the data store to the trading ticket data receiving computer of one of the trading party sites is published using a publish and subscribe protocol to an information channel identifying the trading party site. Also preferably, the data store is arranged to delete trading ticket data records sent to the data record receiving computer upon confirmation of receipt. According to a second aspect of the present invention, there is provided a method of providing a centralised trading service to one or more trading party sites, the method comprising the steps of: a) processing trading data at a trading computer of a service data centre; b) generating, at the trading computer, trading ticket data in respect of confirmed trades on the basis of the trading ticket data; c) temporarily storing generated trading ticket data at a data store of the service data centre; d) transmitting trading data over a packet-switched communications network to one or more trading party sites remote to the data centre, each trading party site comprising at least one user terminal running a hypermedia browser application; and e) presenting, to users of the terminals, hypermedia user interface components comprising trading data received from the trading computer. According to a third aspect of the present invention, there is provided a service data centre for processing and communicating trading data for trading financial instruments, the data centre comprising: a) a trading computer arranged to process trading data and to generate trading ticket data in respect of confirmed trades on the basis of trading data; b) a hypermedia server arranged to communicate with the trading server, the hypermedia server comprising a hypermedia user interface generation component for generating hypermedia content for presenting trading data to a user; and c) a data store accessible to the trading server for temporarily storing trading ticket data records; wherein the hypermedia server is arranged to publish trading data and trading ticket data, for communication from the trading computer to one of one or more trading party sites remote to the data centre, to an information channel identifying the trading party site using a publish and subscribe protocol. According to a fourth aspect of the present invention, there is provided a trading party site for communicating and presenting trading data for trading financial instruments, the trading party site comprising: a) a computer for receiving trading data and trading ticket data from a remote service data centre; and b) at least one user terminal running a hypermedia browser application, the terminal being arranged to present to a user hypermedia user interface components comprising received trading data; wherein the computer is arranged to subscribe to an information channel identifying the trading party site, to receive trading data and trading ticket data from the remote service data centre, using a publish and subscribe protocol. Advantageously, the present invention allows for the business logic components for implementing the trading system to be located at a central server of a service provider remote from the user terminals of the service consumers and, thus, management of business logic components (such as handling upgrades, failures and so on) may be handled by the service provider at a central site without inconveniencing the service consumer. A further or alternate advantage of the present invention is that commercially sensitive trading data and trading ticket data may be securely transferred to the appropriate service consumer for storage or processing. In particular, trading data and trading ticket data may be “pushed” to the appropriate service consumer outside the context of a client/server request-response transaction. A further or alternate advantage of the present invention is that service consumers only require a lightweight data processing infrastructure and can mainly use standard commercial products to access the service. According to a fifth aspect of the present invention, there is provided a system for communicating real-time conversational trading data for trading financial instruments, the system comprising a) a first user terminal associated with a trading party and comprising: i) a real-time conversational trading data communication component; and ii) a hypermedia user interface component for receiving from a user real-time conversational trading data for transmission to a user terminal associated with a counterparty using the conversational trading data communication component and for presenting to a user real-time conversational trading data received by the real-time conversational trading data communication component from the user terminal associated with the counterparty. b) a second user terminal associated with a trading counterparty and comprising: i) a real-time conversational trading data communication component; and ii) a hypermedia user interface component for receiving from a user real-time conversational trading data for transmission to a user terminal associated with a trading party using the conversational trading data communication component and for presenting to a user real-time conversational trading data received by the real-time conversational trading data communication component from the user terminal associated with the trading party.; and c) a communications network connecting the first and second user terminals for communicating real-time conversational trading data. According to a sixth aspect of the present invention, there is provided a method of communicating real-time conversational trading data for trading financial instruments, the method comprising the steps of: a) communicating real-time conversational trading data between a user terminal associated with a trading party and a user terminal associated with a counterparty; and b) presenting, at one of the user terminals, a hypermedia user interface component comprising real-time conversational trading data received from the other user terminal or for transmission to the other user terminal. According to a seventh aspect of the present invention, there is provided a user terminal associated with a trading party, the terminal being for communicating trading data for trading financial instruments, the user terminal comprising: a) a trading data communication component for communicating trading data with a user terminal associated with a counterparty; and b) a hypermedia user interface component for presenting to a user graphical user interface elements received from a remote hypermedia server, the graphical user interface elements comprising trading data received by the trading data communication component; wherein the trading data is communicated over a secure communications channel different the channel over which the graphical user interface elements are communicated. Computer programs and other apparatus are also provided. Further advantages will be apparent from the following description of the invention. There now follows, by way of example only, a detailed description of the present invention in which: |
Monoclonal antibody neutralising cathepsin b activity and uses thereof |
The present invention relates to a monoclonal antibody capable of neutralising cathepsin B. In particular, the present invention is concerned with the use of such an antibody for the detection or treatment of diseases associated with an over-expression and/or excessive activity of cathepsin B, such as cancer or arthritis. |
1. A monoclonal antibody directed against cathepsin B neutralising its enzymatic activity. 2. The antibody according to claim 1, wherein the antibody comprises murine variable regions and human constant regions (chimeric antibody). 3. The antibody according to claim 2, wherein monoclonal antibody heavy chain and light chain variable regions are as represented by SEQ ID NO: 2, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4. 4. The antibody according to claim 1, wherein the antibody is humanised. 5. The antibody according to claim 1, wherein the antibody is a mini-antibody. 6. A cell expressing the monoclonal antibody according to claim 1. 7. The cell according to claim 6, which was deposited on 17 May 2001 with Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ), under the accession No. DSM ACC2506. 8. A clone capable of stable production of the chimeric antibody according to claim 1, which was deposited on 06.03.2002 with Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ), under the accession No. DSM ACC2537. 9. A use of the antibody according to claim 1 for the treatment and/or diagnosing of a disease associated with an increased cathepsin B activity. 10. A use according to claim 9, wherein the increased activity is derived from an increased concentration of cathepsin B. 11. A use according to claim 9, wherein the disease is cancer or arthritis. 12. A pharmaceutical composition containing an antibody according to claim 1. 13. The antibody according to claim 1 for use in the treatment and/or diagnosing of a disease associated with an increased cathepsin B activity. 14. The antibody according to claim 13, wherein the activity derives from an increased concentration of cathepsin B. 15. The antibody according to claim 13, wherein the disease is cancer or arthritis. 16. Use of the antibody according to claim 1 for manufacturing a medicament for the treatment and/or diagnosing of a disease associated with an increased cathepsin B activity. 17. Use according to claim 16, wherein the increased activity derives from an increased concentration of cathepsin B. 18. Use according to claim 16, wherein the disease is cancer or arthritis. 19. The antibody according to claim 2, wherein the antibody is humanised. 20. The antibody according to claim 3, wherein the antibody is humanised. |
<SOH> BACKGROUND OF INVENTION <EOH>Lysosomal cysteine proteinase cathepsin B (Cat B) has been shown to participate in processes of tumour growth, invasion and metastasis (Kos, J. and Lah, T. T., Oncology Reports 5: 1349-1361, 1996). It has been shown that tumour cathepsin B can be translocated to the plasma membrane or secreted either as a pro-form or as an active enzyme from tumour cells where it seems to take part in the degradation of the components of extracellular matrix and basement membrane, which is deemed a crucial step in the metastatic process (Sloane et al., Biochemical and Molecular Aspects of Selected Cancers, T. G. Pretlow and T. P. Pretlow eds., Academic Press, New York, pp. 411-465, 1994). Cathepsin B activity is typically controlled by endogenous inhibitors of cysteine proteinases—such as the intracellular stefins A and B and extracellular cystatins, kininogens and α2-macroglobulin. It has been shown that the increased level of tumour cathepsin B is not balanced by a corresponding increase of cysteine proteinase inhibitors, which may lead to an uncontrolled proteolysis of the extracellular matrix. In clinical studies of breast, head and neck, colorectal and lung cancers, increased Cat B activity in the tumour tissue and increased protein concentration correlated with more aggressive tumour behaviour, early relapse and shorter overall survival (Kos, J. and Lah, T. T., Oncology Reports 5: 1349-1361, 1996). Significantly increased levels of Cat B have also been found in sera of patients with breast, colorectal, liver, pancreatic and melanoma cancers (Kos et al., Int. J. Biol. Markers, 15:84-89, 2000). On the other hand, a decrease in inhibitory ability was also proposed to account for an inadequate control of cathepsin B in cancer progression. For example, stefin A purified from human sarcoma exhibited a lower inhibitory activity as compared to liver stefin A (Lah et al., Biochim. Biophys. Acta 993: 63-73, 1989). In lung tumour tissue cathepsin B was more resistant to inactivation by E-64 than cathepsin B from control lung tissue (Krepela et al., Int. J. Cancer 61: 44-53, 1995). Additionally, cathepsin B from more metastatic lung cells exhibited different rates of inhibition by E-64 than the enzyme from less metastatic lung cancer cell lines (Spiess et al., J. Histochem. Cytochem. 42: 917-929, 1994). The level of cathepsin B/cystatin C complex was shown to be lower in sera of patients with lung and colorectal cancers compared to those with benign diseases or healthy controls (Zore et al., Biol. Chem. 382: 2001). At present it seems that in cancer patients the ability of endogenous inhibitors of cysteine proteinases to effectively balance an over-expression and/or an excessive activity of tumour associated cysteine proteinases is compromised. Yet, there is no direct evidence for tumour associated factors affecting the inhibition of cathepsin B in vivo, however, there are several in vitro studies reporting tumour associated post-translational modifications of cathepsin B, changes in pH stability, the presence of activators or the binding of glycosaminoglycans (GAGs), which all may change the conformation of cathepsin B active site and the consequent binding of the inhibitors (Zore et al., Biol. Chem. 382: 2001). It has also been reported (Kobayashi, H. et al. (1992) Cancer Research 52: 3610-3614) that membrane associated cathepsin B may play an indirect role in cancer invasion, activating pro-uPA. In this paper it was not demonstrated that the polyclonal antibody neutralises cathepsin B endopeptidase activity and, consequently, the invasion of tumour cells. A polyclonal antibody was used without proven inhibitory activity against cathepsin B. Since cysteine proteinase inhibitors could provide a therapeutic tool for the treatment of cancer, various natural protein inhibitors as well as their synthetic analogues have been prepared and tested for anti-tumour effect. Unfortunately, the specificity of natural inhibitors is not limited to one particular enzyme. Further, small synthetic inhibitors, reversible and irreversible, proved to be cytotoxic at higher concentrations. Consequently, there exists a need for additional tools for treating cancer and other disorders associated with over-expression and/or excessive activity of cathepsin B such as arthritis, autoimmune diseases, asthma, neurodegenerative disorders, periodontal disease, muscular dystrophy, osteoporosis, etc. |
<SOH> SUMMARY OF INVENTION <EOH>In the course of the extensive studies leading to the present invention, the inventors have found that neutralising monoclonal antibodies directed against cathepsin B provide an intriguing opportunity for specific inhibition of said proteolytic activity of said enzyme. Consequently, according to a first aspect, the present invention provides for neutralising monoclonal antibodies directed against cathepsin B so as to impair its biological activity. According to another embodiment, the invention provides a monoclonal antibody recognizing cathepsin B and impairing its biological activity, wherein the antibody comprises murine variable regions and human constant regions (chimeric antibody). According to still another aspect, the present invention provides humanised monoclonal antibodies having the above traits. The present invention also provides polypeptide fragments comprising only a portion of the primary antibody structure, which possess one or more immunoglobulin activities (mini-antibodies). According to still another aspect, the present invention provides a hybridoma cell line expressing such a monoclonal antibody, which was deposited with Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ), Mascheroder Weg 1b, D-38124 Braunschweig, Germany on 17.5.2001 and received the accession No. DSM ACC2506. DSMZ has the status of International Depositary Authority according to Budapest Treaty. The present invention also provides for the use of antibodies described herein for the treatment and/or diagnosis of diseases associated with over-expression of cathepsin B and/or its excessive activity. Such diseases are in particular cancer or arthritis. |
Peptide vaccines against group a streptococci |
This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A Streptococcus (GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines. |
1. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:1. 2. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:2. 3. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:3. 4. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:4. 5. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:5. 6. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:6. 7. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:7. 8. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:8. 9. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:9. 10. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:10. 11. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:11. 12. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:12. 13. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:13. 14. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:14. 15. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:15. 16. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:16. 17. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:17. 18. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:18. 19. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:19. 20. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:20. 21. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:21. 22. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:22. 23. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:23. 24. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:24. 25. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:25. 26. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:26. 27. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:27. 28. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:28. 29. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:29. 30. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:30. 31. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:31. 32. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:32. 33. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:33. 34. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:34. 35. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:35. 36. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:36. 37. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:37. 38. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:38. 39. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:39. 40. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:40. 41. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:41. 42. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:42. 43. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:43. 44. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:44. 45. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:45. 46. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:46. 47. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:47. 48. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:48. 49. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:49. 50. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:50. 51. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:51. 52. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:52. 53. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:53. 54. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:54. 55. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:55. 56. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:56. 57. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:57. 58. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:58. 59. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:59. 60. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:60. 61. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:61. 62. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:62. 63. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:63. 64. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:64. 65. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:65. 66. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:66. 67. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:67. 68. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:68. 69. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:69. 70. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:70. 71. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:71. 72. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:72. 73. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:73. 74. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:74. 75. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:75. 76. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:76. 77. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:77. 78. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:78. 79. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:79. 80. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:80. 81. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:81. 82. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:82. 83. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:83. 84. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:84. 85. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:85. 86. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:86. 87. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:87. 88. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:88. 89. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:89. 90. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:90. 91. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:91. 92. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:92. 93. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:93. 94. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:94. 95. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:95. 96. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:96. 97. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:97. 98. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:98. 99. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:99. 100. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:100. 101. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:101. 102. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:102. 103. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:103. 104. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:104. 105. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:105. 106. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:106. 107. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:107. 108. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:108. 109. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:109. 110. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:110. 111. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:111. 112. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:112. 113. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:113. 114. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:114. 115. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:115. 116. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:116. 117. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:117. 118. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:118. 119. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:119. 120. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:120. 121. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:121. 122. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:122. 123. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:123. 124. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:124. 125. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:125. 126. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:126. 127. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:127. 128. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:128. 129. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:129. 130. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:130. 131. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:131. 132. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:132. 133. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:133. 134. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:134. 135. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:135. 136. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:136. 137. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:137. 138. A synthetic peptide consisting essentially of the amino acid sequence of SEQ ID NO:138. 139. A synthetic peptide consisting of an amino acid sequence of about 20-25 amino acids selected from within the about 45 amino-terminal amino acids of the M protein of a serotype of Group A Streptococcus (GAS), wherein the peptide is capable of eliciting an immune response to a serotype of GAS and does not elicit tissue cross-reactive antibodies. 140. The peptide of claim 139 wherein the immune response is induction of opsonic antibodies and/or anti-attachment antibodies. 141. A composition comprising one or more peptides selected from the group consisting of peptides consisting essentially of the amino acid sequences of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, and SEQ ID NO:138. 142. The composition of claim 141 wherein the amino acid sequences are SEQ ID NO:3, SEQ ID NO:14, and SEQ ID NO:32. 143. The composition of claim 141, wherein the composition is a mixture of peptides. 144. The composition of claim 141, wherein the composition is a polypeptide. 145. The composition of claim 141, wherein the composition is a protein. 146. The composition of claim 145, wherein the protein is chimeric. 147. The composition of claim 141, wherein the peptides are linked to a backbone. 148. The composition of claim 141, further comprising additional immune-stimulatory molecules. 149. The composition of claim 148 wherein the additional immune-stimulatory molecules are other GAS-based peptides. 150. The composition of claim 148 wherein the additional immune-stimulatory molecules are non-GAS vaccines/immunogens selected from the group consisting of Hemophilus influenza, pertussis, N. meningitidis, pneumococcus, and Influenzae. 151. The composition of claim 148 wherein the additional immune-stimulatory molecules are adjuvants. 152. The composition of claim 141, further comprising a vehicle or carrier. 153. A chimeric fusion protein comprising an amino acid sequence selected from one or more of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, and SEQ ID NO:138. 154. A composition comprising synthetic amino terminal peptides of streptococcal M proteins wherein the peptides elicit an immune response against multiple serotypes of GAS and do not elicit tissue cross-reactive antibodies. 155. The composition of claim 154 wherein the immune response is induction of opsonic antibodies and/or anti-attachment antibodies. 156. The composition of claim 154, wherein the serotypes are selected from emm1, emm2, emm3, emm4, emm11, emm12, emm22, emm28, emm77, emm89, st2967, emm6, emm82, emm43, emm75, emm33, emm92, emm5, emm94, emm73, emm18, emm58, emm59, emm101, or emm41. 157. The composition of claim 154, wherein the peptides have amino acid sequences selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 or SEQ ID NO:138. 158. A composition comprising peptides of about 20-25 amino acids selected from within the about 45 amino-terminal amino acids of M proteins of GAS wherein the composition is capable of eliciting an immune response against multiple serotypes of GAS and does not elicit tissue cross reactive antibodies. 159. The composition of claim 158 wherein the immune response is induction of opsonic antibodies and/or anti-attachment antibodies. 160. The composition of claim 158, wherein the peptides have the amino acid sequences of at least 2 or more of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, or SEQ ID NO:138. 161. A vaccine for Group A Streptococcus (GAS) comprising an immunogenic amount of peptide immunogens wherein the peptide immunogens are one or more peptides having an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 and SEQ ID NO:138. 162. The vaccine of claim 161 further comprising a pharmaceutically acceptable vehicle or carrier. 163. The vaccine of claim 161 further comprising other immune-stimulatory molecules. 164. The vaccine of claim 163 wherein the other immune-stimulatory molecules are an adjuvant 165. The vaccine of claim 163 wherein the other immune-stimulatory molecules are other GAS-based peptides. 166. The vaccine of claim 163 wherein the other immune-stimulatory molecules are other vaccines selected from the group consisting of Hemophilus influenza, pertussis, N. meningitidis, pneumococcus and Influenzae. 167. The vaccine of claim 161, wherein the vaccine is capable of eliciting functional opsonic antibodies and does not contain epitopes that cross-react with tissues. 168. The vaccine of claim 161 wherein the vaccine is effective in decreasing the nasopharyngeal reservoir of GAS when administered. 169. A vaccine comprising synthetic type-specific peptides from M proteins wherein the vaccine is effective against all relevant M serotypes of strep A wherein the relevant serotypes are those serotypes in a population distribution of epidemiological data which are about equal to or greater than 38% of the disease-causing isolates. 170. The vaccine of claim 169 wherein the relevant serotypes are 3 different serotypes. 171. The vaccine of claim 169 wherein the relevant serotypes are those serotypes in a population distribution of epidemiological data which are about equal to or greater than 65% of the disease-causing isolates. 172. The vaccine of claim 171 wherein the relevant serotypes are 10 different serotypes. 173. The vaccine of claim 169 wherein the relevant serotypes are those serotypes in a population distribution of epidemiological data which are about equal to or greater than 95% of the disease-causing isolates. 174. The vaccine of claim 173 wherein the relevant serotypes are 30 different serotypes. 175. A polypeptide comprising one or more amino acid sequences selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:3 1, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 and SEQ ID NO:138. 176. The polypeptide of claim 175, wherein the polypeptide is a fusion protein. 177. The polypeptide of claim 175, wherein the polypeptide is a conjugated structure. 178. The polypeptide of claim 177, wherein the sequences are conjugated to a backbone. 179. A fusion protein comprising a) one or more of the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 or SEQ ID NO:138; and b) amino acids linking the sequences. 180. A method for immunizing patients against multiple serotypes of Group A Streptococcus comprising administering a prophylactically effective amount of the Group A Streptococcus vaccine of claim 161. 181. The method of claim 180 wherein the administration is via injection. 182. The method of claim 180 wherein the administration is via a mucosal delivery method. 183. A diagnostic kit for detecting the presence of antibodies in a biological sample that specifically bind to a GAS serotype-specific peptide from an M protein which comprises a packaging, containing, separately packaged: (a) a solid phase capable of having attached thereto a peptide; and (b) a synthetic GAS serotype-specific M protein peptide that specifically reacts with antibodies specific for the synthetic GAS serotype-specific M protein peptide. 184. The kit of claim 183, wherein the synthetic GAS serotype-specific M protein peptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 and SEQ ID NO:138. 185. A method for detecting antibodies that bind to a synthetic GAS serotype-specific M protein peptide in a biological sample comprising the steps of: a) contacting a synthetic GAS serotype-specific M protein peptide with the biological sample suspected of containing GAS serotype-specific M protein peptide antibodies under conditions that allow for formation of an antibody-antigen complex; and b) detecting the antibody-antigen complex. 186. The method of claim 185, wherein the synthetic GAS serotype-specific M protein peptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 and SEQ ID NO:138. 187. A method for identifying and tailoring vaccines for a targeted organism for a given population of recipients comprising: a) identifying a population of recipients for the vaccine; b) gathering prevalence data on serotypes of the targeted organism from a sample within that population of recipients; c) choosing a set of the most prevalent serotypes from the gathered data; d) identifying proteins from the chosen serotypes responsible for evading opsonophagocytosis; e) identifying peptides of from about 20-25 amino acids within the identified proteins which elicit opsonic or anti-attachment antibodies against the chosen serotypes; f) synthesizing the identified peptides; and g) formulating a vaccine comprising the peptides identified in step e). 188. The method claim of 187 wherein the targeted organism is GAS. 189. An isolated antibody or fragments thereof wherein the isolated antibody or fragment thereof has binding affinity for the peptides selected from one or more of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ D NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ D NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137 and SEQ ID NO:138. 190. A method for detecting the presence of a serotype of GAS in a sample comprising contacting an antibody-containing sample with one or more of the peptides selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ D NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, and SEQ ID NO:138, and detecting binding of the antibody with the peptide(s). 191. A method for detecting the presence of a serotype of GAS in a sample comprising contacting the sample with an antibody which selectively binds with the peptides selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:;135, SEQ ID NO:136, SEQ ID NO:137,and SEQ ID NO:138, and detecting binding of the anitbody and antigen. 192. A method for diagnosing GAS or detecting the presence of GAS antibodies comprising binding a peptide selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26,SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO;99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:11, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO;119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, and SEQ ID NO:138 to a substrate,contacting the bound peptide with a sample, adding secondary antibodies which bind with the GAS antibodies and which are labeled or bound with a detectable moiety,visualizing the secondary antibody. 193. A method of treating GAS infection comprising administering a therapeutically effective amount of an isolated antibody generated by administering the peptides selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, and SEQ ID NO:138 to a subject. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Group A streptococci (GAS) are responsible for a wide variety of diseases. These range from uncomplicated pharyngitis to more serious invasive diseases such as necrotizing fasciitis (“flesh eating syndrome”) and streptococcal toxic shock syndrome. Additionally, approximately 3% of GAS infections that go untreated will result in acute rheumatic fever. (Brandt, E. R., Good, M. F. 1999. Vaccine strategies to prevent rheumatic fever. Immunol. Res. 19:89-103) All ages are susceptible to GAS attack, but those particularly vulnerable are the elderly, children under 2 years, and African Americans. (Emerging Infections Programs (EIP), supported by the National Center for Infectious Diseases for isolates resulting from active surveillance 1995-1997. California EIP: Arthur Reingold; Connecticut EIP: Matt Carter; Georgia EIP, Monica Farley; Minnesota EIP, Kristine MacDonald; Oregon EIP, Paul Cieslak; Centers for Disease Control and Prevention (CDC), K O'Brien, B. Beall, K Deaver-Robinson, R. Facklam, A. Kraus, A. Schuchat, B. Schwartz) Recently, there has been a significant increase in the number of streptococcal infections (Davies, H. D., McGeer, A., Schwartz, B., et al. 1996. Invasive group A streptococcal infections in Ontario, Canada. Ontario group A streptococcal study group. N. Engl. J. Med. 335:547-54) as well as rheumatic fever (Veasey, L. G., Wiedneier, S. W., Osmond, G. S., et al. Resurgence of acute rheumatic fever in the intermountain region of the United States. N. Engl. J. Med. 316:42-7). Based on recent active surveillance, it is estimated that there are approximately 8,500 cases and 1,300 deaths annually in the United States from invasive GAS disease, (EIP supported by the National Center for Infectious Diseases for isolates resulting from active surveillance 1995-1997. California EIP: Arthur Reingold; Connecticut EIP: Matt Carter; Georgia EIP, Monica Farley; Minnesota EIP, Kristine MacDonald; Oregon EIP, Paul Cieslak; CDC, K. O'Brien, B. Beall, K. Deaver-Robinson, R. Facklam, A. Kraus, A. Schuchat, B. Schwartz). A vaccine against GAS could eliminate millions of dollars in health care costs and numerous physician visits. There are a number of strategies that have been used towards designing an effective streptococcal vaccine (Salvadori, L. G., Blake, M. S., McCarty, M., Tai, J. Y., Zabriskie, J. B. 1995. Group A streptococcus -liposome ELISA antibody titers to group A polysaccharide and opsonophagocytic capabilities of the antibodies. J. Infect. Dis. 171:593-600; Ji, Y. Carlson, B., Kondagunta, A., Cleary, P. P. 1997. Intranasal immunization with C5a peptidase prevents nasopharyngeal colonization of mice by group A streptococcus. Infect Immun. 65:2080-2087; Kapur, V. Maffei, J. T., Greer R. S., Li, L. L., Adams, G. J., Musser, J. M. 1994. Vaccination with streptococcal cysteine protease protects mice against challenge with heterologous group A streptococci. Microb. Pathogenesis. 16:443450; Dale, J. B., Baird, R. W., Courtney, H. S., Hasty, D. L., Bronze, M. S. 1994. Passive protection of mice against group A streptococcal pharyngeal infection by lipoteichoic acid. J. Infect. Dis. 169:319-323; Dale, J. B., Washburn, R. G., Marques, M. B., Wessels, M. R. 1996. Hyuaronated capsule and surface M protein in resistance to opsonization of group A streptococci. Infect. Immun. 64:1495-1501; Fischetti, V. A. 1989. Streptococcal M protein: molecular design and biological behavior. Clin. Microbiol. 2:285-314; Lancefield, R. C. 1962. Current knowledge of the type-specific M antigens of group A streptococci. J. Immun. 89:307-313; Lancefield, R. C. 1959. Persistence of type-specific antibodies in man following infection with group A streptococci. J. Exp. Med. 110:271-283). There are difficulties associated with a vaccine strategy involving the M protein, such as the large number of serologic M (emm) types (over 100 serotypes) and the observation that some M proteins contain epitopes that cross-react with human tissues. In addition to the large number of serotypes, every population has a different subset of GAS serotypes which are the most prevalent. In order to deal with these difficulties, different approaches have been tried. For example, observation that the M protein's C-terminus is conserved while the N-terminus is variable has led some workers to try to focus on the C-terminus for broader protection and others to focus on the N-terminus where the most variability is. Even though some M protein-based vaccines have been designed, for the above reasons, a need still exists for a flexible, effective, multivalent GAS vaccine. |
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