Methods for identifying compounds which lower Axcex2 levels by acting through the Wnt signal transduction pathway are disclosed.

This invention relates to methods and compounds for treating Alzheimer""s disease.
Most current thinking about Alzheimer""s disease suggests that the dementia characteristic of the disease results from aggregates formed in the brains of afflicted individuals. The aggregates are thought to be formed by a peptide of 40-43 amino acids called Axcex2, which is derived from the amyloid precursor protein.
The Axcex2 peptide is normally found in trace amounts in blood and in cerebrospinal fluid. However, it can be found in increased levels in these fluids in patients suffering from some forms of Alzheimer""s disease, and it is thought that increased concentrations of the Axcex2 peptide in these fluids contribute to its tendency to form aggregates. Because Alzheimer""s disease can take many years to become clinically manifest, it is believed that over time even very small increases in circulating or cerebral spinal fluid Axcex2 levels may be damaging.
We have discovered that the addition of Wnt1 protein to Axcex2 peptide-producing cells affects the levels of Axcex2 peptide produced by these cells. Accordingly, the invention features methods of screening for compounds able to bind to the Wnt receptor and decrease the amount of Axcex2 peptide produced by these cells. The invention also features methods for treating Alzheimer""s disease using compounds able to bind to the Wnt receptor and lower the amount of Axcex2 peptide produced.
In one aspect, the invention features a method of identifying a compound that inhibits expression of an Axcex2 peptide by contacting the compound with a Wnt receptor or a Wnt-binding fragment of Wnt receptor and determining the ability of the compound to bind to the Wnt receptor or Wnt-binding fragment of Wnt receptor. The binding of the compound is an indication that the compound lowers the level of Axcex2 peptide.
In one embodiment, the compound is a mammalian Wnt protein or a Wnt-receptor binding fragment of a mammalian Wnt protein, e.g., a human Wnt1 protein or a Wnt1-receptor binding fragment thereof. In another embodiment, the compound is a peptide mimetic of a Wnt protein. In yet another embodiment, the compound is a non-peptide mimetic of a Wnt protein.
In another aspect, the invention features a method of identifying a compound that inhibits expression of Axcex2 peptide by contacting a cell producing detectable levels of Axcex2 peptide with a Wnt antagonist and measuring the amount of Axcex2 peptide produced. A decrease in the amount of Axcex2 peptide produced by cell in the presence of the Wnt antagonist indicates that the Wnt antagonist is a compound that decreases Axcex2 peptide expression. The Wnt antagonist can include, e.g., a cysteine-rich domain (CRD)-containing fragment of the Wnt-receptor or the Fritz protein.
In another aspect, the invention features a method of identifying a compound that inhibits expression of Axcex2 peptide by (a) culturing a cell expressing a Wnt-receptor and Axcex2 peptide in the presence of the compound; and (b) evaluating the expression of Axcex2 peptide by the cell. A lowered level of Axcex2 peptide relative to a control cell indicates the compound inhibits expression of Axcex2 peptide.
In yet another aspect, the invention features a method of evaluating a compound for the ability to lower Axcex2 peptide levels in a mammal by contacting the compound with Wnt or a Wnt receptor-binding fragment of Wnt and Wnt-receptor or a Wnt binding fragment of Wnt receptor and determining the ability of the compound to enhance the binding of the Wnt or a Wnt receptor-binding fragment of Wnt with the Wnt receptor or a Wnt-binding fragment of Wnt receptor. An increase in the binding in the presence of the compound compared to the binding in the absence of the compound indicates that the compound lowers extracellular Axcex2 levels.
In a further aspect, the invention features a method for identifying candidate therapeutic agents for the treatment of Alzheimer""s disease by (a) providing a cell which expresses a mammalian Wnt receptor, the cell comprising a reporter construct, the reporter construct comprising a sequence encoding a detectable protein, the sequence encoding the detectable protein being operably linked to a Wnt receptor responsive regulatory element; (b) contacting the cell with a test compound; (c) measuring the expression of the detectable protein in the presence of the test compound. An increase in the expression of the detectable protein in the presence of the test compound compared to the absence of the test compound indicates that the test compound is a candidate therapeutic agent for treatment of Alzheimer disease.
In one embodiment, the detectable protein is xcex2-lactamase, chloramphenicol acetyltransferase (CAT), adenosine deaminase (ADA), aminoglycoside phosphotransferase (neor, G418r), dihydrofolate reductase (DHFR), hygromycin-B-phosphotransferase (HPH), thymidine kinase (TK), lacZ (encoding xcex2-galactosidase), or xanthine guaninephosphoribosyltransferase (XGPRT). The reporter gene can be alkaline phosphatase.
In another aspect, the invention features a method of inhibiting Axcex2 expression in a cell by identifying a Wnt-responsive cell that expresses Axcex2 peptide and contacting the cell with a compound that binds to Wnt, or to a Wnt receptor. The binding of the compound to Wnt inhibits Axcex2 expression by the cell.
The cell can be in a mammal, e.g., in vivo, or can be a cultured cell, i.e., in vitro. The compound can inhibit secretion of Axcex2 peptide from the cell, or can inhibit intracellular accumulation of Axcex2 from the cell.
Preferably, the Wnt protein is a Wnt1 protein.
In another aspect the invention features a method of inhibiting Axcex2 expression in a cell by identifying a Wnt-responsive cell that expresses Axcex2 peptide, and contacting the cell with a compound that binds to a Wnt receptor, wherein binding of the compound to the Wnt receptor inhibits Axcex2 expression by the cell.
In a further aspect, the invention features a method of treating Alzheimer""s disease by introducing into a human suspected of needing treatment for Alzheimer""s disease an effective amount of a compound binding to the human Wnt receptor. Binding of the compound is associated with decreased levels of Axcex2 polypeptide levels in the patient.
In a still further aspect, the invention features a method of preventing Alzheimer""s disease by introducing into a human indicating as needing prophylactic treatment for Alzheimer""s disease an effective amount of a compound characterized by binding to the human Wnt receptor.
In a further aspect, the invention features a method of lowering Axcex2 peptide levels in an mammal by administering a compound characterized by binding to a Wnt receptor in an amount sufficient to lower Axcex2 peptide levels.
An xe2x80x9cAxcex2 peptidexe2x80x9d includes an extracellular fragment of the xcex2 amyloid precursor protein that is 40-43 amino acids in length and is detected extracellularly.
A xe2x80x9cWnt proteinxe2x80x9d includes a member of the Wnt family of proteins.
A xe2x80x9cWnt receptorxe2x80x9d includes a macromolecule, e.g., a protein, able to confer responsiveness to a Wnt ligand when expressed on the surface of a cell.
A xe2x80x9cpeptide mimeticxe2x80x9d includes a Wnt analog in which one or more peptide bonds have been replaced with an alternative type of covalent bond which is not susceptible to cleavage by peptidases.
A xe2x80x9cWntxe2x80x9d antagonist is a compound that inhibits the activity of a Wnt protein.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.
The present invention is based on the discovery that the Wnt protein, when added to cells that secrete Axcex2 peptide, affects the amount of Axcex2 peptide secreted by these cells.
The Wnt protein is a secreted protein encoded by a family of conserved genes that have been identified as both proto-oncogenes and as having functions important in development (reviewed in Nusse et al., Cell 69:1073, (1992)).
The Wnt protein is thought to act through cellular receptors encoded by members of the frizzled gene family. A receptor protein able to confer responsiveness to Wg, the homolog of Wnt in Drosophila melanogaster, is encoded by the frizzled2 locus (xe2x80x9cDfz2xe2x80x9d) (Bhanot et al., Nature 382:224 (1996); see also Roush, Science 273:309 (1996)). The full-length Dfz2 cDNA (SEQ ID NO:1) and amino acid sequence (SEQ ID NO:2) are shown in Table 1.
Dfz2 is a member of the frizzled (""fz) gene family, which is found in a wide variety of eukaryotes (Wang et al., J. Biol. Chem. 271:4468 (1996)). The Dfz2 gene has sequence features characteristic of this family: an amino terminal signal sequence precedes a domain characterized by ten invariant cysteine residues (the cysteine rich domain, or
xe2x80x9cCRDxe2x80x9d). The CRD is followed by a highly divergent region of 40-100 mainly hydrophilic residues encoding seven putative membrane-spanning segments (Bhanot et al.).
The present invention provides methods of screening for compounds that are able lower the levels of Axcex2 peptide by acting via the Wnt-receptor protein, and for methods of treating Alzheimer""s disease using these compounds. One way to identify compounds able to lower Axcex2 peptide levels is based on the interaction of the compound with the Wnt receptor, and/or compounds which activate other members of the Wnt signal transduction pathway.
Methods of Screening for Wnt-Receptor Binding Compounds Able To Lower Axcex2 Levels
Compounds able to lower levels of Axcex2 peptide can be identified based on their interaction with a Wnt receptor or a Wnt-binding fragment of a Wnt receptor.
Screening assays can be performed with a Wnt receptor, or a Wnt-binding fragment of a Wnt receptor. The Wnt receptor protein can be a member of the frizzled protein family, such as those described in Barnot et al., above. The screening assays can also be performed using the mammalian frizzled sequences Hfz5 (human), mouse Mfz4, Mfz7, or Mfz8 (mouse), or on cells expressing frizzled sequences. The nucleic acid sequences and predicted amino acid sequences of Hfz5, Mfz4, Mfz7, or Mfz8 are shown in Tables 2-5.
When the Wnt receptor is a frizzled protein, a Wnt-binding fragment of the receptor can include the CRD domain of a frizzled protein, e.g., the fragments summarized in FIG. 2 of Mayr et al., Mech. Dev. 63:109-125, 1997. These fragments include amino acids 1-264 (SEQ ID NO:15) of the human Hfz5 amino acid sequence shown in Table 2.
The Wnt receptor can alternatively be a member of the Notch family of proteins. Genetic and biochemical
studies have implicated products of the Notch locus as being involved in the reception of Wnt signals (Couso et al., Cell 79:259 (1994); Axelrod et al., Science 271:1826 (1996). When Notch family members are used, calcium may be added in the medium to facilitate binding (Ingham, Trends Genet. 12:382, 384 (1996)).
One way the Wnt receptor protein can be provided is on a cell responsive to Wnt. Several such cell lines are known, e.g., PC12 pheochromocytoma cells and C57MG mammary carcinoma cells.
Alternatively, the Wnt receptor can be introduced into a cell that is otherwise not responsive to Wnt using methods known in the art, e.g., as a polypeptide or by introducing cDNA encoding a Wnt receptor into an appropriate cell. Thus, the source of Wnt-responsive cell is not critical when compounds are screened using cell-based assays. For example, Barnot et al., supra, have demonstrated that the Dfz2 protein confers Wg-responsiveness on Drosophila S2 cells and human embryonic kidney cells.
Candidate compounds can be screened for binding to the Wnt receptor using methods known in the art. Binding may be assessed by examining compounds for the ability to stimulate the Wnt signal transduction pathway, e.g., by assessing stabilization of proteins in the xcex2-catenin family as is described in Bahnot et al. for the armadillo (Arm) protein. Another way in which Wnt activity can be assessed by measuring activation of the T cell factor lymphoid enhancer factor (TcF-Lef) (Behrens et al., Nature 382:638-42, 1996).
In some situations it may be desirable to first screen candidate compounds for direct binding to the Wnt receptor, or Wnt-binding fragments thereof, such as the CRD domain, in vitro, e.g., in a gel mobility shift assay and/or an immunoprecipitation assay, and then test Wnt-receptor binding proteins for the ability to lower Axcex2 levels in a subsequent step.
Levels of Axcex2 peptide can be measured using methods well-known in the art, e.g., the methods described in Haass et al., Nature 359:322-25, (1992).
The assays described herein are designed to identify compounds that interact with (e.g., bind to) a Wnt receptor. These compounds can include, but are not limited to, those that interact with members of the frizzled family, These compounds can also include those that interact with (e.g., bind to) intracellular proteins that interact with Wnt (including, but not limited to, the Wnt receptor) compounds that interfere with the interaction of Wnt with transmembrane or intracellular proteins involved in Wnt-mediated signal transduction, e.g., proteins analogous to the dishelved and Arm gene products, and to compounds that modulate the activity of a Wnt receptor gene (i.e., modulate the level of Wnt receptor gene expression). Assays can additionally be utilized which identify compounds that bind to Wnt receptor gene regulatory sequences (e.g., promoter sequences) and which may modulate Wnt receptor gene expression.
The compounds can also be those resembling, e.g., having homology to, the Wnt receptor, or fragments thereof, e.g., fragments containing the CRD-domain. Some examples of CRD domain-containing polypeptides are amino acids 1-348 (SEQ ID NO:16) of the Df2z homolog (SEQ ID NO:2) and amino acids 1-264 (SEQ ID NO:15) of the human Hfz5 homolog. An example of a compound of this type is the human Fritz protein (SEQ ID NO:14), which is a secreted protein having homology to the CRD-domain found in members of the frizzled family, and which has been reported to antagonize Wnt function (Lin et al., Proc. Natl. Acad. Sci. (USA) 94:11196-11200 (1997); Mayr et al., Mec. Dev. 63: 109-25 (1997)). Nucleic acids encoding human and mouse Fritz sequences, and the predicted amino acid sequences encoded by these sequences, are shown in Tables 6 and 7, respectively.
In general, compounds that can be screened in accordance with the invention include, but are not limited to polypeptides, peptides, antibodies and fragments thereof, and other organic compounds (e.g., peptidomimetics) that bind to the extra-cellular domain or cysteine-rich domain of a Wnt receptor and either mimic the activity triggered by the natural ligand (i.e., agonists) or inhibit the activity triggered by the natural ligand (i.e., antagonists); as well as peptides, antibodies or fragments thereof, and other organic compounds that binding to Wnt.
Such compounds can include, but are not limited to, peptides such as, for example, soluble peptides, including but not limited to members of random peptide libraries; (see, e.g., Lam, et al., Nature 354:82-84, 1991; Houghten, et al., Nature 354:84-86, 1991), and combinatorial chemistry-derived molecular library made of D- and/or L-configuration amino acids, phosphopeptides (including, but not limited to, members of random or partially degenerate, directed phosphopeptide libraries; see, e.g., Songyang, Z. et al., 1993, Cell limited to, polyclonal, monoclonal, humanized, anti-idiotypic, chimeric or single chain antibodies, and Fab, F(abxe2x80x2)2 and Fab expression library fragments, and epitope-binding fragments thereof), and small organic or inorganic molecules.
Other compounds that can be screened in accordance with the invention include but are not limited to small organic molecules that are able to cross the blood-brain
barrier, gain entry into an appropriate cell (e.g., a neuron, glial cell, microglial cell, or endothelial cell) and affect the expression of a gene involved in the Wnt signal transduction pathway (e.g., by interacting with the regulatory region or transcription factors involved in gene expression); or such compounds that affect the activity of Wnt protein to the Wnt receptor (e.g., by inhibiting or enhancing the enzymatic activity of the CD) or the activity of some other intracellular factor involved in the Wnt signal transduction pathway, such as, e.g., disheveled or delta-catenin.
Computer modelling and searching technologies permit identification of compounds, or the improvement of already identified compounds, that can modulate Wnt expression or activity. Having identified such a compound or composition, the active sites or regions are identified. Such active sites might typically be ligand binding sites, such as the interaction domains of Wnt with the Wnt receptor. The active site can be identified using methods known in the art including, for example, from the amino acid sequences of peptides, from the nucleotide sequences of nucleic acids, or from study of complexes of the relevant compound or composition with its natural ligand. In the latter case, chemical or X-ray crystallographic methods can be used to find the active site by finding where on the factor the complexed ligand is found.
Next, the three dimensional geometric structure of the active site is determined. This can be done by known methods, including X-ray crystallography, which can determine a complete molecular structure. On the other hand, solid or liquid phase NMR can be used to determine certain intra-molecular distances. Any other experimental method of structure determination can be used to obtain partial or complete geometric structures. The geometric structures can be measured with a complexed ligand, natural or artificial, which may increase the accuracy of the active site structure determined.
If an incomplete or insufficiently accurate structure is determined, the methods of computer based numerical modelling can be used to complete the structure or improve its accuracy. Any recognized modelling method may be used, including parameterized models specific to particular biopolymers such as proteins or nucleic acids, molecular dynamics models based on computing molecular motions, statistical mechanics models based on thermal ensembles, or combined models. For most types of models, standard molecular force fields, representing the forces between constituent atoms and groups, are necessary, and can be selected from force fields known in physical chemistry. The incomplete or less accurate experimental structures can serve as constraints on the complete and more accurate structures computed by these modeling methods.
Finally, having determined the structure of the active site, either experimentally, by modeling, or by a combination, candidate modulating compounds can be identified by searching databases containing compounds along with information on their molecular structure. Such a search seeks compounds having structures that match the determined active site structure and that interact with the groups defining the active site. Such a search can be manual, but is preferably computer assisted. Compounds found from this search are potential Wnt modulating compounds.
Alternatively, these methods can be used to identify improved modulating compounds from an already known modulating compound or ligand. The composition of the known compound can be modified and the structural effects of modification can be determined using the experimental and computer modelling methods described above applied to the new composition. The altered structure is then compared to the active site structure of the compound to determine if an improved fit or interaction results. In this manner, systematic variations in composition, such as by varying side groups, can be quickly evaluated to obtain modified modulating compounds or ligands of improved specificity or activity.
Further experimental and computer modeling methods useful to identify modulating compounds based upon identification of the active sites of Wnt, the Wnt receptor, Wnt, and related transduction and transcription factors will be apparent to those of skill in the art.
Examples of molecular modelling systems are the CHARMm and QUANTA programs (Polygen Corporation, Waltham, Mass.). CHARMm performs the energy minimization and molecular dynamics functions. QUANTA performs the construction, graphic modelling and analysis of molecular structure. QUANTA allows interactive construction, modification, visualization, and analysis of the behavior of molecules with each other.
A number of articles review computer modelling of drugs interactive with specific proteins, such as Rotivinen, et al., 1988, Acta Pharmaceutical Fennica 97:159-166; Ripka, New Scientist 54-57 (Jun. 16, 1988); McKinaly and Rossmann, 1989, Annu. Rev. Pharmacol. Toxiciol. 29:111-122; Perry and Davies, OSAR: Quantitative Structure-Activity Relationships in Drug Design pp. 189-193 (Alan R. Liss, Inc. 1989); Lewis and Dean, 1989, Proc. R. Soc. Lond. 236:125-140 and 141-162; and, with respect to a model receptor for nucleic acid components, Askew et al., 1989, J. Am. Chem. Soc. 111:1082-1090. Other computer programs that screen and graphically depict chemicals are available from companies such as BioDesign, Inc. (Pasadena, Calif.), Allelix, Inc. (Mississauga, Ontario, Canada), and Hypercube, Inc. (Cambridge, Ontario). Although these are primarily designed for application to drugs specific to particular proteins, they can be adapted to design of drugs specific to regions of DNA or RNA, once that region is identified.
Although described above with reference to design and generation of compounds which could alter binding, one could also screen libraries of known compounds, including natural products or synthetic chemicals, and biologically active materials, including proteins, for compounds which are inhibitors or activators.
Compounds identified through the assays described herein may be useful, for example, in lowering extracellular Axcex2 levels, and in treating Alzheimer""s disease.
Methods of Lowering Axcex2 Peptide Levels
The methods of the invention are useful in treating diseases characterized by high levels of Axcex2 peptide, e.g., Alzheimer""s disease. The invention provides methods of lowering Axcex2 levels by administering compounds, such as those discussed above, which interact with the Wnt protein and/or the Wnt receptor, or members of the Wnt signal transduction pathway to lower Axcex2 levels.
The term xe2x80x9cfragmentxe2x80x9d, as applied to a peptide, will ordinarily be at least about 10 amino acids, usually about 20 contiguous amino acids, preferably at least 40 contiguous amino acids, more preferably at least 50 contiguous amino acids, and most preferably at least about 60 to 80 or more contiguous amino acids in length. Such peptides can be generated by methods known to those skilled in the art, including proteolytic cleavage of the protein, de novo synthesis of the fragment, or genetic engineering.
Peptide analogs can differ from the native peptides of a Wnt protein by amino acid sequence, or by modifications which do not affect the sequence, or by both. Peptide analogs can have sequences which differ from the wild-type sequence (i.e., the sequence of the homologous portion of the naturally occurring peptide) only by conservative amino acid substitutions, preferably by only one, two, or three, substitutions, for example, substitution of one amino acid for another with similar characteristics (e.g., valine for glycine, arginine for lysine, etc.) or by one or more non-conservative amino acid substitutions, deletions, or insertions which do not abolish the peptide""s biological activity.
Modifications (which do not normally alter primary sequence) include in vivo or in vitro chemical derivitization of peptides, e.g., acetylation or carboxylation. Also included are modifications of glycosylation, e.g., those made by modifying the glycosylation patterns of a peptide during its synthesis and processing or in further processing steps, e.g., by exposing the peptide to enzymes which affect glycosylation e.g., mammalian glycosylating or deglycosylating enzymes. Also included are sequences which have phosphorylated amino acid residues, e.g., phosphotyrosine, phosphoserine, or phosphothreonine.
The invention includes analogs in which one or more peptide bonds have been replaced with an alternative type of covalent bond (a xe2x80x9cpeptide mimeticxe2x80x9d) which is not susceptible to cleavage by peptidases. Where proteolytic degradation of the peptides following injection into the subject is a problem, replacement of a particularly sensitive peptide bond with a noncleavable peptide mimetic will make the resulting peptide more stable and thus more useful as a therapeutic. Such mimetics, and methods of incorporating them into peptides, are well known in the art. Similarly, the replacement of an L-amino acid residue is a standard way of rendering the peptide less sensitive to proteolysis. Also useful are amino-terminal blocking groups such as t-butyloxycarbonyl, acetyl, theyl, succinyl, methoxysuccinyl, suberyl, adipyl, azelayl, dansyl, benzyloxycarbonyl, fluorenylmethoxycarbonyl, methoxyazelayl, methoxyadipyl, methoxysuberyl, and 2,4,-dinitrophenyl. Blocking the charged amino- and carboxy-termini of the peptides would have the additional benefit of enhancing passage of the peptide through the hydrophobic cellular membrane and into the cell.
Modification of these peptides to improve penetration of the blood-brain barrier would also be useful. Peptides may be altered to increase lipophilicity (e.g. by esterification to a bulky lipophilic moiety such as cholesteryl) or to supply a cleavable xe2x80x9ctargetorxe2x80x9d moiety that enhances retention on the brain side of the barrier (Bodor et al., Science 1992, vol. 257, pp. 1698-1700). Alternatively, the peptide may be linked to an antibody specific for the transferrin receptor, in order to exploit that receptor""s role in transporting iron across the blood-brain barrier (Friden et al., Science, 1993, vol. 259, pp. 373-377).
Peptides may be administered to the patient intravenously in a pharmaceutically acceptable carrier such as physiological saline. Standard methods for intracellular delivery of peptides can be used, e.g. delivery via liposomes. Such methods are well known to those of ordinary skill in the art. The formulations of this invention are useful for parenteral administration, such as intravenous, subcutaneous, intramuscular, and intraperitoneal.
Therapeutic administration of a peptide intracellularly can also be accomplished using gene therapy, wherein a nucleic acid which includes a promoter operatively linked to a sequence encoding a heterologous peptide is used to generate high-level expression of the peptide in cells transfected with the nucleic acid. DNA or isolated nucleic acid encoding peptides of the invention may be introduced into cells of the patient by standard vectors and/or gene delivery systems. Suitable gene delivery systems may include liposomes, receptor-mediated delivery systems, naked DNA, and viral vectors such as herpes viruses, retroviruses, and adenoviruses, among others.
Pharmaceutically acceptable carriers are biologically compatible vehicles which are suitable for administration to an animal: e.g., physiological saline. A therapeutically effective amount is an amount of the nucleic acid of the invention which is capable of producing a medically desirable result in a treated animal.
As is well known in the medical arts, dosages for any one patient depends upon many factors, including the patient""s size, body surface area, age, the particular compound to be administered, sex, time and route of administration, general health, and other drugs being administered concurrently. Dosages for the compounds of the invention will vary, but a preferred dosage for intravenous administration is from approximately 106 to 1022 copies of the nucleic acid molecule in the case of gene therapy.

Methods and compounds for treating alzheimer""s disease


The final-hardcopy operating facility, xe2x80x9ctarget facilityxe2x80x9d, converts the content provider""s original data file to a different color space to form a proofing data file. A proofing facility, which is distinct from the target facility, uses the proofing file to produce a visible proof for viewing by the content provider, customer etc. A common proofing file is applied to both preparing the proof and printing the final hardcopy. Because it is the target facility rather than the content provider or the proofing facility that prepares the proofing file, using maximum available knowledge about the printing equipment which will be used and its color characterization and other technical behavior, this approach gives maximum assurance that the final hardcopy will represent the proof as accurately as practical.

This invention relates generally to machines and procedures for printing a document hardcopy at a target printer facility based upon information in an image data file; and more particularly for producing an accurate color proof at a distinct proofing facility. In general the target and proofing facilities are mutually remote, but a more important characteristic for purposes of the invention is that the two facilities be distinct in organizational or business terms.
The invention may be especially useful when either the hardcopy or the proof is produced by incremental printingxe2x80x94i.e. by a swath-based scanning machine and method, or by a pagewide-array machine and method, that construct text or images from individually computer-controlled placement of dots on a printing medium. Although the invention may be practiced using any of a great many different kinds of final-hardcopy printing devices and preliminary proof-producing devices, one kind of proofing device of particular interest is the Hewlett Packard line of large-format printers; exemplary description of these machines appears in U.S. utility-patent application Ser. No. 09/516,323, later issued as U.S. Pat. No. 6,312,098.
(a) Purpose of Proofing; Traditional Methods
A xe2x80x9cproofxe2x80x9d is a visible simulation of the appearance of an anticipated eventual hardcopy. A proof is not just a data file and traditionally is most often not associated with a data file. The general purpose of a proof is to enable printing customers and others to have a preliminary look at how the hardcopy will later appear.
Traditionally a printing facility is a unitary, integrated entity that performs essentially all functions related to a print job under one roof or at least within the scope of operations of a single commercial enterprise. The printing facility""s customer, or sometimes a graphic artist or other intermediary on behalf of the customer, brings the job to the printing facility in the form of materials with written or verbal instructions for execution.
In earlier decades, any artwork that was to appear in the finished hardcopy was most usually handed to the printer in the form of so-called xe2x80x9ccamera-ready copyxe2x80x9dxe2x80x94that is to say, finished art ready for the printer to photograph, so as to make offset-lithographic negatives and plates or even the earlier letterpress engravings. Any text was most commonly provided in the form of manuscript or so-called xe2x80x9ccopyxe2x80x9d, which the printer would assign to a typesetter for preparation of typeset computerized or linotype galleys.
Somewhat more recently, and particularly in the case of high artistic-quality work, an intermediary such as a graphic artist might provide artwork to the printer in the form of already-prepared color-separation negatives or even color-separation plates (or engravings). An intermediary might similarly provide text in the form of computer tapes representing the copy already keyboarded. Although some such efforts represent an effort by the customer or intermediary to control costs, more commonly both these trends are primarily in the interest of more-nearly controlling the quality and accuracy of the ultimate finished product.
The printing facility proceeds with preparations, but pauses before actually producing the final hardcopy. At that point the facility xe2x80x9cshows a proofxe2x80x9d to the customer or intermediary, to enable that person to seexe2x80x94as accurately as possible or practicalxe2x80x94how the job will turn out.
Perhaps most typically to see the proof the customer goes physically to the printing facility where the final job will be done, and where the customer can be side-by-side with that facility""s makeready people for a crucial conference about all the details, and the prospects for a satisfactory completion of the work. Where distances make a personal meeting uneconomic, in some cases proofs are instead sent by mail or courier.
Depending on the type of project, the customer may be particularly interested in seeing how faithful the colors will be in a large, display-format reproduction. In other projects the focus may be upon how well the printshop has implemented complex layout instructions for a creative multiple-fold presentation; or how precisely all the elements of a periodical have been assembled as to sequence, orientation, cropping, size, typesetting and so forth.
(b) Responsibility Allocation
Regardless of all such details or focus, the printshop does not typically show proof as a favor or courtesy to the customer, but rather somewhat the opposite. It is a mechanism for allocating to the customer any liability for errors in the finished job, if the customer fails to object to them in the proof.
The point is that all the makeready processes up to the point of showing proof, though costly, are usually significantly less thanxe2x80x94and perhaps in most cases only a small fraction ofxe2x80x94the total price of the job. Responsibility for the cost of printing, however, is by no means the end of legal liabilities and other obligations that can be associated with an unsatisfactory printed product.
Though the printing may be very expensive, the customer""s objectives may have a value which dwarfs that expense. Another kind of consequence that is still more difficult to quantify and unpleasant to confront is the negative impact which defeated expectations exert on the crucial goodwill of a printing or graphic-arts firm.
Hence a key element in the proofing process is the customer or representative""s signature approving the proof, whether with or without marked changes. In many cases the customer may call for showing of another proof, either full or partial, before finallyxe2x80x94in industry vernacular xe2x80x94xe2x80x9csigning off on the job.xe2x80x9d
A printing proprietor wants to print, and print for profitxe2x80x94not absorb the cost of a printjob gone wrong, or waste time and money in squabbles with customers or litigation with graphic artists. Clearly the role of a proof in the traditional commercial printing environment is enormously important.
(c) Escalated Demands in Printing
All of these traditional practices and concerns carry forward undiminished into the modern world of faster, more widely distributive commercial activities with creative new kinds of proprietary relationships. Perhaps the most important differences are that customers and their intermediaries want to see proofs faster, want to see them in a more convenient place, want them to be more accurately representative of the finished product, and generally want to push on the envelope of what can be humanly accomplishedxe2x80x94all without error.
One modern development that is particularly important to the present invention is introduction of long-distance transactions in which a printing facility may be doing a job for a customer in a faraway city, even on a different continent. In many such situations source personnel working on behalf of the customer may go beyond providing camera-ready artwork, and text manuscript or xe2x80x9ccopyxe2x80x9dxe2x80x94and even negatives and plates, as beforexe2x80x94but now also prepare a computer data file, or great sets of files, for the printer""s use in automatically generating necessary printing materials.
This trend generally continues, into the artwork and layout parts of the printing industry, the earlier introduction of typesetting computer tapes for text. Modernly such files may for example be detailed color-image data.
(d) Modern Printing in Traditional Firms
To avoid losing overall perspective, it will be mentioned here that these files can also exist in the context of a printing project that is all prepared and executed within a traditional single business and single location. In fact such data files can be very efficiently used and integrated into the flow of work within that location.
Such integrated traditional printing establishments still do exist in large numbers, and it is still common for a customer to bring an entire job to a printer in the form of some camera-ready copy, plus manuscript with layout instructionsxe2x80x94or even with instructions for preparation of artwork by a graphic artist who works for the printshop. In this kind of situation the target facility may itself generate not only the original data file but even the artwork which is the precursor of that file.
After the data file is created, a first step is provision of the data file to makeready personnel who modify the file to prepare it for use in the printing machine that is slated to do the final hardcopy.
Then that modified file is used on a different machine, sometimes a proof press, to make a proof. Commonly in an integrated, relatively traditional shop the same makeready personnel who have modified the file also use that revised file in the proofing process; or those makeready personnel confer directly with proofing personnel.
In either case, an intimate knowledge of the character of the final hardcopy printer and its intended special adjustments and settings are thus fully available in the proofing process. Furthermore a complete characterization of that final hardcopy device is likely to pass with the job to the proofing personnel.
For instance, a device-space color characterization of that target printer may be provided to the proofing personnel. In some such situations the makeready personnel may even append or incorporate such information explicitly into the revised proofing file that is provided to the proofing crew within the same company. In a wholly local project conducted within a single organization, it is entirely natural to freely pass such information to the proofing personnel.
(e) Modern Printing in Distributive Projects
No such information flow, however, is known in projects that span two or more organizations and involve mutually remote target and proofing facilities. Here it is more natural for schedules, job priorities, printing-machine capabilities and idiosyncrasies etc. to be regarded as proprietary matters and consequently to stop at the boundaries of business organizations.
Therefore in the context of printing projects that are widely distributive geographically and in terms of different business enterprises, neither typesetting files nor image files fully eliminate the potential for surprises and disappointments in finished hardcopy. Equipment in the target facility may not be exactly the same as anticipated by the typesetter or artist who prepares the filesxe2x80x94and, even if they are the same, they may be adjusted or configured differently, or may be loaded with different inks.
One of the most insidious and difficult sources of diverging expectations is in the setting of a target facility""s printing devices to reproduce color in a slightly different color space, for instance a different so-called xe2x80x9cdevice spacexe2x80x9d, than envisioned by an artist, photographer or other source-associated craftsperson. Besides using fairly standard or nonstandard color spaces as such, specifications for a printjob may include special inksxe2x80x94in the trade often called xe2x80x9cspot colorxe2x80x9dxe2x80x94that have textured, fluorescent, or glittery-fleck inclusions or simply represent a proprietary logo or trademark color.
Other parameters of a printing job that can be easily confused, misunderstood or forgotten include color corrections, cropping, scaling, bleed (forming of a photo or image that appears to run off the edge of a page), setup of signatures; size, placement and orientation of images and type; blind embossing and special registration geometries. All these variables represent powerful tools for producing effects that implement high-level creativity and professional vision on the part of artists and other printing professionalsxe2x80x94but at the same time and by the same token they also represent ways in which things can go terribly wrong.
(f) Short-run Art Projects
The difficulties outlined above appear to be aggravated in extremely high-quality, short-run projects such as art reproductions. In such cases, since makeready operations must be amortized over a relatively small number of prints, the overall cost per hardcopy is proportionately highxe2x80x94while demands on technological performance are especially stringent, particularly as to color accuracy.
Due to these characteristics, many kinds of short-run art projects are nowadays becoming the province of the printing industry""s incremental-printing branch, where no negative, plate or engraving is required. Until relatively recently, incremental printing was known only in small, desk-size office or personal copiers.
This is no longer so. Prime contributors to the expansion into large-format, fine-quality capability are machines designed at Hewlett Packard Espanola, in Barcelona.
Virtually all makeready for incremental printing is performed within a computerxe2x80x94perhaps the only exception being loading of special inks into the machine. Furthermore, proofs are themselves almost by definition short run; therefore they too are natural applications for the modernly emerging field of incremental printing.
It is for these reasons that the present invention may be of particular utility in incremental printing. The invention itself, however, is not thus limited.
(g) Intermediate-technology Proofs
Another relatively modern development is that the printer may send a proof to the customer or graphic artist by facsimile transmission or by electronic mail. In such tactics, however, there is great potential for trouble, due to lack of standardization in color-reproduction capabilities of remote receiving apparatus and in viewing arrangements.
(h) Third-party Proofers and Other Operators
A step in the right direction is emergence of third-party professional proofing facilities 12 (FIGS. 1 and 2), which may tend to have industry-standard, state-of-the-art equipmentxe2x80x94and also may tend to use somewhat better-standardized adjustments, configurations, device-space settings and so forth. Both the final or xe2x80x9ctargetxe2x80x9d printing facility 13 and the source (customer or customer""s representative) 11 are more comfortable with placing their confidence in that kind of service operation.
As a practical matter, some proofing facilities may themselves be printing companies that happen to be more local to the customer or artistxe2x80x94but in general are not part of the same enterprise as the printing firm that will do the final work. While the proofer is ideally much closer to the customer than the target facility is, that latter firm may attract the final-hardcopy printing in any of a great variety of ways.
For instance, the target facility may have very highly specialized equipment, or may be in a state (such as several in the southeastern part of the United States) or country (such as Indonesia or Thailand) where labor or real-estate costs are low and the going rate for long-run or high-quality work is accordingly depressed. Alternatively the target facility may simply be located near the point of intended final use, so that delivery can be made without high cost, delay or added risk of damage in transporting of heavy and bulky pallets of printed materials.
In some major commercial centers, on the other hand, the proofing facility may not do any final-run printing of its own but rather may simply exist to serve the high traffic in out-of-the-area final hardcopy printing. In either case the proofer is generally only a collaborator with the printing firm, not a part of the printing firm, since it would be impractical for most printers to maintain their own offices in every major city or region where customers might materialize.
Hence the modern commercial environment naturally gives rise to the existence of proofing facilities that serve a very valuable purpose. They work hand-in-hand with customer and intermediary, as a new kind and new level of intermediaryxe2x80x94in some cases more closely associated with the printer than with the customer and in other cases the opposite, but in any event proprietarily distinct from both.
In passing it is worth mentioning that further elaboration of interenterprise relationships can occur elsewhere in the chain, particularly with the customer engaging an advertising agency, which may in turn hire a freelance graphic artist or a job-shopper to interface with the printer through the proofer, and so on. All these relationships have their suitable place in the picture, depending upon the capabilities and constraints of the various participants.
(i) Problems in Third-party Proofing
Previous discussion has explored the flow of work (including data files) in a relatively traditional, integrated printshop. This present subsection specifically addresses operations in the more modern, distributive kind of working scheme.
If an input image-data file 17 (FIGS. 1 and 2) is used in this type of operation, one entity which commonly uses that file to generate a proofing file is the proofing facility. This method, although dominant in this niche of the industry, is highly questionable.
As target operations become progressively more complex, more and more information has to go into the proofing. This trend places extreme demands upon the accuracy of that information.
An even more dangerous practice is for an originator of the image dataxe2x80x94a person who lacks any affiliation with the target facilityxe2x80x94to try to define the proofing file. Development of the proofing file by either a proofing facility or an image-data creator is an invitation for error of several different types to creep into the system.
Departing from traditional-shop workflow described earlier, here the precise detailed character of the target printer is outside the information set of the person undertaking to put together the proofing file. Even if such information is available, while that person is making the proofing file the target facility may be changing adjustments to the color rendering transform used in the target printer.
Even after the proof is made, the target facility may make other such changesxe2x80x94or some other new, higher-priority job may bump the subject project to a different machine entirely. While the present invention is particularly effective in very sophisticated projects involving extremely touchy color characterizations, it is also effective in helping to control simple problems arising out of mere complexity in a job.
For instance target-facility personnel may confirm verbally or even in writing the shipping destination of the finished hardcopy, or even identification of the job itself. Spot color or related adjustments in colorimetry may be similarly confirmed, as may cropping, scaling and layout instructions.
None of these precautions is likely to halt the process or sound an alarm when personnel along the way are distracted by events on the job or inattentive due to personal concerns. The object of a proofing process, again, is to prevent undesired characteristics in an ultimate hardcopy output; but the process as described above is flawed and has only a middling-to-good chance of accomplishing that objective.
In a sense, the problem is that partial automation is dangerous: automation tends to lull people into thinking that the machinery is handling the job and will do so correctly; but this particular segment of the workflow path is outside the automatic-control model. Thereby the door is opened to human errorxe2x80x94which as a practical matter can never be entirely avoided, and which may materialize in the form of agreements that have been forgotten, instructions that have been mislaid, and misunderstandings that have never been recognized.
The result, if it includes failure to deliver publication materials when needed critically, may be utterly incurable. Even in lesser catastrophes, the result may include lost profitxe2x80x94and all the difficulties of allocating liability for itxe2x80x94or the actual delivery of final hardcopy that is unacceptable, though expensive in the extreme.
Yet the printing business is extraordinarily competitive. Any solution to these problems, if it is to be accepted, must be one that imposes an absolute minimum of added cost and delay.
In one third-party proofing arrangement, the process may begin with provision of color-rendering characteristics (an I. C. C. profile) 16 from the target printer 25 to guide a conversion process 21 that may be performed by the sourcexe2x80x94or preferably, but less commonly, by the proofing facility 12. (The initials xe2x80x9cI. C. C.xe2x80x9d stand for the xe2x80x9cInterColor Consortiumxe2x80x9d, which has developed an industry standard.)
The conversion process 21 also receives an image data file 17, 17xe2x80x2 andxe2x80x94based upon the target-printer profile 16xe2x80x94prepares an equivalent file 24 in target-printer color space (in other words, in device-color space). This file 24 in principle should produce perfect rendering at the target printer 25.
First, however, the input data 17 themselves, or the adjusted file 24, or possibly a modification in perceptual color space, is used as a file 22 in the proofing facility to prepare a proof 23. Whichever of these three possible genealogies may have been its actual origin, ordinarily the proofing facility can be relied upon to use this file 22 to produce a proof 23 that is entirely true to the assumptions implicit in the selected path, and thus is accurate within those assumptions.
That kind of accuracy is certainly sought, but nevertheless may in fact fail to serve the purpose. What is needed is correspondence between the proof 23 and the final hardcopy output that will result if the converted file 24 is passed with a xe2x80x9cgo aheadxe2x80x9d instruction (based upon examination of the proof) to the target printer 25.
Unfortunately, as printing equipment becomes ever more sophisticatedxe2x80x94and offers ever greater variety in the ways color and other printing details can be implemented xe2x80x94even reasonably well-standardized apparatus and settings 16 can be unintentionally made different from what a graphics house or primary customer has in mind. As noted in this background section, personnel in the target-printer facility 13 can quite innocently make changes in settings and characteristics of the target printer 25 that negate the profile characteristics 16 supplied.
Such a variation is all it takes to invalidate the assumed correspondence between proof and final hardcopy xe2x80x94notwithstanding accuracy in the conversion or other process used to generate the proofing file 22. All of the parameters mentioned in the preceding section of this document, and others, are subject to variation and thereby can generate dissatisfaction with results.
In another representative third-party proofing arrangement, the input data 17 undergo a conversion 31 (FIG. 2)xe2x80x94again either at the source or preferably at the proofing facilityxe2x80x94into some standard color space, most usually another device space such as that of a typical printing press (as distinguished from that of the specific target printer 36).
The converted data 32 pass to the proofing facility""s proofing system, which here too accurately applies suitable transformations to generate a proof 33. In this case furthermore if the proof is approved the same converted data 32 proceed to the target-printer facility 13.
The latter, however, must now apply an adaptation 34 to develop a final data file 35 for use in the target printer 36. The character of the adaptation can be relied upon to correctly prepare for printing in the target printer 36, taking into account the conversion 31 used by the proofer.
The adaptation 34 also, unfortunately, takes into account up-to-the-minute information about the true condition of the target printer 36, which information regrettably is unknown to personnel of both the proofing facility 12 and source 11. It would hardly be appropriate to omit such information from the adaptation 34, since otherwise the adaptation would be wrong on its face.
In fact, some aspects of the adaptation 34 may be called forxe2x80x94within the specialized knowledge of personnel at the target facility 13xe2x80x94specifically by job specifications called out in writing by source personnel. It is, ironically, precisely such special requirements (perhaps not fully considered in the proofing facility 12) that can be the immediate cause of mismatch in the proofing process.
(j) Conclusion
As this discussion shows, limitations in proofing reliability for interenterprise printing projects continue to impede achievement of uniformly excellent final-hardcopy output in high-quality color reproductions and other challenging specialties, especially short-run work. Thus important aspects of the technology used in the field of the invention are amenable to useful refinement.
The present invention introduces such refinement. In its preferred embodiments, the invention has several aspects or facets that can be used independently, although they are preferably employed together to optimize their benefits.
In preferred embodiments of a first of its facets or aspects, the invention is a method of generating an advance proof of an image that is to be printed at a target printer facility. The printing there is to be based upon an original image data file in a particular color space.
In this document the phrase xe2x80x9ctarget printer facilityxe2x80x9d includes a printer that will be used to make a final hardcopy printout of the imagexe2x80x94and, most typically but not necessarily, associated with that printer a computer which performs all or portions of the functions of substantially directly controlling the printer. The target facility typically also includes other related apparatus. As to some printers, equivalent computing capabilities are not xe2x80x9cassociated withxe2x80x9d the printer but rather are wholly incorporated into the printer itself; this too is of course encompassed within the phrase xe2x80x9ctarget printer facilityxe2x80x9d.
As an opposite case, people familiar with this field will understand that in some situations an associated computer is not necessarily in the same room or even the same premises as the printer. Instead such a computer may instead be quite remotexe2x80x94even on a different continentxe2x80x94and may be associated with the printer through a network connection, modernly even an Internet connection.
Thus the concept of a target printer facility or xe2x80x9ctarget facilityxe2x80x9d is to be understood broadly as encompassing a printer with integrated but substantially direct control system, however structured. This concept will shortly be made more clear through examples and also through discussion of contrasting arrangements and complementary facilities.
The method includes the step of converting the original file to a different color space than the original color space, to form a proofing data file. This converting step is performed by the target facility. The method also includes providing the proofing file to a proofing facility which is distinct from the target facility. This providing step need not be performed by the target facility.
The concept of a distinct proofing facility is complementary to that of the target facility or xe2x80x9ctarget printer facilityxe2x80x9d. The proofing facility includes some apparatus that makes a proofxe2x80x94that is, a visible representation of the image substantially as it will appear in the final hardcopy printout to be made by the target facility.
In the printing industry the concept of a proof is traditional and extremely common. As will be seen, for purposes of the present document the proof can be but is not necessarily itself a hardcopy.
Like the target facility, the proofing facility may be all in a single room and embodied in an evidently single, unitary apparatus or may be distributed. Portions may be in very remotely different places.
As a matter of industrial practice according to the invention, the proofing facility is perhaps most typically xe2x80x94but not necessarilyxe2x80x94remote from the target facility. From the earlier discussion of the target facility, however, it will be clear that distance as such is not an important consideration in determining whether a particular piece of apparatus is part of the proofing facility or not xe2x80x94or is part of the target facility or not.
A stated characteristic of the proofing facility is that it is distinct from the target facility. It is important to establish what this means.
Of course the two may be wholly separate operations in different cities. On the other hand, for instance one computer terminal that is part of the proofing facility may be physically adjacent to a computer terminal that is part of the target facility.
Such physical adjacency in itself is not dispositive one way or the other. The two facilities may yet be either xe2x80x9cdistinctxe2x80x9d or not.
These two adjacent terminals may even have some form of interconnection for exchanging data. If this interconnection and the data exchange in the interconnection are completely automatic, and the processing of data in both terminals and in the remainder of their respectively associated facilities is likewise completely automatic, then there may appear no basis for drawing a distinction between the two facilities.
In such a case the two facilities are not distinct. The conclusion will be opposite, however, if some element of divergent human control (different people controlling the two machines) or divergent human intervention appears in association with that physical interconnection, as to the transmission or reception of the data.
Such divergent human intervention may for instance take the form particularly of recognizing that the data are going to or coming from a different legal entity; or in deciding how to use the data in determining how to proceed in dealing with the image and its eventual hardcopy printout for purposes of a different legal entity.
In other words, in this rather extreme casexe2x80x94intentionally introduced for the purpose of illustrating how fine the distinction between facilities may bexe2x80x94the line of division may be exclusively one of different ownerships of relatively closely linked physical apparatuses representing the two entities, or exclusively one of very distinctly different human control on the two sides of the line.
It will be understood, however, that what has been discussed above is a particular extreme case in which relatively great care is required to draw a plain line between the two facilities. In the very large majority of cases, the determination will be much more straightforward and clear as the two facilities will be cleanly distinct in physical, functional, commercial and proprietary terms.
The foregoing may represent a description or definition of the first aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, it is the target facilityxe2x80x94rather than the proofing facility as in the most-relevant prior artxe2x80x94which generates the proofing file. This method is therefore far more reliable, because the more complex the target operations, the more information has to go into the proofing and the more accurate that information must be.
When it is the proofing facility (or even more undesirably a target-facility-unaffiliated person who originated the image data) that undertakes to define the proofing file, myriad insidious sources of error can intervene. A printer profile supplied by the target facility to the proofing facility just last week, or yesterday, may no longer be applicable today.
Some special instructions, too, for scaling, cropping, custom colorimetric adjustments, spot color, and even job identification or destination may be present in a proofing file supplied by the proofing facility (or image-originating personnel)xe2x80x94and these may be xe2x80x9cconfirmedxe2x80x9d by target-facility personnel verballyxe2x80x94but when it is the target facility itself physically incorporates them into the proofing file, they are more-nearly confirmed really.
Although the inventive method described above is only for generation of a proof, and thus does not include final printing of a hardcopy as a step, it is helpful to bear in mind that ordinarily the target facility will in due course print a final hardcopy, and the object of a proofing process is to reduce the incidence of undesired characteristics in such ultimate hardcopy outputs. In particular, the procedure described enables actual application of the target facility""s proofing data file by the proofing facility, in producing a proofxe2x80x94shortly before anticipated final hardcopy printout by the target facility.
Thus the invention has an automatic, built-in hedge against misunderstandings, mislaid instructions, forgotten agreements, and other forms of virtually unavoidable human error. In this way the invention yields much lower incidence of extremely expensive unacceptable final hardcopy, of difficult-to-allocate liability for lost profitxe2x80x94and of major incurable damage through failure to timely provide critically needed publication materials.
Although the first major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics. In particular, preferably the converting step converts the original file into either target-printer native color space or a perceptual color space. Also preferably the method includes the step of applying the proofing file to produce a proofxe2x80x94a step that is performed by the proofing facility.
Another preferable step is that of the target facility receiving the original file. As will be seen, most typically but not at all necessarily the original file is received from target-unaffiliated personnel involved in generating the original artworkxe2x80x94and in many cases received through the intermediary of the proofing facility.
This step is described as xe2x80x9cpreferablexe2x80x9d because in practice the target facility may itself generate the original file. This perhaps anomalous-seeming arrangement may arise in any of a variety of ways, many of which have analogs in conventional practice that will be recognized as commonplace.
One way in which this may occur, as mentioned earlier, is that the target facility may actually be an employer of the art personnel. Another is that the tasks of the target facility may include assembly of many different small pieces of a job, received piecemeal from one or plural sources. Also these two modes of work may occur in combination.
Another pair of preferences, which are alternative to each other, are that the proof be either a computer-generated volatile display or a hardcopy. A volatile display in turn may take the form of a computer monitor (whether a cathode-ray tube, liquid-crystal display, or other type) or of a projection display on a screen.
A hardcopy proof may be made on a very different kind of printing device from the target printer. For instance, the proofing file may correspond to a page size larger than the proofing facility can print; in this case the proofing file is preferably subdivided into data subsets individually sized for printing in the proofing facility.
Such subdividing can be performed by the proofing facility, and this is within the scope of certain of the appended claims; however, this approach is not most-highly preferred as it appears to sacrifice more than necessary of the desirable objective that a common proofing file be used to produce both the proof and the final hardcopy. That goal may be more closely realized by assigning to the target facility the task of forming a subdivided derivative of the proofing filexe2x80x94or, naturally, of a substantial duplicate of the proofing file.
In general, again, the target facility is better able to maintain the integrity of the simulation, through most kinds of transforms (particularly including a subdivision) than the target facility. In this approach at least a common proofing file is appliedxe2x80x94and most-accurately appliedxe2x80x94to produce both the proof and the final hardcopy.
Volatile and hardcopy proofs, in any event, have their respective drawbacks and advantages. A volatile proof may show colors in a nominally representative fashion, and may also show cropping and other characteristics of the desired treatment.
In general, however, a volatile proof cannot effectively show print-medium effects or metameric effects. Such effects are color similarities and differences that appear when an inked image is viewed under different lightingxe2x80x94e.g. skylight, direct sunlight, fluorescent lamps of different types, incandescent lighting at different color temperatures etc.
On the other hand , a volatile proof usually is far preferable in terms of speed of presentation (particularly for remote viewing), economy of production, and all-around convenience. With sufficient attention in programming, a volatile proof may adequately represent the relationships of image size to page size, and the cropping, trimming, bleed and general layout of signatures, etc.
Another preference is that the converting and providing steps be performed automatically. By this it is not meant to suggest that automaticity necessarily extend to the physical makeready of a press, but rather only to the computations involved in transforming color and other image characteristics from the original data-file form into native target-printer form; and to the steps required for forwarding the data in this latter form to the proofing facility.
From the advantages of the invention as described above, it will be understood that automaticity can enhance the favorable effects of the invention by further reducing intrusion of human error. Complete automaticity both in and between the target and proofing facility, however, if coupled with common proprietorship and control may indicate that facilities are not distinct and the invention therefore not present.
Another preference is that, before the applying step, the target facility perform another step of registering with the proofing facility a target printer and corresponding color characterization profile. A subpreference in this case is that, after this registering step and before the supplying step, image-generation personnel perform the step of retrieving that registered color profile and using the profile to refine the dataxe2x80x94so that, at the very outset, they can specify a more nearly desired hardcopy color at the target printer.
Yet another preference is that the method also include the step of the proofing facility also applying a target-printer color-characterization profile in producing the proof. For this preferred form of the invention, virtually the only limitation on the target printer is that it in fact have such a profile. There are two ways in which this step may be implemented.
First it is ideal that the providing step include provision by the target facility to the proofing facility, substantially concurrently, of a target-printer color-characterization profile. In this case, preferably the proofing facility also applies this particular target profile in producing the proof.
The point here is that this procedure minimizes the likelihood of a change in the target-printer profile between the time when the proofing facility acquires the target profile and the time when the final hardcopy is made. Nevertheless, a second way in which the proofing facility can apply a target profile in producing the proof is that the target facility provide a target profile to the proofing facility earlierxe2x80x94and the proofing facility store this information for use in proofing.
For example, as mentioned above the target facility preferably registers the target printer with the proofing facility, and at the time of registration provides a then-current target profile. As can now be understood, however, it is far preferable for such early, and generalized, profile data to be used only by image-generation personnel, and only in preparing a rough first cut at the original data file. In commercial-liability terms it is rather dangerous for the proofing facility and the customer or image-generation personnel to actually rely, at final hardcopy time, upon such a relatively early profile.
Still another preference is that the proofing facility be remote from the target facility. As mentioned earlier, this preferred characteristic is likely most typical but is not necessary.
It is also preferable that the converting step be performed either by a processor in a target printer at the target facility, or by a processor in a computer interconnected with the target printer. It is also preferable that the proofing file further include information about the image, such as may beneficially form part of a positive, technical confirmation to the proofing facility of job specificationsxe2x80x94including for instance:
cropping,
page placement,
scaling multiple,
spot color,
an image-document name,
an image-document date,
identification of one or more people associated with the image, and
identification of one or more organizations associated with the image.
The phrase xe2x80x9cscaling multiplexe2x80x9d refers to an image-dimension adjustment.
Craftsman in the traditional printing arts may conceive of such adjustment in terms of visible dimensions (and indeed may be accustomed to implementation through optical projection devices); while digital-image technicians may instead conceive of the process in terms of changes in resolution (with implementation through computerized calculations e.g. including interpolation). Both conceptualizations are valid and within the scope of the present invention.
The phrase xe2x80x9cspot colorxe2x80x9d refers to specification of a special ink, which may include any of an extremely large variety of coloring materials as explained earlier. People and organizations included in the proofing file may likewise be quite diverse. They mayxe2x80x94merely by way of examplexe2x80x94include a customer, an artist, a proof house that operates the proofing facility, a printing house that operates the target facility, or a third or fifth party that is to receive shipment of the finished hardcopy as a beneficiary of the overall process.
Another preference is that the proofing file be at a coarser resolution than the original file. Generally speaking, except in perhaps the most demanding of fine-art projects, color as well as mechanical specifications can be evaluated quite adequately from a coarser-resolution proofing file and proof.
Another preference, somewhat related, is that the converting step include transforming the data into rasterized form, as part of creating the proofing file. Many original files are not raster or bitmap files but rather vector or vector-equivalent (e.g. text)xe2x80x94and at some point before actual hardcopy printing must be rasterized.
For instance in incremental printing rasterization is required to enable printmasking. In more-traditional printing arts, rasterization is at least required in the process of making an offset-litho plate or engravingxe2x80x94if not before.
In any event a bitmap or raster file is much closer to a final, printing-machine-language representation than is a vector file; and accordingly is subject to much less interpretation and associated ambiguity. In a word, the raster file is more stable.
Some print jobs are extremely color sensitive for particular colorsxe2x80x94again company logos, for instance, and very similar colors with fine distinctions between them. (Such concerns are far from imaginary; to the contrary they have been compiled from actual complaints of printed-hardcopy recipients.) Therefore use of the rasterized filexe2x80x94some form of which must eventually be made anyway for printingxe2x80x94as the proofing file is very helpful to still further reducing the possibility of mismatched understandings about the final outcome of the project.
Since raster files, however, are usually much larger than vector files, transmission of a full-resolution raster file as a proofing file may be very time consuming and expensive. Furthermore, the proofing printer may very well require downsampling (resolution reduction) in production for its own printing, if it receives a full-resolution proofing file.
Thus the preference stated just previouslyxe2x80x94of the proofing file being reduced in resolution for transmission by the target facility to the proofing facilityxe2x80x94serves two purposes: (1) it reduces the time and cost of transmitting the data, and (2) because the rasterization and resolution reduction are performed by the target facility, which better knows the peculiarities of its own target printer, the overall process is once again less subject to corruption by misunderstandings about the nature of the rasterization process to be performed at the target facility. That process has already been done in production of the proof.
Some other operational preferences will now be introduced. Although these operations have their plain analogs in traditional commercial work, the overall method resulting from combination of these operations with the novel, inventive steps described above is believed to be even more strikingly novel and inventive. That is, these preferences represent an ingenious integration of the invention into commercial practice in a way that conventional practitioners will find comfortable and naturalxe2x80x94all the while achieving the above-outlined great benefits of the basic invention.
One of these operational preferences is that the method also include the steps of:
before the supplying step, image-generation personnel presenting the original file to the proofing facility and requesting a proofing document from the proofing facility; and
the proofing facility then performing the supplying step and also requesting a proofing file from the target facility.
Another of these operational preferences is inclusion of these further steps, to be performed by the image-generation personnel:
viewing the proof;
annotating the proofing file based on viewed color quality of the proof; and
furnishing the annotated proofing file to the proofing facility.
Yet another operational preference is that the method include the steps enumerated below. It will be seen that these steps, though set out somewhat in long form, represent essentially an iterationxe2x80x94based upon the first-above-described proofxe2x80x94of the fundamental process steps described earlier:
the image-generation personnel viewing the proof, refining the original file based on viewed color quality of the proof, and supplying the refined file to the proofing facility;
the proofing facility supplying the refined file to the target facility with a request for a refined proofing file;
the target facility converting the refined file into target-printer native color space, to form a refined proofing file;
the target facility providing the refined proofing file to the proofing facility;
the proofing facility applying the proofing file to produce a refined proof; and
the image-generation personnel viewing the refined proof and approving it.
As will be apparent, most of the preferences described above in regard to the first main facet of the invention are equally applicable in practice of the other main aspects of the invention, which are introduced below.
In preferred embodiments of its second major independent facet or aspect, the invention is a method of printing an image, based upon an original image data file in a particular color space. The method includes the step of a target-printer facility converting the original file to a different color space, to form a proofing data file.
It also includes the steps of provision of the proofing file to a proofing facility distinct from the target facility; and the proofing facility applying the proofing file to produce a proof.
This method also includes the step of the target facility applying that proofing file to produce a final hardcopy of the image. Through this process, that proofing filexe2x80x94which is to say, the same proofing filexe2x80x94is applied to producing both the proof and the final hardcopy.
The foregoing may represent a description or definition of the second aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, this method actualizes the relatively abstract previous discussion of the ultimate hardcopy printout by the target facility. All of the incipient benefits to be realized in principlexe2x80x94in the practice of the proofing method that is the first aspect of the invention xe2x80x94can now be seen as realized actually in the present printing method.
Although the second major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics. In particular, some of the previously mentioned preferences for the first facet of the invention can be mirrored here. Preferably:
image-generation personnel supply the original file, in the particular color space, to the target printer facility;
image-generation personnel view and approve the proof;
the providing step includes the target facility also providing to the proofing facility substantially concurrently a color characteristic profile of the target facility;
the converting step includes transforming the data into rasterized form, as part of creating the proofing file;
the proof is a hardcopy;
the proofing file corresponds to a page size larger than the proofing facility can print, but can be subdivided into data subsets individually sized for printing in the proofing facility (in the second aspect of the invention as here described, this subdivision is most naturally conceptualized as performed in the proofing facility, but the contrary will be seen below in another separate aspect of the invention);
the converting and providing steps are performed automatically;
the target facility associates with the proofing file a target-printer color-characterization profile;
the proofing facility also applies such an associated target profile in producing the proof; and
the proofing facility is remote from the target facility.
In preferred embodiments of its third major independent facet or aspectxe2x80x94as with the secondxe2x80x94the invention is a method of printing an image, based upon an original image data file in a particular color space. Also as in the second aspect, this third facet includes the early step of a target-printer facility converting the original file to a different color space, to form a proofing data file.
Also common to both these aspects are certain later steps. One such step is the target facility""s using (but here we shall say xe2x80x9capplyingxe2x80x9d) the proofing file to produce a final hardcopy of the image.
Intermediate steps of this method, however, differ importantly. One such step of the present aspect is the target facility""s application of the proofing filexe2x80x94or, again, a substantial duplicate of that filexe2x80x94to form a subdivided derivative of the proofing data file.
Other such steps are provision of the subdivided derivative file to a proofing facility distinct from the target facility, and the proofing facility""s application of the subdivided derivative to produce a proof in subdivided portions. Thereby the proofing file (once again, a common proofing file) is applied to producing both the proof and the final hardcopy.
The foregoing may represent a description or definition of the third aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, this aspect of the invention implements the earlier-mentioned most-advantageous way of realizing the benefits that flow from applying a common file in production of both a proof and a final hardcopy, by distinctly different entities.
Although the third major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with certain additional features or characteristics. In particular, preferably the proofing file corresponds to a page size larger than the proofing facility can print; however, the subdivided derivative comprises respective data subsets of the proofing file that are individually sized for printing in the proofing facility.
In preferred embodiments of its fourth major independent aspect or facet, the invention is a system for printing an image, based upon original image data. Those data are in a particular color space, and supplied by image-generation personnel. It will be understood that the image, the data, and the image-generation personnel are all only parts of the context or environment of the invention as broadly described herexe2x80x94not elements of the inventive system itself.
(In the bodies of those of the appended claims directed to apparatus, e.g. to the system under discussion here, the term xe2x80x9csuchxe2x80x9d is used instead of xe2x80x9cthexe2x80x9d or xe2x80x9csaidxe2x80x9d in referring back to parts of the environment or context expressed in the preambles of those claims. The purpose of this convention is to more particularly and distinctly emphasize which features are elements of the invention.)
The inventive system includes a target printer facility, including a target printer. The facility receives the data from the personnel and converts the original data to a different color space to form proofing data.
Also included, but distinct from the target facility, is a proofing facility that receives the proofing data and applies the proofing data, together with a color characteristic profile of the target facility, to produce a proof. The target facility also applies those proofing data to print a final hardcopy of the image.
Thus both production of the proof and printing of the final hardcopy are effectuated from application of the proofing data in common. Even though this system overall is distributive, as between at least the two facilities described, the system nevertheless achieves the advantages of minimizing misunderstandings, enhancing reliability in printing a final hardcopy that is what everyone expects to see, and avoiding unsatisfactory deliveries with their associated liabilitiesxe2x80x94all as mentioned earlier for the method aspects of the invention.
In preferred embodiments of its fifth major independent facet or aspect, the invention is a target printer facility. Its purpose is printing a final hardcopy of an image based upon original image data, in a particular color space, and cooperating with a proofing facility that is distinct from the target facility.
From the foregoing it will be understood that the image data, the hardcopy, and the proofing facility are not elements of the invention in its fifth main aspectxe2x80x94but rather are parts of the context or environment of the invention. The image data are supplied by image-generation personnel.
The target printer facility includes a target printer that prints the final hardcopy of the image, and a communication link for receiving such data from such personnel. It also includes one or more computer subsystems for converting such original data to a different color space to form proofing data.
In addition the fifth facet of the invention includes a further communication link. This link is for transmitting the proofing data to such distinct proofing facility for use, together with a color characteristic profile of the target facility, in producing a proof.
The foregoing may represent a description or definition of the fifth aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, this aspect of the invention provides the target facility whichxe2x80x94through interaction with a complementary proofing facilityxe2x80x94makes possible the benefits of the system and method facets of the invention discussed above. Though the fifth major aspect of the invention thus significantly advances the art, nevertheless to optimize enjoyment of its benefits preferably the invention is practiced in conjunction with some of the preferences outlined above for earlier aspects of the invention.
In preferred embodiments of its sixth major independent facet or aspect, as with the fifth, the invention is a target printer facility for printing a final hardcopy of an image, based upon original image data, in a particular color space, supplied by image-generation personnel; and for cooperating with a proofing facility that is distinct from the target facility. Thus once again this language indicates that the proofing facility, image data, and hardcopy are parts of the environment of the invention, not elements of the invention itself.
The target printer facility includes a target printer that prints the final hardcopy of the image, and a communication link for receiving such data from such personnel. It also includes one or more computer subsystems for converting such original data to a different color space to form proofing data.
The target facility also includes a further communication link for transmitting the proofing data to such proofing facility for use, together with a color characteristic profile of the target facility, in producing a proof. The target printer and computer subsystems comprise means for applying the proofing data to print the final hardcopy. Thereby a common proofing file is applied both to producing the proof and to printing the final hardcopy.
The foregoing may represent a description or definition of the sixth aspect or facet of the invention in its most general or broad form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular this facet of the invention, like the fifth, establishes a target printer facility which enables the advantages of the first through fourth aspectsxe2x80x94but here with a focus upon the earlier-discussed benefits of using a single file of data for both producing a proof and printing a final hardcopy. Again the preferences for the previously introduced facets of the invention are applicable here too.
In preferred embodiments of its seventh major independent facet or aspect, as for the fifth and sixth, the invention is a target printer facility for printing a final hardcopy of an image, based upon original image data, in a particular color space, supplied by image-generation personnel; and for cooperating with a proofing facility that is distinct from the target facility. The target printer facility includes a target printer that prints the final hardcopy of the image, and a communication link for receiving such data from such personnel.
Also included are one or more computer capabilities for converting such original data to target printer native color space to form proofing data. The target facility also includes a further communication link for transmitting the proofing data, together with a color characteristic profile of the target facility, to the distinct proofing facility for use in producing a proof.
The foregoing may represent a description or definition of the seventh aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, this aspect of the invention too defines a target facility whichxe2x80x94in conjunction with a complementary proofing facilityxe2x80x94brings into existence the favorable conditions that flow from proofing from the same file as used in printing. This facet of the invention goes further in that this file is specifically provided to the proofing facility by the target facility.
In preferred embodiments of its eighth major independent facet or aspect, the invention is exactly such a complementary proofing facility. That is, it is a facility that produces a proof of an image, based upon a proofing data file; and that cooperates with a target printer facility which is distinct from the proofing facility and which prints a final hardcopy of the image. This preamble expressly indicates that the proof, data file, hardcopy, and target printer facility are parts of the context of the eighth aspect of the inventionxe2x80x94not of the invention itself.
The proofing facility includes a device for producing the proof, and a communication link for receiving such proofing data file from such target facility. Also included are one or more computer subsystems for using such proofing data, together with a color characteristic profile of such target facility, in controlling the proof-producing device to produce a proof.
The foregoing may represent a description or definition of the eighth aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, this aspect of the invention provides a proofing facility which enables the attainment of the advantages asserted earlier for the integrated system and the method facets of the invention. The preferences articulated above for those previously described facets are applicable here as well.
In preferred embodiments of its ninth major independent facet or aspect, too, the invention is a proofing facility for producing a proof of an image, based upon a proofing data file and a color characteristic profile of such target facility. The invention is also for cooperating with a target printer facility that is distinct from the proofing facility and that prints a final hardcopy of the image based upon said proofing data file.
The proofing facility includes a device for producing the proof; and a communication link for receiving, from such target facility, such proofing data file and such color characteristic profile. It also includes one or more computer subsystems for using such proofing data and such color characteristic profile, together, in controlling the proof-producing device to produce a proof. Thus a common proofing file is applied both to producing the proof and to printing the final hardcopy.
The foregoing may represent a description or definition of the ninth aspect or facet of the invention in its broadest or most general form. Even as couched in these broad terms, however, it can be seen that this facet of the invention importantly advances the art.
In particular, the invention in its ninth aspect supplies a proofing facility thatxe2x80x94interacting with a complementary target facilityxe2x80x94can bring about the above-noted virtues of proofing and printing with just one data file in common. Once again, the preferences described for the other facets of the invention apply to this ninth one too.
The many foregoing operational principles and advantages of the invention will be more fully appreciated upon consideration of the following detailed description, with reference to the appended drawings, of which:

Proofing data file generated by target printer facility

Hewlett-Packard Development Company, L.P.