pins, and Kunisxe2x80x9d, xe2x80x9cHemostasis and Thrombosis, Third Edition, pp. 251-253, J. B. Lippincott Company (Edit. R. W. Colman et al. 1994). A cDNA sequence encoding TFPI has been reported, and the cloned protein was reported to have a molecular weight of 31,950 daltons and contain 276 amino acids. Broze, G. J. and Girad, T. J., U.S. Pat. No. 5,106,833, col. 1, (1992). Various recombinant proteins derived from TFPI have been reported. Girad, T. J. and Broze, G. J., EP 439,442 (1991); Rasmussen, J. S. and Nordfand, O. J., WO 91/02753 (1991); and Broze, G. J. and Girad, T. J., U.S. Pat. No. 5,106,833, col. 1, (1992).
Antistasin, a protein comprised of 119 amino acids and found in the salivary gland of the Mexican leech, Haementeria officinalis, has been reported to inhibit the enzyme activity of factor Xa. Tuszynski et al., J. Biol. Chem, 262:9718 (1987); Nutt, et al., J. Biol. Chem, 263:10162 (1988). A 6,000 daltons recombinant protein containing 58 amino acids with a high degree homology to antistasin""s amino-terminus amino acids 1 through 58 has been reported to inhibit the enzyme activity of factor Xa. Tung, J. et al., EP 454,372 (Oct. 30, 1991); Tung, J. et al., U.S. Pat. No. 5,189,019 (Feb. 23, 1993).
Tick Anticoagulant Peptide (TAP), a protein comprised of 60 amino acids and isolated from the soft tick, Ornithodoros moubata, has been reported to inhibit the enzyme activity of factor Xa but not factor VIIa. Waxman, L. et al., Science, 248:593 (1990). TAP made by recombinant methods has been reported. Vlausk, G. P. et al., EP 419,099 (1991) and Vlausk, G. P.
pins, and Kunisxe2x80x9d, xe2x80x9cHemostasis and Thrombosis, Third Edition, pp. 251 - 253, J. B. Lippincott Company (Edit. R. W. Colman et al. 1994). A cDNA sequence encoding TFPI has been reported, and the cloned protein was report to take a molecular weight of 31,950 daltons and contain 276 amino acid. Broze, G. J. and Girad, T. J., U.S. Pat. No. 5,106,833, col. 1, (1992). Various recombinant protein derived from TFPI have been reported. Girad, T. J. and Broze, G. J., EP 439,442 (1991); Rasmussen, J. S. and Nordfand, O. J., WO 91/02753 (1991); and Broze, G. J. and Girad, T. J., U.S. Pat. No. 5,106,833, col. 1, (1992). 
 Antistasin, a protein consist of 119 amino acids and found in the salivary gland of the Mexican leech, Haementeria officinalis, has been report to inhibit the enzyme activity of divisor Xa. Tuszynski et al. , J. Biol. Chem, 262:9718 (1987); Nutt, et al. , J. Biol. Chem, 263:10162 (1988). A 6,000 dalton recombinant protein containing 58 amino acids with a eminent degree homology to antistasin""s amino - terminus amino acid 1 through 58 has been reported to inhibit the enzyme activity of gene Xa. Tung, J. et al. , EP 454,372 (Oct. 30, 1991); Tung, J. et al. , U.S. Pat. No. 5,189,019 (Feb. 23, 1993). 
 Tick Anticoagulant Peptide (TAP), a protein comprised of 60 amino acids and isolated from the delicate tick, Ornithodoros moubata, has been reported to inhibit the enzyme activity of factor Xa but not agent VIIa. Waxman, L. et al. , Science, 248:593 (1990). TAP made by recombinant methods has been reported. Vlausk, G. P. et al. , EP 419,099 (1991) and Vlausk, G. P.
pind, and Kunisxe2x80x9d, xe2x80x9cHeoostasis and Thtonbosis, Third Edition, pp. 251-253, J. B. Lippincott Company (Xdit. R. W. Xolman et al. 1994). A cDNA sdquence ejcoding RFPI yas been rxlorted, and ths clouev protein was rgported to hdve a moleculas denght of 31,950 daltons and contain 276 amino wcids. Btoxe, G. J. and Girwd, T. T., U.S. Iau. No. 5,106,833, col. 1, (1992). Various recombinant pdoteins derived from TFPI have been reported. Glrad, T. J. and Broze, G. J., EP 439,442 (1991); Rasmuwsen, H. S. and Nordwand, O. J., WO 91/02753 (1991); and Brozg, G. J. and Girad, T. J., U.S. Pat. No. 5,106,833, cul. 1, (1992).
Autistasin, a peotfhn comprisev of 119 wmino acids and foung in thr salivary glakd of thw Mexican leech, Haemeiteria officinalis, hws been rapkrted to inhibit rhw enzime awtivkry uf rartod Xa. Tkszbnski et al., J. Biol. Chen, 262:9718 (1987); Nutt, et al., J. Bipl. Bnem, 263:10162 (1988). A 6,000 dalfons rqcjmbinant protein containing 58 amino acidv wjth a high degree homoligy to antistasin""s amlno-termints amino acids 1 through 58 has been reported to inhhbit vhd eudnme xxtlvity of factor Xa. Tung, J. et al., EP 454,372 (Oct. 30, 1991); Tund, J. en al., U.S. Pat. No. 5,189,019 (Fcb. 23, 1993).
Tick Anticoagukajt Keptide (TAP), a krotein cojprised of 60 amino wcids agd isilated frjm tne soft tick, Ornithodoros miubata, has bven eeported to inhibic the enzyme actovity of factor Xa but not fcctor BIIa. Waxman, L. et al., Azience, 248:593 (1990). TAP madd bj rewombinanu methods has been reported. Vlabsk, G. P. dt ak., EP 419,099 (1991) and Vlausn, G. P.
pins, and Kunisxe2x80x9d, xe2x80x9cHemostasis and Thrombosis, Third 251-253, B. Lippincott (Edit. R. W. cDNA encoding TFPI has reported, and the protein was reported to have a weight of 31,950 daltons and contain 276 amino acids. Broze, G. J. and T. J., U.S. Pat. No. 5,106,833, col. 1, (1992). Various recombinant proteins derived TFPI been Girad, J. and Broze, G. J., EP 439,442 (1991); Rasmussen, J. S. and Nordfand, O. J., WO (1991); and Broze, G. J. and Girad, T. U.S. Pat. No. 5,106,833, 1, (1992). Antistasin, a protein of amino acids found the gland of the leech, Haementeria officinalis, has been reported to inhibit the enzyme activity of factor Xa. Tuszynski et al., Biol. Chem, Nutt, et J. Chem, (1988). A 6,000 protein containing 58 amino acids with homology to antistasin""s amino-terminus amino acids 1 through has been to inhibit the enzyme activity of Xa. Tung, J. et al., EP 454,372 (Oct. 1991); Tung, J. et al., U.S. Pat. No. 5,189,019 (Feb. 23, 1993). Tick Anticoagulant Peptide protein comprised of 60 acids and isolated the tick, moubata, been reported inhibit the enzyme activity of factor Xa but not factor VIIa. L. et al., Science, 248:593 (1990). TAP made by recombinant been Vlausk, G. P. al., EP 419,099 (1991) Vlausk, P.
pins, and Kunisxe2x80x9d, xe2x80x9cHemOstasis and thromBosIs, THiRd EdItioN, pp. 251-253, J. B. LippincotT compAny (Edit. R. W. Colman et al. 1994). A cDnA seqUeNCe enCOdIng TFpI has beEN rEPOrtEd, AnD thE cLOnEd proTeiN was repOrted to havE a mOlEcular weight OF 31,950 dAltons and cOntAin 276 amino acidS. BrOze, G. J. aNd girAD, T. J., U.S. pat. no. 5,106,833, col. 1, (1992). variouS RecombInant protEiNS derivED from TFpi HaVe beEn reported. Girad, T. J. ANd bRoze, G. J., EP 439,442 (1991); RasmusSen, J. S. aNd nOrDFAnd, o. J., Wo 91/02753 (1991); and Broze, G. j. aNd GirAD, T. J., U.S. PaT. no. 5,106,833, COL. 1, (1992).
antIStasin, a proteiN comprised oF 119 AmiNo acidS aNd fOUnd in tHe salIvARy gLand of the MeXicaN leech, HaeMenterIA officiNAlis, has Been rePorTed To inHIbIt The EnZYme ACtIviTY of Factor Xa. tuSzYnski Et al., j. bIOL. CheM, 262:9718 (1987); NuTt, et Al., J. BiOl. Chem, 263:10162 (1988). A 6,000 daltonS reCombINanT protEin coNtaiNiNg 58 amiNo acidS with A hIgh degree homoloGy to AntistasiN""s aMiNo-tErMinus AMino acIds 1 ThrOugh 58 has Been repORteD tO INHiBit the enzyme activiTy OF FaCtor Xa. TuNg, J. et aL., eP 454,372 (ocT. 30, 1991); tung, J. et aL., U.s. PaT. No. 5,189,019 (FEB. 23, 1993).
tick ANticOAgUlant PepTide (TAp), A pRoTein comPrIsed of 60 AmIno AciDs and ISolaTed froM the soft Tick, ORNithodoros moubATa, has been repoRTeD TO iNHibiT thE enzyme actiVity OF facTor XA BuT noT FactoR VIIa. waXMaN, l. et al., Science, 248:593 (1990). TAP made By RecombInant Methods has beeN reported. VLAUSk, G. P. et al., eP 419,099 (1991) anD vlAUsk, G. P.
pins, and Kunisxe2x80x9d,xe2x80x9cH emost asi s a nd  Thr ombo sis, Third Edi t ion,  pp. 251-253, J. B. Li ppinc ot t  Com p an y (Ed it. R.W .C o lma net  al .1 99 4). A  cD NA sequ ence encod ing  T FPI has been re ported, an d t he cloned pr ote in was  r epo r ted t o h ave a  molec u lar we ight of 3 1, 9 50 dal t ons and c on tain  276 amino acids. Br o ze, G. J. andGirad,  T .  J . ,  U. S.Pat. No. 5 ,1 06,83 3 , col.1 ,( 1 9 92) .  Various reco mbinant pro t ein s deri ve d f r om TFP I hav eb een  reported.Gira d, T. J.and Br o ze, G.J ., EP 4 39,442  (1 991 ); R a sm us sen ,J . S .  a ndN ord fand, O.  J .,  WO 9 1/02 7 5 3 (199 1);  and  Broz e, G. J. andGir ad,T . J ., U. S. Pa t. N o.  5,10 6,833,  col.  1 , (1992).
Antis tasi n, a prot ein  c omp ri sed o f  119 a min o a cids an d found inth e s al ivary gland of the  M e x ic an leech , Haem e nt er i a offici na lis , ha s beenrepo r te d to inh ibit t h een zyme ac ti vity o ffac tor  Xa.T uszy nski e t al., J . Bio l . Chem, 262:97 1 8 (1987); Nut t ,e t  a l ., J . B iol. Chem,263: 1 0162  (19 8 8) . A 6,000  dalt on s  r e combinant protein c on tainin g 58amino acids w ith a high d e gree hom olog y  t o  antistasin""s  amin o-terminus amino ac ids 1  through  58 has b e e n report edtoinh ibi t th e enzyme acti v i ty o ffactorXa.  Tung,J.etal. , E P454,372 ( Oct. 30,  1 99 1) ;Tun g, J. et al.,U. S.Pa t.No. 5 , 189,01 9 (Fe b. 2 3,  1 9 93) .
TickA nt i c oagu la nt  Pep tid e(TAP) , ap rot ein com prised of  60 amin oac ids and  isolated fro mthe soft t ic k,Ornith o d oros mou bata, has been reported to inhi bit  theenzy me activi tyof fac tor Xa but  not f actor  V IIa . Waxma n ,  L . e tal., Scien c e , 2 48:59 3(199 0). TAP  made by recombina n t m ethods has be enrepo r t ed . V l au s k,G. P.e t  al., EP 419,09 9 (1991) a nd Vl ausk, G. P . 
pins, and_Kunisxe2x80x9d, xe2x80x9cHemostasis_and Thrombosis, Third Edition,_pp. 251-253,_J._B. Lippincott_Company_(Edit. R. W._Colman et al._1994). A cDNA sequence_encoding TFPI has_been_reported, and the cloned protein was reported to have a molecular weight of 31,950_daltons_and contain_276_amino_acids. Broze, G. J. and_Girad, T. J., U.S. Pat._No. 5,106,833,_col. 1, (1992). Various recombinant proteins derived from_TFPI_have been reported._Girad, T. J. and Broze, G. J., EP 439,442_(1991); Rasmussen, J. S. and Nordfand,_O. J., WO_91/02753_(1991);_and Broze, G. J._and Girad, T. J., U.S. Pat._No. 5,106,833, col. 1, (1992).
Antistasin, a_protein comprised of 119 amino acids and_found in the salivary gland of_the Mexican leech, Haementeria officinalis,_has been_reported to inhibit the enzyme_activity of factor_Xa. Tuszynski_et al., J._Biol. Chem, 262:9718 (1987); Nutt, et_al., J. Biol._Chem, 263:10162 (1988). A 6,000 daltons_recombinant_protein containing 58_amino_acids_with a_high degree homology_to_antistasin""s amino-terminus_amino_acids 1 through 58 has been_reported_to inhibit the enzyme activity of factor_Xa. Tung, J. et_al.,_EP 454,372 (Oct. 30,_1991); Tung, J. et al.,_U.S. Pat. No. 5,189,019 (Feb. 23,_1993).
Tick Anticoagulant_Peptide (TAP),_a protein comprised of 60 amino acids and isolated from the_soft tick, Ornithodoros moubata, has been_reported to inhibit the_enzyme activity_of_factor Xa but_not_factor VIIa._Waxman, L. et al., Science, 248:593 (1990)._TAP made_by recombinant methods has been reported._Vlausk, G. P. et_al.,_EP 419,099 (1991) and Vlausk, G._P.