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1. WO1992008472 - AGENTS ANTITHROMBOSE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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Claims

1. A platelet antiadhesive peptide in purified and isolated form obtainable from a snake venom selected from the group consisting of: Agkistrodon acutus ,
Agkistrodon halys blomhoffi, Agkistrodon contortrix mokasen. Bitis arietans . Bitis caudalis. Bitis gabonica. Bitis g. rhinoceros . Bothrops asper. Bothrops alternata. Bothrops atrox, Bothrops cotiara, Bothrops araraca, Bothrops newiedi . Bothrops medusa . Bothrops schlegli. Cerastes cerastes . Cerastes vipera . Crotalus admanteus . C. atrox. C. basilicus. C. durissus totonatacus . C. h. horridus . C. m. molossus. C. ruber. C. scutalatus. C. v. cereberus . C. v. helleri. C. v. lutosus . C. v. oreganus , Echis carinatus sochurecki. Eristicophis macmahoni .
Pseudocerastes persicus . Sistrurus m. barbouri , Sistrurus c. tergeminus . Trimeresurus flavoviridis . Trimeresurus gramineus . Vipera lebetina. Vipera ammondytes . Vipera palastinae, and Vipera r. russelli.

2. The antiadhesive of claim 1 wherein the snake venom is Cerastes cerastes C. h. horridus Vipera r. russeli. or Pseudocerastes persicus.

3. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N- terminal sequence:
Asp-Leu-Glu-Cys-Pro-Ser-Gly-Trp-Ser-Ser-Tyr-Asp-Arg-Tyr-Cys-Tyr-Lys-Pro-Phe-Lys-Gln-Glu-Met-Thr-Trp-Ala-Asp-Ala-Glu-Arg-Phe-Cys-Ser-Glu-Gln-Ala-Lys.

4. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N-terminal sequence:
Asp-Cys-Pro-Ser-Asp-Trp-Ser-Ser-Tyr-Glu-Gly-His-Cys-Tyr-Arg-Val-Phe-Gln-Gln-Glu-Met-Trp-Asp-Asp-Ala-Glu-Lys-Phe.

5. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N-terminal sequence:
Leu-Asp-Cys-Pro-Leu-Asp-Ser-Ser-Xaa-His-Glu-Glu-Lys-Cys-Tyr-Lys-Val-Phe-Phe-Leu-Leu-Xaa-Thr-Trp-Glu.

6. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N-terminal sequence:
Asp-Gln-Asp-Cys-Leu-Pro-Gly-Trp-Ser-Tyr-Tyr-Glu-Lys-Tyr-Cys-Tyr-Lys-Val-Phe-Glu.

7. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N-terminal sequence:
Asp-Cys-Pro-Ser-Asp-Trp-Ser-Ser-His-Glu-Gly- His-Cys-Tyr-Lys-Val-Phe-Asn-Leu-Tyr-Lys-Thr-Trp-Glu-Asp- Ala-Glu-Lys-Phe-Cys-Thr-Glu-Gln-Ala-Asn-Gly-Gly-His-Leu- Val-Ser-Ile-Asp-Ser-Lys-Lys-Glu-Ala-Asn-Phe.

8. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N-terminal sequence:
Ala-Leu-Asn-Cys-Ala-Ser-Gly-Trp-Ser-Ala-Tyr- Asp-Gln-His-Cys-Tyr-Lys-Ala-Phe-Asp-Glu-Pro-Lys-Ser-Trp- Ala-Asp-Asp-Glu-Lys-Phe.

9. The antiadhesive of claim 1 which is a heterodimer wherein one member of said heterodimer has a MW of about 14 kd and has the N-terminal sequence:
Gly-Phe-Ser-Cys-Pro-Asn-Gly-Trp-Ser-Ser-Phe-Gly-Arg-Tyr-Cys-Tyr-Lys-Pro-lie-Glu-Pro-Leu.

10. A pharmaceutical composition which
comprises an amount of the platelet antiadhesive of claim l effective to prevent thrombus formation in admixture with the pharmaceutically acceptable excipient.

11. A method to inhibit platelet adherence and thrombus formation in animal subjects which method comprises administering to a subject in need of such treatment an effective amount of the platelet
antiadhesive of claim 1 or pharmaceutical composition thereof .

12. A method for treating a subject suspected of having a platelet associated ischemic syndrome which method comprises administering to a subject in need of such treatment an effective amount of the platelet antiadhesive of claim 1 or a pharmaceutical composition thereof .

13. A method for preventing restenosis
following angioplasty in animal subjects which method comprises administering to a subject in need of such treatment an effective amount of the platelet
antiadhesive of claim 1 or a pharmaceutical composition thereof .

14. A method for preventing platelet loss during extracorporeal circulation of the blood which comprises contacting blood as it is withdrawn from a subject with the platelet antiadhesive of claim 1 or a pharmaceutical composition thereof.

15. A composition of DNA molecules which consists of DNA molecules comprising a sequence encoding the platelet antiadhesive of claim 1.

16. An expression system capable of producing a platelet antiadhesive peptide, said peptide obtainable from a snake venom selected from the group consisting of that set forth in claim 1, when transformed into a suitable host and when said host is cultured under conditions favoring expression, said expression system comprising DNA encoding the platelet antiadhesive peptide operably linked to control sequences compatible with said hOS -

17. A recombinant host transformed with the expression system of claim 16.

18. A method to produce a platelet
antiadhesive (PAA) peptide which comprises culturing the host cell of claim 17 under conditions favoring
expression of the DNA encoding said PAA peptide; and
recovering said PAA peptide from the cell culture.

19. Antibodies immunoreactive with the platelet antiadhesive of claim 1.