Claims for Patent: 8,507,436

Summary for Patent: 8,507,436

Title:	Peptides derived from plasminogen activator inhibitor-1 and uses thereof
Abstract:	The present invention relates to isolated 18-mer peptides corresponding to amino acid residues 369-386 of human plasminogen activator inhibitor 1 (PAI-1) and fragments thereof, compositions that include such peptides, and uses of such compositions for treating thromboembolic diseases and pathological conditions associated with neurological damage.
Inventor(s):	Higazi; Abd Al-Roof (Mobile Post Shimshon, IL)
Assignee:	D-Pharm Ltd. (Rehovot, IL)
Application Number:	12/670,099
Patent Claims:	1. An isolated peptide having the amino acid sequence as set forth in SEQ ID NO:3: R.sub.1-Arg-Met-Ala-Pro-Glu-Glu-Ile-Ile-Met-Asp-Arg-Pro-Phe-Leu-- Phe-Val-Val-Arg R.sub.2, wherein R.sub.1 is selected from the group consisting of a hydrogen, acetyl, alkyl, and an amino blocking group; and R.sub.2 is selected from the group consisting of a carboxyl, amide, ester, and a carboxyl blocking group. 2. The peptide according to claim 1 which has the amino acid sequence set forth in SEQ ID NOs:1, 4, 5 or 6. 3. The peptide according to claim 1 which has the amino acid sequence set forth in SEQ ID NO:1. 4. A pharmaceutical composition comprising an isolated peptide which has the amino acid sequence set forth in SEQ ID NO:3: R.sub.1-Arg-Met-Ala-Pro-Glu-Glu-Ile-Ile-Met-Asp-Arg-Pro-Phe-Leu-Phe-Val-V- al-Arg R.sub.2, wherein R.sub.1 is selected from the group consisting of a hydrogen, acetyl, alkyl, and an amino blocking group; and R.sub.2 is selected from the group consisting of a carboxyl, amide, ester, and a carboxyl blocking group, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 5. The pharmaceutical composition according to claim 4, wherein the peptide has the amino acid sequence set forth in SEQ ID NOs:1, 4, 5 or 6. 6. The pharmaceutical composition according to claim 4, wherein the peptide has the amino acid sequence set forth in SEQ ID NO:1. 7. A method for reducing neurological damage attributed to a stroke, traumatic brain injury, or ischemic brain injury in a subject comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an isolated peptide which has the amino acid sequence set forth in SEQ ID NO:3: R.sub.1-Arg-Met-Ala-Pro-Glu-Glu-Ile-Ile-Met-Asp-Arg-Pro-Phe-Leu-Phe-Val-V- al-Arg-R.sub.2, wherein R.sub.1 is selected from the group consisting of a hydrogen, acetyl, alkyl, and an amino blocking group; and R.sub.2 is selected from the group consisting of a carboxyl, amide, ester, and a carboxyl blocking group, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 8. The method according to claim 7, wherein the peptide has the amino acid sequence set forth in SEQ ID NOs:1, 4, 5, or 6. 9. The method according to claim 7, wherein the peptide has the amino acid sequence set forth in SEQ ID NO:1. 10. The method according to claim 7, wherein the pharmaceutical composition is administered by intravenous, subcutaneous, intramuscular, intraperitoneal, oral, topical, intradermal, transdermal, intranasal, epidural, ophthalmic, vaginal or rectal administration route. 11. The method according to claim 7, wherein the pharmaceutical composition further comprises a therapeutically effective amount of a fibrinolytic agent. 12. The method according to claim 11, wherein the fibrinolytic agent is selected from the group consisting of tPA, uPA, scuPA, tcuPA, streptokinase, rt-PA, alteplase, reteplase, lanoteplase, TNK-rt-PA, anisoylated plasminogen streptokinase complex, anistreplase, and derivatives thereof. 13. The method according to claim 11, wherein the isolated peptide or fragment thereof is administered after administration of the fibrinolytic agent. 14. A method of fibrinolytic therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a fibrinolytic agent and an isolated peptide which has the amino acid sequence as set forth in SEQ ID NO:3: R.sub.1-Arg-Met-Ala-Pro-Glu-Glu-Ile-Ile-Met-Asp-Arg-Pro-Phe-Leu-Phe-Val-V- al-Arg-R.sub.2, wherein R.sub.1 is selected from the group consisting of a hydrogen, acetyl, alkyl, and an amino blocking group; and R.sub.2 is selected from the group consisting of a carboxyl, amide, ester, and a carboxyl blocking group, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 15. The method according to claim 14, wherein the peptide has the amino acid sequence set forth in SEQ ID NOs: 4, 5, or 6. 16. The method according to claim 14, wherein the peptide has the amino acid sequence set forth in SEQ ID NO:1. 17. The method according to claim 14, wherein the fibrinolytic agent is selected from the group consisting of tPA, uPA, scuPA, tcuPA, streptokinase, rt-PA, alteplase, reteplase, lanoteplase, TNK-rt-PA, anisoylated plasminogen streptokinase complex, anistreplase, and derivatives thereof. 18. The method according to claim 14, wherein the pharmaceutical composition is administered by intravenous, subcutaneous, intramuscular, intraperitoneal, oral, topical, intradermal, transdermal, intranasal, epidural, ophthalmic, vaginal or rectal administration route. 19. The method according to claim 14, wherein the peptide is administered after administration of the fibrinolytic agent.

Details for Patent 8,507,436

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	ACTIVASE	alteplase	For Injection	103172	11/13/1987		2027-07-24
Genentech, Inc.	CATHFLO ACTIVASE	alteplase	For Injection	103172	09/04/2001		2027-07-24
Chiesi Usa, Inc.	RETAVASE	reteplase	For Injection	103786	10/30/1996		2027-07-24