Serine protease derived-polypeptides and anti-peptide antibodies, systems and therapeutic methods for inhibiting coagulation

• US 5,679,639 A
• Filed: 08/22/1994
• Issued: 10/21/1997
• Est. Priority Date: 11/18/1991
• Status: Expired due to Fees

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Griffin, John H., Mesters, Rolf M.
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): MARSHALL, SANDRA GISELE
• Application Number:
  US08/295,411
• Time in Patent Office: 1,156 Days
• Field of Search: 530/326, 530/328, 512/14-15
• US Class Current: 514/13.7
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/755 Factors VIII , e.g. factor VIII C (AHF), factor VIII Ag (VWF)
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 9/647 Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups

Abstract

The present invention describes polypeptides and anti-peptide antibodies capable of inhibiting serine protease enzymatic activity. In particular, polypeptides and anti-peptide antibodies derived from the blood coagulation serine proteases Factor VIIa, Factor IXa, Factor Xa, Factor XIa, thrombin and plasma kallikrein are described that are capable of inhibiting coagulation. The polypeptide and antibody are useful in methods and systems for inhibiting serine proteases, and particularly for inhibiting blood coagulation processes mediated by serine proteases in vitro or in a human patient.

Claims

1. A polypeptide having an amino acid residue sequence that consists of an amino acid residue sequence shown at the residue positions indicated in parenthesis selected from the group consisting of:

(SEQ ID NO 1;

142-155), (SEQ ID NO 1;

311-325), (SEQ ID NO 1;

311-331), (SEQ ID NO 2;

315-330), (SEQ ID NO 2;

316-330), (SEQ ID NO 2;

316-336), (SEQ ID NO 2;

321-330), (SEQ ID NO 2;

321-335), (SEQ ID NO 2;

395-409), (SEQ ID NO 2;

395-414), (SEQ ID NO 2;

400-409), (SEQ ID NO 2;

400-414), (SEQ ID NO 3;

329-344), (SEQ ID NO 3;

330-344), (SEQ ID NO 3;

330-350), (SEQ ID NO 3;

404-418), (SEQ ID NO 3;

409-423), (SEQ ID NO 3;

415-429), (SEQ ID NO 4;

463-477), (SEQ ID NO 4;

463-478), (SEQ ID NO 4;

473-487), (SEQ ID NO 4;

474-487), (SEQ ID NO 4;

474-493), (SEQ ID NO 4;

481-495), (SEQ ID NO 4;

557-571), (SEQ ID NO 5;

289-304), (SEQ ID NO 5;

290-304), (SEQ ID NO 5;

290-310) and (SEQ ID NO 5;

374-388), wherein each polypeptide sequence is taken from a serine protease sequence, and wherein said polypeptide in vitro inhibits 50 percent (IC₅₀) of the activity of said serine protease at a concentration of at least 500 micromolar.

2. A composition comprising a coagulation-inhibiting amount of a polypeptide according to claim 1.

3. The composition of claim 2 wherein said coagulation-inhibiting amount is at least 0.1 weight percent polypeptide per weight of total composition.

4. The composition of claim 2 wherein said polypeptide is dispersed in a pharmaceutically acceptable excipient.