Anti-factor IX/IXa antibodies

• US 6,391,299 B1
• Filed: 06/25/1999
• Issued: 05/21/2002
• Est. Priority Date: 01/17/1996
• Status: Expired due to Fees

• Current Assignee: University of Vermont & State Agricultural College
• Original Assignee: Smithkline Beecham Corporation (GSK plc), University of Vermont & State Agricultural College
• Inventors: Gross, Mitchell Stuart, Feuerstein, Giora Zeev, Patel, Arunbhai Haribhai, Blackburn, Michael Neal, Church, William Robert, Padlan, Eduardo Agustin, Nichols, Andrew John, Sylvester, Daniel Robert
• Primary Examiner(s): Duffy, Patricia A.
• Application Number:
  US09/344,050
• Time in Patent Office: 1,061 Days
• Field of Search: 424/133.1, 424/134.1, 424/139.1, 424/141.1, 424/142.1, 424/145.1, 424/158.1, 530/387.1, 530/387.3, 530/387.9, 530/388.1, 530/388.15, 530/388.25
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C07K 16/36 against blood coagulation factors
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Monoclonal antibodies directed against coagulation factors and their use in inhibiting thrombosis are disclosed.

Claims

1. An altered antibody comprising a heavy chain and a light chain, wherein the framework regions of said heavy and light chains are derived from at least one selected antibody and the amino acid sequences of the heavy chain complementarity determining regions (CDRs) are as set forth in SEQ ID NOs:

8, 9 and 10 and the amino acid sequences of the light chain CDRs are as set forth in SEQ ID NOs;

12, 13 and 14.

2. The altered antibody of claim 1 which is humanized.

3. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequences set forth in SEQ ID NOs:

31, 52 or 89 or of functional fragments thereof.

4. The humanized antibody of claim 2 wherein the light chain has the amino acid sequence set forth in SEQ ID NOs:

44, 57, 62, 74, 78 or 99 or of functional fragments thereof.

5. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequence set forth in SEQ ID NO:

31 and the light chain has the amino acid sequence set forth in SEQ ID NO;

44.

6. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequence set forth in SEQ ID NO:

52 and the light chain has the amino acid sequence set forth in SEQ ID NO;

57.

7. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequence set forth in SEQ ID NO:

52 and the light chain has the amino acid sequence set forth in SEQ ID NO;

62.

8. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequence set forth in SEQ ID NO:

52 and the light chain has the amino acid sequence set forth in SEQ ID NO;

74.

9. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequence set forth in SEQ ID NO:

52 and the light chain has the amino acid sequence set forth in SEQ ID NO;

78.

10. The humanized antibody of claim 2 wherein the heavy chain has the amino acid sequence set forth in SEQ ID NO:

89 and the light chain has the amino acid sequence set forth in SEQ ID NO;

99.

11. A pharmaceutical composition comprising the altered antibody of claim 2 and a pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11 further comprising acetylsalicylic acid.

13. A humanized antibody comprising a heavy chain having the amino acid sequence set forth in SEQ ID NO:

52 and a light chain having the amino acid sequence set forth in SEQ ID NO;

74.