Complement inhibitors and uses thereof

• US 8,221,756 B2
• Filed: 03/11/2011
• Issued: 07/17/2012
• Est. Priority Date: 03/23/2000
• Status: Expired due to Fees

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Fung, Michael S. C., Sun, Cecily R. Y., Sun, William N. C.
• Primary Examiner(s): WEN, SHARON X
• Application Number:
  US13/045,895
• Publication Number:
  US 20110165169A1
• Time in Patent Office: 494 Days
• Field of Search: None
• US Class Current: 424/144.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• 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 2317/55 : Fab or Fab'

Abstract

The invention relates to C2a inhibitors, which bind to C2a and block the functional activity of C2a in complement activation. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab′)₂ and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. A monoclonal antibody, which bound to C2a and blocked its ability to activate complement was generated and designated 175-62. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number PTA-1553.

Claims

1. A method of treating a disease or condition that is mediated by excessive or uncontrolled activation of the complement system comprising administering an antibody that binds complement component C2a or the C2a portion of complement component C2 or a C2a binding fragment thereof, wherein the molar ratio of antibody to C2 is one antibody molecule to two C2 or C2a molecules, and the antibody inhibits the classical or lectin complement activation more than 50%, wherein the disease or condition is tissue damage due to ischemia/reperfusion.

2. The method of claim 1, wherein the antibody is a monoclonal antibody.

3. The method of claim 1, wherein the antibody is chimeric, deimmunized, humanized, or human antibody.

4. The method of claim 1, wherein the antibody is the monoclonal antibody 175-62 produced from the hybridoma deposited with the ATCC and designated PTA-1553.

5. The method of claim 1, wherein the antibody binds to the same epitope as the monoclonal antibody 175-62 produced from the hybridoma deposited with the ATCC and designated PTA-1553.

6. The method of claim 1, wherein the antibody is a humanized antibody that binds to the same epitope as the monoclonal antibody 175-62 produced from the hybridoma deposited with the ATCC and designated PTA-1553.

7. The method of claim 1, wherein the C2a binding fragment is a Fab, F(ab′

)₂, Fv, or single chain Fv.

8. The method of claim 1, wherein the C2a binding fragment is a Fab, F(ab′

)₂, Fv, or single chain Fv of the monoclonal antibody 175-62 produced from the hybridoma deposited with the ATCC and designated PTA-1553.

9. The method of claim 1, wherein the antibody or C2a binding fragment is in a composition comprising a pharmacologically acceptable carrier, excipient, stabilizer, or diluent.

10. The method of claim 1, wherein the antibody or C2a binding fragment is administered by intravenous infusion, intravenous bolus injection, intraperitoneal, intradermal, intramuscular, subcutaneous, intranasal, intratracheal, intraspinal, intracranial or oral routes.

11. The method of claim 1, wherein the antibody or C2a binding fragment is administered ex vivo.

12. The method of claim 1, wherein the inhibition of complement activation is determined in vitro.