Inhibitors Of Complement Activation

Patent metadata

Field	Value
Publication number	US-2016264682-A1
Application number	US-201615075364-A
Country	US
Kind code	A1
Filing date	Mar 21, 2016
Priority date	Feb 20, 1998
Publication date	Sep 15, 2016
Grant date	—

Abstract

The invention relates to factor D inhibitors, which bind to factor D and block the functional activity of factor D 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 factor D and blocked its ability to activate complement was generated and designated 166-32. The hybridoma producing this antibody was deposited at the American Type Culture Collection, 10801 University Blvd., Manassas, Va. 20110-2209, under Accession Number HB-12476.

First claim

1 . An inhibitor of complement activation which specifically binds factor D which at a molar ratio of about 1.5:1 (inhibitor: factor D) can substantially inhibit complement activation.

2 . (canceled)

3 . The inhibitor of claim 1 wherein the inhibition of complement activation is determined in vitro.

4 . The inhibitor of claim 1 wherein the inhibition of complement activation is determined in vitro by an extracorporeal assay.

5 . An inhibitor of complement activation which binds to a region of human factor D between (and including) amino acid residue numbers Cys154 and Cys170.

6 . The inhibitor of claim 5 which does not bind to human factor D if amino acid residues Arg156, His159 and Leu168 are absent.

7 . The inhibitor of claim 1 which is an antibody or a homologue, analogue or fragment thereof, a peptide, a peptidomimetic or an organic compound.

8 . The inhibitor of claim 7 wherein the antibody fragment is Fab, F(ab′) 2 , Fv or single chain Fv.

9 . The inhibitor of claim 7 wherein the antibody is a chimeric, humanized, deimmunised or human antibody.

10 . (canceled)

11 . (canceled)

12 . A monoclonal antibody or a fragment, analogue or homologue thereof, or a peptide, oligonucleotide, peptidomimetic or an organic compound which binds to the same epitope on factor D as the antibody 166-32.

13 . The fragment of claim 12 which is an are Fab, F(ab′) 2 , Fv or single chain Fv.

14 . The chimeric form, having a mouse variable region and a human constant region, of the Fab fragment of claim 13 .

15 . (canceled)

16 . A cell line producing the fragment of claim 13 .

17 . A cell line producing the chimeric Fab fragment of claim 14 .

18 . (canceled)

19 . (canceled)

20 . A method of treating diseases or conditions that are mediated by excessive or uncontrolled activation of the complement system comprising administering, in vivo or ex vivo, an inhibitor according to claim 1 .

21 . A method of treating complement-mediated conditions associated with cardiopulmonary bypass comprising administering, in vivo or ex vivo, an inhibitor according to claim 1 .

Assignees

• Genentech Inc

Inventors

• Fung Michael
• Sun William N C
• Sun Cecily R Y

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title