Novel ctla4-ig immunoadhesins

Patent metadata

Field	Value
Publication number	US-2016264643-A1
Application number	US-201615159667-A
Country	US
Kind code	A1
Filing date	May 19, 2016
Priority date	Feb 19, 2010
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present application relates to CTLA4-Ig immunoadhesins that target CD80 and CD86, and their use, particularly for therapeutic purposes.

First claim

We claim:

1 . An immunoadhesin comprising a first domain comprising a variant CTLA4 as compared to SEQ ID NO:2 and a second domain comprising an IgG Fc region, wherein said CTLA4 variant comprises an amino acid modification selected from the group consisting of T51N, A29H, M53Y, L61E, and K93Q, wherein said variant provides enhanced binding to B7-1, B7-2, or both B7-1 and B7-2.

2 . An immunoadhesin according to claim 1 , wherein said variant comprises a combination of substitutions selected from the group consisting of A29H/K93Q, A29H/M53Y, A29H/T51N, T51N/K93Q, T51N/M53Y, A29H/L61E/K93Q, A29H/M53Y/K93Q, A29H/M53Y/L61E, A29H/T51N/L61E, M53Y/L61E/K93Q, T51N/L61E/K93Q, T51N/M53Y/L61E, A29H/M53Y/L61E/K93Q, A29H/T51N/L61E/K93Q, A29H/T51N/M53Y/K93Q, A29H/T51N/M53Y/L61E, T51N/M53Y/L61E/K93Q, and A29H/T51N/M53Y/L61E/K93Q.

3 . An immunoadhesin according to claim 2 , wherein said variant comprises a combination of substitutions selected from the group consisting of T51N/L61E/K93Q, A29H/T51N/L61E/K93Q, A29H/T51N, T51N/M53Y, and T51N/M53Y/L61E.

4 . A method of treating a patient with an immune related disorder, wherein said treatment comprises the step of administering to said patient an immunoadhesin comprising an amino acid sequence corresponding to SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, or SEQ ID NO:33.

5 . A method of treatment according to claim 4 , wherein said immune related disorder is selected from the group consisting of Crohn's disease, systemic lupus erythematosus (SLE), lupus nephritis, psoriatic arthritis, psoriasis, rheumatoid arthritis, ulcerative colitis, and transplant rejection.

6 . A nucleic acid encoding the immunoadhesin of claim 1 .

7 . A host cell comprising the nucleic acid of claim 6 .

8 . A method of making an immunoadhesin comprising culturing the host cell of claim 7 under conditions wherein said immunoadhesin is produced.

Assignees

• Xencor Inc

Inventors

• Lazar Gregory A
• Bernett Matthew J

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/06

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

• A61P37/02

  Immunomodulators · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P29/00

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