Therapeutic methods using anti-cd200 antibodies

Patent metadata

Field	Value
Publication number	US-2016009803-A1
Application number	US-201514739862-A
Country	US
Kind code	A1
Filing date	Jun 15, 2015
Priority date	Feb 11, 2010
Publication date	Jan 14, 2016
Grant date	—

Abstract

The present disclosure relates to anti-CD200 antibodies and to use of the antibodies in methods for treating autoimmune disorders and cancer. Also featured are biomarkers for use in selecting or prescribing a treatment modality for a patient with an autoimmune disorder and/or cancer. In addition, the disclosure features methods of treatment using an anti-CD200 antibody in combination with one or more additional therapeutic agents such as an anti-CD20 therapeutic agent.

First claim

1 . A method for treating a human afflicted with a cancer, the method comprising administering to the human an anti-CD200 antibody, or a CD200-binding fragment thereof, in an amount that is sufficient to treat the cancer, wherein the cancer is resistant, or is suspected of being resistant, to therapy with an anti-CD20 therapeutic agent, wherein the antibody, or CD200-binding fragment thereof, contains one of the following paired set of CDRs:
(i) a HCDR1 comprising the amino acid sequence: GFNIKDYYMH (SEQ ID NO:10); a HCDR2 comprising the amino acid sequence: WIDPENGDTKYAPKFQG (SEQ ID NO:11); a HCDR3 comprising the amino acid sequence: KNYYVSNYNFFDV (SEQ ID NO:12); a LCDR1 comprising the amino acid sequence: SASSSVRYMY (SEQ ID NO:13); a LCDR2 comprising the amino acid sequence: DTSKLAS (SEQ ID NO:14); and a LCDR3 comprising the amino acid sequence: FQGSGYPLT (SEQ ID NO:15); (ii) a HCDR1 comprising the amino acid sequence: GFNIKDYYIH (SEQ ID NO:16); a HCDR2 comprising the amino acid sequence: WIDPEIGATKYVPKFQG (SEQ ID NO:17); a HCDR3 comprising the amino acid sequence: LYGNYDRYYAMDY (SEQ ID NO:18); a LCDR1 comprising the amino acid sequence: KASQNVRTAVA (SEQ ID NO:19); a LCDR2 comprising the amino acid sequence: LASNRHT (SEQ ID NO:20); and a LCDR3 comprising the amino acid sequence: LQHWNYPLT (SEQ ID NO:21); (iii) a HCDR1 comprising the amino acid sequence: GYSFTDYIIL (SEQ ID NO:22); a HCDR2 comprising the amino acid sequence: HIDPYYGSSNYNLKFKG (SEQ ID NO:23); a HCDR3 comprising the amino acid sequence: SKRDYFDY (SEQ ID NO:24); a LCDR1 comprising the amino acid sequence: KASQDINSYLS (SEQ ID NO:25); a LCDR2 comprising the amino acid sequence: RANRLVD (SEQ ID NO:26); and a LCDR3 comprising the amino acid sequence: LQYDEFPYT (SEQ ID NO:27); (iv) a HCDR1 comprising the amino acid sequence: GYTFTEYTMH (SEQ ID NO:28); a HCDR2 comprising the amino acid sequence: GVNPNNGGALYNQKFKG (SEQ ID NO:29); a HCDR3 comprising the amino acid sequence: RSNYRYDDAMDY (SEQ ID NO:30); a LCDR1 comprising the amino acid sequence: KSSQSLLDIDEKTYLN (SEQ ID NO:31); a LCDR2 comprising the amino acid sequence: LVSKLDS (SEQ ID NO:32); and a LCDR3 comprising the amino acid sequence: WQGTHFPQT (SEQ ID NO:33); or (v) a HCDR1 comprising the amino acid sequence: AFNIKDHYMH (SEQ ID NO:34); a HCDR2 comprising the amino acid sequence: WIDPESGDTEYAPKFQG (SEQ ID NO:35); a HCDR3 comprising the amino acid sequence: FNGYQALDQ (SEQ ID NO:36); a LCDR1 comprising the amino acid sequence: TASSSVSSSYLH (SEQ ID NO:37); a LCDR2 comprising the amino acid sequence: STSNLAS (SEQ ID NO:38); and a LCDR3 comprising the amino acid sequence: RQYHRSPPIFT (SEQ ID NO:39).

2 . The method of claim 1 , further comprising identifying the human as having the cancer that is resistant, or is suspected to be resistant, to treatment with an anti-CD20 therapeutic agent.

3 . The method of claim 1 , wherein the cancer comprises cancer cells that express CD5.

4 . The method of claim 3 , further comprising identifying the cancer as comprising cells that express CD5.

5 . The method of claim 1 , wherein the cancer is a solid tumor.

6 . The method of claim 1 , wherein the cancer is a liquid tumor.

7 . The method of claim 6 , wherein the liquid tumor is a chronic lymphocytic leukemia or multiple myeloma.

8 . The method of claim 7 , wherein the chronic lymphocytic leukemia is a B cell chronic lymphocytic leukemia.

9 . The method of claim 1 , further comprising administering to the human an anti-CD20 therapeutic agent.

10 . The method of claim 9 , wherein the anti-CD20 therapeutic agent is an anti-CD20 antibody or a CD20-binding fragment thereof.

11 . The method of claim 10 , wherein the anti-CD20 antibody is rituximab, ofatumumab, TRU-015, veltuzumab, ocrelizumab, or AME-133v.

12 . The method of claim 10 , wherein the anti-CD20 antibody, or CD20-binding fragment thereof, is conjugated to a toxin.

13 . The method of claim 1 , wherein the anti-CD200 antibody, or CD200-binding fragment thereof, is a bispecific antibody comprising a first antigen combining site that binds to CD200 and a second antigen combining site that binds to CD20.

14 . The method of claim 1 , wherein the anti-CD200 antibody, or CD200-binding fragment thereof, inhibits the interaction between CD200 and CD200R.

15 . The method of claim 1 , wherein the anti-CD200 antibody, or CD200-binding fragment thereof, is murine, chimeric, humanized, or fully human.

16 . The method of claim 1 , wherein the CD200-binding fragment is selected from the group consisting of a Fab fragment, a F(ab′) 2 fragment, a Fab′ fragment, an scFv fragment, a minibody, a diabody, or a triabody.

17 . A method for treating a human afflicted with cancer, the method comprising administering to the human: (a) an anti-CD200 antibody, or CD200-binding fragment thereof, and (b) an anti-CD20 therapeutic agent, to thereby treat the cancer.

18 . A method for treating a human afflicted with a cancer, the method comprising administering to the human an anti-CD200 antibody, or CD200-binding fragment thereof, in an amount that is sufficient to treat the cancer, wherein the cancer comprises cancer cells expressing CD5.

19 - 21 . (canceled)

Assignees

• Alexion Pharma Inc

Inventors

• Rother Russell P
• Yan Yan

Classifications

• C07K2317/31

  multispecific · CPC title

• C07K2317/626

  Diabody or triabody · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title