Biomarkers of immunomodulatory effects in humans treated with anti-CD200 antibodies
US-9180186-B2 · Nov 10, 2015 · US
US9862767B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9862767-B2 |
| Application number | US-201514739862-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jun 15, 2015 |
| Priority date | Feb 11, 2010 |
| Publication date | Jan 9, 2018 |
| Grant date | Jan 9, 2018 |
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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.
Opening claim text (preview).
The invention claimed is: 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 antibody, wherein the anti-CD200 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 , wherein the cancer comprises cancer cells that express CD5. 3. The method of claim 1 , wherein the cancer is a liquid tumor. 4. The method of claim 3 , wherein the liquid tumor is a chronic lymphocytic leukemia or multiple myeloma. 5. The method of claim 4 , wherein the chronic lymphocytic leukemia is a B cell chronic lymphocytic leukemia. 6. The method of claim 1 , further comprising administering to the human an anti-CD20 therapeutic agent. 7. The method of claim 6 , wherein the anti-CD20 therapeutic agent is an anti-CD20 antibody or a CD20-binding fragment thereof. 8. The method of claim 7 , wherein the anti-CD20 antibody is rituximab, ofatumumab, TRU-015, veltuzumab, ocrelizumab, or AME-133v. 9. The method of claim 7 , wherein the anti-CD20 antibody, or CD20-binding fragment thereof, is conjugated to a toxin. 10. 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. 11. The method of claim 1 , wherein the anti-CD200 antibody, or CD200-binding fragment thereof, inhibits the interaction between CD200 and CD200R. 12. The method of claim 1 , wherein the anti-CD200 antibody, or CD200-binding fragment thereof, is murine, chimeric, humanized, or fully human. 13. 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.
Antineoplastic agents · CPC title
Complementarity determining region [CDR] · CPC title
specific for leukemia · CPC title
against CD20 · CPC title
comprising antibodies · CPC title
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