Claims for Patent: 8,637,014

Summary for Patent: 8,637,014

Title:	Antibodies to OX-2/CD200 and uses thereof in inhibiting immune responses
Abstract:	This disclosure provides methods and compositions for inhibiting immune responses. The disclosure also provides methods and compositions for inhibiting graft rejection and promoting or prolonging graft survival.
Inventor(s):	Rother; Russell P. (Oklahoma City, OK), Faas McKnight; Susan (Old Lyme, CT)
Assignee:	Alexion Pharmaceuticals, Inc. (Cheshire, CT)
Application Number:	13/533,546
Patent Claims:	1. A method of inhibiting an immune response in a subject having an autoimmune disease or an antibody mediated inflammatory disease, wherein said method comprises administering to a subject in need thereof an effective amount of i) an agent which inhibits interaction between CD200 and CD200R and ii) an immunosuppressive or immunomodulatory drug, wherein said agent is an antibody, or an antigen-binding fragment thereof, which binds to CD200, and wherein said antibody or antigen-binding fragment thereof has reduced or no effector function. 2. The method of claim 1, wherein said immune response is a humoral response. 3. The method of claim 2, wherein said immune response is an antibody mediated response. 4. The method of claim 1, wherein said immunosuppressive drug is cyclosporine A or rapamycin. 5. The method of claim 1, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of: a human antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a primatized antibody or antigen-binding fragment thereof, a chimeric antibody or antigen-binding fragment thereof, a murine antibody or antigen-binding fragment thereof, and a de-immunized antibody or antigen-binding fragment thereof. 6. The method of claim 1, wherein said antigen-binding fragment is selected from the group consisting of: a single-chain antibody, Fab, Fab', F(ab').sub.2, F(ab').sub.3, Fd, Fv, domain antibody, and any fragment of an anti-CD200 immunoglobulin that confers specific binding to CD200. 7. The method of claim 1, wherein said immunomodulatory or immunosuppressive drug is a calcineurin inhibitor. 8. The method of claim 7, wherein said calcineurin inhibitor is selected from the group consisting of tacrolimus and cyclosporine A. 9. The method of claim 1, wherein said immunomodulatory or immunosuppressive drug is selected from the group consisting of: adriamycin, azathiopurine, busulfan, cyclophosphamide, cyclosporine A, fludarabine, 5-fluorouracil, methotrexate, mycophenolate mofetil, a nonsteroidal anti-inflammatory, sirolimus (rapamycin), and tacrolimus (FK-506). 10. The method of claim 1, wherein said immunomodulatory or immunosuppressive drug is an antibody selected from the group consisting of: muromonab-CD3, alemtuzumab, basiliximab, daclizumab, rituximab, and anti-thymocyte globulin. 11. The method of claim 1, wherein said subject is human. 12. The method of claim 1, wherein said agent is administered i) prior to said drug, ii) subsequently to said drug, or iii) simultaneously with said drug. 13. The method of claim 1, wherein said autoimmune disease is an autoimmune hemolytic anemia. 14. The method of claim 1, wherein said agent is administered systemically. 15. The method of claim 1, wherein said agent is administered locally. 16. The method of claim 1, wherein said immune response is a primary response. 17. The method of claim 1, wherein said immune response is a secondary response. 18. A method of decreasing what constitutes an effective amount of an immunosuppressive or immunomodulatory drug administered to a subject having an autoimmune disease or an antibody mediated inflammatory disease, said method comprising administering to said subject: i) said immunosuppressive or immunomodulatory drug and ii) an agent which inhibits interaction between CD200 and CD200R , wherein less of said drug is required to effect immunosuppression or immunomodulation as compared to administering said drug without said agent, wherein said agent is an antibody, or an antigen-binding fragment thereof, which binds to CD200, and wherein said antibody or antigen-binding fragment thereof has reduced or no effector function. 19. The method of claim 18 wherein said drug is cyclosporine A or rapamycin. 20. The method of claim 18, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of a human antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a primatized antibody or antigen-binding fragment thereof, a chimeric antibody or antigen-binding fragment thereof, a murine antibody or antigen-binding fragment thereof, and a de-immunized antibody or antigen-binding fragment thereof 21. The method of claim 18, wherein said antigen-binding fragment is selected from the group consisting of single-chain antibody, Fab, Fab', F(ab').sub.2, F(ab').sub.3, Fd, Fv, domain antibody, and any fragment of an anti-CD200 immunoglobulin that confers specific binding to CD200. 22. The method of claim 18, wherein said antibody or antigen-binding fragment thereof exhibits: (x) reduced ADCC, (y) reduced CDC activity, or (z) reduced ADCC activity and reduced CDC activity. 23. The method of claim 18, wherein said antibody or antigen-binding fragment thereof exhibits: (x) no ADCC, (y) no CDC activity, or (z) no ADCC activity and no CDC activity. 24. The method of claim 18, wherein said antibody comprises a variant Fc region from an IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgA, IgD, or IgE antibody. 25. The method of claim 18, wherein said antibody comprises a variant Fc constant region that has ADCC activity or CDC activity equal to or less than the ADCC activity or CDC activity the antibody would have if it had a Fc constant region comprising: (a) a glutamic acid substitution at amino acid position 236, (b) a glutamine substitution at amino acid position 298, and (c) an alanine substitution at amino acid positions 319, 321, and 323, wherein each substitution is relative to the amino acid sequence depicted in SEQ ID NO:28. 26. The method of claim 1, wherein said antibody or antigen-binding fragment thereof exhibits: (x) reduced ADCC, (y) reduced CDC activity, or (z) reduced ADCC activity and reduced CDC activity. 27. The method of claim 1, wherein said antibody or antigen-binding fragment thereof exhibits: (x) no ADCC, (y) no CDC activity, or (z) no ADCC activity and no CDC activity. 28. The method of claim 1, wherein said antibody comprises a variant Fc region from an IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgA, IgD, or IgE antibody. 29. The method of claim 1, wherein said antibody comprises a variant Fc constant region that has ADCC activity or CDC activity equal to or less than the ADCC activity or CDC activity the antibody would have if it had a Fc constant region comprising: (a) a glutamic acid substitution at amino acid position 236, (b) a glutamine substitution at amino acid position 298, and (c) an alanine substitution at amino acid positions 319, 321, and 323, wherein each substitution is relative to the amino acid sequence depicted in SEQ ID NO:28.

Details for Patent 8,637,014

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Centocor Ortho Biotech Products, L.p.	ORTHOCLONE OKT3	muromanab-cd3	Injection	103463	09/14/1992		2027-07-25
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2027-07-25
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2027-07-25