Claims for Patent: 10,233,248
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Summary for Patent: 10,233,248
Title: | Treatment of C1013G/CXCR4-associated waldenstroom\'s macroglobulinemia with an anti-CXCR4 antibody |
Abstract: | The present disclosure provides a method for treating a subject afflicted with Waldenstrm\'s macroglobulinemia (WM) comprising administering to the subject a therapeutically effective amount of an antibody or an antigen-binding portion thereof that specifically binds to a CXCR4 receptor expressed on the surface of a WM cell. The disclosure also provides a therapeutic regimen for treating a patient afflicted with C1013G/CXCR4-associated WM. |
Inventor(s): | Ghobrial; Irene M. (Wellesley, MA), Roccaro; Aldo M. (Boston, MA), Cardarelli; Josephine M. (San Carlos, CA), Sacco; Antonio (Boston, MA) |
Assignee: | Bristol-Myers Squibb Company (Princeton, NJ) |
Application Number: | 15/034,964 |
Patent Claims: | 1. A method for treating a subject afflicted with C1013G/CXCR4-associated Waldenstrom's macroglobulinemia comprising administering to the subject a therapeutically effective
amount of an antibody or an antigen-binding portion thereof that specifically binds to a C--X--C chemokine receptor type 4 (CXCR4) receptor expressed on the surface of a Waldenstrom's macroglobulinemia cell.
2. The method of claim 1, wherein the antibody or antigen-binding portion thereof is administered as monotherapy. 3. The method of claim 1, further comprising administering at least one anti-cancer agent in combination with the antibody or antigen-binding portion thereof. 4. The method of claim 3, wherein the at least one anti-cancer agent is rituximab, bortezomib, carfilzomib, ibrutinib, idelalisib, panobinostat, thalidomide, lenalidomide, chlorambucil, cyclophosphamide, doxorubicin, vincristine, prednisone, fludarabine, bendamustine, dexamethasone, and/or cladribine. 5. The method of claim 4, wherein ibrutinib is administered at a dose of 420 mg orally once a day. 6. The method of claim 3, wherein the therapeutically effective amount of the antibody or antigen-binding portion thereof comprises a fixed dose. 7. The method of claim 6, wherein the fixed dose is 350, 750 or 1500 mg. 8. The method of claim 6, wherein the fixed dose is administered in a dosing schedule of once per week, once every two weeks, or once every three weeks. 9. The method of claim 7, wherein the fixed dose is administered in a dosing schedule of once every 7 days or once every 14 days. 10. The method of claim 3, wherein the antibody or antigen-binding portion thereof is administered intravenously or subcutaneously. 11. The method of claim 1, wherein the antibody or antigen-binding portion thereof is administered to the subject after failure of a prior treatment for Waldenstrom's macroglobulinemia. 12. The method of claim 11, wherein the prior treatment is with an agent selected from a mammalian target of rapamycin (mTOR) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and phosphatidylinositol 3-kinase (PI3K) inhibitor. 13. The method of claim 11, wherein the prior treatment is: (a) first-line treatment with ibrutinib; (b) first-line treatment with a BDR (bortezomib, dexamethasone and rituximab) regimen and second-line treatment with ibrutinib; or (c) first-line treatment with a RCD (cyclophosphamide, dexamethasone and rituximab) regimen and second-line treatment with ibrutinib. 14. The method of claim 1, wherein the therapeutically effective amount of the antibody or antigen-binding portion thereof comprises a dose of 0.1, 0.3, 0.5, 1, 3, 5, 10 or 20 mg/kg body weight administered at a dosing schedule of once per week, once every two weeks, once every three weeks, or once a month. 15. The method of claim 14, wherein the dose is 3 or 10 mg/kg body weight. 16. The method of claim 1, wherein the anti-CXCR4 antibody or portion thereof comprises the CDR1, CDR2 and CDR3 domains in a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 25, and the CDR1, CDR2 and CDR3 domains in a light chain variable region having the amino acid sequence set forth in SEQ ID NO: 29. 17. The method of claim 1, wherein the anti-CXCR4 antibody or portion thereof comprises a heavy chain variable region comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 25, and a light chain variable region comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 29. 18. The method of claim 1, wherein the anti-CXCR4 antibody or portion thereof comprises a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 1, a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 5, a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 9, a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 13, a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 17, and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 21. 19. The method of claim 1, wherein the subject is a human and the antibody or antibody or antigen-binding portion thereof binds to human CXCR4 carrying the C1013G mutation. 20. The method of claim 1, wherein the antibody or antigen-binding portion thereof is of an IgG1 or IgG4 isotype. 21. The method of claim 1, wherein the antibody or antigen-binding portion thereof is a monoclonal antibody or an antigen-binding portion thereof. 22. The method of claim 1, wherein the antibody or antigen-binding portion thereof is a chimeric, humanized or human antibody or an antigen-binding portion thereof. 23. The method of claim 1, wherein the antibody or antigen-binding portion thereof is a human antibody or an antigen-binding portion thereof. 24. The method of claim 1, wherein the antibody or antigen-binding portion thereof induces apoptosis of a C1013G/CXCR4-expressing cell. 25. The method of claim 1, wherein the antibody or antigen-binding portion thereof inhibits the activity of the CXCR4 receptor and increases sensitivity of the Waldenstrom's macroglobulinemia cell to an anti-cancer agent. 26. The method of claim 1, wherein the anti-CXCR4 antibody or portion thereof comprises a heavy chain variable region comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 41, and a light chain variable region comprising consecutively linked amino acids having the sequence set forth in SEQ ID NO: 45. 27. The method of claim 1, wherein the antibody is ulocuplumab. |
Details for Patent 10,233,248
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Genentech, Inc. | RITUXAN | rituximab | Injection | 103705 | 11/26/1997 | ⤷ Try a Trial | 2033-11-06 |
Genentech, Inc. | RITUXAN HYCELA | rituximab and hyaluronidase human | Injection | 761064 | 06/22/2017 | ⤷ Try a Trial | 2033-11-06 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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