Claims for Patent: 10,781,261

Summary for Patent: 10,781,261

Title:	Subcutaneous formulations of anti-CD38 antibodies and their uses
Abstract:	The present invention relates to subcutaneous formulations of anti-CD38 antibodies and their uses.
Inventor(s):	Jansson; Richard (Spring House, PA), Kumar; Vineet (Spring House, PA)
Assignee:	JANSSEN BIOTECH, INC. (Horsham, PA)
Application Number:	16/380,994
Patent Claims:	1. A pharmaceutical composition comprising an anti-CD38 antibody at a concentration of about 120 mg/mL and a hyaluronidase at a concentration of about 2000 U/mL, wherein the anti-CD38 antibody is of an IgG1 isotype and comprises a heavy chain variable region sequence of SEQ ID NO: 4 and a light chain variable region sequence of SEQ ID NO: 5, and wherein the hyaluronidase is rHuPH20 (SEQ ID NO: 22). 2. The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable carrier. 3. The pharmaceutical composition of claim 1, wherein the anti-CD38 antibody comprises a heavy chain sequence of SEQ ID NO: 12 and a light chain sequence of SEQ ID NO: 13. 4. The pharmaceutical composition of claim 2, further comprising a) from about 5 mM to about 50 mM histidine; and b) from about 50 mM to about 400 mM sorbitol. 5. The pharmaceutical composition of claim 4, further comprising a) from about 0.01% w/v to about 0.1% polysorbate-20 (PS-20); b) from about 0.1 mg/mL to about 2.5 mg/mL methionine; or c) from about 0.01% w/v to about 0.1% PS-20 and from about 0.1 mg/mL to about 2.5 mg/mL methionine. 6. The pharmaceutical composition of claim 4, comprising a) about 10 mM histidine; and b) from about 100 mM to about 300 mM sorbitol. 7. The pharmaceutical composition of claim 6, further comprising a) from about 0.01% w/v to about 0.04% w/v polysorbate-20 (PS-20); and b) from about 1 mg/mL to about 2 mg/mL methionine. 8. The pharmaceutical composition of claim 5, comprising a) about 10 mM histidine; b) about 300 mM sorbitol; c) about 0.04% w/v PS-20; and d) about 1 mg/mL methionine; pH about 5.6. 9. The pharmaceutical composition of claim 5, comprising a) about 10 mM histidine; b) about 300 mM sorbitol; c) about 0.04% w/v PS-20; and d) about 2 mg/mL methionine; pH about 5.5. 10. The pharmaceutical composition of claim 5, comprising a) about 10 mM histidine; b) about 300 mM sorbitol; c) about 0.01% w/v PS-20; and d) about 2 mg/mL methionine; pH about 5.5. 11. The pharmaceutical composition of claim 5, comprising a) about 10 mM histidine; b) about 300 mM sorbitol; c) about 0.02% w/v PS-20; and d) about 2 mg/mL methionine; pH about 5.5. 12. The pharmaceutical composition of claim 5, comprising a) about 10 mM histidine; b) about 300 mM sorbitol; c) about 0.06% w/v PS-20; and d) about 2 mg/mL methionine; pH about 5.5. 13. The pharmaceutical composition of claim 5, comprising a) about 10 mM histidine; b) about 300 mM sorbitol; c) about 0.04% w/v PS-20; and d) about 1 mg/mL methionine; pH about 5.5. 14. The pharmaceutical composition of claim 2 which is in a dosage unit form. 15. A method of treating a CD38-positive multiple myeloma (MM) in a subject, comprising administering subcutaneously to the subject in need thereof a pharmaceutical composition comprising an anti-CD38 antibody at a concentration of about 120 mg/ml and a hyaluronidase at a concentration of about 2000 U/ml, for a time sufficient to treat the CD38-positive MM, wherein the anti-CD38 antibody is of an IgG1 isotype and comprises a heavy chain variable region sequence of SEQ ID NO: 4 and a light chain variable region sequence of SEQ ID NO: 5, and wherein the hyaluronidase is rHuPH20 (SEQ ID NO: 22). 16. The method of claim 15, wherein the anti-CD38 antibody comprises a heavy chain sequence of SEQ ID NO: 12 and a light chain sequence of SEQ ID NO: 13. 17. The method of claim 15, wherein the pharmaceutical composition further comprises from about 5 mM to about 50 mM histidine and from about 50 mM to about 400 mM sorbitol, and optionally further comprises from about 0.01% w/v to about 0.1% w/v polysorbate-20 (PS-20), from about 0.1 mg/mL to about 2.5 mg/mL methionine, or from about 0.01% w/v to about 0.1% w/v PS-20 and from about 0.1 mg/mL to about 2.5 mg/mL methionine. 18. The method of claim 17, wherein the pharmaceutical composition comprises about 10 mM histidine and from about 100 mM to about 300 mM sorbitol, optionally further comprising from about 0.01% w/v to about 0.04% w/v PS-20, from about 1 mg/mL to about 2 mg/mL methionine, or from about 0.01% w/v to about 0.04% w/v PS-20 and from about 1 mg/mL to about 2 mg/mL methionine. 19. The method of claim 18, wherein the pharmaceutical composition comprises about 10 mM histidine, about 300 mM sorbitol, about 0.04% w/v PS-20 and about 1 mg/mL methionine; pH about 5.6. 20. The method of claim 18, wherein the pharmaceutical composition comprises about 10 mM histidine, about 300 mM sorbitol, about 0.04% w/v PS-20 and about 2 mg/mL methionine; pH about 5.5. 21. The method of claim 15, further comprising administering a second therapeutic agent. 22. The method of claim 21, wherein the second therapeutic agent is a proteasome inhibitor, an alkylating agent or a glutamic acid derivative, or combinations thereof. 23. The method of claim 22, wherein a) the proteasome inhibitor is bortezomib, carfilzomib or ixazomib; b) the alkylating agent is busulfan, cyclophosphamide, bendamustine, chlorambucli, carboplatin, cisplatin, temozolomide, melphalan, carmustine, lomustine, dacarbazine, oxaliplatin, ifosfamide, mechlorethamine, thiotepa, trabectedin or streptozocin; and c) the glutamic acid derivative is lenalidomide, thalidomide or pomalidomide. 24. The method of claim 23, further comprising administering a corticosteroid. 25. The method of claim 24, wherein the corticosteroid is dexamethasone or prednisone. 26. The method of claim 25, wherein the corticosteroid is dexamethasone. 27. A unit dosage form, comprising a) an anti-CD38 antibody at a concentration of about 120 mg/mL, wherein the anti-CD38 antibody is of an IgG1 isotype and comprises a heavy chain variable region sequence of SEQ ID NO: 4 and a light chain variable region sequence of SEQ ID NO: 5; b) a hyaluronidase at a concentration of about 2000 U/mL, wherein the hyaluronidase is rHuPH20 (SEQ ID NO: 22); c) histidine at a concentration of from about 5 mM to about 15 mM; d) sorbitol at a concentration of from about 100 mM to about 300 mM; e) polysorbate-20 (PS-20) at a concentration of from about 0.01% w/v to about 0.04% w/v; and f) methionine at a concentration of from about 1 mg/mL to about 2 mg/mL, at a pH of about 5.5. 28. The unit dosage form of claim 27, wherein histidine is present at a concentration of about 10 mM. 29. The unit dosage form of claim 28, wherein sorbitol is present at a concentration of about 300 mM. 30. The unit dosage form of claim 29, wherein polysorbate is present at a concentration of about 0.04% w/v. 31. The unit dosage form of claim 30 wherein methionine is present at a concentration of about 1 mg/mL. 32. The unit dosage form of claim 31, optionally comprising sucrose at a concentration of from about 100 mM to about 200 mM. 33. The unit dosage form of claim 32, wherein the anti-CD38 antibody comprises a heavy chain sequence of SEQ ID NO: 12 and a light chain sequence of SEQ ID NO: 13. 34. A container comprising the unit dosage form of claim 33. 35. A unit dosage form, comprising a) an anti-CD38 antibody at a concentration of about 120 mg/mL, wherein the anti-CD38 antibody is of an IgG1 isotype and comprises a heavy chain variable region sequence of SEQ ID NO: 4 and a light chain variable region sequence of SEQ ID NO: 5; b) a hyaluronidase at a concentration of about 2000 U/mL, wherein the hyaluronidase is rHuPH20 (SEQ ID NO: 22); c) histidine at a concentration of about 10 mM; d) sorbitol at a concentration of about 300 mM; e) polysorbate-20 (PS-20) at a concentration of about 0.04% w/v; and f) methionine at a concentration of about 1 mg/mL, at a pH of about 5.6. 36. A container comprising the unit dosage form of claim 35. 37. The unit dosage form of claim 35, wherein the anti-CD38 antibody comprises a heavy chain sequence of SEQ ID NO: 12 and a light chain sequence of SEQ ID NO: 13.

Details for Patent 10,781,261

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	May 05, 2004	10,781,261	2039-04-10
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	December 02, 2004	10,781,261	2039-04-10
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	October 26, 2004	10,781,261	2039-04-10
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	October 25, 2005	10,781,261	2039-04-10