Claims for Patent: 10,221,244

Summary for Patent: 10,221,244

Title:	Anti-CSF1R antibody and anti PD-1 antibody combination therapy for cancer
Abstract:	Methods of treating cancer with antibodies that bind colony stimulating factor 1 receptor (CSF1R) in combination with PD-1/PD-L1 inhibitors are provided.
Inventor(s):	Wong; Brian (Los Altos, CA), Hambleton; Julie (San Francisco, CA), Sikorski; Robert (Woodside, CA), Masteller; Emma (Redwood City, CA), Hestir; Kevin (Kensington, CA), Bellovin; David (San Jose, CA), Lewis; Katherine E. (Lake Forest Park, WA)
Assignee:	Five Prime Therapeutics, Inc. (South San Francisco, CA) Bristol-Myers Squibb Company (Princeton, NJ)
Application Number:	15/680,664
Patent Claims:	1. A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and a PD-1/PD-L1 inhibitor, wherein the anti-CSF1R antibody is selected from: a) an antibody comprising a heavy chain comprising the sequence of either SEQ ID NO: 44 or 45 and a light chain comprising the sequence of either SEQ ID NO: 51 or 52; b) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 27, an HC CDR2 having the sequence of SEQ ID NO: 28, and an HC CDR3 having the sequence of SEQ ID NO: 29, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 30, a LC CDR2 having the sequence of SEQ ID NO: 31, and a LC CDR3 having the sequence of SEQ ID NO: 32; and c) an antibody comprising a heavy chain comprising the sequence of either SEQ ID NO: 58 or 59 and a light chain comprising the sequence of either SEQ ID NO: 65 or 66; and wherein the PD-1/PD-L1 inhibitor is an anti-PD-1 antibody selected from: a) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 100 and a light chain comprising the sequence of SEQ ID NO: 102; b) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 105, an HC CDR2 having the sequence of SEQ ID NO: 107, and an HC CDR3 having the sequence of SEQ ID NO: 109, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 112, a LC CDR2 having the sequence of SEQ ID NO: 114, and a LC CDR3 having the sequence of SEQ ID NO: 116; and c) an antibody comprising a heavy chain comprising the sequences of SEQ ID NOs: 100 and 101 and a light chain comprising the sequences of SEQ ID NOs: 102 and 103. 2. The method of claim 1, wherein the anti-CSF1R antibody and the PD-1/PD-L1 inhibitor are administered concurrently or sequentially. 3. The method of claim 1, wherein the anti-CSF1R antibody and the PD-1/PD-L1 inhibitor are administered concurrently. 4. The method of claim 2, wherein one or more doses of the PD-1/PD-L1 inhibitor are administered prior to administering the anti-CSF1R antibody. 5. The method of claim 4, wherein the subject received a complete course of PD-1/PD-L1 inhibitor therapy prior to administration of the anti-CSF1R antibody. 6. The method of claim 5, wherein the anti-CSF1R antibody is administered during a second course of PD-1/PD-L1 inhibitor therapy. 7. The method of claim 4, wherein the subject received at least one, at least two, at least three, or at least four doses of the PD-1/PD-L1 inhibitor prior to administration of the anti-CSF1R antibody. 8. The method of claim 1, wherein at least one dose of the PD-1/PD-L1 inhibitor is administered concurrently with the anti-CSF1R inhibitor. 9. The method of claim 2, wherein one or more doses of the anti-CSF1R antibody are administered prior to administering the PD-1/PD-L1 inhibitor. 10. The method of claim 9, wherein the subject received at least two, at least three, at least three, or at least four doses of the anti-CSF1R antibody prior to administration of the PD-1/PD-L1 inhibitor. 11. The method of claim 9, wherein at least one dose of the anti-CSF1R antibody is administered concurrently with the PD-1/PD-L1 inhibitor. 12. The method of claim 1, wherein the anti-CSF1R antibody is administered at a dose of about 0.1, about 0.3, about 0.5, about 1, about 2, about 3, about 4, about 5, or about 10 mg/kg. 13. The method of claim 1, wherein the PD-1/PD-L1 inhibitor is administered at a dose of about 0.5-10 mg/kg, such as at a dose of about 0.5, about 1, about 2, about 3, about 4, about 5, or about 10 mg/Kg. 14. The method of claim 1, wherein the anti-CSF1R antibody and the PD-1/PD-L1 inhibitor are administered once per 1, 2, 3, 4, or 5 weeks. 15. The method of claim 1, wherein the cancer is selected from non-small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, pancreatic cancer, renal cell carcinoma, hepatocellular carcinoma, bladder cancer, malignant glioma, colorectal cancer, and endometrial cancer. 16. The method of claim 15, wherein the cancer is recurrent or progressive after a therapy selected from surgery, chemotherapy, radiation therapy, or a combination thereof. 17. The method of claim 1, wherein administration of the anti-CSF1R antibody and the PD-1/PD-L1 inhibitor results in synergistic inhibition of tumor growth in a mouse model of the cancer. 18. The method of claim 17, wherein the cancer is a colon, rectum, or colorectal cancer and the mouse model comprises colorectal carcinoma cells, such as MC38 colorectal carcinoma cells. 19. The method of claim 17, wherein the cancer is a pancreatic cancer and the mouse model comprises murine pancreatic ductal adenocarcinoma (PDAC) cells, such as KRas.sup.G12D/Ink4a.sup.-/.sup.- pancreatic ductal adenocarcinoma cells. 20. A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-CSF1R antibody and an anti-PD-1 antibody; (a) wherein the cancer is non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN), ovarian cancer, renal cell carcinoma, or malignant glioma; (b) wherein the anti-CSF1R antibody is administered at a dose of about 1, about 2, or about 3 mg/kg every two weeks and the anti-PD-1 antibody is administered at a dose of about 3 mg/kg every two weeks; (c) wherein the anti-PD-1 antibody is selected from: i) an antibody comprising a heavy chain comprising the sequence of SEQ ID NO: 100 and a light chain comprising the sequence of SEQ ID NO: 102; ii) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 105, an HC CDR2 having the sequence of SEQ ID NO: 107, and an HC CDR3 having the sequence of SEQ ID NO: 109, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 112, a LC CDR2 having the sequence of SEQ ID NO: 114, and a LC CDR3 having the sequence of SEQ ID NO: 116; and iii) an antibody comprising a heavy chain comprising the sequences of SEQ ID NOs: 100 and 101 and a light chain comprising the sequences of SEQ ID NOs: 102 and 103; and (d) wherein the anti-CSF1R antibody is selected from: i) an antibody comprising a heavy chain comprising the sequence of either SEQ ID NO: 44 or 45 and a light chain comprising the sequence of either SEQ ID NO: 51 or 52; ii) an antibody comprising a heavy chain comprising a heavy chain (HC) CDR1 having the sequence of SEQ ID NO: 27, an HC CDR2 having the sequence of SEQ ID NO: 28, and an HC CDR3 having the sequence of SEQ ID NO: 29, and a light chain comprising a light chain (LC) CDR1 having the sequence of SEQ ID NO: 30, a LC CDR2 having the sequence of SEQ ID NO: 31, and a LC CDR3 having the sequence of SEQ ID NO: 32; and iii) an antibody comprising a heavy chain comprising the sequence of either SEQ ID NO: 58 or 59 and a light chain comprising the sequence of either SEQ ID NO: 65 or 66. 21. The method of claim 20, wherein the anti-PD-1 antibody comprises a heavy chain comprising the sequences of SEQ ID NOs: 100 and 101 and a light chain comprising the sequences of SEQ ID NOs: 102 and 103. 22. The method of claim 21, wherein the anti-PD-1 antibody is nivolumab. 23. The method of claim 20, wherein the anti-CSF1R antibody comprises a heavy chain comprising the sequence of either SEQ ID NO: 58 or 59 and a light chain comprising the sequence of either SEQ ID NO: 65 or 66. 24. The method of claim 1, wherein the anti-PD-1 antibody is nivolumab. 25. The method of claim 1, wherein the anti-CSF1R antibody comprises a heavy chain comprising the sequence of either SEQ ID NO: 58 or 59 and a light chain comprising the sequence of either SEQ ID NO: 65 or 66. 26. The method of claim 7, wherein the subject received one dose of the PD-1/PD-L1 inhibitor prior to administration of the anti-CSF1R antibody. 27. The method of claim 12, wherein the anti-CSF1R antibody is administered at a dose of 1, 2, 3, or 4 mg/kg. 28. The method of claim 13, wherein the PD-1/PD-L1 inhibitor is administered at a dose of 3 mg/kg. 29. The method of claim 28, wherein the anti-CSF1R antibody and the PD-1/PD-L1 inhibitor are administered every two weeks. 30. The method of claim 28, wherein the anti-CSF1R antibody is administered at a dose of 1, 2, 3, or 4 mg/kg. 31. The method of claim 30, wherein the anti-CSF1R antibody and the PD-1/PD-L1 inhibitor are administered every two weeks.

Details for Patent 10,221,244

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	12/22/2014		2034-10-29
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	10/04/2017		2034-10-29
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	08/27/2021		2034-10-29