Compositions comprising a combination of an anti-pd-1 antibody and another antibody

Patent metadata

Field	Value
Publication number	US-2016304607-A1
Application number	US-201615130513-A
Country	US
Kind code	A1
Filing date	Apr 15, 2016
Priority date	Apr 17, 2015
Publication date	Oct 20, 2016
Grant date	—

Abstract

This provides pharmaceutical compositions that comprise a combination of an anti-cancer agent which is an first antibody and a second antibody. In some embodiments, the first antibody is an anti-Programmed Death-1 (PD-1) antibody. In certain embodiments, the composition is a fixed dose formulation. In certain embodiments, the composition is administered as a flat-dose. The disclosure also provides a kit for treating a subject afflicted with a disease, the kit comprising a dosage of any composition disclosed herein and instructions for using the composition in any of the disclosed methods for treating a disease.

First claim

What is claimed is:

1 . A pharmaceutical composition comprising an X amount of a first antibody or an antigen-binding fragment thereof, which comprises an anti-PD-1 antibody or an antigen-binding fragment thereof, and a Y amount of a second antibody or an antigen-binding fragment thereof, wherein the ratio of the X amount to the Y amount is about 50:1 to about 1:50.

2 . The composition of claim 1 , wherein the ratio of X to Y is about 50:1, about 40:1, about 30:1, about 20:1, about 10:1, about 5:1, about 3:1, about 1:1, about 1:3, about 1:5, about 1:10, about 1:20, about 1:30, about 1:40, or about 1:50.

3 . The composition of claim 1 or 2 , wherein the anti-PD-1 antibody is nivolumab or pembrolizumab.

4 . The composition of claim 3 , wherein the anti-PD-1 antibody is nivolumab.

5 . The composition of any one of claims 1 to 4 , wherein the X amount of the first antibody or antigen binding fragment thereof is at least about 60 mg, about 80 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, or about 300 mg.

6 . The composition of claim 5 , wherein the X amount of the first antibody is at least about 80 mg, about 160 mg, or about 240 mg.

7 . The composition of any one of claims 1 to 6 , wherein the X amount of the first antibody or antigen-binding fragment thereof is about 60 mg, about 80 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, or about 300 mg.

8 . The composition of claim 7 , wherein the X amount of the first antibody or antigen-binding fragment thereof is about 80 mg or about 240 mg.

9 . The composition of any one of claims 1 - 8 , wherein the second antibody or antigen-binding fragment thereof is an anti-CTLA4 antibody.

10 . The composition of claim 9 , wherein the ratio of X to Y is about 3:1, about 1:1, or about 1:3.

11 . The composition of claim 9 , wherein (i) the X amount is about 240 mg and the Y amount is about 80 mg, (ii) the X amount is about 80 mg and the Y amount is about 80 mg; (iii) the X amount is about 160 mg and the Y amount is about 160 mg; (iv) the X amount is about 240 mg and the Y amount is about 240 mg; or (v) the X amount is about 80 mg and the Y amount is about 240 mg.

12 . The compositions of claim 10 or 11 , wherein the anti-CTLA4 antibody is tremelimumab or ipilimumab.

13 . The composition of any one of claims 1 - 8 , wherein the second antibody is an anti-LAG3 antibody.

14 . The composition of claim 13 , wherein the ratio of X to Y is about 12:1, about 3:1, or about 1:1.

15 . The composition of claim 13 or 14 , wherein the anti-LAG3 antibody is 25F7.

16 . The composition of any one of claims 1 - 8 , wherein the second-antibody is an anti-CD137 antibody.

17 . The composition of claim 16 , wherein the ratio of X to Y is about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:10, about 1:20, about 1:30, about 1:40, about 1:50, about 50:1, about 40:1, about 30:1, about 20:1, about 10:1, about 5:1, about 4:1 or about 2:1.

18 . The composition of claim 16 or 17 , wherein the anti-CD137 antibody is urelumab.

19 . The composition of any one of claims 1 - 8 , wherein the second antibody is an anti-KIR antibody.

20 . The composition of claim 19 , wherein the ratio of X to Y is about 30:1, about 10:1, about 3:1, about 1:1, or about 1:2.

21 . The composition of claim 19 or 20 , wherein the anti-KIR antibody is 1-7F9 or lirilumab.

22 . The composition of any one of claims 1 - 8 , wherein the second antibody is selected from the group consisting of: an anti-TGFβ antibody, an anti-IL-10 antibody, an anti-B7-H4 antibody, an anti-Fas ligand antibody, an anti-CXCR4 antibody, an anti-mesothelin antibody, an anti-CD27 antibody, an anti-CD27 antibody and any combination thereof.

23 . The composition of any one of claims 1 - 8 , wherein the second antibody is an anti-GITR antibody.

24 . The composition of claim 23 , wherein the anti-GITR antibody is MK4166 or TRX518.

25 . The composition of any one of claims 1 to 8 or 22 to 24 , wherein the ratio of X:Y is about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 2:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, or about 10:1.

26 . The composition of any one of claims 1 to 25 , wherein the composition is formulated in a Tris-Cl, histidine, citrate or Tris-citrate buffer.

27 . The composition of claim 26 , wherein the composition is formulated in a Tris-Cl buffer, the concentration of Tris-Cl being at least about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, or about 50 mM.

28 . The composition of claim 27 , wherein the concentration of Tris-Cl is about 20 mM.

29 . The composition of claim 26 , wherein the composition is formulated in a citrate buffer, the concentration of citrate being at least about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, or about 50 mM.

30 . The composition of claim 29 , wherein the citrate concentration is about 10 mM or about 20 mM.

31 . The composition of claim 26 , wherein the composition is formulated in a histidine buffer, the concentration of histidine being at least about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, or about 50 mM.

32 . The composition of claim 31 , wherein the histidine concentration is about 20 mM.

33 . The composition of claim 26 , wherein the composition is formulated in a Tris-citrate buffer, the concentration of Tris-1 being at least about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, or about 50 mM, and the concentration of citrate being at least about 2 mM, about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, or about 50 mM.

34 . The composition of claim 33 , wherein the concentration of Tris-Cl is about 13.3 mM and the concentration of citrate is about 6.7 mM.

35 . The composition of any one of claims 1 - 34 , wherein the pH of the composition is at least about 5, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.0.

36 . The composition of claim 35 , wherein the pH of the composition is at least about 6.0, about 6.2, about 6.5, about 6.6 or about 7.0

37 . The composition of any one of claims 1 - 36 , wherein the composition comprises one or more additional components selected from the group consisting of: a bulking agent, a stabilizing agent, a chelating agent, a surfactant, a buffering agent, and any combination thereof.

38 . The composition of claim 37 , wherein the bulking agent is selected from the group consisting of NaCl, mannitol, glycine, alan

Assignees

• Bristol Myers Squibb Co

Inventors

• SADINENI Vikram
• Quan Yong
• Kaserer Wallace

Classifications

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title