JPWO2021118930A5

JPWO2021118930A5 -

Info

Publication number: JPWO2021118930A5
Application number: JP2022534224A
Authority: JP
Publication date: 2023-12-14

Claims

monoclonal anti-PD-L1 antibody at a concentration of about 100 g/L to about 150 g/L, histidine acetate at a concentration of about 15 mM to about 25 mM, sucrose at a concentration of about 200 mM to about 280 mM, about 0.04% (w/v) A liquid pharmaceutical formulation comprising polysorbate at a concentration of from about 0.08% (w/v) to about 0.08% (w/v), methionine at a concentration of about 5mM to about 15mM, a hyaluronidase enzyme, and a pH of about 5.6 to about 6.0, , monoclonal antibodies,
(a) Light chain variable region comprising:
(1) HVR-L1 containing the amino acid sequence RASQDVSTAVA (SEQ ID NO: l);
(2) HVR-L2 containing the amino acid sequence SASFLYS (SEQ ID NO: 2);
(3) HVR-L3 comprising the amino acid sequence QQYLYHPAT (SEQ ID NO: 3); and (b) heavy chain variable region comprising:
(1) HVR-H1 containing the amino acid sequence GFTFSDSWIH (SEQ ID NO: 4);
(2) HVR-H2 comprising the amino acid sequence AWISPYGGSTYYADSVKG (SEQ ID NO: 5);
(3) HVR-H3 containing the amino acid sequence WPGGFDY (SEQ ID NO: 6)
liquid pharmaceutical preparations, including;

2. The liquid pharmaceutical formulation of claim 1 , wherein the pH is about 5.8.

3. A liquid pharmaceutical formulation according to claim 1 or 2 , wherein the polysorbate in the formulation is polysorbate 20.

4. A liquid pharmaceutical formulation according to any one of claims 1 to 3 , wherein the polysorbate is at a concentration of about 0.05% (w/v) to about 0.07% (w/v).

5. A liquid pharmaceutical formulation according to any one of claims 1 to 4 , wherein the polysorbate is at a concentration of about 0.06% (w/v).

6. A liquid pharmaceutical formulation according to any one of claims 1 to 5 , wherein the methionine is at a concentration of about 10 mM.

monoclonal anti-PD-L1 antibody at a concentration of about 100 g/L to about 150 g/L, histidine acetate at a concentration of about 15 mM to about 25 mM, sucrose at a concentration of about 200 mM to about 280 mM, about 0.01% (w/v) A liquid pharmaceutical formulation comprising polysorbate at a concentration of from about 0.03% (w/v) to about 0.03% (w/v) and a pH of from about 5.3 to about 5.7, wherein the monoclonal antibody is
(a) Light chain variable region comprising:
(1) HVR-L1 containing the amino acid sequence RASQDVSTAVA (SEQ ID NO: l);
(2) HVR-L2 containing the amino acid sequence SASFLYS (SEQ ID NO: 2);
(3) HVR-L3 comprising the amino acid sequence QQYLYHPAT (SEQ ID NO: 3); and (b) heavy chain variable region comprising:
(1) HVR-H1 containing the amino acid sequence GFTFSDSWIH (SEQ ID NO: 4);
(2) HVR-H2 comprising the amino acid sequence AWISPYGGSTYYADSVKG (SEQ ID NO: 5);
(3) HVR-H3 containing the amino acid sequence WPGGFDY (SEQ ID NO: 6)
liquid pharmaceutical preparations, including;

8. A liquid pharmaceutical formulation according to any one of claims 1 to 7 , wherein the monoclonal antibody in the formulation is at a concentration of about 120 g/L to about 130 g/L.

8. A liquid pharmaceutical formulation according to any one of claims 1 to 7 , wherein the monoclonal antibody in the formulation is at a concentration of about 125 g/L.

10. A liquid pharmaceutical formulation according to any one of claims 1 to 9 , wherein the histidine acetate is at a concentration of about 17mM to about 22mM.

10. A liquid pharmaceutical formulation according to any one of claims 1 to 9 , wherein the histidine acetate is at a concentration of about 20mM.

12. A liquid pharmaceutical formulation according to any one of claims 1 to 11 , wherein the sucrose is at a concentration of about 220mM to about 260mM.

12. A liquid pharmaceutical formulation according to any one of claims 1 to 11 , wherein the sucrose is at a concentration of about 240mM.

7. A liquid pharmaceutical formulation according to any one of claims 1 to 6 , wherein the hyaluronidase enzyme is recombinant human hyaluronidase (rHuPH20).

15. The liquid pharmaceutical formulation of claim 14 , wherein the concentration of hyaluronidase enzyme in the mixture is about 1000 U/ml to about 3000 U/ml.

15. A liquid pharmaceutical formulation according to claim 14 , wherein the concentration of hyaluronidase enzyme in the mixture is about 2000 U/ml.

17. Liquid pharmaceutical formulation according to any one of claims 1 to 16 , wherein the monoclonal antibody is not subjected to prior lyophilization.

18. A liquid pharmaceutical formulation according to any one of claims 1 to 17 , wherein the monoclonal antibody is a humanized antibody.

Liquid pharmaceutical according to any one of claims 1 to 18 , wherein the monoclonal antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 8. formulation.

20. A liquid pharmaceutical formulation according to any one of claims 1 to 19 , wherein the monoclonal antibody is a full-length antibody.

21. A liquid pharmaceutical formulation according to claim 20 , wherein the monoclonal antibody is an IgG1 antibody.

22. A liquid pharmaceutical formulation according to any one of claims 1 to 21 , wherein the monoclonal antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 9 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 10.

23. A liquid pharmaceutical formulation according to any one of claims 1 to 22 , wherein the monoclonal antibody is stored in a glass vial or a metal alloy container.

24. A liquid pharmaceutical formulation according to claim 23 , wherein the metal alloy is 316L stainless steel or Hastelloy.

25. A liquid pharmaceutical formulation according to any one of claims 1 to 24 , which is stable for at least 6 months at 2-8°C.

25. A liquid pharmaceutical formulation according to any one of claims 1 to 24 , which is stable for at least 12 months at 2-8°C.

25. A liquid pharmaceutical formulation according to any one of claims 1 to 24 , which is stable for at least 24 months at 2-8°C.

25. A liquid pharmaceutical formulation according to any one of claims 1 to 24, which is stable for 3 months at 25<0>C or 40<0>C.

29. The liquid pharmaceutical formulation of any one of claims 25-28 , wherein the antibody in the formulation retains at least about 80% of its biological activity after storage.

30. The liquid pharmaceutical formulation of claim 29 , wherein biological activity is measured by antibody binding to PD-L1.

31. A liquid pharmaceutical formulation according to any one of claims 1 to 30 , which is sterile.

32. A liquid pharmaceutical formulation according to any one of claims 1 to 31 , suitable for administration to a subject.

33. A liquid pharmaceutical formulation according to any one of claims 1 to 32 , for subcutaneous administration.

34. An article of manufacture comprising a container holding a liquid pharmaceutical formulation according to any one of claims 1 to 33 .

34. A kit comprising a container holding a liquid pharmaceutical formulation according to any one of claims 1 to 33 .

34. An effective amount of a liquid pharmaceutical formulation according to any one of claims 1 to 33 for use in a method of treating a disease or disorder in a subject , wherein the disease or disorder is an infectious disease, cancer. , and inflammatory diseases.

37. A liquid pharmaceutical formulation according to claim 36 , wherein the disease or disorder is cancer.

38. The liquid pharmaceutical formulation of claim 37 , wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, urothelial cancer, and breast cancer.

39. A liquid pharmaceutical formulation according to claim 38 , wherein the breast cancer is triple negative breast cancer.

40. A liquid pharmaceutical formulation according to any one of claims 36 to 39 , wherein the subject is a human.