Compositions comprising a bispecific gprc5d / cd3 antibody

HK40138082APending Publication Date: 2026-09-25JANSSEN BIOTECH INC
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Patent Information

Application Number
HK62026125659
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-10-06
Filing Date
2026-07-03
Publication Date
2026-09-25
Estimated Expiration
2044-02-26

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Abstract

Provided herein are aqueous pharmaceutical compositions comprising formulations of a bispecific GPRC5D / CD3 antibody or an antigen-binding fragment thereof and methods of preparing the same. Also provided herein are methods of treating cancer in a subject in need thereof by administering to the subject the aqueous pharmaceutical compositions as disclosed herein. Further provided herein are kits and articles of manufacture comprising the aqueous pharmaceutical compositions as disclosed herein.
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Description

Abstract This article provides aqueous pharmaceutical compositions comprising a bispecific GPRC5D / CD3 antibody or an antigen-binding fragment thereof, and methods for preparing the same. This article also provides methods for treating a subject's cancer by administering the aqueous pharmaceutical composition disclosed herein to a subject in need. This article also provides kits and articles comprising the aqueous pharmaceutical compositions disclosed herein.

Claims

CLAIMSWhat is claimed:

1. An aqueous pharmaceutical composition comprising: a) a concentration of about 0.5 mg / mL to about 3.5 mg / mL of a bispecific G-protein coupled receptor, class C, group 5, member D (GPRC5D) / cluster of differentiation 3 (CD3) antibody or antigen-binding fragment thereof, the bispecific GPRC5D / CD3 antibody or antigen-binding fragment thereof comprising:(1) a first heavy chain (HC1) comprising a HC1 variable region 1 (VH1), wherein the VH1 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively;(2) a first light chain (LC1) comprising a LC1 variable region (VL1), wherein the VL1 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively;(3) a second heavy chain (HC2) comprising a HC2 variable region 2 (VH2), wherein the VH2 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 11, 12, and 13, respectively; and(4) a second light chain (LC2) comprising a LC2 variable region 2 (VL2), wherein the VL2 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 14, 15, and 16, respectively; b) about 10 mM to about 20 mM of acetate and / or pharmaceutically acceptable acetate salt; c) about 6% (w / v) to about 10% (w / v) of sucrose; d) about 7 pg / mL to about 33 pg / mL of ethylenediaminetetraacetic acid (EDTA); e) about 0.01% to about 0.07% polysorbate 20; and f) a pH from about 4.6 to about 5.8.An aqueous pharmaceutical composition comprising: a) a concentration of about 25 mg / mL to about 55 mg / mL of a bispecific G-protein coupled receptor, class C, group 5, member D (GPRC5D) / cluster of differentiation 3 (CD3) antibody or antigen-binding fragment thereof, the bispecific GPRC5D / CD3 antibody or antigen-binding fragment thereof comprising:(1) a first heavy chain (HC1) comprising a HC1 variable region 1 (VH1), wherein the VH1 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively;(2) a first light chain (LC1) comprising a LC1 variable region (VL1), wherein the VL1 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively;(3) a second heavy chain (HC2) comprising a HC2 variable region 2 (VH2), wherein the VH2 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 11, 12, and 13, respectively; and(4) a second light chain (LC2) comprising a LC2 variable region 2 (VL2), wherein the VL2 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 14, 15, and 16, respectively; b) about 10 mM to about 20 mM of acetate and / or pharmaceutically acceptable acetate salt; c) about 6% (w / v) to about 10% (w / v) of sucrose; d) about 7 pg / mL to about 33 pg / mL of ethylenediaminetetraacetic acid (EDTA); e) about 0.01% to about 0.07% polysorbate 20; and f) a pH from about 4.6 to about 5.8.

3. The aqueous pharmaceutical composition of claim 1 or 2, wherein the bispecific GPRC5D / CD3 antibody comprises a VH1 having the amino acid sequence of SEQ ID NO:7, and a VL1 having the amino acid sequence of SEQ ID NO: 8.

4. The aqueous pharmaceutical composition of claim 1 or 2, wherein the bispecific GPRC5D / CD3 antibody comprising a HC1 having the amino acid sequence of SEQ ID NO:9, and a LC1 having the amino acid sequence of SEQ ID NO: 10.

5. The aqueous pharmaceutical composition of claim 1 or 2, wherein the bispecific GPRC5D / CD3 antibody comprises a VH2 having the amino acid sequence of SEQ ID NO: 17, and a VL2 having the amino acid sequence of SEQ ID NO: 18.

6. The aqueous pharmaceutical composition of claim 1 or 2, wherein the bispecific GPRC5D / CD3 antibody comprises a HC2 having the amino acid sequence of SEQ ID NO: 19, and a LC2 having the amino acid sequence of SEQ ID NO:20.

7. The aqueous pharmaceutical composition of claim 1 or 2, wherein the bispecific GPRC5D / CD3 antibody is talquetamab.

8. The aqueous pharmaceutical composition of claim 1, wherein the bispecific GPRC5D / CD3 antibody has a concentration of about 1 mg / mL to about 3 mg / mL.

9. The aqueous pharmaceutical composition of claim 8, wherein the bispecific GPRC5D / CD3 antibody has a concentration of about 1.5 mg / mL to about 2.5 mg / mL.

10. The aqueous pharmaceutical composition of claim 9, wherein the bispecific GPRC5D / CD3 antibody has a concentration of about 2 mg / mL.

11. The aqueous pharmaceutical composition of claim 2, wherein the bispecific GPRC5D / CD3 antibody has a concentration of about 30 mg / mL to about 50 mg / mL.

12. The aqueous pharmaceutical composition of claim 11, wherein the bispecific GPRC5D / CD3 antibody has a concentration of about 35 mg / mL to about 45 mg / mL.

13. The aqueous pharmaceutical composition of claim 12, wherein the bispecific GPRC5D / CD3 antibody has a concentration of about 40 mg / mL.

14. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 12 mM to about 18 mM of acetate and / or pharmaceutically acceptable acetate salt.

15. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 14 mM to about 16 mM of acetate and / or pharmaceutically acceptable acetate salt.

16. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 15 mM of acetate and / or pharmaceutically acceptable acetate salt.

17. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 7% (w / v) to about 9% (w / v) of sucrose.

18. The aqueous pharmaceutical composition of claim 17, wherein the composition comprises about 8% (w / v) of sucrose.

19. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 15 pg / mL to about 21 pg / mL of EDTA.

20. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 18 pg / mL of EDTA.

21. The aqueous pharmaceutical composition of claim 1 or 2, wherein the composition comprises about 0.02% to about 0.06% of PS-20.

22. The aqueous pharmaceutical composition of claim 21, wherein the composition comprises about 0.03 to about 0.05% of PS-20.

23. The aqueous pharmaceutical composition of claim 22, wherein the composition comprises about 0.04% of PS-20.

24. The aqueous pharmaceutical composition of claim 1 or 2, wherein the pH is about 4.8 to about 5.6.

25. The aqueous pharmaceutical composition of claim 24, wherein the pH is about 4.9 to about 5.5.

26. The aqueous pharmaceutical composition of claim 25, wherein the pH is about 5.2.

27. The aqueous pharmaceutical composition of claim 1, wherein the composition comprises 2 mg / mL of the bispecific GPRC5D / CD3 antibody, 15 mM of acetate and / or pharmaceutically acceptable acetate salt, 8% (w / v) sucrose, 18 pg / mL of EDTA, 0.04% PS 20, and a pH of 5.2.

28. The aqueous pharmaceutical composition of claim 2, wherein the composition comprises 40 mg / mL of the bispecific GPRC5D / CD3 antibody, 15 mM of acetate and / or pharmaceutically acceptable acetate salt, 8% (w / v) sucrose, 18 pg / mL of EDTA, 0.04% PS 20, and a pH of 5.2.

29. The aqueous pharmaceutical composition of any one of claims 1-28, wherein the aqueous pharmaceutical composition is stable.

30. The aqueous pharmaceutical composition of claim 29, wherein stability is defined based on color of solution, pH, turbidity, percentage of purity, percentage of new peaks, percentage of main component, percentage of high molecular weight species (HWMS), percentage of low molecular weight species (LMWS), percentage of sum of acidic peaks, percentage of sum of basic peaks, protein concentration, percentage of T cell activation, percentage of PS 20 (w / v), or any combination thereof.

31. The aqueous pharmaceutical composition of claim 29 or 30, wherein the aqueous pharmaceutical composition is stable at a temperature of about 2-8°C for at least two years.

32. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject the aqueous pharmaceutical composition of any one of claims 1-31.

33. The method of claim 32, wherein the administering is subcutaneous.

34. A method for preparing an aqueous pharmaceutical composition of a bispecific G-protein coupled receptor, class C, group 5, member D (GPRC5D) / cluster of differentiation 3 (CD3) antibody or antigen-binding fragment thereof, the bispecific GPRC5D / CD3 antibody or antigenbinding fragment thereof comprising:(1) a first heavy chain (HC1) comprising a HC1 variable region 1 (VH1), wherein the VH1 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively;(2) a first light chain (LC1) comprising a LC1 variable region (VL1), wherein the VL1 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively;(3) a second heavy chain (HC2) comprising a HC2 variable region 2 (VH2),wherein the VH2 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 11, 12, and 13, respectively; and(4) a second light chain (LC2) comprising a LC2 variable region 2 (VL2), wherein the VL2 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 14, 15, and 16, respectively; the method comprising combining a composition comprising about 2 mg / mL of the bispecific GPRC5D / CD3 antibody, about 15 mM of acetate and / or a pharmaceutically acceptable acetate salt, about 8% (w / v) sucrose, about 18 pg / mL of EDTA, and about 0.04% polysorbate (PS) 20, wherein the stable aqueous pharmaceutical composition has a pH of about 5.2.

35. A method for preparing an aqueous pharmaceutical composition of a bispecific G-protein coupled receptor, class C, group 5, member D (GPRC5D) / cluster of differentiation 3 (CD3) antibody or antigen-binding fragment thereof, the bispecific GPRC5D / CD3 antibody or antigenbinding fragment thereof comprising:(1) a first heavy chain (HC1) comprising a HC1 variable region 1 (VH1), wherein the VH1 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively;(2) a first light chain (LC1) comprising a LC1 variable region (VL1), wherein the VL1 comprises a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively;(3) a second heavy chain (HC2) comprising a HC2 variable region 2 (VH2), wherein the VH2 comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, and a HCDR3 having the amino acid sequences of SEQ ID NOs: 11, 12, and 13, respectively; and(4) a second light chain (LC2) comprising a LC2 variable region 2 (VL2), wherein the VL2 comprises a light chain complementarity determining region 1(LCDR1), a LCDR2, and a LCDR3 having the amino acid sequences of SEQ ID NOs: 14, 15, and 16, respectively; the method comprising combining a composition comprising about 40 mg / mL of the bispecific GPRC5D / CD3 antibody, about 15 mM of acetate and / or a pharmaceutically acceptable acetate salt, about 8% (w / v) sucrose, about 18 pg / mL of EDTA, and about 0.04% polysorbate (PS) 20, wherein the stable aqueous pharmaceutical composition has a pH of about 5.2.

36. The method of claim 34 or 35, wherein the bispecific GPRC5D / CD3 antibody comprises a VH1 having the amino acid sequence of SEQ ID NO: 7, and a VL1 having the amino acid sequence of SEQ ID NO: 8.

37. The method of claim 34 or 35, wherein the bispecific GPRC5D / CD3 antibody comprising a HC1 having the amino acid sequence of SEQ ID NO:9, and a LC1 having the amino acid sequence of SEQ ID NOTO.

38. The method of claim 34 or 35, wherein the bispecific GPRC5D / CD3 antibody comprises a VH2 having the amino acid sequence of SEQ ID NO: 17, and a VL2 having the amino acid sequence of SEQ ID NO: 18.

39. The method of claim 34 or 35, wherein the bispecific GPRC5D / CD3 antibody comprises a HC2 having the amino acid sequence of SEQ ID NO: 19, and a LC2 having the amino acid sequence of SEQ ID NO:20.

40. The method of claim 34 or 35, wherein the bispecific GPRC5D / CD3 antibody is talquetamab.

41. The method of any one of claims 34-40, wherein the aqueous pharmaceutical composition is stable.

42. The method of claim 41, wherein stability is defined based on color of solution, pH, turbidity, percentage of purity, percentage of new peaks, percentage of main component, percentage of high molecular weight species (HWMS), percentage of low molecular weight species (LMWS), percentage of sum of acidic peaks, percentage of sum of basic peaks, protein concentration, percentage of T cell activation, percentage of PS 20 (w / v), or any combination thereof.

43. A kit comprising the aqueous pharmaceutical composition of any one of claims 1-31 and instructions for use.

44. An article of manufacture comprising a container holding the aqueous pharmaceutical composition of any one of claims 1-31.

45. The article of manufacture of claim 44, wherein the container is a vial with a stopper pierceable by a syringe.

46. The aqueous pharmaceutical composition of any one of claims 1-31 for use in the treatment of cancer.

47. The aqueous pharmaceutical composition of any one of claims 1-31 for use in the preparation of a medicament for the treatment of cancer.

48. Use of the aqueous pharmaceutical composition of any one of claims 1-31 for treating a cancer in a subject in need thereof, the use comprising administering the aqueous pharmaceutical composition to the subject in need thereof.

49. The use of claim 48, wherein the administration is subcutaneous.