Anti-RSV monoclonal antibody formulation

Patent metadata

Field	Value
Publication number	US-10774133-B2
Application number	US-201815907876-A
Country	US
Kind code	B2
Filing date	Feb 28, 2018
Priority date	Mar 1, 2017
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

The present invention provides a formulation comprising: (i) an anti-RSV monoclonal antibody; and (ii) an ionic excipient; wherein the monoclonal antibody is present at a concentration of about 50 mg/ml or greater and the ionic excipient is present at a concentration of between 50 and 150 mM and the formulation has a pH of about 5.5 to about 7.5.

First claim

What is claimed is:

1. A formulation comprising:
an anti-Respiratory Syncytial Virus (RSV) monoclonal antibody; and
an ionic excipient;

wherein the monoclonal antibody is present at a concentration of about 50 mg/ml or greater and the ionic excipient is present at a concentration of about 50 to about 150 mM, wherein the monoclonal antibody has a pI in the range of about pH 6.4 to about pH 7.5, and wherein the formulation has a pH of about 5.5 to about 7.5.

2. A formulation according to claim 1 , wherein the monoclonal antibody is an IgG1 monoclonal antibody.

3. A formulation according to claim 1 , wherein the monoclonal antibody has light chain CDR sequences:
CDR-L1 of SEQ ID NO: 3
CDR-L2 of SEQ ID NO: 4
CDR-L3 of SEQ ID NO: 5

and heavy chain CDR sequences:
CDR-H1 of SEQ ID NO: 6
CDR-H2 of SEQ ID NO: 7
CDR-H3 of SEQ ID NO: 8.

4. A formulation according to claim 1 , wherein the monoclonal antibody has a light chain variable region sequence of SEQ ID NO: 9 and a heavy chain variable region sequence of SEQ ID NO: 10.

5. A formulation according to claim 1 , wherein the monoclonal antibody has a light chain sequence of SEQ ID NO: 1 and a heavy chain sequence of SEQ ID NO: 2.

6. A formulation according to claim 1 , wherein the monoclonal antibody is present in the formulation at a concentration of about 100 mg/ml to about 165 mg/ml.

7. A formulation according to claim 1 , wherein the formulation has a pH in the range of about pH 5.7 to about pH 6.1.

8. A formulation according to claim 1 , wherein the ionic excipient is a salt.

9. A formulation according to claim 8 , wherein the salt is arginine hydrochloride.

10. A formulation according to claim 1 , wherein the ionic excipient is present at a concentration of about 75 mM to about 100 mM.

11. A formulation according to claim 10 , wherein the ionic excipient is present at a concentration of about 80 mM.

12. A formulation according to claim 1 , wherein the formulation further comprises a sugar.

13. A formulation according to claim 12 , wherein the sugar is sucrose.

14. A formulation according to claim 12 , wherein the sugar is present at a concentration of about 100 mM to about 140 mM.

15. A formulation according to claim 14 , wherein the sugar is present at a concentration of about 120 mM.

16. A formulation according to claim 1 , wherein the formulation further comprises one or more buffers.

17. A formulation according to claim 16 , wherein the one or more buffers is selected from histidine, histidine hydrochloride, and histidine/histidine hydrochloride.

18. A formulation according to claim 17 , wherein the one or more buffers is L-histidine/L-histidine hydrochloride monohydrate.

19. A formulation according to claim 16 , wherein the one or more buffers is present at a concentration of about 10 mM to about 50 mM.

20. A formulation according to claim 19 , wherein the one or more buffers is present at a concentration of about 30 mM.

21. A formulation according to claim 1 , wherein the formulation further comprises a surfactant.

22. A formulation according to claim 21 , wherein the surfactant is a polysorbate.

23. A formulation according to claim 22 , wherein the surfactant is polysorbate-80.

24. A formulation according to claim 21 , wherein the surfactant is present in the formulation at a concentration from about 0.001% (w/v) to about 0.07% (w/v).

25. A formulation according to claim 24 , wherein the surfactant is present in the formulation at a concentration of about 0.02% (w/v).

26. A formulation according to claim 1 , wherein the formulation further comprises one or more additional excipients.

27. A formulation according to claim 1 , which is a pharmaceutical formulation.

28. A formulation as defined in claim 1 , wherein the formulation is lyophilized.

29. A formulation comprising:
an anti-Respiratory Syncytial Virus (RSV) monoclonal antibody; and
an ionic excipient;
wherein the anti-RSV monoclonal antibody comprises the MEDI 8897 monoclonal antibody having a light chain of SEQ ID NO: 1 and a heavy chain of SEQ ID NO: 2;
wherein the MEDI 8897 monoclonal antibody has a pI in the range of about pH 6.4 to about pH 6.7;
wherein the monoclonal antibody is present at a concentration of 75 mg/ml to 200 mg/ml;
wherein the ionic excipient comprises arginine hydrochloride at a concentration of 75 mM to 100 mM;
wherein the formulation further comprises 10 mM to 50 mM L-histidine/L-histidine hydrochloride monohydrate, 100 mM to 140 mM sucrose, and 0.02% to 0.04% (w/v) polysorbate 80; and
wherein the formulation has a pH of 5.7 to 6.1.

30. A formulation according to claim 29 , wherein the monoclonal antibody has a pI of about pH 6.4.

31. A formulation according to claim 29 , wherein the formulation further comprises one or more additional excipients.

32. A formulation according to claim 29 , which is a pharmaceutical formulation.

33. A formulation according to claim 29 , wherein the formulation is lyophilized.

34. A formulation according to claim 26 , wherein the one or more excipient is selected one or more sugars, salts, amino acids, polyols, chelating agents, emulsifiers and/or preservatives.

35. A formulation comprising a monoclonal antibody that specifically binds the Respiratory Syncytial Virus (RSV) F protein and an ionic excipient;
wherein the monoclonal antibody has a pI of about pH 6.4 to about pH 6.7;
wherein the monoclonal antibody is present at a concentration of 75 mg/ml to 200 mg/ml;
wherein the ionic excipient comprises arginine hydrochloride at a concentration of 75 mM to 100 mM;
wherein the formulation further comprises 10 mM to 50 mM L-histidine/L-histidine hydrochloride monohydrate, 100 mM to 140 mM sucrose, and 0.02% to 0.04% (w/v) polysorbate 80; and
wherein the formulation has a pH of 5.7 to 6.1.

36. A formulation according to claim 35 , wherein the formulation is lyophilized.

37. A formulation according to claim 35 , wherein the monoclonal antibody comprises a light chain comprising a CDR-L1 sequence of QASQDIVNYLN (SEQ ID NO: 3), a light chain CDR-L2 sequence of VASNLET (SEQ ID NO: 4), and a light chain CDR-L3 sequence QQYDNLPLT of (SEQ ID NO: 5) and a heavy chain comprising a CDR-H1 sequence of DYIIN (SEQ ID NO: 6), a CDR-H2 sequence of GIIPVLGTVHYGPKFQG (SEQ ID NO: 7), and a CDR-H3 sequence of ETALVVSETYLPHYFDN (SEQ ID NO: 8).

38. A formulation according to claim 37 , wherein the monoclonal antibody has a pI of about pH 6.4.

39. A formulation according to claim 37 , wherein the formulation is lyophilized.

40. A formulation according to claim 35 , wherein the monoclonal antibody has a light chain variable region sequence of SEQ ID NO: 9 and a heavy chain variable region sequence of SEQ ID NO: 10.

41. A formulation according to claim 40 , wherein the monoclonal antibody has a pI of about pH 6.4.

42. A formulation according to claim 40 , wherein the formulation is lyophilized.

Assignees

• Medimmune Ltd

Inventors

• Lobo Brian
• Goldberg Deborah

Classifications

• C07K16/104

  Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] · CPC title

• C07K16/11 Primary

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• A61K39/39591 Primary

  Stabilisation, fragmentation · CPC title

• A61K39/42

  viral · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title