Anti-RSV monoclonal antibody formulation

Patent metadata

Field	Value
Publication number	US-11286294-B2
Application number	US-202117351348-A
Country	US
Kind code	B2
Filing date	Jun 18, 2021
Priority date	Mar 1, 2017
Publication date	Mar 29, 2022
Grant date	Mar 29, 2022

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;
an ionic excipient; and
one or more buffers;

wherein the monoclonal antibody comprises 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;

wherein the monoclonal antibody is present at a concentration of about 50 mg/ml or greater;
wherein the ionic excipient is present at a concentration of about 50 mM to about 150 mM;
wherein the one or more buffers is present at a concentration of about 10 mM to about 50 mM; 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 comprises a light chain variable region sequence of SEQ ID NO: 9 and a heavy chain variable region sequence of SEQ ID NO: 10.

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

4. A formulation according to claim 1 , wherein the ionic excipient is arginine hydrochloride.

5. A formulation according to claim 4 , wherein the arginine hydrochloride is present at a concentration of about 80 mM.

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

7. A formulation according to claim 6 , wherein the sugar is sucrose.

8. A formulation according to claim 7 , wherein the sucrose is present at a concentration of about 100 mM to about 140 mM.

9. A formulation according to claim 7 , wherein the sucrose is present at a concentration of about 120 mM.

10. A formulation according to claim 1 , wherein the one or more buffers is selected from histidine, histidine hydrochloride, or a combination thereof.

11. A formulation according to claim 1 , wherein the one or more buffers is present at a concentration of about 30 mM.

12. A formulation according to claim 11 , wherein the one or more buffers is selected from L-histidine, L-histidine hydrochloride, or a combination thereof.

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

14. A formulation according to claim 1 , wherein the formulation further comprises polysorbate 80.

15. A formulation according to claim 14 , wherein the polysorbate 80 is present at a concentration of from about 0.001% (w/v) to about 0.07% (w/v).

16. A formulation according to claim 14 , wherein the polysorbate 80 is present at a concentration of about 0.02% (w/v) to about 0 . 04 % (w/v).

17. A formulation according to claim 14 , wherein the polysorbate 80 is present at a concentration of about 0.02% (w/v) or about 0.04% (w/v).

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

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

20. A formulation according to claim 19 , wherein the one or more additional excipients is selected from one or more sugars, salts, amino acids, polyols, chelating agents, emulsifiers and/or preservatives.

21. A formulation according to claim 1 , wherein the formulation has a pH in the range of about 5.7 to about 6.3.

22. A formulation according to claim 1 , wherein the formulation has a pH of about 6.0.

23. A formulation according to claim 1 , wherein the formulation is a pharmaceutical formulation.

24. A formulation according to claim 1 , wherein the formulation is lyophilized.

25. A formulation according to claim 1 , wherein the formulation is liquid.

26. A formulation comprising:
an anti-Respiratory Syncytial Virus (RSV) monoclonal antibody; and
an ionic excipient;
wherein the anti-RSV monoclonal antibody comprises a light chain comprising a CDR-L1 sequence of QASQDIVNYLN (SEQ ID NO: 3), a CDR-L2 sequence of VASNLET (SEQ ID NO: 4), and a CDR-L3 sequence of 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);
wherein the monoclonal antibody is present at a concentration of about 75 mg/ml to about 200 mg/ml;
wherein the ionic excipient comprises arginine hydrochloride at a concentration of about 75 mM to about 100 mM;
wherein the formulation further comprises:
histidine, histidine hydrochloride, or a combination thereof at a concentration of about 10 mM to about 50 mM;
sucrose at a concentration of about 100 mM to about 140 mM; and
polysorbate 80 at a concentration of about 0.02% (w/v) to about 0.04% (w/v); and
wherein the formulation has a pH of about 5.5 to about 6.5.

27. A formulation according to claim 26 , wherein the monoclonal antibody comprises a light chain variable region sequence of SEQ ID NO: 9 and a heavy chain variable region sequence of SEQ ID NO: 10.

28. A formulation comprising:
an anti-Respiratory Syncytial Virus (RSV) monoclonal antibody comprising a light chain sequence of SEQ ID NO: 1 and a heavy chain sequence of SEQ ID NO: 2;
wherein the monoclonal antibody is present at a concentration of about 75 mg/ml to about 200 mg/ml;

arginine hydrochloride at a concentration of about 80 mM;
histidine, histidine/histidine hydrochloride, or a combination thereof at a concentration of about 30 mM;
sucrose at a concentration of about 120 mM; and
polysorbate 80 at a concentration of about 0.02% (w/v) to about 0.04% (w/v); and
wherein the formulation has a pH of about 5.5 to about 6.5.

29. A formulation according to claim 1 , wherein the monoclonal antibody comprises a light chain sequence of SEQ ID NO: 1 and a heavy chain sequence of SEQ ID NO: 2 and the formulation has a pH of about 5.7 to about 6.3.

30. A formulation according to claim 26 , wherein the monoclonal antibody comprises a light chain sequence of SEQ ID NO: 1 and a heavy chain sequence of SEQ ID NO: 2.

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

• A61P31/12

  Antivirals · CPC title