Anti-RSV monoclonal antibody formulation

Patent metadata

Field	Value
Publication number	US-11667698-B2
Application number	US-202016927169-A
Country	US
Kind code	B2
Filing date	Jul 13, 2020
Priority date	Mar 1, 2017
Publication date	Jun 6, 2023
Grant date	Jun 6, 2023

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 method of preventing Respiratory Syncytial Virus (RSV) lower respiratory tract disease in a human subject, comprising administering to the subject a pharmaceutical formulation comprising:
an anti-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; and

wherein the monoclonal antibody is present in the pharmaceutical formulation at a concentration of about 50 mg/ml or greater, the ionic excipient is present in the pharmaceutical formulation at a concentration of about 50 mM to about 150 mM, the one or more buffers is present in the pharmaceutical formulation at a concentration of about 10 mM to about 50 mM, and the pharmaceutical formulation has a pH of about 5.5 to about 7.5.

2. The method of 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. The method of 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. The method of claim 1 , wherein the monoclonal antibody is present in the pharmaceutical formulation at a concentration of about 75 mg/ml to about 200 mg/ml.

5. The method of claim 4 , wherein the monoclonal antibody is present in the pharmaceutical formulation at a concentration of about 100 mg/ml.

6. The method of claim 1 , wherein the ionic excipient comprises arginine or lysine.

7. The method of claim 1 , wherein the ionic excipient is arginine hydrochloride.

8. The method of claim 7 , wherein the arginine hydrochloride is present in the pharmaceutical formulation at a concentration of about 75 mM to about 100 mM.

9. The method of claim 8 , wherein the arginine hydrochloride is present in the pharmaceutical formulation at a concentration of about 80 mM.

10. The method of claim 1 , wherein the one or more buffers is histidine, histidine hydrochloride, or a combination thereof.

11. The method of claim 1 , wherein the one or more buffers is L-histidine, L-histidine hydrochloride, or a combination thereof.

12. The method of claim 11 , wherein the one or more buffers is present in the pharmaceutical formulation at a concentration of about 30 mM.

13. The method of claim 1 , wherein the pharmaceutical formulation further comprises sucrose at a concentration of about 100 mM to about 140 mM.

14. The method of claim 1 , wherein the pharmaceutical formulation further comprises polysorbate-80 at a concentration of about 0.02% (w/v) to about 0.07% (w/v).

15. The method of claim 14 , wherein the polysorbate-80 is present in the pharmaceutical formulation at a concentration of about 0.02% (w/v) or about 0.04% (w/v).

16. The method of claim 1 , wherein the pharmaceutical formulation has a pH of about 5.7 to about 6.3.

17. The method of claim 16 , wherein the pharmaceutical formulation has a pH of about 6.0.

18. The method of claim 1 ,
wherein the monoclonal antibody is present in the pharmaceutical formulation at a concentration of about 75 mg/ml to about 200 mg/ml; the ionic excipient comprises arginine hydrochloride, present in the pharmaceutical formulation at a concentration of about 75 mM to about 100 mM; and the one or more buffers comprises histidine, histidine hydrochloride, or a combination thereof, present in the pharmaceutical formulation at a concentration of about 10 mM to about 50 mM; and
wherein the pharmaceutical formulation further comprises 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 0.07% (w/v); and
wherein the pharmaceutical formulation has a pH of about 5.5 to about 6.5.

19. The method of claim 18 , 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.

20. The method of claim 19 , wherein the arginine hydrochloride is present in the pharmaceutical formulation at a concentration of about 80 mM; the histidine, histidine hydrochloride, or a combination thereof is present in the pharmaceutical formulation at a concentration of about 30 mM; the sucrose is present in the pharmaceutical formulation at a concentration of about 120 mM, the polysorbate 80 is present in the pharmaceutical formulation at a concentration of about 0.02% (w/v) to about 0.04% (w/v); and the pharmaceutical formulation has a pH of about 5.7 to about 6.3.

21. The method of claim 19 , wherein the monoclonal antibody comprises a light chain sequence of SEQ ID NO: 1 and a heavy chain sequence of SEQ ID NO: 2.

22. The method of claim 21 , wherein the arginine hydrochloride is present in the pharmaceutical formulation at a concentration of about 80 mM; the histidine, histidine hydrochloride, or a combination thereof is present in the pharmaceutical formulation at a concentration of about 30 mM; the sucrose is present in the pharmaceutical formulation at a concentration of about 120 mM, the polysorbate 80 is present in the pharmaceutical formulation at a concentration of about 0.02% (w/v) to about 0.04% (w/v); and the pharmaceutical formulation has a pH of about 5.7 to about 6.3.

23. The method of claim 1 , wherein the subject is under 2 years of age.

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

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• A61K47/183

  Amino acids, e.g. glycine, EDTA or aspartame · CPC title

• C07K2317/522

  CH1 domain · CPC title