Protein formulation

Patent metadata

Field	Value
Publication number	US-9308257-B2
Application number	US-74474508-A
Country	US
Kind code	B2
Filing date	Nov 26, 2008
Priority date	Nov 28, 2007
Publication date	Apr 12, 2016
Grant date	Apr 12, 2016

Abstract

The present invention provides stable lyophilized formulations of bispecific antibodies or fragments thereof.

First claim

What is claimed is:

1. A liquid pharmaceutical formulation comprising between about 25 μg/ml and about 250 μg/ml of a single chain bispecific antibody comprising a first and a second binding domain, wherein the first binding domain specifically binds CD3 T cell surface antigen; and
wherein the formulation comprises between about 5 mM and about 125 mM citrate, between about 100 mM and about 300 mM lysine, between about 10% and about 20% trehalose, and between about 0.01% and about 1% Polysorbate 80, and has a pH of between 5.0 and about 8.0.

2. The formulation of claim 1 , wherein the first binding domain comprises the amino acid sequence of residues 283-525 of SEQ ID NO:5.

3. The formulation of claim 1 , wherein the second binding domain specifically binds an antigen selected from the group consisting of CD 19, CD20, CD22, EphA2, EphA4, INFR, ICOS, Ep-CAM, CEA, and IL-5 receptor.

4. The formulation of claim 3 , wherein the second binding domain comprises the amino acid sequence of residues 28-277 of SEQ ID NO:5.

5. The formulation of claim 3 , wherein the bispecific antibody comprises the amino acid sequence of residues 28-525 of SEQ ID NO:5.

6. A lyophilized pharmaceutical formulation comprising between about 25 μg/ml and about 250 μg/ml of a single chain bispecific antibody comprising a first and a second binding domain, wherein the first binding domain specifically binds CD3 T cell surface antigen; and
wherein the formulation comprises between about 5 mM and about 125 mM citrate, between about 100 mM and about 300 mM lysine, between about 0.01% and about 1% Polysorbate 80, and has a pH of between 5.0 and about 8.0.

7. The formulation of claim 6 , wherein the first binding domain comprises the amino acid sequence of residues 283-525 of SEQ ID NO:5.

8. The formulation of claim 6 , wherein the second binding domain specifically binds an antigen selected from the group consisting of CD 19, CD20, CD22, EphA2, EphA4, INFR, ICOS, Ep-CAM, CEA, and IL-5 receptor.

9. The formulation of claim 8 , wherein the second binding domain comprises the amino acid sequence of residues 28-277 of SEQ ID NO:5.

10. The formulation of claim 8 , wherein the bispecific antibody comprises the amino acid sequence of residues 28-525 of SEQ ID NO:5.

11. A liquid reconstituted pharmaceutical formulation comprising between about 25 μg/ml and about 250 μg/ml of a single chain bispecific antibody comprising a first and a second binding domain, wherein the first binding domain specifically binds CD3 T cell surface antigen; and
wherein the formulation comprises between about 5 mM and about 125 mM citrate, between about 100 mM and about 300 mM lysine, between about 10% and about 20% trehalose, and between about 0.01% and about 1% Polysorbate 80, and has a pH of between 5.0 and about 8.0.

12. The formulation of claim 11 , wherein the first binding domain comprises the amino acid sequence of residues 283-525 of SEQ ID NO:5.

13. The formulation of claim 11 , wherein the second binding domain specifically binds an antigen selected from the group consisting of CD 19, CD20, CD22, EphA2, EphA4, INFR, ICOS, Ep-CAM, CEA, and IL-5 receptor.

14. The formulation of claim 13 , wherein the second binding domain comprises the amino acid sequence of residues 28-277 of SEQ ID NO:5.

15. The formulation of claim 13 , wherein the bispecific antibody comprises the amino acid sequence of residues 28-525 of SEQ ID NO:5.

16. The formulation of claim 1 , wherein the formulation comprises about 55 micrograms/ml of a single chain bispecific tandemly arranged antibody or a fragment thereof, about 25 mM citrate, about 200 mM lysine, about 15% trehalose dihydrate and about 0.1% Polysorbate 80, and has a pH of about 7.0.

17. The formulation of claim 11 , wherein the formulation comprises about 55 micrograms/ml of a single chain bispecific tandemly arranged antibody, about 25 mM citrate, about 200 mM lysine, about 15% trehalose dihydrate and about 0.1% Polysorbate 80, and has a pH of about 7.0.

18. The formulation of claim 1 , wherein the formulation comprises between about 10 and about 100 micrograms/ml of a single chain bispecific tandemly arranged antibody or a fragment thereof.

19. The formulation of claim 1 , wherein the formulation comprises between about 50 and about 55 micrograms/ml of a single chain bispecific tandemly arranged antibody or a fragment thereof.

20. The formulation of claim 1 , wherein the formulation comprises between about 10% and about 15% trehalose dihydrate.

21. The formulation of claim 1 , wherein the formulation comprises between about 15% and about 20% trehalose dihydrate.

22. The formulation of claim 1 , wherein the bispecific antibody is a a single chain bispecific tandemly arranged antibody or a fragment thereof.

Assignees

• Sharma Sr Monika S
• Shah Ambarish
• Hammond Scott
• Medimmune Llc

Inventors

• Sharma Sr Monika S
• Shah Ambarish
• Hammond Scott

Classifications

• A61K39/39591 Primary

  Stabilisation, fragmentation · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K16/2809

  against the T-cell receptor (TcR)-CD3 complex · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• A61P35/00

  Antineoplastic agents · CPC title