Liquid formulation comprising GM-CSF neutralizing compound

Patent metadata

Field	Value
Publication number	US-9919051-B2
Application number	US-201314429204-A
Country	US
Kind code	B2
Filing date	Oct 31, 2013
Priority date	Oct 31, 2012
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

The present invention relates to aqueous formulations comprising a compound neutralizing GM-CSF in concentrations of at least about 20 mg/ml, a tonicity modifier and a buffer, wherein the composition is stable. The ingredients of the formulation preferably provide stability to the compound neutralizing GM-CSF in view of long-term storage. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory and autoimmune disorders, preferably including allergic and psoriatic disorders, as well as arthritic and asthmatic disorders. Furthermore, a kit comprising the formulation of the invention is provided.

First claim

The invention claimed is:

1. A composition comprising an antibody or a functional fragment thereof binding to GM-CSF or to the GM-CSF receptor present in a concentration of at least about 100 mg/ml and less than about 200 mg/ml, a tonicity modifier selected from mannitol, sorbitol, sucrose and/or trehalose, present in a concentration from about 3% to about 7% (w/v), and a buffer selected from a histidine, acetate and/or citrate buffer present in a concentration from about 10 mM to about 50 mM, wherein the pH is between about 5 and about 7 and wherein the composition is stable.

2. The composition according to claim 1 , wherein the tonicity modifier is sorbitol and the buffer is a histidine buffer.

3. The composition according to claim 1 , which is free of surfactants or additional amino acids.

4. The composition according to claim 1 , wherein the antibody or the functional fragment thereof is a human monoclonal antibody or a functional fragment thereof.

5. The composition according to claim 1 which comprises:
(i) about 100 mg/ml to about 180 mg/ml of the antibody or functional fragment thereof binding to GM-CSF or to the GM-CSF receptor,
(ii) about 5% (w/v) sorbitol,
(iii) about 30 mM L-histidine and
(iv) has a pH of about 5.8.

6. The composition according to claim 5 , which comprises about 150 mg/ml of the antibody or functional fragment thereof binding to GM-CSF or to the GM-CSF receptor.

7. The composition according to claim 1 , which is a liquid, preferably an aqueous composition.

8. The composition according to claim 1 , which is stable for at least 24 months at about 2-8° C. or at least 28 days at room temperature.

9. The composition according to claim 1 , wherein the antibody or functional fragment is a human monoclonal antibody or functional fragment thereof binding to GM-CSF which comprises in its light chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 16, a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 17 and a CDR3 comprising an amino acid sequence as set out in SEQ ID NO: 18, and which comprises in its heavy chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 14, a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 15 and a CDR3 comprising an amino acid sequence selected from the group consisting of those set out in SEQ ID NOs: 1-13 and 56.

10. The composition according to claim 1 , wherein the antibody or functional fragment is a human monoclonal antibody or functional fragment thereof binding to GM-CSF which comprises in its light chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 16, a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 17 and a CDR3 comprising an amino acid sequence as set out in SEQ ID NO: 18, and which comprises in its heavy chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 14, a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 15 and a CDR3 comprising an amino acid sequence as set out in SEQ ID NO: 2.

11. The composition according to claim 1 , which is for intravenous and/or subcutaneous administration.

12. The composition according to claim 1 for use in therapy.

13. The composition according to claim 1 for use in the treatment of inflammatory and autoimmune disorders.

14. The composition according to claim 13 , wherein the disorders are selected from allergic, psoriatic, arthritic and asthmatic disorders.

15. A kit comprising the composition according to claim 1 .

16. The composition according to claim 10 , wherein the human monoclonal antibody or functional fragment thereof binding to GM-CSF comprises in its heavy chain variable region an amino acid sequence as set out in any one of SEQ ID NOs: 20-33, 52 or 53 and in its light chain variable region an amino acid sequence as set out in any one of SEQ ID NOs: 19, 54 or 55.

17. The composition according to claim 10 , wherein the human monoclonal antibody or functional fragment thereof binding to GM-CSF comprises a light chain amino acid sequence as set out in SEQ ID NO: 34 and a heavy chain amino acid sequence as set out in SEQ ID NO: 35.

18. The composition according to claim 10 , wherein the tonicity modifier is sorbitol and the buffer is a histidine buffer.

19. The composition according to claim 10 , which is free of surfactants or additional amino acids.

20. The composition according to claim 10 which comprises:
(i) about 100 mg/ml to about 180 mg/ml of the antibody or functional fragment thereof binding to GM-CSF or to the GM-CSF receptor,
(ii) about 5% (w/v) sorbitol,
(iii) about 30 mM L-histidine and
(iv) has a pH of about 5.8.

21. The composition according to claim 10 , which comprises about 150 mg/ml of the antibody or functional fragment thereof binding to GM-CSF or to the GM-CSF receptor.

22. The composition according to claim 10 , which is stable for at least 24 months at about 2-8° C. or for at least 28 days at room temperature.

23. A composition which comprises:
(i) about 100 mg/ml to about 180 mg/ml of an antibody or functional fragment thereof binding to GM-CSF, wherein the antibody or functional fragment is a human monoclonal antibody or functional fragment thereof which comprises in its light chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 16, a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 17 and a CDR3 comprising an amino acid sequence as set out in SEQ ID NO: 18, and which comprises in its heavy chain variable region a CDR1 comprising an amino acid sequence as set out in SEQ ID NO: 14, a CDR2 comprising an amino acid sequence as set out in SEQ ID NO: 15 and a CDR3 comprising an amino acid sequence as set out in SEQ ID NO: 2,
(ii) about 5% (w/v) sorbitol,
(iii) about 30 mM L-histidine and
(iv) has a pH of about 5.8;
and wherein the composition is stable.

Assignees

• Amgen Res Munich Gmbh
• Takeda Gmbh

Inventors

• Urbig Thomas
• Boehm Thomas
• Steinhilber Wolfram
• Molhoj Michael

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P17/06

  Antipsoriatics · CPC title