Stabilized formulations containing anti-DLL4 antibodies

Patent metadata

Field	Value
Publication number	US-9675692-B2
Application number	US-201313906479-A
Country	US
Kind code	B2
Filing date	May 31, 2013
Priority date	May 31, 2012
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The present invention provides pharmaceutical formulations comprising an antibody that specifically binds to human delta-like ligand 4 (Dll4). The formulations may contain, in addition to an anti-Dll4 antibody, a phosphate buffer, an organic cosolvent, a disaccharide, and a salt. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months and after being subjected to thermal and other physical stress.

First claim

What is claimed is:

1. A pharmaceutical formulation consisting of
(a) 25 mg/mL±3.75 mg/mL of an anti-Dll4 antibody comprising the HCVD of SEQ ID NO: 1 and the LCVD of SEQ ID NO: 5,
(b) 10 mM±3 mM phosphate, pH 6±0.5,
(c) 0.2%±0.03% polysorbate 20,
(d) 150 mM±22.5 mM sodium chloride, and
(e) 10%±1.5% sucrose, in water
wherein the antibody a molecular weight of about 150 kDa; and about 82% to about 87% of the antibodies are fucosylated.

2. A pharmaceutical composition of claim 1 , wherein said composition is contained in a container.

3. The pharmaceutical composition of claim 2 , wherein the container is a vial.

4. The pharmaceutical composition of claim 3 , wherein the vial is glass.

5. The pharmaceutical composition of claim 2 , wherein the container is an IV drip bag.

6. The pharmaceutical composition of claim 5 , wherein the bag is made of polyvinyl chloride.

7. The pharmaceutical composition of claim 5 , wherein the bag is made of poly olefin.

8. A kit comprising a pharmaceutical composition of claim 1 , a container, and instructions.

9. The kit of claim 8 , wherein the container is a glass vial fitted with a fluorocarbon-coated 4023/50 rubber stopper.

10. The pharmaceutical formulation of claim 1 , wherein after 28 days of storage at 45° C., at least 94% of the antibody has native conformation, or at least 45% of the antibody is the main charge form.

11. The pharmaceutical formulation of claim 1 , wherein after 28 days of storage at 25° C., at least 97% of the antibody has native conformation, or at least 57% of the antibody is the main charge form.

12. The pharmaceutical formulation of claim 1 , wherein after 28 days of storage at 37° C., at least 97% of the antibody has native conformation, or at least 51% of the antibody is the main charge form.

13. The pharmaceutical formulation of claim 1 , wherein after six months of storage at 5° C., at least 98% of the antibody has native conformation, at least 61% of the antibody is the main charge form, or the antibody retains about 100% of the potency of the antibody prior to storage.

14. The pharmaceutical formulation of claim 1 , wherein after six months of storage at −80° C., at least 99% of the antibody has native conformation, at least 57% of the antibody is the main charge form, or the antibody retains about 100% of the potency of the antibody prior to storage.

15. The pharmaceutical formulation of claim 1 , wherein after six months of storage at −30° C., at least 99% of the antibody has native conformation, at least 57% of the antibody is the main charge variant, or the antibody retains at least 65% of the potency of the antibody prior to storage.

16. The pharmaceutical formulation of claim 1 , wherein after six months of storage at −20° C., at least 98% of the antibody has native conformation, at least 60% of the antibody is the main charge variant, or the antibody retains about 100% of the potency of the antibody prior to storage.

Assignees

• Regeneron Pharma

Inventors

• Walsh Scott
• Dix Daniel

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

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

• A61P27/02

  Ophthalmic agents · CPC title