Stabilized formulations containing anti-ngf antibodies

Patent metadata

Field	Value
Publication number	US-2016017029-A1
Application number	US-201514875457-A
Country	US
Kind code	A1
Filing date	Oct 5, 2015
Priority date	Jul 14, 2010
Publication date	Jan 21, 2016
Grant date	—

Abstract

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human nerve growth factor (hNGF). The formulations may contain, in addition to an anti-hNGF antibody, at least one non-ionic surfactant, at least one sugar, and acetate. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.

First claim

1 . A pharmaceutical formulation, comprising
(i) about 0.1 to 1.0% mg/ml of a human antibody that specifically binds to human nerve growth factor (hNGF), wherein the antibody comprises a heavy chain and light chain variable region (HCVR/LCVR) amino acid sequences pairs selected from the group consisting of: (i) SEQ ID NOs: 20/22; and (ii) SEQ ID NOs 4/12; (ii) about 0.01 to 1.0% of a polysorbate 20; (iii) about 1 to 20% of sucrose; and (iv) about 1 mM to about 50 mM acetate; and (v) an amino acid selected from the group consisting of histidine and arginine, whereby 90% or more of the antibody is detected by size-exclusion-high-performance liquid chromatography (SE-HPLC) when stored at 5° C. for six months.

2 - 9 . (canceled)

10 . The pharmaceutical formulation of claim 1 , comprising: (i) about 0.2 to 75 mg/mL of a human antibody that specifically binds to hNGF; (ii) about 0.02 to 0.5% polysorbate 20; and (iii) about 5 to 10% sucrose.

11 . The pharmaceutical formulation of claim 10 , comprising: (i) about 0.6-60 mg/mL of a human antibody that specifically binds to hNGF; (ii) about 0.5% polysorbate 20; and (iii) about 8% sucrose.

12 . (canceled)

13 . The pharmaceutical formulation of claim 1 , further comprising:
a glass container selected from the group consisting of a glass vial, a glass syringe, a plastic vial, and a plastic syringe.

14 . The formulation of claim 13 , wherein the container is a glass vial comprising a silicon dioxide coated glass.

15 . The formulation of claim 14 , wherein the glass vial is filled with the formulation leaving headspace filled with an inert gas.

16 . The formulation of claim 15 , wherein the inert gas is selected from the group consisting of argon and nitrogen.

17 . The pharmaceutical formulation of claim 1 , further comprising:
a container selected from the group consisting of an autoinjector, and a microinfusor.

18 . The pharmaceutical formulation of claim 13 , wherein the glass container is the syringe and the syringe is a syringe comprising a fluorocarbon-coated plunger.

19 . The pharmaceutical formulation of claim 18 , wherein the syringe is a low tungsten syringe.

20 . The pharmaceutical formulation of claim 19 , wherein the syringe comprises a fluorocarbon-coated plunger.

21 .- 27 . (canceled)

28 . A method for maintaining the stability of an antibody in a formulation, comprising:
storing an antibody formulation for six months or more at 5° C. or more; wherein the antibody formulation comprises: (i) about 0.1 to 100 mg/ml of a human antibody that specifically binds to human nerve growth factor (hNGF), wherein the antibody comprises a heavy chain and light chain variable region (HCVR/LCVR) amino acid sequence pairs selected from the group consisting of: (i) SEQ ID NOs:20/22; and (ii) SEQ ID NOs 4/12; (ii) about 0.01 to 1.0% of a polysorbate 20; (iii) about 1 to 20% of sucrose; and (iv) about 1 mM to about 50 mM acetate; whereby the stored formulation maintains stability such that 90% or more of the antibody is detected by size-exclusion high-performance liquid chromatography (SE-HPLC).

Assignees

• Regeneron Pharma

Inventors

• Walsh Scott
• Potocky Terra
• Dix Daniel
• Sivendran Renuka

Classifications

• A61P43/00

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

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title