Low concentration antibody formulations

Patent metadata

Field	Value
Publication number	US-2016000916-A1
Application number	US-201414775900-A
Country	US
Kind code	A1
Filing date	Mar 13, 2014
Priority date	Mar 15, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

The present invention is directed formulations for low concentrations of therapeutic proteins and methods of making the same. In one aspect the present invention is directed to a formulation for a therapeutic protein comprising: a) the therapeutic protein; and b) a surfactant; wherein the molar ratio of surfactant to therapeutic protein is at least 100. In another aspect the present invention is directed to a formulation for a therapeutic protein comprising: a) the therapeutic protein; and b) an antioxidant, wherein the molar ratio of antioxidant to therapeutic protein is at least 750.

First claim

1 - 28 . (canceled)

29 . A formulation for a therapeutic protein comprising: a) the therapeutic protein; and b) a surfactant; wherein the molar ratio of surfactant to therapeutic protein is at least 100.

30 . The formulation according to claim 29 wherein the molar ratio of surfactant to therapeutic protein is selected from the group consisting of at least 150, at least 200, at least 250, at least 300, at least 400, at least 500, and about 545.

31 . The formulation of claim 29 wherein the surfactant is at least one selected from the group consisting of polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-65, polysorbate-80, polysorbate-85 and poloxamer 88.

32 . The formulation of claim 29 wherein the formulation further comprises c) an antioxidant, wherein the molar ratio of antioxidant to therapeutic protein is at least 750.

33 . The formulation of claim 32 wherein the molar ratio of antioxidant to therapeutic protein is selected from the group consisting of at least 5500, at least 6000, at least 6500, at least 7000, and about 7143.

34 . The formulation according to claim 32 wherein the antioxidant is selected from the group consisting of methionine, cysteine, glutathione, and monothioglycerol.

35 . The formulation according to claim 29 wherein the formulation further comprises d) a buffer, wherein the pH of the formulation is 4.0 to 8.0.

36 . The formulation according to claim 35 wherein the buffer is selected from the group consisting of histidine, acetate, citrate, and succinate.

37 . The formulation according to claim 29 wherein the therapeutic protein is an antigen binding protein.

38 . The formulation according to claim 37 , wherein the antigen binding protein is selected from the group consisting of an antibody; an antibody fragment, an immunoglobulin single variable domain, an anti-CD3 antibody, and an anti-CD3 antibody comprising a heavy chain comprising SEQ ID NO:1 and a light chain comprising SEQ ID NO:2.

39 . The formulation according to claim 29 wherein the therapeutic protein is present at a concentration selected from the group consisting of 0.01 mg/ml to 1 mg/ml, 0.1 mg/ml to 0.5 mg/ml, and 0.2 mg/ml.

40 . A formulation for a therapeutic protein comprising: a) the therapeutic protein; and b) 0.01% w/v to 0.5% w/v surfactant, wherein the molar ratio of surfactant to therapeutic protein is at least 100; c) 1 mM to 50 mM antioxidant, wherein the molar ratio of antioxidant to therapeutic protein is at least 750; and d) 1 mM to 100 mM buffer, wherein the pH of the formulation is 4.0 to 8.0.

41 . The formulation of claim 40 wherein the therapeutic protein is an antibody, wherein the surfactant is polysorbate 80, wherein the antioxidant is methionine, and wherein the buffer is histidine.

42 . The formulation according to claim 29 , wherein the formulation further comprises at least one selected from the group consisting of 0.01 mM to 1.0 mM EDTA, 0.01 mM to 0.1 mM EDTA, and 0.05 mM EDTA.

Assignees

• Glaxosmithkline Ip No 2 Ltd

Inventors

• Crotts George
• Morar-Mitrica Sorina

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title