Stable liquid pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-2021101987-A1
Application number	US-201816604031-A
Country	US
Kind code	A1
Filing date	Apr 18, 2018
Priority date	Apr 18, 2017
Publication date	Apr 8, 2021
Grant date	—

Abstract

The present invention provides a stable liquid formulation of an antibody in phosphate-amino acid based dual buffer system. The antibody formulated in phosphate-amino acid based dual buffer system imparts optimum stability to the antibody, at lower as well as higher concentrations. Further, the antibody formulated in phosphate-amino acid based buffer system has low viscosity and is suitable for therapeutic administration of high concentrations of antibody.

First claim

1 . A stable liquid antibody formulation, wherein the formulation comprises a phosphate-amino acid dual buffer system.

2 . The formulation according to claim 1 , wherein the antibody formulated in the phosphate-amino acid buffer remains stable under at least one of the following storage conditions such as at 2-8 CC for at least 6 months or at 25° C. for at least 6 months, or at 40° C. for at least 2 weeks, or at 40° C. for at least 4 weeks.

3 . The formulation according to claim 1 , wherein the amino acid acts as counter ion to the phosphate component of the buffer in the formulation.

4 . The formulation according to claim 1 , wherein the concentration of the antibody in the said formulation ranges from about 10 mg/ml to about 200 mg/ml.

5 . The formulation according to claim 1 , wherein the viscosity of the formulation is less than 10 cp.

6 . The formulation according to claim 1 , further comprises pharmaceutically acceptable excipients such as sugars, amino acids, salts, and surfactant.

7 . The formulation according to claim 6 , wherein the concentration of buffer and/salts in the said formulation is less than 50 mull.

8 . The formulation according to claim 6 , wherein the pharmaceutically acceptable excipients does not include anti-oxidants.

9 . The formulation of claim 1 , wherein the antibody is an anti-IL6R antibody or anti-HER2 antibody.

10 . A stable liquid formulation of anti-IL6R antibody comprising, phosphate-amino acid buffer system, sorbitol and surfactant.

11 . A stable liquid formulation of anti-IL6R antibody comprising, phosphate-amino acid buffer system, sorbitol, surfactant and optionally contains arginine.

12 . The formulation according to claim 10 , wherein the antibody in the said formulation is devoid of anti-oxidant/s.

13 . A stable liquid formulation of tocilizumab in phosphate-amino acid buffer system comprising sorbitol, surfactant and optionally contains arginine wherein, the formulation is devoid of methionine.

14 . A stable liquid formulation of tocilizumab comprising a phosphate-amino acid buffer system, wherein the formulation maintains at least 95% of monomeric content and/or contains less than 5% of aggregates of the antibody, after storage 2-8° C. for at least 6 months or at 25° C. for at least 6 months, or at 40° C. for at least 2 weeks, or at 40° C. for at least 4 weeks.

15 . A stable liquid formulation of tocilizumab comprising a phosphate-histidine buffer, sorbitol and surfactant.

16 . The formulation according to claim 11 , wherein the antibody in the said formulation is devoid of anti-oxidant/s.

Assignees

• Dr Reddys Laboratories Ltd

Inventors

• Jayaraman Murali
• Nair Pravin
• Kaur Navneet
• Thumbrahalli Deepak

Classifications

• 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

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/24

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