Stable liquid pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-11639391-B2
Application number	US-201816604031-A
Country	US
Kind code	B2
Filing date	Apr 18, 2018
Priority date	Apr 18, 2017
Publication date	May 2, 2023
Grant date	May 2, 2023

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

The invention claimed is:

1. A stable liquid tocilizumab formulation, consisting of tocilizumab, a phosphate-amino acid dual buffer system and one or more pharmaceutically acceptable excipients, and wherein the concentration of the antibody stabilized is from about 10 mg/ml to about 200 mg/ml; the amino acid is selected from the group consisting of histidine, glycine, and aspartate, and the excipients are selected from the group consisting of sorbitol, arginine and polysorbate.

2. The formulation according to claim 1 , wherein the tocilizumab formulated in the phosphate-amino acid buffer remains stable under one of the following storage conditions at 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.

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 formulation has a viscosity of less than 10 cp.

5. The formulation according to claim 1 , wherein the concentration of buffer in the said formulation is less than 100 mM.

6. The formulation according to claim 1 , wherein the formulation does not contain anti-oxidants.

7. A stable liquid formulation of tocilizumab according to claim 1 , wherein the formulation maintains at least 95% of monomeric content and/or contains less than 5% of aggregates of the antibody, after storage at 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.

8. The formulation according to claim 1 , wherein the formulation does not contain methionine.

Assignees

• Dr Reddys Laboratories Ltd

Inventors

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

Classifications

• A61K39/39591 Primary

  Stabilisation, fragmentation · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · 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

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• C07K16/32

  against translation products of oncogenes · CPC title