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Publication Number
US-11608357-B2
Publication Date
2023-03-21
Expiration Date
Abstract
There is provided, inter alia, an aqueous solution comprising (i) an antibody protein; and (ii) a antibody protein stabilizing mixture of arginine, methionine, and a C3 polyol.
Core Innovation
The invention provides stabilized aqueous antibody-protein formulations comprising a monoclonal antibody in an aqueous solution and a stabilizing mixture of arginine, methionine, and a C3 polyol. The formulations are defined by quantitative concentration constraints for methionine and the ratio of arginine to methionine, together with the presence of a C3 polyol, which is described as 1,2-propanediol and/or glycerol.
The problem addressed is reduced aggregation and particle formation and reduced chemical degradation of antibody proteins in aqueous solution, including deamidation, oxidation, and related species. The disclosure describes solution conditions including a pH of 4.0-8.0 and optionally other excipients such as buffers, non-ionic surfactants, tonicity modifiers, and preservatives, with the stated aim of stabilizing the monoclonal antibody during storage and administration routes.
The disclosure reports improved stability when the C3 polyol is combined with arginine and methionine versus formulations omitting the C3 polyol. The improved performance is described using measurements including visible particles and analytical assessments such as SEC and HMWS formation, and is attributed to the stabilizing mixture containing arginine, methionine, and a C3 polyol.
Claims Coverage
The independent claim is directed to an aqueous solution of a monoclonal antibody stabilized by arginine, methionine, and a C3 polyol, with defined quantitative constraints for methionine and the arginine-to-methionine ratio. Overall, the claim coverage centers on one core inventive feature with dependent refinements for component concentrations, buffer selection, and administration context.
Aqueous monoclonal antibody solution with stabilizing mixture of arginine, methionine, and C3 polyol
An aqueous solution comprising a monoclonal antibody and a stabilizing amount of arginine, methionine, and a C3 polyol, wherein the concentration of methionine is 2-50 mM and the ratio of arginine to methionine (mM/mM) is 1:1-10:1.
Arginine concentration range
The aqueous solution includes arginine at a concentration of about 5 mM to about 100 mM.
Methionine sub-range
The aqueous solution contains methionine at a concentration of about 2 mM to about 30 mM.
C3 polyol concentration range
The aqueous solution contains the C3 polyol at a concentration of about 150 mM to about 400 mM.
Buffer selection from named buffers
The aqueous solution uses a buffer chosen from histidine, succinate, maleate, acetate, phosphate, or TRIS.
Administration by injection or infusion
The aqueous solution is formulated for administration by subcutaneous or intramuscular injection, or by intravenous injection or infusion.
The claim coverage centers on an aqueous monoclonal antibody formulation stabilized by arginine plus methionine together with a C3 polyol, with quantitative methionine and arginine-to-methionine ratio constraints. Dependent coverage further limits arginine, methionine, and C3 polyol concentrations, specifies buffer options, and defines administration by injection or infusion.
Stated Advantages
Reduced aggregation and particle formation in aqueous antibody-protein formulations.
Reduced chemical degradation of antibody proteins, including reduced deamidation, oxidation, and related species formation.
Documented Applications
Formulations for storage and administration routes, including subcutaneous and intramuscular injection and intravenous injection or infusion.
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