Risankizumab Aqueous Composition Without Polyols for Protein Stability
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Solution Overview
Problem
Existing risankizumab formulations face stability issues due to the use of polyols, which can decompose into monosaccharides, leading to protein denaturation and efficacy risks, necessitating a stabilizer replacement.
Innovation Solution
An aqueous pharmaceutical composition of risankizumab or its antigen-binding fragment, utilizing an amino acid or a pharmaceutically acceptable salt as a stabilizer, without polyols, with a pH of 5.0 to 7.0, and optionally without surfactants or buffers, to enhance stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If polyols are used as stabilizers in risankizumab formulations, then protein stability is improved, but polyols decompose into monosaccharides causing protein denaturation and efficacy loss
Solution Approach 1:
The patent removes polyols from the formulation entirely and replaces them with alternative stabilizers including amino acids (proline, glycine, alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, serine, threonine, cysteine, methionine, asparagine, glutamine, aspartic acid, glutamic acid), metal salts (sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, sodium sulfate, sodium fluoride, sodium bromide, sodium iodide, ammonium sulfate, ammonium chloride, ammonium nitrate, ammonium acetate, ammonium formate, ammonium carbonate, ammonium bicarbonate), and sugar alcohols (xylitol, erythritol, sorbitol, mannitol, inositol). This extraction of the harmful polyol component while maintaining stabilizing function resolves the contradiction between stability and denaturation risk.
2Stability of the object's composition
If polyols are used as stabilizers, then formulation stability is enhanced, but monosaccharide impurities cause glycation reactions affecting protein efficacy
Solution Approach 1:
The patent extracts polyols from the formulation to eliminate the source of monosaccharide impurities that cause glycation. The replacement stabilizers (amino acids, metal salts, sugar alcohols) do not undergo hydrolysis to produce monosaccharides, thereby preventing glycation reactions and maintaining protein efficacy while still providing formulation stability.
Solution Approach 2:
The patent employs stabilizers with different chemical properties than polyols - specifically amino acids and metal salts that are chemically stable and do not decompose into reactive monosaccharides. These alternative stabilizers provide the necessary protection without the long-term degradation issues associated with polyols.
Data Source
AI summary
The present disclosure relates to an aqueous pharmaceutical composition, a method of preparing the same, and use thereof, the aqueous pharmaceutical composition including: risankizumab or an antigen-binding fragment thereof; and a stabilizer, wherein the aqueous pharmaceutical composition does not include a polyol.