Albumin-Binding Moiety Reduces Immunogenicity in Biopharmaceuticals
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Solution Overview
Problem
Current strategies for reducing immunogenicity in biopharmaceuticals face challenges such as difficulty in achieving covalent attachment without obstructing active sites, variability in quality and toxicity of PEGylated products, and high costs, with limited success in improving pharmacological and immunological properties beyond PEGylation.
Innovation Solution
A molecule comprising a biologically active protein and a moiety capable of binding to serum albumin is used to reduce or eliminate immune responses by forming a complex with serum albumin, thereby minimizing immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If PEGylation is used to reduce immunogenicity, then immunogenicity is reduced, but product quality variability and toxicity increase
Solution Approach 1:
The patent changes the chemical modification approach from PEGylation to albumin binding. By altering the fundamental parameter of the modifying group (from PEG chains to albumin protein), the patent achieves reduced immunogenicity while avoiding the quality variability and toxicity issues associated with PEGylation. The albumin binding moiety provides a more biocompatible and consistent modification.
Solution Approach 2:
The patent employs a disposable albumin binding moiety that can be attached to the biologically active protein. This moiety serves its purpose of reducing immunogenicity and then can be naturally cleared by the body's albumin metabolism pathways, avoiding the accumulation and long-term toxicity issues of PEGylation.
2Stability of the object's composition
If covalent attachment is used to modify proteins, then protein stability is improved, but active sites may be obstructed
Solution Approach 1:
The patent applies local quality by attaching the albumin binding moiety to specific regions of the biologically active protein that are distant from the active sites. This localized modification ensures that the stability-enhancing benefits are achieved without interfering with the functional active sites of the protein.
Solution Approach 2:
The albumin binding moiety acts as an intermediary between the biologically active protein and the serum albumin in the body. This intermediary provides the stability benefits through the albumin-protein interaction while keeping the active sites of the biologically active protein accessible and functional.
3Object-affected harmful factors
If albumin binding moiety is used to reduce immunogenicity, then immune response is reduced, but molecular complexity increases
Solution Approach 1:
The albumin binding moiety serves multiple functions: it reduces immunogenicity by binding to endogenous albumin, it extends the half-life of the biologically active protein through albumin-mediated recycling, and it provides a platform for potential further functionalization. This multi-functionality justifies the increased molecular complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The approach significantly reduces or eliminates immune responses to biologically active proteins, as evidenced by reduced antibody production in animal models, without compromising the protein's biological activity.
Implementation Method 1
a molecule comprising a biologically active protein and a moiety capable of binding to a serum albumin of a mammal
Data Source
AI summary
A new use of a molecule comprising at least one moiety which is a biologically active protein and at least one moiety capable of binding to a serum albumin of a mammal is provided, for preparation of a medicament which elicits no or a reduced immune response upon administration to the mammal, as compared to the immune response elicited upon administration to the mammal of the biologically active protein per se. Also provided is a method of reducing or eliminating the immune response elicited upon administration of a biologically active protein to a human or non-human mammal, which comprises coupling the polypeptide to at least one moiety capable of binding to a serum albumin of the mammal.