IgG Fc Polypeptides With Alpha 2,6 Sialylation For Reduced Cytotoxicity
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Solution Overview
Problem
Current methods for therapeutic polypeptides in treating inflammatory diseases do not effectively account for the disparate observations of IVIG properties in vivo, particularly regarding the role of glycosylation in modulating inflammatory responses.
Innovation Solution
Development of isolated polypeptides containing IgG Fc regions with altered sialylation patterns, specifically enriched with galactose moieties connected to terminal sialic acid via α2,6 linkages, which exhibit enhanced anti-inflammatory activity and reduced binding to Fc activating receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional unpurified antibody preparations are used for treating inflammatory diseases, then the treatment can be administered with standard dosing regimens, but the anti-inflammatory activity is insufficient and cytotoxic side effects occur
Solution Approach 1:
The patent applies local quality by specifically modifying the glycosylation pattern at the Fc region of the antibody. By enriching for antibodies with galactose moieties connected to terminal sialic acid via α2,6 linkages at this specific location, the invention achieves enhanced anti-inflammatory activity and reduced cytotoxicity without altering the overall antibody structure or antigen-binding properties.
Solution Approach 2:
The patent employs parameter changes by altering the glycosylation parameters of the antibody Fc region. Specifically, it selects and enriches for antibodies with specific sugar composition (higher galactose and sialic acid content) and linkage types (α2,6 linkages), thereby changing the biochemical parameters of the antibody to achieve the desired therapeutic effect with reduced side effects.
2Reliability
If high doses of conventional antibodies are administered to achieve sufficient anti-inflammatory effect, then the desired therapeutic effect can be obtained, but cytotoxic side effects increase
Solution Approach 1:
The invention focuses on modifying the local properties of the Fc region through specific glycosylation patterns. By enriching for antibodies with galactose-sialic acid structures connected via α2,6 linkages at the Fc region, the patent achieves enhanced anti-inflammatory activity that allows lower dosing, thereby reducing cytotoxic side effects without compromising therapeutic effect.
Solution Approach 2:
The patent changes the biochemical parameters of the antibody by selecting for specific glycosylation patterns. This parameter change in sugar composition and linkage type results in altered biological activity, enabling effective inflammation suppression at lower doses and reducing cytotoxic side effects.
3Ease of operation
If standard antibody preparations are used, then the treatment protocol is simple and well-established, but the therapy does not effectively account for the role of glycosylation in modulating inflammatory responses
Solution Approach 1:
The patent applies parameter changes by enriching for antibodies with specific glycosylation parameters (galactose content, sialic acid content, and α2,6 linkage types). This selective enrichment based on glycosylation parameters creates a more effective therapeutic agent that specifically targets inflammatory diseases while maintaining a relatively straightforward production and purification process.
Data Source
AI summary
The invention provides a polypeptide containing at least one IgG Fc region, wherein said at least one IgG Fc region is glycosylated with at least one galactose moiety connected to a respective terminal sialic acid moiety by a α 2,6 linkage, and wherein said polypeptide having a higher anti-inflammatory activity as compared to an unpurified antibody.