Glycoengineered Polypeptides for Targeted ANCA Autoantibody Depletion
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Solution Overview
Problem
Current therapies for treating autoimmune diseases associated with anti-neutrophil antibodies, such as ANCA vasculitis, lack specificity and often require prolonged dosing, leading to side effects and insufficient reduction of autoantibodies, and do not address the underlying cause of the disease.
Innovation Solution
Development of glycoengineered polypeptides that specifically bind to anti-neutrophil autoantibodies and endocytic receptors, facilitating internalization and degradation of these antibodies, thereby reducing their levels and alleviating disease symptoms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-specific B-cell directed therapies (such as Rituximab) are used to treat ANCA vasculitis, then some relief is provided to patients, but the therapies do not directly act on anti-neutrophil autoantibodies, do not reduce and/or deplete these autoantibodies, and can lead to unwanted side effects such as organ damage or immunosuppression
Solution Approach 1:
The patent extracts and removes the harmful non-specific B-cell depletion mechanism from the treatment approach, replacing it with a specific therapy that targets only anti-neutrophil autoantibodies through glycoengineered polypeptides that bind to these autoantibodies and facilitate their degradation, thereby eliminating side effects while maintaining therapeutic efficacy
Solution Approach 2:
The patent applies local quality by designing glycoengineered polypeptides with specific binding characteristics that target only anti-neutrophil autoantibodies (not all B cells), creating a localized therapeutic effect that spares other immune components and avoids widespread immunosuppression and organ damage
2Reliability
If non-specific B-cell directed therapies are used, then treatment is provided, but these therapies need to be dosed for a longer period of time to achieve a desired result and cannot produce rapid responses
Solution Approach 1:
The patent extracts the delayed response characteristic of non-specific B-cell therapies by directly targeting anti-neutrophil autoantibodies with glycoengineered polypeptides that immediately bind to and degrade pathogenic autoantibodies, eliminating the need for prolonged dosing while achieving rapid clinical response
Solution Approach 2:
The patent implements preliminary action by pre-designing glycoengineered polypeptides with optimized binding affinity and degradation capabilities that are ready to immediately act on anti-neutrophil autoantibodies upon administration, eliminating the delay inherent in non-specific therapies that require prolonged exposure to achieve effect
3Reliability
If non-specific B-cell directed therapies are used, then treatment is provided, but these therapies are not able to disrupt and/or remove anti-neutrophil autoantibodies or pathogenic immune complexes comprising the same
Solution Approach 1:
The patent extracts the lack of target specificity from conventional B-cell therapies by designing glycoengineered polypeptides with precise binding sites for anti-neutrophil autoantibodies and immune complexes, enabling selective removal of pathogenic components while preserving benign immune functions
Solution Approach 2:
The patent applies local quality through glycoengineered polypeptides with specific binding characteristics that distinguish and target only anti-neutrophil autoantibodies and their immune complexes, creating a localized therapeutic effect that precisely addresses the disease mechanism without affecting other immune components
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 glycoengineered polypeptides provide rapid, specific, and durable responses with fewer side effects, effectively depleting anti-neutrophil autoantibodies and immune complexes, thus treating or preventing diseases like ANCA vasculitis.
Implementation Method 1
a first moiety comprising one or more peptides that specifically binds to a target autoantibody
Implementation Method 2
binding of a glycoengineered polypeptide disclosed herein to a target autoantibody and to an endocytic receptor induces internalization of the target autoantibody into a cell
Implementation Method 3
internalization of the target autoantibody results in degradation
Implementation Method 4
a second moiety comprising one or more glycans conjugated to the first moiety at one or more glycosylation sites
Data Source
AI summary
Provided herein are glycoengineered polypeptides comprising a first moiety comprising one or more peptides that specifically binds to an anti-neutrophil autoantibody and a second moiety comprising one or more glycans conjugated to the first moiety at one or more glycosylation sites. Also provided herein are nucleic acid sequence encoding provided glycoengineered polypeptides. Further provided herein are compositions comprising glycoengineered polypeptides and/or nucleic acids encoding the same, as well as methods of making and using the same.