IL-1R1 Antibody Affinity Maturation for Therapeutic Potency
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Solution Overview
Problem
Current treatments for disorders mediated by IL-1R1, such as rheumatoid arthritis and asthma, lack effective solutions to inhibit the biological activity of IL-1α and IL-1β, as existing antibodies are either less potent or have short half-lives, leading to inadequate therapeutic outcomes.
Innovation Solution
Development of binding members, specifically antibodies or antigen-binding portions thereof, that bind to IL-1R1 with high affinity, competing with IL-1 and IL-1Ra for binding, and neutralizing IL-1R1 activity with a KD of 10 pM or less, thereby inhibiting IL-1β-induced IL-6 production and reducing receptor internalization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to inhibit IL-1R1 activity, then some therapeutic effect is achieved, but the half-life is short and potency is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody molecules through affinity maturation to achieve a dissociation constant (KD) of 10 pM or less, significantly improving binding affinity. This parameter optimization enables the antibodies to maintain therapeutic effectiveness for extended periods, resolving the contradiction between therapeutic reliability and duration of action.
2Reliability
If existing antibodies are used to inhibit IL-1R1 activity, then some therapeutic effect is achieved, but the binding affinity is insufficient
Solution Approach 1:
The patent employs affinity maturation techniques to optimize the binding affinity parameter, achieving KD values of 10 pM or less. This precise parameter improvement ensures high therapeutic effectiveness by enhancing the antibody's ability to bind and neutralize IL-1R1.
3Reliability
If binding members with high affinity are developed, then therapeutic potency is improved, but development complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-defining the target epitope on IL-1R1 and designing antibodies with predetermined high-affinity binding characteristics. This planning approach streamlines the development process while achieving the desired therapeutic potency, reducing overall development complexity.
Data Source
AI summary
This invention relates to binding members, especially antibody molecules, specific for interleukin 1 receptor 1 (IL-1R1). For example, isolated binding members specific for IL-1R1 which competes with IL-1 and IL-1Ra for binding to IL-1R1 and binds Il-1R1 with a KD of 10 pM or less when measured by Kinexa™. The binding members are useful for, inter alia, treatment of disorders mediated by IL-1R1 including rheumatoid arthritis, asthma and chronic obstructive pulmonary disease (COPD).