TIM Receptor Compounds for Antigen-Specific Immune Tolerance
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Solution Overview
Problem
Existing enzyme and protein replacement therapies and gene therapies face challenges due to unwanted immune responses, leading to neutralization of the therapeutic agents and immunogenicity, while autoimmune disorders result in the body attacking healthy cells, necessitating improved immune tolerance strategies.
Innovation Solution
The use of compounds that modulate T-cell immunoglobulin mucin protein (TIM) receptors to induce antigen-specific and self-tolerance, administered in lipid particles or compositions, to reduce immunogenicity and increase regulatory T-cell and B-cell populations, thereby mitigating immune intolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enzyme or protein replacement therapy is administered, then therapeutic effect is achieved, but unwanted immune response develops leading to neutralization of the therapeutic agent
Solution Approach 1:
The patent applies preliminary action by administering tolerance-inducing compositions containing the therapeutic enzyme or protein together with immunosuppressive agents before the actual replacement therapy. This pre-treatment approach conditions the immune system to accept the therapeutic agent, preventing unwanted immune responses and neutralization that would otherwise occur during subsequent therapeutic administrations
Solution Approach 2:
The patent uses immunosuppressive agents as intermediaries to mediate between the therapeutic enzyme/protein and the patient's immune system. These agents temporarily suppress immune function or specifically target immune cells, creating a protective environment that allows the therapeutic agent to be accepted without triggering unwanted immune responses
2Reliability
If gene therapy is administered, then treatment of congenital disorders is achieved, but immunogenicity of carrier and genetic material prevents repeat dosing
Solution Approach 1:
The patent applies preliminary action by administering tolerance-inducing compositions containing the gene therapy carrier or genetic material together with immunosuppressive agents before actual gene therapy administration. This pre-conditioning of the immune system prevents the development of anti-carrier and anti-genetic material antibodies, enabling successful repeat dosing while maintaining treatment efficacy
Solution Approach 2:
The patent uses immunosuppressive agents as intermediaries to protect the gene therapy components (carrier and genetic material) from immune attack. These agents temporarily reduce immune system activity or specifically inhibit antibody production, allowing the gene therapy to be administered without triggering immunogenic responses that would prevent repeat dosing
3Reliability
If general immune suppression is used to treat autoimmune disorders, then self-tolerance is increased, but patients become immunocompromised and susceptible to infections
Solution Approach 1:
The patent applies local quality by using antigen-specific tolerance induction rather than general immune suppression. The tolerance-inducing compositions target specific self-antigens associated with the autoimmune disorder, inducing regulatory T cells and B cells that specifically modulate the immune response against those antigens while leaving the rest of the immune system functional and resistant to infections
Solution Approach 2:
The patent uses antigen-specific peptides or proteins as intermediaries to induce tolerance. These specific antigens act as mediators that selectively engage and modulate the immune response toward self-antigens, promoting the development of regulatory immune cells that specifically target the autoimmune pathology without causing broad immunosuppression and infection susceptibility
Data Source
AI summary
Provided herein are compounds and their pharmaceutically acceptable salts, lipid particles comprising such compounds or pharmaceutically acceptable salts thereof and compositions of the foregoing that can be used to reduce immune intolerance in a subject, for example, to treat autoimmune disorders, or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy. The compounds have the following structural formula:wherein values for the variables (e.g., Ring A, L, R1, R2, R3, m) are as described herein.