TIM-Modulating Compounds and Lipid Particles for Immune Tolerance
Find Innovative SolutionsGenerate Solutions
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 without effective treatment options.
Innovation Solution
Compounds and lipid particles are developed to modulate T-cell immunoglobulin mucin protein (TIM) family receptors, inducing antigen-specific and self-tolerance by activating regulatory T-cells and B-cells, reducing immune intolerance and treating autoimmune disorders.
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 enzyme/protein
Solution Approach 1:
The patent applies preliminary action by administering tolerogenic agents or modifying the therapeutic enzyme/protein beforehand to induce immune tolerance before the unwanted immune response develops. This prevents neutralization by establishing tolerance in advance through repeated low-dose exposures or co-administration of immunosuppressive agents
Solution Approach 2:
The patent uses intermediary substances such as immunosuppressive agents, tolerogenic molecules, or modified protein structures that mediate between the therapeutic enzyme/protein and the immune system. These intermediaries reduce immunogenicity while preserving therapeutic activity, allowing the therapeutic agent to function without triggering strong immune responses
2Reliability
If gene therapy is administered, then treatment effect is achieved, but immunogenicity of carrier and genetic material develops leading to anti-carrier antibodies
Solution Approach 1:
The patent applies local quality by modifying specific regions of the viral carrier or genetic material to reduce immunogenicity while preserving essential therapeutic functions. This includes modifying viral capsid proteins or promoter regions to minimize immune recognition while maintaining gene delivery capability
Solution Approach 2:
The patent uses copying by creating modified versions of viral carriers with altered genetic sequences that replicate the essential functions of the original carrier but with reduced immunogenicity. These modified carriers can be repeatedly administered without triggering strong anti-carrier antibody responses
3Object-affected harmful factors
If general immune suppression is used to treat autoimmune disorders, then self-tolerance is increased, but patients become immunocompromised and susceptible to opportunistic infections
Solution Approach 1:
The patent applies segmentation by targeting specific immune pathways or cell types involved in autoimmune pathology rather than suppressing the entire immune system. This includes selectively modulating T-cell subsets, B-cell activity, or cytokine pathways to restore self-tolerance while preserving protective immune functions against infections
Solution Approach 2:
The patent uses inversion by instead of suppressing the immune system, actively inducing or enhancing regulatory mechanisms that promote tolerance. This includes stimulating regulatory T-cell function, inducing anergy in autoreactive cells, or promoting immune deviation toward tolerance-inducing pathways
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.