Mannan-Peptide Conjugates for T-Cell Tolerance Induction
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Solution Overview
Problem
Current therapies for Multiple Sclerosis (MS), such as interferons and glatiramer acetate, have marginal benefits and significant side effects, while oral administration of autoantigens shows promise but faces challenges related to peptidic nature and cost, necessitating a more stable and effective therapeutic approach.
Innovation Solution
Conjugation of immunodominant peptide analogues of Myelin Oligodendrocyte Glycoprotein (MOG) with oxidized or reduced mannan via a (Lys-Gly)5 bridge to induce peripheral T-cell tolerance, potentially inhibiting disease progression and preventing autoimmune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies (interferons and glatiramer acetate) are used for MS treatment, then disease symptoms are managed, but significant side effects occur and benefits are marginal
Solution Approach 1:
The patent changes the fundamental parameter of therapeutic approach from immunomodulation (interferons, glatiramer acetate) to induction of peripheral T-cell tolerance through conjugate vaccines. This parameter change aims to achieve therapeutic effectiveness while avoiding the side effects associated with immunomodulators by fundamentally altering how the immune system responds to myelin antigens.
Solution Approach 2:
The patent introduces mannan conjugates as intermediary molecules that link myelin peptide epitopes to a carrier protein. This intermediary approach allows the vaccine to present myelin antigens in a controlled manner that induces tolerance rather than activation, thereby treating MS without the harmful side effects of traditional immunomodulators.
2Reliability
If oral administration of autoantigens is used, then peripheral T-cell tolerance may be induced, but issues related to peptidic nature and cost arise
Solution Approach 1:
The patent creates composite conjugate molecules consisting of myelin peptide epitopes chemically linked to mannan carriers. This composite structure combines the specificity of peptide antigens with the stability and immunogenicity of polysaccharide carriers, thereby improving manufacturing stability and reducing costs compared to pure peptide formulations while maintaining therapeutic potential.
Solution Approach 2:
The patent changes the administration route parameter from oral to parenteral (subcutaneous or intramuscular injection). This parameter change overcomes the limitations of oral administration (peptidic degradation, poor bioavailability, high cost) while achieving the same therapeutic goal of inducing peripheral T-cell tolerance through a more stable and cost-effective delivery method.
3Reliability
If peptide analogues are used to induce T-cell tolerance, then therapeutic effect is achieved, but stability and cost-effectiveness need improvement
Solution Approach 1:
The patent creates composite conjugate molecules where unstable peptide epitopes are chemically attached to stable mannan carriers. This composite structure provides the stability needed for storage and handling while maintaining the peptide's ability to induce T-cell tolerance, thereby resolving the contradiction between therapeutic effect and compositional stability.
Solution Approach 2:
The mannan carrier acts as an intermediary that stabilizes the peptide epitopes without interfering with their immunological function. The carrier protects the peptides from degradation while presenting them to the immune system in a manner that induces tolerance, thus maintaining therapeutic effect while improving stability.
Data Source
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AI summary
A first aspect of the invention relates to a conjugate comprising: (i) mannan; and (ii) at least one epitope comprising a peptide fragment of a protein selected from myelin basic protein (MBP), myelin oligodentrocyte glycoprotein (MOG) and proteolipid protein (PLP), said peptide fragment being in linear or cyclic form; wherein said epitope is linked to mannan via a[(LyS-Gly)n] bridge, where n is an integer from 1 to 10. Further aspects of the invention relate to pharmaceutical compositions comprising said conjugates, and their use in the preparation of a medicament for treating an immune disorder.