Compositions, methods and kits for treating complement related disorders
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Solution Overview
Problem
Current treatments for complement-related disorders, such as age-related macular degeneration and rheumatoid arthritis, are limited by the availability of effective FDA-approved inhibitors and the side effects associated with repeated injections of complement inhibitors, particularly in chronic conditions where long-term attenuation of complement activation is necessary.
Innovation Solution
A pharmaceutical composition comprising a recombinant chimeric protein with amino acid sequences from CD46, CD55, and CD59 proteins, engineered to modulate classical and alternative complement pathways, is developed. This protein, either as a soluble active complement terminator (SACT) or dual terminator (DTAC), is designed to be administered via gene therapy using vectors like adeno-associated virus (AAV) to provide sustained inhibition of complement activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If repeated injections of complement inhibitors are administered to treat chronic complement-related disorders, then complement activation is suppressed, but side effects increase and treatment compliance becomes difficult
Solution Approach 1:
The invention introduces complement inhibitor genes into the patient's cells beforehand, enabling the cells to produce the inhibitor continuously without requiring repeated external administrations. This preliminary genetic modification establishes a sustained therapeutic effect that eliminates the need for frequent injections and reduces associated side effects
Solution Approach 2:
The patient's own cells are engineered to serve as continuous sources of complement inhibitors through genetic modification. The modified cells autonomously produce and secrete the inhibitor proteins, making the therapeutic system self-sustaining without requiring ongoing external intervention or repeated administrations
2Adaptability or versatility
If current FDA-approved complement inhibitors are used, then some complement-related conditions are treated, but the availability of effective inhibitors is limited and side effects occur
Solution Approach 1:
The invention creates entirely new complement inhibitors with modified amino acid sequences that differ from existing FDA-approved inhibitors. These novel proteins have altered biochemical parameters including enhanced stability, improved half-life, and modified binding characteristics, providing new therapeutic options with potentially reduced side effects
Solution Approach 2:
The invention generates chimeric complement inhibitors by combining functional domains from different complement regulatory proteins. These composite proteins integrate multiple functional elements to achieve broader complement pathway coverage and enhanced therapeutic efficacy compared to single-protein inhibitors
3Duration of action of stationary object
If long-term attenuation of complement activation is achieved through repeated injections, then chronic disorders are treated, but treatment complexity and patient burden increase
Solution Approach 1:
The therapeutic effect is established in advance through genetic modification of patient cells, creating a persistent source of complement inhibitors. This one-time preliminary intervention provides long-duration protection without requiring complex repeated administrations, thereby reducing treatment burden while maintaining extended therapeutic action
Data Source
AI summary
Compositions, methods and kits are provided for treating complement related disorders in a subject with protein in combination having protein fusions of at least two of a CD46 protein, a CD55 protein and a CD59 protein or with a recombinant chimeric protein having at least two of a CD46 protein, a CD55 protein and a CD59 protein or with nucleic acids encoding these proteins. The composition negatively modulates classical and alternative complement pathways thereby treating complement related disorder such as macular degeneration, age-related macular degeneration, diabetic retinopathy, inflammatory bowel disease, thyroiditis, cryoglobulinaemia, fetal loss, organ graft rejection, cancer, etc.