Compositions, methods and kits for treating complement related disorders
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for complement-related disorders, such as age-related macular degeneration and rheumatoid arthritis, lack effective inhibitors that can provide long-term attenuation of complement activation without significant side effects, and existing FDA-approved inhibitors require frequent injections with associated complications.
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 is formulated to be soluble and membrane-independent, allowing for systemic delivery via gene therapy vectors like adeno-associated virus (AAV) to target complement-related conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FDA-approved complement inhibitors are administered via repeated injections, then complement activation is inhibited, but significant side effects occur
Solution Approach 1:
The patent uses adeno-associated virus (AAV) as a viral vector intermediary to deliver the complement inhibitor gene to the liver. The liver then produces the inhibitor protein endogenously, eliminating the need for repeated injections and reducing associated side effects while maintaining effective complement inhibition
Solution Approach 2:
The invention enables the body's own liver cells to produce the complement inhibitor protein through gene transfer. This self-service mechanism allows continuous production of the therapeutic protein without external intervention, avoiding the side effects of repeated injections while ensuring reliable complement inhibition
2Reliability
If membrane-associated complement regulators (CD46, CD55, CD59) are used, then complement activation is regulated, but membrane dependence limits delivery and distribution
Solution Approach 1:
The patent extracts the functional complement-regulating domains from the membrane-associated proteins CD46, CD55, and CD59, and combines them into a soluble chimeric protein that lacks membrane-anchoring sequences. This extracted functional core can be produced systemically by the liver and distributed throughout the body via bloodstream, overcoming the delivery limitations of membrane-dependent proteins
Solution Approach 2:
The invention changes the physical state of the complement regulators from membrane-bound to soluble form by removing transmembrane and GPI-anchoring domains. This parameter change from membrane-associated to soluble allows systemic circulation and widespread distribution while preserving complement regulatory function
Data Source
Figure 1A~1B
Figure 2A~2D
Figure 3A~3C
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.