Compositions, methods and kits for treating complement related disorders

Solution Overview

Problem

Current treatments for complement-related disorders, such as age-related macular degeneration and rheumatoid arthritis, are limited by the availability of few FDA-approved inhibitors and the need for repeated injections, which can cause significant side effects.

Innovation Solution

A pharmaceutical composition comprising a recombinant chimeric protein with amino acid sequences from CD46, CD55, and CD59 proteins, engineered to negatively modulate classical and alternative complement pathways, is developed, allowing for a single administration via gene therapy to provide long-term attenuation of complement activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If repeated injections of complement inhibitors are administered to treat chronic disorders such as AMD, then therapeutic effect is maintained, but significant side effects occur and treatment convenience deteriorates

Engineering Contradiction:

Improvetherapeutic effectVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by using gene therapy to deliver complement regulator genes (such as CD46, CD55, CD59) directly to target tissues before disease progression or at disease onset. This establishes long-term protective expression of complement regulators, eliminating the need for repeated injections and preventing complement-mediated damage proactively rather than requiring continuous therapeutic intervention

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements self-service by enabling target cells to produce their own complement regulator proteins through introduced genes. The treated cells autonomously express functional complement regulators (e.g., membrane cofactor protein, decay accelerating factor, protectin) that continuously protect against complement activation without requiring external administration of inhibitors, thereby eliminating injection-related side effects

Inventive Principle:

Principle #25Self-service

2Reliability

If repeated injections of complement inhibitors are administered to treat chronic disorders, then therapeutic effect is maintained, but treatment convenience and patient burden worsen

Engineering Contradiction:

Improvetherapeutic effectVSAvoidtreatment convenience

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies preliminary action by using gene therapy to deliver complement regulator genes (such as CD46, CD55, CD59) directly to target tissues before disease progression or at disease onset. This establishes long-term protective expression of complement regulators, eliminating the need for repeated injections and preventing complement-mediated damage proactively rather than requiring continuous therapeutic intervention

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements self-service by enabling target cells to produce their own complement regulator proteins through introduced genes. The treated cells autonomously express functional complement regulators (e.g., membrane cofactor protein, decay accelerating factor, protectin) that continuously protect against complement activation without requiring external administration of inhibitors, thereby eliminating injection-related side effects

Inventive Principle:

Principle #25Self-service

3Device complexity

If few FDA-approved inhibitors are used to treat complement-related disorders, then treatment simplicity is maintained, but therapeutic effectiveness and disease coverage are limited

Engineering Contradiction:

Improvetreatment simplicityVSAvoidtherapeutic effectiveness

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The patent applies universality by developing a platform technology that can deliver multiple different complement regulator genes (CD46, CD55, CD59, and other complement control proteins) using the same gene therapy approach. This multi-functional platform can be adapted to treat various complement-mediated diseases by selecting appropriate regulator genes, thereby expanding therapeutic effectiveness without proportionally increasing treatment complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent employs composite materials by creating chimeric complement regulator proteins that combine functional domains from multiple natural complement control proteins. These engineered chimeric proteins integrate regulatory domains from different sources to produce enhanced or multi-functional complement inhibition, expanding therapeutic options while maintaining the simplicity of single-agent gene therapy delivery

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS10813977B2Compositions, methods and kits for treating complement related disorders

Publication Date: 2020.10.27 TRUSTEES OF TUFTS COLLEGE

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.