Complement Proteins Modulate AMD Progression

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Solution Overview

Problem

Current methods are inadequate for effectively predicting and managing age-related macular degeneration (AMD), a leading cause of irreversible blindness, due to limited understanding of its etiology and pathogenesis, and a lack of effective treatments for identifying at-risk individuals and delaying disease progression.

Innovation Solution

The use of specific polymorphisms in the BF and C2 genes, such as R32Q, L9H, E318D, and protective forms of the CFH protein, to modulate the complement cascade system, thereby delaying the onset or progression of AMD through therapeutic and prophylactic administration of protective human BF and C2 proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If complement pathway activation is used to fight infection and inflammation, then immune defense is improved, but bystander damage to macular cells occurs leading to atrophy and degeneration

Engineering Contradiction:
Improveimmune defenseVSAvoidbystander damage to macular cells
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces protective proteins (CFH, BF, C2) as intermediaries that modulate the complement pathway. These proteins act as mediators between the immune system and macular cells, allowing the complement pathway to maintain its immune defense function while preventing excessive activation that causes bystander damage. The protective proteins regulate complement activation to protect macular cells from damage.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes polymorphisms in complement genes (CFH, BF, C2) that change the parameters of complement pathway activation. These genetic variations alter the sensitivity and intensity of complement activation, creating protective variants that reduce bystander damage while maintaining adequate immune defense. The polymorphisms effectively tune the complement system's response parameters.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If genetic screening for AMD risk factors is performed, then identification of at-risk individuals is improved, but limited treatment options remain available

Engineering Contradiction:
Improveidentification of at-risk individualsVSAvoidtreatment options
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent implements preliminary prophylactic treatment by administering protective complement proteins to individuals identified as at-risk through genetic screening. This preliminary action prevents or delays AMD development before clinical symptoms appear, expanding treatment options from merely diagnostic to actually preventive and therapeutic.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs the individual's own protective complement protein variants (encoded by protective polymorphisms in CFH, BF, or C2 genes) to treat AMD risk. The body's natural protective mechanisms are harnessed and enhanced through supplementation with protective protein variants, creating a self-service therapeutic approach.

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP1996214B1Complement proteins for protection against age-related macular degeneration
Publication Date: 2016.05.04 NAT INST OF HEALTH DHHS
  • EP1996214B1 patent drawingFigure 1
  • EP1996214B1 patent drawingFigure 2A~2B
  • EP1996214B1 patent drawingFigure 2C~2D

AI summary

Methods for identifying a subject at risk for developing AMD are disclosed. The methods include identifying specific protective or risk polymorphisms or genotypes from the subject's genetic material. Therapeutic compositions and methods are also provided for delaying the progression or onset of the development of AMD in a subject, including treating a subject having signs and/or symptoms of AMD or who has been diagnosed with AMD.