Saposin B Binding A2E Bisretinoid to Reduce Macular Degeneration

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Solution Overview

Problem

Current therapeutic methods are inadequate in effectively addressing the accumulation of bisretinoid A2E, which contributes to macular degeneration and other eye diseases by failing to adequately target and degrade this harmful compound, leading to cellular damage and vision loss.

Innovation Solution

The use of Saposin B, a protein that binds to A2E, preventing its enzymatic and photo-induced degradation, combined with enzyme co-administration to facilitate targeted degradation of A2E, thereby reducing its accumulation and associated cellular damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If therapeutic methods are used to address A2E accumulation, then vision loss and cellular damage may be reduced, but current methods are inadequate and fail to effectively target and degrade A2E

Engineering Contradiction:
Improveeffectiveness of A2E degradationVSAvoidA2E accumulation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces saposin B as an intermediary protein that binds to A2E, facilitating its degradation. The saposin B-A2E complex acts as a mediator that enables enzymatic breakdown of A2E by horseradish peroxidase, thereby resolving the contradiction between reducing A2E accumulation and achieving effective degradation through existing therapeutic methods

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts and isolates the harmful A2E compound from the cellular environment through binding with saposin B, which facilitates its removal and degradation. This extraction mechanism allows targeted elimination of A2E from the retina, addressing the inadequacy of current methods that fail to effectively remove this harmful substance

Inventive Principle:
Principle #2Taking out (Extraction)

2Object-affected harmful factors

If A2E is bound and protected from degradation, then its harmful effects are reduced, but its accumulation may be promoted

Engineering Contradiction:
ImproveA2E toxicityVSAvoidA2E accumulation
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by having saposin B bind to A2E before it can cause harmful effects. This pre-binding facilitates subsequent enzymatic degradation by horseradish peroxidase, thereby reducing A2E toxicity while preventing accumulation through active breakdown rather than passive protection

Inventive Principle:
Principle #10Preliminary action

3Productivity

If enzymatic degradation of A2E is facilitated, then A2E levels are reduced, but the complexity of the degradation system increases

Engineering Contradiction:
Improverate of A2E degradationVSAvoiddegradation system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies universality by using saposin B, a lysosomal protein with multiple functions, to facilitate A2E degradation. Saposin B is already present in lysosomes for other functions, and its ability to bind and present A2E to horseradish peroxidase adds a new function without requiring a completely new degradation system, thereby reducing the increase in system complexity while maintaining high degradation productivity

Inventive Principle:
Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Saposin B effectively binds and protects A2E from degradation, reducing its harmful effects and promoting its enzymatic and photo-protective degradation, offering a potential therapeutic approach to treat conditions like macular degeneration by reducing A2E accumulation.

Implementation Method 1

Saposin B binds the lipofuscin bisretinoid A2E

Methodology Applied
Scientific EffectMolecular recognition:

Implementation Method 2

Saposin B binds the lipofuscin bisretinoid A2E and prevents its enzymatic and photo degradation

Methodology Applied
Scientific EffectEnzymatic degradation prevention:

Implementation Method 3

Saposin B binds the lipofuscin bisretinoid A2E and prevents its enzymatic and photo degradation

Methodology Applied
Scientific EffectPhoto degradation prevention:

Data Source

PatentUS10813981B2Saposin B binds the lipofuscin bisretinoid A2E and prevents its enzymatic and photo degradation
Publication Date: 2020.10.27 ICHOR THERAPEUTICS INC
  • US10813981B2 patent drawing
  • US10813981B2 patent drawing
  • US10813981B2 patent drawing

AI summary

Disclosed herein are methods and compositions useful in the treatment and/or prevention of a disease or indication associated with accumulation of a bisretinoid, for example A2E. In many embodiments, the disclosed methods and compositions are useful in treating an eye disease, for example macular degeneration.