Anti-CFD Antibody Conjugates for Longer Ocular Residence
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Solution Overview
Problem
There is currently no effective treatment for dry AMD or geographic atrophy (GA), and existing therapies for wet AMD, such as intravitreal injections, are cumbersome and have low patient compliance due to discomfort and side effects, necessitating a need for less frequent and more tolerable treatments.
Innovation Solution
Development of anti-complement factor D (CFD) antibodies and conjugates that specifically inhibit CFD activity, allowing for less frequent dosing intervals and potential treatment of dry AMD and GA.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intravitreal injections are used for wet AMD treatment, then treatment effectiveness is achieved, but patient compliance deteriorates due to discomfort and side effects
Solution Approach 1:
The patent modifies the pharmacokinetic parameters of the therapeutic antibody by conjugating it to polymers with specific molecular weights (600,000-900,000 Da) and zwitterionic characteristics. This changes the residence time parameter in the eye from days to months, allowing dosing intervals to be extended from monthly to every 2-4 months, thereby improving patient compliance while maintaining treatment effectiveness.
Solution Approach 2:
The patent creates a composite therapeutic agent by covalently conjugating an anti-CFD antibody to a zwitterionic polymer consisting of multiple monomer units (including phosphorylcholine-containing monomers). This composite structure combines the biological activity of the antibody with the pharmacokinetic benefits of the polymer, achieving both effective treatment and improved compliance.
2Reliability
If frequent dosing is used to maintain treatment effectiveness, then treatment reliability is improved, but loss of time increases due to frequent administrations
Solution Approach 1:
The patent changes the pharmacokinetic parameter of residence time in the eye from approximately 1 week to approximately 3 months by using polymer-conjugated antibodies. This parameter change enables dosing intervals to be extended from every 4 weeks to every 8-16 weeks, significantly reducing the time loss associated with frequent dosing while maintaining treatment effectiveness.
3Reliability
If conventional antibody therapy is used, then treatment effectiveness is achieved, but duration of action is limited requiring frequent re-administration
Solution Approach 1:
The patent dramatically changes the duration of action parameter by conjugating the antibody to polymers with molecular weights of 600,000-900,000 Da. This increases the resident half-life in the eye from approximately 1 week to approximately 3 months, allowing the treatment to maintain effectiveness for much longer periods between dosing administrations.
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
The anti-CFD antibodies and conjugates provide a longer resident half-life in the eye, enabling effective treatment of dry AMD and GA with reduced frequency of administration, potentially improving patient compliance and reducing side effects.
Implementation Method 1
an isolated antagonist antibody is provided that specifically binds to complement factor D (CFD) and directly inhibits a proteolytic activity of CFD
Implementation Method 2
a conjugate is provided that comprises: a) any of the isolated antagonistic antibodies provided herein; and b) a polymer, wherein the polymer is covalently attached to the antibody
Data Source
AI summary
The present invention provides antagonizing antibodies that bind to complement factor D (CFD), conjugates thereof, and methods of using same. The anti-CFD antibodies can be used therapeutically alone or in combination with other therapeutics to treat age related macular degeneration and other diseases.