Caninized Anti-PD-L1 Antibody for Canine Checkpoint Blockade
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Solution Overview
Problem
Current PD-1/PD-L1 blockade therapies for cancer in humans and canines have limited response rates (10-40%) and rodent models are not predictive for canine immune checkpoint blockade therapy, necessitating an animal model that can optimize checkpoint inhibitor treatment in humans and effectively treat canine cancers.
Innovation Solution
Development of a caninized antibody or antigen binding fragment that specifically binds canine PD-L1, comprising specific amino acid and nucleotide sequences, which can inhibit the PD-L1/PD-1 interaction in canines, and is administered in therapeutically effective amounts to treat invasive urothelial carcinoma.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If rodent models are used to study immune checkpoint blockade therapy, then cancer research can be conducted, but the models are not predictive for canine therapy and lack critical features for studying bladder cancer molecular subtypes
Solution Approach 1:
The patent creates a caninized mouse model by replacing the mouse PD-L1 gene with the canine PD-L1 gene sequence. This copying approach allows the model to accurately replicate canine immune checkpoint biology while maintaining the ease of use of rodent models, thereby resolving the contradiction between model simplicity and predictive accuracy for canine therapy
Solution Approach 2:
The patent modifies a fundamental parameter of the mouse model by substituting the murine PD-L1 genetic sequence with the canine PD-L1 sequence. This parameter change transforms the model from being non-predictive for canine therapy to highly predictive, while retaining the advantages of rodent model complexity
2Reliability
If PD-1/PD-L1 blockade therapy is administered to cancer patients, then immune response is enhanced, but response rates remain limited at 10-40%
Solution Approach 1:
The patent introduces a caninized anti-PD-L1 antibody as an intermediary therapeutic agent that specifically targets the canine PD-L1/PD-1 interaction. This specialized antibody serves as a more effective mediator of immune checkpoint blockade in canine patients, potentially improving response rates beyond current human therapy levels by addressing species-specific biological differences
Solution Approach 2:
The patent segments the therapeutic approach by developing species-specific antibodies (caninized for canine patients) rather than using human antibodies in canine patients. This segmentation allows for optimized therapeutic efficacy in each species by accounting for immunological differences, thereby improving overall response rates
Data Source
AI summary
Caninized antibodies and antigen binding fragments thereof are provided that bind programmed death ligand 1 in a canine subject. Methods of treating cancer in a canine subject using the caninized antibodies and/or antigen binding fragments are also provided, as are methods for predicting and modeling anti-cancer activity of a test compound in a subject.