Antigen-Binding Protein AXL Binding Consistency
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Solution Overview
Problem
Current anti-AXL antibodies fail to consistently bind to both surface and soluble AXL across various cancer cell lines, limiting their effectiveness in cancer therapy.
Innovation Solution
Development of a novel antigen-binding protein with specific heavy and light chain variable domain sequences that competes with AXL receptor tyrosine kinase, potentially conjugated with cytotoxins or radioisotopes, to target and bind to AXL, enhancing therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If commercially available anti-AXL antibodies are used, then AXL binding is achieved, but binding consistency across surface and soluble AXL and across cancer cell lines is poor
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure through specific CDR sequences (VH CDR1: GFTFTSYYMY, VH CDR2: GVSPSNGGANFNEKFKT, VH CDR3: FLYGPRYFDV, VL CDR1: RASESVDNYGISFMN, VL CDR2: GASNQGS, VL CDR3: QQSKEVPYT) to achieve consistent binding across different AXL forms and cell lines, transforming the binding parameters to overcome the limitations of commercial antibodies
2Productivity
If available anti-AXL antibodies are used, then some AXL targeting is achieved, but therapeutic effectiveness is limited due to inconsistent binding
Solution Approach 1:
The patent changes the binding parameters through optimized CDR sequences to achieve reliable and consistent AXL binding across multiple cancer cell lines, thereby improving therapeutic effectiveness by ensuring predictable antibody performance in cancer treatment applications
3Reliability
If novel antigen-binding protein with specific CDR sequences is developed, then specific binding to AXL and inhibition of cell proliferation is achieved, but development complexity increases
Solution Approach 1:
The patent applies segmentation by focusing on the specific CDR regions (six distinct CDR sequences) as the functional segments that provide specific AXL binding, while the rest of the antibody structure can be standardized or humanized, thereby achieving specific binding without excessive overall complexity
Solution Approach 2:
The patent applies local quality by optimizing only the CDR regions (the local binding sites) with specific amino acid sequences to achieve high specificity for AXL, while the framework regions can use standard or humanized sequences, concentrating the complexity only where needed for specific binding
Data Source
AI summary
The present invention relates to antigen-binding proteins, or antigen-binding fragments thereof that bind to a glycan on the AXL receptor tyrosine kinase. The present invention also relates to antigen-binding proteins, or antigen-binding fragment conjugated to a radioisotope or cytotoxin, and wherein said antigen-binding proteins, or antigen-binding fragment is internalised into a cell upon binding to AXL receptor tyrosine kinase. Compositions comprising a physiologically acceptable carrier and a therapeutically effective amount of the antigen-binding protein, or antigen-binding fragment thereof, therapeutic use of the antigen-binding protein, or antigen-binding fragment thereof, methods for detecting cancer as well as kits when used in such methods are also provided.