BCMA Binding Proteins for B Cell Lineage Cancer Treatment
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Solution Overview
Problem
Current treatments for deadliest cancers lack effective and non-toxic systemic therapies, and there is a need for targeted therapies that can specifically address B cell lineage cancers such as multiple myeloma, leukemias, and lymphomas by targeting the B cell maturation antigen (BCMA).
Innovation Solution
Development of single domain BCMA binding proteins that comprise specific complementarity determining regions (CDR1, CDR2, and CDR3) with defined amino acid sequences, which can be used for diagnosing and treating B cell lineage cancers by binding to BCMA on cancer cells, potentially combined with an Fc domain or anti-cancer agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional systemic therapies are used for cancer treatment, then broad cancer coverage is achieved, but toxicity increases and effectiveness decreases
Solution Approach 1:
The patent segments the therapeutic approach by developing single domain proteins that specifically target BCMA antigen on B cell lineage cancer cells. This segmentation allows selective targeting of cancer cells expressing BCMA while sparing normal cells, thereby improving effectiveness and reducing systemic toxicity compared to conventional non-specific chemotherapy agents
Solution Approach 2:
The invention applies local quality by designing proteins with specific amino acid sequences in CDR regions that confer high affinity and specificity for BCMA antigen. This localized specificity ensures the therapeutic agent acts precisely on target cells expressing BCMA, improving therapeutic index by concentrating effect where needed while minimizing off-target toxicity
2Manufacturing precision
If targeted therapies targeting BCMA are developed, then specificity for B cell lineage cancers is improved, but manufacturing complexity increases
Solution Approach 1:
The patent extracts only the essential antigen-binding domain (single variable domain) from complete antibodies, creating simplified single domain proteins that retain BCMA specificity. This extraction eliminates unnecessary structural complexity while preserving the critical CDR regions responsible for antigen recognition, thereby reducing manufacturing complexity while maintaining high specificity
Solution Approach 2:
The invention employs parameter changes by defining specific amino acid sequences in CDR regions (CDR1, CDR2, CDR3) that optimize BCMA binding affinity and specificity. By carefully selecting and optimizing these sequence parameters, the patent achieves high manufacturing precision for specific cancer cell targeting while using relatively simple protein structures that are easier to manufacture than full-length antibodies
Data Source
AI summary
Disclosed herein are B cell maturation antigen binding proteins with improved binding affinities and improved ability to mediate killing of cancer cells expressing B cell maturation antigen (BCMA). Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of treatment of a cancer or a metastasis thereof using such formulations are further provided.