Ankyrin Repeat Domain CD70 Engagers for AML Therapy
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Solution Overview
Problem
Current treatments for acute myeloid leukemia (AML) are limited by poor efficacy and safety concerns, with existing antibody therapies facing challenges such as treatment resistance and side effects.
Innovation Solution
Development of recombinant binding proteins with an ankyrin repeat domain that specifically targets human CD70, which can be combined with other functional moieties like binding moieties for immune cells or cytotoxic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used to target CD70, then CD70 binding is achieved, but treatment resistance and safety concerns arise
Solution Approach 1:
The patent changes the molecular structure parameter from traditional monoclonal antibodies to ankyrin repeat domain proteins, which have different binding characteristics and immunogenicity profiles, thereby maintaining CD70 targeting efficacy while reducing safety concerns and treatment resistance
Solution Approach 2:
The patent creates composite therapeutic molecules by combining CD70-specific ankyrin repeat domains with other functional moieties such as immune cell targeting domains or cytotoxic agents, enabling multifunctional therapy that improves efficacy while mitigating adverse effects
2Reliability
If existing antibody therapies are applied, then CD70 targeting is achieved, but poor efficacy and side effects occur
Solution Approach 1:
The patent modifies the therapeutic agent structure from conventional antibodies to ankyrin repeat domain-based proteins with altered pharmacokinetic and pharmacodynamic properties, achieving better therapeutic efficacy with reduced side effects through improved specificity and controlled activity
Solution Approach 2:
The ankyrin repeat domain serves as an intermediary binding protein that provides more precise and controllable interaction with CD70 compared to conventional antibodies, enabling targeted therapy with reduced off-target effects and improved safety profile
3Reliability
If tumor surface marker downregulation occurs, then antibody therapy resistance develops, but alternative targeting mechanisms are needed
Solution Approach 1:
The patent designs composite molecules where the ankyrin repeat domain binds to CD70 with high affinity and specificity, and can be combined with additional functional domains that provide alternative mechanisms of action, making the therapy effective even when CD70 expression is downregulated
Data Source
AI summary
The present invention relates to recombinant binding proteins comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has binding specificity for human CD70. In addition, the invention relates to nucleic acids encoding such recombinant binding proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer, e.g., acute myeloid leukemia (AML), in a mammal, including a human.