Multivalent Antibody Complexes Targeting IGF-1R
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Solution Overview
Problem
Current anti-IGF-1R inhibitors often cross-react with the insulin receptor, leading to toxicity and limited effectiveness in cancer therapy due to their agonist or non-specific binding properties.
Innovation Solution
Development of multivalent complexes comprising specific anti-IGF-1R antibodies or fragments that bind to the IGF-1R without activating it, combined with other antibodies or cytokines like interferon-α2b, to target cancer cells expressing IGF-1R, such as in DOCK-AND-LOCK™ (DNL™) complexes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-IGF-1R inhibitors are used to target IGF-1R, then cancer cell growth inhibition is achieved, but cross-reactivity with insulin receptor causes toxicity
Solution Approach 1:
The patent divides the therapeutic function into separate components: one component specifically targets and blocks IGF-1R without activating it, while another component (such as interferon-α2b or other antibodies) provides additional anti-cancer activity. This segmentation allows each component to be optimized for its specific function, with the IGF-1R blocking component designed to avoid insulin receptor cross-reactivity, thereby reducing toxicity while maintaining cancer cell growth inhibition.
2Measurement precision
If anti-IGF-1R inhibitors with high binding affinity are used, then IGF-1R targeting is improved, but agonist activity increases causing unintended activation
Solution Approach 1:
The patent extracts and eliminates the agonist activity component from the anti-IGF-1R inhibitor design. The blocking component is specifically engineered to bind to IGF-1R with high affinity and specificity while lacking the ability to activate the receptor's kinase domain. This extraction of harmful agonist activity allows the maintenance of high binding precision for targeted inhibition without the side effect of unintended receptor activation.
3Device complexity
If monovalent anti-IGF-1R antibodies are used, then simplicity is maintained, but therapeutic effectiveness is limited
Solution Approach 1:
The patent combines multiple therapeutic components into a single complex: a non-agonistic IGF-1R blocking antibody or fragment is merged with additional anti-cancer agents such as interferon-α2b, other antibodies against tumor-associated antigens, or cytotoxic agents. This merging creates a multi-functional complex that delivers both specific IGF-1R blockade and additional anti-cancer mechanisms, thereby enhancing therapeutic effectiveness beyond what a simple monovalent antibody could achieve.
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
These complexes demonstrate enhanced activity in inhibiting cancer cell growth and synergistic effects with therapeutic agents like mTOR inhibitors, reducing toxicity and improving treatment outcomes for cancers with IGF-1R overexpression.
Implementation Method 1
comprises specific anti-IGF-1R antibodies or fragments that bind to the IGF-1R without activating it
Implementation Method 2
demonstrate enhanced activity in inhibiting cancer cell growth and synergistic effects with therapeutic agents like mTOR inhibitors
Data Source
AI summary
The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-α2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.