Anti-CTLA-4 Antibody Selection for KRAS-Mutant Tumors

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Solution Overview

Problem

Existing anti-CTLA-4 antibodies, including next generation antibodies, do not provide therapeutic benefits in all cancer patients, necessitating a method to identify and treat only those patients with KRAS mutations who are most likely to benefit from such treatment.

Innovation Solution

Administer anti-CTLA-4 antibodies, including next generation antibodies, selectively to cancer patients with KRAS mutations in their tumors, determined by detecting KRAS mutations in patient tumors, and optionally combine with anti-PD1 or anti-PD-L1 antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-CTLA-4 antibodies are administered to all cancer patients, then some patients may benefit from treatment, but treatment resources are wasted on patients unlikely to respond and side effects occur in non-responders

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidtreatment resources

Core Design Contradiction:

ReliabilityVSLoss of substance

Solution Approach 1:

The patent performs KRAS mutation detection before administering anti-CTLA-4 antibodies to identify patients who are likely to respond to treatment. This preliminary screening action ensures that only patients with KRAS mutations receive the therapy, preventing waste of treatment resources on non-responders while maintaining therapeutic benefit for appropriate candidates

Inventive Principle:

Principle #10Preliminary action

2Adaptability or versatility

If anti-CTLA-4 antibodies are administered to all cancer patients, then treatment coverage is maximized, but side effects occur in patients who will not benefit

Engineering Contradiction:

Improvetreatment coverageVSAvoidside effects

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies a selective treatment approach where anti-CTLA-4 antibodies are administered only to patients with KRAS mutations rather than all cancer patients. This localized quality control based on molecular characteristics ensures that therapeutic benefits are concentrated in the responsive subgroup while side effects are avoided in non-responders, optimizing the risk-benefit ratio

Inventive Principle:

Principle #3Local quality

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

Patients with KRAS mutant tumors show significant benefit from anti-CTLA-4 antibody treatment, including improved progression-free survival and overall survival, while wild-type KRAS tumors do not, demonstrating targeted therapy's effectiveness.

Implementation Method 1

Antibody blockade of CTLA-4/B7 interactions is thought to promote Teff activation by interfering with negative signals transmitted by CTLA-4 engagement

Methodology Applied

Scientific EffectAntibody blockade:

Implementation Method 2

determining which patients have KRAS mutations in their tumors, and selectively administering anti-CTLA-4 antibodies

Methodology Applied

Scientific EffectMutation detection:

Data Source

PatentUS20260048119A1Anti-CTLA4 antibodies for treatment of KRAS mutant cancers

Publication Date: 2026.02.19 BRISTOL MYERS SQUIBB CO

AI summary

The present invention provides methods of treating cancer patients having KRAS mutant tumors, and methods of selecting such patients for treatment, comprising selectively administering an anti-CTLA-4 antibody to those patients having KRAS mutations. Exemplary anti-CTLA-4 antibodies for use in the methods of the invention include ipilimumab, nonfucosylated anti-CTLA-4 antibodies, activatable anti-CTLA-4 antibodies, and nonfucosylated activatable anti-CTLA-4 antibodies. Such methods optionally comprise concurrent treatment with an anti-PD-1 or anti-PD-L1 antibody.