Anti-CTLA-4 Antibody Dosing via Breakthrough Event Feedback

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current cancer treatments using CTLA-4 antibodies often result in under-dosing patients and lack predictability, with adverse events being a major concern, limiting their effectiveness in inducing a therapeutic response.

Innovation Solution

Administering escalating doses of anti-CTLA-4 antibodies to induce a breakthrough event, which is a reversible and predictable autoimmune response, allowing for a therapeutically effective dosage regimen to be determined and monitored, thereby enhancing cancer treatment outcomes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-CTLA-4 antibodies are administered to treat cancer, then therapeutic efficacy is improved, but adverse events increase

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidadverse events
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent implements dynamic dose adjustment by establishing a feedback mechanism where breakthrough events trigger dose modifications. The treatment regimen transitions from static dosing to dynamic dosing, where the antibody dose is adjusted based on the occurrence and severity of breakthrough events, thereby optimizing the balance between therapeutic efficacy and adverse event management

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the dosage parameter from fixed to variable, establishing specific dose reduction criteria based on breakthrough event severity. By defining clear parameter thresholds (e.g., Grade 3 or 4 adverse events trigger dose reduction), the patent transforms the dosage regimen into an adaptive system that responds to patient-specific responses, resolving the contradiction between maintaining efficacy and reducing toxicity

Inventive Principle:
Principle #35Parameter changes

2Reliability

If escalating doses are administered to induce breakthrough events, then therapeutic response is improved, but dosage precision requirements increase

Engineering Contradiction:
Improvetherapeutic responseVSAvoiddosage precision
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent establishes a feedback loop where breakthrough events serve as biological markers indicating adequate dosing. The occurrence of breakthrough events provides real-time feedback on whether the escalating dose regimen has achieved the intended immunological effect, allowing clinicians to adjust subsequent dosing decisions based on observed patient responses rather than relying solely on predetermined dosing schedules

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patient's immune system serves as the dosing monitor through breakthrough events. Rather than requiring external monitoring tools or complex assays, the body's own immune response (manifesting as breakthrough events) provides the information needed to determine whether therapeutic dosing has been achieved, simplifying the dosing decision-making process

Inventive Principle:
Principle #25Self-service

Data Source

PatentUS7465446B2Surrogate therapeutic endpoint for anti-CTLA4-based immunotherapy of disease
Publication Date: 2008.12.16 ER SQUIBB & SONS LLC

AI summary

The present invention provides a method of treatment using human sequence antibodies against human CTLA-4. In particular, methods of treating cancer are provided.