Anti-PD-1 Antibody CDR Sequences Block PD-L1 Binding

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current checkpoint inhibitor antibodies, such as those targeting PD-1, have limitations in effectively blocking the binding of PD-1 to PD-L1, leading to suboptimal cancer treatment outcomes, particularly in tumors resistant to standard therapies.

Innovation Solution

Development of murine, chimeric, or humanized antibodies with specific heavy and light chain CDR sequences that effectively block the PD-1/PD-L1 interaction, potentially used alone or in combination with other therapeutic agents like interferons or antibody-drug conjugates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current checkpoint inhibitor antibodies are used to target PD-1, then the treatment can be administered, but the binding of PD-1 to PD-L1 is not effectively blocked, resulting in suboptimal cancer treatment outcomes

Engineering Contradiction:

Improvebinding blocking efficacyVSAvoidcancer treatment outcome

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by optimizing the antibody structure through specific CDR sequences and framework region modifications to enhance binding affinity and blocking efficacy against the PD-1/PD-L1 interaction, thereby improving both reliability of binding blockade and productivity of cancer treatment outcomes

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by creating chimeric and humanized antibody constructs that combine murine CDR sequences with human framework regions, optimizing both binding effectiveness and immunogenicity properties to achieve superior therapeutic results

Inventive Principle:

Principle #40Composite materials

2Productivity

If tumors are resistant to standard therapies, then treatment options are limited, but checkpoint inhibitor antibodies alone achieve insufficient efficacy

Engineering Contradiction:

Improvetreatment efficacyVSAvoidresponse to therapy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies merging by combining the optimized anti-PD-1 antibody with other therapeutic agents such as interferons and antibody-drug conjugates, creating combination therapies that produce synergistic effects and overcome tumor resistance to standard treatments

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent uses interferons as intermediary substances that mediate between the antibody therapy and the immune system, enhancing the overall therapeutic effect and improving treatment efficacy in tumors resistant to standard therapies

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10669338B2Anti-PD-1 checkpoint inhibitor antibodies that block binding of PD-L1 to PD-1

Publication Date: 2020.06.02 IMMUNOMEDICS INC

AI summary

The present invention concerns compositions and methods of use of anti-PD-1 antibodies comprising CDR sequences corresponding to SEQ ID NO:1 to SEQ ID NO:6. Preferably the antibody is a humanized antibody comprising the variable region amino acid sequences of SEQ ID NO: 9 and SEQ ID NO:10. The antibodies are of use to treat cancer and may be administered alone or with another standard anti-cancer therapy. The methods may comprise administering the anti-PD-1 antibody or antigen-binding fragment thereof in combination with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-α), and/or other checkpoint inhibitor antibodies.