Chimeric And Humanized Anti-CD45 Antibodies for Reduced HAMA Responses

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current anti-CD45 murine antibodies, such as BC8, cause significant infusion toxicities and human anti-mouse antibody (HAMA) immunization, limiting their use in immunotherapy for hematologic malignancies like acute leukemia due to their immunogenicity.

Innovation Solution

Development of chimeric and humanized forms of the BC8 antibody, which include murine variable chain regions and human constant regions, reducing or eliminating toxicities and HAMA responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If murine anti-CD45 antibodies (e.g., BC8) are used for immunotherapy, then therapeutic efficacy against hematologic malignancies is achieved, but significant infusion toxicities and HAMA immunization occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidinfusion toxicities and HAMA

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the antibody's species composition parameters - transitioning from fully murine to chimeric (murine variable regions with human constant regions) or humanized (murine CDRs grafted onto human frameworks) forms. This changes the immunogenicity parameter while preserving CD45 binding affinity, thereby reducing infusion toxicities and HAMA responses while maintaining therapeutic efficacy against hematologic malignancies.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If murine anti-CD45 antibodies are administered, then CD45-positive cancer cells are targeted, but immune activation and HAMA response are triggered

Engineering Contradiction:

Improvetargeting accuracyVSAvoidimmune activation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The chimeric and humanized antibodies serve as intermediary forms that bridge the gap between murine antibody efficacy and human tolerance. By incorporating human constant regions or human frameworks, these intermediary forms reduce recognition by the human immune system while maintaining the ability to bind CD45 on cancer cells, thus reducing immune activation and HAMA responses.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If humanized antibodies are used, then HAMA response is reduced, but manufacturing complexity increases

Engineering Contradiction:

ImproveHAMA responseVSAvoidantibody structure complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The antibody molecule is segmented into functional regions with different species origins: variable regions (CDRs) from murine BC8 for antigen specificity, and constant regions or frameworks from human immunoglobulins for reduced immunogenicity. This segmentation allows independent optimization of binding function and immunogenicity reduction, achieving HAMA response reduction while managing manufacturing complexity through modular construction.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250326856A1Humanized Anti-CD45 antibodies and uses thereof

Publication Date: 2025.10.23 FRED HUTCHINSON CANCER CENT

AI summary

Novel chimeric and/or humanized forms of the anti-CD45 BC8 antibody are described. The disclosed chimeric or humanized antibodies can be used as research, diagnostic, or therapeutic tools against CD45-related disorders, such as hematologic malignancies including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), other myeloid and lymphoid disorders, other cancers, as well as non-malignant disorders, such as autoimmune disorders, infections, inherited blood disorders, and metabolic disorders.