Anti-CD45 antibody-drug conjugates and uses thereof

By employing ADCs with anti-CD45 antibodies conjugated to cytotoxins like PBD or IGN, the challenge of ensuring hematopoietic stem cell graft engraftment is addressed, achieving effective reduction of CD45+ cells and improved treatment efficacy for hematopoietic system-related disorders.

JP7650819B2Active Publication Date: 2025-03-25REGENERON PHARMACEUTICALS INC
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Patent Information

Application Number
JP2021563185
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-04-24
Filing Date
2020-04-24
Publication Date
2025-03-25
Estimated Expiration
2040-04-24

AI Technical Summary

Technical Problem

Current treatments for hematopoietic system-related disorders, such as blood diseases, cancer, and autoimmune diseases, face challenges in ensuring the engraftment of hematopoietic stem cell grafts due to immune stimulatory and effector functions induced by antibodies targeting cell surface antigens on endogenous HSCs.

Method used

Development of antibody-drug conjugates (ADCs) comprising an anti-CD45 antibody or its antigen-binding portion conjugated to a cytotoxin with a benzodiazepine partial structure, such as pyrrolobenzodiazepine (PBD) or indolinobenzodiazepine (IGN), to reduce CD45+ cells.

Benefits of technology

The use of ADCs effectively reduces CD45+ cell populations, thereby minimizing immune interference and enhancing the engraftment potential of exogenous hematopoietic stem cell grafts, improving treatment outcomes for various hematopoietic system-related disorders.

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Abstract

The present invention provides anti-CD45 antibody-drug conjugates (ADCs) and methods of use thereof. In one embodiment, the present invention provides a method of depleting a population of CD45+ cells from a subject by administering an anti-CD45 ADC provided herein. In some embodiments, the ADC includes a cytotoxin containing a benzodiazepine moiety, e.g., a pyrrolobenzodiazepine (PBD) or indolinobenzodiazepine (IGN) moiety.
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