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Publication Number
US-11787860-B2
Publication Date
2023-10-17
Expiration Date
Abstract
Provided herein are compositions, methods and uses involving antibodies that specifically bind to human CD47. Also provided are uses and methods, such as therapeutic methods, diagnostic methods, and methods of making such antibodies.
Core Innovation
The disclosure relates to a monoclonal anti-CD47 antibody that specifically binds human CD47 and comprises specified heavy-chain and light-chain variable-region characteristics. The independent claim covers administering this monoclonal antibody to treat cancer or alleviate a symptom of cancer in a subject in need thereof. These sequence-defined antibody variants target human CD47, block the CD47-SIRPalpha interaction, and promote phagocytosis.
Framework-modified antibody variants improve cell-free expression yield over parental antibodies while retaining CD47 binding and increasing Fab thermal stability. The modified antibodies limit agglutination, red-cell hemagglutination, hematologic effects, and Fc effector activity. In evaluated models, these antibodies optimize protein expression titers while demonstrating reduced tumor volume in a mouse xenograft.
Claims Coverage
The claim coverage identifies one independent claim directed to a method of treating cancer or alleviating a cancer symptom using a monoclonal anti-CD47 antibody, defining two inventive features.
Administration of an anti-CD47 antibody to treat cancer
The method treats cancer or alleviates a symptom of cancer by administering a monoclonal antibody that specifically binds human CD47 to a subject in need thereof.
Specified antibody variable-region characteristics
The monoclonal antibody comprises specified heavy-chain and light-chain variable-region features, including sequence-defined framework modifications and complementarity-determining regions.
The independent claim combines the cancer treatment method with administration of the sequence-defined, human-CD47-binding monoclonal antibody, alongside dependent claim elements concerning antibody properties, formats, and conjugates.
Stated Advantages
Higher cell-free expression titer or yield than parental anti-CD47 antibodies.
Retained CD47 binding and increased Fab thermal stability for framework-modified antibody variants.
Blockade of the CD47-SIRPalpha interaction and promotion of phagocytosis.
Limitation or absence of substantial red-cell depletion, anemia, platelet depletion, cell agglutination, red-cell hemagglutination, and Fc effector activity.
Demonstrated reduction of tumor volume in a mouse xenograft.
Documented Applications
Treatment of cancer or alleviation of a symptom of cancer by administering the sequence-defined monoclonal anti-CD47 antibody.
Cancer treatment involving combination therapy and promotion of tumor-cell phagocytosis.
Diagnostic detection and diagnostic uses of CD47.
Cell-free production systems for framework-modified anti-CD47 antibodies.
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