HER2 targeting agent
Inventors
Kato, Yukinari • Kaneko, Mika • Nakayama, Daisuke • KUROGI, Masayuki
Assignees
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Publication Number
US-11981747-B1
Publication Date
2024-05-14
Expiration Date
Abstract
An antibody or antigen-binding fragment thereof is disclosed. The antibody or antigen-binding fragment thereof binds to HER2 expressed on a cancer cell or a fragment of the HER2. A HER2-targeting agent containing any of the antibody or antigen-binding fragment thereof, and a pharmaceutical composition containing the HER2-targeting agent are disclosed.
Core Innovation
The invention relates to isolated antibodies that bind HER2 on cancer cells. The antibodies include antigen-binding fragments and are defined by heavy chain variable region complementarity determining regions and light chain variable region complementarity determining regions, with specific embodiments identified by SEQ ID NOs. The described antibodies are designed to show minimal reactivity to HER2 on non-cancer cells while maintaining HER2 binding.
The document presents epitope mapping of anti-HER2 monoclonal antibodies H2Mab-214 and H2Mab-250. Epitope mapping is performed using overlapping synthetic peptides and epitope region mutants spanning the HER2 extracellular region, including residues 603-622 and related peptide regions, to determine which amino acid residues contribute to antibody binding. The disclosed antigen-binding behavior is characterized using flow cytometry, immunohistochemistry, and binding measurements correlated with Biacore.
The document further describes generation of additional anti-HER2 antibody clones H2Mab-279 to H2Mab-299 using an immunogen peptide HER2_604-622C. It reports that these clones have epitopes located within regions containing W614, K615, and F616, and includes observations using FACS/IHC along with variable region/CDR sequence information. The disclosed scope extends to HER2-targeting agents and pharmaceutical compositions, including antibody-drug conjugates and cytotoxic conjugates.
Claims Coverage
The claim coverage centers on an isolated antibody or antigen-binding fragment defined by six heavy-chain and light-chain CDR amino acid sequences, with protection extending across multiple antigen-binding fragment formats. The inventive features are the specified CDR sequences and the permitted fragment formats.
Isolated antibody defined by specified heavy-chain and light-chain CDR sequences
An isolated antibody comprising a heavy chain variable region with heavy chain CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs 24, 25, and 26, and a light chain variable region with light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs 27, 28, and 29.
Permitted antigen-binding fragment formats
The isolated antibody or an antigen-binding fragment thereof is selected from Fab, Fab’, F(ab’)2, Fv, scFv, diabody, scDb, tandem scFv, leucine zipper type, and sc(Fv)2.
ScFv narrowing
The antigen-binding fragment is specifically an scFV.
Overall, the claim coverage is directed to antibodies or HER2 antigen-binding fragments defined by the stated heavy- and light-chain CDR amino acid sequence embodiments, with an additional narrowing of the fragment format to scFv in the dependent refinement.
Stated Advantages
Shows minimal reactivity to HER2 on non-cancer cells while binding HER2 on cancer cells.
Provides cancer-preferential binding via epitope recognition within the HER2 extracellular domain.
Industrial applicability for cancer detection and/or treatment.
Documented Applications
HER2-targeting agents and pharmaceutical compositions, including antibody-drug conjugates and cytotoxic conjugates.
Cancer detection and/or treatment.
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