Antibody-drug conjugates comprising anti-B7-H3 antibodies
Inventors
Park, Taekyo • Kim, Sunyoung • Park, Suho • Jung, Doohwan • Seo, Donghoon • Lee, Sangkwang • Yun, Sanghyeon • Ha, Jihyeon • Lee, Hyang Sook • Park, Okku • Seo, Beomseok • Kim, Sena • Seol, Minah • Song, Jina • Woo, Sung Ho • Cho, Jongun • Lee, Jaeho • Lee, Hyun Mi • Park, Jae Eun • Song, Youngja • Lee, Eunjin • Lee, Hyun Ju • Shim, Eun-young • Ko, Yunjung • Lee, Minju • Park, Young Woo • Rew, Yosup
Assignees
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Publication Number
US-12168060-B2
Publication Date
2024-12-17
Expiration Date
Abstract
The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-B7-H3 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind B7-H3, as well as methods of making and using these anti-B7-H3 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications.
Core Innovation
The invention relates to an antibody conjugate represented by Formula I, or a pharmaceutically acceptable salt or solvate thereof, in which Ab is an anti-B7-H3 antibody or antigen-binding fragment comprising specified CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences. The conjugate is defined as Ab-(G)n, where each G is independently a chemical moiety comprising one or more active agents and a linker that links Ab to the active agent(s), and n is an integer between 1 and 20.
The disclosure further defines structural embodiments for the conjugate moiety G, including Formula II with a TG-triggering group connected through Q′-L′ to an X-SO2-Ar-Z′ framework and ring-formation rules, and an alternative compound of formula (III) with a substituent A. The text also describes active-agent scope that includes immunomodulatory, anticancer, antiviral, antibacterial, antifungal, antiparasitic agents, and combinations of these.
Additional disclosed embodiments describe linker-related chemistry and ADC preparation concepts, including MPS-based one-step conjugation, activated Michael acceptors, maleimide-containing precursors, and complementary azide/alkyne reactive groups. The document also reports specific antibody CDR sequence sets, specific anti-B7-H3 antibody variants, and representative conjugate intermediates and products with structure depictions and mass spectrometry characterization.
Claims Coverage
The independent claim is directed to an anti-B7-H3 antibody conjugate Ab-(G)n defined by specified CDRH/CDRL sequences and a linker-active-agent moiety G in Formula I, with n between 1 and 20. Across the provided claim content, there are 4 recurring inventive feature groups: the anti-B7-H3 antibody definition, the linker-linked active-agent moiety G, the stoichiometric range n, and formula-based refinements of G and its payload categories.
Anti-B7-H3 antibody defined by specific CDR sequences
An antibody conjugate represented by Formula I or a pharmaceutically acceptable salt or solvate thereof, wherein Ab is an anti-B7-H3 antibody or antigen-binding fragment comprising specified CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences, including multiple SEQ ID NO combinations.
Linker-linked active-agent moiety G
Each G is independently a chemical moiety comprising one or more active agents and a linker that links Ab to the active agent(s).
Conjugate stoichiometry n between 1 and 20
The Ab-(G)n conjugate includes n as an integer between 1 and 20.
Triggered or alternative formula-based G definitions
Dependent claim coverage further defines G by Formula II with a TG-triggering group and an X-SO2-Ar-Z′ framework, and by a compound of formula (III) with a substituent A and n constrained to 1 to 4.
Overall, the claim coverage centers on an anti-B7-H3 antibody conjugate with specified CDR sequences and a linker-linked active-agent moiety G, with n limited to 1 to 20. Additional claim coverage refines G by formula-based structural definitions and restricts the active-agent categories.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer by administering the antibody conjugate to a subject who needs it.
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