Antibody beneficial for treatment of solid tumors, antibody-drug conjugate, and cancer drug including same
Inventors
Matsumura, Yasuhiro • Yasunaga, Masahiro • SAIJO, Shinji • TSUMURA, Ryo
Assignees
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Publication Number
US-11377504-B2
Publication Date
2022-07-05
Expiration Date
Abstract
The present invention provides an antibody beneficial for treatment of a solid tumor, an antibody-drug conjugate thereof, and an anticancer agent comprising these. The present invention provides, for example, an antibody that binds to tissue factor or an antigen-binding fragment thereof, wherein the antibody has a dissociation rate constant kd of 5×10−4 s−1 or more and an association rate constant Ka of 1×104 M−1 s−1 or more.
Core Innovation
The disclosed invention relates to an anti-tissue factor antibody, or an antigen-binding fragment, for solid tumor treatment. The antibodies are defined by binding kinetics to tissue factor, including a dissociation rate constant Kd of 5×10 24 s1 or more and an association rate constant Ka of 1×10^4 M1 s1 or more.
The invention further specifies that the antibody comprises a heavy chain variable region and a light chain variable region in which complementarity-determining regions (CDRs) 1 to 3 are defined by amino acid sequences given by SEQ ID NOs. In particular, the heavy chain CDRs 1 to 3 have amino acid sequences of SEQ ID NOs: 2 to 4, respectively, and the light chain CDRs 1 to 3 have amino acid sequences of SEQ ID NOs: 6 to 8, respectively.
In the document, exemplary embodiments include the generation of antibody clones and the construction of antibody-drug conjugates (ADCs) for comparison. The disclosure states that an ADC based on an antibody with a specified kinetic profile shows superior efficacy, with intratumoral distribution results indicating uniform penetration for one ADC compared to localization near vessels for another.
Claims Coverage
The partial content provides one independent claim. The claim coverage focuses on a tissue factor-binding antibody, or antigen-binding fragment, with specified kinetic thresholds and CDR-defined heavy and light variable regions, together forming the principal inventive features.
Kinetics-defined tissue factor-binding antibody with specified heavy/light CDR sequences
An antibody that binds tissue factor, or an antigen-binding fragment, having a dissociation rate constant Kd of 5×10 24 s1 or more and an association rate constant Ka of 1×10^4 M1 s1 or more, comprising a heavy chain variable region with CDRs 1 to 3 amino acid sequences of SEQ ID NOs: 2 to 4, respectively, and a light chain variable region with CDRs 1 to 3 amino acid sequences of SEQ ID NOs: 6 to 8, respectively.
Based on the provided partial content, the independent claim’s coverage is directed to tissue factor-binding antibodies defined by both binding kinetics and CDR1–3 sequence assignments for the heavy and light chains, as specified by SEQ ID NOs.
Stated Advantages
Greater tumor penetration
Improved antitumor activity
Superior efficacy of the referenced ADC
Uniform intratumoral penetration
Documented Applications
Solid tumor treatment using anti-tissue factor antibodies and antibody-drug conjugates (ADCs).
Antibody and ADC evaluation including tumor growth suppression and intratumoral distribution assessment in a pancreatic cancer xenograft model.
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