Anti-c-Met agonist antibody and use thereof
Inventors
Shin, Young Kee • Lee, Ji Hye • Kim, Young Deug • Choi, Jun Young
Assignees
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Publication Number
US-12173074-B2
Publication Date
2024-12-24
Expiration Date
Abstract
The present invention relates to an anti-c-Met agonist antibody and use thereof, and more particularly, to an agonist antibody or fragment thereof that specifically binds to a human-derived c-Met protein, to a method for producing the same, to c-Met specific detection method using this, to a composition for preventing or treating cancer comprising the same, to a composition for inducing stem cell differentiation, and a culture medium for stem cells. The method of the present invention can be usefully used for detecting c-Met antibodies, inducing stem cell differentiation using the antibody, and treating or preventing cancer.
Core Innovation
The invention relates to an agonist antibody or fragment thereof that specifically binds to a human-derived c-Met protein. The antibody is defined by an antibody light chain variable region comprising complementarity determining regions CDR L1, CDR L2, and CDR L3, wherein the CDR L1 amino acid sequence is defined by SEQ ID NO: 1, the CDR L2 amino acid sequence is defined by SEQ ID NO: 2, and the CDR L3 amino acid sequence is defined by SEQ ID NO: 3.
The antibody is further defined by an antibody heavy chain variable region comprising complementarity determining regions CDR H1, CDR H2, and CDR H3, wherein the CDR H1 amino acid sequence is defined by SEQ ID NO: 4, the CDR H2 amino acid sequence is defined by SEQ ID NO: 5, and the CDR H3 amino acid sequence is defined by SEQ ID NO: 6. The problem being solved is the provision of an agonist antibody that specifically binds human-derived c-Met protein and is supported by experimental embodiments showing binding to natural c-Met.
The provided embodiments include phage-display screening yielding multiple scFv hits that are converted to human IgG, and antibodies exemplified as A8, A11, B10, and C8. Binding to natural c-Met is documented using flow cytometry, and affinity is reported using Octet, including KD values reported for A8.
Agonist activity and downstream signaling are documented through increased c-Met phosphorylation and increased downstream p-Erk and p-Akt using Western blot for certain antibodies. Functional cell effects are shown using a WST proliferation assay, and the document also supports stem-cell differentiation compositions with HGF-like effects and differentiation outcomes using adipose-derived mesenchymal stem cells.
Claims Coverage
The independent claim is directed to an agonist antibody or fragment that specifically binds a human-derived c-Met protein with defined light- and heavy-chain CDR sequences (seven inventive sequence-defined CDR features).
Defined agonist antibody with human-derived c-met CDR L1/L2/L3 and CDR H1/H2/H3
An agonist antibody or fragment thereof that specifically binds to a human-derived c-Met protein, wherein the antibody light chain variable region comprises CDR L1 defined by SEQ ID NO: 1, CDR L2 defined by SEQ ID NO: 2, and CDR L3 defined by SEQ ID NO: 3, and wherein the antibody heavy chain variable region comprises CDR H1 defined by SEQ ID NO: 4, CDR H2 defined by SEQ ID NO: 5, and CDR H3 defined by SEQ ID NO: 6.
Across the claim set, the core inventive concept is a sequence-defined agonist antibody or fragment that specifically binds human-derived c-Met via specified CDR amino-acid sequences, with further coverage extending to allowed fragment formats, encoding polynucleotides, producing cells, c-Met-specific detection using the antibody, and stem-cell differentiation compositions using a fat-derived mesenchymal stem cell.
Stated Advantages
Binding to natural c-Met is documented using flow cytometry.
Affinity is reported using Octet, including KD values reported for A8.
Agonist activity and downstream signaling are documented through increased c-Met phosphorylation and increased downstream p-Erk and p-Akt using Western blot for certain antibodies.
Functional cell effects are shown using a WST proliferation assay.
The document supports stem-cell differentiation compositions with HGF-like effects and differentiation outcomes using adipose-derived mesenchymal stem cells.
Documented Applications
A c-Met-specific detection method by contacting a sample with the agonist antibody or fragment and detecting the agonist antibody or fragment.
A therapeutic or preventive cancer composition.
A composition for inducing stem cell differentiation, including a stem-cell culture medium, producing differentiation outcomes described with adipose-derived mesenchymal stem cells.
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