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US 2015/0030535 A1Published application
Meditopes and meditope-binding antibodies and uses thereof
AssigneeCity of Hope
InventorsJohn C. WILLIAMS, David A. HORNE, Yuelong MA, Heng Wei CHANG, Joshua M. DONALDSON, Cindy ZER, Krzysztof BZYMEK, Kendra N. AVERY, Jun XIE
Life of this patent
Estimating the term…
Abstract
Antibodies and meditopes that bind to the antibodies are provided, as well as complexes, compositions and combinations containing the meditopes and antibodies, and methods of producing, using, testing, and screening the same, including therapeutic and diagnostic methods and uses.
Claims21
(canceled)
A method comprising:
- administering to a subject having cancer, a meditope-enabled antibody or antigen-binding fragment thereof and a meditope that binds to a meditope binding site in the meditope-enabled antibody or antigen-binding fragment thereof, wherein:
- said meditope-enabled antibody or antigen-binding fragment thereof comprises a heavy chain variable (VH) region;
- a heavy chain constant region (CH) or portion thereof;
- a light chain variable (VL) region comprising a threonine, serine, or aspartate at position 40, a residue other than glycine at position 41, a residue other than phenylalanine at position 83, and an aspartate or asparagine at position 85, according to Kabat numbering;
- and a light chain constant region (CL) or portion thereof;
- said meditope-enabled antibody or antigen-binding fragment thereof is a meditope-enabled variant of a human or humanized template antibody or antigen-binding fragment thereof, said variant comprising a plurality of framework region (FR) modifications compared to the template antibody or antigen-binding fragment thereof;
- and
- said meditope-enabled antibody or antigen-binding fragment thereof is capable of binding, via the meditope-binding site, to a cyclic peptide comprising the amino acid sequence of SEQ ID NO:
- 1.
6 more elements
A method for generating a meditope-enabled antibody or antigen-binding fragment thereof, the method comprising:
- effecting one or more amino acid substitutions in a template antibody or an antigen-binding fragment thereof, the one or more substitutions comprising a substitution at position 9, 10, 39, 40, 41, 42, 43, 45, 83, 85, or 100 of a light chain variable (VL) region of the template antibody or antigen-binding fragment thereof, according to Kabat numbering, or at position 40 or 89 of a heavy chain variable (VH) region of the template antibody or antigen-binding fragment thereof, according to Kabat numbering,
- thereby generating a meditope-enabled antibody or antigen-binding fragment thereof that binds via a meditope-binding site to a meditope.
A pharmaceutical composition comprising:
- a meditope, a meditope-enabled antibody or antigen-binding fragment thereof, and a pharmaceutically-acceptable carrier, wherein:
- said meditope-enabled antibody or antigen-binding fragment thereof comprises a heavy chain variable (VH) region;
- a heavy chain constant region (CH) or portion thereof;
- a light chain variable (VL) region comprising a threonine, serine, or aspartate at position 40, a residue other than glycine at position 41, a residue other than phenylalanine at position 83, and an aspartate or asparagine at position 85, according to Kabat numbering;
- and a light chain constant region (CL) or portion thereof;
- said meditope-enabled antibody or antigen-binding fragment thereof is a meditope-enabled variant of a human or humanized template antibody or antigen-binding fragment thereof, said variant comprising a plurality of framework region (FR) modifications compared to the template antibody or antigen-binding fragment thereof;
- said meditope-enabled antibody or antigen-binding fragment thereof is capable of binding, via the meditope-binding site, to a cyclic peptide comprising the amino acid sequence of SEQ ID NO:
- 1;
- and
- said meditope is coupled to a therapeutic or diagnostic agent.
7 more elements
Dependencies are inferred from the claim text.