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US 12,714,753 B2Granted
Meditopes and meditope-binding antibodies and uses thereof
AssigneeCity of Hope
InventorsJohn C. Williams, David A. Horne, Yuelong Ma, Heng Wei Chang, Joshua Michael Donaldson, Cindy Zer, Krzysztof Bzymek, Kendra Nicole Avery, Jun Xie
Life of this patent
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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.
Claims10
A complex comprising:
- a meditope-enabled antibody or antigen-binding fragment thereof, wherein the meditope-enabled antibody or antigen-binding fragment thereof comprises a meditope-binding site which (i) comprises a light chain variable (VL) region comprising a threonine at position 40, an asparagine at position 41, and an aspartate at position 85, according to Kabat numbering, and a heavy chain variable (VH) region comprising a serine or proline at position 40 and an isoleucine, tyrosine, methionine, phenylalanine, or a tryptophan at position 89, according to Kabat numbering and (ii) can bind to a peptide comprising the amino acid sequence of SEQ ID NO:
- 1 or 2;
- a meditope bound to the meditope-binding site;
- and
- a chemotherapeutic agent conjugated to the meditope,
- wherein the meditope comprises the formula:
- X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 (SEQ ID NO:191) (Formula I), wherein:
- X1=Cys, Gly, β-alanine, 2,3-diaminopropionic acid, or null;
- X2=Gln or null;
- X3=Phe, Tyr, β-β′-diphenyl-Ala, 2-bromo-L-phenylalanine, 3-bromo-L-phenylalanine, or 4-bromo-L-phenylalanine;
- X4=Asp or Asn;
- X5=Leu, β-β′-diphenyl-Ala or Phe;
- X6=Ser;
- X7=Thr or Ser;
- X8=Arg or a modified Arg;
- X9=Arg or Ala;
- X10=Leu, Gln, or Glu;
- X11=Lys;
- and
- X12=Cys, 7-aminoheptanoic acid, β-alanine, or null,
- wherein:
- the modified Arg has a structure of the formula
- and
- wherein the meditope-enabled antibody or antigen-binding fragment thereof is not cetuximab.
21 more elements
Dependencies are inferred from the claim text.