Patent RU-2765410-C2 (RU)
Title: Methods for treating cancer, including tigit-binding agents
Inventor: DYUPON DZHEJKOB
IPC: A61K39/00
Filed: 2017-11-30
Granted: 2022-01-28
Abstract: FIELD: medicine. 
     SUBSTANCE: group of inventions relates to a method for inhibiting the growth of a TIGIT-expressing tumour in a subject, including administering a therapeutically effective amount of an antibody specifically binding the extracellular human TIGIT domain to said subject, wherein the TIGIT-expressing tumour constitutes a colorectal cancer with high microsatellite instability, microsatellite-stable colorectal cancer, triple negative breast cancer, carcinoma from Merkel cells, endometrial cancer, or esophageal cancer; wherein the antibody binding to human TIGIT comprises a heavy chain CDR1 containing the sequence TSDYAWN (SEQ ID NO: 4), heavy chain CDR2 containing YISYSGSTSYNPSLRS (SEQ ID NO: 5), heavy chain CDR3 containing ARRQVGLGFAY (SEQ ID NO: 6), light chain CDR1 containing KASQDVSTAVA (SEQ ID NO: 7), light chain CDR2 containing SASYRYT (SEQ ID NO: 8), and light chain CDR3 containing QQHYSTP (SEQ ID NO: 9), also relates to a method for inhibiting the growth of a TIGIT-expressing tumour in a subject, including administering a therapeutically effective amount of the antibody specifically binding to the extracellular human TIGIT domain to said subject in combination with a PD-1 antagonist or a PD-L1 antagonist, also relates to a method for inhibiting the growth of a TIGIT-expressing tumour in a subject, including administering a therapeutically effective amount of an antibody specifically binding to the extracellular human TIGIT domain to said subject in combination with a PD-1 antagonist or a PD-L1 antagonist, wherein said TIGIT-expressing tumour is resistant or refractory to treatment with the PD-1 antagonist or the PD-L1 antagonist as a separate agent, or wherein said subject has previously received treatment with a PD-1 antagonist or a PD-L1 antagonist as a separate agent, also relates to a method for inhibiting growth of a TIGIT-expressing tumour in a subject, including administering a therapeutically effective amount of an antibody specifically binding to the extracellular human TIGIT domain to said subject, wherein said TIGIT-expressing tumour expresses the poliovirus receptor (PVR) and/or the poliovirus receptor-like protein 2 (PVRL2), and also relates to a method for inhibiting growth of TIGIT-expressing tumor in a subject including administering a therapeutically effective amount of an antibody specifically binding to the extracellular human TIGIT domain to said subject in combination with a PD-1 antagonist or a PD-L1 antagonist, wherein said TIGIT-expressing tumour expresses the poliovirus receptor (PVR) and/or the poliovirus receptor-like protein 2 (PVRL2), or said TIGIT-expressing tumour comprises tumour infiltrating lymphocytes (TIL), or said TIGIT-expressing tumour comprises regulatory T-cells. 
     EFFECT: group of inventions provides a possibility of specifically binding to human TIGIT, while not exhibiting cross-reactivity with TIGIT of other species, and also provides a higher affinity for human TIGIT compared to other antibodies against TIGIT, leading to an improved anti-tumour response compared to other antibodies against TIGIT. 
     54 cl, 2 dwg, 4 ex, 3 tbl