JPWO2019075216A5 - - Google Patents

Claims (27)

A composition comprising (i) an antibody that specifically binds to plectin 1 exposed to the surface of cancer cells; and (ii) an anti-cancer agent.
A composition in which the antibody and the anticancer agent are not bound. A composition comprising (i) an antibody or antigen binding fragment that specifically binds to an amino acid sequence having at least 85% identity with SEQ ID NO: 2; and (ii) an anticancer agent.
A composition in which the antibody and the anticancer agent are not bound. The composition of claim 2, wherein the antibody or antigen binding fragment comprises a heavy chain variable region having the sequence set forth as SEQ ID NO: 23 or SEQ ID NO: 67. The composition of claim 3, wherein the antibody or antigen binding fragment further comprises a light chain variable region having the sequence set forth as SEQ ID NO: 45 or SEQ ID NO: 89. The composition according to any one of claims 1 to 4, wherein the antibody comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 23 and a light chain variable region having the sequence set forth in SEQ ID NO: 45. thing. The composition according to any one of claims 1 to 4, wherein the antibody comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 67 and a light chain variable region having the sequence set forth in SEQ ID NO: 89. thing. The composition according to any one of claims 2 to 6, wherein the antibody or antigen-binding fragment binds to plectin 1 exposed to the cell surface. The anticancer agents include abraxane (pacrytaxelalbumin-stabilized nanoparticle preparation), adolcil (fluorouracil), affinitol (everolimus), efdex (fluorouracil), errotinib hydrochloride, everolimus, fluoroplex (fluorouracil), fluorouracil, gemcitabine hydrochloride, gemzar (fluorouracil). Gemcitabine hydrochloride), mitomycin C, mitozitelex (mitomycin C), mutamycin (mitomycin C), paclitaxelalbumin-stabilized nanoparticle formulation, snitinib malate, sutent (snitinib malate), and tarseva (errotinib hydrochloride), altretamine, Alkeran (Melfaran), Avastin (Vevasizumab), Vevasizumab, Carboplatin, Clade (Cyclophosphamide), Sisplatin, Cyclophosphamide, Citoxan (Cyclophosphamide), Doxorubicin hydrochloride, Dox-SL (Doxorubicin hydrochloride liposome) , DOXIL (doxorubicin hydrochloride liposome), doxorubicin hydrochloride liposome, evaset (doxorubicin hydrochloride liposome), gemcitabine hydrochloride, gemzar (gemcitabine hydrochloride), hycamtin (topotecan hydrochloride), LipoDox (doxorubicin hydrochloride liposome), limpaza (oraparib) Melfaran, Neozar (Cyclophosphamide), Nilaparib tosylate monohydrate, Olaparib, Paclitaxel, Paraplat (Carboplatin), Paraplatin (Carboplatin), Platinol (Sisplatin), Platinol-AQ (Sisplatin), Lubraca (Lucapari) Any one of claims 1-7, selected from the group consisting of doxorubecinate), lucaparibucansilate, taxol (pacrytaxel), thiotepa, topotecan hydrochloride, zedura (doxorubicin monohydrate). The composition according to the section. The composition according to any one of claims 1 to 8, wherein the anticancer agent is gemcitabine or cisplatin. The composition according to any one of claims 1 to 9, wherein the anti-plectin 1 antibody and the anti-cancer agent act synergistically (for example, measured by the Chou-Talalay method). An antibody-drug conjugate (ADC) comprising an antibody or antigen-binding fragment that specifically binds to plectin 1 exposed on the surface of cancer cells bound to one or more anti-cancer drug molecules. An antibody drug conjugate (ADC) comprising an antibody or antigen binding fragment that specifically binds to an amino acid sequence having at least 85% identity with SEQ ID NO: 2 bound to one or more anticancer agent molecules. The ADC according to claim 11 or 12, wherein the one or more anticancer agent molecules are directly bound to the antibody or antigen binding fragment. The ADC according to claim 11 or 12, wherein the one or more anticancer agent molecules are indirectly bound to the antibody or antigen binding fragment via a linker, optionally a photolinker or a mobile amino acid sequence linker. .. The ADC according to any one of claims 11 to 14, wherein 2, 3, 4, or 5 anticancer agent molecules are bound to the antibody or antigen-binding fragment. The ADC according to any one of claims 11 to 15, wherein each of the one or more anticancer agent molecules is auristatin or pyrolobenzodiazepine (PBD), and optionally each PBD is a PBD dimer. .. The ADC according to any one of claims 11 to 16, wherein the antibody or antigen binding fragment comprises a heavy chain variable region having the sequence set forth as SEQ ID NO: 23 or SEQ ID NO: 67. The ADC according to any one of claims 11 to 16, wherein the antibody or antigen binding fragment further comprises a light chain variable region having the sequence set forth as SEQ ID NO: 45 or SEQ ID NO: 89. The ADC according to any one of claims 11 to 18, wherein the antibody comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 23 and a light chain variable region having the sequence set forth in SEQ ID NO: 45. .. The ADC according to any one of claims 11 to 18, wherein the antibody comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 67 and a light chain variable region having the sequence set forth in SEQ ID NO: 89. .. The ADC according to any one of claims 12 to 20, wherein the antibody or antigen-binding fragment binds to plectin 1 exposed to the cell surface. A method of treating cancer, in which a subject with cancer is administered an effective amount of an antibody or antigen binding fragment and an anticancer agent that specifically binds to an amino acid sequence having at least 85% identity with SEQ ID NO: 2. The method, including that. Claimed that the antibody or antigen binding fragment and the anticancer agent are administered together as the composition according to any one of claims 1 to 10 or the ADC according to any one of claims 11 to 21. Item 22. 22. The method of claim 22, wherein the antibody or antigen binding fragment and the anticancer agent are administered separately. The method according to any one of claims 22 to 24, wherein the cancer is characterized by the expression of plectin 1 on the surface of the cancer cells. The cancer according to any one of claims 22 to 25, wherein the cancer is ovarian cancer, esophageal cancer, squamous cell carcinoma of the head and neck, or pancreatic cancer, and in some cases, the pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). The method described. The method according to any one of claims 22 to 26, wherein the subject is a mammal, and in some cases, a human.