Title:
EPITOPE REGION-BRIDGING BIPARATOPIC ANTIBODY AND METHOD FOR PRODUCING SAME
Document Type and Number:
WIPO Patent Application WO/2021/200840
Kind Code:
A1
Abstract:
The present disclosure provides a technique for designing an epitope region-bridging biparatopic antibody, and also provides, through this technique, an antibody that has an improved agonist or antagonist function for an antigen or that promotes or enhances a chemical reaction catalyzed by an enzyme serving as an an antigen. Provided is an epitope region-bridging biparatopic antibody, an antigen-binding fragment thereof or a functional equivalent of the same that has antigen specificities to a first epitope belonging to a first epitope group, among a plurality of epitope region groups in an antigen, and to a second epitope belonging to a second epitope group contained in an epitope region different from the epitope region in which the first epitope group is contained, said antibody comprising the sequences of a heavy chain variable region and a light chain variable region derived from an antibody against the first epitope and the sequences of a heavy chain variable region and a light chain variable region derived from an antibody against the second epitope.
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Inventors:
AKIBA HIROKI (JP)
TSUMOTO KOUHEI (JP)
NAGATA SATOSHI (JP)
TSUMOTO KOUHEI (JP)
NAGATA SATOSHI (JP)
Application Number:
PCT/JP2021/013341
Publication Date:
October 07, 2021
Filing Date:
March 29, 2021
Export Citation:
Assignee:
NAT INST BIOMEDICAL INNOVATION HEALTH & NUTRITION (JP)
International Classes:
C07K16/00; C07K16/28; C07K16/46; C12N15/13; C40B40/10
Domestic Patent References:
| WO2018092907A1 | 2018-05-24 | |||
| WO2018092907A1 | 2018-05-24 | |||
| WO2017143838A1 | 2017-08-31 | |||
| WO2017014383A1 | 2017-01-26 |
Foreign References:
| JP2020061014A | 2020-04-16 |
Other References:
AKIBA, HIROKI ET AL.: "Development and activities, including immunocomplex formation, of biparatopic antibodies and alternative scaffold proteins", TRANSLAT REGULAT SCI., vol. 2, no. 1, 23 January 2020 (2020-01-23), pages 1 - 6, XP055926078
BONNIE HAMMER, MANDAR BAWADEKAR, MATTHEW BISSEN, JOHN PAINTER, LAUREN LEHMANN, FRANCIS QUFEI LI, LUCAS BAILEY, BRYAN GLASER AND RO: "Abstract 563: A biparatopic agonist antibody for OX40 that exhibits superior activity without secondary crosslinking", CANCER RESEARCH , vol. 79, no. 13, Suppl., 1 July 2019 (2019-07-01), GB , pages 563 - 563, XP009517082, ISSN: 0019-2805, DOI: 10.1158/1538-7445.AM2019-563
KOHEI TSUMOTO: "Current status of antibody therapy in the drug development", JIKKEN IGAKU, vol. 36, no. 11, 1 July 2018 (2018-07-01), JP , pages 1818 - 1822, XP009540204, ISSN: 0288-5514
HAN, LEI ET AL.: "Efficient generation of bispecific IgG antibodies by split intein mediated protein trans-splicing system", SCIENTIFIC REPORTS, vol. 7, no. 8360, 2017, pages 1 - 11, XP055548370
SCIENTIFIC REPORTS, vol. 7, 2017, pages 8360
CROFT MLBENEDICT CAWARE CF: "Clinical targeting of the TNF and TNFR superfamilies", NAT REV DRUG DISCOV, vol. 12, no. 2, 2013, pages 147 - 68, XP055806988, DOI: 10.1038/nrd3930
GRELL MDOUNI EWAJANT HLOHDEN MCLAUSS MMAXEINER B ET AL.: "The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumornecrosis factor receptor", CELL, vol. 83, no. 5, pages 793 - 802
LUBRANO DI RICCO M, RONIN E, COLLARES D, DIVOUX J, GREGOIRE S, WAJANT H, GOMES T, GRINBERG-BLEYER Y, BAUD V: "Tumor necrosis factor receptor family co-stimulation increases regulatory T cell activation and function via NF-kappaB", EUR J IMMUNOL, 2020
CHOU CKCHEN X: "Preferential Expansion of CD4(+)Foxp3(+) Regulatory T Cells (Tregs) In Vitro by Tumor Necrosis Factor", METHODS MOL BIOL, vol. 2111, 2020, pages 71 - 78
ATRETKHANY KNGOGOLEVA VSDRUTSKAYA MSNEDOSPASOV SA: "Distinct modes of TNF signaling through its two receptors in health and disease", J LEUKOC BIOL, 2020
WAJANT HBEILHACK A: "Targeting Regulatory T Cells by Addressing Tumor Necrosis Factor and Its Receptors in Allogeneic Hematopoietic Cell Transplantation and Cancer", FRONT IMMUNOL, vol. 10, 2019, pages 2040
TORREY HKHODADOUST MTRAN LBAUM DDEFUSCO AKIM YHFAUSTMAN DL: "Targeted killing of TNFR2-expressing tumor cells and Tregs by TNFR2 antagonistic antibodies in advanced Sezary syndrome", LEUKEMIA, vol. 33, no. 5, 2019, pages 1206 - 1218
TAM EMFULTON RBSAMPSON JFMUDA MCAMBLIN ARICHARDS JKOSHKARYEV ATANG JKURELLA VJIAO Y: "Antibody-mediated targeting of TNFR2 activates CD8(+) T cells in mice and promotes antitumor immunity", SCI TRANSL MED, vol. 11, no. 512, 2019, XP055820628, DOI: 10.1126/scitranslmed.aax0720
MEDLER JWAJANT H: "Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target", EXPERT OPIN THER TARGETS, vol. 23, no. 4, 2019, pages 295 - 307
CHEN XPLEBANSKI M: "Editorial: The Roleof TNF-TNFR2 Signal in Immunosuppressive Cells and Its Therapeutic Implications", FRONT IMMUNOL, vol. 10, 2019, pages 2126
AL-HATAMLEH MAI, E ARE, BOER JC, FERJIK, SIX JL, CHEN X, ELKORD E, PLEBANSKI M, MOHAMUD R: "Synergistic Effects of Inhibitor-An Opportunity for Cancer Treatment", CELLS, vol. 9, no. 1, 2019
ZOU HLI RHU HHU YCHEN X: "Modulation of Regulatory T Cell Activity by TNF Receptor Type II-Targeting Pharmacological Agents", FRONT IMMUNOL, vol. 9, no. 594, 2018
SHENG YLI FQIN Z: "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors", FRONT IMMUNOL, vol. 9, 2018, pages 1170, XP055895943, DOI: 10.3389/fimmu.2018.01170
SHAIKH FHE JBHADRA PCHEN XSIU SWI: "TNF Receptor Type II as an Emerging Drug Target for the Treatment of Cancer, Autoimmune Diseases, and Graft-Versus-Host Disease: Current Perspectives and In Silico Search for Small Molecule Binders", FRONT IMMUNOL9, 2018, pages 1382, XP055812975, DOI: 10.3389/fimmu.2018.01382
SALOMON BLLECLERC MTOSELLO JRONIN EPIAGGIO ECOHEN JL: "Tumor Necrosis Factor alpha and Regulatory T Cells in Oncoimmunology", FRONT IMMUNOL, vol. 9, 2018, pages 444
NIE YHE JSHIROTA HTRIVETT ALYANG, KLINMAN DMOPPENHEIM JJCHEN X: "Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer", SCISIGNAL, vol. 11, no. 511, 2018
FISCHER RPROSKE MDUFFEY MSTANGL HMARTINEZ GFPETERS NKRASKE ASTRAUB RHBETHEA JRKONTERMANN RE: "Selective Activation of Tumor Necrosis Factor Receptor II Induces Antiinflammatory Responses and Alleviates Experimental Arthritis", ARTHRITIS RHEUMATOL, vol. 70, no. 5, 2018, pages 722 - 735
FAUSTMAN DL: "TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment", DIABETES METAB RES REV, vol. 34, no. 1, 2018
TORREY HBUTTERWORTH JMERA TOKUBO YWANG LBAUM DDEFUSCO APLAGER SWARDEN SHUANG D: "Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs", SCI SIGNAL, vol. 10, no. 462, 2017, XP009511349, DOI: 10.1126/scisignal.aaf8608
WILLIAMS GS, MISTRY B, GUILLARD S, ULRICHSEN JC,SANDERCOCK AM, WANG J, GONZALEZ-MUNOZ A, PARMENTIER J,BLACK C, SODEN J, FREETH J, : "Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy", ONCOTARGET, vol. 7, no. 42, 2016, pages 68278 - 68291, XP055486990, DOI: 10.18632/oncotarget.11943
OKUBO YTORREY HBUTTERWORTH JZHENG HFAUSTMAN DL: "Treg activation defect in type ldiabetes: correction with TNFR2 agonism", CLIN TRANSL IMMUNOLOGY, vol. 5, no. 1, 2016, pages e56, XP055570983, DOI: 10.1038/cti.2015.43
WARE, C.F ET AL.: "Tumor necrosis factor (TNF) receptor expression in T lymphocytes. Differential regulation of the type I TNF receptor during activation of resting and effector T cells", J. IMMUNOL., vol. 147, 1991, pages 4229 - 4238
KIM EYPRIATEL JJTEH SJTEH HS, TNF RECEPTOR TYPE 2 (P75) FUNCTIONS AS A COSTIMULATOR FOR ANTIGEN DRIVEN T CELL RESPONSES IN VIVO. JOURNAL OF IMMUNOLOGY, vol. 176, no. 2, 2006, pages 1026 - 35
NAKAMURA TYOSHIKAWA MYOSHIOKA YTSUNODA SNAKAGAWA SYAMAGATA YTSUTSUMI Y: "Solution of the structure of the TNF-TNFR2 complex", SCI SIGNAL, vol. 3, no. 148, 2010, pages ra83, XP009512083, DOI: 10.1126/scisignal.2000954
GRELL M,DOUNI E, WAJANT H, LOHDEN M, CLAUSS M, MAXEINER B,GEORGOPOULOS S, LESSLAUER W, KOLLIAS G, PFIZENMAIER K, SCHEURICH P: "The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor", CELL, vol. 83, no. 5, 1995, pages 793 - 802
NAUDE PJDEN BOER JALUITEN PGEISEL UL: "Tumor necrosis factor receptor cross-talk", FEBS J, vol. 278, no. 6, 2011, pages 888 - 98, XP055486979, DOI: 10.1111/j.1742-4658.2011.08017.x
HAN, LCHEN, J ET AL.: "7", SCI. REP, 2017, pages 8360
STEVENS, A.JBROWN, Z. ZSHAH, N.HSEKAR, GCOWBURN, DMUIR, T. W, J. AM. CHEM. SOC., vol. 138, 2016, pages 2162 - 2165
MERCHANT, A. MZHU, ZYUAN, J. QGODDARD, AADAMS, C. WPRESTA, L. GCARTER, P: "An efficient route to human bispecific IgG", NAT. BIOTECHNOL., vol. 16, 1998, pages 677 - 681, XP002141015, DOI: 10.1038/nbt0798-677
AKIBA, H.SATOH, RNAGATA, STSUMOTO, K, ANTIB. THER, vol. 2, 2019, pages 65 - 69
BONNIE HAMMER, MANDAR BAWADEKAR, MATTHEW BISSEN, JOHN PAINTER, LAUREN LEHMANN, FRANCIS QUFEI LI, LUCAS BAILEY, BRYAN GLASER AND RO: "Abstract 563: A biparatopic agonist antibody for OX40 that exhibits superior activity without secondary crosslinking", CANCER RESEARCH , vol. 79, no. 13, Suppl., 1 July 2019 (2019-07-01), GB , pages 563 - 563, XP009517082, ISSN: 0019-2805, DOI: 10.1158/1538-7445.AM2019-563
KOHEI TSUMOTO: "Current status of antibody therapy in the drug development", JIKKEN IGAKU, vol. 36, no. 11, 1 July 2018 (2018-07-01), JP , pages 1818 - 1822, XP009540204, ISSN: 0288-5514
HAN, LEI ET AL.: "Efficient generation of bispecific IgG antibodies by split intein mediated protein trans-splicing system", SCIENTIFIC REPORTS, vol. 7, no. 8360, 2017, pages 1 - 11, XP055548370
SCIENTIFIC REPORTS, vol. 7, 2017, pages 8360
CROFT MLBENEDICT CAWARE CF: "Clinical targeting of the TNF and TNFR superfamilies", NAT REV DRUG DISCOV, vol. 12, no. 2, 2013, pages 147 - 68, XP055806988, DOI: 10.1038/nrd3930
GRELL MDOUNI EWAJANT HLOHDEN MCLAUSS MMAXEINER B ET AL.: "The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumornecrosis factor receptor", CELL, vol. 83, no. 5, pages 793 - 802
LUBRANO DI RICCO M, RONIN E, COLLARES D, DIVOUX J, GREGOIRE S, WAJANT H, GOMES T, GRINBERG-BLEYER Y, BAUD V: "Tumor necrosis factor receptor family co-stimulation increases regulatory T cell activation and function via NF-kappaB", EUR J IMMUNOL, 2020
CHOU CKCHEN X: "Preferential Expansion of CD4(+)Foxp3(+) Regulatory T Cells (Tregs) In Vitro by Tumor Necrosis Factor", METHODS MOL BIOL, vol. 2111, 2020, pages 71 - 78
ATRETKHANY KNGOGOLEVA VSDRUTSKAYA MSNEDOSPASOV SA: "Distinct modes of TNF signaling through its two receptors in health and disease", J LEUKOC BIOL, 2020
WAJANT HBEILHACK A: "Targeting Regulatory T Cells by Addressing Tumor Necrosis Factor and Its Receptors in Allogeneic Hematopoietic Cell Transplantation and Cancer", FRONT IMMUNOL, vol. 10, 2019, pages 2040
TORREY HKHODADOUST MTRAN LBAUM DDEFUSCO AKIM YHFAUSTMAN DL: "Targeted killing of TNFR2-expressing tumor cells and Tregs by TNFR2 antagonistic antibodies in advanced Sezary syndrome", LEUKEMIA, vol. 33, no. 5, 2019, pages 1206 - 1218
TAM EMFULTON RBSAMPSON JFMUDA MCAMBLIN ARICHARDS JKOSHKARYEV ATANG JKURELLA VJIAO Y: "Antibody-mediated targeting of TNFR2 activates CD8(+) T cells in mice and promotes antitumor immunity", SCI TRANSL MED, vol. 11, no. 512, 2019, XP055820628, DOI: 10.1126/scitranslmed.aax0720
MEDLER JWAJANT H: "Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target", EXPERT OPIN THER TARGETS, vol. 23, no. 4, 2019, pages 295 - 307
CHEN XPLEBANSKI M: "Editorial: The Roleof TNF-TNFR2 Signal in Immunosuppressive Cells and Its Therapeutic Implications", FRONT IMMUNOL, vol. 10, 2019, pages 2126
AL-HATAMLEH MAI, E ARE, BOER JC, FERJIK, SIX JL, CHEN X, ELKORD E, PLEBANSKI M, MOHAMUD R: "Synergistic Effects of Inhibitor-An Opportunity for Cancer Treatment", CELLS, vol. 9, no. 1, 2019
ZOU HLI RHU HHU YCHEN X: "Modulation of Regulatory T Cell Activity by TNF Receptor Type II-Targeting Pharmacological Agents", FRONT IMMUNOL, vol. 9, no. 594, 2018
SHENG YLI FQIN Z: "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors", FRONT IMMUNOL, vol. 9, 2018, pages 1170, XP055895943, DOI: 10.3389/fimmu.2018.01170
SHAIKH FHE JBHADRA PCHEN XSIU SWI: "TNF Receptor Type II as an Emerging Drug Target for the Treatment of Cancer, Autoimmune Diseases, and Graft-Versus-Host Disease: Current Perspectives and In Silico Search for Small Molecule Binders", FRONT IMMUNOL9, 2018, pages 1382, XP055812975, DOI: 10.3389/fimmu.2018.01382
SALOMON BLLECLERC MTOSELLO JRONIN EPIAGGIO ECOHEN JL: "Tumor Necrosis Factor alpha and Regulatory T Cells in Oncoimmunology", FRONT IMMUNOL, vol. 9, 2018, pages 444
NIE YHE JSHIROTA HTRIVETT ALYANG, KLINMAN DMOPPENHEIM JJCHEN X: "Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer", SCISIGNAL, vol. 11, no. 511, 2018
FISCHER RPROSKE MDUFFEY MSTANGL HMARTINEZ GFPETERS NKRASKE ASTRAUB RHBETHEA JRKONTERMANN RE: "Selective Activation of Tumor Necrosis Factor Receptor II Induces Antiinflammatory Responses and Alleviates Experimental Arthritis", ARTHRITIS RHEUMATOL, vol. 70, no. 5, 2018, pages 722 - 735
FAUSTMAN DL: "TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment", DIABETES METAB RES REV, vol. 34, no. 1, 2018
TORREY HBUTTERWORTH JMERA TOKUBO YWANG LBAUM DDEFUSCO APLAGER SWARDEN SHUANG D: "Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs", SCI SIGNAL, vol. 10, no. 462, 2017, XP009511349, DOI: 10.1126/scisignal.aaf8608
WILLIAMS GS, MISTRY B, GUILLARD S, ULRICHSEN JC,SANDERCOCK AM, WANG J, GONZALEZ-MUNOZ A, PARMENTIER J,BLACK C, SODEN J, FREETH J, : "Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy", ONCOTARGET, vol. 7, no. 42, 2016, pages 68278 - 68291, XP055486990, DOI: 10.18632/oncotarget.11943
OKUBO YTORREY HBUTTERWORTH JZHENG HFAUSTMAN DL: "Treg activation defect in type ldiabetes: correction with TNFR2 agonism", CLIN TRANSL IMMUNOLOGY, vol. 5, no. 1, 2016, pages e56, XP055570983, DOI: 10.1038/cti.2015.43
WARE, C.F ET AL.: "Tumor necrosis factor (TNF) receptor expression in T lymphocytes. Differential regulation of the type I TNF receptor during activation of resting and effector T cells", J. IMMUNOL., vol. 147, 1991, pages 4229 - 4238
KIM EYPRIATEL JJTEH SJTEH HS, TNF RECEPTOR TYPE 2 (P75) FUNCTIONS AS A COSTIMULATOR FOR ANTIGEN DRIVEN T CELL RESPONSES IN VIVO. JOURNAL OF IMMUNOLOGY, vol. 176, no. 2, 2006, pages 1026 - 35
NAKAMURA TYOSHIKAWA MYOSHIOKA YTSUNODA SNAKAGAWA SYAMAGATA YTSUTSUMI Y: "Solution of the structure of the TNF-TNFR2 complex", SCI SIGNAL, vol. 3, no. 148, 2010, pages ra83, XP009512083, DOI: 10.1126/scisignal.2000954
GRELL M,DOUNI E, WAJANT H, LOHDEN M, CLAUSS M, MAXEINER B,GEORGOPOULOS S, LESSLAUER W, KOLLIAS G, PFIZENMAIER K, SCHEURICH P: "The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor", CELL, vol. 83, no. 5, 1995, pages 793 - 802
NAUDE PJDEN BOER JALUITEN PGEISEL UL: "Tumor necrosis factor receptor cross-talk", FEBS J, vol. 278, no. 6, 2011, pages 888 - 98, XP055486979, DOI: 10.1111/j.1742-4658.2011.08017.x
HAN, LCHEN, J ET AL.: "7", SCI. REP, 2017, pages 8360
STEVENS, A.JBROWN, Z. ZSHAH, N.HSEKAR, GCOWBURN, DMUIR, T. W, J. AM. CHEM. SOC., vol. 138, 2016, pages 2162 - 2165
MERCHANT, A. MZHU, ZYUAN, J. QGODDARD, AADAMS, C. WPRESTA, L. GCARTER, P: "An efficient route to human bispecific IgG", NAT. BIOTECHNOL., vol. 16, 1998, pages 677 - 681, XP002141015, DOI: 10.1038/nbt0798-677
AKIBA, H.SATOH, RNAGATA, STSUMOTO, K, ANTIB. THER, vol. 2, 2019, pages 65 - 69
Attorney, Agent or Firm:
YAMAMOTO, Shusaku et al. (JP)
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