Title:
COMPOSITION FOR PREVENTING OR TREATING CANCER COMPRISING NOVEL BISPECIFIC FUSION ANTIBODY AS ACTIVE INGREDIENT
Document Type and Number:
WIPO Patent Application WO/2023/153756
Kind Code:
A1
Abstract:
The present invention relates to: an anti-CD20 antibody in a novel form in which a TNFα mutant is bound to the Fc region of the antibody; and a pharmaceutical composition for preventing or treating cancer, the composition comprising the anti-CD20 antibody. According to the present invention, the TNFα mutant that binds to a TNF receptor but does not generate a signal is bound to the anti-CD20 antibody to simultaneously induce an apoptosis mechanism by means of TNFR1 and a unique apoptosis mechanism through binding to CD20, thus increasing the rate of cancer cell apoptosis due to the antibody, and the antibody acts as a competitive inhibitor against normal TNFα, and thus can be effectively used as an efficient therapeutic antibody for controlling excessive inflammatory response.
Inventors:
KIM JOO YOUNG (KR)
KIM JEONG RYEOL (KR)
LEE DONG HYUK (KR)
KIM JEONG RYEOL (KR)
LEE DONG HYUK (KR)
Application Number:
PCT/KR2023/001703
Publication Date:
August 17, 2023
Filing Date:
February 07, 2023
Export Citation:
Assignee:
UNIV YONSEI IACF (KR)
International Classes:
C07K16/28; A61K39/00; A61P35/00; C07K14/525
Foreign References:
| KR20040086383A | 2004-10-08 |
Other References:
DOMAGALA ANTONI, FIDYT KLAUDYNA, BOBROWICZ MALGORZATA, STACHURA JOANNA, SZCZYGIEL KACPER, FIRCZUK MALGORZATA: "Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 19, no. 8, 1 August 2018 (2018-08-01), pages 2256, XP093084199, DOI: 10.3390/ijms19082256
ULLIO CHIARA, CASAS JOSEFINA, BRUNK ULF T., SALA GIUSEPPINA, FABRIÀS GEMMA, GHIDONI RICCARDO, BONELLI GABRIELLA, BACCINO FRANCESCO: "Sphingosine mediates TNFα-induced lysosomal membrane permeabilization and ensuing programmed cell death in hepatoma cells", JOURNAL OF LIPID RESEARCH, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, INC., US, vol. 53, no. 6, 1 June 2012 (2012-06-01), US , pages 1134 - 1143, XP093084201, ISSN: 0022-2275, DOI: 10.1194/jlr.M022384
SHIBATA HIROKO, YOSHIOKA YASUO, OHKAWA AKIKO, MINOWA KYOKO, MUKAI YOHEI, ABE YASUHIRO, TANIAI MADOKA, NOMURA TETSUYA, KAYAMURO HIR: "Creation and X-ray Structure Analysis of the Tumor Necrosis Factor Receptor-1-selective Mutant of a Tumor Necrosis Factor-α Antagonist", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 283, no. 2, 1 January 2008 (2008-01-01), US , pages 998 - 1007, XP093084204, ISSN: 0021-9258, DOI: 10.1074/jbc.M707933200
KHAM R. TRINH, ALEX VASUTHASAWAT, KRISTOPHER K. STEWARD, REIKO E. YAMADA, JOHN M. TIMMERMAN, SHERIE L. MORRISON: "Anti-CD20-Interferon-β Fusion Protein Therapy of Murine B-Cell Lymphomas :", JOURNAL OF IMMUNOTHERAPY, LIPPINCOTT WILLIAMS & WILKINS, US, vol. 36, no. 5, 1 June 2013 (2013-06-01), US , pages 305 - 318, XP055563365, ISSN: 1524-9557, DOI: 10.1097/CJI.0b013e3182993eb9
ALDUAIJ WALEED, IVANOV ANDREI, HONEYCHURCH JAMIE, CHEADLE ELEANOR J., POTLURI SANDEEP, LIM SEAN H., SHIMADA KAZUYUKI, CHAN CLAUDE : "Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 117, no. 17, 28 April 2011 (2011-04-28), US , pages 4519 - 4529, XP093084198, ISSN: 0006-4971, DOI: 10.1182/blood-2010-07-296913
"Master's thesis", 9 February 2022, DEPARTMENT OF MEDICAL SCIENCE, THE GRADUATE SCHOOL OF YONSEI UNIVERSITY, Korea, article KIM, J. R.: "Anti-CD20 / TNFR1 bispecific and fusion antibodies for improving treatment of B cell Non-Hodgkin’s lymphoma", pages: 1 - 33, XP009548679
KIM JEONG RYEOL, LEE DONGHYUK, KIM YERIM, KIM JOO YOUNG: "CD20/TNFR1 dual-targeting antibody enhances lysosome rupture-mediated cell death in B cell lymphoma", CANCER IMMUNOLOGY IMMUNOTHERAPY, SPRINGER, BERLIN/HEIDELBERG, vol. 72, no. 6, 1 June 2023 (2023-06-01), Berlin/Heidelberg , pages 1567 - 1580, XP093084211, ISSN: 0340-7004, DOI: 10.1007/s00262-022-03344-9
"Mid-career researcher support project, final report", 1 March 2020, YONSEI UNIVERSITY, Korea, article KIM, JU YOUNG: "A Study on the Mechanism of B-cell Apoptosis Induced by Only CD20 Protein Binding of Obinutuzumab", pages: 1 - 31, XP009548685
ULLIO CHIARA, CASAS JOSEFINA, BRUNK ULF T., SALA GIUSEPPINA, FABRIÀS GEMMA, GHIDONI RICCARDO, BONELLI GABRIELLA, BACCINO FRANCESCO: "Sphingosine mediates TNFα-induced lysosomal membrane permeabilization and ensuing programmed cell death in hepatoma cells", JOURNAL OF LIPID RESEARCH, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, INC., US, vol. 53, no. 6, 1 June 2012 (2012-06-01), US , pages 1134 - 1143, XP093084201, ISSN: 0022-2275, DOI: 10.1194/jlr.M022384
SHIBATA HIROKO, YOSHIOKA YASUO, OHKAWA AKIKO, MINOWA KYOKO, MUKAI YOHEI, ABE YASUHIRO, TANIAI MADOKA, NOMURA TETSUYA, KAYAMURO HIR: "Creation and X-ray Structure Analysis of the Tumor Necrosis Factor Receptor-1-selective Mutant of a Tumor Necrosis Factor-α Antagonist", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 283, no. 2, 1 January 2008 (2008-01-01), US , pages 998 - 1007, XP093084204, ISSN: 0021-9258, DOI: 10.1074/jbc.M707933200
KHAM R. TRINH, ALEX VASUTHASAWAT, KRISTOPHER K. STEWARD, REIKO E. YAMADA, JOHN M. TIMMERMAN, SHERIE L. MORRISON: "Anti-CD20-Interferon-β Fusion Protein Therapy of Murine B-Cell Lymphomas :", JOURNAL OF IMMUNOTHERAPY, LIPPINCOTT WILLIAMS & WILKINS, US, vol. 36, no. 5, 1 June 2013 (2013-06-01), US , pages 305 - 318, XP055563365, ISSN: 1524-9557, DOI: 10.1097/CJI.0b013e3182993eb9
ALDUAIJ WALEED, IVANOV ANDREI, HONEYCHURCH JAMIE, CHEADLE ELEANOR J., POTLURI SANDEEP, LIM SEAN H., SHIMADA KAZUYUKI, CHAN CLAUDE : "Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 117, no. 17, 28 April 2011 (2011-04-28), US , pages 4519 - 4529, XP093084198, ISSN: 0006-4971, DOI: 10.1182/blood-2010-07-296913
"Master's thesis", 9 February 2022, DEPARTMENT OF MEDICAL SCIENCE, THE GRADUATE SCHOOL OF YONSEI UNIVERSITY, Korea, article KIM, J. R.: "Anti-CD20 / TNFR1 bispecific and fusion antibodies for improving treatment of B cell Non-Hodgkin’s lymphoma", pages: 1 - 33, XP009548679
KIM JEONG RYEOL, LEE DONGHYUK, KIM YERIM, KIM JOO YOUNG: "CD20/TNFR1 dual-targeting antibody enhances lysosome rupture-mediated cell death in B cell lymphoma", CANCER IMMUNOLOGY IMMUNOTHERAPY, SPRINGER, BERLIN/HEIDELBERG, vol. 72, no. 6, 1 June 2023 (2023-06-01), Berlin/Heidelberg , pages 1567 - 1580, XP093084211, ISSN: 0340-7004, DOI: 10.1007/s00262-022-03344-9
"Mid-career researcher support project, final report", 1 March 2020, YONSEI UNIVERSITY, Korea, article KIM, JU YOUNG: "A Study on the Mechanism of B-cell Apoptosis Induced by Only CD20 Protein Binding of Obinutuzumab", pages: 1 - 31, XP009548685
Attorney, Agent or Firm:
PADO IP LAW PLLC (KR)
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