Title:
ANTI-CTLA4-ANTI-PD-1 BISPECIFIC ANTIBODY AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/023117
Kind Code:
A1
Abstract:
Provided are an anti-CTLA4-anti-PD-1 bispecific antibody and uses thereof. The bispecific antibody comprises: a first protein functional area targeting PD-1 and a second protein functional area targeting CTLA4, where, according to the EU numbering system, the constant region of an immunoglobulin heavy chain is mutated at any two loci or three loci of locus 234, locus 235, and locus 237, and after the mutation, the affinity constant of the bispecific antibody with FcγRIIIa and/or C1q is reduced compared to that before the mutation. The bispecific antibody is capable of specifically binding with CTLA4 and PD-1, disabling the immunosuppression of CTLA4 and PD-1 with respect to the body, and activating T lymphocytes, and is applicable in preventing, treating, or diagnosing a tumor or anemia.
Inventors:
XIA YU (CN)
WANG ZHONGMIN (CN)
ZHANG PENG (CN)
LI BAIYONG (CN)
WANG ZHONGMIN (CN)
ZHANG PENG (CN)
LI BAIYONG (CN)
Application Number:
PCT/CN2020/106309
Publication Date:
February 11, 2021
Filing Date:
July 31, 2020
Export Citation:
Assignee:
AKESO PHARMACEUTICALS INC (CN)
International Classes:
C07K16/46; A61K39/395; A61P7/06; A61P35/00; A61P35/02; C07K16/28; C12N15/13; C12N15/62; C12N15/63; G01N33/577; G01N33/68
Domestic Patent References:
| WO2018107058A1 | 2018-06-14 | |||
| WO2018227018A1 | 2018-12-13 | |||
| WO2008112407A1 | 2008-09-18 | |||
| WO2017148424A1 | 2017-09-08 |
Foreign References:
| CN106967172A | 2017-07-21 | |||
| CN102711810A | 2012-10-03 | |||
| CN103351434A | 2013-10-16 | |||
| CN109762068A | 2019-05-17 | |||
| US7612208B2 | 2009-11-03 | |||
| US7253286B2 | 2007-08-07 | |||
| US4816567A | 1989-03-28 | |||
| CN106967172A | 2017-07-21 |
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HOMET M. B.PARISI G. ET AL., SEMIN ONCOL., vol. 42, no. 3, 2015, pages 466 - 473
HELD SAHEINE A ET AL., CURR CANCER DRUG TARGETS., vol. 13, no. 7, 2013, pages 768 - 74
CHAVEZ, A.R. ET AL., ANN. N. Y. ACAD. SCI., vol. 1182, 2009, pages 14 - 27
DAFNE MULLERKONTERMANN R E., BIODRUGS, vol. 24, no. 2, 2010, pages 89 - 98
COLOMA MJMORRISON SL., NAT BIOTECHNOL., vol. 15, 1997, pages 159 - 163
MILLER BRDEMAREST SJ ET AL., PROTEIN ENG DES SEL, vol. 23, 2010, pages 549 - 57
FITZGERALD JLUGOVSKOY A., MABS, vol. 3, 2011, pages 299 - 309
HOGARTH PMPIETERSZ GA., NATURE REVIEWS DRUG DISCOVERY, vol. 11, no. 4, 2012, pages 311 - 331
HE JIE ET AL.: "Clinical Oncology", 2016, PEOPLE'S MEDICAL PUBLISHING HOUSE, pages: 230 - 237
HAN B ET AL., BR J CANCER, vol. 118, no. 5, 2018, pages 654 - 661
HAN B ET AL., JAMA ONCOL., vol. 4, no. 11, November 2018 (2018-11-01), pages 1569 - 1575
BARETTI M ET AL., PHARMACOL THER., vol. 189, 2018, pages 45 - 62
CHOTHIALESK, J. MOL. BIOL., vol. 196, 1987, pages 901 - 3242
CHOTHIA ET AL., NATURE, vol. 342, 1989, pages 878 - 883
KOHLER ET AL., NATURE, vol. 256, 1975, pages 495
JONES ET AL., NATURE, vol. 321, 1986, pages 522 - 525
REICHMANN ET AL., NATURE, vol. 332, 1988, pages 323 - 329
PRESTA, CURR. OP. STRUCT. BIOL., vol. 2, 1992, pages 593 - 596
CLARK: "Immunol", TODAY, vol. 21, 2000, pages 397 - 402
"Epitope Mapping Protocols in Methods in Molecular Biology", vol. 66, 1996
BRANCH P ET AL., CANCER RES, vol. 55, no. 11, 1995, pages 2304 - 2309
ACIERNOACIERNO ET AL.: "Affinity maturation increases the stability and plasticity of the Fv domain of anti-protein antibodies", J MOL BIOL., vol. 374, no. 1, 2007, pages 130 - 146, XP022310713, DOI: 10.1016/j.jmb.2007.09.005
EFREMOVA M ET AL., NAT COMMUN., vol. 9, no. 1, 2018, pages 32
ZHANG T ET AL., CANCER IMMUNOL IMMUNOTHER., vol. 67, no. 7, 2018, pages 1079 - 1090
DAHAN R ET AL., CANCER CELL, vol. 28, no. 3, 2015, pages 285 - 95
GUO ET AL., CANCER RES., vol. 71, no. 8, 2011, pages 2978 - 2987
Attorney, Agent or Firm:
CCPIT PATENT AND TRADEMARK LAW OFFICE (CN)
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