Title:
PHARMACEUTICAL COMBINATION CONTAINING ANTI-PD-1-ANTI-VEGFA BISPECIFIC ANTIBODY, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/188832
Kind Code:
A1
Abstract:
The present invention relates to the field of tumor treatment and immunology biology. Provided are a pharmaceutical combination containing an anti-PD-1-anti-VEGFA bispecific antibody, and the use thereof. Specifically, the pharmaceutical combination comprises at least one bispecific antibody and at least one PARP inhibitor, wherein the bispecific antibody comprises a first protein functional region for targeting PD-1 and a second protein functional region for targeting VEGFA; and according to the EU numbering system, the heavy chain constant region of an immunoglobulin contained in the bispecific antibody is mutated at two sites, i.e. site 234 and site 235, and after mutation, the affinity constant of the bispecific antibody to FcγRI, FcγRIIa, FcγRIIIa and/or C1q is reduced compared with the affinity constant of the bispecific antibody thereto before mutation. The combined administration of the PARPi and the bispecific antibody has a significantly better therapeutic effect on tumors than the individual use of the PARPi or the bispecific antibody; and the present invention has good application prospects.
Inventors:
WANG ZHONGMIN (CN)
LI BAIYONG (CN)
XIA YU (CN)
LI BAIYONG (CN)
XIA YU (CN)
Application Number:
PCT/CN2022/080107
Publication Date:
September 15, 2022
Filing Date:
March 10, 2022
Export Citation:
Assignee:
AKESO BIOPHARMA INC (CN)
International Classes:
C07K16/46; A61K39/395; A61P35/00; C07K16/30
Domestic Patent References:
| WO2019152642A1 | 2019-08-08 |
Foreign References:
| CN112830972A | 2021-05-25 | |||
| CN109053895A | 2018-12-21 | |||
| CN112300286A | 2021-02-02 | |||
| CN110831580A | 2020-02-21 | |||
| US5747654A | 1998-05-05 | |||
| US4816567A | 1989-03-28 | |||
| CN1259962A | 2000-07-12 | |||
| CN106967172A | 2017-07-21 |
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JONES ET AL., NATURE, vol. 321, 1986, pages 522 - 525
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ACIERNO 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 - 46, XP022310713, DOI: 10.1016/j.jmb.2007.09.005
GHONIM MOHAMED A, TARHUNI ABDELMETALAB, LUU HANH, DEAN MATTHEW, AL‐KHAMI AMIR, OCHOA AUGUSTO, BOULARES HAMID: "Low Doses of PARP Inhibitors As A novel Therapeutic Approach to Enhance The Anti‐Cancer Immunotherapy of PD‐1 Immune Checkpoint Blockade", THE FASEB JOURNAL, FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY, US, vol. 33, no. S1, 1 April 2019 (2019-04-01), US, pages 680.15, XP009539485, ISSN: 0892-6638, DOI: 10.1096/fasebj.2019.33.1_supplement.680.15
MA LI, CHINESE JOURNAL OF BIRTH HEALTH AND HEREDITY, vol. 24, no. 5, 2016, pages 146 - 148
ROSKOSKI R JR. ET AL., CRIT REV ONCOL HEMATOL, vol. 62, no. 3, 2007, pages 179 - 213
TAKAHASHI T ET AL., ONCOGENE, vol. 18, no. 13, 1999, pages 2221 - 2230
DONG HONGCHAO ET AL., JOURNAL OF MODERN ONCOLOGY, vol. 22, no. 9, September 2014 (2014-09-01), pages 2231 - 3
HOMET M. B.PARISI G. ET AL.: "Anti-PD-1 Therapy in Melanoma", SEMIN ONCOL., vol. 42, no. 3, 2015, pages 466 - 473
HELD S.A.HEINE A. ET AL.: "Advances in immunology of biliary muscular tissue CML", CURR. CANCER DRUG TARGETS, vol. 13, no. 7, 2013, pages 768 - 74
JOYCE F. LIU ET AL., JAMA ONCOL., vol. 5, no. 12, 2019, pages 1731 - 1738
MANEGOLD C ET AL., J THORAC ONCOL., vol. 12, no. 2, February 2017 (2017-02-01), pages 194 - 207
DUDEK AZ ET AL., J CLIN ONCOL., vol. 36, 2018
STEIN S ET AL., J CLIN ONCOL, vol. 36, 2018
BENDELL JC ET AL., AMERICAN SOCIETY OF CLINICAL ONCOLOGY; MAY 29-JUNE 2, 2015; CHICAGO, IL, 2015
HOCHSTER HS ET AL., AMERICAN SOCIETY OF CLINICAL ONCOLOGY GASTROINTESTINAL CANCERS SYMPOSIUM; JANUARY 19-21, 2017; SAN FRANCISCO, CA, 2017
YUKINORI OZAKI ET AL.: "AACR", CANCER RES, vol. 80, no. 4, 2020
SCHERPEREEL A ET AL., LANCET ONCOL., vol. 20, no. 2, 2019, pages 1109 - 1123
KRISHNANSU S. ET AL., N ENGL J MED, vol. 370, 2014, pages 734 - 743
ANTONARAKIS ES ET AL., J CLIN ONCOL., vol. 38, no. 5, 10 February 2020 (2020-02-10), pages 395 - 405
JOAQUIM BELLMUNT ET AL., N ENGL J MED, vol. 376, 2017, pages 1015 - 1026
KATO K ET AL., LANCET ONCOL, vol. 20, no. 11, 2019, pages 1506 - 17
LORD CJASHWORTH A, SCIENCE, vol. 355, no. 6330, 2017, pages 1152 - 1158
TURNER NC., N ENGL J MED., vol. 377, no. 25, 2017, pages 2490 - 2492
J. MATEO ET AL., ANN ONCOL., vol. 30, no. 9, 1 September 2019 (2019-09-01), pages 1437 - 1447
MIRZA MR ET AL., N ENGL J MED, vol. 375, no. 22, 2016, pages 2154 - 2164
MULLER DKONTERMANN RE: "Bispecific antibodies for cancer immunotherapy: current perspectives", BIODRUGS, vol. 24, 2010, pages 89 - 98, XP009164507, DOI: 10.2165/11530960-000000000-00000
COLOMA M. J.MORRISON S. L.: "Design and production of novel tetravalent bispecific antibodies", NAT BIOTECHNOL., vol. 15, 1997, pages 159 - 163, XP000647731, DOI: 10.1038/nbt0297-159
MILLER B. R.DEMAREST S. J. ET AL., PROTEIN ENG DES SEL, vol. 23, 2010, pages 549 - 57
FITZGERALD JLUGOVSKOY A, MABS, vol. 3, 2011, pages 299 - 309
MATEO J ET AL., ANN ONCOL., vol. 30, no. 9, 2019, pages 1437 - 1447
JIAO S ET AL., CLIN CANCER RES., vol. 23, no. 14, 2017, pages 3711 - 3720
RAJAGOPAL ET AL., PROT. ENGIN., vol. 10, 1997, pages 1453 - 1459
REITER ET AL., NAT. BIOTECHNOL., vol. 14, 1996, pages 1239 - 1245
REITER ET AL., PROTEIN ENGINEERING, vol. 8, 1995, pages 1323 - 1331
WEBBER ET AL., MOLECULAR IMMUNOLOGY, vol. 32, 1995, pages 249 - 258
REITER ET AL., IMMUNITY, vol. 2, 1995, pages 281 - 287
REITER ET AL., JBC, vol. 269, 1994, pages 18327 - 18331
REITER ET AL., INTER. J. OF CANCER, vol. 58, 1994, pages 142 - 149
REITER ET AL., CANCER RES., vol. 54, 1994, pages 2714 - 2718
CHOTHIALESK, J. MOL. BIOL., vol. 196, 1987, pages 901 - 3242
EHRENMANN, FRANCOISQUENTIN KAASMARIE-PAULE LEFRANC: "IMGT/3Dstructure-DB and IMGT/DomainGapAlign: a database and a tool for immunoglobulins or antibodies, T cell receptors, MHC, IgSF and MhcSF.", NUCLEIC ACIDS RESEARCH, vol. 38, 2009, pages D301 - D307, XP055247165, DOI: 10.1093/nar/gkp946
CHOTHIA ET AL., NATURE, vol. 341, 1989, pages 544 - 546
"Fundamental Immunology", 1989, RAVEN PRESS
BIRD ET AL., SCIENCE, vol. 242, 1988, pages 423 - 426
HUSTON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 5879 - 5883
HOLLIGER P. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 6444 - 6448
ALFTHAN ET AL., PROTEIN ENG, vol. 8, 1995, pages 725 - 731
CHOI ET AL., EUR. J. IMMUNOL., vol. 31, 2001, pages 94 - 106
HU ET AL., CANCER RES., vol. 56, 1996, pages 3055 - 3061
KIPRIYANOV ET AL., J. MOL. BIOL., vol. 293, 1999, pages 41 - 56
ROOVERS ET AL., CANCER IMMUNOL, 2001
POLJAK R.J. ET AL., STRUCTURE, vol. 2, 1994, pages 1121 - 1123
KOHLER ET AL., NATURE, vol. 256, 1975, pages 495
MORRISON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 81, 1984, pages 6851 - 6855
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", METHODS IN MOLECULAR BIOLOGY, vol. 66, 1996
"Remington's Pharmaceutical Sciences", 1995, MACK PUBLISHING COMPANY
ACIERNO 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 - 46, XP022310713, DOI: 10.1016/j.jmb.2007.09.005
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