Title:
4-1BB BINDING PROTEIN AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/002063
Kind Code:
A1
Abstract:
The present invention relates to a 4-1BB binding protein and an application thereof. The 4-1BB binding protein comprises a heavy chain variable region. The heavy chain variable region contains HCDR1, HCDR2 and HCDR3. The HCDR1 contains sequences shown in SEQ ID NO: 15 or variant 1 thereof or SEQ ID NO: 16. The HCDR2 contains sequences selected from sequences as shown in SEQ ID NO: 60 or variant 2 thereof, or SEQ ID NO: 50 or variant 4 thereof. The HCDR3 comprises sequences as shown in SEQ ID NO: 103 or variant 3 thereof, SEQ ID NO: 333 or variant 5, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 116, SEQ ID NO: 326, SEQ ID NO: 331, SEQ ID NO: 334 or SEQ ID NO: 96. The 4-1BB binding protein is a fully human antibody and has the activity of binding to human 4-1BB and cynomolgus 4-1BB. The size of some 4-1BB binding protein is only half of the size of a traditional IgG antibody, and the 4-1BB binding protein is used well for bispecific antibodies.
Inventors:
SHI LEI (CN)
HUANG BING (CN)
HE YUN (CN)
GAN XIN (CN)
CHEN FEI (CN)
ZHAO JIANXUN (CN)
XIANG BO (CN)
HUANG BING (CN)
HE YUN (CN)
GAN XIN (CN)
CHEN FEI (CN)
ZHAO JIANXUN (CN)
XIANG BO (CN)
Application Number:
PCT/CN2021/103158
Publication Date:
January 06, 2022
Filing Date:
June 29, 2021
Export Citation:
Assignee:
HARBOUR BIOMED SHANGHAI CO LTD (CN)
International Classes:
C07K16/28; A61P35/00; C12N15/13
Domestic Patent References:
| WO2018134787A2 | 2018-07-26 | |||
| WO2019092451A1 | 2019-05-16 | |||
| WO2002085945A2 | 2002-10-31 | |||
| WO2015103072A1 | 2015-07-09 |
Foreign References:
| CN109651507A | 2019-04-19 | |||
| CN110325209A | 2019-10-11 | |||
| US20190031765A1 | 2019-01-31 | |||
| US10239949B2 | 2019-03-26 | |||
| CN202010619500A | 2020-06-30 | |||
| CN201910944996A | 2019-09-30 |
Other References:
CHEM, vol. 17, pages 114 - 124
BERKOW ET AL.: "The Merck Manual of Medical Information and", 2000, MERCK & CO. INC
EBADI, CRC DESK REFERENCE OF CLINICAL PHARMACOLOGY, 1998
J. BIOL. CHEM, vol. 243, 1968, pages 3558
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1991, NATIONAL INSTITUTES OF HEALTH (U.S.
J MOL BIOL, vol. 273, 1997, pages 927 - 48
D. ZHANG ET AL.: "found that the introduction of an E345R mutation at site E345 in the Fc of human IgG was effective in increasing the activation of agonistic OX40 antibodies", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, 2016, pages 27134 - 27146
BERTRAM EMLAU PWATTS TH: "Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection", JOURNAL OF IMMUNOLOGY, vol. 168, 2002, pages 3777 - 85, XP009105539
KAWALEKAR OUO'CONNOR RSFRAIETTA JA ET AL.: "Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.", IMMUNITY, vol. 44, 2016, pages 380 - 90, XP029428484, DOI: 10.1016/j.immuni.2016.01.021
YE ZHELLSTROM IHAYDEN-LEDBETTER MDAHLIN ALEDBETTER JAHELLSTROM KE: "Gene therapy for cancer using single-chain Fv fragments specific for 4-1BB", NATURE MEDICINE, vol. 8, 2002, pages 343 - 8, XP002316896, DOI: 10.1038/nm0402-343
ZHANG HKNUTSON KLHELLSTROM KEDISIS MLHELLSTROM I: "Antitumor efficacy of CD 137 ligation is maximized by the use of a CD137 single-chain Fv-expressing whole-cell tumor vaccine compared with CD137-specific monoclonal antibody infusion", MOLECULAR CANCER THERAPEUTICS, vol. 5, 2006, pages 149 - 55, XP055391958, DOI: 10.1158/1535-7163.MCT-05-0206
YANG YYANG SYE Z ET AL.: "Tumor cells expressing anti-CD137 scFv induce a tumor-destructive environment", CANCER RESEARCH, vol. 67, 2007, pages 2339 - 44, XP055851794, DOI: 10.1158/0008-5472.CAN-06-3593
MARTINET ODIVINO CMZANG Y ET AL.: "T cell activation with systemic agonistic antibody versus local 4- 1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer", GENE THERAPY, vol. 9, 2002, pages 786 - 92, XP037772200, DOI: 10.1038/sj.gt.3301687
BERKOW ET AL.: "The Merck Manual of Medical Information and", 2000, MERCK & CO. INC
EBADI, CRC DESK REFERENCE OF CLINICAL PHARMACOLOGY, 1998
J. BIOL. CHEM, vol. 243, 1968, pages 3558
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1991, NATIONAL INSTITUTES OF HEALTH (U.S.
J MOL BIOL, vol. 273, 1997, pages 927 - 48
D. ZHANG ET AL.: "found that the introduction of an E345R mutation at site E345 in the Fc of human IgG was effective in increasing the activation of agonistic OX40 antibodies", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, 2016, pages 27134 - 27146
BERTRAM EMLAU PWATTS TH: "Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection", JOURNAL OF IMMUNOLOGY, vol. 168, 2002, pages 3777 - 85, XP009105539
KAWALEKAR OUO'CONNOR RSFRAIETTA JA ET AL.: "Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.", IMMUNITY, vol. 44, 2016, pages 380 - 90, XP029428484, DOI: 10.1016/j.immuni.2016.01.021
YE ZHELLSTROM IHAYDEN-LEDBETTER MDAHLIN ALEDBETTER JAHELLSTROM KE: "Gene therapy for cancer using single-chain Fv fragments specific for 4-1BB", NATURE MEDICINE, vol. 8, 2002, pages 343 - 8, XP002316896, DOI: 10.1038/nm0402-343
ZHANG HKNUTSON KLHELLSTROM KEDISIS MLHELLSTROM I: "Antitumor efficacy of CD 137 ligation is maximized by the use of a CD137 single-chain Fv-expressing whole-cell tumor vaccine compared with CD137-specific monoclonal antibody infusion", MOLECULAR CANCER THERAPEUTICS, vol. 5, 2006, pages 149 - 55, XP055391958, DOI: 10.1158/1535-7163.MCT-05-0206
YANG YYANG SYE Z ET AL.: "Tumor cells expressing anti-CD137 scFv induce a tumor-destructive environment", CANCER RESEARCH, vol. 67, 2007, pages 2339 - 44, XP055851794, DOI: 10.1158/0008-5472.CAN-06-3593
MARTINET ODIVINO CMZANG Y ET AL.: "T cell activation with systemic agonistic antibody versus local 4- 1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer", GENE THERAPY, vol. 9, 2002, pages 786 - 92, XP037772200, DOI: 10.1038/sj.gt.3301687
Attorney, Agent or Firm:
SHANGHAI BESHINING LAW OFFICE (CN)
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