Title:
MONOCLONAL ANTIBODY TARGETING SIRPα AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/020459
Kind Code:
A1
Abstract:
The present invention relates to the field of biomedicine, and specifically relates to a monoclonal antibody targeting SIRPα, and a preparation method therefor and the use thereof. The SIRPα antibody or the antigen-binding portion thereof prepared by the present invention has a high affinity for SIRPα and a low affinity for SIRPγ, which differ by two orders of magnitude. The SIRPα antibody or the antigen-binding portion thereof can efficiently block the binding of CD47 to SIRPα-V1, SIRPα-V2 and SIRPα-V8, thereby promoting the activation of macrophages, particularly enhancing the regulatory antibody-dependent cellular phagocytosis (ADCP) of a targeted tumor cell, bridging about innate and adaptive immune responses, and promoting the synergistic anti-cancer effect of the SIRPα antibody or the antigen-binding portion thereof and an immune checkpoint inhibitor PD-(L)1 monoclonal antibody. The antibody can be used for treating various cancers and microbial infectious diseases.
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Inventors:
HE LIZHEN (US)
YU PIN (CN)
XU FEIHU (CN)
ZHOU LIANG (CN)
GUO XUANCHENG (CN)
PENG YONGBO (CN)
CHEN HONG (CN)
WANG TONGYING (CN)
SUN HANDONG (CN)
LI CHEN (CN)
YU PIN (CN)
XU FEIHU (CN)
ZHOU LIANG (CN)
GUO XUANCHENG (CN)
PENG YONGBO (CN)
CHEN HONG (CN)
WANG TONGYING (CN)
SUN HANDONG (CN)
LI CHEN (CN)
Application Number:
PCT/CN2022/112677
Publication Date:
February 23, 2023
Filing Date:
August 16, 2022
Export Citation:
Assignee:
HANGZHOU JIUYUAN GENE ENG CO LTD (CN)
International Classes:
C07K16/28; A61K39/395; A61P35/00; C12N5/10; C12N15/13; C12N15/63
Domestic Patent References:
| WO2018057669A1 | 2018-03-29 | |||
| WO2018026600A1 | 2018-02-08 | |||
| WO2017178653A2 | 2017-10-19 | |||
| WO2017068164A1 | 2017-04-27 | |||
| WO2016063233A1 | 2016-04-28 | |||
| WO2016205042A1 | 2016-12-22 | |||
| WO2015138600A2 | 2015-09-17 | |||
| WO2013956352A1 | ||||
| WO2009091547A1 | 2009-07-23 | |||
| WO2009131453A1 | 2009-10-29 | |||
| WO2009046541A1 | 2009-04-16 |
Foreign References:
| CN112574310A | 2021-03-30 | |||
| CN110799536A | 2020-02-14 | |||
| CN106456749A | 2017-02-22 | |||
| CN111448210A | 2020-07-24 | |||
| US20180312587A1 | 2018-11-01 | |||
| CN110325549A | 2019-10-11 | |||
| CN111995682A | 2020-11-27 | |||
| CN201780023581A | 2017-04-14 |
Other References:
ADAMS ET AL.: "Signal-Regulatory Protein Is Selectively Expressed by Myeloid and Neuronal Cells", J IMMUNOL, vol. 161, 1998, pages 1853 - 1859
SEIFFERT ET AL.: "Signal-regulatory protein α (SIRP α ) but not SIRP β is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34+ CD38- hematopoietic cells", BLOOD, vol. 97, 2001, pages 2741 - 2749
VEILLETTE: "SIRP α -CD47 Immune Checkpoint Blockade in Anticancer Therapy", TREIMM, vol. 1449, 2017, pages 1 - 12
FUJIOKA ET AL.: "A Novel Membrane Glycoprotein, SHPS-1, That Binds the SH2-Domain-Containing Protein Tyrosine Phosphatase SHP-2 in Response to Mitogens and Cell Adhesion", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 12, 1996, pages 6887 - 6899, XP002072087
KHARITONENKOV ET AL.: "A family of proteins that inhibit signalling through tyrosine kinase receptors", NATURE, vol. 386, 1997, pages 181 - 186, XP002064043, DOI: 10.1038/386181a0
LIU X: "CD47 blockade triggers T cell-mediated destruction of immuno-genic tumors", NAT MED, vol. 21, 2015, pages 1209 - 1215
TSAIDISCHER ET AL.: "Self inhibition of phagocytosis: The affinity of 'marker of self' CD47 for SIRP α dictates potency of inhibition but only at low expression levels", BLOOD CELLS, MOLECULES, AND DISEASES, vol. 45, 2010, pages 67 - 74
LOGTENBERG MEW ET AL.: "The CD47-SIRP α Immune Checkpoint", IMMUNITY, vol. 52, 2020, pages 742 - 752
CHAO MPALIZADEH AATANG C ET AL.: "Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma", CELL, vol. 142, 2010, pages 699 - 713, XP002769488, DOI: 10.1016/j.cell.2010.07.044
ZHAO XW ET AL.: "CD47-signal regulatory protein- α (SIRP α ) interactions form a barrier for antibody-mediated tumor cell destruction", PNAS, vol. 108, 2011, pages 18342 - 18347, XP055232927, DOI: 10.1073/pnas.1106550108
FENG M.: "Phagocytosis Checkpoints as New Targets for Cancer Immunotherapy", NATURE REVIEWS CANCER, vol. 19, 2019, pages 568 - 586, XP036888518, DOI: 10.1038/s41568-019-0183-z
OLDENBORG, P.A., GRESHAM, H.D., AND LINDBERG, F.P: "CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis", J. EXP. MED., vol. 193, 2001, pages 855 - 862
WEISKOPF K ET AL.: "Cancer immunotherapy targeting the CD47/SIRP α axis", EUR J CANCER, vol. 76, 2017, pages 100 - 109
ADVANI R. ET AL.: "CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin' s Lymphoma", NEW ENG J MED, vol. 379, 2018, pages 1711 - 21, XP055730266, DOI: 10.1056/NEJMoa1807315
SALLMAN DA, MALKI MA, ASCH AS: "Tolerability and efficacy of the first-in-class nti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results", J CLIN ONCOL., vol. 38, 2020, pages 7507
TREFFERS ET AL.: "Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis", CELL REPORTS, vol. 23, 2018, pages 3946 - 3959
SIM ET AL.: "Discovery of high affinity, pan-allelic, and pan-mammalian reactive antibodies against the myeloid checkpoint receptor SIRP α", MABS, vol. 11, 2019, pages 1036 - 52, XP055921232, DOI: 10.1080/19420862.2019.1624123
BARCLAY AN. ET AL.: "The SIRP family of receptors and immune regulation", NATURE REVIEWS IMMUNOLOGY, vol. 6, 2006, pages 457 - 464, XP055252565, DOI: 10.1038/nri1859
HAYASHI ET AL.: "Positive Regulation of Phagocytosis by SIRP β and Its Signaling Mechanism in Macrophages", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 28, 2004, pages 29450 - 29460
SAKAMOTO ET AL.: "Anticancer efficacy of monotherapy with antibodies to SIRP α /SIRP 0 1 mediated by induction of antitumorigenic macrophages", PNAS, vol. 1, 2022, pages 119
BROOKE ET AL.: "Human Lymphocytes Interact Directly with CD47 through a Novel Member of the Signal Regulatory Protein (SIRP) Family", J IMMUNOL, vol. 173, 2004, pages 2562 - 2570, XP008138739
PICCIO, L.: "Adhesion of human T cells to antigen-presenting cells through SIRP β 2 CD47 interaction costimulates T-cell proliferation. ", BLOOD, vol. 105, 2005, pages 2421 - 2427, XP002525575, DOI: 10.1182/blood-2004-07-2823
DEHMANI: "SIRP γ -CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation", FRONT. IMMUNOL, vol. 12, 2021, pages 732530, XP055885944, DOI: 10.3389/fimmu.2021.732530
CHAMPIAT S. ET AL.: "Safety, pharmacokinetics, efficacy, and preliminary biomarker data of first-in-class BI 765063, a selective SIRP α inhibitor: Results of monotherapy dose escalation in phase 1 study in patients with advanced solid tumors", ASCO ANNUAL MEETING, 2021
KOTECKI N. ET AL.: "Phase I dose escalation study in patients (pts) with advanced solid tumours receiving first-in-class BI 765063, a selective signal-regulatory protein α (SIRP α ) inhibitor, in combination with ezabenlimab (BI 754091", ESMO 2021 CONGRESS POSTER
STRATI P. ET AL.: "Interim results from the first clinical study of CC-95251, an Anti-signal regulatory protein-alpha (SIRP α ) antibody, in combination with rituximab in patients with relapsed and/or refractory non-Hodgkin lymphoma (R/R NHL", BLOOD, vol. 138, 2021
VOETS ET AL.: "Functional characterization of the selective pan-allele anti-SIRP α antibody ADU-1805 that blocks the SIRP α -CD47 innate immune checkpoint", JOURNAL FOR, vol. 7, 2019, pages 340
ANDREJEVA ET AL.: "Novel SIRP α Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells", J IMMUNOL, 2021
KABAT, E.A. ET AL.: "Sequences of Proteins of Immunological Interest", 1991, U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES, pages: 91 - 3242
SEIFFERT ET AL.: "Signal-regulatory protein α (SIRP α ) but not SIRP β is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34+ CD38- hematopoietic cells", BLOOD, vol. 97, 2001, pages 2741 - 2749
VEILLETTE: "SIRP α -CD47 Immune Checkpoint Blockade in Anticancer Therapy", TREIMM, vol. 1449, 2017, pages 1 - 12
FUJIOKA ET AL.: "A Novel Membrane Glycoprotein, SHPS-1, That Binds the SH2-Domain-Containing Protein Tyrosine Phosphatase SHP-2 in Response to Mitogens and Cell Adhesion", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 12, 1996, pages 6887 - 6899, XP002072087
KHARITONENKOV ET AL.: "A family of proteins that inhibit signalling through tyrosine kinase receptors", NATURE, vol. 386, 1997, pages 181 - 186, XP002064043, DOI: 10.1038/386181a0
LIU X: "CD47 blockade triggers T cell-mediated destruction of immuno-genic tumors", NAT MED, vol. 21, 2015, pages 1209 - 1215
TSAIDISCHER ET AL.: "Self inhibition of phagocytosis: The affinity of 'marker of self' CD47 for SIRP α dictates potency of inhibition but only at low expression levels", BLOOD CELLS, MOLECULES, AND DISEASES, vol. 45, 2010, pages 67 - 74
LOGTENBERG MEW ET AL.: "The CD47-SIRP α Immune Checkpoint", IMMUNITY, vol. 52, 2020, pages 742 - 752
CHAO MPALIZADEH AATANG C ET AL.: "Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma", CELL, vol. 142, 2010, pages 699 - 713, XP002769488, DOI: 10.1016/j.cell.2010.07.044
ZHAO XW ET AL.: "CD47-signal regulatory protein- α (SIRP α ) interactions form a barrier for antibody-mediated tumor cell destruction", PNAS, vol. 108, 2011, pages 18342 - 18347, XP055232927, DOI: 10.1073/pnas.1106550108
FENG M.: "Phagocytosis Checkpoints as New Targets for Cancer Immunotherapy", NATURE REVIEWS CANCER, vol. 19, 2019, pages 568 - 586, XP036888518, DOI: 10.1038/s41568-019-0183-z
OLDENBORG, P.A., GRESHAM, H.D., AND LINDBERG, F.P: "CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis", J. EXP. MED., vol. 193, 2001, pages 855 - 862
WEISKOPF K ET AL.: "Cancer immunotherapy targeting the CD47/SIRP α axis", EUR J CANCER, vol. 76, 2017, pages 100 - 109
ADVANI R. ET AL.: "CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin' s Lymphoma", NEW ENG J MED, vol. 379, 2018, pages 1711 - 21, XP055730266, DOI: 10.1056/NEJMoa1807315
SALLMAN DA, MALKI MA, ASCH AS: "Tolerability and efficacy of the first-in-class nti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results", J CLIN ONCOL., vol. 38, 2020, pages 7507
TREFFERS ET AL.: "Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis", CELL REPORTS, vol. 23, 2018, pages 3946 - 3959
SIM ET AL.: "Discovery of high affinity, pan-allelic, and pan-mammalian reactive antibodies against the myeloid checkpoint receptor SIRP α", MABS, vol. 11, 2019, pages 1036 - 52, XP055921232, DOI: 10.1080/19420862.2019.1624123
BARCLAY AN. ET AL.: "The SIRP family of receptors and immune regulation", NATURE REVIEWS IMMUNOLOGY, vol. 6, 2006, pages 457 - 464, XP055252565, DOI: 10.1038/nri1859
HAYASHI ET AL.: "Positive Regulation of Phagocytosis by SIRP β and Its Signaling Mechanism in Macrophages", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 28, 2004, pages 29450 - 29460
SAKAMOTO ET AL.: "Anticancer efficacy of monotherapy with antibodies to SIRP α /SIRP 0 1 mediated by induction of antitumorigenic macrophages", PNAS, vol. 1, 2022, pages 119
BROOKE ET AL.: "Human Lymphocytes Interact Directly with CD47 through a Novel Member of the Signal Regulatory Protein (SIRP) Family", J IMMUNOL, vol. 173, 2004, pages 2562 - 2570, XP008138739
PICCIO, L.: "Adhesion of human T cells to antigen-presenting cells through SIRP β 2 CD47 interaction costimulates T-cell proliferation. ", BLOOD, vol. 105, 2005, pages 2421 - 2427, XP002525575, DOI: 10.1182/blood-2004-07-2823
DEHMANI: "SIRP γ -CD47 Interaction Positively Regulates the Activation of Human T Cells in Situation of Chronic Stimulation", FRONT. IMMUNOL, vol. 12, 2021, pages 732530, XP055885944, DOI: 10.3389/fimmu.2021.732530
CHAMPIAT S. ET AL.: "Safety, pharmacokinetics, efficacy, and preliminary biomarker data of first-in-class BI 765063, a selective SIRP α inhibitor: Results of monotherapy dose escalation in phase 1 study in patients with advanced solid tumors", ASCO ANNUAL MEETING, 2021
KOTECKI N. ET AL.: "Phase I dose escalation study in patients (pts) with advanced solid tumours receiving first-in-class BI 765063, a selective signal-regulatory protein α (SIRP α ) inhibitor, in combination with ezabenlimab (BI 754091", ESMO 2021 CONGRESS POSTER
STRATI P. ET AL.: "Interim results from the first clinical study of CC-95251, an Anti-signal regulatory protein-alpha (SIRP α ) antibody, in combination with rituximab in patients with relapsed and/or refractory non-Hodgkin lymphoma (R/R NHL", BLOOD, vol. 138, 2021
VOETS ET AL.: "Functional characterization of the selective pan-allele anti-SIRP α antibody ADU-1805 that blocks the SIRP α -CD47 innate immune checkpoint", JOURNAL FOR, vol. 7, 2019, pages 340
ANDREJEVA ET AL.: "Novel SIRP α Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells", J IMMUNOL, 2021
KABAT, E.A. ET AL.: "Sequences of Proteins of Immunological Interest", 1991, U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES, pages: 91 - 3242
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