Title:
ANTIBODY MUTANT AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/031930
Kind Code:
A1
Abstract:
Provided is a mutant of an antibody or fragment thereof, characterized in that the antibody or fragment thereof contains a light-chain constant region, and according to the Kabat numbering system, the amino acid at position 166 is mutated to cysteine.
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Inventors:
MA NINGNING (CN)
WANG LIN (CN)
SONG CHUNYU (CN)
LI MINGYING (CN)
XUE SHIPING (CN)
LIU YONGXIANG (CN)
XU WEIWEI (CN)
ZHU LIFENG (CN)
WANG LIN (CN)
SONG CHUNYU (CN)
LI MINGYING (CN)
XUE SHIPING (CN)
LIU YONGXIANG (CN)
XU WEIWEI (CN)
ZHU LIFENG (CN)
Application Number:
PCT/CN2020/108434
Publication Date:
February 25, 2021
Filing Date:
August 11, 2020
Export Citation:
Assignee:
UNIV SHENYANG PHARMACEUTICAL (CN)
International Classes:
C07K16/18; A61K47/68; A61K51/10; C07K16/28; C07K16/30; C07K16/32
Foreign References:
| CN107108724A | 2017-08-29 | |||
| CN107108724A | 2017-08-29 | |||
| CN101065151A | 2007-10-31 |
Other References:
DATABASE PROTEIN 20 December 2018 (2018-12-20), "Chain A, Herceptin Fab (antibody) - light chain", XP055782495, retrieved from NCBI Database accession no. 1N8Z_A
MORITZ ET AL: "Assessment of disulfide and hinge modifications in monoclonal antibodies", ELECTROPHORESIS, vol. 38, 1 March 2017 (2017-03-01), pages 769 - 785, XP002772592, DOI: 10.1002/elps.201600425
DATABASE PROTEIN 5 October 2018 (2018-10-05), "Chain J, Fab fragment, light chain,", XP055782750, retrieved from NCBI Database accession no. 1BJ1_J
DATABASE PROTEIN 13 March 2019 (2019-03-13), "immunoglobulin heavy chain [Homo sapiens]", XP055782484, retrieved from NCBI Database accession no. QBK47431
DATABASE PROTEIN 22 October 2018 (2018-10-22), "Chain B, light chain of the Rituximab Fab fragment,light chain of the Rituximab Fab fragment", XP055782487, retrieved from NCBI Database accession no. 2OSL_B
DATABASE Protein 18 July 2017 (2017-07-18), . :: "herceptin heavy chain [synthetic construct]", XP055782481, retrieved from NCBI Database accession no. APZ76730
DATABASE Protein 18 July 2017 (2017-07-18), "herceptin light chain [synthetic construct]", XP055707308, retrieved from NCBI Database accession no. APZ76731
HANHUA HUANGJING-YU LAIJANET DODINGGUO LIULINGNA LIJOSELYN DEL ROSARIO: "Specifically Targeting Angiopoietin-2 Inhibits Angiogenesis, Tie2-Expressing Monocyte Infiltration, and Tumor Growth", CLIN CANCER RES, vol. 17, no. 5, 1 March 2011 (2011-03-01), pages 1001 - 1011, XP002663787, DOI: 10.1158/1078-0432.CCR-10-2317
DOPPALAPUDI VRHUANG JLIU D JIN PLIU BLI L: "Chemical generation cf bispecific antibodies", PROC NATL ACAD SCI USA., vol. 107, 2010, pages 22611 - 22616, XP055003821, DOI: 10.1073/pnas.1016478108
ALLEN, T. M.: "Ligand-targeted therapeutics in anticancer therapy", NAT. REV. CANCER, vol. 2, 2002, pages 750 - 763
HAMHLETT, K 1: "Effects of Drug Loading on the Antitumor Activity of a Monoclonal Antibody Drug Conjugate", CLIN. CANCER RES., vol. 10, 2004, pages 7063 - 7070
JUNUTULA J RBHAKTA SRAAB H ET AL.: "Rapid identifi cation of reactive cysteine residues for site-specific labeling of antibody-Fabs", J IMMUNOL METHODS, vol. 332, 2008, pages 41 - 52
JUNUTULA J RFLAGELLA K MGRAHAM R A ET AL.: "Engineered thiotrastuzumab- DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2-positive breast cancer", CLIN CANCER RES, vol. 16, 2010, pages 4769 - 4778, XP002727053, DOI: 10.1158/1078-0432.CCR-10-0987
JUNUTULA J RRAAB HCLARK S ET AL.: "Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index", NAT BIOTECHNOL, vol. 26, 2008, pages 925 - 932
KUNG SUTHERLAND M SWALTER R BJEFFREY S C ET AL.: "SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML", BLOOD, vol. 122, 2013, pages 1455 - 1463, XP055173229, DOI: 10.1182/blood-2013-03-491506
See also references of EP 4019544A4
MORITZ ET AL: "Assessment of disulfide and hinge modifications in monoclonal antibodies", ELECTROPHORESIS, vol. 38, 1 March 2017 (2017-03-01), pages 769 - 785, XP002772592, DOI: 10.1002/elps.201600425
DATABASE PROTEIN 5 October 2018 (2018-10-05), "Chain J, Fab fragment, light chain,", XP055782750, retrieved from NCBI Database accession no. 1BJ1_J
DATABASE PROTEIN 13 March 2019 (2019-03-13), "immunoglobulin heavy chain [Homo sapiens]", XP055782484, retrieved from NCBI Database accession no. QBK47431
DATABASE PROTEIN 22 October 2018 (2018-10-22), "Chain B, light chain of the Rituximab Fab fragment,light chain of the Rituximab Fab fragment", XP055782487, retrieved from NCBI Database accession no. 2OSL_B
DATABASE Protein 18 July 2017 (2017-07-18), . :: "herceptin heavy chain [synthetic construct]", XP055782481, retrieved from NCBI Database accession no. APZ76730
DATABASE Protein 18 July 2017 (2017-07-18), "herceptin light chain [synthetic construct]", XP055707308, retrieved from NCBI Database accession no. APZ76731
HANHUA HUANGJING-YU LAIJANET DODINGGUO LIULINGNA LIJOSELYN DEL ROSARIO: "Specifically Targeting Angiopoietin-2 Inhibits Angiogenesis, Tie2-Expressing Monocyte Infiltration, and Tumor Growth", CLIN CANCER RES, vol. 17, no. 5, 1 March 2011 (2011-03-01), pages 1001 - 1011, XP002663787, DOI: 10.1158/1078-0432.CCR-10-2317
DOPPALAPUDI VRHUANG JLIU D JIN PLIU BLI L: "Chemical generation cf bispecific antibodies", PROC NATL ACAD SCI USA., vol. 107, 2010, pages 22611 - 22616, XP055003821, DOI: 10.1073/pnas.1016478108
ALLEN, T. M.: "Ligand-targeted therapeutics in anticancer therapy", NAT. REV. CANCER, vol. 2, 2002, pages 750 - 763
HAMHLETT, K 1: "Effects of Drug Loading on the Antitumor Activity of a Monoclonal Antibody Drug Conjugate", CLIN. CANCER RES., vol. 10, 2004, pages 7063 - 7070
JUNUTULA J RBHAKTA SRAAB H ET AL.: "Rapid identifi cation of reactive cysteine residues for site-specific labeling of antibody-Fabs", J IMMUNOL METHODS, vol. 332, 2008, pages 41 - 52
JUNUTULA J RFLAGELLA K MGRAHAM R A ET AL.: "Engineered thiotrastuzumab- DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2-positive breast cancer", CLIN CANCER RES, vol. 16, 2010, pages 4769 - 4778, XP002727053, DOI: 10.1158/1078-0432.CCR-10-0987
JUNUTULA J RRAAB HCLARK S ET AL.: "Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index", NAT BIOTECHNOL, vol. 26, 2008, pages 925 - 932
KUNG SUTHERLAND M SWALTER R BJEFFREY S C ET AL.: "SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML", BLOOD, vol. 122, 2013, pages 1455 - 1463, XP055173229, DOI: 10.1182/blood-2013-03-491506
See also references of EP 4019544A4
Attorney, Agent or Firm:
CHINA SCIENCE PATENT & TRADEMARK AGENT LTD. (CN)
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