JP-2022532991-A5 -

Dates

Publication Date

20230502

Application Date

20200423

Description

Experiments revealed high antitumor activity in the BCD-166-01-014 and BCD-166-02-01 products, while the BCD-166-01-01 product showed no significant antitumor activity. The results are shown in Figures 32 and 33. Non-limitingly, the present invention includes the following embodiments. [Aspect 1] An isolated monoclonal antibody or its antigen-binding fragment that specifically binds to GITR, (a)(i) The following groups: NYGMH (SEQ ID NO: 1) or YYWMY (SEQ ID NO: 12) CDR1 containing an amino acid sequence selected from; (ii) The following groups: VIWFDGSNKFYTDSVKG (Sequence No. 2) or AISWNGGRTYYAESMKG (Sequence No. 13) CDR2 containing an amino acid sequence selected from; (iii) The following groups: ELGGYYYDSSGRPYYYGMDV (Sequence ID 3) or NRYYSDPNYGMNL (Sequence ID 14) CDR3 containing an amino acid sequence selected from Heavy chain variable domains including, (b)(i) The following groups: RASQSIGSWLA (SEQ ID NO: 7) or TGTSTDIGTYKYIS (SEQ ID NO: 17) CDR1 containing an amino acid sequence selected from; (ii) The following groups: AASTLQR (SEQ ID NO: 8) or GVSHRPS (SEQ ID NO: 18) CDR2 containing an amino acid sequence selected from; (iii) The following groups: QQSHSHPLT (SEQ ID NO: 9) or SSYTSSGTVV (SEQ ID NO: 19) CDR3 containing an amino acid sequence selected from A monoclonal antibody or its antigen-binding fragment containing a light chain variable domain. [Aspect 2] The heavy chain variable domain, (i) The amino acid sequences of CDR1, CDR2, and CDR3, represented by the sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively (ii) A monoclonal antibody or antigen-binding fragment according to embodiment 1, comprising the CDR1, CDR2, and CDR3 amino acid sequences represented by the sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. [Appearance 3] The light chain variable domain is (i) CDR1, CDR2, and CDR3, each containing an amino acid sequence represented by the sequences of SEQ ID NOs. 7, 8, and 9, (ii) CDR1, CDR2, and CDR3 each containing the amino acid sequences represented by the sequences of SEQ ID NOs: 17, 18, and 19, respectively. including, A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Aspect 4] - The heavy chain variable domain, It comprises CDR1, CDR2, and CDR3, each containing an amino acid sequence represented by the sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; - The light chain variable domain includes CDR1, CDR2, and CDR3, each containing amino acid sequences represented by the sequences of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively. A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Aspect 5] - The heavy chain variable domains include CDR1, CDR2, and CDR3, each containing amino acid sequences represented by the sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively; - The light chain variable domain includes CDR1, CDR2, and CDR3, each containing amino acid sequences represented by the sequences of SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19, respectively. A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Pattern 6] The heavy chain variable domain, (i) an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 4; or (ii) an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 15 A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Appearance 7] (i) The heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 4, or (ii) The heavy chain variable domain contains the amino acid sequence of SEQ ID NO: 15. A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Patent 8] The light chain variable domain is (i) an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 10; or (ii) an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 20 A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Aspect 9] (i) The light chain variable domain contains the amino acid sequence of SEQ ID NO: 10; or (ii) The light chain variable domain contains the amino acid sequence of SEQ ID NO: 20 A monoclonal antibody or its antigen-binding fragment according to Embodiment 1. [Aspect 10] (i) - The heavy chain variable domain contains an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 4; - The light chain variable domain contains an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 10; or (ii) - The heavy chain variable domain contains an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 15; - The light chain variable domain contains an amino acid sequence that is at least 90% homologous to the amino acid sequence of SEQ ID NO: 20. A monoclon