Anti-CD3E/BCMA bispecific antibody and use thereof
A bispecific antibody, which comprises an antigen-binding portion against human CD3E and/or an antigen-binding portion against human BCMA. Additionally, provided are medical and biological uses of the bispecific antibody.
1 . A bispecific antibody comprising an antigen-binding portion against human CD3 epsilon (CD3E) and an antigen-binding portion against human B-cell maturation antigen (BCMA), wherein the antigen-binding portion against human CD3E comprises:
HCDR1 as set forth in SEQ ID NO:1,
HCDR2 as set forth in SEQ ID NO:2,
HCDR3 as set forth in SEQ ID NO:3,
LCDR1 as set forth in SEQ ID NO:4,
LCDR2 as set forth in SEQ ID NO:5, and
LCDR3 as set forth in SEQ ID NO:6;
and the antigen-binding portion against human BCMA comprises:
HCDR1 as set forth in SEQ ID NO:7,
HCDR2 as set forth in SEQ ID NO:8,
HCDR3 as set forth in SEQ ID NO:9,
LCDR1 as set forth in SEQ ID NO:4,
LCDR2 as set forth in SEQ ID NO:5, and
LCDR3 as set forth in SEQ ID NO:6;
wherein HCDRs and LCDRs are defined according to Kabat.
2 . The bispecific antibody of claim 1 , wherein the antigen-binding portion against human CD3E and the antigen-binding portion against human BCMA comprise the same light chain variable region.
3 . The bispecific antibody of claim 2 , wherein the antigen-binding portion against human CD3E and the antigen-binding portion against human BCMA comprise the same light chain.
4 . The bispecific antibody of claim 1 , wherein the bispecific antibody is an IgG1 antibody comprising two heavy chain constant regions having the same hinge region, and the amino acid sequence of the hinge region is shown in SEQ ID NO:15.
5 . The bispecific antibody of claim 1 , wherein the bispecific antibody is an IgG1 antibody comprising a first heavy chain constant region and a second heavy chain constant region, wherein
the first heavy chain constant region comprises a C at amino acid position 354 and a W at amino acid position 366, and the second heavy chain constant region comprises a C at amino acid position 349, an S at amino acid position 366, an A at amino acid position 368, and a V at amino acid position 407;
the amino acid position of the antibody constant region is determined according to EU numbering.
6 . The bispecific antibody of claim 1 , wherein the bispecific antibody is an IgG1 antibody comprising a first heavy chain constant region and a second heavy chain constant region, wherein the first and/or second heavy chain constant regions comprise an F at amino acid position 234, an E at amino acid position 235, and an S at amino acid position 331;
the amino acid position of the antibody constant region is determined according to EU numbering.
7 . The bispecific antibody of claim 1 , wherein the antigen-binding portion against human CD3E comprises a heavy chain variable region as set forth in SEQ ID NO:12 and a light chain variable region as set forth in SEQ ID NO:14.
8 . The bispecific antibody of claim 1 , wherein the antigen-binding portion against human BCMA comprises a heavy chain variable region as set forth in SEQ ID NO:10 and a light chain variable region as set forth in SEQ ID NO:14.
9 . The bispecific antibody of claim 1 , wherein the antigen-binding portion against human CD3E comprises a single chain antibody (scFv) or a Fab fragment.
10 . The bispecific antibody of claim 1 , wherein the antigen-binding portion against human BCMA comprises a single chain antibody (scFv) or a Fab fragment.
11 . The bispecific antibody of claim 1 , wherein the antigen-binding portion against human CD3E comprises a Fab fragment and the antigen-binding portion against human BCMA comprises a Fab fragment; or
the antigen-binding portion against human CD3E comprises a Fab fragment, and the antigen-binding portion against human BCMA comprises a single chain antibody (scFv); or
the antigen-binding portion against human CD3E comprises a single chain antibody (scFv), and the antigen-binding portion against human BCMA comprises a Fab fragment; or
the antigen-binding portion against human CD3E comprises a single chain antibody (scFv), and the antigen-binding portion against human BCMA comprises a single chain antibody (scFv).
12 . The bispecific antibody of claim 1 , wherein the antibody has a first arm and a second arm, wherein the first arm comprises an antigen-binding portion against human CD3E and the second arm comprises an antigen-binding portion against human BCMA:
the first arm comprises the amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO:12, the amino acid sequence of the heavy chain constant region as set forth in SEQ ID NO:19, the amino acid sequence of the light chain variable region as set forth in SEQ ID NO:14, and the amino acid sequence of the light chain constant region as set forth in SEQ ID NO:20;
the second arm comprises the amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO:10, the amino acid sequence of the heavy chain constant region as set forth in SEQ ID NO:18, the amino acid sequence of the light chain variable region as set forth in SEQ ID NO:14, and the amino acid sequence of the light chain constant region as set forth in SEQ ID NO:20.
13 . A pharmaceutical composition comprising the bispecific antibody of claim 1 .