Bispecific antibodies against CD9 and CD7
The present invention relates to multispecific antibodies against a novel targets' combination of CD7 and CD9, and their use in the treatment of cancer and infectious diseases.
1 . An antibody which comprises a first antigen-binding portion binding CD7 and a second antigen-binding portion binding CD9, wherein the first antigen-binding portion binding CD7 comprises a first heavy chain variable region and a first light chain variable region, wherein the second antigen-binding portion binding CD9 comprises a second heavy chain variable region and a second light chain variable region, and wherein:
a. the first heavy chain variable region comprises a CDR-H1 comprising SEQ ID NO: 3, a CDR-H2 comprising SEQ ID NO: 4 and a CDR-H3 comprising SEQ ID NO: 5; and
b. the first light chain variable region comprises a CDR-L1 comprising SEQ ID NO: 6, a CDR-L2 comprising SEQ ID NO: 7 and a CDR-L3 comprising SEQ ID NO: 8; and
c. the second heavy chain variable region comprises a CDR-H1 comprising SEQ ID NO: 9, a CDR-H2 comprising SEQ ID NO: 10 and a CDR-H3 comprising SEQ ID NO: 11; and
d. the second light chain variable region comprises a CDR-L1 comprising SEQ ID NO: 12, a CDR-L2 comprising SEQ ID NO: 13 and a CDR-L3 comprising SEQ ID NO: 14.
2 . The antibody according to claim 1 , wherein each of the antigen-binding portions is a monoclonal antigen-binding portion.
3 . The antibody according to claim 1 , wherein each of the antigen-binding portions is independently selected from a Fab, a Fab′, or a scFv.
4 . The antibody according to claim 1 , wherein the antigen-binding portions are the antigen-binding portions of an IgG.
5 . The antibody according to claim 1 , wherein the antibody comprises a heavy chain constant region selected from an IgG1, an IgG2, an IgG3 or an IgG4 isotype, or a variant thereof.
6 . The antibody according to claim 1 , wherein the antibody further comprises at least an additional antigen-binding portion.
7 . The antibody according to claim 6 , wherein the additional antigen-binding portion increases the half-life of the antibody.
8 . The antibody according to claim 7 , wherein the additional antigen-binding portion binds albumin.
9 . The antibody according to claim 1 , wherein:
a. the first heavy chain variable region comprises SEQ ID NO: 15 and the first light chain variable region comprises SEQ ID NO: 17; and the second heavy chain variable region comprises SEQ ID NO: 19 and second light chain variable region comprises SEQ ID NO: 21;
or
b. the first heavy chain variable region is encoded by a nucleotide sequence comprising SEQ ID NO: 16 and the first light chain variable region is encoded by a nucleotide sequence comprising SEQ ID NO: 18; and the second heavy chain variable region is encoded by a nucleotide sequence comprising SEQ ID NO: 20 and second light chain variable region is encoded by a nucleotide sequence comprising SEQ ID NO: 22.
10 . A pharmaceutical composition comprising the antibody according to claim 1 and one or more pharmaceutically acceptable excipients.
11 . A method of treating a subject afflicted with cancer, an infectious disease, or combinations thereof comprising administering to the subject a pharmaceutically effective amount of the antibody according to claim 1 or a pharmaceutical composition comprising the antibody and one or more pharmaceutically acceptable excipients.
12 . The method according to claim 11 , wherein the antibody or the composition is administered concomitantly or sequentially to one or more additional cancer therapies.
13 . The method according to claim 11 , wherein the antibody promotes NK cell activity.
14 . The method according to claim 11 , wherein the subject is afflicted with cancer.
15 . The method according to claim 11 , wherein the pharmaceutical composition promotes NK cell activity.