US 12,577,314 B2 · Anti-BCMA/anti-4-1BB bispecific antibodies and uses thereof

Abstract

An anti-B-cell maturation antigen (BCMA)/anti-4-1BB bispecific antibody or an antigen-binding fragment thereof, and use thereof, are provided. The bispecific antibody or an antigen-binding fragment thereof may have high binding affinity to both of a BCMA protein and a 4-1BB protein and may be effectively used to prevent or treat a disease related to BCMA, 4-1BB, or both thereof.

An anti-B-cell maturation antigen (BCMA)/anti-4-1BB bispecific antibody or an antigen-binding fragment thereof, comprising:

an anti-BCMA antibody or an antigen-binding fragment thereof;
and
an anti-4-1BB antibody or an antigen-binding fragment thereof,
wherein anti-B-cell maturation antigen (BCMA)/anti-4-1BB bispecific antibody or an antigen-binding fragment thereof is selected from the group consisting of:
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
12, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
16, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
20, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
24, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
27, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
31, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
12, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
16, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
20, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
54, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
27, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
31, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
12, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
16, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
20, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
55, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
27, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
31, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
12, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
16, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
20, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
56, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
27, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
31, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
12, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
16, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
20, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
57, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
27, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
31, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
12, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
16, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
20, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
58, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
27, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
31, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
25, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
32, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
59, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
32, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
60, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
32, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
25, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
63, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
25, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
64, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
61, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
63, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
61, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
64, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
62, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
63, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96;
and
a bispecific antibody comprising an anti BCMA antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
13, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
17, and a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
21, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
62, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
28, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
64, and an anti-4-1BB antibody or an antigen-binding fragment thereof comprising a CDR-H1 consisting of the amino acid sequence of SEQ ID NO:
81, a CDR-H2 consisting of the amino acid sequence of SEQ ID NO:
84, a CDR-H3 consisting of the amino acid sequence of SEQ ID NO:
88, a CDR-L1 consisting of the amino acid sequence of SEQ ID NO:
92, a CDR-L2 consisting of the amino acid sequence of SEQ ID NO:
94, and a CDR-L3 consisting of the amino acid sequence of SEQ ID NO:
96.

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Anti-BCMA/anti-4-1BB bispecific antibodies and uses thereof

Life of this patent

Anti-BCMA/anti-4-1BB bispecific antibodies and uses thereof

Life of this patent

Abstract

Claims11