US 2023/0416396 A1 · MULTISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND CD38 AND 4-1BB, AND USES THEREOF

Abstract

CD38 is expressed on malignant plasma cells. 4-1BB is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel multispecific antigen binding molecules (MABMs) that bind to both CD38 and 4-1BB, for example, to provide “signal 2” in order to enhance the activation of T cells in the presence of a “signal 1”, provided by a Tumor-associated antigen (TAA)×CD3 bispecific antibody or an allogeneic response provided by an antigen presenting cell. In certain embodiments, the multispecific antigen binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The multispecific antigen binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and/or therapeutically beneficial. For example, the multispecific antigen binding molecules of the invention are useful for the treatment of various cancers, including multiple myeloma, lymphoma, and leukemia.

Claims62

Dependent claims

A bispecific antigen-binding molecule comprising:

(a) a first antigen-binding arm comprising three complementarity determining regions (CDRs) of a heavy chain variable region (HCVR) and three CDRs of a LCVR, wherein the first antigen-binding arm binds specifically to CD38, wherein the first antigen-binding arm comprises three CDRs of a HCVR comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
2 and 40 and three CDRs of a LCVR comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
18 and 48;
and
(b) a second antigen-binding arm comprising a first antigen-binding region (R1) comprising three CDRs of a HCVR (R1-HCVR) and three CDRs of a LCVR (R1-LCVR);
and a second antigen-binding region (R2) comprising three CDRs of a HCVR (R2-HCVR) and three CDRs of a LCVR (R2-LCVR), wherein the second antigen-binding arm binds specifically to 4-1BB.

3 more elements

A bispecific antigen-binding molecule comprising a first antigen binding arm that binds specifically to CD38 and a second antigen-binding arm that binds specifically to 4-1BB, wherein:

(a) the first antigen binding arm comprises three CDRs of a HCVR comprising the amino acid sequence of SEQ ID NO:
40, and three CDRs of LCVR comprising the amino acid sequence of SEQ ID NO:
48;
and
(b) the second antigen-binding arm comprises:
(i) a first antigen-binding region (R1) comprising three CDRs of a HCVR (R1-HCVR) comprising the amino acid sequence of SEQ ID NO:
62, and three CDRs of a LCVR (R1-LCVR) comprising the amino acid sequence of SEQ ID NO:
48;
and
(ii) a second antigen-binding region (R2) comprising three CDRs of a HCVR (R2-HCVR) comprising the amino acid sequence of SEQ ID NO:
62, and three CDRs of a LCVR (R2-LCVR) comprising the amino acid sequence of SEQ ID NO:
48.

9 more elements

Dependencies are inferred from the claim text.

Multispecific antigen binding molecules that bind cd38 and 4-1bb, and uses thereof

Life of this patent

Multispecific antigen binding molecules that bind cd38 and 4-1bb, and uses thereof

Life of this patent

Abstract

Claims62