US 2022/0089734 A1 · Activatable Anti-CTLA-4 Antibodies and Uses Thereof

Abstract

Provided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain. Such activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor-specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor.

Claims27

Dependent claims

An activatable anti-human CTLA-4 antibody comprising a heavy chain and a light chain, wherein:

(i) the heavy chain comprises a heavy chain variable domain (VH) comprising CDRH1:
SYTMH (SEQ ID NO:
557);
CDRH2:
FISYDGNNKYYADSVKG (SEQ ID NO:
558);
and CDRH3:
TGWLGPFDY (SEQ ID NO:
559);
and
(ii) the light chain comprises:
(a) a light chain variable domain (VL) comprising CDRL1:
RASQSVGSSYLA (SEQ ID NO:
560);
CDRL2:
GAFSRAT (SEQ ID NO:
561);
and CDRL3:
QQYGSSPWT (SEQ ID NO:
562);
(b) a cleavable moiety (CM);
and
(c) a masking moiety (MM),
wherein the light chain has the structural arrangement, from N-terminus to C-terminus, as follows:
MM-CM-VL;
and
wherein the activatable anti-human CTLA-4 antibody is nonfucosylated.

24 more elements

An activatable anti-human CTLA-4 antibody comprising a heavy chain and a light chain, wherein the light chain comprises:

(a) a light chain variable domain (VL);
(b) a cleavable moiety (CM);
and
(c) a masking moiety (MM),
wherein the MM is selected from the group consisting of YV01, YV02, YV03, YV04, YV05, YV06, YV07, YV08, YV09, YV10, YV11, YV12, YV13, YV14, YV15, YV16, YV17, YV18, YV19, YV20, YV21, YV22, YV23, YV24, YV25, YV26, YV27, YV28, YV29, YV30, YV31, YV32, YV33, YV34, YV35, YV36, YV37, YV38, YV39, YV40, YV41, YV42, YV43, YV44, YV45, YV46, YV47, YV48, YV49, YV50, YV51, YV52, YV53, YV54, YV55, YV56, YV57, YV58, YV59, YV60, YV61, YV62, YV63, YV64, YV65, and YV66;
and
wherein the light chain has the structural arrangement from N-terminus to C-terminus as follows:
MM-CM-VL.

5 more elements

Dependencies are inferred from the claim text.

Activatable Anti-CTLA-4 Antibodies and Uses Thereof

Life of this patent

Activatable Anti-CTLA-4 Antibodies and Uses Thereof

Life of this patent

Abstract

Claims27