US 12,735,476 B2Granted

Anti-GARP/TGF-β antibodies and methods of use

AssigneeShanghai Henlius Biotech, Inc.

InventorsJiin-Tarng Wang, Chi-Ling Tseng, Wei-Dong Jiang, Bin Chen, Yao Xu, Jie Gao

Life of this patent

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Abstract

Provided are antibodies and antibody derivatives that bind to GARP (also known as LRRC32 and CPPRDD) and/or GARP/TGFβ complex and methods of using the same. In certain embodiments, an anti-GARP/TGFβ antibody or antibody derivative provided herein can inhibit a TGFβ signal pathway in a target cell.

Claims19

Dependent claims

An antibody that binds to a GARP/TGFβ complex comprising:

a) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
1, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
3;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
4, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
6;
b) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
11, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
12, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
13;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
14, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
15, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
16;
c) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
21, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
22, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
23;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
24, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
25, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
26;
d) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
31, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
32, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
33;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
34, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
35, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
36;
e) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
41, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
42, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
43;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
44, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
45, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
46;
f) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
51, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
52, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
53;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
54, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
55, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
g) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
61, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
62, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
63;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
64, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
65, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
66;
or
h) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
105, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
108, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
109, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
110.

62 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/326,748Filed 31 May 2023 · continuation
Priority: 24 Nov 2021
Published: US 2023/0340098 A126 Oct 2023
Granted: 15 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07K 16/22
Against material from animals or humans: against growth factors ; against growth regulators
A61P 35/00
Antineoplastic agents
C07K 16/2818
Against the immunoglobulin superfamily: against CD28 or CD152
C07K 16/2863
Against receptors, cell surface antigens or cell surface determinants: against receptors for growth factors, growth regulators

Family

PCT/CN2021/132753Parent of this continuation · filed 24 Nov 2021
US 2023/0340098 A1Pre-grant publication · published 26 Oct 2023
US 12,735,476 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

An antibody that binds to a GARP/TGFβ complex comprising:

a) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
1, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
2, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
3;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
4, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
5, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
6;
b) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
11, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
12, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
13;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
14, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
15, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
16;
c) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
21, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
22, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
23;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
24, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
25, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
26;
d) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
31, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
32, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
33;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
34, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
35, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
36;
e) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
41, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
42, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
43;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
44, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
45, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
46;
f) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
51, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
52, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
53;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
54, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
55, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
56;
g) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
61, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
62, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
63;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
64, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
65, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
66;
or
h) a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence set forth in SEQ ID NO:
105, (2) a CDR-H2 comprising the amino acid sequence set forth in SEQ ID NO:
106, and (3) a CDR-H3 comprising the amino acid sequence set forth in SEQ ID NO:
107;
and a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence set forth in SEQ ID NO:
108, (2) a CDR-L2 comprising the amino acid sequence set forth in SEQ ID NO:
109, and (3) a CDR-L3 comprising the amino acid sequence set forth in SEQ ID NO:
110.

62 more elements

Facts

Application

18/326,748Filed 31 May 2023 · continuation

Priority

24 Nov 2021

Published

US 2023/0340098 A126 Oct 2023

Granted

15 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07K 16/22
Against material from animals or humans: against growth factors ; against growth regulators
A61P 35/00
Antineoplastic agents
C07K 16/2818
Against the immunoglobulin superfamily: against CD28 or CD152
C07K 16/2863
Against receptors, cell surface antigens or cell surface determinants: against receptors for growth factors, growth regulators