IP Library › Granted Patent US 11,873,346
Granted Patent B2
US 11,873,346 · App. 16/823,280 · Granted Jan 16, 2024

VISTA antigen-binding molecules

Inventors: Jerome Douglas Boyd-Kirkup (Singapore, SG); Piers Ingram (Singapore, SG); Dipti Thakkar (Singapore, SG); Zhihao Wu (Singapore, SG); Konrad Paszkiewicz (Singapore, SG); Vicente Sancenon (Singapore, SG); Siyu Guan (Singapore, SG)
Assignee: Hummingbird Bioscience Pte. Ltd.
C07K16/464C07K16/468C07K2317/522C07K2317/524C07K2317/526C07K2317/565C07K2317/567C07K2317/72
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Quick Facts
Patent No.
US 11,873,346
App. No.
16/823,280
Granted
Jan 16, 2024
Kind
B2
Abstract

VISTA antigen-binding molecules are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods using, the VISTA antigen-binding molecules.

Claims (443)

1. An antigen-binding molecule comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the antigen-binding molecule binds specifically to and displays cross-reactivity with both to human VISTA and mouse VISTA, wherein the antigen-binding molecule inhibits VISTA-mediated signalling independently of Fc-mediated function, and wherein the antigen-binding molecule comprises:

a VH region incorporating the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:305

HC-CDR2 having the amino acid sequence of SEQ ID NO:306

HC-CDR3 having the amino acid sequence of SEQ ID NO:307; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:308

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

2. The antigen-binding molecule according to claim 1 , wherein the antigen-binding molecule comprises:

(a)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:309

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(b)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:295

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(c)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:300

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(d)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(e)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:277

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(f)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:286

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(g)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:244

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:245

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(h)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:53

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:58

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:67

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(j)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

3. The antigen-binding molecule according to claim 1 , wherein the antigen-binding molecule comprises:

(a) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:310; or

(b) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:297; or

(c) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:294; or

(d) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:299; or

(e) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:301; or

(f) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:302; or

(g) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:285; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:287; or

(h) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:52; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:57; or

(i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:62; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:66; or

(j) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:32; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40.

4. A nucleic acid, or a plurality of nucleic acids, encoding an antigen-binding molecule comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the antigen-binding molecule binds specifically to and displays cross-reactivity with both human VISTA and mouse VISTA, wherein the antigen-binding molecule inhibits VISTA-mediated signalling independently of Fc-mediated function, and wherein the antigen-binding molecule comprises:

a VH region incorporating the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:305

HC-CDR2 having the amino acid sequence of SEQ ID NO:306

HC-CDR3 having the amino acid sequence of SEQ ID NO:307; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:308

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

5. The nucleic acid or plurality of nucleic acids according to claim 4 , wherein the antigen-binding molecule comprises:

(a)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:309

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(b)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:295

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(c)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:300

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(d)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(e)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:277

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(f)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:286

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(g)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:244

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:245

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(h)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:53

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:58

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:67

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(j)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

6. The nucleic acid or plurality of nucleic acids according to claim 4 , wherein the antigen-binding molecule comprises:

(a) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:310; or

(b) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:297; or

(c) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:294; or

(d) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:299; or

(e) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:301; or

(f) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:302; or

(g) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:285; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:287; or

(h) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:52; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:57; or

(i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:62; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:66; or

(j) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:32; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40.

7. A cell comprising a nucleic acid, or a plurality of nucleic acids, encoding an antigen-binding molecule comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the antigen-binding molecule binds specifically to and displays cross-reactivity with both human VISTA and mouse VISTA, wherein the antigen-binding molecule inhibits VISTA-mediated signalling independently of Fc-mediated function, and wherein the antigen-binding molecule comprises:

a VH region incorporating the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:305

HC-CDR2 having the amino acid sequence of SEQ ID NO:306

HC-CDR3 having the amino acid sequence of SEQ ID NO:307; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:308

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

8. The cell according to claim 7 , wherein the antigen-binding molecule comprises:

(a)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:309

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(b)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:295

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(c)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:300

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(d)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(e)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:277

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(f)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:286

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(g)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:244

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:245

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(h)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:53

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:58

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41 LC-CDR2 having the amino acid sequence of SEQ ID NO:67 LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(j)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

9. The cell according to claim 7 , wherein the antigen-binding molecule comprises:

(a) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:310; or

(b) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:297; or

(c) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:294; or

(d) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:299; or

(e) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:301; or

(f) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:302; or

(g) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:285; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:287; or

(h) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:52; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:57; or

(i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:62; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:66; or

(j) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:32; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40.

10. A method of treating a cancer in a subject, comprising administering to a subject a therapeutically effective amount of an antigen-binding molecule comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the antigen-binding molecule binds specifically to and displays cross-reactivity with both human VISTA and mouse VISTA, wherein the antigen-binding molecule inhibits VISTA-mediated signalling independently of Fc-mediated function, and wherein the antigen-binding molecule comprises:

a VH region incorporating the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:305

HC-CDR2 having the amino acid sequence of SEQ ID NO:306

HC-CDR3 having the amino acid sequence of SEQ ID NO:307; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:308

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

11. The method according to claim 10 , wherein the antigen-binding molecule comprises:

(a)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:309

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(b)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:295

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(c)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:300

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(d)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:290

HC-CDR2 having the amino acid sequence of SEQ ID NO:291

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(e)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:277

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(f)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:286

HC-CDR3 having the amino acid sequence of SEQ ID NO:278; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(g)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:244

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:245

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(h)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:53

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:58

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:67

LC-CDR3 having the amino acid sequence of SEQ ID NO:43; or

(j)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:33

HC-CDR2 having the amino acid sequence of SEQ ID NO:34

HC-CDR3 having the amino acid sequence of SEQ ID NO:35; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:41

LC-CDR2 having the amino acid sequence of SEQ ID NO:42

LC-CDR3 having the amino acid sequence of SEQ ID NO:43.

12. The method according to claim 10 , wherein the antigen-binding molecule comprises:

(a) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:310; or

(b) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:297; or

(c) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:294; or

(d) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:299; or

(e) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:301; or

(f) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:289; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:302; or

(g) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:285; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:287; or

(h) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:52; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:57; or

(i) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:62; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:66; or

(j) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:32; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40.

13. The method according to claim 10 , wherein the cancer is selected from the group consisting of: a cancer comprising cells expressing VISTA, a cancer comprising infiltration of cells expressing VISTA, a cancer comprising cancer cells expressing VISTA, a hematological cancer, leukemia, acute myeloid leukemia, lymphoma, B cell lymphoma, T cell lymphoma, multiple myeloma, mesothelioma, a solid tumor, lung cancer, non-small cell lung carcinoma, gastric cancer, gastric carcinoma, colorectal cancer, colorectal carcinoma, colorectal adenocarcinoma, uterine cancer, uterine corpus endometrial carcinoma, breast cancer, triple negative breast invasive carcinoma, liver cancer, hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, thyroid cancer, thymoma, skin cancer, melanoma, cutaneous melanoma, kidney cancer, renal cell carcinoma, renal papillary cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck (SCCHN), ovarian cancer, ovarian carcinoma, ovarian serous cystadenocarcinoma, prostate cancer and prostate adenocarcinoma.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2022
From: HUMMINGBIRD BIOSCIENCE HOLDINGS LIMITED
To: HUMMINGBIRD BIOSCIENCE PTE. LTD.
Reel/Frame 059519/0410 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2021
From: BOYD-KIRKUP, JEROME DOUGLAS; THAKKAR, DIPTI; INGRAM, PIERS; PASZKIEWICZ, KONRAD; WU, ZHIHAO; SANCENON, VICENTE; GUAN, SIYU
To: HUMMINGBIRD BIOSCIENCE HOLDINGS PTE. LTD.
Reel/Frame 057270/0640 →
CHANGE OF NAME Recorded Jul 12, 2021
From: HUMMINGBIRD BIOSCIENCE HOLDINGS PTE. LTD.
To: HUMMINGBIRD BIOSCIENCE HOLDINGS LIMITED
Reel/Frame 056832/0875 →
Continuity (3)
Continuation 16596739 · Oct 8, 2019
Continuation PCTEP2019058036 · Mar 29, 2019
Related Publication 20200308308A1 · Oct 1, 2020