IP Library › Granted Patent US 11,780,933
Granted Patent B2
US 11,780,933 · App. 16/805,620 · Granted Oct 10, 2023

HER3 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.
C07K16/32A61P35/00C07K14/7051C07K16/28C12N15/62C12N15/85A61K2039/505C07K2317/24C07K2317/33C07K2317/522C07K2317/524C07K2317/526C07K2317/565C07K2317/622C07K2317/72C07K2317/76C07K2317/77C07K2317/92
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Quick Facts
Patent No.
US 11,780,933
App. No.
16/805,620
Granted
Oct 10, 2023
Kind
B2
Abstract

HER3 antigen-binding molecules are disclosed. Also disclosed are nucleic acids and expression vectors encoding, compositions comprising, and methods using, the HER3 antigen-binding molecules.

Claims (469)

1. An antigen-binding molecule comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the antigen-binding molecule specifically binds to HER3, wherein binding to HER3 comprises contact with one or more amino acid residues of the region of HER3 shown in SEQ ID NO:229, 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:43

HC-CDR2 having the amino acid sequence of SEQ ID NO:46

HC-CDR3 having the amino acid sequence of SEQ ID NO:51; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:91

LC-CDR2 having the amino acid sequence of SEQ ID NO:94

LC-CDR3 having the amino acid sequence of SEQ ID NO:99.

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:41

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(b)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:89

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(c)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:90

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:96; or

(d)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(e)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:49; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(f)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:50; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(g)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(h)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:97; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:42

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(j)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:98.

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:24; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:74; 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:25; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:75; 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:26; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:76; 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:27; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:77; 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:28; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:29; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:30; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:31; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:79; 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: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:79; 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:33; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:80; or

(k) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:34; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:81; or

(l) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:35; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:82; or

(m) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83; or

(n) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:37; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:84; or

(o) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:38; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:85; or

(p) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:86; or

(q) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:87.

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 specifically binds to HER3, wherein binding to HER3 comprises contact with one or more amino acid residues of the region of HER3 shown in SEQ ID NO:229, 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:43

HC-CDR2 having the amino acid sequence of SEQ ID NO:46

HC-CDR3 having the amino acid sequence of SEQ ID NO:51; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:91

LC-CDR2 having the amino acid sequence of SEQ ID NO:94

LC-CDR3 having the amino acid sequence of SEQ ID NO:99.

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:41

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(b)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:89

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(c)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:90

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:96; or

(d)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(e)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:49; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(f)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:50; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(g)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(h)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:97; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:42

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(j)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:98.

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:24; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:74; 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:25; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:75; 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:26; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:76; 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:27; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:77; 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:28; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:29; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:30; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:31; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:79; 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: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:79; 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:33; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:80; or

(k) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:34; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:81; or

(l) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:35; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:82; or

(m) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83; or

(n) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:37; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:84; or

(o) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:38; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:85; or

(p) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:86; or

(q) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:87.

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 specifically binds to HER3, wherein binding to HER3 comprises contact with one or more amino acid residues of the region of HER3 shown in SEQ ID NO:229, 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:43

HC-CDR2 having the amino acid sequence of SEQ ID NO:46

HC-CDR3 having the amino acid sequence of SEQ ID NO:51; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:91

LC-CDR2 having the amino acid sequence of SEQ ID NO:94

LC-CDR3 having the amino acid sequence of SEQ ID NO:99.

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:41

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(b)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:89

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(c)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:90

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:96; or

(d)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(e)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:49; and

(f)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:50; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(g)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(h)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:97; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:42

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(j)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:98.

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:24; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:74; 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:25; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:75; 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:26; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:76; 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:27; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:77; 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:28; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:29; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:30; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:31; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:79; 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: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:79; 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:33; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:80; or

(k) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:34; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:81; or

(l) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:35; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:82; or

(m) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83; or

(n) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:37; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:84; or

(o) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:38; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:85; or

(p) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:86; or

(q) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:87.

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 specifically binds to HER3, wherein binding to HER3 comprises contact with one or more amino acid residues of the region of HER3 shown in SEQ ID NO:229, 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:43

HC-CDR2 having the amino acid sequence of SEQ ID NO:46

HC-CDR3 having the amino acid sequence of SEQ ID NO:51; and

a VL region incorporating the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:91

LC-CDR2 having the amino acid sequence of SEQ ID NO:94

LC-CDR3 having the amino acid sequence of SEQ ID NO:99.

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:41

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(b)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:89

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(c)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:90

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:96; or

(d)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(e)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:49; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(f)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:50; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:93

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(g)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(h)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:97; or

(i)

a VH region having the following CDRs:

HC-CDR1 having the amino acid sequence of SEQ ID NO:42

HC-CDR2 having the amino acid sequence of SEQ ID NO:45

HC-CDR3 having the amino acid sequence of SEQ ID NO:48; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:95; or

(j)

a VH region having the following CDRs:

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

HC-CDR2 having the amino acid sequence of SEQ ID NO:44

HC-CDR3 having the amino acid sequence of SEQ ID NO:47; and

a VL region having the following CDRs:

LC-CDR1 having the amino acid sequence of SEQ ID NO:88

LC-CDR2 having the amino acid sequence of SEQ ID NO:92

LC-CDR3 having the amino acid sequence of SEQ ID NO:98.

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:24; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:74; 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:25; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:75; 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:26; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:76; 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:27; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:77; 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:28; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:29; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:30; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78; 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:31; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:79; 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: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:79; 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:33; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:80; or

(k) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:34; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:81; or

(l) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:35; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:82; or

(m) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:36; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:83; or

(n) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:37; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:84; or

(o) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:38; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:85; or

(p) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:39; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:86; or

(q) a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:40; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:87.

13. The method according to claim 10 , wherein the cancer is selected from: a cancer comprising cells expressing an EGFR family member, a cancer comprising cells expressing HER3, a solid tumor, breast cancer, breast carcinoma, ductal carcinoma, gastric cancer, gastric carcinoma, gastric adenocarcinoma, colorectal cancer, colorectal carcinoma, colorectal adenocarcinoma, head and neck cancer, squamous cell carcinoma of the head and neck (SCCHN), lung cancer, lung adenocarcinoma, squamous cell lung carcinoma, ovarian cancer, ovarian carcinoma, ovarian serous adenocarcinoma, kidney cancer, renal cell carcinoma, renal clear cell carcinoma, renal cell adenocarcinoma, renal papillary cell carcinoma, pancreatic cancer, pancreatic adenocarcinoma, pancreatic ductal adenocarcinoma, cervical cancer, cervical squamous cell carcinoma, skin cancer, melanoma, esophageal cancer, esophageal adenocarcinoma, liver cancer, hepatocellular carcinoma, cholangiocarcinoma, uterine cancer, uterine corpus endometrial carcinoma, thyroid cancer, thyroid carcinoma, pheochromocytoma, paraganglioma, bladder cancer, bladder urothelial carcinoma, prostate cancer, prostate adenocarcinoma, sarcoma and thymoma.

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 057270/0697 →
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 16596723 · Oct 8, 2019
Continuation PCTEP2019058035 · Mar 29, 2019
Related Publication 20200308275A1 · Oct 1, 2020