IP Library › Granted Patent US 12,742,013
Granted Patent B2
US 12,742,013 · App. 18/331,535 · Granted Sep 22, 2026

IGF1R antibodies

Inventors: Christopher Davidson Ward (Kensington, MD); Martin Jack Borrok, III (North Potomac, MD)
Assignee: Horizon Therapeutics Ireland DAC
C07K16/2863A61P3/00C07K2317/24C07K2317/565C07K2317/92
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Quick Facts
Patent No.
US 12,742,013
App. No.
18/331,535
Granted
Sep 22, 2026
Kind
B2
Abstract

Described herein are antibodies that bind and inhibit signaling through the insulin-like growth factor receptor 1.

Claims (85)

1 . An antibody or antigen binding fragment thereof that binds insulin like growth factor 1 receptor (IGF1R), wherein the antibody or antigen binding fragment thereof comprises an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region, wherein the immunoglobulin heavy chain variable region comprises:

a. an immunoglobulin heavy chain CDR1 (HCDR1) comprising the amino acid sequence SX 1 GMH, wherein X 1 is H, Y, A, or T;

b. an immunoglobulin heavy chain CDR2 (HCDR2) comprising the amino acid sequence X 1 IX 2 X 3 DX 4 SX 5 TYYADSVRG, wherein X 1 is I, T, or Y, X 2 is W, N, or A, X 3 is F, H, A, or G, X 4 is G or A, X 5 is S or T; and

c. an immunoglobulin heavy chain CDR3 (HCDR3) comprising the amino acid sequence ELX 1 RRYFDL, wherein X 1 is G or N; and

wherein the immunoglobulin light chain variable region comprises:

d. an immunoglobulin light chain CDR1 (LCDR1) comprising the amino acid sequence RASQSVSSX 1 LA, wherein X 1 is Y, A, or T;

e. an immunoglobulin light chain CDR2 (LCDR2) comprising the amino acid sequence DASKRAT; and

f. an immunoglobulin light chain CDR3 (LCDR3) comprising the amino acid sequence QQRX 1 KX 2 PPWT, wherein X 1 is S or G, X 2 is Y.

2 . The antibody or antigen binding fragment thereof of claim 1 , wherein:

a. the HCDR1 comprises the amino acid sequence of SEQ ID NO: 30 (SHGMH);

b. the HCDR2 comprises the amino acid sequence of SEQ ID NO: 35 (YIWFDGSSTYYADSVRG);

c. the HCDR3 comprises the amino acid sequence of SEQ ID NO: 41 (ELGRRYFDL);

d. the LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 (RASQSVSSALA);

e. the LCDR2 comprises the amino acid sequence of SEQ ID NO: 46 (DASKRAT); and

f. the LCDR3 comprises the amino acid sequence of SEQ ID NO: 48 (QQRSKYPPWT).

3 . The antibody or antigen binding fragment thereof of claim 1 , wherein:

a. the HCDR1 comprises the amino acid sequence of SEQ ID NO: 33 (SYGMH);

b. the HCDR2 comprises the amino acid sequence of SEQ ID NO: 38 (IIWFDGSSTYYADSVRG);

c. the HCDR3 comprises the amino acid sequence of SEQ ID NO: 41 (ELGRRYFDL);

d. the LCDR1 comprises the amino acid sequence of SEQ ID NO: 45 (RASQSVSSYLA);

e. the LCDR2 comprises the amino acid sequence of SEQ ID NO: 46 (DASKRAT); and

f. the LCDR3 comprises the amino acid sequence of SEQ ID NO: 48 (QQRSKYPPWT).

4 . The antibody or antigen binding fragment thereof of claim 1 , wherein:

a. the HCDR1 comprises the amino acid sequence of SEQ ID NO: 30 (SHGMH);

b. the HCDR2 comprises the amino acid sequence of SEQ ID NO: 34 (IIAGDASTTYYADSVRG);

c. the HCDR3 comprises the amino acid sequence of SEQ ID NO: 41 (ELGRRYFDL);

d. the LCDR1 comprises the amino acid sequence of SEQ ID NO: 45 (RASQSVSSYLA);

e. the LCDR2 comprises the amino acid sequence of SEQ ID NO: 46 (DASKRAT); and

f. the LCDR3 comprises the amino acid sequence of SEQ ID NO: 48 (QQRSKYPPWT).

5 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 3; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 4.

6 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 5; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 6.

7 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 7; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 8.

8 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 9; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 10.

9 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 11; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 12.

10 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 13; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 14.

11 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 15; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 16.

12 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 17; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 18.

13 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 20.

14 . The antibody or antigen binding fragment thereof of claim 1 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 21; and wherein the immunoglobulin light chain variable region comprises the amino acid sequence to that set forth in SEQ ID NO: 22.

15 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is an IgG antibody or antigen binding fragment thereof.

16 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antigen binding fragment is a Fab, F(ab) 2 , or a single chain variable fragment (scFv).

17 . The antibody or antigen binding fragment thereof of claim 1 , comprising an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the immunoglobulin heavy chain comprises M252Y, S254T, and T256E substitutions according to EU numbering.

18 . The antibody or antigen binding fragment thereof of claim 17 , wherein the antibody or antigen binding fragment thereof is characterized by a half-life of 25 days or longer in a human.

19 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof inhibits signaling through IGF1R.

20 . The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody binds to human IGF1R with a K D of less than 5×10 −9 M.

21 . A nucleic acid encoding an antibody or antigen binding fragment thereof that binds IGF1R, wherein the antibody or antigen binding fragment thereof comprises an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region, wherein the immunoglobulin heavy chain variable region comprises:

a. an immunoglobulin heavy chain CDR1 (HCDR1) comprising the amino acid sequence SX 1 GMH, wherein X 1 is H, Y, A, or T;

b. an immunoglobulin heavy chain CDR2 (HCDR2) comprising the amino acid sequence X 1 IX 2 X 3 DX 4 SX 5 TYYADSVRG, wherein X 1 is I, T, or Y, X 2 is W, N, or A, X 3 is F, H, A, or G, X 4 is G or A, X 5 is S or T; and

c. an immunoglobulin heavy chain CDR3 (HCDR3) comprising the amino acid sequence ELX 1 RRYFDL, wherein X 1 is G or N; and

wherein the immunoglobulin light chain variable region comprises:

d. an immunoglobulin light chain CDR1 (LCDR1) comprising the amino acid sequence RASQSVSSX 1 LA, wherein X 1 is Y, A, or T;

e. an immunoglobulin light chain CDR2 (LCDR2) comprising the amino acid sequence DASKRAT; and

f. an immunoglobulin light chain CDR3 (LCDR3) comprising the amino acid sequence QQRX 1 KX 2 PPWT, wherein X 1 is S or G, X 2 is Y.

22 . A cell line comprising the nucleic acid of claim 21 .

23 . The cell line of claim 22 , wherein the cell line is a Chinese Hamster Ovary cell line.

24 . A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable excipient, carrier, or diluent.

25 . The pharmaceutical composition of claim 24 , formulated for intravenous administration.

26 . The pharmaceutical composition of claim 24 , formulated for subcutaneous administration.

27 . A monoclonal antibody that binds IGF1R comprising an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the immunoglobulin heavy chain comprises an immunoglobulin heavy chain variable region comprising:

an HCDR1 comprising the amino acid sequence of SEQ ID NO: 30 (SHGMH);

an HCDR2 comprising the amino acid sequence of SEQ ID NO: 35 (YIWFDGSSTYYADSVRG); and

an HCDR3 comprising the amino acid sequence of SEQ ID NO: 41 (ELGRRYFDL); and

wherein the immunoglobulin light chain comprises an immunoglobulin light chain variable region comprising:

a LCDR1 comprising the amino acid sequence of SEQ ID NO: 43 (RASQSVSSALA);

a LCDR2 comprising the amino acid sequence of SEQ ID NO: 46 (DASKRAT); and

a LCDR3 comprising the amino acid sequence of SEQ ID NO: 48 (QQRSKYPPWT).

28 . The monoclonal antibody of claim 27 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17 and the immunoglobulin light chain variable region comprises the amino acid sequence of SEQ ID NO: 18.

29 . The monoclonal antibody of claim 27 , wherein the immunoglobulin heavy chain comprises a human IgG1 constant region having M252Y, S254T, and T256E substitutions according to EU numbering.

30 . The monoclonal antibody of claim 27 , wherein the immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 51 and the immunoglobulin light chain comprises the amino acid sequence of SEQ ID NO: 52.

31 . A pharmaceutical composition comprising the monoclonal antibody of claim 27 and a pharmaceutically acceptable excipient, carrier, or diluent.

32 . A pharmaceutical composition comprising the monoclonal antibody of claim 28 and a pharmaceutically acceptable excipient, carrier, or diluent.

33 . A pharmaceutical composition comprising the monoclonal antibody of claim 30 and a pharmaceutically acceptable excipient, carrier, or diluent.

34 . A nucleic acid encoding a monoclonal antibody that binds IGF1R, said monoclonal antibody comprising an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the immunoglobulin heavy chain comprises an immunoglobulin heavy chain variable region comprising:

an HCDR1 comprising the amino acid sequence of SEQ ID NO: 30 (SHGMH);

an HCDR2 comprising the amino acid sequence of SEQ ID NO: 35 (YIWFDGSSTYYADSVRG); and

an HCDR3 comprising the amino acid sequence of SEQ ID NO: 41 (ELGRRYFDL); and

wherein the immunoglobulin light chain comprises an immunoglobulin light chain variable region comprising:

a LCDR1 comprising the amino acid sequence of SEQ ID NO: 43 (RASQSVSSALA);

a LCDR2 comprising the amino acid sequence of SEQ ID NO: 46 (DASKRAT); and

a LCDR3 comprising the amino acid sequence of SEQ ID NO: 48 (QQRSKYPPWT).

35 . The nucleic acid of claim 34 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17 and the immunoglobulin light chain variable region comprises the amino acid sequence of SEQ ID NO: 18.

36 . The nucleic acid of claim 34 , wherein the immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 51 and the immunoglobulin light chain comprises the amino acid sequence of SEQ ID NO: 52.

37 . A cell line comprising the nucleic acid of claim 34 .

38 . A cell line comprising the nucleic acid of claim 35 .

39 . A cell line comprising the nucleic acid of claim 36 .

Assignments (2)
CHANGE OF ADDRESS Recorded Dec 23, 2025
From: HORIZON THERAPEUTICS IRELAND DAC
To: HORIZON THERAPEUTICS IRELAND DAC
Reel/Frame 074050/0087 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 13, 2023
From: WARD, CHRISTOPHER DAVIDSON; BORROK, MARTIN JACK, III
To: HORIZON THERAPEUTICS IRELAND DAC
Reel/Frame 063932/0264 →
Continuity (3)
Provisional Application 63500168 · May 4, 2023
Provisional Application 63351077 · Jun 10, 2022
Related Publication 20230406942A1 · Dec 21, 2023
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