IP Library › Granted Patent US 12,448,455
Granted Patent B2
US 12,448,455 · App. 18/510,412 · Granted Oct 21, 2025

Combination therapies with bispecific anti-EGFR/c-met antibodies and third generation EGFR tyrosine kinase inhibitors

Inventors: Sylvie Laquerre (Chesterbrook, PA); Matthew Lorenzi (Philadelphia, PA); Sheri Moores (Wayne, PA)
Assignee: Janssen Biotech, Inc.
C07K16/2863A61K31/5377A61K39/39558A61P35/00A61K2039/505C07K2317/31C07K2317/51C07K2317/515C07K2317/56C07K2317/565
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Quick Facts
Patent No.
US 12,448,455
App. No.
18/510,412
Granted
Oct 21, 2025
Kind
B2
Abstract

The present invention relates to combination therapies with bispecific anti-EGFR/c-Met antibodies and 3 rd generation EGFR tyrosine kinase inhibitors.

Claims (52)

1. A pharmaceutical combination comprising:

a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody; and

a therapeutically effective amount of a compound of formula (I)

or a pharmaceutically acceptable salt or hydrate thereof,

wherein the isolated bispecific EGFR/c-Met antibody comprises:

(a) a first domain that binds EGFR, the first domain comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and

(b) a second domain that binds c-Met, the second domain comprising a HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, a HCDR2 comprising the amino acid sequence of SEO ID NO: 8, a HCDR3 comprising the amino acid sequence of SEO ID NO: 9, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

2. The pharmaceutical combination of claim 1 , wherein the compound of formula (I)

or a pharmaceutically acceptable salt or hydrate thereof is a mesylate salt of formula (I).

3. The pharmaceutical combination of claim 1 , comprising about 350 mg to about 1400 mg of the bispecific EGFR/c-Met antibody and about 160 mg to about 240 mg of the compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof.

4. The pharmaceutical combination of claim 2 , wherein the mesylate salt of formula (I) is represented by formula (II)

5. The pharmaceutical combination of claim 1 , wherein the pharmaceutical combination is a non-fixed combination.

6. The pharmaceutical combination of claim 1 , wherein the first domain that binds EGFR comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14; and the second domain that binds c-Met comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

7. The pharmaceutical combination of claim 6 , wherein the bispecific anti-EGFR/c-Met antibody comprises a first heavy chain (HC1) comprising the amino acid sequence of SEQ ID NO: 17, a first light chain (LC1) comprising the amino acid sequence of SEQ ID NO: 18, a second heavy chain (HC2) comprising the amino acid sequence of SEQ ID NO: 19, and a second light chain (LC2) comprising the amino acid sequence of SEQ ID NO: 20.

8. The pharmaceutical combination of claim 1 , wherein the bispecific anti-EGFR/c-Met antibody is an IgG1 isotype.

9. The pharmaceutical combination of claim 1 , wherein the bispecific anti-EGFR/c-Met antibody has a biantennary glycan structure with a fucose content of about 1% to about 15%.

10. The pharmaceutical combination of claim 1 , wherein the bispecific EGFR/c-Met antibody and the compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof are formulated in separate compositions.

11. A pharmaceutical combination comprising:

a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody; and

a therapeutically effective amount of a compound of formula (I)

or a pharmaceutically acceptable salt or hydrate thereof;

wherein the bispecific anti-EGFR/c-Met antibody comprises:

(a) a first domain that binds EGFR, the first domain comprising the first heavy chain complementarity determining region 1 (HCDR1), the first HCDR2, and the first HCDR3 of the heavy chain variable region (VH) of the amino acid sequence of SEQ ID NO: 13 and the first light chain complementarity determining region 1 (LCDR1), the first LCDR2, and the first LCDR3 of the light chain variable region (VL) of the amino acid sequence of SEQ ID NO: 14; and

(b) a second domain that binds c-Met, the second domain comprising the second HCDR1, the second HCDR2, and the second HCDR3 of the VH of the amino acid sequence of SEQ ID NO: 15 and the second LCDR1, the second LCDR2, and the second LCDR3 of the amino acid sequence of the VL of SEQ ID NO: 16.

12. The pharmaceutical combination of claim 11 , wherein

(a) the first HCDR1 comprises the amino acid sequence of SEQ ID NO: 1, the first HCDR2 comprises the amino acid sequence of SEQ ID NO: 2, the first HCDR3 comprises the amino acid sequence of SEQ ID NO: 3, the first LCDR1 comprises the amino acid sequence of SEQ ID NO: 4, the first LCDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the first LCDR3 comprises the amino acid sequence of SEQ ID NO: 6; and

(b) the second HCDR1 comprises the amino acid sequence of SEQ ID NO: 7, the second HCDR2 comprises the amino acid sequence of SEQ ID NO: 8, the second HCDR3 comprises the amino acid sequence of SEQ ID NO: 9, the second LCDR1 comprises the amino acid sequence of SEQ ID NO: 10, the second LCDR2 comprises the amino acid sequence of SEQ ID NO: 11, and the second LCDR3 comprises the amino acid sequence of SEQ ID NO: 12.

13. The pharmaceutical combination of claim 12 , wherein

(a) the first domain that binds EGFR comprises a VH comprising the amino acid sequence of SEQ ID NO: 13 and a VL comprising the amino acid sequence of SEQ ID NO: 14; and

(b) the second domain that binds c-Met comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

14. The pharmaceutical combination of claim 13 , wherein

(a) the first domain that binds EGFR comprises the VH of SEQ ID NO: 13 and the VL of SEQ ID NO: 14; and

(b) the second domain that binds c-Met comprises the VH of SEQ ID NO: 15 and the VL of SEQ ID NO: 16.

15. The pharmaceutical combination of claim 11 , wherein the compound of formula (I)

or a pharmaceutically acceptable salt or hydrate thereof is a mesylate salt of formula (I).

16. The pharmaceutical combination of claim 15 , wherein the mesylate salt of formula (I) is represented by formula (II)

17. The pharmaceutical combination of claim 11 , wherein the bispecific EGFR/c-Met antibody and the compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof are formulated in separate compositions.

18. A pharmaceutical combination comprising:

a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody;

and a therapeutically effective amount of a compound of formula (I)

or a pharmaceutically acceptable salt or hydrate thereof;

wherein the bispecific anti-EGFR/c-Met antibody comprises:

(a) a first heavy chain comprising the amino acid sequence of SEQ ID NO: 17 and a first light chain comprising the amino acid sequence of SEQ ID NO: 18; and

(b) a second heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a second light chain comprising the amino acid sequence of SEQ ID NO: 20.

19. The pharmaceutical combination of claim 18 , comprising:

(a) the first heavy chain of SEQ ID NO: 17 and the first light chain of SEQ ID NO: 18; and

(b) the second heavy chain of SEQ ID NO: 19 and the second light chain of SEQ ID NO: 20.

20. The pharmaceutical combination of claim 18 , comprising about 350 mg to about 1400 mg of the bispecific EGFR/c-Met antibody and about 160 mg to about 240 mg of the compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof.

21. The pharmaceutical combination of claim 18 , wherein the compound of formula (I)

or a pharmaceutically acceptable salt or hydrate thereof is a mesylate salt of formula (I).

22. The pharmaceutical combination of claim 21 , wherein the mesylate salt of formula (I) is represented by formula (II)

23. The pharmaceutical combination of claim 18 , wherein the bispecific EGFR/c-Met antibody and the compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof are formulated in separate compositions.

Continuity (4)
Division 15931726 · May 14, 2020
Provisional Application 62847563 · May 14, 2019
Provisional Application 62847605 · May 14, 2019
Related Publication 20240199748A1 · Jun 20, 2024
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