Quaternary amine compounds and antibody-drug conjugates thereof

Patent metadata

Field	Value
Publication number	US-11104673-B2
Application number	US-201916697706-A
Country	US
Kind code	B2
Filing date	Nov 27, 2019
Priority date	Dec 3, 2014
Publication date	Aug 31, 2021
Grant date	Aug 31, 2021

Abstract

This invention relates to quaternary amine linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.

First claim

What is claimed is:

1. An antibody-drug conjugate prepared by conjugating an antibody with a linker-drug intermediate compound selected from:

2. The antibody-drug conjugate of claim 1 , wherein the antibody is a cysteine engineered antibody.

3. The antibody-drug conjugate of claim 1 , wherein the antibody binds to one or more of polypeptides selected from the group consisting of: BMPR1B; E16; STEAP1; 0772P (Muc16); MPF; NaPi2b (NaPi3b); Sema 5b; PSCA hlg; ETBR; MSG783; STEAP2; TrpM4; CRIPTO; CD21; CD79b; FcRH2; HER2; NCA; MDP; IL20Rα; Brevican; EphB2R; ASLG659; PSCA; GEDA, BAFF-R; CD22; CD79a; CXCR5; HLA-DOB; P2X5; CD72; LY64; FcRH1; IRTA2; TENB2; PMEL17; TMEFF1; GDNF-Ra1; Ly6E; TMEM46; Ly6G6D; LGR5; RET; LY6K; GPR19; GPR54; ASPHD1; Tyrosinase; TMEM118; GPR172A; CD33; and CLL1.

4. The antibody-drug conjugate of claim 3 , wherein the antibody binds to NaPi2b.

5. The antibody-drug conjugate of claim 4 , wherein the NaPi2b antibody comprise an HVR-L1 comprising the amino acid sequence of SEQ ID NO:1, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:2, an HVR-L3 comprising the amino acid sequence of SEQ ID NO:3, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 4, an HVR-H2 comprising the amino acid sequence of SEQ NO:5, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 6.

6. The antibody-drug conjugate of claim 5 , wherein said NaPi2b antibody comprises a VL domain comprising the amino acid sequence of SEQ NO:7 and a VH domain comprising the amino acid sequence of SEQ ID NO:8.

7. The antibody-drug conjugate of claim 5 , wherein said NaPi2b antibody comprises an amino acid sequence of SEQ ID NO:9 and an amino acid sequence of SEQ ID NO: 10.

8. The antibody-drug conjugate of claim 5 , wherein said NaPi2b antibody comprises an amino acid sequence that has at least 95% sequence identity with amino acid sequence of SEQ ID NO:9 and that comprises an amino acid sequence that has at least 95% sequence identity with an amino acid sequence of SEQ ID NO: 10.

9. The antibody-drug conjugate of claim 3 , wherein the antibody binds to CD22.

10. The antibody-drug conjugate of claim 9 , wherein the CD22 antibody comprise an HVR-L1 comprising the amino acid sequence of SEQ ID NO:41, an HVR-L2 comprising the amino acid sequence of SEQ ID NO:42, an HVR-L3 comprising the amino acid sequence of SEQ ID NO:43, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 44, an HVR-H2 comprising the amino acid sequence of SEQ ID NO:45, and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 46.

11. The antibody-drug conjugate of claim 9 , wherein said CD22 antibody comprises a VL domain comprising the amino acid sequence of SEQ ID NO:47 and a VH domain comprising the amino acid sequence of SEQ ID NO:48.

12. The antibody-drug conjugate of claim 9 , wherein said CD22 antibody comprises an amino acid sequence of SEQ ID NO:49 and an amino acid sequence of SEQ ID NO: 50.

13. The antibody-drug conjugate of claim 9 , wherein said CD22 antibody comprises an amino acid sequence that has at least 95% sequence identity with amino acid sequence of SEQ ID NO:49 and that comprises an amino acid sequence that has at least 95% sequence identity with an amino acid sequence of SEQ ID NO: 50.

14. A pharmaceutical composition comprising the antibody-drug conjugate of claim 1 and a pharmaceutically acceptable carrier thereof.

15. The antibody-drug conjugate of claim 1 wherein the linker-drug intermediate compound has the structure:

16. The antibody-drug conjugate of claim 1 wherein the linker-drug intermediate compound has the structure:

17. The antibody-drug conjugate of claim 1 wherein the linker-drug intermediate compound has the structure:

18. The antibody-drug conjugate of claim 1 wherein the linker-drug intermediate compound has the structure:

Assignees

• Genentech Inc

Inventors

• Flygare John A
• Pillow Thomas
• Staben Leanna

Classifications

• A61K47/6803 Primary

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6851

  the antibody targeting a determinant of a tumour cell · CPC title

• A61K47/6889

  Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title