Nectin-4 antibodies and antibody-drug conjugates

Patent metadata

Field	Value
Publication number	US-2025000991-A1
Application number	US-202418747793-A
Country	US
Kind code	A1
Filing date	Jun 19, 2024
Priority date	Jun 20, 2023
Publication date	Jan 2, 2025
Grant date	—

Abstract

The present disclosure provides nectin-4 antibody drug conjugates and pharmaceutical compositions thereof, and methods of using for the treatment of cancer.

First claim

We claim:

1 . An antibody that binds human nectin-4, wherein the antibody comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the HCVR comprises heavy chain complementarity determining regions (HCDR) HCDR1, HCDR2, and HCDR3, and the LCVR comprises light chain complementarity determining regions (LCDR) LCDR1, LCDR2, and LCDR3, wherein:
a) the HCDR1 comprises SEQ ID NO: 4, the HCDR2 comprises SEQ ID NO: 5, the HCDR3 comprises SEQ ID NO: 6, the LCDR1 comprises SEQ ID NO: 7, the LCDR2 comprises SEQ ID NO: 8, and the LCDR3 comprises SEQ ID NO: 9; b) the HCDR1 comprises SEQ ID NO: 18, the HCDR2 comprises SEQ ID NO: 19, the HCDR3 comprises SEQ ID NO: 20, the LCDR1 comprises SEQ ID NO: 21, the LCDR2 comprises SEQ ID NO: 22, and the LCDR3 comprises SEQ ID NO: 23; c) the HCDR1 comprises SEQ ID NO: 28, the HCDR2 comprises SEQ ID NO: 29, the HCDR3 comprises SEQ ID NO: 30, the LCDR1 comprises SEQ ID NO: 31, the LCDR2 comprises SEQ ID NO: 32, and the LCDR3 comprises SEQ ID NO: 33; d) the HCDR1 comprises SEQ ID NO: 38, the HCDR2 comprises SEQ ID NO: 39, the HCDR3 comprises SEQ ID NO: 40, the LCDR1 comprises SEQ ID NO: 41, the LCDR2 comprises SEQ ID NO: 42, and the LCDR3 comprises SEQ ID NO: 43; e) the HCDR1 comprises SEQ ID NO: 48, the HCDR2 comprises SEQ ID NO: 49, the HCDR3 comprises SEQ ID NO: 50, the LCDR1 comprises SEQ ID NO: 41, the LCDR2 comprises SEQ ID NO: 42, and the LCDR3 comprises SEQ ID NO: 51; f) the HCDR1 comprises SEQ ID NO: 56, the HCDR2 comprises SEQ ID NO: 57, the HCDR3 comprises SEQ ID NO: 58, the LCDR1 comprises SEQ ID NO: 59, the LCDR2 comprises SEQ ID NO: 60, and the LCDR3 comprises SEQ ID NO: 61; g) the HCDR1 comprises SEQ ID NO: 66, the HCDR2 comprises SEQ ID NO: 67, the HCDR3 comprises SEQ ID NO: 68, the LCDR1 comprises SEQ ID NO: 69, the LCDR2 comprises SEQ ID NO: 70, and the LCDR3 comprises SEQ ID NO: 71; or h) the HCDR1 comprises SEQ ID NO: 76, the HCDR2 comprises SEQ ID NO: 77, the HCDR3 comprises SEQ ID NO: 78, the LCDR1 comprises SEQ ID NO: 69, the LCDR2 comprises SEQ ID NO: 70, and the LCDR3 comprises SEQ ID NO: 79.

2 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 4, the HCDR2 comprises SEQ ID NO: 5, the HCDR3 comprises SEQ ID NO: 6, the LCDR1 comprises SEQ ID NO: 7, the LCDR2 comprises SEQ ID NO: 8, and the LCDR3 comprises SEQ ID NO: 9.

3 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 18, the HCDR2 comprises SEQ ID NO: 19, the HCDR3 comprises SEQ ID NO: 20, the LCDR1 comprises SEQ ID NO: 21, the LCDR2 comprises SEQ ID NO: 22, and the LCDR3 comprises SEQ ID NO: 23.

4 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 28, the HCDR2 comprises SEQ ID NO: 29, the HCDR3 comprises SEQ ID NO: 30, the LCDR1 comprises SEQ ID NO: 31, the LCDR2 comprises SEQ ID NO: 32, and the LCDR3 comprises SEQ ID NO: 33.

5 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 38, the HCDR2 comprises SEQ ID NO: 39, the HCDR3 comprises SEQ ID NO: 40, the LCDR1 comprises SEQ ID NO: 41, the LCDR2 comprises SEQ ID NO: 42, and the LCDR3 comprises SEQ ID NO: 43.

6 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 48, the HCDR2 comprises SEQ ID NO: 49, the HCDR3 comprises SEQ ID NO: 50, the LCDR1 comprises SEQ ID NO: 41, the LCDR2 comprises SEQ ID NO: 42, and the LCDR3 comprises SEQ ID NO: 51.

7 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 56, the HCDR2 comprises SEQ ID NO: 57, the HCDR3 comprises SEQ ID NO: 58, the LCDR1 comprises SEQ ID NO: 59, the LCDR2 comprises SEQ ID NO: 60, and the LCDR3 comprises SEQ ID NO: 61.

8 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 66, the HCDR2 comprises SEQ ID NO: 67, the HCDR3 comprises SEQ ID NO: 68, the LCDR1 comprises SEQ ID NO: 69, the LCDR2 comprises SEQ ID NO: 70, and the LCDR3 comprises SEQ ID NO: 71.

9 . The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO: 76, the HCDR2 comprises SEQ ID NO: 77, the HCDR3 comprises SEQ ID NO: 78, the LCDR1 comprises SEQ ID NO: 69, the LCDR2 comprises SEQ ID NO: 70, and the LCDR3 comprises SEQ ID NO: 79.

10 . The antibody of claim 1 , wherein:
a) the HCVR comprises SEQ ID NO: 10 and the LCVR comprises SEQ ID NO: 11; b) the HCVR comprises SEQ ID NO: 14 and the LCVR comprises SEQ ID NO: 15; c) the HCVR comprises SEQ ID NO: 24 and the LCVR comprises SEQ ID NO: 25; d) the HCVR comprises SEQ ID NO: 34 and the LCVR comprises SEQ ID NO: 35; e) the HCVR comprises SEQ ID NO: 44 and the LCVR comprises SEQ ID NO: 45; f) the HCVR comprises SEQ ID NO: 52 and the LCVR comprises SEQ ID NO: 53; g) the HCVR comprises SEQ ID NO: 62 and the LCVR comprises SEQ ID NO: 63; h) the HCVR comprises SEQ ID NO: 72 and the LCVR comprises SEQ ID NO: 73; or i) the HCVR comprises SEQ ID NO: 80 and the LCVR comprises SEQ ID NO: 81.

11 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 10 and a LCVR comprising SEQ ID NO: 11.

12 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 14 and a LCVR comprising SEQ ID NO: 15.

13 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 24 and a LCVR comprising SEQ ID NO: 25.

14 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 34 and a LCVR comprising SEQ ID NO: 35.

15 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 44 and a LCVR comprising SEQ ID NO: 45.

16 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 52 and a LCVR comprising SEQ ID NO: 53.

17 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 62 and a LCVR comprising SEQ ID NO: 63.

18 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 72 and a LCVR comprising SEQ ID NO: 73.

19 . The antibody of claim 10 , wherein the antibody comprises a HCVR comprising SEQ ID NO: 80 and a LCVR comprising SEQ ID NO: 81.

20 . The antibody of claim 10 , wherein the antibody has a human IgG1 or IgG4 isotype.

21 . The antibody of claim 20 , wherein the antibody has a human IgG1 isotype.

22 . The antibody of claim 21 , comprising alanine at residues 234 and 235 (according to EU Index numbering).

23 . The antibody of claim 22 , further comprising serine at position 265 (according to EU Index numbering).

24 . The antibody of claim 1 , wherein the antibody comprises a heavy chain (HC) and a light chain (LC), wherein:
a) the HC comprises amino acids 2-444 of SEQ ID NO: 2 and the LC comprises amino acids 2-215 of SEQ ID NO: 3; b) the HC comprises amino acids 2-444 of SEQ ID NO: 12 and the LC comprises amino acids 2-215 of SEQ ID NO: 13; c) the HC comprises amino acids 2-443 of SEQ ID NO: 16 and the LC consists of SEQ ID NO: 17; d) the HC comprises amino acids 2-447 of SEQ ID NO: 26 and the LC consists of SEQ ID NO: 27; e) the HC comprises amino acids 2-446 of SEQ ID NO: 36 and the LC consists of SEQ ID NO: 37; f) the HC comprises amino acids 2-446 of SEQ ID NO: 46 and the LC consists of SEQ ID NO: 47; g) the HC comprises amino acids 2-446 of SEQ ID NO: 54 and the LC consists of SEQ ID NO: 55; h) the HC comprises amino acids 2-450 of SEQ ID NO: 64 and the LC comprises amino acids 2-216 of SEQ ID NO: 65; or i) the HC comprises amino acids 2-450 of SEQ ID NO: 74 and the LC comprises ami

Assignees

• Lilly Co Eli

Inventors

• Boyles Jeffrey Streetman
• Driscoll Kyla Elizabeth
• Duramad Omar
• Guo Qianxu
• Holmgaard Rikke Bæk
• Lindquist Kevin Charles
• Park Joshua Inshik
• Sagar Divya
• Srinivasan Mohan
• Verdino Petra
• Zhou Jieyu

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · 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

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title