Anti-claudin antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10053511-B2
Application number	US-201415034992-A
Country	US
Kind code	B2
Filing date	Nov 5, 2014
Priority date	Nov 6, 2013
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

Provided herein are anti-CLDN antibodies and antibody drug conjugates (ADC), including derivatives thereof, and methods of using the same to treat proliferative disorders.

First claim

The invention claimed is:

1. An anti-Claudin 6 (“anti-CLDN6”) antibody comprising:
(a) three CDRs of a light chain variable region set forth as SEQ ID NO: 21 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 23; or
(b) three CDRs of a light chain variable region set forth as SEQ ID NO: 25 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 27; or
(c) three CDRs of a light chain variable region set forth as SEQ ID NO: 29 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 31; or
(d) three CDRs of a light chain variable region set forth as SEQ ID NO: 33 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 35; or
(e) three CDRs of a light chain variable region set forth as SEQ ID NO: 37 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 39; or
(f) three CDRs of a light chain variable region set forth as SEQ ID NO: 41 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 43; or
(g) three CDRs of a light chain variable region set forth as SEQ ID NO: 45 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 47; or
(h) three CDRs of a light chain variable region set forth as SEQ ID NO: 49 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 51; or
(i) three CDRs of a light chain variable region set forth as SEQ ID NO: 53 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 55; or
(j) three CDRs of a light chain variable region set forth as SEQ ID NO: 57 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 59; or
(k) three CDRs of a light chain variable region set forth as SEQ ID NO: 61 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 63; or
(l) three CDRs of a light chain variable region set forth as SEQ ID NO: 65 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 67; or
(m) three CDRs of a light chain variable region set forth as SEQ ID NO: 69 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 71; or
(n) three CDRs of a light chain variable region set forth as SEQ ID NO: 73 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 87.

2. The anti-CLDN6 antibody of claim 1 comprising three CDRs of a light chain variable region set forth as SEQ ID NO: 73 and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 87.

3. The anti-CLDN6 antibody of claim 1 , wherein the antibody binds specifically to CLDN6 and CLDN9.

4. The anti-CLDN6 antibody of claim 1 , wherein the antibody is an internalizing antibody.

5. The anti-CLDN6 antibody of claim 2 , wherein the CDR residues are numbered according to Kabat.

6. The anti-CLDN6 antibody of claim 2 , wherein the CDR residues are numbered according to Chothia.

7. The anti-CLDN6 antibody of claim 2 , wherein the CDR residues are numbered according to MacCallum.

8. The anti-CLDN6 antibody of claim 1 , comprising:
(a) a light chain variable region set forth as SEQ ID NO: 21 and a heavy chain variable region set forth as SEQ ID NO: 23; or
(b) a light chain variable region set forth as SEQ ID NO: 25 and a heavy chain variable region set forth as SEQ ID NO: 27; or
(c) a light chain variable region set forth as SEQ ID NO: 29 and a heavy chain variable region set forth as SEQ ID NO: 31; or
(d) a light chain variable region set forth as SEQ ID NO: 33 and a heavy chain variable region set forth as SEQ ID NO: 35; or
(e) a light chain variable region set forth as SEQ ID NO: 37 and a heavy chain variable region set forth as SEQ ID NO: 39; or
(f) a light chain variable region set forth as SEQ ID NO: 41 and a heavy chain variable region set forth as SEQ ID NO: 43; or
(g) a light chain variable region set forth as SEQ ID NO: 45 and a heavy chain variable region set forth as SEQ ID NO: 47; or
(h) a light chain variable region set forth as SEQ ID NO: 49 and a heavy chain variable region set forth as SEQ ID NO: 51; or
(i) a light chain variable region set forth as SEQ ID NO: 53 and a heavy chain variable region set forth as SEQ ID NO: 55; or
(j) a light chain variable region set forth as SEQ ID NO: 57 and a heavy chain variable region set forth as SEQ ID NO: 59; or
(k) a light chain variable region set forth as SEQ ID NO: 61 and a heavy chain variable region set forth as SEQ ID NO: 63; or
(l) a light chain variable region set forth as SEQ ID NO: 65 and a heavy chain variable region set forth as SEQ ID NO: 67; or
(m) a light chain variable region set forth as SEQ ID NO: 69 and a heavy chain variable region set forth as SEQ ID NO: 71; or
(n) a light chain variable region set forth as SEQ ID NO: 73 and heavy chain variable region set forth as SEQ ID NO: 87.

9. The anti-CLDN6 antibody of claim 8 , comprising a light chain variable region set forth as SEQ ID NO: 73 and heavy chain variable region set forth as SEQ ID NO: 87.

10. The anti-CLDN6 antibody of claim 9 , wherein the anti-CLDN6 antibody comprises two light chains and two heavy chains, and wherein the anti-CLDN6 antibody comprises two unpaired cysteine residues.

11. The anti-CLDN6 antibody of claim 10 , wherein each of the two light chains comprises an unpaired cysteine residue.

12. The anti-CLDN6 antibody of claim 11 , wherein each unpaired cysteine residue is at position C214.

13. The anti-CLDN6 antibody of claim 10 , wherein each of the two heavy chains comprises an unpaired cysteine residue.

14. The anti-CLDN6 antibody of claim 13 , wherein each of the two heavy chains is IgG1 and each unpaired cysteine residue is at position C220.

15. The anti-CLDN6 antibody of claim 1 comprising:
(a) a full length light chain set forth as SEQ ID NO: 114 and a full length heavy chain set forth as SEQ ID NO: 115; or
(b) a full length light chain set forth as SEQ ID NO: 116 and a full length heavy chain set forth as SEQ ID NO: 117; or
(c) a full length light chain set forth as SEQ ID NO: 116 and a full length heavy chain set forth as SEQ ID NO: 122; or
(d) a full length light chain set forth as SEQ ID NO: 118 and a full length heavy chain set forth as SEQ ID NO: 119; or
(e) a full length light chain set forth as SEQ ID NO: 120 and a full length heavy chain set forth as SEQ ID NO: 121; or
(f) a full length light chain set forth as SEQ ID NO: 120 and a full length heavy chain set forth as SEQ ID NO: 137.

16. The anti-CLDN6 antibody of claim 1 , wherein the antibody is selected from the group consisting of monoclonal antibody, chimeric antibody, CDR-grafted antibody, humanized antibody, primatized antibody, multispecific antibody, bispecific antibody, monovalent antibody, multivalent antibody, Fab fragment, F(ab′) 2 fragment, Fv fragment, and scFv fragment; or an immunoreactive fragment thereof that binds CLDN6.

17. The anti-CLDN6 antibody of claim 16 , wherein the antibody is selected from the group consisting of chimeric antibody, CDR-grafted antibody, and humanized antibody.

18. The anti-CLDN6 antibody of claim 1 , wherein the anti-CLDN6 antibody is conjugated to a cytotoxic agent.

19. The anti-CLDN6 antibody of claim 18 , wherein the cytotoxic agent is a pyrrolobenzodiazepine (PBD), an auristatin, a maytansinoid, a calicheamicin or a radioisotope.

20. The anti-CLDN6 antibody of claim 19 , wherein the cytotoxic agent is a pyrrolobenzodiazepine (PBD).

21. The anti-CLDN6 antibody of claim 10 , wherein the anti-CLDN6 antibody is conjugated to a cytotoxic agent, and wherein the cytotoxic agent is conjugated to the two unpai

Assignees

• Abbvie Stemcentrx Llc

Inventors

• Santaguida Marianne
• Aujay Monette
• Saunders Laura
• Liu David
• Foord Orit
• Stull Robert A
• Escarpe Paul Anthony

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/522

  CH1 domain · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C07K2317/53

  Hinge · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title