Anti-podocalyxin antibodies and methods of using the same

Patent metadata

Field	Value
Publication number	US-2018296673-A1
Application number	US-201615765233-A
Country	US
Kind code	A1
Filing date	Sep 30, 2016
Priority date	Oct 1, 2015
Publication date	Oct 18, 2018
Grant date	—

Abstract

The present invention is directed to anti-podocalyxin antibodies, compositions comprising the same, and methods of using such antibodies and compositions for the prevention, diagnosis and treatment of cancer.

First claim

What is claimed is:

1 . An anti-podocalyxin antibody that binds to a podocalyxin tumor epitope.

2 . The anti-podocalyxin antibody according to claim 1 , wherein said podocalyxin tumor epitope comprises a post-translational modification of a podocalyxin polypeptide.

3 . The anti-podocalyxin antibody according to claim 2 , wherein said post-translational modification of said podocalyxin polypeptide comprises an O-linked glycan moiety that is linked to said podocalyxin polypeptide.

4 . The anti-podocalyxin antibody according to claim 2 , wherein said post-translational modification of said podocalyxin polypeptide comprises a glycan moiety that is linked to said podocalyxin polypeptide, wherein said glycan moiety comprises a beta-N-acetyl-galactosamine.

5 . The anti-podocalyxin antibody according to claim 4 , wherein said beta-N-acetyl-galactosamine is a terminal beta-N-acetyl-galactosamine.

6 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising an amino acid sequence selected from the group consisting of: GFSLSGYQ (SEQ ID NO:33); GFSLSGY (SEQ ID NO:34); and GYQMN (SEQ ID NO:35).

7 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising an amino acid sequence selected from the group consisting of: IWSDGGT (SEQ ID NO:36); WSDGG (SEQ ID NO:37); and YIWSDGGTDYASWAKG (SEQ ID NO:38).

8 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising an amino acid sequence selected from the group consisting of: AREGYWLGAFDP (SEQ ID NO:39) and EGYWLGAFDP (SEQ ID NO:40).

9 . The anti-podocalyxin antibody according to claim 1 , comprising a light chain variable region comprising an amino acid sequence selected from the group consisting of: QSVHHKND (SEQ ID NO:42) and QSVHHKNDLA (SEQ ID NO:43).

10 . The anti-podocalyxin antibody according to claim 1 , comprising a light chain variable region comprising an amino acid sequence selected from the group consisting of: YTS (SEQ ID NO:45) and YTSLAS (SEQ ID NO:46).

11 . The anti-podocalyxin antibody according to claim 1 , comprising a light chain variable region comprising the amino acid sequence AGVYEGSSDNRA (SEQ ID NO:48).

12 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising a CDR1 selected from SEQ ID NOs: 33-35; a CDR2 selected from SEQ ID NOs: 36-38; and a CDR3 selected from SEQ ID NOs: 39-41.

13 . The anti-podocalyxin antibody according to claim 1 , comprising a light chain variable region comprising a CDR1 selected from SEQ ID NOs: 42-44; a CDR2 selected from SEQ ID NOs: 45 and 46; and a CDR3 set forth by SEQ ID NO:48.

14 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising a CDR1 selected from SEQ ID NOs: 33-35; a CDR2 selected from SEQ ID NOs: 36-38; and a CDR3 selected from SEQ ID NOs: 39-41; and further comprising a light chain variable region comprising a CDR1 selected from SEQ ID NOs: 42-44; a CDR2 selected from SEQ ID NOs: 45 and 46; and a CDR3 set forth by SEQ ID NO: 48.

15 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising SEQ ID NO: 27.

16 . The anti-podocalyxin antibody according to claim 1 , comprising a light chain variable region comprising SEQ ID NO: 29.

17 . The anti-podocalyxin antibody according to claim 1 , comprising a heavy chain variable region comprising SEQ ID NO:27 and a light chain variable region comprising SEQ ID NO:29.

18 . The anti-podoclayxin antibody according to claim 1 , wherein the anti-podoclayxin antibody is a chimeric, humanized, or human antibody.

19 . The anti-podoclayxin antibody according to claim 1 , wherein the anti-podoclayxin antibody is a monoclonal antibody.

20 . The anti-podoclayxin antibody according to claim 1 , wherein the anti-podoclayxin antibody is an antibody fragment.

21 . A modified immune cell, comprising a chimeric antigen receptor (CAR), wherein said CAR comprises the anti-podoclayxin antibody according to claim 20 .

22 . The modified immune cell according to claim 21 , wherein said modified immune cell is a modified T cell.

23 . The modified immune cell according to claim 21 , wherein said modified immune cell is a modified NK cell.

24 . An antibody-drug conjugate (ADC), comprising the antibody according to claim 1 .

25 . A method of inhibiting the growth of a cell that displays a podocalyxin tumor epitope, comprising contacting said cell with the anti-podocalyxin antibody according to claim 1 , the modified immune cell according to claim 21 , or the ADC according to claim 24 .

26 . A method of treating a subject having cancer, comprising administering to said subject the anti-podocalyxin antibody according to claim 1 , the modified immune cell according to claim 21 , or the ADC according to claim 24 .

27 . The method according to claim 26 , wherein said subject is a human.

28 . The method according to claim 26 , wherein said cancer is breast cancer, ovarian cancer, melanoma, glioblastoma, AML, or ALL.

29 . A pharmaceutical composition comprising an antibody according to claim 1 , and a pharmaceutically acceptable carrier.

30 . A pharmaceutical composition comprising the modified immune cell according to claim 21 , and a pharmaceutically acceptable carrier.

31 . Use of the antibody according to claim 1 in the preparation of a medicament for the treatment of cancer.

32 . Use of the modified immune cell according to claim 21 in the preparation of a medicament for the treatment of cancer.

33 . Use of the ADC according to claim 24 in the preparation of a medicament for the treatment of cancer.

34 . An anti-podocalyxin antibody that competes with the anti-podocalyxin antibody according to claim 17 for binding to said podocalyxin tumor epitope.

35 . An anti-podocalyxin antibody that binds to essentially the same epitope as the anti-podocalyxin antibody according to claim 17 .

Assignees

• The Centre For Drug Res And Development
• Univ British Columbia

Inventors

• Mcnagny Kelly Marshall
• Roskelley Calvin D
• Hughes Michael R
• Hernaez Diana Canals
• Blixt Klas Ola
• Babcook John Stephen
• Bond Christopher John
• Samudio Ismael
• Bergqvist Jan Peter
• Macdonald Katherine Grace
• Von Rossum Anna
• Hedberg Bradley John

Classifications

• C07K16/30

  from tumour cells · CPC title

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• C12N5/10

  Cells modified by introduction of foreign genetic material · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K35/17

  Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) · CPC title