INTESTINAL ANTIGENS FOR PHARMACODELIVERY APPLICATIONS

• US 20190309060A1
• Filed: 01/13/2017
• Published: 10/10/2019
• Est. Priority Date: 01/15/2016
• Status: Abandoned Application

• Current Assignee: Philogen S.P.A.
• Original Assignee: Philogen S.P.A.
• Inventors: VILLA, Alessandra, PEMBERTON ROSS, Catherine, PRETTO, Francesca, FLEETWOOD, Filippa, FUGMANN, Tim
• Application Number:
  US16/070,032
• Publication Number:
  US 20190309060A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to the treatment of intestinal diseases and disorders, such as inflammatory bowel disease (IBD). The invention involves antibodies and the use of antibodies which bind antigens that have been shown to be over-expressed in the intestine compared to other organs, including antigens cadherin-17, anterior gradient protein 2 homolog, galectin-4, and galectin-2. The antibodies may be conjugated to anti-inflammatory or immunosuppressive agents, as required.

Claims

1-10. -10. (canceled)

11. An antibody molecule, or fragment thereof, which binds cadherin-17, wherein the antibody molecule, or fragment, comprises a VH domain comprising a framework and a set of complementarity determining regions HCDR1, HCDR2 and HCDR3, and a VL domain comprising a framework and a set of complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein:

HCDR3 has the amino acid sequence set forth in SEQ ID NO;

28, or the amino acid sequence set forth in SEQ ID NO;

28 with three or fewer amino acid substitutions.

12. The antibody molecule, or fragment, according to claim 11, wherein LCDR3 has the amino acid sequence set forth in SEQ ID NO:

33, or the amino acid sequence set forth in SEQ ID NO;

33 with three or fewer amino acid substitutions.

13. The antibody molecule, or fragment, according to claim 11, wherein

HCDR1 has the amino acid sequence set forth in SEQ ID NO:

29, or the amino acid sequence set forth in SEQ ID NO;

29 with three or fewer amino acid substitutions;

HCDR2 has the amino acid sequence set forth in SEQ ID NO;

30, or the amino acid sequence set forth in SEQ ID NO;

30 with three or fewer amino acid substitutions;

LCDR1 has the amino acid sequence set forth in SEQ ID NO;

31, or the amino acid sequence set forth in SEQ ID NO;

31 with three or fewer amino acid substitutions; and

/or

LCDR2 has the amino acid sequence set forth in SEQ ID NO;

32, or the amino acid sequence set forth in SEQ ID NO;

32 with three or fewer amino acid substitutions.

14. The antibody molecule, or fragment, according to claim 13, wherein the VH domain comprises or consist of the amino acid sequence set forth in SEQ ID NO:

34, and/or the VL domain comprises or consist of the amino acid sequence set forth in SEQ ID NO;

35.

15. The antibody molecule, or fragment, according to claim 14, wherein the antibody molecule, or fragment, is an scFv and comprises the amino acid sequence set forth in SEQ ID NO:

36.

50. The antibody molecule, or fragment, according to claim 12, wherein

HCDR1 has the amino acid sequence set forth in SEQ ID NO:

29, or the amino acid sequence set forth in SEQ ID NO;

29 with three or fewer amino acid substitutions;

HCDR2 has the amino acid sequence set forth in SEQ ID NO;

30, or the amino acid sequence set forth in SEQ ID NO;

30 with three or fewer amino acid substitutions;

LCDR1 has the amino acid sequence set forth in SEQ ID NO;

31, or the amino acid sequence set forth in SEQ ID NO;

31 with three or fewer amino acid substitutions; and

/or

LCDR2 has the amino acid sequence set forth in SEQ ID NO;

32, or the amino acid sequence set forth in SEQ ID NO;

32 with three or fewer amino acid substitutions.

16. An antibody molecule, or fragment thereof, which binds cadherin-17, wherein the antibody molecule, or fragment, comprises a VH domain comprising a framework and a set of complementarity determining regions HCDR1, HCDR2 and HCDR3, and a VL domain comprising a framework and a set of complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein:

HCDR3 has the amino acid sequence set forth in SEQ ID NO;

42, or the amino acid sequence set forth in SEQ ID NO;

42 with three or fewer amino acid substitutions.

17. The antibody molecule, or fragment, according to claim 16, wherein LCDR3 has the amino acid sequence set forth in SEQ ID NO:

47, or the amino acid sequence set forth in SEQ ID NO;

47 with three or fewer amino acid substitutions.

18. The antibody molecule, or fragment, according to claim 16, wherein

HCDR1 has the amino acid sequence set forth in SEQ ID NO:

43, or the amino acid sequence set forth in SEQ ID NO;

43 with three or fewer amino acid substitutions;

HCDR2 has the amino acid sequence set forth in SEQ ID NO;

44, or the amino acid sequence set forth in SEQ ID NO;

44 with three or fewer amino acid substitutions;

LCDR1 has the amino acid sequence set forth in SEQ ID NO;

45, or the amino acid sequence set forth in SEQ ID NO;

45 with three or fewer amino acid substitutions; and

/or

LCDR2 has the amino acid sequence set forth in SEQ ID NO;

46, or the amino acid sequence set forth in SEQ ID NO;

46 with three or fewer amino acid substitutions.

19. The antibody molecule, or fragment, according to claim 18, wherein the VH domain comprises or consist of the amino acid sequence set forth in SEQ ID NO:

48, and/or the VL domain comprises or consist of the amino acid sequence set forth in SEQ ID NO;

49.

20. The antibody molecule, or fragment, according to claim 19, wherein the antibody molecule, or fragment, is an scFv and comprises the amino acid sequence set forth in SEQ ID NO:

50.

51. The antibody molecule, or fragment, according to claim 17, wherein

HCDR1 has the amino acid sequence set forth in SEQ ID NO:

43, or the amino acid sequence set forth in SEQ ID NO;

43 with three or fewer amino acid substitutions;

HCDR2 has the amino acid sequence set forth in SEQ ID NO;

44, or the amino acid sequence set forth in SEQ ID NO;

44 with three or fewer amino acid substitutions;

LCDR1 has the amino acid sequence set forth in SEQ ID NO;

45, or the amino acid sequence set forth in SEQ ID NO;

45 with three or fewer amino acid substitutions; and

/or

LCDR2 has the amino acid sequence set forth in SEQ ID NO;

46, or the amino acid sequence set forth in SEQ ID NO;

46 with three or fewer amino acid substitutions.

21-49. -49. (canceled)