Wt1 antigen peptide conjugate vaccine

Patent metadata

Field	Value
Publication number	US-2016114019-A1
Application number	US-201514984763-A
Country	US
Kind code	A1
Filing date	Dec 30, 2015
Priority date	Mar 29, 2013
Publication date	Apr 28, 2016
Grant date	—

Abstract

A compound represented by the formula (1):

wherein X a and Y a are each a single bond and the like, cancer antigen peptide A is an MHC class I-restricted WT1 peptide consisting of 7-30 amino acid residues, R 1 is a hydrogen atom, a group represented by the formula (2):

wherein X b and Y b are each a single bond and the like, cancer antigen peptide B has a sequence different from that of the cancer antigen peptide A, and is an MHC class I-restricted WT1 peptide consisting of 7-30 amino acid residues, or cancer antigen peptide C, and cancer antigen peptide C has a sequence different from that of the cancer antigen peptide A, and is an MHC class I-restricted WT1 peptide or an MHC class II-restricted WT1 peptide, consisting of 7-30 amino acid residues containing one cysteine residue, or a salt thereof, and the like.

First claim

1 . A compound of formula (1):

wherein X a and Y a are each a single bond,
cancer antigen peptide A is an MHC class I-restricted WT1 peptide consisting of 7-30 amino acid residues,
an amino group of an N-terminal amino acid of the cancer antigen peptide A binds to Y a in the formula (1), and
a carbonyl group of a C-terminal amino acid of the cancer antigen peptide A binds to a hydroxyl group in the formula (1),
R 1 is a hydrogen atom, a group of formula (2), or cancer antigen peptide C:

wherein X b and Y b are each independently a single bond or a divalent peptide group consisting of 1-4 amino acid residues wherein X b and Y b together have 0-4 amino acid residues,
cancer antigen peptide B has a sequence different from a sequence of the cancer antigen peptide A and is an MHC class I-restricted WT1 peptide consisting of 7-30 amino acid residues,
an amino group of an N-terminal amino acid of the cancer antigen peptide B binds to Y b in the formula (2), and
a carbonyl group of a C-terminal amino acid of the cancer antigen peptide B binds to a hydroxyl group in the formula (2), and
a thioether group in the formula (2) binds to a thioether group in the formula (1),
cancer antigen peptide C is an MHC class I-restricted WT1 peptide different from the cancer antigen peptide A in the sequence and consisting of 7-30 amino acid residues containing one cysteine residue or an MHC class II-restricted WT1 peptide consisting of 7-30 amino acid residues containing one cysteine residue, wherein a thioether group of the cysteine residue of the cancer antigen peptide C binds to the thioether group in the formula (1),

or a pharmaceutically acceptable salt thereof,
provided when R 1 is a hydrogen atom, the sequence of the compound of the formula (1) is not the same as a partial sequence of a WT1 protein,
and the compound of the formula (1) is not a compound of formula (4) or formula (5)

2 . The compound according to claim 1 , wherein the cancer antigen peptide A is
a peptide comprising an amino acid sequence selected from the group consisting of:
RMFPNAPYL (SEQ ID NO: 2),
CMTWNQMNL (SEQ ID NO: 3),
CYTWNQMNL (SEQ ID NO: 4),
ALLPAVPSL (SEQ ID NO: 5),
SLGEQQYSV (SEQ ID NO: 6) and
RVPGVAPTL (SEQ ID NO: 7), or
a peptide comprising an altered amino acid sequence, which is an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 3, 5, 6 and 7 but containing alteration of amino acid residue(s), and having a CTL induction activity, or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 1 , wherein R 1 is a hydrogen atom,
or a pharmaceutically acceptable salt thereof.

4 . The compound according to claim 1 , wherein the compound of the formula (1) is a peptide consisting of an amino acid sequence selected from the group consisting of:
CRMFPNAPYL (SEQ ID NO: 13), CALLPAVPSL (SEQ ID NO: 16), CSLGEQQYSV (SEQ ID NO: 17) and CRVPGVAPTL (SEQ ID NO: 18),
or a pharmaceutically acceptable salt thereof.

5 . The compound according to claim 1 , wherein R 1 is a group of the formula (2),
or a pharmaceutically acceptable salt thereof.

6 . The compound according to claim 5 , wherein X b is a single bond, and Y b is a single bond or an alanine residue, or a pharmaceutically acceptable salt thereof.

7 . The compound according to claim 5 , wherein the cancer antigen peptide B is
a peptide comprising an amino acid sequence selected from the group consisting of:
RMFPNAPYL (SEQ ID NO: 2),
CMTWNQMNL (SEQ ID NO: 3),
CYTWNQMNL (SEQ ID NO: 4),
ALLPAVPSL (SEQ ID NO: 5),
SLGEQQYSV (SEQ ID NO: 6) and
RVPGVAPTL (SEQ ID NO: 7), or
a peptide comprising an altered amino acid sequence, which is an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 3, 5, 6 and 7 but containing alteration of amino acid residue(s), and having a CTL induction activity, or a pharmaceutically acceptable salt thereof.

8 . The compound according to claim 1 , wherein the compound of the formula (1) is a compound of formula (3):

wherein the bond between C and C is a disulfide bond, or a pharmaceutically acceptable salt thereof.

9 . The compound according to claim 1 , wherein, when the cancer antigen peptide B is an MHC class I-restricted WT1 peptide containing one cysteine residue, the thioether group in the cancer antigen peptide B is bonded to a thioether group in formula (16):

wherein X d and Y d are each a single bond,
cancer antigen peptide D is an MHC class II-restricted WT1 peptide consisting of 7-30 amino acid residues,
an amino group of an N-terminal amino acid of the cancer antigen peptide D binds to Y d in the formula (16), and
a carbonyl group of a C-terminal amino acid of the cancer antigen peptide D binds to a hydroxyl group in the formula (16), or to the thioether group of the cysteine residue of the cancer antigen peptide E, which is an MHC class II-restricted WT1 peptide consisting of 7-30 amino acid residues containing one cysteine residue,

or a pharmaceutically acceptable salt thereof.

10 . The compound according to claim 9 , wherein the cancer antigen peptide B is a peptide consisting of:
CYTWNQMNL (SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof.

11 . The compound according to claim 9 , wherein the cancer antigen peptide D is a peptide consisting of:
SGQARMFPNAPYLPSC (SEQ ID NO: 19), SGQAYMFPNAPYLPSC (SEQ ID NO: 25), SGQARMFPNAPYLPSCLES (SEQ ID NO: 11), SGQAYMFPNAPYLPSCLES (SEQ ID NO: 12), PGCNKRYFKLSHLQMHSRK (SEQ ID NO: 20), PGCNKRYFKLSHLQMHSRKH (SEQ ID NO: 21), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 10), CNKRYFKLSHLQMHSRK (SEQ ID NO: 22), CNKRYFKLSHLQMHSRKH (SEQ ID NO: 23), CNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 24) or WAPVLDFAPPGASAYGSL (SEQ ID NO: 244), or a pharmaceutically acceptable salt thereof.

12 . The compound according to claim 11 , wherein the cancer antigen peptide D is a peptide consisting of:
WAPVLDFAPPGASAYGSL (SEQ ID NO: 244), or a pharmaceutically acceptable salt thereof.

13 . The compound according to claim 1 , wherein the compound of the formula (1) is a compound of formula (15):

wherein the bond between C and C is a disulfide bond, or a pharmaceutically acceptable salt thereof.

14 . The compound according to claim 1 , wherein R 1 is cancer antigen peptide C,
or a pharmaceutically acceptable salt thereof.

15 . The compound according to claim 14 , wherein the cancer antigen peptide C is
a peptide comprising an amino acid sequence selected from the group consisting of:
CMTWNQMNL (SEQ ID NO: 3),
CYTWNQMNL (SEQ ID NO: 4),
SGQARMFPNAPYLPSC (SEQ ID NO: 19),
SGQAYMFPNAPYLPSC (SEQ ID NO: 25),
SGQARMFPNAPYLPSCLES (SEQ ID NO: 11),
SGQAYMFPNAPYLPSCLES (SEQ ID NO: 12),
PGCNKRYFKLSHLQMHSRK (SEQ ID NO: 20),
PGCNKRYFKLSHLQMHSRKH (SEQ ID NO: 21),
PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 10),
CNKRYFKLSHLQMHSRK (SEQ ID NO: 22),
CNKRYFKLSHLQMHSRKH (SEQ ID NO: 23) and
CNKRYFKLSHLQMHSRKHTG (

Assignees

• Sumitomo Dainippon Pharma Co Ltd
• Int Inst Cancer Immunology Inc

Inventors

• Li Chiang Jia
• Ban Hitoshi
• Nishio Yukihiro
• Goto Masashi
• Nishihara Toshio
• Takanashi Yosuke

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title

• C07K14/00

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title

• A61K2039/55511

  Organic adjuvants · CPC title