US 10,588,952 B2 · Conjugate vaccine using trimming function of ERAP1

Abstract

The present invention provides a compound represented by the formula (1): wherein Xa and Ya are each a single bond or the like, cancer antigen peptide A is an MHC class I-restricted cancer antigen peptide, and R1 is a hydrogen atom; a group represented by the formula (2): wherein Xb and Yb are each a single bond or the like, and cancer antigen peptide B is different from the cancer antigen peptide A and is an MHC class I or II-restricted cancer antigen peptide; a group represented by the formula (3): wherein Xc and Yc are each a single bond or the like, and cancer antigen peptide C is an MHC class II-restricted cancer antigen peptide; or cancer antigen peptide D, wherein the cancer antigen peptide D is an MHC class I or II-restricted cancer antigen peptide containing one cysteine residue, or a salt thereof, for example.

A compound represented by formula (1):

or a pharmaceutically acceptable salt thereof,
wherein Xa and Ya are each independently a single bond,
cancer antigen peptide A is an MHC class I-restricted cancer antigen peptide consisting of an amino acid sequence selected from the group consisting of
(SEQ ID NO:
1)
EADPTGHYS,
(SEQ ID NO:
2)
SLFRAVITK,
(SEQ ID NO:
3)
NYKHCFPEI,
(SEQ ID NO:
4)
EVYDGREHSA,
(SEQ ID NO:
5)
REPVTKAEML,
(SEQ ID NO:
6)
DPARYEFLW,
(SEQ ID NO:
7)
SAFPTTINF,
(SEQ ID NO:
8)
SAYGEPRKL,
(SEQ ID NO:
9)
SAYGEPRKL,
(SEQ ID NO:
10)
KMVELVHFL,
(SEQ ID NO:
11)
EYLQLVFGI,
(SEQ ID NO:
12)
EADPIGHLY,
(SEQ ID NO:
13)
FLWGPRALV,
(SEQ ID NO:
14)
TFPDLESEF,
(SEQ ID NO:
15)
MEVDPIGHLY,
(SEQ ID NO:
16)
WQYFFPVIF,
(SEQ ID NO:
17)
GVYDGREHTV,
(SEQ ID NO:
18)
MVKISGGPR,
(SEQ ID NO:
19)
GLYDGMEHL,
(SEQ ID NO:
20)
VRIGHLYIL,
(SEQ ID NO:
21)
AARAVFLAL,
(SEQ ID NO:
22)
FLWGPRAYA,
(SEQ ID NO:
23)
YRPRPRRY,
(SEQ ID NO:
24)
YYWPRPRRY,
(SEQ ID NO:
25)
MTQGQHFLQKV,
(SEQ ID NO:
26)
SLLMWITQCFL,
(SEQ ID NO:
27)
QLSLLMWIT,
(SEQ ID NO:
28)
ASGPGGGAPR,
(SEQ ID NO:
29)
AAGIGILTV,
(SEQ ID NO:
30)
AEEAAGIGIL,
(SEQ ID NO:
31)
TILLGIFFL,
(SEQ ID NO:
32)
KTWGQYWQV,
(SEQ ID NO:
33)
LIYRRRLMK,
(SEQ ID NO:
34)
VYFFLPDHL,
(SEQ ID NO:
35)
SNDGPTLI,
(SEQ ID NO:
36)
VSHSFPHPLY,
(SEQ ID NO:
37)
FLTPKKLQCV,
(SEQ ID NO:
38)
HSTNGVTRIY,
(SEQ ID NO:
39)
KCDICTDEY,
(SEQ ID NO:
40)
YMDGTMSQV,
(SEQ ID NO:
41)
AFLPWHRLF,
(SEQ ID NO:
42)
SEIWRDIDF,
(SEQ ID NO:
43)
VLQELNVTV,
(SEQ ID NO:
44)
MSLQRQFLR,
(SEQ ID NO:
45)
SVYDFFVWL,
(SEQ ID NO:
46)
LLGPGRPYR,
(SEQ ID NO:
47)
ANDPIFVVL,
(SEQ ID NO:
48)
AFLRHAAL,
(SEQ ID NO:
49)
MLMAQEALAFL,
(SEQ ID NO:
50)
YLSGANLNL,
(SEQ ID NO:
51)
HLFGYSWYK,
(SEQ ID NO:
52)
KFHRVIKDF,
(SEQ ID NO:
53)
KIFGSLAFL,
(SEQ ID NO:
54)
VLRENTSPK,
(SEQ ID NO:
55)
ILAKFLHWL,
(SEQ ID NO:
56)
SPRWWPTCL,
(SEQ ID NO:
57)
STAPPAHGV,
(SEQ ID NO:
58)
STAPPVHNV,
(SEQ ID NO:
59)
LLNQLQVNL,
(SEQ ID NO:
60)
LYVDSLFFL,
(SEQ ID NO:
61)
AYGLDFYIL,
(SEQ ID NO:
62)
VPYGSFKHV,
(SEQ ID NO:
63)
LPRWPPPQL,
(SEQ ID NO:
64)
EYRGFTQDF,
(SEQ ID NO:
65)
DYSARWNEI,
(SEQ ID NO:
66)
AYIDFEMKI,
(SEQ ID NO:
67)
GVALQTMKQ,
(SEQ ID NO:
68)
SYLDSGIHF,
(SEQ ID NO:
69)
FPSDSWCYF,
(SEQ ID NO:
70)
ACDPHSGHFV,
(SEQ ID NO:
71)
ETVSEQSNV,
(SEQ ID NO:
72)
VLPDVFIRC,
(SEQ ID NO:
73)
HLSTAFARV,
(SEQ ID NO:
74)
SLFEGIDIY,
(SEQ ID NO:
75)
YSWMDISCWI,
(SEQ ID NO:
76)
EEKLIVVLF,
(SEQ ID NO:
77)
SELFRSGLDY,
(SEQ ID NO:
78)
FRSGLDSYV,
(SEQ ID NO:
79)
EAFIQPITR,
(SEQ ID NO:
80)
KINKNPKYK,
(SEQ ID NO:
81)
SPSSNRIRNT,
(SEQ ID NO:
82)
RVAALARDA,
(SEQ ID NO:
83)
AYACNTSTL,
(SEQ ID NO:
84)
KWFPSCQFLL,
(SEQ ID NO:
85)
GYDQIMPKK,
(SEQ ID NO:
87)
VYGFVRACL
and
(SEQ ID NO:
88)
SLLMWITQC,
or a peptide comprising an amino acid sequence which is one of SEQ ID NOs:
1-85, 87 and 88 where an amino acid is deleted from, substituted in, or added to the original amino acid sequence, and having a CTL induction activity,
an amino group of an N-terminal amino acid of the cancer antigen peptide A binds to Ya in the formula (I), 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), and
R1 is a group represented by formula (2):
wherein Xb and Yb are each independently a single bond,
cancer antigen peptide B is different from the cancer antigen peptide A, and is an MHC class I-restricted cancer antigen peptide consisting of an amino acid sequence selected from the group consisting of
(SEQ ID NO:
1)
EADPTGHYS,
(SEQ ID NO:
2)
SLFRAVITK,
(SEQ ID NO:
3)
NYKHCFPEI,
(SEQ ID NO:
4)
EVYDGREHSA,
(SEQ ID NO:
5)
REPVTKAEML,
(SEQ ID NO:
6)
DPARYEFLW,
(SEQ ID NO:
7)
SAFPTTINF,
(SEQ ID NO:
8)
SAYGEPRKL,
(SEQ ID NO:
9)
SAYGEPRKL,
(SEQ ID NO:
10)
KMVELVHFL,
(SEQ ID NO:
11)
EYLQLVFGI,
(SEQ ID NO:
12)
EADPIGHLY,
(SEQ ID NO:
13)
FLWGPRALV,
(SEQ ID NO:
14)
TFPDLESEF,
(SEQ ID NO:
15)
MEVDPIGHLY,
(SEQ ID NO:
16)
WQYFFPVIF,
(SEQ ID NO:
17)
GVYDGREHTV,
(SEQ ID NO:
18)
MVKISGGPR,
(SEQ ID NO:
19)
GLYDGMEHL,
(SEQ ID NO:
20)
VRIGHLYIL,
(SEQ ID NO:
21)
AARAVFLAL,
(SEQ ID NO:
22)
FLWGPRAYA,
(SEQ ID NO:
23)
YRPRPRRY,
(SEQ ID NO:
24)
YYWPRPRRY,
(SEQ ID NO:
25)
MTQGQHFLQKV,
(SEQ ID NO:
26)
SLLMWITQCFL,
(SEQ ID NO:
27)
QLSLLMWIT,
(SEQ ID NO:
28)
ASGPGGGAPR,
(SEQ ID NO:
29)
AAGIGILTV,
(SEQ ID NO:
30)
AEEAAGIGIL,
(SEQ ID NO:
31)
TILLGIFFL,
(SEQ ID NO:
32)
KTWGQYWQV,
(SEQ ID NO:
33)
LIYRRRLMK,
(SEQ ID NO:
34)
VYFFLPDHL,
(SEQ ID NO:
35)
SNDGPTLI,
(SEQ ID NO:
36)
VSHSFPHPLY,
(SEQ ID NO:
37)
FLTPKKLQCV,
(SEQ ID NO:
38)
HSTNGVTRIY,
(SEQ ID NO:
39)
KCDICTDEY,
(SEQ ID NO:
40)
YMDGTMSQV,
(SEQ ID NO:
41)
AFLPWHRLF,
(SEQ ID NO:
42)
SEIWRDIDF,
(SEQ ID NO:
43)
VLQELNVTV,
(SEQ ID NO:
44)
MSLQRQFLR,
(SEQ ID NO:
45)
SVYDFFVWL,
(SEQ ID NO:
46)
LLGPGRPYR,
(SEQ ID NO:
47)
ANDPIFVVL,
(SEQ ID NO:
48)
AFLRHAAL,
(SEQ ID NO:
49)
MLMAQEALAFL,
(SEQ ID NO:
50)
YLSGANLNL,
(SEQ ID NO:
51)
HLFGYSWYK,
(SEQ ID NO:
52)
KFHRVIKDF,
(SEQ ID NO:
53)
KIFGSLAFL,
(SEQ ID NO:
54)
VLRENTSPK,
(SEQ ID NO:
55)
ILAKFLHWL,
(SEQ ID NO:
56)
SPRWWPTCL,
(SEQ ID NO:
57)
STAPPAHGV,
(SEQ ID NO:
58)
STAPPVHNV,
(SEQ ID NO:
59)
LLNQLQVNL,
(SEQ ID NO:
60)
LYVDSLFFL,
(SEQ ID NO:
61)
AYGLDFYIL,
(SEQ ID NO:
62)
VPYGSFKHV,
(SEQ ID NO:
63)
LPRWPPPQL,
(SEQ ID NO:
64)
EYRGFTQDF,
(SEQ ID NO:
65)
DYSARWNEI,
(SEQ ID NO:
66)
AYIDFEMKI,
(SEQ ID NO:
67)
GVALQTMKQ,
(SEQ ID NO:
68)
SYLDSGIHF,
(SEQ ID NO:
69)
FPSDSWCYF,
(SEQ ID NO:
70)
ACDPHSGHFV,
(SEQ ID NO:
71)
ETVSEQSNV,
(SEQ ID NO:
72)
VLPDVFIRC,
(SEQ ID NO:
73)
HLSTAFARV,
(SEQ ID NO:
74)
SLFEGIDIY,
(SEQ ID NO:
75)
YSWMDISCWI,
(SEQ ID NO:
76)
EEKLIVVLF,
(SEQ ID NO:
77)
SELFRSGLDY,
(SEQ ID NO:
78)
FRSGLDSYV,
(SEQ ID NO:
79)
EAFIQPITR,
(SEQ ID NO:
80)
KINKNPKYK,
(SEQ ID NO:
81)
SPSSNRIRNT,
(SEQ ID NO:
82)
RVAALARDA,
(SEQ ID NO:
83)
AYACNTSTL,
(SEQ ID NO:
84)
KWFPSCQFLL,
(SEQ ID NO:
85)
GYDQIMPKK,
(SEQ ID NO:
87)
VYGFVRACL
and
(SEQ ID NO:
88)
SLLMWITQC,
or a peptide comprising an amino acid sequence which is one of SEQ ID NOs:
1-85, 87 and 88 where an amino acid is deleted from, substituted in, or added to the original amino acid sequence, and having a CTL induction activity,
or an MHC class II-restricted cancer antigen peptide consisting of an amino acid sequence selected from the group consisting of
(SEQ ID NO:
101)
AKFVAAWTLKAAA
and
(SEQ ID NO:
102)
aKFVAAWTLKAAa,
or a peptide comprising an amino acid sequence which is one of SEQ ID NOs:
101 and 102 where an amino acid is deleted from, substituted in, or added to the original amino acid sequence, and having a helper T cell induction activity,
an amino group of an N-terminal amino acid of the cancer antigen peptide B binds to Yb 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).

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Conjugate vaccine using trimming function of ERAP1

Life of this patent

Conjugate vaccine using trimming function of ERAP1

Life of this patent

Abstract

Claims8