IP Library › Granted Patent US 10,588,952
Granted Patent B2
US 10,588,952 · App. 14/780,241 · Granted Mar 17, 2020

Conjugate vaccine using trimming function of ERAP1

Inventors: Hitoshi Ban (Osaka, JP); Yukihiro Nishio (Osaka, JP); Masashi Goto (Osaka, JP); Yosuke Takanashi (Osaka, JP)
Assignee: SUMITOMO DAINIPPON PHARMA CO., LTD.
A61K39/0011A61K47/646C12N9/12A61K2039/572A61K2039/627C12Y207/10001
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Quick Facts
Patent No.
US 10,588,952
App. No.
14/780,241
Granted
Mar 17, 2020
Kind
B2
Abstract

The present invention provides a compound represented by the formula (1): wherein X a and Y a are each a single bond or the like, cancer antigen peptide A is an MHC class I-restricted cancer antigen peptide, and R 1 is a hydrogen atom; a group represented by the formula (2): wherein X b and Y b 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 X c and Y c 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.

Claims (399)

1. A compound represented by formula (1):

or a pharmaceutically acceptable salt thereof,

wherein X a and Y a 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 Y a 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

R 1 is a group represented by formula (2):

wherein X b and Y b 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 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).

2. The compound of claim 1 , wherein the cancer antigen peptide A is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 19)

GLYDGMEHL,

(SEQ ID NO: 43)

VLQELNVTV

and

(SEQ ID NO: 53)

KIFGSLAFL,

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the cancer antigen peptide B is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 19)

GLYDGMEHL,

(SEQ ID NO: 43)

VLQELNVTV

and

(SEQ ID NO: 53)

KIFGSLAFL,

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the cancer antigen peptide B is a peptide consisting of an amino acid sequence selected from the following amino acid sequences:

(SEQ ID NO: 101)

AKFVAAWTLKAAA

and

(SEQ ID NO: 102)

aKFVAAWTLKAAa,

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. The compound of claim 1 , wherein the cancer antigen peptide A is a peptide consisting of an amino acid sequence which is one of SEQ ID NOs: 1-85, 87 and 88, the cancer antigen peptide B is a peptide consisting of an amino acid sequence which is one of SEQ ID NOs: 1-85, 87 and 88, or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the cancer antigen peptide A is a peptide consisting of an amino acid sequence which is one of SEQ ID NOs: 3, 11, 13, 19, 26, 27, 29, 33, 40, 41, 43, 50, 53, 66, 83, 84, 85, 87 and 88,

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , wherein the cancer antigen peptide B is a peptide consisting of an amino acid sequence which is one of SEQ ID NOs: 3, 11, 13, 19, 26, 27, 29, 33, 40, 41, 43, 50, 53, 66, 83, 84, 85, 87 and 88,

or a pharmaceutically acceptable salt thereof.

Assignments (2)
CHANGE OF NAME Recorded Jun 10, 2022
From: SUMITOMO DAINIPPON PHARMA CO., LTD.
To: SUMITOMO PHARMA CO., LTD.
Reel/Frame 060161/0046 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 25, 2015
From: BAN, HITOSHI; NISHIO, YUKIHIRO; GOTO, MASASHI; TAKANASHI, YOSUKE
To: SUMITOMO DAINIPPON PHARMA CO., LTD.
Reel/Frame 036659/0411 →