Immunity inducer for saccharide antigens

Patent metadata

Field	Value
Publication number	US-10307471-B2
Application number	US-201414888353-A
Country	US
Kind code	B2
Filing date	May 2, 2014
Priority date	May 2, 2013
Publication date	Jun 4, 2019
Grant date	Jun 4, 2019

Abstract

The present invention provides an immunity inducer and an immunity inducing method using same. The immunity inducer has an immunopotentiation effect on any target oligosaccharide antigen, in particular oligosaccharide antigens included in mammal-derived glycoprotein N-linked sugar chains; is capable of providing a monoclonal antibody having high specificity to and affinity with target oligosaccharide antigens; and has as an effective component thereof a glycolipid including a target oligosaccharide antigen (R) and indicated by general formula (2), or a salt thereof. General formula (2): R—Z—Y—CH(NH—CO—(CH 2 ) n1 —CH 3 )—CH 2 ) n2 —CH 3 (in the formula, R indicates a straight-chain or branched oligosaccharide comprising 2-30 of at least one type of monosaccharide. Z indicates a single bond, O, S or NH, a linker bound to thiomethyl, amino methylated sugar alcohol. Y indicates —(CH 2 ) m —. n 1 indicates an integer of 2-40, n 2 indicates an integer of 1-27, and m indicates an integer of 1-30).

First claim

The invention claimed is:

1. An immunity inducer comprising an artificial glycolipid or a salt thereof as an effective component, wherein the artificial glycolipid has the chemical formula (2) and includes the target oligosaccharide antigen R:
R—Z—Y—CH(NH—CO—(CH 2 ) n1 —CH 3 )—(CH 2 ) n2 —CH 3   chemical formula (2)

wherein, in the chemical formula (2), R represents a linear chain or branched oligosaccharide constituted with 2 to 30 of one type or plural types of monosaccharides , Z represents a single bond, O, S or NH, a linker bound to thiomethyl, or an aminomethylated sugar alcohol, Y represents —(CH 2 ) m —, n 1 represents an integer from 2 to 40, n 2 represents an integer from 1 to 27, and m represents an integer from 1 to 30, and
wherein the target oligosaccharide antigen R is selected from the group consisting of
an oligosaccharide antigen included in a mammal-derived glycoprotein N-linked sugar chain selected from the group consisting of Siaα2,6Galβ1,4GlcNAc, Siaα2,3Galβ1,4GlcNAc, Galβ1,4GlcNAc, Galβ1,3GlcNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAc, Galβ1,4(Fucα1,3)GlcNAc, Siaα2,3Galβ1,3(Fucα1,4)GlcNAc, Siaα2,3Galβ1,3GlcNAc, Galβ1,3(Fucα1,4)GlcNAc, Siaα2,3Galβ1,3 (Siaα2,6)GlcNAc, Siaα2,3Galβ1,3 (Fucα1,4)(Siaα2,6)GlcNAc, Fucα1,2Galβ1,3(Fucα1,4)GlcNAc, Fucα1,2Galβ1,4GlcNAc, Fucα1,2Galβ1,4(Fucα1,3)GlcNAc, Fucα1,6GlcNAc, GlcNAcβ1,4(Fucα1,6)GlcNAc, Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAc, Manα1,6(Manα1,3)Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAc, Manα1,6(GlcNAcβ1,4) (Manα1,3)Manβ1,4GlcNAcβ1,4GlcNAc, Manα1,6(GlcNAcβ1,4) (Manα1,3)Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAc, GlcNAcβ1,4GlcNAc, Manβ1,4GlcNAcβ1,4GlcNAc, GlcNAcβ1,2Man, GlcNAcβ1,4Man, GlcNAcβ1,6Man, Galβ1,3GlcNAcβ1,2Man, Galβ1,3GlcNAcβ1,4Man, Galβ1,3GlcNAcβ1,6Man, Galβ1,4GlcNAcβ1,2Man, Galβ1,4GlcNAcβ1,4Man, Galβ1,4GlcNAcβ1,6Man, Siaα2,3Galβ1,4GlcNAcβ1,2Man, Siaα2,3Galβ1,4GlcNAcβ1,4Man, Siaα2,3Galβ1,4GlcNAcβ1,6Man, Siaα2,3Galβ1,3GlcNAcβ1,2Man, Siaα2,3Galβ1,3GlcNAcβ1,4Man, Siaα2,3Galβ1,3GlcNAcβ1,6Man, Siaα2,6Galβ1,4GlcNAcβ1,2Man, Siaα2,6Galβ1,4GlcNAcβ1,4Man, Siaα2,6Galβ1,4GlcNAcβ1,6Man, GalNAcβ1,4GlcNAc, GalNAcβ1,4GlcNAcβ1,2Man, GalNAc(4SO 4 )β1,4GlcNAc, GalNAc(4SO 4 )β1,4GlcNAcβ1,2Man, GalNAc(4SO 4 )β1,4GlcNAcβ1,4Man, GalNAc(4SO 4 )β1,4GlcNAcβ1,6Man, GlcAβ1,3Galβ1,4GlcNAc, GlcA(3SO 4 )β1,3Galβ1,4GlcNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAc(6 SO 4 ), Siaα2,3Galβ1,4GlcNAc(6SO 4 ), Galβ1,4GlcNAc(6SO 4 ), Galβ1,4(Fucα1,3) GlcNAc(6SO 4 ), Siaα2,3Gal(6SO 4 )β1,4 (Fucα1,3)GlcNAc, Siaα2,3Gal(6SO 4 )β1,4GlcNAc, Gal(6SO 4 )β1,4GlcNAc, Gal(6SO 4 )β1,4GlcNAc(6SO 4 ), Galβ1,4GlcNAcβ1,3Gal, GlcNAcβ1,3Galβ1,4GlcNAc, Galβ1,4GlcNAc(6SO 4 )β1,3Gal, GlcNAc(6SO 4 )β1,3Galβ1,4GlcNAc, Gal(6SO 4 )β1,4GlcNAc(6SO 4 )β1,3Gal, GlcNAc(6SO 4 )β1,3Gal(6SO 4 )β1,4GlcNAc, Siaα2,3Galβ1,4GlcNAcβ1,3Galβ1,4(Fucα1,3)GlcNAc, Fucα1,2Galβ1,3GlcNAc, Galα1,3(Fucα1,2)Galβ1,3GlcNAc, Galα1,3(Fucα1,2)Galβ1,4GlcNAc, GalNAcα1,3(Fucα1,2)Galβ1,3GlcNAc, GalNAcα1,3(Fucα1,2)Galβ1,4GlcNAc, Fucα1,2Galβ1,4(Fucα1,3)GlcNAcβ1,3Gal, Gal(3SO 4 )β1,4GlcNAc, Gal(3SO 4 )β1,4(Fucα1,3)GlcNAc, Gal(3SO 4 )β1,3GlcNAc, Gal(3SO 4 )β1,3(Fucα1,4)GlcNAc, Gal(3SO 4 )β1,4GlcNAc(6SO 4 ), Gal(3SO 4 )β1,4(Fucα1,3)GlcNAc(6SO 4 ), Siaα2,8Siaα2,8Sia, Siaα2,6GalNAcβ1,4GlcNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAcβ1,3Galβ1,4(Fucα1,3)GlcNAc, Galβ1,4GlcNAcβ1,3(Galβ1,4GlcNAcβ1,6)Gal, and Siaα2,3Galβ1,4GlcNAcβ1,3(Siaα2,3Galβ1,4GlcNAcβ1,6)Gal,
an oligosaccharide antigen included in a mammal-derived glycoprotein O-linked sugar chain selected from the group consisting of Siaα2,3Galβ1,3GalNAc, Galβ1,3GalNAc, Siaα2,3Galβ1,3(GlcNAcβ1,6)GalNAc, GalNAcα1,3GalNAc, GlcNAcβ1,3(Siaα2,6)GalNAc, GalNAcα1,6GalNAc, GlcNAcβ1,6GalNAc, Fucα1,2GalNAc, Galβ1,3(GlcNAcβ1,6)GalNAc, Siaα2,6GalNAc, Siaα2,6(GlcNAcβ1,6)GalNAc, Siaα2,3Galβ1,3(Siaα2,6)GalNAc, Galβ1,4GalNAc, Siaα2,3Galβ1,4GalNAc, GlcNAcα1,4Gal, GlcNAcα1,4Galβ1,4GlcNAc, GlcNAcα1,4Galβ1,4GalNAc, GlcNAcα1,4Galβ1,4(GlcNAcα1,4Galβ1,4GlcNAcβ1,6)GalNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAc(6SO 4 )β1,6GalNAc, Gal(3SO 4 )β1,4GlcNAcβ1,6(Siaα2,3Galβ1,3)GalNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAc(6SO 4 )β1,3Galβ1,3GalNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAc(6SO 4 )β1,3Galβ1,3(Siaα2,3Galβ1,4(Fucα1,3)GlcNAc(6SO 4 )β1,6)GalNAc, Siaα2,3Gal(6SO 4 ) β1,4GlcNAcβ1,3Galβ1,3GalNAc, Gal(3SO 4 )β1,3GalNAc(6SO 4 ), Siaα2,3Galβ1,3GalNAc(6SO 4 ), Gal(3SO 4 )β1,3(Siaα2,6)GalNAc, and Gal(3SO 4 )β1,3GalNAc, and
an oligosaccharide antigen included in a mammal-derived glycosaminoglycan type sugar chain selected from the group consisting of Galβ1,4Xyl, Galβ1,3Galβ1,4Xyl, GlcAβ1,3Galβ1,3Galβ1,4Xyl, GalNAcβ1,4IdoAα1,3Galβ1,3Galβ1,4Xyl, GalNAcβ1,4GlcAβ1,3Galβ1,3Galβ1,4Xyl, GlcNAcα1,4GlcAβ1,3Galβ1,3Galβ1,4Xyl, GlcAβ1,3GalNAcβ1,4GlcA, GalNAcβ1,4GlcAβ1,3GalNAc, GlcAβ1,3GalNAc(4SO 4 )β1,4GlcA, GalNAc(4SO 4 )β1,4GlcAβ1,3GalNAc, GlcAβ1,3GalNAc(6SO 4 )β1,4GlcA, GalNAc(6SO 4 )β1,4GlcAβ1,3GalNAc, GlcA(2SO 4 )β1,3(6SO 4 )GalNAcβ1,4GlcA, GalNAc(6SO 4 )β1,4GlcA(2SO 4 )β1,3GalNAc, GlcAβ1,3GalNAc(4,6SO 4 )β1,4GlcA, GalNAc(4,6SO 4 )β1,4GlcAβ1,3GalNAc, GalNAc(4,6SO 4 )β1,4GlcA(2SO 4 )β1,3GalNAc(6SO 4 ), IdoAα1,3GalNAcβ1,4IdoA, GalNAcβ1,4IdoAα1,3GalNAc, IdoAα1,3GalNAc(4SO 4 )β1,4IdoA, GalNAc(4SO 4 )β1,4IdoAα1,3GalNAc, GlcAβ1,4GlcNAcα1,4GlcA, GlcNAcα1,4GlcAβ1,4GlcNAc, GlcA(2SO 4 )β1,4GlcNAcα1,4GlcA, GlcNAcα1,4GlcA(2SO 4 )β1,4GlcNAc, IdoA(2SO 4 )α1,4GlcNAcα1,4GlcA, GlcNAcα1,4IdoA(2SO 4 )α1,4GlcNAc, GlcA(2SO 4 )β1,4GlcNSO 3 α1,4GlcA, GlcNSO 3 α1,4GlcA(2SO 4 )β1,4GlcNAc, IdoA(2SO 4 )α1,4GlcNSO 3 Hα1,4GlcA, GlcNSO 3 α1,4IdoA(2SO 4 )α1,4GlcNAc, GlcAβ1,4GlcNα1,4GlcA, GlcAβ1,4GlcNSO 3 α1,4GlcA, GlcNSO 3 α1,4GlcAβ1,4GlcNAc, IdoAα1,4GlcNSO 3 α1,4GlcA, GlcNSO 3 α1,4IdoAα1,4GlcNAc, GlcAβ1,4GlcNSO 3 (6SO 4 )α1,4GlcA, GlcNSO 3 (6SO 4 )α1,4GlcAβ1,4GlcNAc, IdoAα1,4GlcNSO 3 (6SO 4 )α1,4GlcA, GlcNSO 3 (6SO 4 )α1,4IdoAα1,4GlcNAc, IdoA(2SO 4 )α1,4GlcNSO 3 (6SO 4 )α1,4GlcA, GlcNSO 3 (6SO 4 )α1,4IdoA(2SO 4 )α1,4GlcNAc, IdoAα1,4GlcNSO 3 α1,4IdoA, GlcAβ1,3GlcNAcβ1,4GlcA, GlcNAcβ1,4GlcAβ1,3GlcNAc, IdoAα1,4GlcNSO 3 , IdoAα1,4GlcNSO 3 (6SO 4 ), IdoA(2SO 4 )α1,4GlcNSO 3 , IdoA(2SO 4 )α1,4GlcNSO 3 (6SO 4 ), IdoA(2SO 4 )α1,4GlcNSO 3 (3SO 4 ), GlcAβ1,4GlcNSO 3 , GlcAβ1,4GlcNSO 3 (6SO 4 ), GlcA(2SO 4 )β1,4GlcNAc, GlcA(2SO 4 )β1,4GlcNSO 3 (3SO 4 ), GlcAβ1,4GlcNSO 3 (3,6SO 4 ), and GlcAβ1,4GlcNSO 3 (3SO 4 ).

2. The immunity inducer according to claim 1 , wherein the target oligosaccharide antigen R is an oligosaccharide antigen included in a mammal-derived glycoprotein N-linked sugar chain selected from the group consisting of Siaα2,6Galβ1,4GlcNAc, Siaα2,3Galβ1,4GlcNAc, Galβ1,4GlcNAc, Galβ1,3GlcNAc, Siaα2,3Galβ1,4(Fucα1,3)GlcNAc, Galβ1,4 (Fucα1,3)GlcNAc, Siaα2,3Galβ1,3(Fucα1,4)GlcNAc, Siaα2,3Galβ1,3GlcNAc, Galβ1,3(Fucα1,4)GlcNAc, Siaα2,3Galβ1,3 (Siaα2,6)GlcNAc, Siaα2,3Galβ1,3(Fucα1,4)(Siaα2,6)GlcNAc, Fucα1,2Galβ1,3(Fucα1,4)GlcNAc, Fucα1,2Galβ1,4GlcNAc, Fucα1,2Galβ1,4(Fucα1,3)GlcNAc, Fucα1,6GlcNAc, GlcNAcβ1,4 (Fucα1,6)GlcNAc, Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAc, Manα1,6(Manα1,3)Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAc, Manα1,6(GlcNAcβ1,4) (Manα1,3)Manβ1,4GlcNAcβ1,4GlcNAc, Manα1,6 (GlcNAcβ1,4) (Manα1,3)Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAc, GlcNAcβ1,4GlcNAc, Manβ1,4GlcNAcβ1,4GlcNAc, GlcNAcβ1,2Man, GlcNAcβ1,4Man, GlcNAcβ1,6Man, Galβ1,3GlcNAcβ1,2Man, Galβ1,3GlcNAcβ1,4Man, Galβ1,3GlcNAcβ1,6Man, Galβ1,4GlcNAcβ1,2Man, Galβ1,4GlcNAcβ1,4Man, Galβ1,4GlcNAcβ1,6Man, Siaα2,3Galβ1,4GlcNAcβ1,2Man, Siaα2,3Galβ1,4GlcNAcβ1,4Man, Siaα2,3Galβ1,4GlcNAcβ1,6Man, Siaα2,3Galβ1,3GlcNAcβ1,2Man, Siaα2,3Galβ1,3GlcNAcβ1,4Man, Siaα2,3Galβ1,3GlcNAcβ1,6Man, Siaα2,6Galβ1,4GlcNAcβ1,2Man, Siaα2,6Galβ1,4GlcNAcβ1,4Man, Siaα2,6Galβ1,4GlcNAcβ1,6Man, GalNAcβ1,4GlcNAc, GalNAcβ1,4GlcNAcβ1,2Man, GalNAc(4SO 4 )β1,4GlcNAc, GalNAc(4SO 4 )β1,4GlcNAcβ1,2Man, GalNAc(4SO 4 )β1,4GlcNAcβ1,4Man, GalNAc(4SO 4 )β1,4GlcNAcβ1,6Man, GlcAβ1,3Galβ1,4GlcNAc, GlcA(3SO 4 )β1,3Galβ1,4GlcNAc, Siaα2,3Galβ1,4 (Fucα1,3)GlcNAc(6SO 4 ), Siaα2,3Galβ1,4GlcNAc(6SO 4 ), Galβ1,4GlcNAc(6SO 4 ), Galβ1,4(Fucα1,3) GlcNAc(6SO 4 ), Siaα2,3Gal(6SO 4 )β1,4 (Fucα1,3)GlcNAc, Siaα2,3Gal(6SO 4 )β1,4GlcNAc, Gal(6SO 4 )β1,4GlcNAc, Gal(6SO 4 )

Assignees

• Aist

Inventors

• Okuda Tetsuya
• Shimizu Hiroki

Classifications

• A61K2039/627

  characterised by the linker · CPC title

• A61K31/702 Primary

  Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K47/543

  Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine · CPC title

• C07H15/10

  containing unsaturated carbon-to-carbon bonds · CPC title