Compositions and methods for the treatment and prevention of prion disease
AssigneesNew York University, Instituto Nacional de Tecnologia Agropecuaria (INTA), Universidad de la República
InventorsFernando GONI, Thomas WISNIEWSKI, Lucia YIM, Jose Alejandro CHABALGOITY, Analia ELISEI
Life of this patent
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Abstract
The present disclosure is directed to a multi-species prion protein or peptide thereof, and vaccine compositions comprising the same that are useful for the vaccination and treatment of mammalian subjects at risk of having or having prion disease. Also disclosed herein are isolated proteins and peptides, polymers, vaccines, animal bait or feed, antibodies, and methods of inhibiting the onset of or treating a prion disease.
Claims79
An isolated protein or peptide thereof comprising the amino acid sequence of
- (SEQ ID NO:
- 1)
- MX2X3X4X5X6GX8WX10LX12LFVX16X17WX19DX21GX23CKKX27
- PKPGGX33WNTGGX39SRYPGQGX47PGGNRYPX55QGGX59X60
- WGQPHGGGWGQPHGGX76WGQPHGGX84WGQPHGGX92X93X94
- X95X96X97X98X99X100GWGQX105GX107X108HX110QWX113KPX116
- KPKTX121X122KHX125AGAAAAGAVVGGLGGYX142LGSAMSRP
- X151IHFGX156DX158EDRYYRENMX168RYPX172QVYYX177PX179
- X180X181YX183X184QNX187FVX190DCVNITX197KX199HTVTTTT
- KGENFTETDX216KX218ME X221VVEQMCX228TQYX232X233 EX235
- X236 AX238X239 X240 X241 X242 X243 X244 X245 X246 X247
- X248 X249 FSX252PPVX256LLISX261LIX264 LIVX268
- wherein X2 is V or A;
- X3 is K or null;
- X4 is S or null;
- X5 is N or H;
- X6 is I, V, L or M;
- X8 is S, G, Y or C;
- X10 is I, L or M;
- X12 is V, A, or L;
- X16 is A, T, or V;
- X17 is T or M;
- X19 is S or T;
- X21 is V, I, M;
- X23 is L or F;
- X27 is R or W;
- X33 is G or null;
- X39 is G or null;
- X47 S or I;
- X55 is P or S;
- X59 is G or null;
- X60 is G or T;
- X76 is G or S;
- X84 is G or S;
- X92 is G or null;
- X93 is W or null;
- X94 is G or null;
- X95 is Q or null;
- X96 is P or null;
- X97 is H or null;
- X98 is G or null;
- X99 is G or null;
- X100 is G or null;
- X105 is G or S;
- X107 is G or null;
- X108 is T, A, or S;
- X110 is G, N, or S;
- X113 is N or G;
- X116 is S or N;
- X121 is N or S;
- X122 is M or L;
- X125 is V or M;
- X142 is M or L;
- X151 is L, M or I;
- X156 is N or S;
- X158 is Y or W;
- X168 is Y or H;
- X172 is N or E;
- X177 is R or K;
- X179 is V or M;
- X180 is D, N or S;
- X181 is Q, R or E;
- X183 is S or N;
- X184 is N or S;
- X187 is N, S, or T, X190 is H or R;
- X197 is V or I;
- X199 is Q or E;
- X216 is V, M or I;
- X218 is M or I;
- X221 is R or Q;
- X228 is I or V;
- X232 is Q, E, or R;
- X233 R, Q, or K;
- X235 is S or Y;
- X236 is Q or E;
- X238 is Y, S, F, or A;
- X239 is Y or Q;
- X240 is Q, D, or G;
- X241 is G or null;
- X242 R or null;
- X243 is R or K;
- X244 is G, S, or A;
- X245 is A or S;
- X246 is S or G;
- X247 is V, T, A, M or null;
- X248 is I, L, V;
- X249 is L or I;
- X252 is S or P;
- X256 is I or V;
- X261 is F or L;
- X264 is F or L;
- X268 is G or R;
- and
- wherein the isolated protein or peptide thereof does not comprise an amino acid sequence of a corresponding protein of any one of SEQ ID Nos:
- 2-34 or a corresponding peptide thereof.
The vaccine composition of any one of claims 38-41, wherein said composition further comprises an adjuvant.
The isolated polynucleotide of claim 64, wherein said polynucleotide comprises the nucleotide sequence of SEQ ID NO:
- 45.
An isolated antibody or epitope-binding portion thereof, wherein said antibody or epitope-binding portion thereof binds to an epitope of a protein or peptide thereof comprising the amino acid sequence of:
- (SEQ ID NO:
- 1)
- MX2X3X4X5X6GX8WX10LX12LFVX16X17WX19DX21GX23CKKX27
- PKPGGX33WNTGGX39SRYPGQGX47PGGNRYPX55QGGX59X60
- WGQPHGGGWGQPHGGX76WGQPHGGX84WGQPHGGX92X93X94
- X95X96X97X98X99X100GWGQX105GX107X108HX110QWX113KPX116
- KPKTX121X122KHX125AGAAAAGAVVGGLGGYX142LGSAMSRP
- X151IHFGX156DX158EDRYYRENMX168RYPX172QVYYX177PX179
- X180X181YX183X184QNX187FVX190DCVNITX197KX199HTVTTTT
- KGENFTETDX216KX218ME X221VVEQMCX228TQYX232X233 EX235
- X236 AX238X239 X240 X241 X242 X243 X244 X245 X246 X247
- X248 X249 FSX252PPVX256LLISX261LIX264 LIVX268
- wherein X2 is V or A;
- X3 is K or null;
- X4 is S or null;
- X5 is N or H;
- X6 is I, V, L or M;
- X8 is S, G, Y or C;
- X10 is I, L or M;
- X12 is V, A, or L;
- X16 is A, T, or V;
- X17 is T or M;
- X19 is S or T;
- X21 is V, I, M;
- X23 is L or F;
- X27 is R or W;
- X33 is G or null;
- X39 is G or null;
- X47 S or I;
- X55 is P or S;
- X59 is G or null;
- X60 is G or T;
- X76 is G or S;
- X84 is G or S;
- X92 is G or null;
- X93 is W or null;
- X94 is G or null;
- X95 is Q or null;
- X96 is P or null;
- X97 is H or null;
- X95 is G or null;
- X99 is G or null;
- X100 is G or null;
- X105 is G or S;
- X107 is G or null;
- X108 is T, A, or S;
- X110 is G, N, or S;
- X113 is N or G;
- X116 is S or N;
- X121 is N or S;
- X122 is M or L;
- X125 is V or M;
- X142 is M or L;
- X151 is L, M or I;
- X156 is N or S;
- X158 is Y or W;
- X168 is Y or H;
- X172 is N or E;
- X177 is R or K;
- X179 is V or M;
- X180 is D, N or S;
- X181 is Q, R or E;
- X183 is S or N;
- X184 is N or S;
- X187 is N, S, or T, X190 is H or R;
- X197 is V or I;
- X199 is Q or E;
- X216 is V, M or I;
- X218 is M or I;
- X221 is R or Q;
- X228 is I or V;
- X232 is Q, E, or R;
- X233 R, Q, or K;
- X235 is S or Y;
- X236 is Q or E;
- X238 is Y, S, F, or A;
- X239 is Y or Q;
- X240 is Q, D, or G;
- X241 is G or null;
- X242 R or null;
- X243 is R or K;
- X244 is G, S, or A;
- X245 is A or S;
- X246 is S or G;
- X247 is V, T, A, M or null;
- X248 is I, L, V;
- X249 is L or I;
- X252 is S or P;
- X236 is I or V;
- X261 is F or L;
- X264 is F or L;
- X268 is G or R;
- and
- wherein the protein or peptide thereof does not comprise an amino acid sequence of a corresponding protein of any one of SEQ ID Nos:
- 2-34 or a corresponding peptide thereof.
An isolated antibody or epitope-binding portion thereof, wherein said antibody or epitope-binding portion thereof binds to a polymer of a protein or peptide thereof, wherein said protein or peptide thereof of the polymer comprises the amino acid sequence of:
- (SEQ ID NO:
- 1)
- MX2X3X4X5X6GX8WX10LX12LFVX16X17WX19DX21GX23CKKX27
- PKPGGX33WNTGGX39SRYPGQGX47PGGNRYPX55QGGX59X60
- WGQPHGGGWGQPHGGX76WGQPHGGX84WGQPHGGX92X93X94
- X95X96X97X98X99X100GWGQX105GX107X108HX110QWX113KPX116
- KPKTX121X122KHX125AGAAAAGAVVGGLGGYX142LGSAMSRP
- X151IHFGX156DX158EDRYYRENMX168RYPX172QVYYX177PX179
- X180X181YX183X184QNX187FVX190DCVNITX197KX199HTVTTTT
- KGENFTETDX216KX218ME X221VVEQMCX228TQYX232X233 EX235
- X236 AX238X239 X240 X241 X242 X243 X244 X245 X246 X247
- X248 X249 FSX252PPVX256LLISX261LIX264 LIVX268
- wherein X2 is V or A;
- X3 is K or null;
- X4 is S or null;
- X5 is N or H;
- X6 is I, V, L or M;
- X8 is S, G, Y or C;
- X10 is I, L or M;
- X12 is V, A, or L;
- X16 is A, T, or V;
- X17 is T or M;
- X19 is S or T;
- X21 is V, I, M;
- X23 is L or F;
- X27 is R or W;
- X33 is G or null;
- X39 is G or null;
- X47 S or I;
- X55 is P or S;
- X59 is G or null;
- X60 is G or T;
- X76 is G or S;
- X84 is G or S;
- X92 is G or null;
- X93 is W or null;
- X94 is G or null;
- X9 is Q or null;
- X96 is P or null;
- X97 is H or null;
- X98 is G or null;
- X99 is G or null;
- X100 is G or null;
- X105 is G or S;
- X107 is G or null;
- X108 is T, A, or S;
- X110 is G, N, or S;
- X113 is N or G;
- X116 is S or N;
- X121 is N or S;
- X122 is M or L;
- X125 is V or M;
- X142 is M or L;
- X151 is L, M or I;
- X156 is N or S;
- X158 is Y or W;
- X168 is Y or H;
- X172 is N or E;
- X177 is R or K;
- X179 is V or M;
- X180 is D, N or S;
- X181 is Q, R or E;
- X183 is S or N;
- X184 is N or S;
- X187 is N, S, or T, X190 is H or R;
- X197 is V or I;
- X199 is Q or E;
- X216 is V, M or I;
- X218 is M or I;
- X221 is R or Q;
- X228 is I or V;
- X232 is Q, E, or R;
- X233 R, Q, or K;
- X235 is S or Y;
- X236 is Q or E;
- X238 is Y, S, F, or A;
- X239 is Y or Q;
- X240 is Q, D, or G;
- X241 is G or null;
- X242 R or null;
- X243 is R or K;
- X244 is G, S, or A;
- X245 is A or S;
- X246 is S or G;
- X247 is V, T, A, M or null;
- X248 is I, L, V;
- X249 is L or I;
- X252 is S or P;
- X236 is I or V;
- X261 is F or L;
- X264 is F or L;
- X268 is G or R;
- and
- wherein the protein or peptide thereof does not comprise an amino acid sequence of a corresponding protein of any one of SEQ ID Nos:
- 2-34 or a corresponding peptide thereof.
The method of 75, wherein the prion disease is bovine spongiform encephalopathy, chronic wasting disease, scrapie, feline spongiform encephalopathy, transmissible mink encephalopathy, exotic ungulate encephalopathy, or any form of camelid spongiform encephalopathy.
The method of 75, wherein the mammalian subject is a human, and the prion disease is selected from sporadic or familial Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker Syndrome, Fatal Familial Insomnia, and Kuru.
Dependencies are inferred from the claim text.