US2007072176A1PendingUtilityA1
Novel peptide compositions and their use in particular in the preparation of pharmaceutical compositions active against the hepatitis C virus
Est. expiryMay 17, 2022(expired)· nominal 20-yr term from priority
C12N 2770/24222A61P 31/00C07K 14/005A61K 38/00A61P 37/04A61P 31/14A61K 39/00
53
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Claims
Abstract
The invention relates to peptide compositions for use in the preparation of pharmaceutical compositions against hepatitis C virus, as well as corresponding methods.
Claims
exact text as granted — not AI-modified1 - 88 . (canceled)
89 . Fusion peptide characterized in that it comprises a fusion of at least two peptides chosen from the group consisting of A, B, C, and D peptides, B′ and C′ epitopes,
said A peptide having at least the following amino acid sequence SEQ ID NO: 1: X 1 AX 2 QGYKVX 3 VLNPSVX 4 ATLX 5 FGX 6 YMSKAX 7 GX 8 , in which X 1 is Y or H, X 2 is A, G or T, X 3 is R or L, X 4 is A or T, X 5 is G or S, X 6 is A, T or V, X 7 is H or Y and X 8 is I, T, M, or V, and at most sequence the following amino acid sequence SEQ ID NO: 2, SX 9 X 10 VPX 11 X 12 X 1 AX 2 QGYKVX 3 VLNPSVX 4 ATLX 5 FGX 6 YMSKAX 7 GX 8 X 13 P X 14 X 15 X 16 X 17 GV, in which X 1 to X 8 are as defined above, and X 9 is T or N, X 10 is K or R, X 11 is A or V, X 12 is A or E, X 13 is E or D, X 14 is N or S, X 15 is I, L or V, X 16 is R or S, and X 17 is T or S, said B peptide having at least the following amino acid sequence SEQ ID NO: 45: GX 18 X 19 X 20 X 21 X 22 X 23 TSLTGRDX 24 NX 25 X 26 X 27 GEX 28 QX 29 X 30 STAX 31 X 32 X 33 FL X 34 X 35 X 36 X 37 NGX 38 X 39 WTVX 40 in which X 18 is L or V, X 19 is L or F, X 20 is G or S, X 21 is C or T, X 22 is I or V, X 23 is I or V, X 24 is K, R or T, X 25 is Q or E, X 26 is V or N, X 27 is D, E or C, X 28 is V or A, X 29 is V, I, E or M, X 30 is L or V, X 31 is T, K or A, X 32 is Q or H, X 33 is S or T, X 34 is A or G, X 35 is T or S, X 36 is C or A, X 37 is V, I or T, X 38 is V or A, X 39 is C or M, and X 40 is Y or F, and at most the following sequence SEQ ID NO: 46: AX 41 TX 42 YX 43 X 44 QTRGX 18 X 19 X 20 X 21 X 22 X 23 TSLTGRDX 24 NX 25 X 2 6X 27 GEX 28 Q X 29 X 30 STAX 31 X 32 X 33 FLX 34 X 3 X 36 X 37 NGX 38 X 39 WTVX 40 HGAGX 45 X 4 X 7 in which X 18 to X 40 are as defined above and X 41 is P, S or H, X 42 is A or T, X 43 is S, A, T or C, X 44 is Q or R, X 45 is S, T or A, X 46 is K or R, and X 47 is T or I, said C peptide having at least the following amino acid sequence SEQ ID NO: 127: SX 47′ M X 48 FTX 49 X 50 X 51 TSPLX 52 X 53 X 54 X 55 TLX 56 FNIX 57 GGWVAX 58 QX 59 in which X 47′ is L or P, X 48 is A or S, X 49 is A or S, X 50 is A or S, X 51 is I or V, X 52 is T, S or A, X 53 is T or I, X 54 is Q, S or G, X 55 is N, Q, H, S, Y or T, X 56 is L or M, X 57 is L or W, X 58 is A or S, and X 59 is L, P or I, and at most the following sequence SEQ ID NO: 128: NFIX 60 GX 61 QYLAX 62 LSTLPGNX 63 AX 64 X 65 SX 47′ MX 48 FTX 49 X 50 X 51 TSPLX 52 X 53 X 54 X 55 TLX 56 FNIX 57 GGWVAX 58 QX 59 X 66 X 67 X 68 in which X 47′ to X 59 are as defined above and X 60 is T or S, X 61 is I, T or V, X 62 is G or A, X 63 is P or L, X 64 is I or M, X 65 is A, V or R, X 66 is A or R, X 67 is P, A, or D, and X 68 is P, A, or S, said D peptide having at least the following amino acid sequence SEQ ID NO: 174:
X 69 KX 70 ARX 71 IVX 72 PX 73 LGX 74 RVCEKX 75 ALX 76 X 77 VX 78 X 79 X 80 X 81
in which X 69 is R or Q, X 70 is P or A, X 71 is L or F, X 72 is F or Y, X 73 is D or E, X 74 is V or S, X 75 is M or R, X 76 is Y or H, X 77 is D or N, X 78 is V or I, X 79 is S, T or K, X 80 is T, K, I or N and X 81 is L or T, and
at most the following amino acid sequence SEQ ID NO: 175: KGGX 69 KX 70 ARX 711 VX 72 PX 73 LGX 74 RVCEKX 75 ALX 76 X 77 VX 78 X 79 X 80 X 81 X 82 X 83 X 84 VMG X 85 X 86 YX 87 X 88 Q in which X 69 to X 8 , are as defined above and X 82 is P or A, X 83 is Q, L, H, R, K or P, X 84 is A, T, V or P, X 85 is P, S or A, X 86 is S or A, X 87 is G or R and X 88 is F or C, said B′ epitope having the following sequence SEQ ID NO: 213:
GX 18 X 19 X 20 X 21 X 22 X 23 TSL
in which X 18 is L or V, X 19 is L or F, X 20 is G or S, X 21 is C or T, X 22 is I or V and X 23 is I or V, and
said C′ epitope having the following sequence SEQ ID NO: 221:
SPLX 52 X 53 X 54 X 55 TL
in which X 52 is T, S or A, X 53 is T or I, X 54 is Q, S or G and X 55 is N, Q, H, S, Y or T.
90 . The fusion peptide according to claim 89 , wherein the A peptide is chosen from:
the peptides having at least sequence SEQ ID NO: 3 and at most sequence SEQ ID NO: 19, the peptides having at least sequence SEQ ID NO: 4 and at most a sequence chosen from sequences SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 32 and SEQ ID NO: 34, the peptides having at least sequence SEQ ID NO: 5 and at most a sequence chosen from sequences SEQ ID NO: 21, SEQ ID NO: 28 and SEQ ID NO: 36, the peptides having at least sequence SEQ ID NO: 6 and at most a sequence chosen from sequences SEQ ID NO: 22, SEQ ID NO: 27 and SEQ ID NO: 41, the peptides having at least sequence SEQ ID NO: 7 and at most a sequence chosen from sequences SEQ ID NO: 23 and SEQ ID NO: 37, the peptides having at least sequence SEQ ID NO: 8 and at most sequence SEQ ID NO: 25, the peptides having at least sequence SEQ ID NO: 9 and at most sequence SEQ ID NO: 26, the peptides having at least sequence SEQ ID NO: 10 and at most sequence SEQ ID NO: 29, the peptides having at least sequence SEQ ID NO: 11 and at most sequence SEQ ID NO: 30, the peptides having at least sequence SEQ ID NO: 12 and at most sequence SEQ ID NO: 31, the peptides having at least sequence SEQ ID NO: 13 and at most sequence SEQ ID NO: 33, the peptides having at least sequence SEQ ID NO: 14 and at most a sequence chosen from sequences SEQ ID NO: 35 and SEQ ID NO: 39, the peptides having at least sequence SEQ ID NO: 15 and at most sequence SEQ ID NO: 38, the peptides having at least sequence SEQ ID NO: 16 and at most a sequence chosen from sequences SEQ ID NO: 40 and SEQ ID NO: 42, the peptides having at least sequence SEQ ID NO: 17 and at most sequence SEQ ID NO: 43, and the peptides having at least sequence SEQ ID NO: 18 and at most sequence SEQ ID NO: 44.
91 . The fusion peptide according to claim 89 , wherein the A peptide is chosen from the peptides of sequences SEQ ID NO: 3 to 18.
92 . The fusion peptide according to claim 89 , wherein the B peptide is chosen from:
the peptides having at least sequence SEQ ID NO: 47 and at most sequence SEQ ID NO: 81, the peptides having at least sequence SEQ ID NO: 48 and at most sequence SEQ ID NO: 82, the peptides having at least sequence SEQ ID NO: 49 and at most sequence SEQ ID NO: 83, the peptides having at least sequence SEQ ID NO: 50 and at most a sequence chosen from sequences SEQ ID NO: 84, SEQ ID NO: 90, SEQ ID NO: 105, SEQ ID NO: 107 and SEQ ID NO: 116, the peptides having at least sequence SEQ ID NO: 51 and at most a sequence chosen from sequences SEQ ID NO: 85 and SEQ ID NO: 124, the peptides having at least sequence SEQ ID NO: 52 and at most a sequence chosen from sequences SEQ ID NO: 86 and SEQ ID NO: 120, the peptides having at least sequence SEQ ID NO: 53 and at most sequence SEQ ID NO: 87, the peptides having at least sequence SEQ ID NO: 54 and at most a sequence chosen from sequences SEQ ID NO: 88 and SEQ ID NO: 117, the peptides having at least sequence SEQ ID NO: 55 and at most sequence SEQ ID NO: 89, the peptides having at least sequence SEQ ID NO: 56 and at most a sequence chosen from sequences SEQ ID NO: 91 and SEQ ID NO: 92, the peptides having at least sequence SEQ ID NO: 57 and at most sequence SEQ ID NO: 93, the peptides having at least sequence SEQ ID NO: 58 and at most a sequence chosen from sequences SEQ ID NO: 94 and SEQ ID NO: 110, the peptides having at least sequence SEQ ID NO: 59 and at most sequence SEQ ID NO: 95, the peptides having at least sequence SEQ ID NO: 60 and at most a sequence chosen from sequences SEQ ID NO: 96 and SEQ ID NO: 115, the peptides having at least sequence SEQ ID NO: 61 and at most sequence SEQ ID NO: 97, the peptides having at least sequence SEQ ID NO: 62 and at most a sequence chosen from sequences SEQ ID NO: 98 and SEQ ID NO: 109, the peptides having at least sequence SEQ ID NO: 63 and at most sequence SEQ ID NO: 99, the peptides having at least sequence SEQ ID NO: 64 and at most sequence SEQ ID NO: 100, the peptides having at least sequence SEQ ID NO: 65 and at most sequence SEQ ID NO: 101, the peptides having at least sequence SEQ ID NO: 66 and at most sequence SEQ ID NO: 102, the peptides having at least sequence SEQ ID NO: 67 and at most sequence SEQ ID NO: 103, the peptides having at least sequence SEQ ID NO: 68 and at most sequence SEQ ID NO: 104, the peptides having at least sequence SEQ ID NO: 69 and at most sequence SEQ ID NO: 106, the peptides having at least sequence SEQ ID NO: 70 and at most sequence SEQ ID NO: 108, the peptides having at least sequence SEQ ID NO: 71 and at most sequence SEQ ID NO: 111, the peptides having at least sequence SEQ ID NO: 72 and at most sequence SEQ ID NO: 112, the peptides having at least sequence SEQ ID NO: 73 and at most sequence SEQ ID NO: 113, the peptides having at least sequence SEQ ID NO: 74 and at most sequence SEQ ID NO: 114, the peptides having at least sequence SEQ ID NO: 75 and at most a sequence chosen from sequences SEQ ID NO: 118 and SEQ ID NO: 119, the peptides having at least sequence SEQ ID NO: 76 and at most sequence SEQ ID NO: 121, the peptides having at least sequence SEQ ID NO: 77 and at most sequence SEQ ID NO: 122, the peptides having at least sequence SEQ ID NO: 78 and at most sequence SEQ ID NO: 123, the peptides having at least sequence SEQ ID NO: 79 and at most sequence SEQ ID NO: 125, and the peptides having at least sequence SEQ ID NO: 80 and at most sequence SEQ ID NO: 126.
93 . The fusion peptide according to claim 89 , wherein the B peptide is chosen from the peptides of sequences SEQ ID NO: 47 to 80.
94 . The fusion peptide according to claim 89 , wherein the C peptide is chosen from:
the peptides having at least sequence SEQ ID NO: 129 and at most a sequence chosen from sequences SEQ ID NO: 147, SEQ ID NO: 153, SEQ ID NO: 162 and SEQ ID NO: 167, the peptides having at least sequence SEQ ID NO: 130 and at most a sequence chosen from sequences SEQ ID NO: 148 and SEQ ID NO: 150, the peptides having at least sequence SEQ ID NO: 131 and at most sequence SEQ ID NO: 149, the peptides having at least sequence SEQ ID NO: 132 and at most a sequence chosen from sequences SEQ ID NO: 151, SEQ ID NO: 155, SEQ ID NO: 168 and SEQ ID NO: 171, the peptides having at least sequence SEQ ID NO: 133 and at most sequence SEQ ID NO: 152, the peptides having at least sequence SEQ ID NO: 134 and at most a sequence chosen from sequences SEQ ID NO: 154 and SEQ ID NO: 169, the peptides having at least sequence SEQ ID NO: 135 and at most sequence SEQ ID NO: 156, the peptides having at least sequence SEQ ID NO: 136 and at most a sequence chosen from sequences SEQ ID NO: 157 and SEQ ID NO: 170, the peptides having at least sequence SEQ ID NO: 137 and at most sequence SEQ ID NO: 158, the peptides having at least sequence SEQ ID NO: 138 and at most sequence SEQ ID NO: 159, the peptides having at least sequence SEQ ID NO: 139 and at most sequence SEQ ID NO: 160, the peptides having at least sequence SEQ ID NO: 140 and at most sequence SEQ ID NO: 161, the peptides having at least sequence SEQ ID NO: 141 and at most sequence SEQ ID NO: 163, the peptides having at least sequence SEQ ID NO: 142 and at most sequence SEQ ID NO: 164, the peptides having at least sequence SEQ ID NO: 143 and at most sequence SEQ ID NO: 165, the peptides having at least sequence SEQ ID NO: 144 and at most sequence SEQ ID NO: 166, the peptides having at least sequence SEQ ID NO: 145 and at most sequence SEQ ID NO: 172, and the peptides having at least sequence SEQ ID NO: 146 and at most sequence SEQ ID NO: 173.
95 . The fusion peptide according to claim 89 , wherein the C peptide is chosen from the peptides of sequences SEQ ID NO: 129 to 146.
96 . The fusion peptide according to claim 89 , wherein the D peptide is chosen from:
the peptides having at least sequence SEQ ID NO: 176 and at most a sequence chosen from sequences SEQ ID NO: 188, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205 and SEQ ID NO: 210, the peptides having at least sequence SEQ ID NO: 177 and at most a sequence chosen from sequences SEQ ID NO: 189 and SEQ ID NO: 190, the peptides having at least sequence SEQ ID NO: 178 and at most sequence SEQ ID NO: 191, the peptides having at least sequence SEQ ID NO: 179 and at most sequence SEQ ID NO: 195, the peptides having at least sequence SEQ ID NO: 180 and at most a sequence chosen from sequences SEQ ID NO: 196 and SEQ ID NO: 206, the peptides having at least sequence SEQ ID NO: 181 and at most sequence SEQ ID NO: 197, the peptides having at least sequence SEQ ID NO: 182 and at most a sequence chosen from sequences SEQ ID NO: 198 and SEQ ID NO: 209, the peptides having at least sequence SEQ ID NO: 183 and at most a sequence chosen from sequences SEQ ID NO: 199 and SEQ ID NO: 200, the peptides having at least sequence SEQ ID NO: 184 and at most sequence SEQ ID NO: 207, the peptides having at least sequence SEQ ID NO: 185 and at most sequence SEQ ID NO: 208, the peptides having at least sequence SEQ ID NO: 186 and at most sequence SEQ ID NO: 211, and the peptides having at least sequence SEQ ID NO: 187 and at most sequence SEQ ID NO: 212.
97 . The fusion peptide according to claim 89 , wherein the D peptide is chosen from the peptides of sequences SEQ ID NO: 176 to 187.
98 . The fusion peptide according to claim 89 , wherein the B′ epitope is chosen from the epitopes of sequences SEQ ID NO: 214 to SEQ ID NO: 220.
99 . The fusion peptide according to claim 89 , wherein the C′ epitope is chosen from the epitopes of sequences SEQ ID NO: 222 to SEQ ID NO: 232.
100 . The fusion peptide according to claim 89 , characterized in that it comprises the fusion of two peptides chosen among:
i) the A peptide as defined in claim 89 and another peptide chosen from the B to D peptides as defined in claim 89 , or ii) the B peptide as defined in claim 89 and another peptide chosen from the A, C or D peptides as defined in claim 89 , or iii) the C peptide as defined in claim 89 and another peptide chosen from the A, B or D peptides as defined in claim 89 , or iv) the D peptide as defined in claim 89 and another peptide chosen from the A, B or C peptides as defined in claim 89 .
101 . The fusion peptide according to claim 89 , characterized in that it comprises the fusion of three peptides chosen among:
i) the A peptide as defined in claim 89 and two other peptides chosen from the B to D peptides as defined in claim 89 , or ii) the B peptide as defined in claim 89 and two other peptides chosen from the A, C or D peptides as defined in claim 89 , or iii) the C peptide as defined in claim 89 and two other peptides chosen from the A, B or D peptides as defined in claim 89 , or iv) the D peptide as defined in claim 89 and two other peptides chosen from the A, B or C peptides as defined in claim 89 .
102 . The fusion peptide according to claim 89 , characterized in that it comprises a fusion of the four A to D peptides.
103 . The fusion peptide according to claim 89 , characterized in that it comprises a fusion of A to D peptides with a B peptide as defined in claim 89 located at the N-terminus of the fusion which is fused to a A peptide as defined in claim 89 which is fused to a C peptide as defined in claim 89 which is fused to a D peptide as defined in claim 89 .
104 . The fusion peptide according to claim 103 , characterized in that the A peptide has at least SEQ ID NO: 3 and at most SEQ ID NO: 19; and/or the B peptide has at least SEQ ID NO: 47 and at most SEQ ID NO: 81; and/or the C peptide has at least SEQ ID NO: 129 and at most SEQ ID NO: 147, SEQ ID NO: 153, SEQ ID NO: 162 or SEQ ID NO: 167; and/or the D peptide has at least SEQ ID NO: 176 and at most SEQ ID NO: 188, SEQ ID NO: 192, SEQ ID NO: 193 or SEQ ID NO: 194, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205 or SEQ ID NO: 210.
105 . The fusion peptide according to claim 104 , characterized in that the A peptide has the amino acid sequence defined in SEQ ID NO: 3, the B peptide has the amino acid sequence defined in SEQ ID NO: 47, the C peptide has the amino acid sequence defined in SEQ ID NO: 129 and the D peptide has the amino acid sequence defined in SEQ ID NO: 176.
106 . The fusion peptide according to claim 105 , characterized in that it comprises the amino acid sequence defined in SEQ ID NO: 234.
107 . A peptide composition characterized in that it comprises at least a fusion peptide according to claim 89 .
108 . Nucleotide sequences coding for any one of the fusion peptides as defined in claim 89 .
109 . An expression vector characterized in that it comprises a nucleotide sequence according to claim 108 , as well as the means necessary for its expression.
110 . Expression vector according to claim 109 , characterized in that said vector is a replication-defective adenoviral vector.
111 . Expression vector according to claim 109 , characterized in that said vector is a MVA vaccinia vector.
112 . A microorganism or a host cell transformed by an expression vector as defined in claim 109 .
113 . Antibodies directed against at least one fusion peptide as defined in claim 89 .
114 . A method for inhibiting, preventing, or treating an infection caused by the hepatitis C virus or a HCV-associated disease or pathologic conditions, in an animal, such as a human, the method comprising the administration of a composition of claim 107 to the animal.
115 . A method for inhibiting, preventing, or treating an infection caused by the hepatitis C virus or a HCV-associated disease or pathologic conditions, in an animal, such as a human, the method comprising the administration of at least one fusion peptide of claim 89 to the animal.
116 . A method for inhibiting, preventing, or treating an infection caused by the hepatitis C virus or a HCV-associated disease or pathologic conditions, in an animal, such as a human, the method comprising the administration of at least one expression vector of claim 109 to the animal.
117 . A method for inhibiting, preventing, or treating an infection caused by the hepatitis C virus or a HCV-associated disease or pathologic conditions, in an animal, such as a human, the method comprising the administration of at least one microorganism or host cell of claim 112 to the animal.
118 . A method for inhibiting, preventing, or treating an infection caused by the hepatitis C virus or a HCV-associated disease or pathologic conditions, in an animal, such as a human, the method comprising the administration of at least one nucleotide sequence of claim 108 to the animal.
119 . A pharmaceutical composition, in particular vaccine, containing as active ingredient at least one peptide composition according to claim 107 , in combination with a pharmaceutically appropriate vehicle.
120 . A pharmaceutical composition, in particular vaccine, containing as active ingredient at least one of the antibodies as defined in claim 113 , in combination with a pharmaceutically appropriate vehicle.
121 . Pharmaceutical composition, in particular vaccine, containing as active ingredient at least a fusion peptide according to claim 89 , or at least a nucleotide sequence coding for said fusion peptide, or at least a vector containing said nucleotide sequence placed under the control of the elements necessary for a constitutive and/or inducible expression of said fusion peptide in a host cell, or at least a microorganism or a host cell transformed by said vector, in combination with a pharmaceutically appropriate vehicle.
122 . A diagnostic composition for the detection and/or quantification of the hepatitis C virus comprising at least one peptide composition according to claim 107 .
123 . A diagnostic composition for the detection and/or quantification of the hepatitis C virus comprising at least one antibody according to claim 113 .
124 . A process for detection and/or quantification of the hepatitis C virus in a biological sample taken from an individual capable of being infected by said virus, such as plasma, serum or tissue, characterized in that it comprises stages consisting of:
bringing said biological sample into contact with the antibodies according to claim 113 , under conditions allowing the formation of a complex between the virus and the antibody, and detecting and/or quantifying the formation of said complex by any appropriate means.
125 . A method for the in vitro diagnosis of the hepatitis C virus in a biological sample, comprising contacting the sample with a pharmaceutical composition, in particular vaccine, containing as active ingredient at least a fusion peptide according to claim 89 , or at least a nucleotide sequence coding for said fusion peptide, or at least a vector containing said nucleotide sequence placed under the control of the elements necessary for a constitutive and/or inducible expression of said fusion peptide in a host cell, or at least a microorganism or a host cell transformed by said vector, in combination with a pharmaceutically appropriate vehicle.
126 . A method for the in vitro diagnosis of the hepatitis C virus in a biological sample, comprising contacting the sample with a diagnostic composition as defined in claim 122 or 123 .
127 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the peptide composition according to claim 107 , so as to induce or stimulate said immune response.
128 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the fusion peptide according to claim 89 , so as to induce or stimulate said immune response.
129 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the nucleotide sequence according to claim 108 , so as to induce or stimulate said immune response.
130 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the microorganism or host cell according to claim 112 , so as to induce or stimulate said immune response.
131 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the vector according to claim 109 , so as to induce or stimulate said immune response.
132 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the antibodies according to claim 113 , so as to induce or stimulate said immune response.
133 . A method of inducing or stimulating an immune response against HCV in a host organism comprising administering to said organism the pharmaceutical composition according to any one of claims 119 to 121 , so as to induce or stimulate said immune response.Cited by (0)
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