US2013316448A1PendingUtilityA1
Peptides and related molecules that modulate nerve growth factor activity
Est. expirySep 19, 2022(expired)· nominal 20-yr term from priority
A61P 31/18A61P 43/00A61P 9/00A61P 39/00A61P 41/00A61P 35/00A61P 31/22A61P 3/10A61P 25/04A61P 25/00A61P 25/32A61P 27/02A61P 29/00A61P 25/06A61P 25/08A61P 19/02A61P 1/04C07K 14/001A61P 1/02A61P 17/16A61P 17/10C07K 7/08A61P 11/00A61P 11/06A61P 11/02A61P 17/06A61K 38/00A61P 13/00A61P 13/10A61P 15/00C07K 16/22A61P 17/02A61P 17/00A61P 17/04C07H 21/04
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Claims
Abstract
The present invention relates to certain biologically active peptides and polypeptides which can be used as therapeutics or prophylactics against diseases or disorders linked to NGF as the causative agent. In one aspect of the present invention, pharmacologically active polypeptides comprising peptides linked to one or more Fc domains are provided.
Claims
exact text as granted — not AI-modified1 . A peptide comprising an amino acid sequence of the formula:
(SEQ ID NO: 276)
a 1 a 2 a 3 Ca 5 a 6 a 7 a 8 a 9 a 10 a 11 LQSCa 16 a 17 a 18
wherein:
a 1 is L, P, W, F, S, Y, N, R, or H;
a 2 is L, W, F, S, Y, D, or R;
a 3 is L, I, W, Y, D, or E;
a 5 is A, L, G, D, E, or K;
a 6 is A, L, F, S, N, E, K, or H;
a 7 is L, P, Y, or N;
a 8 is A, P, M, F, G, Q, or D;
a 9 is P, M, T, G, or S;
a 10 is A, V, F, H, G, or S;
a 11 is V, L, I, F, T, N, or K;
a 16 is L, I, W, M, or F;
a 17 is A, G, S, W, or N;
a 18 is F, W, or Y; or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
2 . The peptide according to claim 1 wherein:
a 1 is W;
a 2 is D;
a 6 is F;
a 10 is A;
a 11 is K;
a 16 is F.
3 . The peptide according to claim 1 comprising the amino acid sequence of WDMCHFSHAAKLQSCFPH (SEQ ID NO:273).
4 - 16 . (canceled)
17 . A polynucleotide comprising a polynucleotide sequence encoding the peptide according to claim 1 , 2 , or 3 .
18 - 22 . (canceled)
23 . A peptide comprising an amino acid sequence of the formula:
(SEQ ID NO: 274)
b 1 b 2 b 3 CWb 6 b 7 b 8 b 9 GCb 12 b 13 b 14
wherein:
b 1 is V, L, I, W, T, Y, or E;
b 2 is L, W, M, Q, or H;
b 3 is W, M, G, Q, or E;
b 6 is F or W;
b 7 is T or S;
b 8 is A, P, W, S, E, or D;
b 9 is A, G, Q, E, or K;
b 12 is V, I, P, D, or E;
b 13 is V, W, or Y; and
b 14 is P, S, or Q; or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
24 . The peptide according to claim 23 wherein:
b 1 is L or I;
b 2 is Q or H;
b 3 is G or M;
b 6 is F or W;
b 7 is T or S;
b 8 is E or D;
b 9 is E or K;
b 12 is V or E;
b 13 is V, W, or Y;
b 14 is P, S, or Q.
25 - 26 . (canceled)
27 . A composition of matter comprising at least one peptide according to claim 23 and at least one vehicle, wherein said composition of matter is capable of inhibiting NGF activity.
28 - 38 . (canceled)
39 . A polynucleotide comprising a polynucleotide sequence encoding the peptide according to claim 23 .
40 . An expression vector comprising the polynucleotide of claim 39 .
41 - 44 . (canceled)
45 . A peptide comprising an amino acid sequence of the formula:
c 1 c 2 QCc 5 c 6 Sc 8 c 9 GCc 12 c 13 c 14 c 15 c 16
wherein:
c 1 is V, I, T, Y, N, or K;
c 2 is L, M, or F;
c 5 is S, Q, or E;
c 6 is L, F, W, or Y;
c 8 is W, M, T, G, S, or N;
c 9 is A, V, G, S, or E;
c 12 is L, P, G, D, or E;
c 13 is K, I, L, Y, or Q;
c 14 is A, S, P, V, M, or Q;
c 15 is L or absent; and
c 16 is E or absent; or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
46 . The peptide according to claim 45 wherein:
c 1 is K or T;
c 2 is L or F;
c 5 is E or Q;
c 6 is L, F, or Y;
c 8 is T;
c 9 is S or A; and
c 12 is P or L.
47 . A peptide selected from the group consisting of SEQ ID NOS: 208, 209, 224, 233, 234, 241, 246, 279, and 280, or a physiologically acceptable salt thereof, wherein said peptide is capable of inhibiting NGF activity.
48 . A composition of matter comprising at least one peptide according to claim 47 and at least one vehicle, wherein said composition of matter is capable of inhibiting NGF activity.
49 - 51 . (canceled)
52 . A composition of matter having the formula:
( X 1 ) a —F 1 —( X 2 ) b
wherein:
F 1 is a vehicle;
X 1 and X 2 are each independently selected from
-(L 1 ) c -P 1 ;
-(L 1 ) c -P 1 -(L 2 ) d -P 2 ;
-(L 1 ) c -P 1 -(L 2 ) d -P 2 -(L 3 ) c -P 3 ; and
-( L 1 ) c - P 1 -( L 2 ) d - P 2 -( L 3 ) c - P 3 -( L 4 ) f - P 4 ; and
wherein one or more of P 1 , P 2 , P 3 , and P 4 each independently comprise a peptide selected from the group consisting of SEQ ID NOS: 208, 209, 224, 233, 234, 241, 246, 279, and 280;
L 1 , L 2 , L 3 , and L 4 are each independently linkers; and a, b, c, d, e, and f are each independently 0 or 1, provided that at least one of a and b is 1; or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
53 - 58 . (canceled)
59 . A polynucleotide comprising a polynucleotide sequence encoding the peptide according to claim 45 .
60 . An expression vector comprising the polynucleotide of claim 59 .
61 - 64 . (canceled)
65 . A peptide comprising an amino acid sequence of the formula:
d 1 d 2 d 3 d 4 d 5 d 6 d 7 PPd 10 d 11 d 12 d 13 d 14 d 15 Pd 17 d 18
d 19 d 20 d 21 d 22 d 23 d 24
wherein:
d 1 is a W, Y, Q, or E;
d 2 is a V, L, F, S, or Q;
d 3 is a W, F, G, S, or Q;
d 4 is a A, Q, D, E, or K;
d 5 is a V, W, G, or R;
d 6 is a M, S, Y, Q, N, E, K, or R;
d 7 is a A, V, L, P, W, Q, or H;
d 10 is a D or E;
d 11 is a V or I;
d 12 is a V, L, F, or Y;
d 13 is a V, L, G, Q, or E;
d 14 is a Q, D, or E;
d 15 is a W or C;
d 17 is a W, Y, or Q;
d 18 is a V, T, Q, N, or K;
d 19 is a A, L, or P;
d 20 is a P, Q, R, or H;
d 21 is a V, I, W, D;
d 22 is a A, I, S, Q, or D;
d 23 is a L or absent;
d 24 is a E or absent;
or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
66 . The peptide according to claim 65 wherein:
d 1 is Q or Y;
d 2 is L;
d 3 is W or D;
d 4 is D, E, or K;
d 5 is V, W, or G;
d 6 is Q, K, or R;
d 7 is W or L;
d 10 is E or D;
d 11 is V or I;
d 12 is V, L, or F;
d 13 is V, L, or G;
d 14 is Q, D, or E;
d 15 is W or C;
d 17 is W or Y;
d 18 is Q, K, or N;
d 19 is P, V, or L;
d 20 is P or S;
d 21 is V;
d 22 is Q or D;
d 23 is a L or absent;
d 24 is a E or absent.
67 . A peptide selected from the group consisting of SEQ ID NOS: 203, 228, 240, 247, and 266, inclusive, or a physiologically acceptable salt thereof, wherein said peptide is capable of inhibiting NGF activity.
68 . A composition of matter comprising at least one peptide according to claim 65 and at least one vehicle, wherein said composition of matter is capable of inhibiting NGF activity.
69 - 79 . (canceled)
80 . A polynucleotide comprising a polynucleotide sequence encoding the peptide according to claim 65 .
81 - 85 . (canceled)
86 . A peptide comprising an amino acid sequence of the formula:
f 1 f 2 f 3 f 4 f 5 f 6 f 7 f 8 f 9 f 10 f 11 Lf 13 EQYFf 18 Lf 20 PPGf 24 f 25 f 26
wherein:
f 1 is A or absent;
f 2 is Q or absent;
f 3 is L, M, T, Q or N;
f 4 is A, I, P, T, G, or Q;
f 5 is M, G, E, or D;
f 6 is W or H;
f 7 is L, P, or M;
f 8 is G, L, R, or S;
f 9 is A, Q, D, or E;
f 10 is L, N, or M;
f 11 is P, R, or S;
f 13 is L, F, or Y;
f 18 is A, Q, E, or R;
f 20 is T, M, or I;
f 24 is L, I, V, or Y;
f 25 is a L or absent; and
f 26 is a E or absent, or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
87 . (canceled)
88 . A peptide selected from the group consisting of SEQ ID NOS: 210, 230, 232, 236, 239, and 251, inclusive, or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
89 - 100 . (canceled)
101 . A polynucleotide comprising a polynucleotide sequence encoding the peptide according to claim 86 .
102 . An expression vector comprising the polynucleotide of claim 101 .
103 - 106 . (canceled)
107 . A peptide comprising an amino acid sequence of the formula:
h 1 h 2 h 3 h 4 h 5 h 6 LGh 9 h 10 h 11 Lh 13 YFh 16 Lh 18 PPGh 22 h 23 h 24
wherein:
h 1 is A or absent;
h 2 is Q or absent;
h 3 is V, G, P, or absent;
h 4 is V, T, S, K, or absent;
h 5 is S, E, Q, or D;
h 6 is Q, N, K, or M;
h 9 is S, G, Q, or D;
h 10 is W, Y, Y or F;
h 11 is A, L, or M;
h 13 is Q, N, or Y;
h 16 is K, H, S, or R;
h 18 is A, V, L, or I;
h 22 is S, T, or G;
h 23 is L or absent;
h 24 is E or absent; or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
108 . (canceled)
109 . A peptide selected from the group consisting of SEQ ID NOS: 202, 211, 219, 221, 231, 237, and 272, inclusive, or a physiologically acceptable salt thereof, and wherein said peptide is capable of inhibiting NGF activity.
110 . (canceled)
111 . A composition of matter comprising at least one peptide selected from the group consisting of SEQ ID NOS: 202, 211, 219, 221, 231, 237, and 272, inclusive, and a vehicle, and wherein said composition of matter is capable of inhibiting NGF activity.
112 - 131 . (canceled)
132 . A composition of matter comprising an amino acid sequence of the formula:
( X 1 ) a —F 1 —( X 2 ) b
wherein:
F 1 is an Fc domain;
X 1 and X 2 are each independently selected from -(L 1 ) c -P 1 , -(L 1 ) c -P 1 -(L 2 ) d -P 2 , -(L 1 ) c -P 1 -(L 2 ) d -P 2 -(L 3 ) e -P 3 , and -(L 1 ) c -P 1 -(L 2 ) d -P 2 -(L 3 ) e -P 3 -(L 4 ) f -P 4 ;
L 1 , L 2 , L 3 , and L 4 are each independently linkers;
a, b, c, d, e, and f are each independently 0 or 1, provided that at least one of a and b is 1; and
P 1 , P 2 , P 3 , and P 4 are each independently sequences selected from the group consisting of:
i. SEQ ID NO: 1 to SEQ ID NO: 58, inclusive;
ii. SEQ ID NO: 202 to SEQ ID NO: 280, inclusive;
iii. an analog of (i) or (ii); and
iv. a derivative of (i), (ii) or (iii); or a physiologically acceptable salt thereof, and wherein said composition of matter is capable of inhibiting NGF activity.
133 - 138 . (canceled)
139 . A peptide comprising an amino acid sequence selected from the group consisting of:
i. SEQ ID NOS: 8, 10, 23, or 24; ii. an analog of (i); and iii. a physiologically acceptable salt of (i) or (ii), wherein said peptide is capable of inhibiting NGF activity.
140 - 149 . (canceled)
150 . A polynucleotide comprising a polynucleotide sequence encoding the peptide according to claim 139 .
151 - 163 . (canceled)Join the waitlist — get patent alerts
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