US2023113836A1PendingUtilityA1
New conjugates of peptides and polysaccharide
Assignee: ENLITISA SHANGHAI PHARMACEUTICAL CO LTDPriority: Dec 2, 2019Filed: Dec 2, 2020Published: Apr 13, 2023
Est. expiryDec 2, 2039(~13.3 yrs left)· nominal 20-yr term from priority
C08J 2305/08C08J 2389/00C08J 3/075C08B 37/0072C07K 7/08C07K 7/06A61K 9/06A61K 9/0014A61P 11/00A61P 17/10A61P 29/00A61P 33/12A61Q 19/00A61K 8/64A61P 17/02A61K 8/735C07K 9/00A61P 1/04A61P 17/00A61K 38/00A61Q 19/08A61P 17/06A61P 11/02A61Q 19/02C07K 14/43504A61K 47/61A61K 9/0019A61K 47/6903
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Claims
Abstract
Provided is a conjugate formed between one or more linear polysaccharide chains and a peptide selected from one or more of the peptide components (a), (b), (c) or (d) as defined below: (a) a peptide component of formula (I), A-Q-B I wherein Q represents a structural fragment of formula (II), wherein: the squiggly lines and m have meanings given in the description and A and B have meanings given in the description, but may represent a peptide component of the amino acid sequence: [W-Lys-X1-Ser-U-X2-Y] n-W-Lys-X1-Ser-U-X2-Y--- (SEQ ID No: 3), wherein the dashed line, n, W, X1, U, X2 and Y have meanings given in the description; (b) a peptide component of the amino acid sequence: [Ala-Lys-X1-Ser-U-X2-Y] p-Ala-Lys-X1-Ser-U-X1-Y-G (SEQ ID No: 4) wherein p, G, X1, U, X2 and Y have meanings given in the description; (c) a peptide component of the amino acid sequence: W-Lys-X1-Ser-U-X2-Y-G (SEQ ID No: 5), wherein W, X1, U, X2, Y and G have meanings given in the description; or (d) a peptide component of the amino acid sequence: K-W1-Lys-X1-Ser-U1-X2-Y1-I-J (SEQ ID No: 6), wherein K, W1, U1, Y1, I, J, X1 and X2 have meanings as well as regioisomers, stereoisomers, and pharmaceutically- or cosmetically-acceptable salts of said conjugates, which conjugates are particularly useful in the treatment of conditions characterised by inflammation, including wounds, burns, and disorders of the mucosa, such as anorectal diseases, inflammatory bowel diseases, gynaecological diseases and dental diseases. Preferred linear polysaccharides include hyaluronic acid.
Claims
exact text as granted — not AI-modified1 . A conjugate formed between one or more linear polysaccharide chains and a peptide, which peptide component is selected from one or more of the peptide components (a), (b), (c) or (d) as defined below:
(a) a peptide component of formula I,
A-Q-B I
wherein:
A and B independently represent Z or A 1 -Q 1 -B 1 ;
Q represents a structural fragment of formula II,
wherein:
the squiggly lines represent points of attachment of Q to A and/or B; and
m represents an integer 1 to 4;
A 1 and B 1 independently represent Z or A 2 -Q 2 -B 2 ;
A 2 and B 2 independently represent Z or Z-Q 3 -Z;
Q 1 , Q 2 and Q 3 independently represent structural fragments of formula III,
wherein:
the squiggly lines adjacent to the NH groups represent the points of attachment of Q 1 , Q 2 and Q 3 to A 1 and/or B 1 , A 2 and/or B 2 , and Z, respectively; and the squiggly line adjacent to the O atom represents the point of attachment of Q 1 , Q 2 and Q 3 to Q, Q 1 and Q 2 , respectively; and m is as defined above;
on each occasion that it is employed, Z represents a peptide component of the amino acid sequence:
(SEQ ID No: 3)
[W-Lys-X 1 -Ser-U-X 2 -Y] n -W-Lys-X 1 -Ser-U-X 2 -Y---
wherein:
the dashed line represents the point of attachment of Z to the rest of the molecule;
n represents 0 or an integer 1 to 4; and,
on each occasion that they are employed:
W is absent or represents a 1 or 2 amino acid sequence, in which the amino acids are selected from one or more of the group Lys, Ala, DOPA and a 3,4-dihydrocinnamic acid (HCA) residue, provided that, when present, the HCA residue is located at the N-terminus of the peptide sequence Z;
X 1 represents Pro, Hyp or diHyp;
U represents Tyr, DOPA or a single bond;
X 2 represents Ser, Pro, Hyp or diHyp;
Y represents a single bond or represents a 1 to 5 amino acid sequence, in which the amino acids are selected from one or more of the group Lys, Ala, Pro, Hyp, diHyp, Thr, DOPA and Tyr; or
(b) a peptide component of the amino acid sequence:
(SEQ ID No: 4)
[Ala-Lys-X 1 -Ser-U-X 2 -Y] p -Ala-Lys-X 1 -Ser-U-X 2 -Y-G
wherein:
p represents an integer 1 to 4;
G is absent or represents DOPA or dopamine; and
X 1 , U, X 2 and Y are as defined above; or
(c) a peptide component of the amino acid sequence:
(SEQ ID No: 5)
W-Lys-X 1 -Ser-U-X 2 -Y-G
wherein W, X 1 , U, X 2 , Y and G are as defined above; or
(d) a peptide component of the amino acid sequence:
(SEQ ID No: 6)
K-W 1 -Lys-X 1 -Ser-U 1 -X 2 -Y 1 -I-J
wherein K represents an optional N-terminal HCA group;
W may be absent or represents a 1 or 2 amino acid sequence, in which the amino acids are selected from one or more of the group Ser, Lys, Ala and DOPA;
U 1 represents Tyr, DOPA or a single bond;
Y 1 represents a single bond or represents Y;
I represents Pro, Hyp, diHyp, Thr, DOPA or Tyr; and
J represents Lys or is absent; and
X 1 , X 2 and Y are as defined above,
as well as regioisomers, stereoisomers, and pharmaceutically- or cosmetically-acceptable salts of said conjugate.
2 . The conjugate as claimed in claim 1 , wherein the polysaccharide chain is hyaluronic acid.
3 . The conjugate as claimed in claim 1 , wherein X 1 represents Pro.
4 . The conjugate as claimed in claim 1 , X 2 represents Pro or Hyp.
5 . The conjugate as claimed in claim 1 , wherein W represents HCA, HCA-Ala-, Ala, DOPA, Lys-Ala or DOPA-Ala-.
6 . (canceled)
7 . The conjugate as claimed in claim 1 , wherein Y represents a 4 amino acid sequence, in which the amino acids are selected from one or more of the group Lys, Ala, Hyp, Thr, DOPA and Tyr.
8 . The conjugate as claimed in claim 7 , wherein Y represents an amino acid sequence selected from the group -Hyp-Y 1 -Y 2 -Lys- (SEQ ID No: 156) and -Thr-Y 1 -Y 2 -Lys- (SEQ ID No: 157), wherein Y 1 and Y 2 are each independently selected from the group Ala, Hyp, Thr, DOPA and Tyr.
9 . The conjugate as claimed in claim 7 , wherein the amino acid sequence defined by Y is selected from the group -Pro-Thr-DOPA-Lys- (SEQ ID No: 158), -Pro-Thr-Tyr-Lys- (SEQ ID No: 159), -Thr-Tyr-Pro-Lys- (SEQ ID No: 160), -Thr-DOPA-Pro-Lys- (SEQ ID No: 161), -Hyp-Thr-Tyr-Lys- (SEQ ID No: 162), -Hyp-Thr-DOPA-Lys- (SEQ ID No: 163), -Hyp-Thr-Ala-Lys- (SEQ ID No: 164), -Thr-Tyr-Hyp-Lys- (SEQ ID No: 165), -Thr-DOPA-Hyp-Lys- (SEQ ID No: 166), -Thr-Ala-Hyp-Lys- (SEQ ID No: 167), -Hyp-Thr-, -Thr-Tyr-, -Pro-Thr-, -Thr-DOPA-, -Thr-Tyr-Lys-, -Tyr-Pro-Lys-, -DOPA-Pro-Lys, -Hyp-Thr-Tyr-, -Thr-Tyr-Hyp-Lys-DOPA- (SEQ ID No: 169), -Hyp-Thr-Tyr-Hyp-Lys- (SEQ ID No: 168) and -Hyp-Thr-DOPA.
10 . The conjugate as claimed in claim 1 , wherein m represents 4.
11 . The conjugate as claimed in claim 1 , wherein A and B both represent Z, or both represent A 1 -Q 1 -B 1 .
12 . The conjugate as claimed in claim 1 , wherein A 1 and B 1 both represent Z, or both represent A 2 -Q 2 -B 2 .
13 . The conjugate as claimed in claim 1 , wherein A 2 and B 2 both represent Z, or both represent Z-Q 3 -Z.
14 . The conjugate as claimed in claim 1 , wherein n is 0.
15 . (canceled)
16 . The conjugate as claimed in claim 1 , wherein G is absent and the peptide component as defined under (b) comprises the amino acid sequence:
(SEQ ID No: 7)
Ala-Lys-Pro-Ser-Tyr-Ser-Hyp-Thr-Tyr-Lys-Ala-Lys-
Pro-Ser-Tyr-Ser-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 8)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys-Ala-Lys-
Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys-Ala-Lys-Pro-Ser-
Tyr-Hyp-Hyp-Thr-Tyr-Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-
Hyp-Thr-Tyr-Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-
Tyr-Lys;
(SEQ ID No: 9)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 10)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-
Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-
Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-Ser-
DOPA-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 11)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 12)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-
Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 13)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-
Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-
Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys;
or
(SEQ ID No: 14)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-
Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-
Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-Ser-
Tyr-Hyp-Hyp-Thr-DOPA-Lys.
17 . The conjugate as claimed in claim 1 , wherein U represents Tyr and/or W represents Ala-.
18 . The conjugate as claimed in claim 17 , wherein Z in the peptide component defined under (a) is selected from the group:
(SEQ ID No: 2)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 1)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 15)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 16)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 17)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys-DOPA---;
(SEQ ID No: 18)
Ala-Lys-Pro-Ser-Tyr-Ser-Hyp-Thr-Tyr-Lys-Ala-Lys-
Pro-Ser-Tyr-Ser-Hyp-Thr-Tyr-Lys--;
and
(SEQ ID No: 19)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys-Ala-Lys-
Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys-Ala-Lys-Pro-Ser-
Tyr-Hyp-Hyp-Thr-Tyr-Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-
Hyp-Thr-Tyr-Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-
Tyr-Lys---.
19 . The conjugate as claimed in claim 1 , wherein U represents Tyr and/or W represents Lys-Ala-.
20 . The conjugate as claimed in claim 19 , wherein Z in the peptide component defined under (a) is selected from the group:
Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr--- (SEQ ID No: 37); Lys-Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr-DOPA--- (SEQ ID No: 38); and Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA--- (SEQ ID No: 39).
21 . The conjugate as claimed in claim 1 , wherein U represents Tyr and/or W represents HCA-, HCA-Ala-, DOPA- or DOPA-Ala-.
22 . The conjugate as claimed in claim 21 , wherein Z in the peptide component defined under (a) is selected from the group:
(SEQ ID No: 45)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 46)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 47)
HCA-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Ala-Lys---;
(SEQ ID No: 48)
HCA-Lys-Pro-Ser-Tyr-Hyp-Thr-Ala-Hyp-Lys---;
(SEQ ID No: 49)
DOPA-Lys-Pro-Ser-Tyr-Hyp-Thr-Ala-Hyp-Lys---;
(SEQ ID No: 50)
DOPA-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Ala-Lys---;
(SEQ ID No: 51)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
and
(SEQ ID No: 52)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---.
23 . The conjugate as claimed in claim 1 , wherein U represents DOPA and/or W represents Ala or Lys-Ala-.
24 . The conjugate as claimed in claim 23 , wherein Z in the peptide component defined under (a) is selected from the group:
(SEQ ID No: 65)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 66)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 67)
Lys-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA---;
(SEQ ID No: 68)
Lys-Ala-Lys-Hyp-Ser-DOPA-Hyp-Hyp-Thr-DOPA---;
(SEQ ID No: 69)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-
lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys---;
and
(SEQ ID No: 70)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-
Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-
Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-
Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Ala-Lys-Pro-Ser-
DOPA-Hyp-Hyp-Thr-DOPA-Lys---.
25 . The conjugate as claimed in claim 1 , wherein U represents DOPA and/or W represents HCA-, HCA-Ala-, DOPA- or DOPA-Ala-.
26 . The conjugate as claimed in claim 25 , wherein Z is selected from the group:
(SEQ ID No: 94)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 95)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 96)
HCA-Lys-Pro-Ser-DOPA-Hyp-Thr-Ala-Hyp-Lys---;
(SEQ ID No: 96)
HCA-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Ala-Lys---;
(SEQ ID No: 98)
DOPA-Lys-Pro-Ser-DOPA-Hyp-Thr-Ala-Hyp-Lys---;
(SEQ ID No: 99)
DOPA-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Ala-Lys---;
(SEQ ID No: 100)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 101)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Tyr-Lys---;
and
(SEQ ID No: 102)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys---.
27 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (a), A and B both represent Z, and one or both Z groups represent:
(SEQ ID No: 1)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 2)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 15)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 16)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 45)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 48)
HCA-Lys-Pro-Ser-Tyr-Hyp-Thr-Ala-Hyp-Lys---;
(SEQ ID No: 51)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 65)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 67)
Lys-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA---;
(SEQ ID No: 94)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 99)
DOPA-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Ala-Lys---;
or
(SEQ ID No: 100)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---,
and
Q represents a Lys residue.
28 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (a), A and B both represent A 1 -Q 1 -B 1 , A 1 and B 1 both represent Z, and one or both Z groups represent:
(SEQ ID No: 1)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 2)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 15)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 16)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 38)
;Lys-Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr-DOPA---;
(SEQ ID No: 39)
Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA---;
(SEQ ID No: 45)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 46)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 51)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 65)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 66)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 96)
HCA-Lys-Pro-Ser-DOPA-Hyp-Thr-Ala-Hyp-Lys---;
(SEQ ID No: 98)
DOPA-Lys-Pro-Ser-DOPA-Hyp-Thr-Ala-Hyp-Lys---;
or
(SEQ ID No: 100
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---,
and
Q 1 represents a Lys residue.
29 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (a), A and B both represent A 1 -Q 1 -B 1 , A 1 and B 1 both represent A 2 -Q 2 -B 2 , A 2 and B 2 both represent Z, one or both Z groups represent:
(SEQ ID No: 1)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys---;
(SEQ ID No: 2)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 15)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 16)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys---;
(SEQ ID No: 45)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 51)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys---;
(SEQ ID No: 52)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys---;
(SEQ ID No: 66)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys---;
or
(SEQ ID No: 100)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys---,
and
Q 1 and Q 2 both represent Lys residues.
30 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (a), A and B both represent A 1 -Q 1 -B 1 , A 1 and B 1 both represent A 2 -Q 2 -B 2 , A 2 and B 2 both represent Z-Q 3 -Z, one or both Z groups represent:
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys--- (SEQ ID No: 1); or Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys--- (SEQ ID No: 2), and Q 1 , Q 2 and Q 3 all represent Lys residues.
31 . The conjugate as claimed in claim 17 , wherein the peptide component defined under (c) comprises the amino acid sequence:
(SEQ ID No: 20)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys-DOPA;
(SEQ ID No: 21)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys-Dopamine;
(SEQ ID No: 22)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys-Dopamine;
(SEQ ID No: 23)
Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-DOPA-Lys;
(SEQ ID No: 24)
Ala-Lys-Pro-Ser-Tyr-Pro-Thr-Tyr-Pro-Lys;
(SEQ ID No: 25)
Ala-Lys-Pro-Ser-Tyr-Pro-Thr-DOPA-Pro-Lys;
(SEQ ID No: 26)
Ala-Lys-Pro-Ser-Tyr-Pro-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 27)
Ala-Lys-Pro-Ser-Tyr-Pro-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 28)
Ala-Lys-Pro-Ser-Tyr-Hyp-Pro-Thr-Tyr-Lys;
(SEQ ID No: 29)
Ala-Lys-Pro-Ser-Tyr-Hyp-Pro-Thr-DOPA-Lys;
(SEQ ID No: 30)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 31)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 32)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys-DOPA;
(SEQ ID No: 33)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-DOPA;
(SEQ ID No: 34)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys-Dopamine;
(SEQ ID No: 35)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys-DOPA;
or
(SEQ ID No: 36)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys-Dopamine.
32 . The conjugate as claimed in claim 19 , wherein the peptide component defined under (c) comprises the amino acid sequence:
(SEQ ID No: 40)
Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA;
(SEQ ID No: 41)
Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Dopamine;
and
(SEQ ID No: 42)
Lys-Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr-DOPA;
(SEQ ID No: 43)
Lys-Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr-Tyr;
or
(SEQ ID No: 44)
Lys-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr.
33 . The conjugate as claimed in claim 21 , wherein the peptide component defined under (c) comprises the amino acid sequence:
(SEQ ID No: 53)
DOPA-Lys-Pro-Ser-Tyr-Hyp-Thr-Ala-Hyp-Lys;
(SEQ ID No: 54)
DOPA-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Ala-Lys;
(SEQ ID No: 55)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 56)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 57)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 58)
DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 59)
HCA-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Ala-Lys;
(SEQ ID No: 60)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 61)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 62)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 63)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys;
or
(SEQ ID No: 64)
HCA-Lys-Pro-Ser-Tyr-Hyp-Thr-Ala-Hyp-Lys.
34 . The conjugate as claimed in claim 23 , wherein the peptide component defined under (c) comprises the amino acid sequence:
(SEQ ID No: 71)
Lys-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Dopamine;
(SEQ ID No: 72)
Lys-Ala-Lys-Hyp-Ser-DOPA-Hyp-Hyp-Thr-DOPA;
(SEQ ID No: 73)
Lys-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA;
(SEQ ID No: 74)
Ala-Lys-Pro-Ser-DOPA-Pro-Pro-Thr-Tyr-Lys;
(SEQ ID No: 75)
Ala-Lys-Pro-Ser-DOPA-Pro-Pro-Thr-DOPA-Lys;
(SEQ ID No: 76)
Ala-Lys-Pro-Ser-DOPA-Pro-Thr-Tyr-Pro-Lys;
(SEQ ID No: 77)
Ala-Lys-Pro-Ser-DOPA-Pro-Thr-DOPA-Pro-Lys;
(SEQ ID No: 78)
Ala-Lys-Pro-Ser-DOPA-Pro-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 79)
Ala-Lys-Pro-Ser-DOPA-Pro-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 80)
Ala-Lys-Pro-Ser-DOPA-Hyp-Pro-Thr-Tyr-Lys;
(SEQ ID No: 81)
Ala-Lys-Pro-Ser-DOPA-Hyp-Pro-Thr-DOPA-Lys;
(SEQ ID No: 82)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 83)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 84)
Lys-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Tyr;
(SEQ ID No: 85)
Lys-Ala-Lys-Hyp-Ser-DOPA-Hyp-Hyp-Thr-Tyr;
(SEQ ID No: 86)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Tyr-Lys-DOPA;
(SEQ ID No: 87)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-DOPA;
(SEQ ID No: 88)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Tyr-Lys-Dopamine;
(SEQ ID No: 89)
Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys-Dopamine;
(SEQ ID No: 90)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-Tyr-Hyp-Lys-DOPA;
(SEQ ID No: 91)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys-DOPA;
(SEQ ID No: 92)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-Tyr-Hyp-Lys-Dopamine;
or
(SEQ ID No: 93)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys-Dopamine.
35 . The conjugate as claimed in claim 25 , wherein the peptide component defined under (c) comprises the amino acid sequence:
(SEQ ID No: 103)
DOPA-Lys-Pro-Ser-DOPA-Hyp-Thr-Ala-Hyp-Lys;
(SEQ ID No: 104)
DOPA-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Ala-Lys;
(SEQ ID No: 105)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 106)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 107)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 108)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 109)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 110)
HCA-Lys-Pro-Ser-DOPA-Hyp-Thr-Ala-Hyp-Lys;
(SEQ ID No: 111)
HCA-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Ala-Lys;
(SEQ ID No: 112)
DOPA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 113)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-Tyr-Hyp-Lys;
or
(SEQ ID No: 114)
HCA-Ala-Lys-Pro-Ser-DOPA-Hyp-Hyp-Thr-Tyr-Lys.
36 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), W 1 represents Ala or Ser, or is absent.
37 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), X 2 represents Pro, Hyp or diHyp.
38 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), when K is not present, W 1 represents Ala or is absent and J represents Lys, then I represents Pro, Hyp, diHyp or Thr.
39 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), in the sequence defined by Y 1 :
the amino acid DOPA, Thr or Tyr is linked to I; and/or the amino acid Pro, Hyp or Thr is linked to X 2 .
40 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), K is absent.
41 . The conjugate as claimed in claim 40 , wherein the peptide component defined under (d) comprises the amino acid sequence:
(SEQ ID No: 115)
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 116)
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 117)
Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 118)
Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 119)
Ser-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys;
(SEQ ID No: 120)
Ser-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys;
(SEQ ID No: 121)
Ser-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 122)
Ser-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 123)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 124)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 125)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys;
or
(SEQ ID No: 126)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys.
42 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), J is absent.
43 . The conjugate as claimed in claim 42 , wherein the peptide component defined under (d) comprises the amino acid sequence:
(SEQ ID No: 127)
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Hyp;
(SEQ ID No: 128)
Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 129)
Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp;
(SEQ ID No: 130)
Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 131)
Ser-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr;
(SEQ ID No: 132)
Ser-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp;
(SEQ ID No: 133)
Ser-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 134)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Hyp;
(SEQ ID No: 135)
Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 136)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp;
(SEQ ID No: 137)
Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 138)
Ser-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA;
(SEQ ID No: 146)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr;
(SEQ ID No: 147)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 148)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp;
(SEQ ID No: 149)
Ala-Lys-Pro-Ser-Pro-Thr-Tyr-Pro;
(SEQ ID No: 150)
Ala-Lys-Hyp-Ser-Tyr-Hyp-Thr-Tyr-Hyp;
(SEQ ID No: 151)
Ala-Lys-Hyp-Ser-DOPA-Hyp-Thr-DOPA-Hyp;
or
(SEQ ID No: 152)
Ala-Lys-Hyp-Ser-Tyr-Hyp-Thr-DOPA-Hyp.
44 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), K is an N-terminal HCA group.
45 . The conjugate as claimed in claim 44 , wherein the peptide component defined under (d) comprises the amino acid sequence:
(SEQ ID No: 139)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys;
or
(SEQ ID No: 140)
HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys.
46 . The conjugate as claimed in claim 1 , wherein, in the peptide component defined under (d), W 1 is Ala and J is Lys.
47 . The conjugate as claimed in claim 46 , wherein the peptide component defined under (d) comprises the amino acid sequence:
(SEQ ID No: 141)
Ala-Lys-Pro-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys;
(SEQ ID No: 142)
Ala-Lys-Pro-Ser-Pro-Thr-Tyr-Pro-Lys;
(SEQ ID No: 143)
Ala-Lys-Hyp-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys;
(SEQ ID No: 144)
Ala-Lys-Hyp-Ser-DOPA-Hyp-Thr-DOPA-Hyp-Lys;
or
(SEQ ID No: 145)
Ala-Lys-Hyp-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys.
48 - 49 . (canceled)
50 . A pharmaceutical formulation comprising a conjugate as defined in claim 1 and a pharmaceutically- or cosmetically-acceptable, adjuvant, diluent or carrier.
51 . The pharmaceutical formulation as claimed in claim 50 that is suitable for, adapted for, and/or packaged and presented for, topical administration, wherein the pharmaceutically- or cosmetically-acceptable adjuvant, diluent or carrier is a topical adjuvant, diluent or carrier.
52 . The pharmaceutical formulation as claimed in claim 50 , which is in the form of a gel, a spray, a cream, an ointment or a dry powder.
53 . The pharmaceutical formulation as claimed in claim 50 that is suitable for, adapted for, and/or packaged and presented for, administration by injection.
54 . (canceled)
55 . The pharmaceutical formulation as claimed in claim 50 , which further includes a pharmaceutically-active ingredient.
56 . A kit of parts comprising components:
(A) the conjugate as defined in claim 1 ; and (B) a pharmaceutical formulation including a pharmaceutically-active ingredient in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier, which components (A) and (B) are each provided in a form that is suitable for administration in conjunction with the other.
57 . The pharmaceutical formulation as claimed in claim 55 , wherein the pharmaceutically-active ingredient is an anti-inflammatory agent, a pro-inflammatory agent, an antibiotic, an anti-bacterial and/or antiprotozoal agent, an antiviral agent, an anaesthetic and/or a wound recovery drug.
58 . The pharmaceutical formulation as claimed in claim 57 , wherein the pharmaceutically-active ingredient is an anti-inflammatory agent.
59 - 60 . (canceled)
61 . A method of treatment of inflammation, an inflammatory disorder, and/or of a disorder characterised by inflammation, which method comprises the administration of a conjugate as defined in claim 1 to a patient in need of such treatment.
62 . The method as claimed in claim 61 , wherein the inflammation, inflammatory disorder, and/or disorder characterised by inflammation is selected from the group of radiation vaginitis, fibrosis of the vagina and/or nasosinusitis.
63 . The method as claimed in claim 61 , wherein the disorder characterised by inflammation is, or results in, a wound or a burn.
64 . The method as claimed in claim 63 , wherein the disorder resulting in a wound is hemorrhoids or ulcerative colitis.
65 . The method as claimed in claim 61 , wherein the conjugate(s) or salt thereof is administered topically in the form of a topical formulation.
66 . The method as claimed in claim 65 wherein the relevant condition is treated by way of direct topical administration to the skin.
67 . The method as claimed in claim 65 , wherein the administration is carried out by way of direct topical administration to a mucosal surface.
68 . The method as claimed in claim 61 , wherein the conjugate(s) is/are administered by oral, intravenous, cutaneous or subcutaneous, nasal, intramuscular, intraperitoneal, pulmonary or anorectal delivery.
69 . (canceled)
70 . The method as claimed in claim 61 , wherein the conjugate is crosslinked, before or after administration to the patient.
71 - 77 . (canceled)Join the waitlist — get patent alerts
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