Drug delivery system

Patent metadata

Field	Value
Publication number	US-2016333073-A1
Application number	US-201515113091-A
Country	US
Kind code	A1
Filing date	Jan 21, 2015
Priority date	Jan 21, 2014
Publication date	Nov 17, 2016
Grant date	—

Abstract

The present invention concerns peptides comprising at least one motif having the amino acid sequence B 1 -X 3-10 -B 2 , wherein B 1 and B 2 are identical or different and each is a basic amino acid and X 3-10 is a sequence of 3 to 10 identical or different non-acidic amino acids, and wherein the N-terminus of the peptide comprises a D-amino acid and/or includes a protecting group, collagen or hyaluronic acid conjugates comprising the same peptides and a therapeutic or diagnostic agent, and compositions and uses thereof. It also concerns peptides comprising at least one motif having the amino acid sequence B 1 -X 3-10 -B 2 , wherein B 1 and B 2 are identical or different and each is a basic amino acid and X 3-10 is a sequence of 3 to 10 identical or different non-acidic amino acids, for use in the treatment or prevention of ocular diseases or conditions. Furthermore, it relates to a method of detecting a hyaluronic acid binding substance, the method comprising providing a sample of hyaluronic acid, contacting the sample of hyaluronic acid with a test substance, and detecting the presence of binding between the test substance and the hyaluronic acid.

First claim

1 . An isolated peptide comprising at least one motif having the amino acid sequence B 1 -X 3-10 -B 2 , wherein B 1 and B 2 are identical or different and each is a basic amino acid and X 3-10 is a sequence of 3 to 10 identical or different non-acidic amino acids, and wherein the N-terminus of the peptide comprises a D-amino acid and/or includes a protecting group.

2 . The peptide according to claim 1 , wherein the peptide has a sequence with at least 60% homology to SEQ ID No. 1, or a functional portion or fragment thereof

3 . The peptide according to claim 1 or claim 2 , wherein the N-terminus of the peptide comprises a D-amino acid.

4 . The peptide according to claim 1 or claim 2 , wherein the the N-terminus of the peptide includes a protecting group.

5 . The peptide according to claim 4 , wherein the protecting group is selected from the group consiting of acetyl, benzoyl, benzyl, tert-butoxycarbonyl, carbobenzyloxy, p-methoxybenyl carbonyl, p-methoxybenzyl, 9-fluorenylmethyloxycarbonyl, 3,4-dimethoxybenzyl, p-methoxyphenyl, tosyl, and nosyl.

6 . The peptide according to claim 5 , wherein the protecting group is acetyl.

7 . The peptide according to any one of claims 2 to 6 , wherein the functional portion or fragment comprises at least 5 contiguous amino acids from SEQ ID No. 1 and shows at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to hyaluronic acid and/or at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to collagen.

8 . The peptide according to any one of claims 2 to 7 , wherein the peptide is a functional portion/fragment thereof having a sequence according to any of those shown in Table 1, and which shows at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to hyaluronic acid and/or at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to collagen.

9 . A collagen or hyaluronic acid binding conjugate comprising a peptide comprising at least one motif having the amino acid sequence B 1 -X 3-10 -B 2 , wherein B 1 and B 2 are identical or different and each is a basic amino acid and X 3-10 is a sequence of 3 to 10 identical or different non-acidic amino acids, wherein the N-terminus of the peptide comprises a D-amino acid and/or includes a protecting group, and a therapeutic or diagnostic agent, wherein the therapeutic or diagnostic agent is optionally bound to the peptide by means of a linker.

10 . The collagen or hyaluronic acid binding conjugate according to claim 9 , wherein the peptide has a sequence with at least 60% homology to SEQ ID No. 1, or a functional portion or fragment thereof.

11 . The collagen or hyaluronic acid binding conjugate according to claim 9 or claim 10 , wherein the protecting group is a nitrogen protecting group located on the nitrogen of the N-terminal amino acid of the peptide and is selected from the group consisting of acetyl, benzoyl, benzyl, tert-butoxycarbonyl, carbobenzyloxy, p-methoxybenyl carbonyl, p-methoxybenzyl, 9-fluorenylmethyloxycarbonyl, 3,4-dimethoxybenzyl, p-methoxyphenyl, tosyl, and nosyl.

12 . The collagen or hyaluronic acid binding conjugate according to claim 11 , wherein the protecting group is acetyl.

13 . The collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 12 , wherein the therapeutic or diagnostic agent is covalently bound to the peptide.

14 . The collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 12 , wherein the therapeutic or diagnostic agent is non-covalently bound to the peptide.

15 . The collagen or hyaluronic acid binding conjugate according to claim 14 , wherein the therapeutic or diagnostic agent is non-covalently bound to the peptide by means of a biotin-streptavidin complex.

16 . The collagen or hyaluronic acid binding conjugate according to claim 15 , wherein the peptide is covalently bound to the biotin moiety, optionally via a linker, and the therapeutic or diagnostic agent is covalently bound to the streptavidin moiety, optionally via a linker.

17 . The collagen or hyaluronic acid binding conjugate according to claim 15 , wherein the peptide is covalently bound to the streptavidin moiety, optionally via a linker, and the therapeutic or diagnostic agent is covalently bound to the biotin moiety, optionally via a linker.

18 . The collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 17 , wherein the linker, when present, comprises a short-chain peptide, a polyethylene glycol oligomer, a C 1-20 alkylene group, a C 2-20 alkenylene group, maleimide and hydrazide functional groups separated by a C 1-20 alkylene or C 2-20 alkenylene group, or any combination thereof.

19 . The collagen or hyaluronic acid binding conjugate according to claim 18 , wherein the short-chain peptide of the linker comprises the amino acids glycine, serine, lysine, cysteine, glutamic acid and/or aspartic acid.

20 . The collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 19 , wherein the linker, when present, is located at the C-terminus of the peptide.

21 . The collagen or hyaluronic acid binding conjugate according to any one of claims 10 to 20 , wherein the functional fragment comprises at least 5 contiguous amino acids from SEQ ID No. 1 and shows at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to hyaluronic acid and/or at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to collagen.

22 . The collagen or hyaluronic acid binding conjugate according to any one of claims 10 to 20 , wherein the peptide is a functional portion/fragment thereof having a sequence according to any of those shown in Table 1, and which shows at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to hyaluronic acid and/or at least 70% of the affinity of the peptide having at least 60% homology to SEQ ID No. 1 to collagen.

23 . The collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 22 , wherein the diagnostic agent comprises a fluorescent, luminescent, or radionuclide label.

24 . The collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 22 , wherein the therapeutic agent is at least one selected from the group consisting of VEGF inhibitors, alpha2-adrenergic agonists, beta-adrenergic antagonists, Angiotensin II antagonists, ACE inhibitors, NSAIDs, antimalarials, corticosteroids, immune suppressants, monoclonal antibodies, retinoids, DMARDs, biologics, nitrates, prostaglandins, and endothelin antagonists.

25 . A pharmaceutical composition comprising a peptide according to any one of claims 1 to 8 , or a collagen or hyaluronic acid binding conjugate according to any one of claims 9 to 24 , and at least one pharmaceutically acceptable excipient.

26 . The pharmaceutical composition according to claim 25 , further comprising at least one additional unconjugated therapeutic agent selected from the group consisting of VEGF inhibitors, alpha2-adrenergic agonists, beta-adrenergic antagonists, Angiotensin II antagonists, ACE inhibitors, NSAIDs, antimalarials, corticosteroids, immune suppressants, monoclonal antibodies, retinoids, DMARDs, biologics, nitrates, prostaglandins, and endothelin antagonists.

Assignees

• Ucl Business Plc

Inventors

• Shima David
• Anderson Owen

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K47/6425

  the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell · CPC title