# US 9,517,275 B2 · Targeted therapy for the prevention of restenosis in the cardiovascular system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,517,275 B2 - Document ID: US9517275B2 - Status: Granted - Kind: B2 - Application number: 14/502,252 - Filed: 2014-09-30 - Published: 2015-06-04 - Granted: 2016-12-13 - Earliest claimed: 2013-09-30 - Assignees: Northwestern University - Applicants: Northwestern University - Inventors: Melina R. Kibbe; Samuel I. Stupp; Tyson J. Moyer; Edward Moreira Bahnson - Web page: https://patentgrep.com/patent/US9517275B2 ## CPC - A61K 47/66: the modifying agent being a pre-targeting system involving a peptide or protein for targeting specific cells - A61K 33/00: Medicinal preparations containing inorganic active ingredients - C07K 14/78: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Provided herein are compositions and methods for targeted drug delivery to prevent restenosis in the cardiovascular system. In particular, provided herein are nanoscale delivery vehicles for drugs that prevent proliferation and neointimal hyperplasia. ## Claims ### Claim 1 A peptide amphiphile comprising: (a) a hydrophobic non-peptidic segment; (b) a β-sheet-forming peptide segment; (c) a charged peptide segment; (d) a targeting moiety, wherein the targeting moiety comprises a binding sequence for collagen IV and comprises a 6 amino acid segment with at least 50% sequence identity with KLVWLPK (SEQ ID NO: 2); and (e) a therapeutic agent; wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the β-sheet-forming peptide segment; wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the charged peptide segment; and wherein the C-terminus of the charged peptide segment is covalently attached to the N-terminus of the targeting moiety. ### Claim 2 (depends on 1) The peptide amphiphile of claim 1, wherein the hydrophobic non-peptidic segment comprises an acyl chain. ### Claim 3 (depends on 2) The peptide amphiphile of claim 2, wherein the acyl chain comprises C6-C20. ### Claim 4 (depends on 3) The peptide amphiphile of claim 3, wherein the acyl chain comprises lauric acid. ### Claim 5 (depends on 1) The peptide amphiphile of claim 1, wherein the β-sheet-forming peptide segment comprises AAVV (SEQ ID NO: 3). ### Claim 6 (depends on 1) The peptide amphiphile of claim 1, wherein the charged peptide segment comprises a plurality of Lys (K), Arg (R), Glu (E) and/or Asp (D) residues. ### Claim 7 (depends on 1) The peptide amphiphile of claim 1, wherein the targeting moiety comprises a binding sequence for a target protein. ### Claim 8 (depends on 1) The peptide amphiphile of claim 1, wherein the binding sequence comprises KLVWLPK (SEQ ID NO: 2). ### Claim 9 (depends on 1) The peptide amphiphile of claim 1, wherein the therapeutic agent is covalently linked to a portion of (b)-(d). ### Claim 10 (depends on 9) The peptide amphiphile of claim 9, wherein the therapeutic agent is nitric oxide (NO). ### Claim 11 (depends on 10) The peptide amphiphile of claim 10, wherein the NO is covalently linked to a portion of (b)-(d) as a nitroso group. ### Claim 12 (depends on 11) The peptide amphiphile of claim 11, wherein the nitroso group is attached via nitrosylation of a cysteine residue. ### Claim 13 (depends on 1) The peptide amphiphile of claim 1, comprising an S-nitrosylated cysteine residue. ### Claim 14 (depends on 1) A self-assembled nanofiber formed of the peptide amphiphiles of claim 1. ### Claim 15 (depends on 14) A method of treating or preventing cardiovascular restenosis comprising administering to a subject the self-assembled nanofiber of claim 14. ### Claim 16 (depends on 7) The peptide amphiphile of claim 7, wherein the target protein is selected from the list consisting of elastin, laminin, fibroinectin, collagen I, collagen III, collagen IV, and collagen V. ### Claim 17 (depends on 16) The peptide amphiphile of claim 16, wherein the target protein is collagen IV. ### Claim 18 A peptide amphiphile comprising: (a) a hydrophobic non-peptidic segment comprising a (CH2)12 tail; (b) a peptide portion with at least 50% sequence identity with KLVWLPKCK2A2V2K (SEQ ID NO: 1); and (c) a therapeutic agent; wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the peptide portion. ### Claim 19 (depends on 18) The peptide amphiphile of claim 18, comprising KLVWLPKCK2A2V2K—(CH2)12 (SEQ ID NO: 1) tail. ### Claim 20 (depends on 18) The peptide amphiphile of claim 18, comprising an S-nitrosylated cysteine residue. ### Claim 21 (depends on 18) A self-assembled nanofiber formed of the peptide amphiphiles of claim 18.