# US 9,290,538 B2 · Cell-permeable peptide inhibitors of the JNK signal transduction pathway > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,290,538 B2 - Document ID: US9290538B2 - Status: Granted - Kind: B2 - Application number: 14/144,938 - Filed: 2013-12-31 - Published: 2014-07-17 - Granted: 2016-03-22 - Earliest claimed: 2005-09-12 - Assignees: Xigen Inflammation Ltd. - Applicants: Xigen Inflammation Ltd. - Inventors: Christophe Bonny - Web page: https://patentgrep.com/patent/US9290538B2 ## CPC - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - C07K 14/005: from viruses - A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04) - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/12: Antihypertensives - A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers - A61P 11/00: Drugs for disorders of the respiratory system - A61P 11/16: Central respiratory analeptics - A61P 17/00: Drugs for dermatological disorders - A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like - A61P 17/06: Antipsoriatics - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 27/16: Otologicals - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/04: Antibacterial agents - A61P 31/18: for HIV - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 37/00: Drugs for immunological or allergic disorders - A61P 37/02: Immunomodulators - A61P 37/04: Immunostimulants - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - A61P 39/06: Free radical scavengers or antioxidants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - C07K 14/47: from mammals - C07K 14/4703: {Inhibitors; Suppressors} - C07K 16/18: against material from animals or humans - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - 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) - C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22 - C12N 2740/16322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2740/16371: Demonstrated in vivo effect - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) ## Abstract Protein kinase inhibitors and more specifically inhibitors of the protein kinase c-Jun amino terminal kinase are herein described. Additionally, JNK inhibitor sequences, chimeric peptides, nucleic acids encoding same as well as pharmaceutical compositions for treating pathophysiologies associated with JNK signaling are herein provided. ## Claims ### Claim 1 A chimeric peptide consisting of a first domain and a second domain directly linked by a covalent bond or linked by a linker sequence of 1 to 10 amino acids, the first domain comprising a trafficking sequence, and the second domain consisting of a c-Jun N-terminal kinase (JNK) inhibitor sequence of SEQ ID NO: 2 or a variant sequence of SEQ ID NO: 2 with 1 or 2 amino acids deleted from either terminus of SEQ ID NO: 2, wherein the trafficking sequence comprises the amino acid sequence of SEQ ID No: 5, 6, 7 or 8 or a sequence variant of SEQ ID NO: 5 or 6 with 1 or 2 amino acids deleted from either terminus of SEQ ID NO: 5 or 6, and wherein the trafficking sequence and the JNK inhibitor sequence are composed exclusively of D-enantiomeric amino acids. ### Claim 2 (depends on 1) The peptide of claim 1, wherein the trafficking sequence comprises the amino acid sequence of a human immunodeficiency virus TAT polypeptide. ### Claim 3 (depends on 1) The peptide of claim 1, wherein the trafficking sequence comprises the amino acid sequence of SEQ ID NO: 5, 6, 7 or 8. ### Claim 4 (depends on 1) The peptide of claim 1, wherein the trafficking sequences augments cellular uptake of the peptide. ### Claim 5 (depends on 1) The peptide of claim 1, wherein the trafficking sequence directs nuclear localization of the peptide. ### Claim 6 (depends on 1) The peptide of claim 1, wherein the peptide comprises the amino acid sequence of any of SEQ ID NO: 11, or a fragment, or variant thereof. ### Claim 7 (depends on 1) A pharmaceutical composition comprising a chimeric peptide of claim 1 and a pharmaceutically acceptable carrier. ### Claim 8 (depends on 1) A Kit comprising a chimeric peptide of claim 1, and/or a nucleic acid encoding a chimeric peptide of claim 1, and/or a vector comprising a nucleic acid encoding a chimeric peptide of claim 1, and/or a cell comprising the vector comprising a nucleic acid encoding a chimeric peptide of claim 1, and/or an antibody which binds immunospecifically to to a chimeric peptide of claim 1. ### Claim 9 (depends on 1) The peptide of claim 1, comprising at least one modification at the C-terminus and/or at least one modification at the N-terminus. ### Claim 10 (depends on 9) The peptide of claim 9, wherein the peptide comprises an amidation modification at the C-terminus and/or an NH2-protection group modification at the N-terminus. ### Claim 11 (depends on 10) The peptide of claim 10, wherein the peptide comprises an acylation modification at the N-terminus. ### Claim 12 (depends on 9) The peptide of claim 9, wherein the peptide comprises the amino acid sequence of SEQ ID NO: 11. ### Claim 13 (depends on 12) The peptide of claim 12, wherein the peptide comprises an amidation modification at the C-terminus. ### Claim 14 (depends on 1) The peptide of claim 1, wherein the peptide is selected from the group consisting of QSRPVQPFLNLTTPRKPR-Xn-RRRQRRKKRG, SRPVQPFLNLTTPRKPR-Xn-RRRQRRKKRG, DQSRPVQPFLNLTTPRKP-Xn-RRRQRRKKRG, DQSRPVQPFLNLTTPRK-Xn-RRRQRRKKRG, QSRPVQPFLNLTTPRKP-Xn-RRRQRRKKRG, SRPVQPFLNLTTPRKP-Xn-RRRQRRKKRG, SRPVQPFLNLTTPRK-Xn-RRRQRRKKRG, QSRPVQPFLNLTTPRKPR-Xn-RRRQRRKKR, QSRPVQPFLNLTTPRKPR-Xn-RRRQRRKK, QSRPVQPFLNLTTPRKPR-Xn-RRQRRKKRG, QSRPVQPFLNLTTPRKPR-Xn-RQRRKKRG, QSRPVQPFLNLTTPRKPR-Xn-RRQRRKKR, QSRPVQPFLNLTTPRKPR-Xn-RQRRKKR, QSRPVQPFLNLTTPRKPR-Xn-RQRRKK SRPVQPFLNLTTPRKPR-Xn-RRRQRRKKR, DQSRPVQPFLNLTTPRKP-Xn-RRRQRRKKR, DQSRPVQPFLNLTTPRK-Xn-RRRQRRKKR, SRPVQPFLNLTTPRKP-Xn-RRRQRRKKR, SRPVQPFLNLTTPRK-Xn-RRRQRRKKR, DQSRPVQPFLNLTTPRKP-Xn-RRRQRRKK, DQSRPVQPFLNLTTPRK-Xn-RRRQRRKK, QSRPVQPFLNLTTPRKP-Xn-RRRQRRKK, SRPVQPFLNLTTPRKP-Xn-RRRQRRKK, SRPVQPFLNLTTPRK-Xn-RRRQRRKK, SRPVQPFLNLTTPRKPR-Xn-RRQRRKKR, DQSRPVQPFLNLTTPRKP-Xn-RRQRRKKR, DQSRPVQPFLNLTTPRK-Xn-RRQRRKKR, QSRPVQPFLNLTTPRKP-Xn-RRQRRKKR, SRPVQPFLNLTTPRKP-Xn-RRQRRKKRG, SRPVQPFLNLTTPRK-Xn-RRQRRKKRG, SRPVQPFLNLTTPRKPR-Xn-RRQRRKKRG, DQSRPVQPFLNLTTPRK-Xn-RRQRRKKRG, QSRPVQPFLNLTTPRKP-Xn-RRQRRKKRG, SRPVQPFLNLTTPRKP-Xn-RRQRRKKRG, SRPVQPFLNLTTPRKPR-Xn-RQRRKKRG, DQSRPVQPFLNLTTPRKP-Xn-RQRRKKRG, DQSRPVQPFLNLTTPRK-Xn-RQRRKKRG, QSRPVQPFLNLTTPRKP-Xn-RQRRKKRG, SRPVQPFLNLTTPRKP-Xn-RQRRKKRG, SRPVQPFLNLTTPRK-Xn-RQRRKKRG, QSRPVQPFLNLTTPRKP-Xn-RRRQRRKKR, QSRPVQPFLNLTTPRKPR-Xn-RRRQRRKK, and DQSRPVQPFLNLTTPRKP-Xn-RRQRRKKRG, wherein X is any L enantiomer or D enantiomer amino acid, n is 0-10, and the amino acids except for X are D enantiomer amino acids. ### Claim 15 (depends on 14) The peptide of claim 14, wherein n is 1-10. ### Claim 16 (depends on 14) The peptide of claim 14, wherein n is 1-5. ### Claim 17 (depends on 14) The peptide of claim 14, wherein X is an L enantiomer amino acid. ### Claim 18 (depends on 14) The peptide of claim 14, wherein X is a D enantiomer amino acid.