USOO894.6381 B2 (12) United States Patent (10) Patent No.: US 8,946,381 B2 Fear et al. (45) Date of Patent: Feb. 3, 2015 (54) COMPOSITIONS AND USES THEREOF FOR 6,316.223 B1 1 1/2001 Payan et al. THE TREATMENT OF WOUNDS g R 1 $38, E. i al. (75) Inventors: Mark Fear, Mundaring (AU); Paul 6.436,694 B1 8, 2002 Ea. Watt, Mount Claremont (AU); Richard 6,475,726 B1 1 1/2002 Tally et al. Hopkins, North Perth (AU): Nadia 6,521,425 B2 2/2003 Perler et al. Milech, Daglish (AU) 55: R 538. Manillet al. (73) Assignees: Phylogica Limited, Subiaco (AU); The 6.583.10s B1 6, 2003 Marini et al. McComb Foundation, Inc., Wembley 6,583,275 B1 6/2003 Doucette-Stamm et al. (AU) 6,610,820 B1* 8/2003 Bonny . 530/300 (*) Notice: Subject to any disclaimer, the term of this 6,720,4136,720,139 B1 4/2004 ZyskindSchweinfest et al. et al. patent is extended or adjusted under 35 6,846,625 B1 1/2005 Tally et al. U.S.C. 154(b) by 810 days. 6,962.904 B1 * 1 1/2005 Sandberg et al. ............ 514, 18.8 7,041,868 B2 * 5/2006 Greene et al. ................... 602/48 (21) Appl. No.: 12/441,691 7,053,046 B2 * 5/2006 McGrath ...................... 514,216 7,117,096 B2 10/2006 Luo et al. (22) PCT Filed: Feb. 6, 2007 7,303,885 B1* 12/2007 Brunner et al. ................ 435/71 2002fO150906 A1 10, 2002 Debe 2002fO155564 A1 10, 2002 Medrano et al. (86). PCT No.: PCT/AU2OOTAOOO121 2002fO164735 A1 11, 2002 Olson et al. S371 (c)(1) 2005/0287580 A1 12/2005 Watt et al. (2), (4) Date: Feb. 17, 2010 2007/0031832 A1 2/2007 Watt et al. ......................... 435/6 s 9 (Continued) (87) PCT Pub. No.: WO2008/034.162 FOREIGN PATENT DOCUMENTS (65) Prior Publication Data AU 48O8597 5, 1998 US 2010/0166835 A1 Jul. 1, 2010 (Continued) OTHER PUBLICATIONS Related U.S. Application Data Schuetz et al. 2005. Expert Opin Drug Deliv. 2:533-548.* HeSS et al. 2004. J. Cell Sci 1 17:5695-5973. (60) Royal application No. 60/826,208, filed on Sep. Vives et al. 1997. J. Biol Chem 272:16010-16017. s Bennett, B.L., “c-Jun N-Terminal Kinase-Dependent Mechanisms in Respiratory Disease.” Eur, Respir, Journal, 2006, pp. 651-661, vol. (51) Int. Cl 28. A6 IK38/00 (2006.01) Florin, I. et al., “Identification of Novel AP-1 Target9. Genes in Fibro A6 IK38/6 (2006.01) blasts Regulated During Cutaneous Wound Healing.” Oncogene, A61L 15/00 (2006.01) SECARNguyen, U. et al., emogenomic AG intificationIdlenullcation oof Rep.e- AP- aS a A6IL 15/16 (2006.01) Therapeutic Target for Asthma.” Proc. Nat. Acad. Sci., Feb. 4, 2003, C07K I4/47 (2006.01) pp. 1169-1173, vol. 100, No. 3. (52) U.S. Cl. PCT International Search Report, PCT Application No. PCT/ CPC ............. C07K 14/4703 (2013.01); A61 K38/00 FFRE,international Preliminary 2007, E.Examination tion Report,Keport, PCT Applipplica USPC ........ 530/324;E. 514/18.6; Co.K. 514/18.9; | 9/00 514/21.3;3. tionPCT No. International PCT/AU2007/000092, Search Report Mar. and 24, Written 2009, Opinion, 7 pages. PCT Appli 424/445; 424/447 cation No. PCT/AU2007/000121, Apr. 5, 2007, 8 pages. (58) Field of Classification Search (Continued) None See application file for complete search history. Primary Examiner — Shulamith H Shafer (56) References Cited (74) Attorney, Agent, or Firm — Fenwick & West LLP U.S. PATENT DOCUMENTS (57) ABSTRACT The present invention provides a topical composition com 5,516,637 A 5/1996 Huang et al. 5,763,239 A 6, 1998 Short et al. prising (i) an amount of an AP-1 signaling inhibitor Sufficient 5,783,431 A 7, 1998 Peterson et al. to reduce, delay or prevent apoptosis and/or necrosis induced 5,821,047 A 10, 1998 Garrard et al. by dermal wounding and/or to induce and/or enhance prolif 5,834,247 A 11/1998 Comb et al. eration of a cell; and (ii) a Suitable carrier or excipient e.g., a 5,843,698 A 12/1998 Sorensen topical carrier or excipient or other carrier or excipient for 6,074,815 A 6, 2000 Sorensen dermal application. For example, the AP-1 signaling inhibitor 6,083,715 A 7/2000 Georgiou et al. is a peptide analog comprising the sequence set forth in SEQ 6,150,127 A 11/2000 Sorensen 6,174,673 B1 1/2001 Short et al. ID NO: 104. The present invention also provides a method of 6,190,908 B1 2/2001 Kang treating a dermal wound comprising topically administering 6,221.355 B1 * 4/2001 Dowdy ...................... 424,192.1 said topical composition to a Subject Suffering from a dermal 6,225,530 B1 5/2001 Weigel et al. wound. 6,238,884 B1 5, 2001 Short et al. 6,297.004 B1 10/2001 Russell et al. 21 Claims, 25 Drawing Sheets US 8,946.381 B2 Page 2 (56) References Cited Display and Designed Combinatorial Peptide Libraries.” Bioorganic & Medicinal Chemistry 13(2):563-573. U.S. PATENT DOCUMENTS Angrist, M. (1998) "Less is More: Compact Genomes Pay Divi dends. Genome Research 8:683-685. 2007/0060514 A1 3/2007 Bonny 2009/0170722 A1 7, 2009 Watt et al. Arenkov, P. etal (2000). “Protein Microchips: Use for Immunoassay 2010.0029552 A1* 2/2010 Watt et al. ....................... 514/12 and Enzymatic Reactions.” Analytical Biochemistry 278:123-131. Balaban, N. et al. (Apr. 17, 1998). "Autoinducer of Virulence as a FOREIGN PATENT DOCUMENTS Target for Vaccine and Therapy Against Staphylococcus aureus,' Science 280:438-440. AU 2258799 7, 1999 Basbous, J. et al. (Oct. 31, 2003). “The HBZ Factor of Human T-cell AU T566.17 B2 1, 2003 Leukemia Virus Type 1 Dimerizes with Transcription Factors JunB AU T71534 B2 3, 2004 and c-Jun Modulates Their Transcriptional Activity.” The Journal of CN 1629637 6, 2005 Biological Chemistry 278 (44): 43620-43627. EP 1277835 A1 1, 2003 EP 1776958 A2 4/2007 Baud, F. et al. (Oct. 26, 1999). “Measures of Residue Density in EP 1811033 A1 7/2007 Protein Structures. Proc. Natl. Acad. Sci. USA 96:12494-12499. WO WO95/17412 6, 1995 Behrens, A. etal. (Mar. 1999). "Amino-Terminal Phosphorylation of WO WO98, 15172 4f1998 c-Jun Regulates Stress-Induced Apoptosis and Cellular Prolifera WO WO98, 16835 4f1998 tion.” Nature Genetics 21:326-329. WO WO99,35282 7, 1999 Berzofsky, J.A. (Sep. 6, 1985). “Intrinsic and Extrinsic Factors in WO WOOOf 68373 11, 2000 Protein Antigenic Structure.” Science 229(4717):932-940. WO WOOO.76308 12/2000 WO WO 01/11086 2, 2001 Blum, J.H. etal. (Feb. 29, 2000), “Isolation of Peptide Aptamers That WO WOO1/32156 A2 5, 2001 Inhibit Intracellular Processes.” Proc. Natl. Acad. Sci. USA WO WOO3/O12055 2, 2003 97(5):2241-2246. WO WO 03/040 168 5, 2003 Bonaldo, M. et al. (1997). "Normalisation and Subtraction: Two WO WO 03/046147 6, 2003 Approaches to Facilitate Gene Discovery.” Genome Res.6:791-806. WO WOO3,O76621 9, 2003 Bremnes, T. et al. (1998). "Selection of Phage Displayed Peptides WO WO 2004/074479 9, 2004 From a Random 10-mer Library Recognising a Peptide Target.” WO WO 2004/074479 A1 9, 2004 WO WO 2006/017913 2, 2006 Immunotechnology 4:21-28. WO WO 2006/017913 A1 2, 2006 Britten, R.J. et al. (Aug. 9, 1968). “Repeated Sequences in DNA.” WO WO 2007/031098 A1 3, 2007 Science 161(3841):529-540. WO WO 2008/034161 A1 3, 2008 Brodin, N.T. et al (May 15, 1990). “Rat Monoclonal Antibodies WO WO 2008/034162 A1 3, 2008 Produced Against Rat Colorectal Adenocarcinomas Define Tumor WO WO 2008,154700 A1 12/2008 and Colon-Associated, Auto-Immunogenic Antigens.” Int. J. Cancer OTHER PUBLICATIONS 45(5):902-910. Burioni, R. etal. (1998). “A New Subtraction Technique for Molecu PCT International Preliminary Examination Report, PCT Applica lar Cloning of Rare Antiviral Antibody Specificities From Phage tion No. PCT/AU2007/000121, Mar. 24, 2009, 4 pages. Display Libraries.” Res. Virol. 149:327-330. PCT International Search Report and Written Opinion, PCT Appli Campbell, A.P. et al. (1997). "Solution Secondary Structure of a cation No. PCT/AU2008/000903, Oct. 15, 2008, 13 pages. Bacterially Expressed Peptide from the Receptor Binding Domain of PCT International Preliminary Report on Patentability, PCT Appli Pseudomonas aeruginosa Pili Strain PAK: A Heteronuclear Multi cation No. PCT/AU2008/000903, Dec. 22, 2009, 7 pages. dimensional NMR Study,” Biochem. 36(42): 12791-12801. RefSeq Accession No. XP 975325.1, NCBI Sequence Viewer v2.0, Caponigro, G. et al. (Jun. 1998). “Transdominant Genetic Analysis 1 page. Online Retrieved on May 3, 2007. of a Growth Control Pathway.” Proc. Natl. Acad. Sci USA95:7508 RefSeq Accession No.YP 284595.1, NCBI Sequence Viewer v2.0, 7513. 2 pages. Online Retrieved on May 3, 2007). Chapman, M.D. et al. (Nov. 1984). “Recognition of two Yates, S. et al. “Transcription Factor Activation in Response to Cuta Dermatophagoides pteronyssinus-specific Epitopes on Antigen P1 neous Injury: Role of AP-1 in Reepithelialization.” Wound Repair by using Monoclonal Antibodies: Binding to Each Epitope can be Regeneration, 2002, pp. 5-15, vol. 10, No. 1. Inhibited by Serum from Dust Mite-Allergic Patients.” J Immunol Hooper, R.G. et al., “Established ARDS Treated with a Sustained 133(5):2488-2495. Course of Adrenocortical Steroids.” Chest, 1990, pp. 138-143, vol. Chevray, PM.