Patent SG-11201903961R-A (SG)
Title: Antimicrobial peptides comprising epsilon lysine residues
Inventor: RAJAMANI LAKSHMINARAYANAN
IPC: C07K14/00
Filed: 2017-10-31
Abstract: StructureSequence 1.IN,, NI.1 2 HU ' NH ; I' HN, I . 1. 11 d , o Nit Nw KRKRKRKRKRKR (HO 1; SEQ ID NO: 3), where K and R are natural a-L-lysyl and a-L-arginine residues N N ~ NNi HN, o NH; N 0 KRKRKRKRKRKR (HC 2; SEQ ID NO: 17), where Kis E-L-lysyl residue H,N,.., 1. ,,, H , . ., 4 14,,,,,,:, 1 41:1 NH i N H . KrKrKrKrKrKr (HC 4; SEQ ID NO: 18), where Kis a-L-lysyl residue and r is D-arginyl residue HN, Nit 'r HN . .2 HgN ] H I H C. H ,N' ~ kRkRkRkRkRkR (HC 6; SEQ ID NO: 19) where k is E-D-lysyl residue and R is L-arginyl residue Figure 21 W O 20 18/08 4807 Al (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 11 May 2018 (11.05.2018) WIPO I PCT oimitia °nolo omm mom mo Immo oimIE (10) International Publication Number WO 2018/084807 Al (51) International Patent Classification: C07K 14/00 (2006.01) A61K 38/08 (2006.01) CO7K 7/02 (2006.01) A61P 31/04 (2006.01) (21) International Application Number: PCT/SG2017/050548 (22) International Filing Date: 31 October 2017 (31.10.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 10201609136R 01 November 2016 (01.11.2016) SG (71) Applicants: SINGAPORE HEALTH SERVICES PTE LTD [SG/SG]; 31, Bowyer Block, Third Hospital Avenue, #03-03, Singapore 168753 (SG). NANYANG TECH- NOLOGICAL UNIVERSITY [SG/SG]; 50 Nanyang Av- enue, Singapore 639798 (SG). (72) Inventors: RAJAMANI, Lakshminarayanan; c/o Sin- gapore Health Services Pte Ltd, 31, Bowyer Block, Third Hospital Avenue, #03-03, Singapore 168753 (SG). MAYANDI, Venkatesh; c/o Singapore Health Services Pte Ltd, 31, Bowyer Block, Third Hospital Avenue, #03-03, Singapore 168753 (SG). GOH, Tze Leng Eunice; c/o Singapore Health Services Pte Ltd, 31, Bowyer Block, Third Hospital Avenue, #03-03, Singapore 168753 (SG). BEUERMAN, Roger Wilmer; c/o Singapore Health Ser- vices Pte Ltd, 31, Bowyer Block, Third Hospital Avenue, #03-03, Singapore 168753 (SG). VERMA, Navin Kumar; c/o Nanyang Technological University, 50 Nanyang Av- enue, Singapore 639798 (SG). (74) Agent: SPRUSON & FERGUSON (ASIA) PTE LTD; P.O. Box 1531, Robinson Road Post Office, Singapore 903031 (SG). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (54) Title: ANTIMICROBIAL PEPTIDES COMPRISING EPSILON LYSINE RESIDUES (57) : The present disclosure relates to a peptide com- prising at least five amino acid residues, wherein at least one amino acid residue is modified to an epsilon-lysine, delta-or- nithine, gamma-2, 4-diaminobutyric acid, beta-2,3-diaminopropi- onic acid, with the peptide also comprising at least one non-epsilon lysine, non-delta-ornithine, non-gamma-2, 4-diaminobutyric acid or non-beta-2,3-diaminopropionic acid, and wherein the peptide displays a reduced or no cytotoxicity when compared to an equiv- alent non-modified peptide. In a preferred embodiment, the mod- ifications are to the melittin or mastoparan B peptides, and com- prise the substitution of at least one a-lysine residue for an c-lysine residue, and the modified peptides display antimicrobial activity. The present disclosure is also directed to pharmaceutical compo- sitions, kits, ophthalmic preparations comprising the modified an- timicrobial peptides and use of the modified antimicrobial pep- tides in methods of inhibiting growth of microorganisms, methods of managing microbial colonization, methods of treating prolifer- ative disease, and methods of treating inflammation. The present disclosure also relates to a method of improving the therapeutic index (safety) of an isolated peptide comprising the aforementione d modification. [Continued on next page] WO 2018/084807 Al MIDEDIMOMOIDEIREEMOOMMMOHNONERVOIMIE UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: of inventorship (Rule 4.17(iv)) Published: — with international search report (Art. 21(3)) with sequence listing part of description (Rule 5.2(a))