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1. (WO2017184082) A LYMPHOCYTE PERMEATING CHIMERIC OLIGONUCLEOTIDE, METHODS AND USES THEREOF
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Pub. No.: WO/2017/184082 International Application No.: PCT/SG2017/050221
Publication Date: 26.10.2017 International Filing Date: 20.04.2017
IPC:
A61K 31/712 (2006.01) ,C12N 15/113 (2010.01) ,A61P 35/00 (2006.01) ,A61P 37/00 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
70
Carbohydrates; Sugars; Derivatives thereof
7088
Compounds having three or more nucleosides or nucleotides
712
Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
11
DNA or RNA fragments; Modified forms thereof
113
Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37
Drugs for immunological or allergic disorders
Applicants: NANYANG TECHNOLOGICAL UNIVERSITY[SG/SG]; 50 Nanyang Avenue Singapore 639798, SG
THE UNIVERSITY OF BRITISH COLUMBIA[CA/CA]; 103-6190 Agronomy Road Vancouver, British Columbia V6T 1Z3, CA
Inventors: VERMA, Navin Kumar; SG
FAZIL, Mobashar Hussain Urf Turabe; SG
ONG, Seow Theng; SG
SOMARAJU, Madhavi Latha; SG
LOW, Jian Hui; SG
KELLEHER, Dermot; SG
Agent: YUSARN AUDREY; 24 Raffles Place #27-01 Clifford Centre Singapore 048621, SG
Priority Data:
10201603208W22.04.2016SG
Title (EN) A LYMPHOCYTE PERMEATING CHIMERIC OLIGONUCLEOTIDE, METHODS AND USES THEREOF
(FR) OLIGONUCLÉOTIDE CHIMÈRE DE PERMÉATION DE LYMPHOCYTES, PROCÉDÉS ET UTILISATIONS ASSOCIÉS
Abstract:
(EN) The present invention relates to short antisense lymphocyte-permeable locked nucleic acid (LNA)-modified gapmer oligonucleotides that target mRNA encoding proteins and methods for effectively inhibiting the expression of target proteins in hard-to-transfect lymphocytes such as primary and cultured human T-cells, leading to the reduced expression of targeted proteins such as CG-NAP, Talin l, CD1 1a, PKCε or Stathmin. In a specific embodiment, said oligonucleotide is used to knockdown the expression of CG-NAP/AKAP450 protein in primary T cells and cutaneous T cell-lymphoma cell line (CTCL); HuT78 and suppressed T-cell migration. The invention is further directed to the use of said LNA-modified oligonucleotides to treat autoimmune diseases and cancers such as lymphomas having Sezary Syndrome or Mycosis Fungoides.
(FR) La présente invention concerne des oligonucléotides gapmères antisens courts modifiés par acide nucléique bloqué (LNA) qui ont une capacité de perméation dans des lymphocytes et ciblent un ARNm codant pour des protéines, et des procédés pour inhiber efficacement l'expression de protéines cibles dans des lymphocytes difficiles à transfecter tels que des lymphocytes T humains primaires et de culture, conduisant à l'expression réduite de protéines ciblées telles que CG-NAP, taline l, CD11a, PKCε ou stathmine. Dans un mode de réalisation spécifique, ledit oligonucléotide est utilisé pour inactiver l'expression de la protéine CG-NAP/AKAP450 dans des lymphocytes T primaires et la lignée cellulaire de lymphome T cutané (CTCL); Hut78 et supprimer la migration des lymphocytes T. L'invention concerne en outre l'utilisation desdits oligonucléotides modifiés par LNA pour traiter des maladies auto-immunes et des cancers tels que des lymphomes associés au syndrome de Sezary ou au mycosis fongoïde.
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Designated States: 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, 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
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (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)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)