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1. (WO2018042390) GENETICALLY MODIFIED BACTERIA STABLY EXPRESSING IL-10 AND INSULIN
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Pub. No.: WO/2018/042390 International Application No.: PCT/IB2017/055287
Publication Date: 08.03.2018 International Filing Date: 02.09.2017
IPC:
A61K 39/008 (2006.01) ,A61K 35/744 (2015.01) ,C12N 15/74 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39
Medicinal preparations containing antigens or antibodies
02
Bacterial antigens
08
Clostridium, e.g. Clostridium tetani
[IPC code unknown for A61K 35/744]
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
63
Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
74
Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
Applicants:
INTREXON ACTOBIOTICS N.V. [BE/BE]; Industriepark Zwijnaarde 7C, Building D 9052 Zwijnaarde, Belgium, BE
Inventors:
ROTTIERS, Pieter; BE
STEIDLER, Lothar; BE
Priority Data:
62/383,07902.09.2016US
Title (EN) GENETICALLY MODIFIED BACTERIA STABLY EXPRESSING IL-10 AND INSULIN
(FR) BACTÉRIES GÉNÉTIQUEMENT MODIFIÉES EXPRIMANT DE FAÇON STABLE IL-10 ET L'INSULINE
Abstract:
(EN) The current disclosure provides microorganisms, such as lactic acid bacteria (e.g., Lactococcus lactis) containing an exogenous nucleic acid encoding an IL-10 polypeptide and an exogenous nucleic acid encoding a TlD-specific antigen (e.g., a proinsulin) polypeptide, wherein both exogenous nucleic acids are integrated into the bacterial chromosome. Such microbial strains are suitable for human therapy. The disclosure further provides compositions (e.g., pharmaceutical compositions) methods of using the microorganisms and compositions, e.g., for the treatment of type 1 diabetes (T1D), including those with residual beta-cell function, e.g., recent-onset T1D. The microorganism may be administered orally, delivers the microorganism into the gastrointestinal tract, where it is released and expresses the bioactive polypeptides, The methods of the present disclosure are particularly well suited for subjects possessing residual beta-cell function, e.g., for subjects with recent-onset T1D.
(FR) La présente invention concerne des microorganismes, tels que des bactéries lactiques (par exemple, Lactococcus lactis) contenant un acide nucléique exogène codant un polypeptide d'IL-10 et un acide nucléique exogène codant un polypeptide d'antigène spécifique de T1D (par exemple, une pro-insuline), les deux acides nucléiques exogènes étant intégrés dans le chromosome bactérien. Ces souches microbiennes conviennent à une thérapie humaine. L'invention concerne en outre des compositions (par exemple, des compositions pharmaceutiques) et des procédés d'utilisation des microorganismes et des compositions, par exemple, pour le traitement du diabète de type 1 (T1D), notamment ceux ayant une fonction de cellule bêta résiduelle, par exemple, un T1D à déclenchement récent. Le microorganisme peut être administré par voie orale, délivre le microorganisme dans le tractus gastro-intestinal, dans lequel il est libéré et exprime les polypeptides bioactifs. Les procédés de la présente invention sont particulièrement bien adaptés à des sujets présentant une fonction de cellule bêta résiduelle, par exemple, des sujets atteint d'un T1D à déclenchement récent.
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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, 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
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)