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1. (WO2016105536) MUC1 DECOY PEPTIDES FOR TREATMENT AND PREVENTION OF BACTERIAL INFECTIONS
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/2016/105536 International Application No.: PCT/US2015/000313
Publication Date: 30.06.2016 International Filing Date: 23.12.2015
IPC:
A61K 39/00 (2006.01) ,A61K 38/16 (2006.01) ,A61K 38/17 (2006.01) ,C12P 21/02 (2006.01) ,C07K 14/435 (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
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38
Medicinal preparations containing peptides
16
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
38
Medicinal preparations containing peptides
16
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
17
from animals; from humans
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
P
FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
21
Preparation of peptides or proteins
02
having a known sequence of two or more amino acids, e.g. glutathione
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
14
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435
from animals; from humans
Applicants:
UNIVERSITY OF MARYLAND, BALTIMORE [US/US]; 620 West Lexington Street, 4th Floor Baltimore, MD 21201, US
THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS [US/US]; Department of Veterans Affairs Office of General Counsel - Psg IV (024) 810 Vermont Avenue, N.W. Washington, DC 20420, US
Inventors:
LILLEHOJ, Erik, P.; US
VERCELES, Avelino, C.; US
GOLDBLUM, Simeon, E.; US
Agent:
HISSONG, Drew; US
Priority Data:
62/096,16623.12.2014US
62/197,29927.07.2015US
Title (EN) MUC1 DECOY PEPTIDES FOR TREATMENT AND PREVENTION OF BACTERIAL INFECTIONS
(FR) PEPTIDES LEURRES MUC1 POUR LE TRAITEMENT ET LA PRÉVENTION D'INFECTIONS BACTÉRIENNES
Abstract:
(EN) Pseudomonas aeruginosa flagellin protein recruits the mammalian host sialidase enzyme neuraminidase- 1 (NEU1) to remove sialic acid residues from the extracellular domain of the mammalian cell-surface protein MUC l (MUC l -ED), thereby exposing a cryptic binding site on the MUC l -ED protein backbone for flagellin binding. NEU1 -driven MUC l -ED desialylation rapidly increases P. aeruginosa adhesion to the airway epithelium. MUCl -ED desialylation also increases MUC l -ED cleavage and shedding from the cell surface, where desialylated, shed MUCl -ED competitively blocks P. aeruginosa adhesion to cell-associated MUCl -ED. Presented herein are data showing that exogenously-administered, deglycosylated MUCl -ED peptides reduced adhesion of P. aeruginosa to airway epithelial cells. Also presented are data showing that administration of P. aeruginosa to mice in combination with deglycosylated MUC 1 -ED decreased P. aeruginosa recovered from the lungs at 48 hr and 72 hr post-infection. Such findings are extended to the methods of treatment and prevention of bacterial infections defined herein.
(FR) La protéine flagelline de Pseudomonas aeruginosa recrute l'enzyme sialidase neuraminidase-1 (NEU1) de l'hôte mammifère pour retirer les résidus d'acide sialique du domaine extracellulaire de la protéine de surface cellulaire de mammifère MUC1 (MUC1-ED), ce qui permet d'exposer un site de liaison cryptique sur le squelette de la protéine MUC1-ED pour la liaison de la flagelline. La désialylation de MUC1-ED dirigée par NEU1 augmente rapidement l'adhésion de P. aeruginosa à l'épithélium des voies respiratoires. La désialylation de MUC1-ED augmente également le clivage de MUC1-ED et son exfoliation de la surface cellulaire, MUC1-ED exfolié bloquant par compétition l'adhésion de P. aeruginosa à MUCl-ED associée aux cellules. Dans la description sont présentées des données montrant que les peptides de MUC1-ED déglycosylés, administrés par voie exogène réduisent l'adhésion de P. aeruginosa aux cellules épithéliales des voies respiratoires. Dans la description sont également présentées des données montrant que l'administration de P. aeruginosa à des souris en combinaison avec MUC1-ED déglycosylé diminue la quantité de P. aeruginosa récupérée dans les poumons 48 h et 72 h après l'infection. Ces découvertes sont étendues aux procédés de traitement et de prévention d'infections bactériennes tels que définis dans la description.
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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, 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, KN, KP, KR, 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 Organization (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (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)