USOO9452198B2

(12) United States Patent (10) Patent No.: US 9,452,198 B2 Ribbeck et al. (45) Date of Patent: Sep. 27, 2016

(54) LECTIN CONUGATES FOR MIUCN 2015,003.0661 A1 1/2015 Ribbeck et al. HYDRATION 2015,005.1139 A1 2, 2015 Lieleg et al. 2015,00942.55 A1 4/2015 Ribbeck et al. 2015,0283208 A1 10, 2015 Ribbeck et al. (71) Applicant: Massachusetts Institute of Technology, Cambridge, MA (US) FOREIGN PATENT DOCUMENTS (72) Inventors: Katharina Ribbeck, Cambridge, MA JP O2-191225 A 7, 1990 (US); Thomas Crouzier, Somerville, WO WOOO, 23O23 A1 4/2000 MA (US) WO WO O3,O14078 A2 2, 2003 WO WO 2007 132355 A2 11/2007 WO WO 2013, 119668 A1 8, 2013 (73) Assignee: Massachusetts Institute of WO WO 2013,1197OO A1 8, 2013

- OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 Gao et al. Lectin-conjugated PEG-PLA nanoparticles:Preparation U.S.C. 154(b) by 0 days. and brain delivery after intranasal administration. Biomaterials. 2006. vol. 27, pp. 3482-3490.* (21) Appl. No.: 14/394,947 Gipson et al. Visualization of Conjunctival Goblet Cell Actin Cytoskeleton and Content in Tissue Whole Mounds. Exp Eye (22) PCT Filed: Mar. 15, 2013 Res,Shinogi 1997, et al.vol. Quantitative 65, pp. 407-415.* Analysis of Mucin and Lectin in Max illary Sinus Fluids in Patients With Acute and Chronic Sinusitis. The (86). PCT No.: PCT/US2O13/032442 Laryngospcope. 2001. vol. 111, pp. 240-251.* S 371 (c)(1), Ogasawara et al. Sialic acid is an essential moiety of mucin as a (2) Date: Oct. 16, 2014 hydroxyl radical scavenger. FEBS Letters, 2007. vol. 581, pp. 2473-2477.* (87) PCT Pub. No.: WO2013/162771 Liu et al. Nose-to-Brain Transport Pathways of Wheat Germ. Agglu tinin Conjugated PEG-PLA Nanoparticles. Pharm Res. 2012. Pub PCT Pub. Date: Oct. 31, 2013 lished online Dec. 4, 2011. vol. 29, pp. 546-558.* Roberts et al. Chemistry for peptide and protein PEGylation. (65) Prior Publication Data Advanced Drug Delivery Reviews, 2002. vol. 54, pp. 459-476.* Andrews, G.P. et al., “Mucoadhesive Polymeric Platforms for US 2015/OO942.55 A1 Apr. 2, 2015 Controlled Drug Delivery'. European Journal of Pharmaceutics and Biopharmaceutics, 71: 505-518 (2009). Cao, Y, et al., “Initiation of Glycogen Synthesis,” Journal of Related U.S. Application Data Biological Chemistry, 268(29):21717-21721 (1993). Caruso, F. et al., “Characterization of Polyelectrolyte-Protein (60) Provisional application No. 61/637,017, filed on Apr. Multilayer Films by Atomic Force Microscopy, Scanning Electron 23, 2012. Microscopy, and Fourier Transfor Infrared Reflection-Absorption Spectroscopy”. Langmuir, 14(16): 4559-4655 (1998). (51) Int. Cl. Celli, J. et al., “Viscoclastic Properties and Dynamics of Porcine AOIN 37/18 (2006.01) Gastric Mucin”, Biomacromolecules, 6., 1329-1333 (2005). A6 IK 38/00 (2006.01) Celli, J.P., et al., "Rheology of Gastric Mucin Exhibits a pH A6IP3I/00 (2006.01) Dependent Sol-Gel Transition'. Biomacromolecules, 8(5): 1580 1586 (2007). A6 IK 38/17 (2006.01) Cheetham, S., et al., “Binding Patterns of Human Norovirus-Like A6 IK 47/48 (2006.01) Particles to Buccal and Intestinal Tissues of Gnotobiotic Pigs in (52) U.S. Cl. Relation to AH Histo-Blood Group Antigen Expression”, Journal CPC ..... A61K 38/1732 (2013.01); A61K 47/48215 of Virology, 81(7): 3535-3544 (2007). (2013.01) (Continued) (58) Field of Classification Search CPC ...... A61K 47/48215: A61K 38/1732 Primary Examiner — Marcela M Cordero Garcia See application file for complete search history. (74) Attorney, Agent, or Firm — Hamilton, Brook, Smith & (56) References Cited Reynolds, P.C. U.S. PATENT DOCUMENTS (57) ABSTRACT The invention provides, interalia, conjugates of a hydratable 4,996,296 A 2f1991 Pecht et al. polymer (such as PEG, polyethylene glycol) and a lectin 5,284.934 A 2/1994 Allen, Jr. 7,687,608 B2 * 3/2010 Lancaster ...... A61K 38.25 (such as wheat germ agglutinin, WGA), compositions com 424,124 prising these conjugates, as well as methods and targeted 2003, OO77317 A1 4, 2003 Santos et al. uses of these conjugates and compositions for, e.g., lubri 2004/0086499 All 52004 Caldwell et al. cating, maintaining hydration of rehydrating, and/or inhib 2005/0112188 A1* 5, 2005 EliaZ ...... A61K424/450 9,0004 iting microorganism colonization of a biological Surface in 2006/0058736 A1 3f2006 Alchas et al. need thereof. 2008/O151180 A1 6, 2008 Vanderbilt et al. 2008/0286211 A1 11/2008 Barker 7 Claims, 9 Drawing Sheets US 9,452,198 B2 Page 2

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