I1111111111111111 1111111111 11111 1111111111 11111 11111 11111 lll111111111111111 USO 10082506B2 c12) United States Patent (IO) Patent No.: US 10,082,506 B2 Kiessling et al. (45) Date of Patent: Sep.25,2018 (54) MICROBIAL GLYCANS AS A TARGET OF OTHER PUBLICATIONS HUMAN INTELECTIN Tsuji et al., The Journal of Biological Chemistry, 200 l; 276(26): (71) Applicant: Wisconsin Alumni Research 23456-23463. * Foundation, Madison, WI (US) Wesener et al., Nature Structural and Molecular Biology, 2015; 22(8): 603-610.* (72) Inventors: Laura L. Kiessling, Madison, WI (US); Blixt et al., "Printed covalent glycan array for ligand profiling of Darryl A. Wesener, Madison, WI (US); diverse glycan binding proteins," Proc Natl Acad Sci USA, Kittikhun Wangkanont, Bangkok (TH) 101(49):17033-17038, 2004. Datta et al., "Identification of novel genes in intestinal tissue that are (73) Assignee: Wisconsin Alumni Research regulated after infection with an intestinal nematode parasite," Foundation, Madison, WI (US) Infect. Immun., 73(7):4025-4033, 2005. French et al., "Up-regulation of intelectin in sheep after infection ( *) Notice: Subject to any disclaimer, the term ofthis with Teladorsagia circumcincta," Int. J Parasitol., 38(3-4):467- patent is extended or adjusted under 35 475, 2008. U.S.C. 154(b) by O days. Kincaid et al., "Virtual screening for UDP-galactopyranose mutase ligands identifies a new class of antimycobacterial agents," ACS (21) Appl. No.: 14/933,891 Chem. Biol., 10:2209-2218, 2015. Nassau et al., "Galactofuranose biosynthesis in Escherichia coli (22) Filed: Nov. 5, 2015 K-12: identification and cloning ofUDP-galactopyranose mutase ," J Bacterial, 178(4):1047-1052, 1996. (65) Prior Publication Data Pedersen and Turco, "Galactofuranose metabolism: a potential target for antimicrobial chemotherapy," Cell Mo! Life Sci, 60(2):259- US 2016/0131649 Al May 12, 2016 266, 2003. Pemberton et al., "Proteomic analysis of mouse jejuna! epithelium Related U.S. Application Data and its response to infection with the intestinal nematode, Trichinella (60) Provisional application No. 62/075,369, filed on Nov. spiralis," Proteomics, 4(4):1101-1108, 2004. Tefsen et al., "Galactofuranose in eukaryotes: aspects ofbiosynthe­ 5, 2014. sis and functional impact," Glycobiology, 22:456-469, 2012. Voehringer et al., "Nippostrongylus brasiliensis: identification of (51) Int. Cl. intelectin-1 and -2 as Stat6-dependent genes expressed in lung and GOIN 33/53 (2006.01) intestine during infection," Exp Parasitol, 116:458-466, 2007. C12Q 1168 (2018.01) Wesener et al., "Recognition ofmicrobial glycans by human intelectin- GOIN 33/554 (2006.01) 1," Nature Structural & Molecular Biology, 22(8):603-613, and GOIN 33/569 (2006.01) Supplementary Information, 2015. C07K 141705 (2006.01) Wesener et al., "UDP-galactopyranose mutase in nematodes ," C07K 14147 (2006.01) Biochemistry, 52:4391-4398, 2013. C07K 7164 (2006.01) A61K 38/00 (2006.01) * cited by examiner Cl2Q 1/689 (2018.01) Primary Examiner - Gary B Nickol (52) U.S. Cl. Assistant Examiner - Lakia J Jackson-Tongue CPC .......... GOIN 33/56911 (2013.01); C07K 7164 (2013.01); C07K 1414726 (2013.01); C07K (74) Attorney, Agent, or Firm - Parker Highlander, 1417056 (2013.01); GOIN 33/56961 (2013.01); PLLC A61K 38/00 (2013.01); C07K 2319/00 (57) ABSTRACT (2013.01); Cl2Q 1/689 (2013.01); GOIN 33/56944 (2013.01); GOIN 2333/705 The present disclosure provides for methods of diagnosing (2013.01) and treating bacterial infections. Human Intelectin 1 (hlntL- (58) Field of Classification Search 1) has been shown to bind selectively to glycan components None on bacteria including Streptococcus pneumonia, Proteus See application file for complete search history. mirabilis, Proteus vulgaris, Klebsiella pneumonia and Yers­ inia pestis. This interaction can be targeted to identify, purify (56) References Cited and therapeutically target such organisms. U.S. PATENT DOCUMENTS 10 Claims, 35 Drawing Sheets (30 of 35 Drawing Sheet(s) Filed in Color) 7,312,197 B2 * 12/2007 Gong ................... C07K 14/575 514/15.7 Specification includes a Sequence Listing. U.S. Patent Sep.25,2018 Sheet 1 of 35 US 10,082,506 B2 A Bo,o. OR 00,..... -~ ' fl·-L"'-lff OH OH ,-::, ' [l~3alp p-(~~lacfofwf"<~lK)~3 ~ 0 l~i. !P,;t,:i;;s, ;.io---., .,....61Y{ d ...ix Q, t "'6 01 / .i";:; H6 1< it 02:;. 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