Granted Patent
B2
US 12,214,029 · App. 18/305,948 · Granted Feb 4, 2025
Polysaccharide and uses thereof
Inventors:
Michael T. Kowarik (Zurich, CH); Michael L. Wetter (Zurich, CH); Stefan J. Kemmler (Zurich, CH); Micha A. Häuptle (Zurich, CH); Veronica Gambillara (Meilen, CH); Manuela Mally (Watt, CH)
Assignee:
GLAXOSMITHKLINE BIOLOGICALS S.A.
A61K39/0258A61K39/02A61K47/646C07K14/21C08B37/0063C08B37/0066A61K2039/55583A61K2039/6037A61K2039/6087A61K2039/70C07K14/245Y02A50/30
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Provided herein is an E. coli O polysaccharide, O25B. Also provided herein are prokaryotic host cells containing enzymes (e.g., glycosyltransferases) used in O25B production. The host cells provided herein produce O25B bioconjugates, wherein said bioconjugates contain O25B linked to a carrier protein. Further provided herein are compositions, e.g., pharmaceutical compositions, including O25B and/or bioconjugates containing O25B. Such compositions can be used as vaccines against infection with ExPEC, and may further include one or more additional bioconjugates.
Claims (28)
1. A pharmaceutical composition comprising a glycoconjugate of an E. coli O25B antigen covalently coupled to a carrier protein, wherein the E. coli O25B antigen comprises the structure of Formula O25B′:
wherein n is an integer of 1 to 30; and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1 , wherein the carrier protein is selected from the group consisting of detoxified Exotoxin A of P. aeruginosa (EPA), CRM197, maltose binding protein (MBP), Diphtheria toxoid, Tetanus toxoid, detoxified hemolysin A of S. aureus , clumping factor A, clumping factor B, E. coli FimH, E. coli FimHC, E. coli heat labile enterotoxin, detoxified variants of E. coli heat labile enterotoxin, Cholera toxin B subunit (CTB), cholera toxin, detoxified variants of cholera toxin, E. coli Sat protein, the passenger domain of E. coli Sat protein, Streptococcus pneumoniae Pneumolysin and detoxified variants thereof, C. jejuni AcrA, and C. jejuni natural glycoproteins.
3. The pharmaceutical composition of claim 2 , wherein the carrier protein is detoxified EPA or CRM197.
4. The pharmaceutical composition of claim 1 , wherein the E. coli O25B antigen is covalently coupled to an Asn residue in the carrier protein.
5. The pharmaceutical composition of claim 4 , wherein the Asn residue of the carrier protein is positioned in the consensus sequence Asp (Glu)-X-Asn-Z-Ser(Thr), wherein X and Z are independently selected from any natural amino acid except Pro (SEQ ID NO:15).
6. The pharmaceutical composition of claim 1 , further comprising a conjugate of an E. coli O1 antigen covalently coupled to a carrier protein, a conjugate of an E. coli O2 antigen covalently coupled to a carrier protein, and a conjugate of an E. coli O6 antigen covalently coupled to a carrier protein.
7. The pharmaceutical composition of claim 6 , wherein the E. coli O1 antigen comprises the structure of Formula O1A′:
the E. coli O2 antigen comprises the structure of Formula O2′:
and
the 06 antigen comprises the structure of Formula 06GlcNAc′:
wherein n is an integer of 1 to 30.
8. The pharmaceutical composition of claim 1 , wherein the glycoconjugate of the E. coli O25B antigen is a bioconjugate.
9. The pharmaceutical composition of claim 8 , wherein the carrier protein is detoxified EPA.
10. The pharmaceutical composition of claim 9 , wherein the E. coli O25B antigen is covalently coupled to an Asn residue in the carrier protein, wherein the Asn residue of the carrier protein is positioned in the consensus sequence Asp (Glu)-X-Asn-Z-Ser(Thr), wherein X and Z are independently selected from any natural amino acid except Pro (SEQ ID NO:15).
11. The pharmaceutical composition of claim 1 , further comprising an adjuvant.
12. The pharmaceutical composition of claim 8 , further comprising an adjuvant.
13. A method of inducing an immune response in a subject against extra-intestinal pathogenic Escherichia coli comprising administering to the subject an effective amount of the pharmaceutical composition of claim 1 .
14. A composition comprising a conjugate of an E. coli O25B polysaccharide antigen covalently coupled to an Asn residue in a carrier protein.
15. The composition of claim 14 , wherein the Asn residue of the carrier protein is positioned in the consensus sequence Asp (Glu)-X-Asn-Z-Ser(Thr), wherein X and Z are independently selected from any natural amino acid except Pro (SEQ ID NO:15).
16. The composition of claim 14 , wherein the carrier protein is detoxified Exotoxin A of P. aeruginosa.
17. The composition of claim 14 , further comprising a conjugate of an E. coli O1 antigen covalently coupled to a carrier protein, a conjugate of an E. coli O2 antigen covalently coupled to a carrier protein, and a conjugate of an E. coli O6 antigen covalently coupled to a carrier protein.
18. A pharmaceutical composition comprising the composition of claim 14 , and a pharmaceutically acceptable carrier.
19. A method of inducing an immune response in a subject against extra-intestinal pathogenic Escherichia coli comprising administering to the subject an effective amount of the pharmaceutical composition of claim 18 .
20. A method of producing a pharmaceutical composition comprising the step of combining:
a) an E. coli O25B glycoconjugate comprising an O25B′ antigen covalently joined a carrier, wherein the O25B′ antigen has the structure:
wherein n is an integer of 1 to 30; and
b) a pharmaceutically acceptable carrier.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 26, 2024
From: KOWARIK, MICHAEL T.; WETTER, MICHAEL L.; KEMMLER, STEFAN J.; HAUPTLE, MICHA A.; GAMBILLARA, VERONICA; MALLY, MANUELA
To: GLYCOVAXYN AG
Reel/Frame 067845/0393 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 26, 2024
From: GLYCOVAXYN AG
To: GLAXOSMITHKLINE BIOLOGICALS S.A.
Reel/Frame 067845/0695 →
Continuity (6)
Provisional Application
61943710
· Feb 24, 2014
References Cited (230)
US 3700612A
· Joseph
· 1972
[cited by applicant]
US 5057540A
· Kensil
· 1991
[cited by applicant]
US 5370872A
· Cryz
· 1994
[cited by applicant]
US 6331415B1
· Cabilly
· 2001
[cited by applicant]
US 6858211B1
· Szu
· 2005
[cited by applicant]
US 9700612B2
· Kowarik
· 2017
[cited by applicant]
US 9849169B2
· Nagy
· 2017
[cited by applicant]
US 20210004617A1
· Gouraud
· 2021
[cited by applicant]
CN 1554759
· 2004
[cited by applicant]
CN 101983070
· 2011
[cited by applicant]
CN 105008539
· 2015
[cited by applicant]
CN 105828839
· 2016
[cited by applicant]
EP 2289911
· 2011
[cited by applicant]
EP 3941516A1
· 2022
[cited by applicant]
GB 2220211A
· 1990
[cited by applicant]
JP S62500173
· 1987
[cited by applicant]
JP H10500102A
· 1998
[cited by applicant]
JP 2004515450A
· 2004
[cited by applicant]
JP 2007256214
· 2007
[cited by applicant]
JP 2008539743A
· 2008
[cited by applicant]
JP 2011514155
· 2011
[cited by applicant]
JP 4791866B2
· 2011
[cited by applicant]
JP 2012525376A
· 2012
[cited by applicant]
JP 2017507178
· 2017
[cited by applicant]
JP 2018525423A
· 2018
[cited by applicant]
RU 2189253C1
· 2002
[cited by applicant]
WO 8601806
· 1986
[cited by applicant]
WO 8601806A1
· 1986
[cited by applicant]
WO 86001806
· 1986
[cited by applicant]
WO 9303765A1
· 1993
[cited by applicant]
WO 9522563A1
· 1995
[cited by applicant]
WO 9523256
· 1995
[cited by applicant]
WO 0178787
· 2001
[cited by applicant]
WO 2001078787A2
· 2001
[cited by applicant]
WO 2003074679
· 2003
[cited by applicant]
WO 2003074687A1
· 2003
[cited by applicant]
WO 2004078209A1
· 2004
[cited by applicant]
WO 2006119987
· 2006
[cited by applicant]
WO 2006119987A2
· 2006
[cited by applicant]
WO 2007109812A2
· 2007
[cited by applicant]
WO 2007109813A1
· 2007
[cited by applicant]
WO 2009036379
· 2009
[cited by applicant]
WO 2009089396A2
· 2009
[cited by applicant]
WO 2009104074
· 2009
[cited by applicant]
WO 2009104074A2
· 2009
[cited by applicant]
WO 2010105256
· 2010
[cited by applicant]
WO 2010125565
· 2010
[cited by applicant]
WO 2010125565A2
· 2010
[cited by applicant]
WO 2011062615
· 2011
[cited by applicant]
WO 2012009568
· 2012
[cited by applicant]
WO 2012078482A1
· 2012
[cited by applicant]
WO 2013034664A1
· 2013
[cited by applicant]
WO 2014037585A1
· 2014
[cited by applicant]
WO 2014057109A1
· 2014
[cited by applicant]
WO 2014072405
· 2014
[cited by applicant]
WO 2014102265A1
· 2014
[cited by applicant]
WO 2014111516A1
· 2014
[cited by applicant]
WO 2015052344
· 2015
[cited by applicant]
WO 2015068129
· 2015
[cited by applicant]
WO 2015117711A1
· 2015
[cited by applicant]
WO 2015124769
· 2015
[cited by applicant]
WO 2015124769A1
· 2015
[cited by applicant]
WO 2016107818A1
· 2016
[cited by applicant]
WO 2016107819A1
· 2016
[cited by applicant]
WO 2017035181
· 2017
[cited by applicant]
WO 2017035181A1
· 2017
[cited by applicant]
WO 2018077853A1
· 2018
[cited by applicant]
WO 2019016187A1
· 2019
[cited by applicant]
WO 2020191082
· 2020
[cited by applicant]
WO 2020191088
· 2020
[cited by applicant]
“Typhoid Vi Polysaccharide Vaccine Typhim VI,” Sanofi Pasteur Inc., vol. 3., pp. 1-26 (Mar. 2014).
[cited by applicant]
A. Cross et al, “Safety and Immunogenicity of a Polyvalent
[cited by applicant]
Amor et al., “Distribution of Core Oligosaccharide Types in Lipopolysaccharides from
[cited by applicant]
Banerjee et al., “A new clone sweeps clean: the enigmatic emergence of
[cited by applicant]
Blanco et al., “Virulence factors and 0 groups of
[cited by applicant]
Blanco et al., “Molecular epidemiology of
[cited by applicant]
Bowie et al., Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions, (Science, 1990, 247:1306-1310).
[cited by applicant]
Burgess et al., Possible Dissociation of the Heparin-binding and Mitogenic Activities of Heparin-binding (Acidic Fibroblast) Growth Factor-1 from Its Receptor-binding Activities by Site-directed Mutagenesis of a Single …
[cited by applicant]
Clermont et al.,“The CTX-M-15-producing
[cited by applicant]
O. Clermont et al, “Rapid detection of the O25b-ST131 clone of
[cited by applicant]
Cryz et al., “Synthesis and Characterization of
[cited by applicant]
Cryz S J et al, “Synthesis and characterization of a polyvalent
[cited by applicant]
Datsenko et al., “One-step inactivation of chromosomal genes in
[cited by applicant]
Debroy et al., “Detection of O antigens in
[cited by applicant]
Extended Search Report dated Apr. 12, 2017 in EP Application No. 16195256.9, 8 pages.
[cited by applicant]
Foxman, “Epidemiology of Urinary Tract Infections: Incidence, morbidity, and Economic Costs”, The American Journal of Medicine, vol. 113(1A), 5S-13S, Jul. 2002.
[cited by applicant]
Fratamico et al., “
[cited by applicant]
Frenck, et al., “Safety and Immunogenicity of a vaccine for extra-intestinal pathogenic
[cited by applicant]
Fundin et al., “NMR analysis of the O-antigen polysaccharide from
[cited by applicant]
Glover et al., “Chemoenzymatic synthesis of Glycopeptides with PglB, a bacterial oligosaccharyl transferase from Campylobacter jejuni,” Chemistry and Biology, Current Biology, vol. 12, No. 12, pp. 1311-1316 (2005).
[cited by applicant]
Ho et al., Preclinical Laboratory Evaluation of a Bivalent
[cited by applicant]
Ihssen et al., “Production of glycoprotein vaccines in
[cited by applicant]
Int'l Preminary Report on Patentability dated Feb. 14, 2019 in Int'l Application No. PCT/EP2017/077123, 16 pages.
[cited by applicant]
Int'l Search Report and Written Opinion dated Jul. 20, 2017 in Int'l Application No. PCT/US2016/048278, 9 pages.
[cited by applicant]
Int'l Search Report and Written Opinion issued Jun. 15, 2015 in Int'l Application No. PCT/EP2015/053739, 10 pages.
[cited by applicant]
Int'l Search Report and Written Opinion issued Oct. 27, 2016 in Int'l Application No. PCT/US2016/048278, 16 pages.
[cited by applicant]
Int'l Search Report issued Jan. 24, 2018 in Int'l Application No. PCT/EP2017/077123, 6 pages.
[cited by applicant]
International Search Report and Written Opinion for App. No. PCT/US2020/023415, dated Jun. 12, 2020, 21 pages.
[cited by applicant]
Savita Jadhav et al, “Virulence Characteristics and Genetic Affinities of Multiple Drug Resistant Uropathogenic
[cited by applicant]
Jann et al., “Structural Comparison of the O6 Specific Polysaccharides From
[cited by applicant]
Jansson et al., “Structural studies of the
[cited by applicant]
Jansson et al., “Structural studies of the O-specific side-chains of the
[cited by applicant]
Jiang et al., “Tungsten-Induced Protein Aggregation: Solution Behavior,” Wiley InterScience, vol. 98, No. 12, pp. 4695-4710 (2009).
[cited by applicant]
Johnson et al., “
[cited by applicant]
Johnson et al., Extraintestinal Pathogenic Escherichi coli: “The other bad
[cited by applicant]
Kenne et al., “Structural studies of the Escherichia coli O-antigen 25,” Carbohydrate Research, vol. 122, No. 2, pp. 249-256 (1983).
[cited by applicant]
Kim et al., “Efficiency of a pneumococal Opsonophagocytic Killing Assay Improved by Multiplexing and by Colloring Colonies”, Clinical and Dianostic laboratory Immunology, pp. 616-621, Jul. 2003.
[cited by applicant]
Kohler et al., “What defines extraintestinal pathogenic
[cited by applicant]
Laurentin et al., “A Microtiter Modification of the anthrone-sulfuric acid colorimetric assay for glucose- based carbohydrates”, Analytical Biochemistry, 315, pp. 143-145, 2003.
[cited by applicant]
Lazar et al., Transforming Growth Factor alpha: Mutations of Aspartic Acid 47 and Leucine 48 Results in Different Biological Activities, (Mol. Cell. Biol., 8:1247-1252, 1988).
[cited by applicant]
Lipsitch, “Bacterial vaccines and Serotype Replacement: Lessons from Haemophilus Influenzae and Prospects for
[cited by applicant]
Lukac et al., “Toxoid of Pseudomonas aeruginosa exotoxin A generated by deletion of an active-site residue,” Infect Immun, vol. 56, No. 12, pp. 3095-3098 (1988).
[cited by applicant]
Mario F Feldman et al, “Engineering N-linked protein glycosylation with diverse O antigen lipopolysaccharide structures in
[cited by applicant]
Molina-Lopez et al., “Drug resistance, serotypes, and phylogenetic groups among uropathogenic Escherichia coli including O25-ST131 in Mexico City,” J Infect Dev Ctries, vol. 5, No. 12, pp. 840-849 (2011).
[cited by applicant]
Mora A et al., “Emergence of clonal groups O1:HNM-D-ST59, O15:H1-D-ST393, O20:H34/HNM-D-ST354, O25b:H4-B2-ST131 and ONT:H21,42-B1-ST101 among CTX-M-14-producing
[cited by applicant]
Phan et al., “The serum resistome of a globally disseminated multidrug resistant uropathogenic
[cited by applicant]
Pitout et al., “Extraintestinal Pathogenic
[cited by applicant]
Poolman et al., “Extraintestinal Pathogenic
[cited by applicant]
Poolman, J.T., et al, “The history of pneumococcal conjugate vaccines development: dose selection,” Expert Reviews Vaccines, vol. 12 (12), pp. 1379-1394 (2013).
[cited by applicant]
B. A. Rogers et al, “
[cited by applicant]
Russo et al., “A killed, genetically engineered derivative of a wild-type extraintestinal pathogenic
[cited by applicant]
Russo et al., “Medical and Exonomic impact of extraintestinal infections due to
[cited by applicant]
Schito et al., “The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections”, Elsevier, International Journal of Antimicrobial Agents 34, pp. …
[cited by applicant]
Seidl et al., “Tungsten-Induced Denaturation and Aggregation of Epoetin Alfa During Primary Packaging as a Cause of Immunogenicity,” Pharm. Res., vol. 29, pp. 1454-1467 (2012).
[cited by applicant]
Stenutz Roland et al., “The structures of
[cited by applicant]
Stevenson et al., “Structure of the O antigen of
[cited by applicant]
Stoute et al., “A Preliminary Evaluation of a Recombinant Circumsporozoite Protein Vaccine Against Plasmodium Falciparum Malaria,” New England Journal of Medicine, vol. 336, pp. 86-91 (1997).
[cited by applicant]
Valéria Szijártó et al., “The rapidly emerging ESBL-producing
[cited by applicant]
Terai et al., “
[cited by applicant]
Szijarto et al., “Diagnostic Potential of Monoclonal Antibodies Specific to the Unique O-Antigen of Multidrug-Resistant Epidemic
[cited by applicant]
Van Den Dobbelsteen et al., “Immunogenicity and safety of tetravalent
[cited by applicant]
Wacker et al., “N-linked glycosylation in Campylobacter jejuni and its functional transfer into
[cited by applicant]
Written Opinion dated Dec. 21, 2018 in Int'l Application No. PCT/EP2017/077123, 8 pages.
[cited by applicant]
Written opinion of the Int'l Searching Authority dated Jan. 24, 2018 in Int'l Application No. PCT/EP2017/077123, 6 pages.
[cited by applicant]
Written Opinion of the International Preliminary Examining Authority dated Sep. 11, 2018 in PCT/EP2017/077123, 8 pages.
[cited by applicant]
Extended Search Report dated Sep. 10, 2021 in EP Application No. 21154782.3, 6 pages.
[cited by applicant]
Saade, Elie, et al., “Characertization of
[cited by applicant]
International Search Report issued in International Application No. PCT/EP2014/050895 dated Mar. 14, 2014. 2 pages.
[cited by applicant]
Written Opinion of the International Searching Authority dated Mar. 14, 2014, in connection with corresponding International Application No. PCT/EP2014/050895. 8 pages.
[cited by applicant]
European Search Report issued in International Application No. 13151627.0 dated Mar. 28, 2013. 7 pages.
[cited by applicant]
B.R. Brodeur et al., “Mouse-Human Myelome Partners for the Production of Heterohybridomas”, Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., 1987, pp. 51-63.
[cited by applicant]
J. Wibbenmeyer et al., “Cloning, expression, and characterization of the Fab fragment of the anti-lysozyme antibody HyHEL-5”, Biochimica et Biophysica Acta, 1999, vol. 1430, No. 2, pp. 191-202.
[cited by applicant]
N. Woodford et al., “Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance”, FEMS Microbiol Rev, 2011, vol. 35, No. 5, pp. 736-755.
[cited by applicant]
Duda et al., “The lipopolysaccharide of the mastitis isolate
[cited by applicant]
G. Kohler et al., “Continuous cultures of fused cells secreting antibody of predefined specificity”, Nature, Aug. 7, 1975, vol. 256, pp. 495-497.
[cited by applicant]
D. Kozbor et al., “A Human Hybrid Myeloma for Production of Human Monoclonal Antibodies”, The Journal of Immunology, Dec. 1984, vol. 133, No. 6, pp. 3001-3005.
[cited by applicant]
Myung-Hoon Lee, et al., “Expression and functional reconstitution of a recombinant antibody (Fab′) specific for human apolipoprotein B-100”, Journal of Biotechnology, 2003, vol. 101, pp. 189-198.
[cited by applicant]
S. Muller-Loennies, et al., “Structural Analysis of Oligosaccharides from Lipopolysaccharide (LPS) of
[cited by applicant]
G. Peirano, et al., “Molecular characteristics of extended-spectrum β-lactamase-producing
[cited by applicant]
Extended European Search Report dated Mar. 14, 2017, including the European Search Report and the European Search Opinion, in connection with corresponding EP Application No. 16201732.1 (10 pgs.).
[cited by applicant]
European Office Action dated Mar. 7, 2017, in connection with corresponding EP Application No. 14703783.2 (7 pgs.).
[cited by applicant]
Szijarto et al., “Bactericidal Monoclonal Antibodies Specific to the Lipopolysaccharide 0 Antigen from Multidrug-Resistant
[cited by applicant]
Nagy, Gábor and Pál, Tibor. “Lipopolysaccharide: a tool and target in enterobacterial vaccine development” , vol. 389, No. 5, 2008, pp. 513-520, downloaded from the Internet https://www.degruyter.com/document/doi/10.151…
[cited by applicant]
Simone Cagnacci, et al., “European Emergence of Ciprofloxacin-Resistant
[cited by applicant]
Vajdos et al., “Comprehensive Functional Maps of the Antigen-binding Site of an Anti-ErbB2 Antibody Obtained with Shotgun Scanning Mutagenesis,” J Mol. Biol. 2002, vol. 320(2), pp. 415-428.
[cited by applicant]
Brown et al., “Tolerance to Single, but Not Multiple, Amino Acid Replacements in Antibody Vh CDR2,” The Journal of Immunology, 1996, 156: 3285-3291.
[cited by applicant]
Notification Concerning Transmittal of International Preliminary Report on Patentability dated Aug. 18, 2016, in connection with corresponding international Application No. PCT/EP2014/078709 (7 pgs.).
[cited by applicant]
International Search Report and Written Opinion issued in International Application No. PCT/EP2014/078709 dated May 12, 2015, 4 pages.
[cited by applicant]
Extended European Search Report dated Jul. 16, 2014, in connection with corresponding EP Application No. 14154158.1 (5 pgs.).
[cited by applicant]
Denka Seiken Co. Ltd.(Catalogue), Bacterial Antisera “Seiken”, [Denka Seiken Co.,Ltd, MSDS No. 200000-01, Feb. 16, 2010. 13 pages.
[cited by applicant]
G. Peirano, et al., “Molecular epidemiology of
[cited by applicant]
Cristina Caldas, et al., “Humanization of the anti-CD18 antibody 6.7: an unexpected effect of a framework residue in binding to antigen”, in Molecular Immunology, vol. 39, 2003, pp. 941-952 (12 pgs.).
[cited by applicant]
Arturo Casadevall, et al., “Immunoglobulin isotype influences affinity and specificity”, in PNAS, vol. 109, No. 31, Jul. 31, 2012, pp. 12272-12273 (2 pgs.).
[cited by applicant]
Nadine C. Chien, et al., “Significant structural and functional change of an antigen-binding site by a distant amino acid substitution: Proposal of a structural mechanism”, in Proc. Natl. Acad. Sci., vol. 86, Jul. 1989,…
[cited by applicant]
Chris Galanos, et al., “Galactosamine-induced sensitization to the lethal effects of endotoxin”, in Proc. Natl. Acad. Sci., vol. 76, No. 11, Nov. 1979, pp. 599-5943 (5 pgs.).
[cited by applicant]
Angela M. Giusti, et al., “Somatic diversification of S107 from an antiphosphocholine to an anti-DNA autoantibody is due to a single base change in its heavy chain variable region”, in Proc. Natl. Acad. Sci., vol. 84, M…
[cited by applicant]
Neil S. Greenspan, et al., “Defining epitopes: It's not as easy as it seems”, in Nature Biotechnology, vol. 17, Oct. 1999, pp. 936-937 (2 pgs.).
[cited by applicant]
Marie-Paule Lefranc, et al., “IMGT, the international ImMunoGeneTics database”, in Nucleic Acids Research, vol. 27, No. 1, 1999, pp. 209-212 (4 pgs.).
[cited by applicant]
Helen Miajlovic, et al., “Response of Extraintestinal Pathogenic
[cited by applicant]
Angela Novais, et al., “Contribution of IncFII and Broad-Host IncA/C and IncN Plasmids to the Local Expansion and Diversification of Phylogroup B2
[cited by applicant]
Gisele Peirano, et al., “Characteristics of
[cited by applicant]
Josef Prassler, et al., “In vitro affinity maturation of HuCAL antibodies: complementarity determining region exchange and RapMat technology”, in Immunotherapy, vol. 1, No. 4, 2009, pp. 571-583 (13 pgs.).
[cited by applicant]
Jeffrey Skolnick, et al., “From genes to protein structure and function: novel applications of computational approaches in the genomic era”, in TIBTECH, vol. 18, Jan. 2000, pp. 34-39 (6 pgs.).
[cited by applicant]
Claudia Sheedy, et al., “Isolation and affinity maturation of hapten-specific antibodies”, in Biotechnolgy Advances 25, 2007, pp. 333-352 (20 pgs.).
[cited by applicant]
Pablo Umaña, et al., “Engineeredglycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cyto9toxic activity”, in Nature Biotechnology, vol. 17, Feb. 1999, pp. 176-180 (5 pgs.).
[cited by applicant]
Russian Office Action dated Dec. 27, 2017, in connection with corresponding RU Application No. 2015134413/10 (052839) (18 pgs., including English translation).
[cited by applicant]
Russian Office Action dated Apr. 24, 2018, in connection with corresponding RU Application No. 2016135962/10 (056446) (5 pgs.).
[cited by applicant]
Office Action issued on Aug. 23, 2018 in corresponding Russian Application No. 2016135962, 17 pages including English-language translation.
[cited by applicant]
Reschedko, G.K. et al., “
[cited by applicant]
Office Action issued on Oct. 4, 2018 in corresponding Japanese Application No. 2016-550556; 9 pages including English-language translation.
[cited by applicant]
Office Action issued on Aug. 28, 2018 in corresponding Japanese Application No. 2015-553093; 12 pages including English-language translation.
[cited by applicant]
Royt A et al., “Hypervariable sequences of antigen-recognition centers enable binding of various antigens by antibodies”, Immunology, Moscow, “Mir” Publishers 2000, 4 pages including English-language translation, abstra…
[cited by applicant]
Office Action dated Oct. 17, 2018 in corresponding Russian Application No. 2015134413/10(052839), 17 pages including English-language translation.
[cited by applicant]
Office Action dated Mar. 29, 2018 in Russian Patent Application No. 2015134413, with English translation. 12 pages.
[cited by applicant]
Response to Austrian Office Action dated Mar. 12, 2019 in Austrian Patent Application No. 2018204437. 6 pages.
[cited by applicant]
Abbanat et al., Poster presented at ASM's Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC), Jun. 16-20, 2016, Boston, 1 page.
[cited by applicant]
Huttner et al., “Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic
[cited by applicant]
Office Action issued Apr. 22, 2021 in corresponding Russian Patent Application No. 2019144146/10(085375), 9 pages, with English Translation.
[cited by applicant]
Pinayev et al., “The Cell Cultures”, Information Gazette, 2010, Issue 26, St. Petersburg, 61 pages.
[cited by applicant]
Yakubke et al., “Amino acids, peptides, proteins”, MTR Publishers, 1985, 456 pages.
[cited by applicant]
Wacker, M., et al., “Substrate specificity of bacterial oliogsaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems,” PNAS, vol. 103, No. 18, pp. 7088-7093, May 2, 2006.
[cited by applicant]
International Search Report issued Jun. 12, 2020 in PCT/US2020/023404, 5 pages.
[cited by applicant]
Written Opinion issued Jun. 12, 2020 in PCT/US2020/023404, 6 pages.
[cited by applicant]
Van Den Dobbelsteen Germie P J M et al., “Immunogenicity and safety of a tetravalent
[cited by applicant]
Ihssen Julian et al., “Production of glycoprotein vaccines in
[cited by applicant]
ClinicalTrials.gov archive, “History of Changes for Study: NCT03819049, A Study of Three Different Doses of VAC52416 (ExPEC10V) in Adults Aged 60 to 85 Years in Stable Health”, https://clinicaltrials.gov/ct2/history/NCT…
[cited by applicant]
Jansson et al., “Sturctural Studies of the O-Antigen Polysaccharide of
[cited by applicant]
DebRoy et al., “Comparison of O-Antigen Gene Clusters of All O-Serogroups of
[cited by applicant]
Office Action issued Feb. 3, 2023 in corresponding Korean Patent Application No. 10-2019-7011812, 8 pages, with English Translation.
[cited by applicant]
DebRoy C, Fratamico PM, Yan X, Baranzoni G, Liu Y, et al. (2016) Correction: Comparison of O-Antigen Gene Clusters of All O-Serogroups of
[cited by applicant]
Sela-Culang et al. The structural basis of antibody-antigen recognition, Frontiers in Immunology, 2013 vol. 4, article 302, pp. 1-13.
[cited by applicant]
Moll et al. “A Reexamination of the O1 Lipopolysaccharide antigen group of
[cited by applicant]
Chorro et al. “Preclinical validation of an
[cited by applicant]