# US 10,865,222 B2 · Neisseria gonorrhoeae therapeutic based on CMP-nonulosonate sugars > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,865,222 B2 - Document ID: US10865222B2 - Status: Granted - Kind: B2 - Application number: 15/693,852 - Filed: 2017-09-01 - Published: 2017-12-21 - Granted: 2020-12-15 - Earliest claimed: 2014-02-20 - Assignees: National Research Council of Canada; University of Massachusetts Medical School - Applicants: National Research Council of Canada; University of Massachusetts Medical School - Inventors: Ian Schoenhofen; Dennis M. Whitfield; Sanjay Ram - Web page: https://patentgrep.com/patent/US10865222B2 ## CPC - C07H 19/10: with the saccharide radical esterified by phosphoric or polyphosphoric acids - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - A61P 31/04: Antibacterial agents - C12Q 1/18: Testing for antimicrobial activity of a material - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract N. gonorrhoeae has become resistant to almost every conventional antibiotic. Described herein is the use of CMP-nonulosonate analogues to counter gonococcal complement evasion. The nonulosonate sugar is incorporated into the lipooligosaccharide of the N. gonorrhoeae which in turn reduces the serum resistance of the bacteria. This provides a novel therapeutic strategy against the global threat of multi-drug resistant gonorrhea. ## Claims ### Claim 1 A method for identifying a cytidine 5′-monophospho-nonulosonate (CMP-nonulosonate) sugar capable of reducing virulence of N. gonorrhoeae comprising: incubating a control culture of N. gonorrhoeae with a first CMP-nonulosonate sugar under conditions that result in incorporation of the nonulosonate sugar of the first CMP-nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae; incubating a test culture of N. gonorrhoeae with the first CMP-nonulosonate sugar and a second CMP-nonulosonate sugar under conditions that result in incorporation of the nonulosonate sugar of the first CMP-nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae; and determining if serum resistance of the test culture of N. gonorrhoeae after incubation with the first and second CMP-nonulosonate sugars is Rower than serum resistance of the control culture of N. gonorrhoeae after incubation with the first CMP-nonulosonate sugar, wherein the first CMP-nonulosonate sugar is a CMP-nonulosonate sugar that is able to confer serum resistance to serum-sensitive N. gonorrhoeae. ### Claim 2 (depends on 1) The method according to claim 1 wherein the serum resistance is determined by measuring factor H binding. ### Claim 3 (depends on 1) The method according to claim 1 wherein the serum resistance is determined by measuring C4 deposition. ### Claim 4 (depends on 1) The method according to claim 1 wherein the serum resistance is determined by measuring IgG binding. ### Claim 5 (depends on 1) The method according to claim 1, wherein the first CMP-nonulosonate sugar is a CMP-sialic acid. ### Claim 6 (depends on 1) The method according to claim 1, wherein the first CMP-nonulosonate sugar is cytidine 5′-monophospho-N-glycolylneuraminic acid (CMP-Neu5Gc). ### Claim 7 (depends on 1) The method according to claim 1, wherein the first CMP-nonulosonate sugar is cytidine 5′-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac). ### Claim 8 (depends on 1) The method according to claim 1, wherein incubation of the test culture with the first CMP-nonulosonate sugar is initiated prior to incubation of the test culture with the second CMP-nonulosonate sugar. ### Claim 9 (depends on 8) The method according to claim 8, wherein the first CMP-nonulosonate sugar is cytidine 5′-monophospho-N-glycolylneuraminic acid (CMP-Neu5Gc). ### Claim 10 (depends on 8) The method according to claim 8, wherein the first CMP-nonulosonate sugar is cytidine 5′-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac). ### Claim 11 (depends on 8) The method according to claim 8, wherein the serum resistance is determined by at least one of measuring factor H binding, measuring C4 deposition, and measuring IgG binding. ### Claim 12 (depends on 1) The method according to claim 1, wherein the first CMP-nonulosonate sugar and the second CMP-nonulosonate sugar are added to the test culture of N. gonorrhoeae at the same time. ### Claim 13 (depends on 12) The method according to claim 12, wherein the first CMP-nonulosonate sugar is cytidine 5′-monophospho-N-glycolylneuraminic acid (CMP-Neu5Gc). ### Claim 14 (depends on 12) The method according to claim 12, wherein the first CMP-nonulosonate sugar is cytidine 5′-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac). ### Claim 15 (depends on 12) The method according to claim 12, wherein the serum resistance is determined by at least one of measuring factor H binding, measuring C4 deposition, and measuring IgG binding. ### Claim 16 A method for identifying a cytidine 5′-monophospho-nonulosonate (CMP-nonulosonate) sugar capable of reducing virulence of N. gonorrhoeae, the method comprising: incubating a control culture of N. gonorrhoeae with cytidine 5′-monophospho-N-glycolylneuraminic acid (CMP-Neu5Gc) under conditions that result in incorporation of the nonulosonate sugar of CMP-Neu5Gc into lipooligosaccharide of the N. gonorrhoeae; incubating a test culture of N. gonorrhoeae with a second CMP-nonulosonate sugar under conditions suitable for incorporation of the nonulosonate sugar of the second CMP-nonulosonate sugar into lipooligosaccharide of the N. gonorrhoeae; and determining if serum resistance of the test culture of N. gonorrhoeae after incubation with the second CMP-nonulosonate sugar is lower than serum resistance of the control culture of N. gonorrhoeae after incubation with CMP-Neu5Gc, wherein the control culture of N. gonorrhoeae is serum sensitive prior to incubation with the CMP-Neu5Gc, and wherein the test culture of N. gonorrhoeae is serum sensitive prior to incubation with the second CMP-nonulosonate sugar. ### Claim 17 (depends on 16) The method according to claim 16, further comprising determining if the nonulosonate sugar from the second CMP-nonulosonate sugar has been incorporated into lipooligosaccharide of the N. gonorrhoeae. ### Claim 18 (depends on 16) The method according to claim 16, wherein the serum resistance is determined by at least one of measuring factor H binding, measuring C4 deposition, and measuring IgG binding.