# US 2013/0157932 A1 · Ngal and urinary tract infection > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0157932 A1 - Document ID: US20130157932A1 - Status: Published application - Kind: A1 - Application number: 13/671,533 - Filed: 2012-11-07 - Published: 2013-06-20 - Earliest claimed: 2010-05-07 - Assignees: The Trustees of Columbia University in the City of New York - Inventors: Jonathan BARASCH; Neal Paragas - Web page: https://patentgrep.com/patent/US20130157932A1 ## CPC - A61K 38/1709: {from mammals} - A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants} - A61K 31/7028: Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages - A61K 31/7088: Compounds having three or more nucleosides or nucleotides - A61K 31/739: Lipopolysaccharides - A61K 38/05: Dipeptides - A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)} - C12Q 1/6883: for diseases caused by alterations of genetic material - G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels} - C12Q 2600/136: Screening for pharmacological compounds - C12Q 2600/158: Expression markers - G01N 2333/82: Translation products from oncogenes - G01N 2500/00: Screening for compounds of potential therapeutic value - G01N 2500/10: involving cells - 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 - 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) - 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 - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract In some embodiments, the present invention is directed to compositions and methods for the treatment and prevention of urinary tract infections (UTIs) and urosepsis. In some embodiments, the methods of the invention comprise administering to a subject in need thereof a therapeutically effective amount of an agent that stimulates genito-urinary tract epithelial cells to produce NGAL, and/or an NGAL protein or a functional derivative thereof, and optionally also administering to the subject an additional agent useful for treating or preventing UTI or urosepsis. In other embodiments, the present invention also provides methods of screening for agents that stimulate urinary tract epithelial cells to produce NGAL. ## Claims ### Claim 1 A method for treating or preventing a bacterial infection of the urinary tract, or urosepsis associated therewith, in a subject, the method comprising administering to the subject a therapeutically effective amount of one or more agents selected from the group consisting of: (a) an agent that stimulates genito-urinary tract epithelial cells to produce NGAL, (b) an NGAL protein, and (c) a functional derivative of an NGAL protein. ### Claim 2 (depends on 1) The method of claim 1, wherein the subject is a human. ### Claim 3 (depends on 1) The method of claim 1, wherein the bacterial infection is an infection with a catecholate siderophore-dependent bacterium. ### Claim 4 (depends on 1) The method of claim 1, wherein the bacterial infection is an infection with an enterochelin-dependent bacterium. ### Claim 5 (depends on 1) The method of claim 1, wherein the bacterial infection is an infection with an enterochelin-dependent E. coli bacterium. ### Claim 6 (depends on 1) The method of claim 1, further comprising administering to the subject an additional bacteriostatic or antibiotic agent. ### Claim 7 (depends on 1) The method of claim 1, wherein the genito-urinary tract epithelial cells are kidney epithelial cells. ### Claim 8 (depends on 7) The method of claim 7, wherein the kidney epithelial cells are collecting duct epithelial cells or epithelial cells of the thick ascending limb of Henlé. ### Claim 9 (depends on 1) The method of claim 1, wherein the agent that stimulates genito-urinary tract epithelial cells to produce NGAL is an NFκB activator, a NRF2 modulator, or a HIF modulator. ### Claim 10 (depends on 1) The method of claim 1, wherein the agent that stimulates genito-urinary tract epithelial cells to produce NGAL is an activator of a TLR-NFκB pathway. ### Claim 11 (depends on 10) The method of claim 10, wherein the activator of a TLR-NFκB pathway is an activator of a TLR4-NFκB pathway. ### Claim 12 (depends on 10) The method of claim 10, wherein the activator of a TLR-NFκB pathway is an activator of a TLR11-NFκB pathway. ### Claim 13 (depends on 1) The method of claim 1, wherein the agent that stimulates genito-urinary tract epithelial cells to produce NGAL is a non-toxic derivative of either lipid A, lipopolysaccharide, or endotoxin. ### Claim 14 (depends on 1) The method of claim 1, wherein the agent that stimulates genito-urinary tract epithelial cells to produce NGAL, and/or the NGAL or functional derivative thereof, are administered systemically. ### Claim 15 (depends on 1) The method of claim 1, wherein the agent that stimulates genito-urinary tract epithelial cells to produce NGAL, and/or the NGAL or functional derivative thereof, are administered locally to the genitourinary tract. ### Claim 16 A method for treating or preventing bacterial infection of the urinary tract, or urosepsis associated therewith, in a subject, the method comprising stimulating genito-urinary tract epithelial cells of the subject to produce NGAL. ### Claim 17 (depends on 16) The method of claim 16, wherein the subject is a human. ### Claim 18 (depends on 16) The method of claim 16, wherein the bacterial infection is an infection with a catecholate siderophore-dependent bacterium. ### Claim 19 (depends on 16) The method of claim 16, wherein the bacterial infection is an infection with an enterochelin-dependent bacterium. ### Claim 20 (depends on 16) The method of claim 16, wherein the bacterial infection is an infection with an enterochelin-dependent E. coli bacterium. ### Claim 21 (depends on 16) The method of claim 16, wherein the genito-urinary tract epithelial cells are kidney epithelial cells. ### Claim 22 (depends on 21) The method of claim 21, wherein the kidney epithelial cells are collecting duct epithelial cells or epithelial cells of the thick ascending limb of Henlé. ### Claim 23 (depends on 16) The method of claim 16, wherein the step of stimulating genito-urinary tract epithelial cells to produce NGAL comprises administering to the subject a therapeutically effective amount one or more agent selected from the group consisting of: (a) a therapeutically effective derivative of lipid A, (b) a therapeutically effective derivative of lipopolysaccharide, (c) a therapeutically effective derivative of endotoxin, (d) an activator of the TLR4-NFkB pathway, (e) an activator of the TLR11-NFkB pathway, (f) an NFκB activator, (g) a NRF2 modulator, and (h) a HIF modulator. ### Claim 24 (depends on 23) The method of claim 23, wherein the agent is administered systemically. ### Claim 25 (depends on 23) The method of claim 23, wherein the agent is administered locally to the genitourinary tract. ### Claim 26 A pharmaceutical composition for use in treating or preventing a bacterial urinary tract infection, or urosepsis associated therewith, the composition comprising a therapeutically effective amount of an agent that stimulates genito-urinary tract epithelial cells to produce NGAL, and a therapeutically effective amount of an NGAL protein or a functional derivative thereof. ### Claim 27 (depends on 26) The composition of claim 26, wherein the agent that stimulates genito-urinary tract epithelial cells to produce NGAL is selected from the group consisting of: (a) a non-toxic derivative of lipid A, (b) a non-toxic derivative of lipopolysaccharide, (c) a non-toxic derivative of endotoxin, (d) an activator of the TLR4-NFkB pathway, (e) an activator of the TLR11-NFkB pathway, (f) an NFκB activator, (g) a NRF2 modulator, and (h) a HIF modulator. ### Claim 28 A method of identifying an agent that stimulates epithelial cells of the urinary tract to produce NGAL mRNA or NGAL protein, the method comprising: (a) providing a test population of urinary tract epithelial cells and a control population of urinary tract epithelial cells, (b) contacting the test population of urinary tract epithelial cells with one or more test agents, (c) contacting the control population of urinary tract epithelial cells with no agent or with one or more negative control agents, and (d) determining the level of NGAL mRNA or NGAL protein in the test population and the control population, or in a culture supernatant thereof, wherein a level of NGAL mRNA or NGAL protein in the test population, or a culture supernatant thereof, that is higher than the level of NGAL mRNA or NGAL protein in the control population, or a culture supernatant thereof, indicates that the test agent is an agent that stimulates production of NGAL mRNA or NGAL protein by the urinary tract epithelial cells. ### Claim 29 A method of identifying an agent that stimulates epithelial cells of the urinary tract to produce NGAL mRNA or NGAL protein, the method comprising: (a) providing a population of urinary tract epithelial cells, (b) determining the control level of NGAL mRNA or NGAL protein in the population of urinary tract epithelial cells, or in a culture supernatant thereof, wherein the control level is the level of NGAL mRNA or NGAL protein present prior to contacting the urinary tract epithelial cells with one or more test agents, (c) contacting the urinary tract epithelial cells with one or more test agents, (d) determining the test level of NGAL mRNA or NGAL protein in the population of urinary tract epithelial cells, or in a culture supernatant thereof, wherein the test level is the level of NGAL mRNA or NGAL protein present subsequent to contacting the urinary tract epithelial cells with the one or more test agents, wherein if the test level of NGAL mRNA or NGAL protein exceeds the control level of NGAL mRNA or NGAL protein, the test agent is an agent that stimulates production of NGAL mRNA or NGAL protein by the urinary tract epithelial cells.