# US 2013/0251702 A1 · Method for screening compounds for treating sepsis targeting nod2 signalling pathway and composition for treating sepsis comprising nod2 signalling pathway inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0251702 A1 - Document ID: US20130251702A1 - Status: Published application - Kind: A1 - Application number: 13/848,286 - Filed: 2013-03-21 - Published: 2013-09-26 - Earliest claimed: 2012-03-21 - Assignees: Snu R&Db Foundation - Inventors: Doo Hyun CHUNG; Sae Jin OH; Ji Hyung KIM - Web page: https://patentgrep.com/patent/US20130251702A1 ## CPC - C12Q 1/485: {involving kinase} - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - C12Q 1/68: involving nucleic acids - G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} - G01N 2500/02: Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) - G01N 2800/26: Infectious diseases, e.g. generalised sepsis - 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 - 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) - 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) ## Abstract Methods for screening compounds for treating sepsis are disclosed. The present methods and compositions are targeting NOD2 mediated signaling pathway and the agents identified by the present methods are qualified as drug candidates for clinical development. Further Methods and composition for treating sepsis are disclosed. ## Claims ### Claim 1 A method of screening a therapeutic agent for sepsis, which comprises: (i) providing a RIP2 protein; (ii) contacting the RIP2 protein with a test substance wherein the substance is expected to inhibit the phosphorylation or kinase activity of the RIP2 protein; and (iii) selecting a test substance as a candidate that decreases the phosphorylation level or the kinase activity of the RICK protein in comparison to a negative control that is not contacted with a test substance. ### Claim 2 (depends on 1) The method according to claim 1, wherein the RIP2 protein is provided as a cell. ### Claim 3 (depends on 2) The method according to claim 2, wherein the cell is a dendritic cell, a neutrophil, an epithelial cell, 293T, 293 or 293A or any combination thereof. ### Claim 4 (depends on 1) The method according to claim 1, further comprising selecting a test substance that increases the expression of a CD55 and/or decreases the level of C5a. ### Claim 5 (depends on 1) The method according to claim 1, wherein the test substance is derived from small molecules or biologics. ### Claim 6 A method of screening a therapeutic agent for sepsis comprising: (i) providing either a NOD2 or the CARD region of a NOD2 protein, and either a RIP2 or the CARD region of a RIP2 protein; (ii) contacting the proteins with a test substance wherein the substance is expected to interfere with the interaction of the NOD2 or the CARD region of the NOD2 with the RIP2 or the CARD region of the RIP2 protein; and (iii) detecting the interaction of (ii) and selecting a test substance as a candidate that interfere with the interaction. ### Claim 7 (depends on 6) The method according to claim 6, wherein the NOD2, the CARD region of the NOD2 protein, the RIP2 and the CARD region of the RIP2 protein are provided as cells. ### Claim 8 (depends on 7) The method according to claim 7, wherein the cells are a dendritic cell, a neutrophil, an epithelial cell, 293T, 293 or 293A or any combination thereof. ### Claim 9 (depends on 7) The method according to claim 7, further comprising selecting a test substance that increases the expression of a CD55 and/or decreases the level of C5a. ### Claim 10 A method of treating sepsis comprising administering to a subject in need thereof an effective amount of an inhibitor of the kinase activity of a RIP2 protein and/or an inhibitor of the phosphorylation of a RIP2 protein. ### Claim 11 (depends on 10) The method according to claim 10, wherein the inhibitor of kinase activity is selected from the group consisting of Imatinib, Dasatinib, Niolotinib, Gefitinib, Erlotinib, Afatinib, Dacomitinib, Crizotinib, Sorafenib, Sunitinib, Pazopanib, Axitinib, Lapatinib, Vemurafenib, Everolimus, Temsirolimus, Dovitinib and SB203580. ### Claim 12 A method of treating sepsis comprising administering to a subject in need thereof an effective amount of one or more NOD2 inhibitors. ### Claim 13 (depends on 12) The method according to claim 12, wherein the NOD2 inhibitor suppresses the expression or activity of the NOD2, which includes small molecules, antibodies, antisense oligonucleotides, siRNAs, shRNAs miRNAs and polypeptides. ### Claim 14 A method of treating sepsis comprising administering to a subject in need thereof an effective amount of one or more RIP2 inhibitors. ### Claim 15 (depends on 14) The method according to claim 14, wherein the RIP2 inhibitor inhibit the expression or activity of the RIP2, which includes small molecules, antibodies, antisense oligonucleotides, siRNAs, shRNAs miRNAs and polypeptides. ### Claim 16 A method of treating sepsis comprising administering to a subject in need thereof an effective amount of one or more inhibitors that interfere with RIP2 and NOD2 interaction.