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WO 2016/203014 Al O (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/203014 Al 22 December 2016 (22.12.2016) P O P C T (51) International Patent Classification: (74) Agent: BASF IP ASSOCIATION; BASF SE, ZRX-C6, G01N 33/68 (2006.01) 67056 Ludwigshafen (DE). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP20 16/064078 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) Date: International Filing BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 17 June 2016 (17.06.2016) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 62/182,037 19 June 2015 (19.06.2015) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: BASF SE [DE/DE]; Carl-Bosch-Str. 38, 67056 Ludwigshafen am Rhein (DE). (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (72) Inventors: VON DEYN, Wolfgang; An der Bleiche 24, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 67435 Neustadt (DE). NESTEROV, Alexandre; 13 103 TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, Drew Hill Lane, Chapel Hill, North Carolina 275 14 (US). TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, KANDASAMY, Ramani; 303 Tramore Drive, Chapel DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Hill, North Carolina 275 16 (US). LONDON, Damian; LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 3521 Buck Run Trail, Wake Forest, North Carolina 27587 SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, (US). SALGADO, Vincent L.; 25 19 Baptist Road, GW, KM, ML, MR, NE, SN, TD, TG). Durham, nc 27703 (US). LELITO, Katherine; 26 Davis Drive, Research Triangle Park, North Carolina 27709 Published: (US). — with international search report (Art. 21(3)) [Continued on next page] (54) Title: METHODS FOR IDENTIFYING COMPOUNDS THAT DIRECTLY BIND TO INSECT TRANSIENT RECEPTOR POTENTIAL CHANNELS (57) Abstract: The present invention relates B to a screening method for determining wheth er or not a candidate compound directly binds Nan + lav to an insect transient receptor potential V Nan Nan + lav • av Nan (TRPV) channel. The present invention fur ther provides a method of identifying a com pound that directly binds to a Nanchung pro Nan + lav Man tein, TRP and/or TRPV protein and/or chan High L w High L w affinity affinitv affinity affinity nel using a binding assay. The present inven tion further provides a method of classifying fm mg 87 7 ND 242 an insecticide compound by its mode of ac 0Λ32 2 3 ND 2.1 tion using the binding assay and/or a func tional assays. 0 < 100 160 2 0 260 [ H]-Afidopyropen n } Bound (fmol/mg) Figure 8 . [ H]-Afidopyropen binds to Nan protein, and binding affinity is increased in the presence of lav. (A) Saturation binding of [ H]-afidopyropen to membranes obtained from CHO cells expressing fruit fly Nan and lav, either alone or together. Binding isotherms were fit into < two-sites binding model ( averages ± S.D. of 3 repetitions). No specific binding to lav was detected. Membranes obtained from both Nan-lav co-expressing cells, and from the cells expressing Nan alone demonstrated specific binding with comparable number of total binding o sites at concentration of radioligand approaching saturation. Co-expression of lav together with Nan revealed the presence of high affinity binding sites, which were not detectable in Nan alone- o expressing membranes (table insert). (B) Scatchard transformation of the binding isoterms illustrates presence of high affinity sites in the membranes co-expressing Nan and lav, but not Nan alone. v o o — with sequence listing part of description (Rule 5.2(a)) METHODS FOR IDENTIFYING COMPOUNDS THAT DIRECTLY BIND TO INSECT TRANSIENT RECEPTOR POTENTIAL CHANNELS CROSS-REFERENCE TO RELATED APPLICATION The present patent document claims the benefit of the filing date under 35 U.S.C. § 119(e) of Provisional U.S. Patent Application Serial No. 62/182,037, filed June 19, 2015, which is hereby incorporated by reference in its entirety. SUBMISSION OF SEQUENCE LISTING The Sequence Listing associated with this application is filed in electronic format via EFS-Web and hereby incorporated by reference into the specification in its entirety. The name of the text file containing the Sequence Listing is PF78630 SEQLIST. The size of the text file is 619 KB, and the text file was created on June 18, 2015. BACKGROUND The present invention generally relates to methods for determining agents that bind directly to one or more Nanchung proteins, transient receptor potential (TRP) protein complexes and/or channels and/or transient receptor potential V (TRPV) protein complexes and/or channels. The present invention also relates to compositions and methods of insect control as well as mode of action classification for an insecticide composition comprising a compound capable of binding directly to the one or more Nanchung proteins, transient receptor potential (TRP) protein complexes and/or channels and/or transient receptor potential V (TRPV) protein complexes and/or channels. The present invention further relates to compositions and methods of insect control, as well as mode of action classification for an insecticide composition comprising a compound capable of directly binding to the one or more Nanchung proteins, transient receptor potential (TRP) protein complexes and/or channels and/or transient receptor potential V (TRPV) protein complexes and/or channels. The present invention even further relates to compositions and methods of insect control as well as mode of action classification for an insecticide composition comprising a compound capable of directly binding to the one or more Nanchung proteins, transient receptor potential (TRP) protein complexes and/or channels and/or transient receptor potential V (TRPV) protein complexes and/or channels wherein the compound is also capable of modulating the one or more TRP and/or TRPV channels. Almost all field crops, plants, and commercial farming areas are susceptible to attacks by plant insect pests. Plant insect pests are a major factor in the loss of the world's commercially 2 important agricultural crops resulting both, in economic hardship to farmers and nutritional deprivation for local populations in many parts of the world. In other words, insect pests cause great loses and damages to human agriculture, food supply, post-harvest storage, horticulture, animal health and public health. While advances have been made in the control of these insects, these insects have been able to adopt and evade the control measures, resulting in resistant insect populations. As a result, there remains a need for better understanding of the mechanisms that underlie feeding and other behaviors of insect pests. Such knowledge would allow for the design of agents and strategies for intervening or preventing attacks on field crops, plants, and commercial farming areas by the insect pests. Broad spectrum chemical pesticides and insecticides have been used extensively to control or eradicate plant insect pests of agricultural importance. There is, however, substantial interest in identifying and/or developing effective alternative insecticides. As such, effective methods for screening of the new insecticides would be desirable. What are needed, then, are new methods that can be employed in screening for agents that modulate insect behavior, bind directly to one or more Nanchung proteins, transient receptor potential (TRP) and/or transient receptor potential V (TRPV) protein complexes and/or channels and in some cases, screening for agents that can act as insecticides. BRIEF SUMMARY OF THE INVENTION In one embodiment, the present invention relates to a method for determining whether or not a candidate compound binds directly to one or more Nanchung proteins, transient receptor potential (TRP) and/or transient receptor potential V (TRPV) protein complexes and/or channels. The method may include providing one or more Nanchung proteins, transient receptor potential (TRP) and/or transient receptor potential V (TRPV) proteins, protein complexes and/or channels that may be located in a cell, derived from a cell, produced by a cell or produced in a cell-free system, contacting the one or more Nanchung proteins, TRP , and/or TRPV proteins, protein complexes and/or channels with a candidate compound, and assaying to determine the binding affinity of a candidate compound to the one or more Nanchung proteins, TRP , and/or TRPV proteins, protein complexes and/or channels, wherein the binding affinity of the candidate compound is indicative of the candidate compounds ability to directly bind to one or more Nanchung proteins, TRP , and/or TRPV proteins, protein complexes and/or channels. For example, in certain embodiments, the binding assay step may include at least one of the following steps: (1) contacting the one or more Nanchung proteins, TRP, and/or TRPV proteins, protein complexes and/or channels with a compound, wherein the compound may be labeled or unlabeled; (2)
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