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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau I (10) International Publication Number (43) International Publication Date 29 December 2011 (29.12.2011) P O WO 2011/163241 A3 PCT DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, 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. (51) International Patent Classification: A01N 43/90 (2006.01) (21) International Application Number: PCT/US201 1/041265 (22) International Filing Date: 2 1 June 201 1 (21 .06.201 1) (84) Designated States (unless otherwise indicated, for every kind o regional protection available): ARIPO (BW, GH, f English (26) Publication Language: GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 61/356,925 2 1 June 2010 (21.06.2010) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (71) Applicant (for all designated States except US): GEOR¬ MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, GETOWN UNIVERSITY [US/US]; A Congressionally TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Chartered Institution, of Higher Education, 37th & O ML, MR, NE, SN, TD, TG). Streets, N.W., Washington, District of Columbia 20057 Declarations under Rule 4.17 : (US). (25) Filing Language: English (72) Inventors; and (75) Inventors/Applicants (for US only): DJAKIEW, Daniel [US/US]; 1536 Longfellow Street, McLean, Virginia 22101 (US). EL TOUNY, Lara, H. [EG/US]; 4440 Willard Ave., Apt. 417, Chevy Chase, Maryland 20815 (US). (74) Agent: MCKEON, Tina, Williams; McKeon, Meunier, Carlin & Curfman, LLC, Suite 900, 817 W . Peachtree Street NW, Atlanta, Georgia 30308 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, — as to applicant's entitlement to apply for and be granted a patent (Rule 4.1 7(H)) — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.1 7(in)) — o inventorship (Rule 4. 1 7(iv)) f Published: — with international search report (Art. 21(3)) (88) Date of publication of the international search report: 20 March 2014 (54) Title: NEUROPROTECTIVE COMPOUNDS (57) Abstract: This disclosure relates to compounds that can be utilized to treat a neural injury or disorder. Methods of identifying and making these compounds are also set forth herein. INTERNATIONAL SEARCH REPORT International application PCT/US A . CLASSIFICATION O F SUBJECT IPC(8) - A01 N 43/90, USPC - 5 14/259.3 According B. to International FIELDS 43/14; 1 1/41265 MATTER (201 1 .01 ) Patent Classification (IPC) o r to both national classification and IPC SEARCHED Minimum documentation searched (classification IPC(8): A01N 43/90, 43/14; (201 1.01) USPC: 514/259.3 system followed Documentation searched other than minimum documentation IPC(8): A01N 43/90; A 6 1 31/535, 31/44 (201 1 .01) USPC: 514/259.3,263.3,229.8,290,437 Electronic data base consulted during the international by classification symbols) to the extent that such documents are included in the fields searched search (name of data base and, where practicable, search terms used) PubWEST;PGPB, USPT, EPAB, JPAB, GoogleScholar, ScienceDirect, Dialog Biochanin-A Biochanin 4'-Methylgenistein olmelin Biochanine A Biochanin-A Genistein isoflavones injury neuroprotection Low-Affinity Nerve Growth Factor Receptor, LNGFR, p75 neurotropfiin receptor, C. No. DOCUMENTS CONSIDERED Citation Category* p75NTR p38-MAPK P38 mitogen-activated T O B E RELEVANT o f document, with indication, where appropriate, o f the relevant passages Relevant 12-14, U S 2006/0276393 A 1 (MILBURN e t al.) 7 December para-para, para, para[1 153] 2006 (07.12.2006) Abstract, 23-25 and 34-36 1-3 1-3, 47-50 U S 2008/0064036 A 1 (BRUINZEEL 46-53 U S 2005/0239882 A 1 (KIM e t al.) 2 7 October U S 2003/0109027 A 1 (MURAKAMI e t al.) 13 March 2008 (13.03.2008) 2005 (27.10.2005) e t al.) 12 June 2003 Abstract, Abstract, (12.06.2003) para para para, CONTINUED Further documents O N NEXT are listed in the continuation Special categories of cited documents: earlier application or patent but published on or after the international filing date L" document which may throw doubts on priority claim(s) or which is cited to establish the publication date of another citation or other special reason (as specified) O" document referring to an oral disclosure, use, exhibition means P" document published prior to the international filing date but later than the priority date claimed search 201 1 (09.1 1 .201 1) address o f the ISA/US Mail Stop PCT, Attn: ISA/US, Commissioner for Patents P.O. Box 1450, Alexandria, Virginia 22313-1450 Facsimile No. Form PC T SA 10 (second sheet) (July 2009) 51-52 "T" E" and mailing RNA □ o f Box C . later document published after the international filing date or priority date and not in conflict with the application but cited to understand the principle or theory underlying the invention "X" document of particular relevance; the claimed invention cannot be considered novel or cannot be considered to involve an inventive step when the document is taken alone "Y" document of particular relevance; the claimed invention cannot be considered to involve an inventive step when the document is combined with one or more other such documents, such combination being obvious to a person skilled in the art "&" document member of the same patent family document defining the general state of the art which is not considered to be of particular relevance o f the international 48-50 SHEET A" Date o f the actual completion 46-53 para Quann e t al. The p38 MAPK Pathway Mediates Aryl Propionic Acid. Induced Messenger Stability o f p75NTR in Prostate Cancer Cells. Cancer Res 2007;67:1 1402-1 1410. Abstract Name to claim No. para, Culmsee e t al. NERVE GROWTH FACTOR SURVIVAL SIGNALING IN CULTURED HIPPOCAMPAL NEURONS IS MEDIATED THROUGH TRKA AND REQUIRES THE COMMON NEUROTROPHIN RECEPTOR P75. Neuroscience Vol. 1 15, No. 4 , pp. 1089-1 108, 2002 Abstract 9 November neural protein.... or other Date o f mailing o f the international 2 5 NOV Authorized search report 2011 officer: Lee W . Young INTERNATIONAL SEARCH REPORT International application No. PCT/US 11/41265 Box No. II Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet) This international search report has not been established in respect of certain claims under Article 17(2)(a) for the following reasons: Claims Nos.: because they relate to subject matter not required to be searched by this Authority, namely: □ Claims Nos.: because they relate to parts of the international application that do not comply with the prescribed requirements to such an extent that no meaningful international search can be carried out, specifically: Claims Nos.: 4-1 1,15-22,26-33,37-45 because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4(a). 3. Box No. Ill Observations where unity of invention is lacking (Continuation of item 3 of first sheet) This International Searching Authority found multiple inventions in this international application, as follows: □ □ □ As all required additional search fees were timely paid by the applicant, this international search report covers all searchable claims. As all searchable claims could be searched without effort justifying additional fees, this Authority did not invite payment of additional fees. As only some of the required additional search fees were timely paid by the applicant, this international search report covers only those claims for which fees were paid, specifically claims Nos.: No required additional search fees were timely paid by the applicant. Consequently, this international search report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.: □ □ The additional search fees were accompanied by the applicant's protest and, where applicable, the payment of a protest fee. * The additional search fees were accompanied by the applicant's protest but the applicable protest fee was not paid within the time limit specified in the invitation. No protest accompanied the payment of additional search fees. Form PCT/lSA/210 (continuation of first sheet (2)) (July 2009) INTERNATIONAL SEARCH REPORT International application No. PCT/US 11/41265 C (Continuation). Category* DOCUMENTS CONSIDERED T O BE RELEVANT Citation o f document, with indication, where appropriate, of the relevant passages Relevant to claim No. CONTINUED FROM PRIOR SHEET A Nguyen et al. The intracellular genistein metabolite 5,7,3-tetrahydroxyisoflavone mediates G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling pathway. Free Radical Biology & Medicine 4 1 (2006) 1225.1239 Abstract A Munoz et al. Targeting p38 MAPK pathway for the treatment of Alzheimer's disease. Neuropharmacology 58 (2010) 561-568 Abstract A Sonee et al. The Soy Isoflavone, Genistein, Protects Human Cortical Neuronal Cells from Oxidative Stress. NeuroToxicology 25 (2004) 885.891 Abstract A Schroeter et al. Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem. J. (2001) 358, 547-557 Abstract Form PCT/lSA/210 (continuation of second sheet) (July 2009) 1-3, 12-14, 23-25, 34-36 and 46-53 1-3, 12-14, 23-25, 34-36 and 46-53 1-3, 12-14, 23-25, 34-36 and 46-53 1-3, 12-14, 23-25, 34-36 and 46-53