(12) 特許協力条約に基づいて公開 された国際出願 (19
Contents
1. PCT 1SA 2 10 1 2 2009 7 PCT JP2011 051807 5 6 6 S 10 9 S 10 0A 8 9 S 10 0 9 S 10 0 8 A 92. x IER SER X AD 2 2012 017700 10 PCT JP2011 051807 0027
3. 0030 KUJA IF REIF C 2012 017700 11 PCT JP2011 051807 0031 1 0032 0033 0034
4. 2 7 lt E 7 U 0028 0 000 1 20 0 7 0 0001 10 08 89 0029
5. A 1 S 100A 9 GST S 100 A9 S100A8 A 9 LC MS MS 755 LCYMSYM S 4100 gt ym 120O0mm New Objetive 5 um A qua C18 P henomenex 100mm
6. 5 1 0 0A 8 A 9 2012 017700 8 PCT JP2011 051807 0020 0021 0022 S 10 0 A 8 A9 DNAR 8 Hum Genet 2002 111 310 31 3 10 gt S 1 0 0 A 8 A9 RRB S 100A8 A 9 P CREA WAR LES 10 0A 8 A 9 cDNA
7. S 10 0A 9 1 7 2 LC MS MS S 100A9 31 s iRNA 41 9 MMP 6 S 100A9 2012 017700 6 PCT JP2011 051807 0014 7 MMP 1 8 S 1 0 0 8B
8. C S 10 0A 9 12 2012 017700 9 PCT JP2011 051807 0023 0024 0025 0026 T6588 X
9. 5 10 0 A 9 EpiLife 1ng m 1mg ml 1Ong m 1 8 5100 4 n gm 10 gm 5 10 0 A 9 S 100A8 A9 a 00A9 S 100A8 A 9 Ur o 3 0 3 7 CC 1 14 34 3 7 C 2 7 CO 5 S 10 0A8 A 9 khe
10. 0071 S 10 0 A 9 411 412 2012 017700 25 PCT JP2011 051807 1 2 3 4 5 6 7 8 9 S 10 0A9 S 100A8 A 9
11. 2 Roth J et al Trends Im un ol 2003 24 155 1 58 S 100A8 S 100A 9 3 Odink K et al Nature 1987 330 80 82 4 Liao al Arthr itis Rheum 2004 50 3792 3803 GRX 5 Bogumi T et al Neurosc i Lett 1998 247 195 1 97 6 Luger ing et al Digest ion 1995 56 406 41 4 7 Kuruto et al J Biochem Tokyo 1990 108 650 653 S 10 0A8 S 100A9 S 100A8 S 10 0A9 2012 017700 2 PCT JP2011 051807 0003 0004 0005 S 10 0 8 100A9 S 100A8 S100A9 S 100A 8 9 585 NHEK
12. S 100A8 A9 NH EK S 100 8 3 100A9 8 J Cell Biochem 2007 Nov 28 Epub ahe ad of print S 10 0 8 9 NHEK S 10 8 A9 NHEK S 10 0A8 A9 S100A8 A9 S 10 0A8 A9
13. 2012 017700 4 PCT JP2011 051807 001 0 001 1 1 S 100 A 9 S 10 0A8 A 92 2 S 100A9 S100A8 A9 S 100A9 S 100A8 A 9 1 1 2 4 EL ISA 1 3 5 S 10 0 A 9
14. 2 17 4 HA sigma tb 6 S 10 0 G mycHAF lag 6 is S 10 0 Ss 100 8 3 10 0 A 9 s HA HEK293 2012 017700 19 PCT JP2011 051807 0057 S 10 0A 8 S 10 0 A 9 HA Myc
15. 5 1 0 S 10 0 9
16. MMP S 10 0A 9 S 1 0 9 B5 4 S 1 0 0 1 HEK293 ATGG HEK293 0UMS 24 8 Gibco DMEMF1 2 HRB 10 2 ewi PDNR IF FAQ GMvi es mycHAF IageH is cDNA pGMVi_exE g p
17. 6 S 10 0 A 8 3 2 k Da Emprin 10048 S 1 0 0 A 9 Empri 10049 47 5 k Da S 100A9 0058 5 MMP MMP MMP MMP MMP lt 0059
18. 1 3 MMP IL 8 CXCL 8 FPNE 11 1_ F9 7001 S100A8 A9 Cell Biochem 2008 104 453 464 8 5 10OA9 IL_ 8 CXCL 8 T NF 1L 1 F9 CXCL 1 PCR S 100A9 MMPpP 1 MMP 10 PCR KG2 Cascade Biologies NH EK 2 mM s 10 0 A 8 s 10 0 9 1 Ou g m 3 KACO RRE MagNA Pure mRNA MagNA Pure Ro che Diagnost ics m RNA
19. S 1 0 0A8 A9 MM P MMP MMP S 10 0A9 S 10 0A9 S 10 OA 9 MMP S 100A9 S 100A9
20. 6 6 7 S 10 0 A 9 8 9 MMP S 100A8 A9 V EGF TNF S 100A8 A9 2012 017700 5 PCT JP2011 051807 001 2 001 3 GER MRO Nature Cell Biol 2006 8 12 1369 1 375
21. 4 S 100AB8 A 9 LC MS MS S10 0A8 A9 S 100A9 ce prin The extrace Ilular matr ix meta lloprote inase inducer lt CD 147 S 10 OA 9 S 100A9 S 100A9 n
22. HLTQ Deca Thermo Fisher amp cientific 0042 m z 400 1400 MS 1 MS MS 3 3 59 MS MSMS 3 1 0 5 0 25 10 OOP ELE 0043 n tMS MSA NZ 7 Th ermo Fisher Scientifict ECH lt SEQUE ST ftp 7 ft p ncb nih gov b Ia st db FASTA nr gz 2007 2 8 0044 2 CNS 7
23. 1 3 1 3 1 3
24. 1 Biochem Biophys Res 2004 322 1111 1122 2 Trends Im 2003 24 155 1 58 3 Nature 1987 330 80 82 4 Arthr it is Rheum 2004 50 3792 3803 5 Neurosc i Lett 1998 247 195 1 97 6 Digest ion 1995 56 406 41 4 7 Biochem Tokyo 1990 108 650 653 8 J Gell Biochem 2008 104 453 464 2012 017700 3 PCT JP2011 051807 0006 0007 0008 0009 9 Nature Gell Biol 2006 8 12 1369 1 375 10 Hum 2002 111 310 31 3 11 Morr ison TB et alc Biotechn iques 1998 24 954 958 96 0 962 S 100A9 100 RAGE Rec eptor for advanced ion endoproducts S 100A9 s iRNA
25. 6 1 5 A 5 B 0 15 60 B 4 5 10 B 7 5 5 2 6 1 A 4 C X 5 C 0 15 60 C 4 5 10 C 75 2012 017700 13 PCT JP2011 051807 5 2 5 0 L 3 00 4 0 0nL 10041 ES MS MS
26. S 100A9 S100A8 A9 S 10 0A9 S100A8 A 9 1 1 2 EL 1SA 1 3 1 S 100A9 S100A8A 9 SBR 5 S 10 0 A 9 S 10 0A8 A 9
27. Ad_exE p 20 1 OUMS 24 10 cm dish x 20 0UMS 24 2 3 OUMS 24 2 4 DMEM F12 3 4 C 3 0 2L 80 5Om
28. S 10 0A 9 PR 4805 S 10 0A9 s level 111 S 10 0A9 S 100 A9 S100A9 CD147 HMB4 5 8 2012 017700 21 PCT JP2011 051807 0064 0065 0066 2 Y 10765 10 0 9 S 10 0A 9 PLA Prox
29. S 1 0 0 A 9 10 20 30 WE 50 70 100 S 10 0A 9 S 100A 8 S 10 0 S 10 0 A 9 EL ISA S 100A9 S 10 0A8 A9 5
30. Superscr PAM 11 InVitrogen Corporat ion PCR LightGyc ler FastStart DNA master SYBR green 1 Roche Diagnost ics LightGyc ler 1 2012 017700 15 PCT JP2011 051807 0 9 5 C 15 6 0 O 10 7 2C 10 4 0 1 2 0 1 0 2 0 25 gt M _ 3 GA PDH LightGyc Iler 1 1 Morr ison TB et alc Biotechn iques 1998 24 954 958
31. jeuuepide ejsjexsoyo unes NVMTH 3zzy 82 VOO IAOV 2 suaides uu0jos 2 pue OISBGID Jo JeuJeo ANOS 92 suaides elaq uod ECHO6 x2ous Eeay sz snyey jequieu pig wy PZ alnlos sueides ZY zz suaides 9696 Jon susldes uleloud oz ulos NI H09E ZEZS LEZVA0CZVV6ZZ1Y9ZZO 99 VN3INAHYH LE LuniejsoApig v JO enonas v 61 SugideS B19d gr sueides 20782 uiad g e 04 OOUS 1 suaides JosJnoaJd eydje 4 H dLY 94 suetdes 1050994 86 ulaloud 12098 SL sueides suaides jonpoud sueides ouuoH auoe 2 02 0 01 30 0 L uneioxoi amp 2 OF Balsaysol SA OLOVA LE suaides 01 Sualdes
32. t0 IE K L IY 1 EHET IO IP I amp 112 ROS ORB 1 SA JP 100 8915 4 3 03 3581 1101 3252
33. ISA 210 2 20099 7 PCT JP2011 051807 1 2 8 3 17 0 1 7 10 DEW 7 10 PCT 6 4 a 2 3 1 3 1 4 S 100A9 S100A8 9
34. 9 1 0 S 10 0A9 PLA 49 Ss 1 0 0 A 9 S 10 0 A 8 SS 10 0 A 9 7 S 10 0A8 S100A92 1 S 100A8 S100A9 S 10 0A8 S100A92 GST GST S 100 8 S 10 0A9 3 Biot in AC5 2Su Ifo 0Su indo 2 Nap 5 G
35. SBR 7 S 100A9 2012 017700 26 PCT JP2011 051807 S 10 0A8A 9 10 SER 9 1 19 PCT JP2011 051807 WO 2012 017700 81 5 sUBIQUISUISUBL J su OUAOVd GVAAIN INAH TASUDOSSSAAAAMSASONWI 3p pug 501 dd9H IOINVIONWdHJ Id JSADTOMOCASGAMAAIN 81 381 sc SO IGMA LLAA LO SVOHLIOTIVAIOTIAATVVVIN 9 eusig bs 219 PCT JP2011 051807 WO 2012 017700 842 v 5 1v 1 M ennags IB1SAO v ze slosnu ugoe LE suaides uuojosl og 105119844 uipuodsoquioJ4 NYWmH 1484 82 ez 8
36. cDNA DNA 3 pGMV i_exE g p FuGENE_HD Rohe 293 4 Sigma HA tag 4 c 3 LE 5000 1 12 SDS PAGE pvpF esT HA ta g 2012 017700 18 PCT JP2011 051807 0054 0055 0056 4 p pGMVi_exE V Adeno_X express ion system Clontech 5
37. PC Int Cl GO1N33 50 A61K36 23 61 36 28 A61K36 53 61 45 00 A61P29 00 A61P35 00 GO1N33 15 GO1N33 53 BA 2 CA MEDL INE EMBASEPB 051 STN C SMR X Hibino T et 1dentincation of a Novel Receptor For 1 4 5100 8 9 of Inflammation human Skin J Invest A Dermatol 2009 09 Volume 129 Issue S2 S88 5 6 et 5100 8 9 key mediator for positive feedback 1 6 growth stimulation of normal human keratinocytes J Ceil Biochera 2008 05 15 104 2 453 464 D C 5 IA
38. 12 S 100A9 2 1 9 1 MMP 1 2012 017700 7 PCT JP2011 051807 001 5 001 6 001 7 001 8 001 9 1 1 MMP 1 Ig 1 S 10 0 A 9 S 1 0 0 A 9 S 10 0A9
39. V 0 025 0 25 2 5 UM MMP_ 1 S 10 0A 9 MMP 1 S 10 0A9 S 1 0 0 A 9 MMP 1 7 S 10 0 A 9 M M P MMP S 100A9 AB S 10 0A 9 MMP H V 2012 017700 20 PCT JP2011 051807 0060 0061 0062 0063 MMP_ 10 TNF IL 8 6
40. 2 5 0 m 15Omm gi lent 5 gm Pa rt isphere SCX res ins Whatman 5 x xm Po IyWAX LP PolyLC 2 1 5 m A q ua C18 Phenomenex 5mm S X 2012 017700 12 PCT JP2011 051807 0035 0036 0037 0038 0039 0040 6 MudPIlT
41. 1051152 6 sueides g suaides Jonpold eue JuueueudoupAulQ 01 6 0 6 101 16 WIAA pO L L Ld aselajsueJ1 S JO jeSAID v 9 IB19I9YSOIAS edA zn Hep S 6 6 642 6 uneJexo1A 6 AASA NvWnH 8013 euoldlelnIS 4 snJIA JO 1749 edoyd3 pgAl9Suo v 8 6203 8 9 646 1 6 sustdes 2 suaides 0015 5 3 19 2012 017700 PCT JP2011 051807 243 5 x M S e 5 22 o TIT X x x e x V 90 x X ON M N aro oO DE dv9 9 g Oey t 00 419 2012 017700 PCT JP2011 051807 4 Ratio to A8 control 0001 DO 3 5 NE lt 0 05 lt 0 1 lt 2 25 8 5 2 215 1 0 5 0 eo
42. S 100 8G S 1 0 0 8O S100A8 27E10 Dapi 8E S 10 0A 9 27E10 Dap i 8F S 100A 9 0 RE 9 HE S 100A9 DAPI 8G S 10 0A9 8 49 P L A Prox imity Ligat ion Assay S 100A9 200 101 1PLA S 100A9 4008 111S 10 0A9
43. 5 S 100A 9 S100A8 A 9 5 PCT 1SA 210 2009 7
44. 55 5186 15 19 2012 017700 PCT JP2011 051807 8H S100A9 amp 45 lt Swe T eo kl 16 19 2012 017700 PCT JP2011 051807 249 Emmprin amp 10049 x 200 SEE SS SNE SS WES S PLA 18 19 2012 017700 PCT JP2011 051807 411 19 19 2012 017700 PCT JP2011 051807 8412 312 Absorbance at 405 nm INTERNATIONAL SEARCH REPORT A CLASSIFICATION OF SUBJECT MATTER G01N33 50 2006 01 1 A61K3 6 23 2006 01 i 61 450 012006 01 G01N33 1 5 2006 01 3 G01N33 53 According to International Patent Classification FIELDS SEARCHED 2006 01 61 29 0 2006 01 1 IPC or to both national classification and IPC International application No PCT JP2 011 051807 A61K362 8 2006 01 i 0 2006 01 1 A61P35 0 61 6 53 0 2006 01 Minimum documentation searched classification system followed classification symbols GO1N3 3 50 A61P35 00 A61K3 6 23 GO1N3 3 15 A61K36 28 GO1N3 3 53 A61K3 6 53 61 4 5 00 A61P29 00 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Koho Shinan Jitsuyo Shinan Kokai 1922 1 996 Jitsuyo Koho 1971 2011 Electronic data consulted during international EMBASE 1 OSI S STN
45. DOCUMENTS CONSIDERED TOBERELEVANT CONSIDERED RELEVANT Category Hibino al denti Recepto S100a8 A9 Skin 1 sue f i For human 129 nflammat ion 2009 09 in lume Nukui posit ive et al S100A8 9 feedback growth inocyte Ss ad 453 464 human kerat 104 2 L Further documents are listed in the continuation of Box C Special categories of cited documents document defining the general state of the art which is not considered to be of particular relevance earlier application patent but published on or after the international filing date or which is date of another citation or other document which may throw doubts on priority claim s cited to establish the publication special reason as specified document referring to an oral disclosure use exhibition other means document published prior to the international filing date but later than the priority date claimed Date of the actual completion of the international 11 March 2011 11 03 11 search Name and mailing address of the ISA Japane Patent Office Facsimile Form PCT ISA 210 second sheet July 2009 Jitsuyo Toroku Citation of document with indication where appropriate of the relevant passages Key 2 s timulati Koho Koho 1996 2011 1994 2011 Shinan Toroku Jitsuyo Shinan search name of data base and where practicable search term
46. Ratio to A8 LF control 5 0 001 p 0 01 5 0 05 lt 0 1 Ratio to control control neg RNA siRNA A9 LF A9 negRNA 9 5 19 PCT JP2011 051807 WO 2012 017700 845 545 KA BER 9 71 Mb e e gt aseeioul 5 04 6 19 2012 017700 PCT JP2011 051807 206 246 Myc lt lt antibody amp WB anti HA agarose 325228 ul o 17572 83 62 47 5 32 25 16 5 7 19 WO 2012 017700 PCT JP2011 051807 847 7 5 4 D 5 3 2 ie 1 0 9 D j 2 Ss S lt aS lt lt lt 5 D 8 19 2012 017700 PCT JP2011 051807 8 8 9 19 2012 017700 PCT JP2011 051807 2488 5198 _S100A8 10 19 2012 017700 PCT JP2011 051807 2480 3150 11 19 PCT JP2011 051807 WO 2012 017700 2480 10 013 2 87 1805 12 19 PCT JP2011 051807 WO 2012 017700 8E idgD 013 Z 6V 08q dep 0 LJAZ46V av 0V 4 8 5 2012 017700 SEE SS N N SS 13 19 PCT JP2011 051807 14 19 2012 017700 PCT JP2011 051807 NY SS SN X SR
47. YAMADA Shoko JPJP 2368643 2 12 1 _ ems JP 55 2 JP JP T2368643 2 5 2 a 12 1 Kanagawa 54 Title METHOD FOR SCREENING CHRONIC INFLAMMATION SUPPRESSION AGENT OR CANCER METASTASIS SUPPRESisioN AGENT HAVING INHIBITION OF BONDING OF EMMPRIN AND S100A9 AS INDICATOR 54 12 7UZ2 8100A 9 0f amp amp 0I E CT el tt 2 E D ml AJ X 3 3m Sz 35 0 del A 57 Abstract The present invention provides a method for screening chronic intlammaiion suOpression agents cancer metasta sis suppression agents that when a candidate substance for being a chronic inflammation suppression agent or a cancer metastasis suppression agent significantly inhibits the bonding of EMMPRIN and S100A9 5100 8 9 evaluates the candidate substance as significantly suppressing chronic inflammation or cancer metastasis 57 S 100A9 S 10 0
48. 960 962 mRNA A 8 contro siRNA A santa Cruz 8 37007 8 1 mRNA LE 0048 PCT JP2011 051807 16 WO 2012 017700 81 dq 002 81 1408 2 91 911 22111 9991 514 9 11 999 80499 dq 070 61581604 19191Y91V99199199V991919IIIV09 21858 4680 OVVIOLOVOVIVIS3LI19999199199 640015 dq 616 11884 81509 191119999111010419 912 19 00 0188 1608 9 191V91V9999199919WV9999 810015 688545 4 29 211912 219111 99119 84581409 0V9V299V1VOIOVVOOQVV L IOXO 09 842 181588 9VV9919 191999919 VY 938 809 1VV21V191922999VY99V 6411 4 548 1808 1199 99 9 9 2991 911 v edd 19199999V191999VV9V9 91481 aq g VVJ991999VY99VOLVV 10 VOV9V99 9 V9 8 11 zg beL uUa ug h ELANET 9 1 S 100A9 4 0049 SiRNA 8 21094 i RNA 95 2012 017700 17 PCT JP2011 051807 0050 0051 1 0052 0053 siRNA S 10 0o 9
49. CRAEHPLCYESI M SYMS LE 4 g 10 A 7 9 5 5 0 1 pH 2 6 1 0 BBA Upchurch Scientific 2 0 10 0 m Nanospace 51 28 HPLC 248 1 1 S CX WA X 1 2 2 0 A B 20 80 0 1 C 50OmM A pH 6 8 C
50. 5 5 10 0 FF 0045 2 s 1 RNA RNA Max s Santa Cruz sc 35298 40 nM 80 nM 3 M3 non treated con 1 contro siRNA A Santa Cruz Biotechno logy Inc sc 3707 3 LF 2012 017700 14 PCT JP2011 051807 0046 0047 2 4 S 1 0 0A9 2 4 RNA 3 s iRNA 2 4 4 8 7 2
51. t o methods for treatment by therapy 2 Claims because they relate to parts of the international application that not comply with the prescribed requirements to such extent that no meaningful international search can be carried out specifically Claims because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6 4 a Observations where unity of invention islacking Continuation of item 3 of first sheet This International Searching Authority found multiple inventions in this international application as follows invent ions claims 1 4 relate a method for screening a subs tance whi ch signifi cant inhibi ts the bindi ng of n to 5100 9 S100A8 A9 The i nventi ons in claims 5 10 10 relate to chroni i nflammat ion inhibi tor meta stas s i nhibitor each compri sing a drug inhibi ti ng the binding of Emmprin to S100A9 and method for inhibi ting chroni c i nflammat ion cancer metas tasis using said drug required additional search fees were timely paid by the applicant this international search report covers all searchable claims searchable claims could be searched without effort justifying additional fees this Authority did not invite payment of additional fees Asonly some of the required additional search fees were timely paid by the applicant t
52. 1 S 10 0 8A C AD S 10 0 S 1 0 0A8 S 100A9 S 100A8 A9 27E10 P so S 10 0A8 A9 8 D 8E S 100A8 A9 S 10 0 A 9
53. 2012 01 00 1 UN N UDUT 43 10 2012 2 9 09 02 2012 WO 2012 017700 Al 61 SAKAGUCHI Masakyo JP JP 7008558 GO1N 33 50 2006 01 A61P 29 00 2006 01 5 1 A61K 36 23 2006 01 6 35 00 2006 01 A61K 36 28 2006 01 GOIN 33 15 2006 01 Okayama ho A61K 36 53 2006 01 GO1N 33 53 2006 01 70088 MURMUR eM HT 5 15 461 45 00 2006 01 E o 21 20 11 05 1807 kaama agp 74 Atsushi 22 201 14 1 A 28 H 2801 201 1 1058423 5 1 37 Tokyo 26 GR OUR U ETORO BW AG AM AO AT AU AZ BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI 3558 2010 174038 2010 2 02 0
54. 8 2010 jp HRA lt GB GD GE GH GM GT HN HR HU ID IL IN IS slsEfo COMPANY KE KG KM KN KP KR KZ LA LC LK LR LS T 1048010 7 5 Ets CEU MD MW a eum MY MZ NA NO PE PG PH PL 5 RO RS RU SC SD SE SG SK SL SM ST SV 72 SY TJ TM TN TR TT TZ UA UG US 02 VC 75 lt ALR VN ZA ZM ZW lt Fe IRAB kana ARIPO BW GH GM KE LR LS MW 2 3 3y 7 JP EHAMA Ritsuko JP JP NDE SI SE ME 2248558 2 2 1 2 KG KZ TMD TM Gi AL AT BE BG CY CZ DE DK EE ES Fl FR d GB GR HR HU IE IS IT LT LU LV MC MK MT Kanagawa 5 4OTOYAMA Akira PUP s NL NO PL PT RO RS SE SI SK SM TR OAPI BF BJ CF CG GA GN GQ GW ML MR NE SN TD TG 2 2 1 Kanapwa JP
55. A8 A9 2012 017700 1 PCT JP2011 051807 H SS 10 0A9 0001 1 00021 S 10 0A9 S 10 0A 8 S 100A9 S100A8 S100 A 9 20 EF S 1 0 0 1 Marenho 12 et Biochem Biophys Res Commun 2004 322 1111 1122
56. E Hea hcare ft 2 S 10 0A8 S100A9 1 signal pept ide h D transmembrane 0 5 12283 24 96 well Pierce 5 BSA ORK LTE BROA 1 gt s100A9W ti 1 HRP s100A9 ELISA o D 492 nm 2012 017700 24 PCT JP2011 051807 S 100 9 Xl S100A8 A9
57. imity Ligat ion Assay PLA DNA 2 DuA PLA 0 1ink Duolink in situ PLA 4 4 m pgs ATOR 1 4 lt C PBs PLA 1 3 7 lt C 2 2012 017700 22 PCT JP2011 051807 3521 0067 a ane a xe 2012 017700 23 PCT JP2011 051807 0068 0069 0070 NA Detect ion 613 Olinktt
58. ms 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 Remark on Protest The additional search fees were accompanied by applicant s protest and where applicable the payment of aprotest fee The additional search fees were accompanied by applicant s protest but the applicable protest fee was not paid within the time limit specified in the invitation No protest accompanied payment of additional search fees Form PCT ISA 210 continuation of first sheet 2 July 2009 th var pport db pt 5100 9 h th hbt arbat th invention Form PCT ISA 210 sheet July 2009 descript pt Eh 3 t Hh bit th t h h b t h b tingth pt p f h th PCT 2011 051807 PC Int Cl GO1N33 50 2006 01 A61K36 23 2006 01 i A61K36 28 2006 01 i A61K36 53 2006 01 i 61 45 00 2006 01 A61P29 00 2006 01 i A61P35 00 2006 01 i 601 33 15 2006 01 i G01N33 53 2006 01 i B
59. s used Relevant to claim No ion a Novel Medi J Inve st 88 ator of Dermato mediato r for on key of normal Bi ochem 2008 05 15 patent family I ater 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 tiie invention document of particular relevance the claimed considered novel or cannot be considered step when the document istaken alone invention cannot be to involve an inventive 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 person skilled in the art document member of the same patent family Date of mailing of the international 29 Mach 2011 search report 29 03 11 Authorized officer Telephone No INTERNATIONAL SEARCH REPORT International application No PCT JP2 011 051807 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 1 claims Nos 7 10 because they relate to subject matter not required to be searched by this Authority namely The invent ions set forth claims 7 to 10 pertain
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