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JP 2008-527009 A 2008.7.24 10 (57)【要約】 組成

Contents

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5. Beckmn Optima LO 0
6. 13 STF2 4100 0000 000 000 00000 3500 0 STF2 1000000
7. 700 710 1000000000 0 0
8. 5 5 2 3 LTSGHLKCRVKMEKLQLKGTIT O0 1000 F Bachem PamBCys WAVO
9. nnmg 10001000 1000000600 TLR9 TLR7O 0 D 0 000 0 TERA TLR8 0 10001000 0000000 001 00 1000 10001000 10 000000000060 n2 100000000000 Den2 100000000000 0 0000 2 0 000000000 4
10. pET24AR 5 TCCGGCGTAGAGGATCGAGA 0 0 0 450 STF2 E3R3 CAATTGACCTT CAAGCTT CGAAT TGCCCT TACGTAACAGAGACAGCACGTTCTG 0 H 460 AX E3F3 AAGCTTGAAGGTCAATTGGAATTCCCTAGGACTAGTATGGAAAAATTGCAGTTGAAG 470 pET24AF GCTTAATGCGCCGCTACAGG 0000 480 5 WE28 GCGGCCGCTCATGGAAAAATT GCAGT T GAAGGGAACAAC 490 3 28 CCGCGGTTTGCCAATGCTGCTTCCAGACTTGTIT 0 0 50 Ndel STF2 CCGGCAT GCCATAT GGCACAAGT AAT CAACACT AACAGT
11. Om 2x Life 0000 0 0000000000 1000 0000 1000 STF2A 5 STFA 0 0 0 0 0 0 0 0 0 0 0
12. 000000 000 000000 0000 PRRO Toll I H HH E TER Tol Drosophila mel angogaster Tol I 0 00 0000 TLR 21 TLR3Q TLRA TLR5 TLRe TLR7 TLR80 TLR9 TLR10Q TLR110 O0 O TLR120
13. N m st L Oo L3 L3 C x L C Oo EE Eo ug ues xs SE NT lt E gt rj L O C Top E N L3 moo _ O C Oo 2 EE T I y use N ca Ole E COO
14. 0000000 000000 0000000 Ul Den2 Den2 100000000 22 40 97 um 000 000000600 1 2 PHUUUUGUUO Den3
15. i 10 1 Den2j Den3 0 Den4dg 00 0 0 0 JE Weaver S C et al Nat Mcrobiol 10 7890 8010 2 00 DEN 1 j DEN 27 DEN DEN 20 SOLUM ER a nnm a 11
16. o o in 5 ass es __ __ __ 5 E E E E 3 2 L3 E3 E3 L3 E3 25 E3 L3 E3 E3 oO C C C d E3 a L3 E3 E3 2 E3 E3 E3 gt E
17. Bg 0000 PAMP Pan Cys PargCys PAM Ip 110 HII 000000 20 0 0 5280 12451 1760 41 O O O O 690 5220 1266 68 1740 422 59 5190 13920 000000000005890 000 1730 4640 0 0 176 415 1000000 0000000000000 0000 truncated versi 0 0 I ID mH 0 ID 0 000 00000 ID fljBO 00000 011 B STF2 STF2 20 0 0 5280 1245 1760 41610 0 flj B STF2 10000 2009 2009 3007000001
18. 3 32 STF2A 760 10000000000 0 STFA QGIJEII OUD MKLALD 0 0 0 1738 00 000000000000 1110000 KGTTYGMCTEKF SF AKNPVDTGHGTVVI ELSYSGSDGPCKI VSVASLNDMTPVGRLVT PFVATSSANSKVL VEMEPPF GDSYI VVGRGDKQI NHHWHKAGSTLGKA 1720 D ID IiInnuduguudjE eama 0 00 0 33 76 770 ugue STF2A I 1 FEE T ERO EE E JE 0 00 0 34 7
19. d Springs Harb Symp Quant Biol 64 429 1999 Pasare Senin Immunol 1 6 23 2004 Medzhitov Nature 388 394 1997 Barton Curr Opin I munol 14 380 2002 Bendelac J Exp Med 195 F19 2002 00000 Pan Cys 000 000 TLR50 0 D FIJB STF2H l D n t muenchen fli 0 0 0000000 00000 O fljB JST2 00000
20. 460 pET24Q0 ODO U 0 00 0 U O0 contructh O0 0 O0 O T70 T7U D 00 0000 57220 0 00000000000 0 0 stF2A 400000 STF20 BUI n nun ni Cee 60 00 08 00 01070 00 00700 101110000 47A STF2A 700 7170 0000000 5 10 000000000000 0 0 HEK2939 TLRS 00000 OO IL 8 ELI SAJ H UU U STF2 800 0 0 0 4740 4780 STF2 El ILI 540 55700000000 ER 5t UU 2 93 TLR5 4 7 0000 00 t IL 8 ELI 5 100600 O00 TLR 20 O0 O Panmscskan n 00000 47B 480 ELI SA 5 2 1 4 0 000 00000 390 0 0 O sTF2A
21. uu Den1 Den2 Den3 Den4 0 66 67 64 650 E CR n Den2 Den3 4 AAGGGCAAT TCGAAGCT TGAAGGT CAAT T GGAAT TCCCTAGGACT AGT 25 GAATTC TGCAGATATCCAGCACAGTGGCGGCCGCT 27 GAATTCTCTAGATATCCAGCACAGT GGCGGCCGC T 611 AAGGGCAATTCGAAGCTT GAAGGT CAATTGGAATT CCCT AGGACTAGT CCAGT GT GGT GGAA TT CT GCAGATATCCAGCACAGT GGCGGCCGCCAGT GT GAT GGATAT CT GCAGAATT CGCCCTTGCGGCCGCTC J 63 GAATTCTCTAGATATCCAGCACAGTGGCGGCCGCT Hi H O 740 000000 0 O KGNSKLEGQ LEFPRTS O 260 O 280 EFSRYPAQWPRPLE O O H O 600 GNSKLEGQLEF PRTSPVMWANSAD
22. 1710 0000 O 0 0 00000000000000 00000010 utt INS3SOO000 00 000000 NTPase N5J 000000 RNAI 0 Bg NS2A NS2B Ns4B0o 0000000000000000 0 0 NS2BI NS3J D H B BH Hl D D NS2A NS4A NS1 10000 0 NS1 0 1000000 Brinton MA Annu Rev Mcrobio 56 371 2002 l Smthburn et al Trop Med
23. 111000000000 00 0 Lescar et al Cell 105 1379 148 2001 0 Rey et al Nature 375 291 298 Kuhn et al Cell 108 717 725 2002 Mukhopadhyay et al Sci ence 302 248 2003 100000000060 Ib OO tt In dg 000000000000 Modis et al Nature 427 3130 319 2004 Bressanelli et al EMBOJ 23 7280 738 2004 08 D 000 D 111 100060
24. STF2A Ell 100000000000 0 0 0 STF2A Eliis4 0000 0000 STF2A 11 41 5 gt 2 C3H HeN o B p a Eb DEI Dn n uD n n D s c 0000000 WNV E 199 D D 0 54 ELI SA D 0 0 199 D STFA 11 5 2 5 STF2 11 5 2
25. lOO 0 0 5 Prot ein Assay Reagent Kit 0 0 0 D Pierce Biotechnology Rockford IL I SE TLR5 HEK293 ATCC Catalog No CRL 1573 Manassas Virginia 0 0 0 TLR5 0 0 0 TLR5 8 IL 89 0 0 0 Pierce AZWBOIE O B02B Rockford L 8 FARCyte Amersham Biosciences Piscataway
26. PBSO 5 0 0 0 0 0 0 0 0 0 T STF2A uD 0 STF2A Elll s c H 00 STF2 E 1 1 STF2 Elll s c 0000 000 00000000 STF2A El Il log 0 000 STF2 STF2A ElllI i p D D 0 STF2A s c 0 D STF2 El PSODODOOODO0O00000000000000000000000000000 STF2 El TLR5 UE STF2A Ell l D0O0000C00C00C0000000 000000000000000 JP 2008 527009 2008 7 24 41
27. 300 850 000000 1000 31 320 0 0 0 320 1000700 000000 1000 33 UU 340 00 000 34 100 0 700000000 350 00000000000 360 00000 1000 36 000080000000 3700 38 HOOO0ddag 380 0 0 700 000000000 540 IOUUUUUUUUU 550 0 H 700 0000000 0000 71 10 00 720 00000600 70 7200000000000 71 10 0 700000000 700 76 1006000 10 20 30 40 50 JP 2008 527009 2008 7 24 10 50 6000 840 10 850
28. Pfu Ultra Hotstart PCR Maste Si Genos Stratagene 20 30 40 30 JP 2008 527009 2008 7 24 5 STF28BGF 1 CTCGGGAGATCTGCACAAGTAATCAACACTAACAGTCT 0 O 410 STF28MCR 1 CCATGGGCTAGCAGGATCCACCGGCGCTCCCTGCACGTTCA O 420 STF28MCF 2 GGAGCGCCGGT GGATCCT GCTAGCCCATGGACCGAAAACCCG 0 430 STF28ECR 2 TCT GCAGAATT CACGT AACAGAGACAGCACGT T CT GCGGGACGT CCCGCAGAACGT GCT GT CT CT GTTACGT GAATT CTG CAG 440
29. 27411 00000 2100000000000 10 0 520 0 00000 000 000 000 000 0 194 00000 0 O 5 2 10 019590000000 00 14000 220000000 PE 00000 25 STF2A El I1 0060 700 710 0 045 000 0 10 O STF2A 0670 STF2A 11 0700 STF2A 1154 H H O00 0 720 730 0690 330 0 000000000000000 ELISA gG VWV E 000 0601 his 000000 53 WAV STF2A Elll 4 70 71 STF2A 5 D 720 700000000000 38 274147 0000000 210 10 54 10 2 5 30 00000000 7H20 0 OOOO ELISA 0800 0 00 0 0 000 0 0000 mAb 7920 00 0 0 0 0 0 0 0 00 0000 00 00 55 STF2A Ell I 720 738 0 0 0 HN 00 00 0 0 0 0 0 C 00000 000600 SIF2A D H OO U 0 E2 219 E27 E52 60 1000100 0000000000000 00 0 0 0000000000 000000000 0 00000 56 STFA El
30. 5 10 20 30 40 50 JP 2008 527009 2008 7 24 6 DU l Pan Cys 10 20
31. 00000000000 1000000 0 0 0 Ausubel 1997 Short Protocols in Molecular ol John Wiley Sons New York N Y Units 2 8 2 11 3 18 3 19 4 64 9 H OO 5 Den1 Den2 Den3 n4 PanBCys PARE aa Herc P nn 5 0 O 000 Deni 00000 0 Den2 Den3 000 4 5 0000000000000 0000000000000 000000010000 000000000000 000000000000 0000000001060 0 0 0 00000 0 ELI SA D Pl aque Reduction Neutralization Test 0 0 0 0000000000 0000000000000 00000 Vaccine 23 44420 4452 2005 000000 00000 27 JP 2008 527009 2008 7 24
32. 2 89 2 8121355 55 2 BASS BLU STF2 E 159 CM a KOI 86 2 7742 WI SLAE KU PRNT oti E Cv oo oO Oe ooo oo cg ooo Li oo Oo oo x O oo ooo oo oo DOF Fe See oo ESI ES oo oo E oo r3 m EX EE Ez E EE E m o lt 5 o E EL E EI a a E ES oo E3 F3 O x ES EXE FEE E313 ET Li OO E 5 mal 5 o ooo _ ooo
33. 730000000000000000000000 LB B 00 5 50 100 NaCl pH 8 00 000 0000000000 0 0 50nM Tri s 100nM AM 0 0 pH 80 5 2 5 2 1151 00000 000 0 Streamine CSTO GE Healthcare 0 0 D 0 STF2A Ellls 0 Trit 1 80 1 505 505 0 D Dn g 000000000000 00 0 5 6 000 5 5 1000 Quanti tati ve Chromogeni LAL 0 O oWhittaker 50 6480 kersv 0
34. o o A oe n Ed eo noo So SSS ea Soo Seo oo E E E ETE E noo E noo noo Soo E34 eee ES EJ E3 DI E EE EE noo maaa aaa m El zd El Es See eS EST EE E EE a ooo lt noo gt 0 C2 C2 C3 C2 C2 tg C3 ET noo Ei pisi ss ese eo noo ooo r3 4 F rr LE ooo EP EL CETELELETE C1 E 3 rd odo Cv Z noo nooo o o E EE EE ee SSS 02 02 05 5202 F E3 F3 F3 pop es EFEPELE PUN
35. HWHKG 0000 190 0 O GVSYSMCTGKFKVVKEI AETQHGTI VI RVQYEGDGSPCKI PFEI MOLEKRHVLGR LI TVNPI VTEKDSPVNI EAEPPF GDSYI GVEPGQLKLNVF K 1400 000000000600 120 130 140 150 160 170 180 19 40 110000000 Den2 000 Den2 00 0 EAEPPFGDSYI GVEPQQLKL O0 0 00 220 0000 0 400000000 970 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1000000000000 0 0 Den EAEPPFGESYI VVGAGEKA LKLSWFKK 200 Den 1 PR 940 1 0000 0 0 1994 ETEPPFGESYI VVGAGEKALK LSVF KK 210 l Den EAEPPFGESNI VI GDKALKI NWKK O 0 0 0 2300000 Den 40 ELEPPFGESYI V GVGNSALTLHVWFRK O0 OO O 24000 0 00 0 0 0 0 0 0 200 210 22 23 240 Den2 Den3j 0 0 00 00000000 01110000 IU U ivnetion jiunuuuiluludausuludgsuulililiiluilllililil 160071 Den2 5168030 Den3 534891 0 Den4 j 7030 enapgugagagaagagaggaggauaguugugagagagaauaguuguu 10 20 30 40 50 22 JP 2008 527009 2008 7 24
36. 85 9509 000000000000 99 jiumnuuiululdagasuuiiili ltll 000 GLTYTVCDKTKFTVKRAPTDSGHDTVVVEVGF SGTRPCRI PVRAVAHGVPEVNVAMLI TP NPTMENNGGGF EMQLPPGDNI YVGDLNHQVF CKG 12 GTTYGVCSKAF RFLGTPADTGHGTVVLELQYTGTDGPCKI PI SSVASLNDLTPVGRLVTVNPF VSVSTANAKVLI ELEPPF GDSYI VVGRGEQOI NHHWHKSG 130 0 O FSKNPADTGHGTVVLELQYTGSDGPCKI SSVASLNDMT PVGRM TANPYVASSTANAKVLVEI EPPF GDSYI VVGRGD NHHWHKEG 140000000000000 GTITYGMCTEKF SFAKNPADTGHGTVVI ELSYSGSDGPCKI VSVASLNDMTPVGRLVTVNPF VATSSANSK VLVEMEPPFGSDYI VVGMGDKQI NHHWHKAG H O O 2500 0 EMEPPFGDSYI VV MGDKQ OO 0 0 160 00 0000000060 l uju GLTYTMCDKTKFTWKRAPT DSGHDT VVIMEVTF SGTKPCRI PVRAVA HGSPDVNVAMLI TPNPTI ENNGGGF EMQLPPGDNI YVGELSHQMF 17 100000 iunndgugudguiuliuludusiuiululusluulllul GLTYTMCDKTFTWKRAPTDSGHDT VVME VTFSGTKPCRI PVRAVAHGSPDVNVAMLI ENNGGGF EMQLPPGDNI YVGELSHQVFOK O O 180 jiund
37. SCS 7H10 2 5 2 5 2 EL II 4 STF2A Ell I um Ul STF2A Elll 550 7 2 STF2 El I 00 STF2A EL L1 6H11 STF2 El II 00000 uuu El STF2A Ell I 000000 00 5 2 11 C3H He
38. 44 JP 2008 527009 2008 7 24 STF2A El II D PB Dn tut STF2A srF2A Elll iupndguudguuululululslliuilldiuiliiliiilbiiuWiiuliutliu oa L3 oa L3 L1 pop Bog mum 20 0 fljB STF2 STF2 1 4 a N gt B STF2A STF2A 010000 5 3 0000040000 WOO L3 L3 L3
39. 5841 1 000 O 5 2 0 0 0 4 00000 000000 0 5 2 A Elll HJ STF2A 700 717 OO 00000 Ndel STF2Q Bl p I Edl I I 0 0 u PCR 000 6 2 PCR NelG O O Blpip d 00 0 0 d 0 00 Mch 1 trogen Carlsbad 50 g m0 80 0000000000000 pET 5 2 Ell pET STF2 EI I I 540 pETSTF2 E 158 159 702 000000 0 390 2920 406 0 5 2 11 506 1000 pET STF2 11 11 0 0 0 pET24AR 5 45 STF2 E3R3 46 AX E3F3 47 48 PCR O 5 20 EI II 1000 340bp0p 0 0000000 1 5kb PCRO Uu utl 24 0 45 pET24AF j 0 00 0 480 0 PCR 00000000 000000000 elt 178 2920 4060 000 STF2 10010 1 8 kb PCR BI p
40. De Den2 30 40 Den3 flj STF20 Den3 Den2 Den4 Langat Den2 Den4 50 fli Pan Cys 1 n2 2008 527009 2008 7 24 7
41. 80 820 84 86 159 10000000 700 730 290 310 330 370 540 770 50 819 830 850 870 0 0 15800 0 U 0 0 0 0 0 0 D 00 0 00000 711 720 300 320 340 360 380 550 750 6 80 820 840 86 1910000000000000 0 700 730 290 310 330 350 3 540 770 50 810 830 850 87 1588 1000000000000 7000000 75 80 850 90 00000 95 98 99 00000 ood 10 30 58 68 00000 20 40 59 69 70 75 80 85 90 95 99 p E 710 720 309 320 340 36 38 750 60 80r 820 840 860 0 159 PAMP TR nnm 30 40 60 000 70 75 80 85 90 95 98 99 1000 D0 0 00 0000000000000 0 0000000080 Karling 00 O Proc Natl Acad Sci USA 20 5873 5877 1 3 1000000 Schafferggggaggugg Nucleic Aci ds Res 29 29941 3005 2001 BL BLASTX 2 27 00000000 0 BLASTO 0 Gapped BLAST BLASTN National Center for Biotechnology Information 000000000000000000000000 0000000000000 0 0 0 0 9000000000 00000000100 10 30 0000000 tence 110 0 Extension 1 1000000100 25 JP 2008 527009
42. Beckman Avanti J 20 XP JLA 8 10000 10k x g 50nM Tris 100mM NaCl InM EDTA pH8 0 0000000000000 iU UU HULBHUUEBHBUBBuLbliuuilublui i5usbuiuiluiui i iulkl 5 gt 2 000000000 00000080 0050000000000 0 0 Becknan Avanti J 20 200 000 0 20kx 9 0 50mM tri 50 1m 1 EDTA 196 0 D 0 0 D O 0 5 Triton 1000 pH 8 5 42 T U
43. 51 NS2A NS2B NS3 NSAA O 5 0 Weaver et al Annu Rev Mcrobi ol 1990 441 6490 2004 000 10440 0000000600 9 0 0 Waver S et al Nat Rev Mcrobiol 10 7890 8010 20040 Chambers et al Annu Rev Mcrobiol 44 6490 6889 1990 30 EIS aah ete ae MD E pH D D m m 40 0000000000000 00000 10000000000 0000000000000 00 000 Roehri g Adv Virus Res 59 1410 175 20030 0000100100000 10000000000 0 0 Chu et al J Virol 78 105439 105550 2004 Hei nz et al Adv Virus Res 59 631 970 2003 Chu et al J Gen Viro 86 4050 412 20055 0000 00 0 0 0 0 0 00 0 0 0 0 0 000 0 00000 0 20 Den 20 0 00 000 0 0 00 0 0 00 0 0 0 0 tl 0 0 Rey et al Nature 375 291 298 1995 Modis et al Proc Nat Acad Sci USA 100 6986 6991 50 16 JP 2008 527009 A 2008 7 24
44. J Ann Acad Med Singapore 27 2279 34 19980 0000000000000000 peri domestic OD 100000 100000000000 DF 1 00000060 0000000000000 0000 600 00000060 100000 0000000000000 000 000 000000000 20559 0000000000 DHF 0 0 DENG 10 0000 1000000000 API UU B0 0 Uu 500 0000 DHF O 50000 O 600 000 00000 JOU d 0 H DU 60 000 000 0000 60 00000 00000 00 0 O 0000 DEN 000000 DEN 0000000 O Barrett AD Ann NY Acad Sci 951 262 2001 0 00000000000 17D O SA14 14 2 YF JE n 5414 143 42 JE Bei j i ng 1 P3 0 0 Neud orf K230 0000000000 0 0 0 0 2050000000000 1100020 0000000000 3000 4 1000000000000000
45. TLR50 0 TLR5 1000060 flj B STF2 JUD D 0 1 2 Den3 Deng 00000060 JUD DJ 000 000 000 1 Uu 2 Den3 1000000000100 100000060 1000000 100000000000 000 ELE 000 10 0000000000000 10 00000 10 20 30 40 50 5 JP 2008 527009 2008 7 24
46. STFAAQGOUOO OD fli 2A 30000000 210000000000000 BO Genbank O AF0451510 5 00000000 1 1 amp 9 00000 0 0 Genbank AB028476 5 00 0001 10 00 5 mvenchen 5 menchen 00000 fli 100000000000 0000 0 000000000000 li 1000003 580 0 68 100100 100000000003 580 li 68 200000 400 59 69 0020000004000 59 69 0000 li 1580 50 280 319 330 370 390 41 43 000 60 7
47. 0 0 0 0O O 172 00000 LKGTTYGVCSKAF KF LGTPADTGHGT VVLELQYTGTDGPCKVPI SSVASLNDLTPVGRLVTVNPF VSVATANAKVLI ELEPPFGDSYI VVGRGEQQ NHHWHKSGS SI 17600 00 00 0000 00 0 00 0 000 0 00 0 0 0 00 01110 0 UJ JP 2008 527009 2008 7 24
48. 10 20 30 40 50 31 JP 2008 527009 2008 7 24 10000000000 0000 UU 0000 11 4060 390 000000000 0 0 STF2 10 506 0 0 10 00 0 0 5 2 ED 0 0 u 0 1580 0000 AX 1 DMO 00000000000 5 28 49 3 WNE28 0 O 0 500 O 0000 000 aB D EE CREE EJ s 005000 0 Notl New Eng Biolabls Beverly 3 0 5 Elll DNAD O O 0 0 345bp 3907 00 292 406 1780 pCR Blunt 11 I nVi trogen Carlsbad 00000 O TOPOEIII T4 5 li STF2A 190 0000 700 71700000000 0 00 0 0 0 II HJ 1 10 0000000 00 p
49. 760 800 820 840 860 0 0 159 60 290 300 321 369 380 400 0 0 420 000 10000000 5722 00 000 1 5 20 00000000060 l BB LJ OF P iu o 5 2 0000000000060 15 JP 2008 527009 2008 7 24
50. RACGAAATCGACCOT GGCCAGACTCAGTTCAACGGCCTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTG ARGCAGATCAACTCTCAGACCCTGGGTICTGGACTCACTGAACGTGCAGARAGCGTATGAT GTGARAGATACAGCASTAACAACGAAAGCT TATGCCAATAATGSTACTACACTGGATGTA GGGTCTTGATGATGCAGCTATTAAAGCGGCTACGGCTGGTACGAATGGTACGGCTTCT AACCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGGT GSCTTTACTGGTGCTGATGCCGCCAAAAARTGSCGATTATGAAGTTAACGTTGCTACTGAC GSTACACTARCCCTTGCSGCTGGCGCAACTAARAACCACAATGCCTGCTGGTGCGACAACT AARACAGAAGTACAGGAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAAT GCCTTAATTGCTGGCGGCGTTGACSCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATG TCTTATACCGATAAAAATGCTAAGACAATTGAAGGCGGTTATGCGCTTARAAGCTGGCGAT AAGTATTACGCCGCAGATTACGATGAAGCGACAGGACCAATTAARAGCTAAAACTACAAGT TATACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGCT AAAACCGARGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGCTCAT GATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAACCCGCTG CAGAAARTTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTA CAAAACCGTTTCAACTCTGCTATCACCAARCCTGGGCAATACCGTAAACAATCTGTCTGAA GCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCG CAGATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCC AGAAC GTGCCTGTCTCTGTTACGTAAGGGCAATTCGAAGCTTGAAGGTCAATTGGAATTCCCTAGG ACTAGTATGGAAAAATTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGGCTTTC AAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTGTGGTGTTGGAATTGCAGTAC ACTGGCACGGATGGACCTTGCAAAGTTCCTATCTCGTCAGTGGCTTCATTGAACGACCTA A
51. 1000000 1760 4150 0 0 0 0 0 680 0000 1740 4220 DO0000 0 58000001 4640 00000 sTF20 fliCU S muenchen 0 000000 000000 0 0 000000 000000 0 0 0000000000000 000 0000 000000 0 176 186 14 2008 527009 2008 7 24 ogoogo TLR5 U UULHUYBHB5HBBHUubu uuiuiu uiill llu t
52. oa a u mu ZJ n n oa na L3 L L3 a L3 710 720 300 320 340 360 380 550 76
53. 00000005 STF2A II 1010000 m N L3 p c 10000005 61000000 STF2A Q J EL I 1 ELI I ll A jiundgbuguuduulululbulLlu iili ll 29 20000000000000 STF2A Ell I d 0 STF2Q 290 7 N m L1 L1 UJ e H UJ HM 11 STF2A El I I D 10000000 300 0000 STF2A El I IL 12 33 5 2
54. 181 21 000000000 0 0 0 Sankaran K et al J Biol Chem 269 197060 1994 000000 0 808 0 tripa U PAP 0000000 0 U 0 0 5 0 00000000 0 D 13 2008 527009 2008 7 24
55. 30 1 flj 5 2 n 40 1760 DU 0 DU l flj B STF2 U l HGAPVDP 1750 1860 3 1 IUD 30 fl j B STF2A 183 50 1110 4150 ASPW 24 JP 2008 527009 2008 7 24 B STF2 muenchen fli C
56. E3 Ej E gt E3 E3 ie 5 E3 g gt zi 2 nooo s D Es E ue T c gt _ Ex gt 5 G rai 29 JP 2008 527009 2008 7 24 Pharmaceuti cal Sci ences 170 Mack Pub Co Ea wo 96 05309
57. Langat 10000000000 1000900000000 1000900000000 10001000 JUD D Uu 000 000000 000000000000 000000000000 1000000000 10001000 00000100000 1000 1000000000 10001000 0 10 20 30 40 50 4 JP 2008 527009 2008 7 24
58. r HM 3 3 PansCys 001 TLR2 oaa oa L3 Oo L3 Oo Oo E L Oo L3 Oo Oo L3 oana 5 0 0000000000 00000000 1000000000000 000 72000 ELISA 0 O Bioreli ance Road Rockville MD 00000000000 00000000
59. 820 83 80 81 760 l 70 86 87 84 700 82 800 20 1590 000 15800 0 1590 30 40 Pan Cys Den2 Den2 40 50
60. 10000 0001000 10000000 Roehrig Adv Virus Res 59 141 175 2003 000 1000000000 00 00 Mande et al Virol 75 5627 5637 10000 5 dv Virus Res 59 2299 274 2003 III DD 11000 E D D J U Rey F A
61. oa a L3 moO L3 oana a 0O 1 5 2 55 45 kU STF2AEIIT 8831288 71 amp amp 5 7752 9E TLR 5 STEZ STEHT STFZEIIF 3 8 4 34 ng ml RIF ES 572528 mg TLR 5 LA BU ug 2 000 1 L3 L3 E Ooo Zr L1 L3 L3 OOO ELI SAD STF2A EL E l 4 r T m O 1 n 4 L3 L3 Oo C3 E EM ES EE L3 L3 Cj n 000 O L3 L3 L3 oana a L3 n Ez 1 E ts EST ET n oaan aa L3 O STF2A EL I I1 STF2A EL I 1 STF2 1000 n n 6 1 I not ek n n
62. EU H 280 260 n 1 n n uu STFA EI II st ME cm Lx Ee n STFA STFA Ellls 0 B EI EI II E2 219 CRVKMEKLQLKGTT 125 10000 Ee K11 0000000 100060 100000060 5 001 PamBCys i pi dated 1000100 LTSGHLKCRVKMEKLQLKGT Putnak R et al Vacci ne 23 4442 4452 2005 C3H Heng O00000 PanBCys r3 r3 r3 r3 r3 r3 m w In 5
63. 1004 90 4 80 704 60 WNV g nt C3H HeN v 92046 eo 50 M OPES 2 e STF2A ELLE 045 304 2 067 1 HHHH HHHO 204 _y_ STR2A EIMIs 069 HJ 104 8 2 070 0 Eror 7 et peg 0 2 4 6 8 1 1 14 16 18 20 REROAR Figure 53 STF2A EDst 0 8 0 7 0 6 e 0 5 6 0 4 02 0 1 N 9 Ty e gh DER P P NBM SO X gt XY N EA OP oo NERO ei D D DES IPO PISS d RIFE Figure 56 58 J P 2008 527009 A 2008 7 24 WNE IgG yet 0 8 4 0 61 8 O PBS 4 004 1 021 e STF2A 0 T V 10 100 1000 10000 Dr LL Figure 54 STF2A EUIst 2 1 84 1 64 14 4 8 124 14 8 0 8 4 9 64 0 4 4 0 2 4 0 4 5 RIFE Figure 55 E2 21 CRVKMEKLQLKGTTYGVCSK mS 100 E2 21 1 SRVKMEKLOLKGTTYGVCSK EIES 101 2 21 2 CRVKMEKLQLKGTTYGVSSK BEES 102 E2 21 3 SRVKMEKLQLKGTTYGVSSK BABS 103 E2 21 4 CRVKMBKLOLKGTTYGVCSK BABS 104 E2 21 5 ARVKMEKLOLKGTITYGVCSK MASS 105 E2 21 6 CAVKMEKLOLKGTTYGVCSK MASS 106 E2 21 7 CRAKMBKLOLKGTTYGVCSK Bum 107 E2 21 8 CRVA
64. 25 10 111 OO 0 00 0 0 37 15 50 d 16 50 0 0 37 40 C 0 5 100 0 0 MRSFO 0 0 1 0 25 33 3 2 20 35 JP 2008 527009 2008 7 24 MRBR 1000 foo 23 ____ g L g 3 A 20 EDTA FUA 5 KH3PO 22 FeSO4 7H20 10 NH4 2804 4 5 7180790 2 2rvK amp 1 0 MnSO4 F50 2 MgSO4 7H350 1 0 CoC1 6H20 0 2 CaCl 0 04 CuSO4GH20 0 1 1ml Na2MoO4Q2H50 0 2 0 01 0 1 e rl 0 05 MRSF Hh Mink g L FWA z 105 7 7 929 28 2 lt 2o NaCl 0 5 7 8 FeSO4 7H20 2 504 2 33 CaCis 3 5 1 0 MgSO4 7H350 12 MgSO4 7H50 1 0 1 CaCh 0 04 fite dr iml fig de ER iml ZVy3 A 100 7 gt 0 01 0 0075 488 2222302 STF2A Ellls JU UUUUUUYUEUUoUoU i
65. oa a O oa j B STF2 s CI CI CI jiupndgiuudgsuluuldiulililuslulululululLlull liu B STF2 L1 Pan Cys PamBCys 1 L1 1 40 50 3 2008 527009 2008 7 24
66. 10 20 30 40 18 JP 2008 527009 2008 7 24
67. H Pro 2 Fmoc 000000 Fmoc PanBCys HOBt 5 100060 000000000000 0 0 0 Genosys Wood ands 000 5 2 STF2 STF2 EI I I 0 11000000 EAE p Es nnmg E z m z STF2A 000 STF2A El I1 STF2 ST
68. 0000 EIER 2 fijB STF2 REEI 6 TREZI BLISS 4 fljB STF2A MRA PORA S CCAGTCCGCACTGGGCACCGCTATCGAGCGTCT AGRSAGCSCGAANGACGATGCGGCAGGTCAGGCGA TTG I CARRTCCCASTCCGCACTGGGCACOGCTATCGAGCSTCTGTCTTCTGGTCTGCGTA BACATCAARGGTCTGACTCAGGCTTCCOGTAA CS TCARCAGCGCGAAAGACGACGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCG RROPROCACTGAAGGOGCGCTGARCGAAATCARCARCAR C AACATCARAGGTCTGACTCAGGCTTCCCSTAACGCTAACGACGGTATCTCCATTGC e TI GCAGACCACTGAAGGCGCGCTGAACGAAATCAACARCAACCTGCAGCGTGTGCGTC CAGGCTGAAATCACCCAGCGCOTGARCGAAATCORCCOM CTAACAGCACCAACTCCCAGTCTGACCTCGACTCCATC GTTCAACGGCGTGARAGTCCTGGCGORSGACARCRCCOS CAGCGCCTGAACGAAATCGACCGTCTATCCGGCCAGACTCA LACGACGGTGARACTATCGATATCGATCTCAAGCA GTTCAACGGCGTGARAGTCCTGGCGCAGGACAACACCCTGACCATCCAGGTTGGCG CTSGACTCACTGAACGTECATGGA CCAACGACGGTGARACTATCGATATCCATCTGAAGCAGATCRACTCTCAGACCCTG AGTOTGTCGCTGCTGACCCAGAATAACCTCAA GTCTTCTGGTCTGCCTA ACGGCACARGCTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAA CTGACCTCGACTCCATC GTATCCGGCCAGACTCA CTGACCATCCAGGTTGGCG ATCTGAAGCAGAT TCTCAGACCCTG SCGCCGGTGGATCCTGCTAGCCCATGGAC SCGCTGGCGCAGGTGGATGCECTGCECT CGAAAACCCGCTGCAGAAAATTGATGC GGTCTGGACTCACTGAACCTGCAGRAAGCGTATGAT GT GAAAGATACAGCAGTARC wong J SGCTGCCGTACAAAACCGTTTCAACTOTGC TAN
69. Figure 26 2 70 STF2AEIIE HERMA ATGGCACAACTARTCAACACTAR AT CAGTCTGCTCGCTGCTGACC ACTGGGCACCG TCG CSCGAACATCAAAGGTCTGA GSTATCTCCATT SCGCAGAC CCTGCAGCGTCTG AACTCCCAGTCTC GOCTGAACG CAACGGCGTGAAAGTCCTG CAGGTTGGCGCCAACGACGGTG AAACTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTGSG TTGCTAAC TTCCOOT ACCTCGACTCCA CCARCCTGGGCARTACCGTAAACAATCTGTCT ATCGAAGATTC CTACGCGACCGAAGTTT CAGGCCGGTACTTCCGT TCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTA CSTGAATTCTGCAGATATCCAGCACAGTGGCGGCCGCTCATGGAAA AATTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGGCTTT CAAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTGTGOGTG TTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTTCCTA TCTCGTCAGTGGCTTCATTGAACGACCTAACGCCAGTGGGCAGATT GGTCACTGTCAACCCTTTTGTTTCAGCTGGCCACGGCCAACGCTAAG GTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTGG TGGGCAGAGGAGAACAACAGATCARATCACCATTGGCACAAGTCTOG AAGCAGCATTGGCAAACCCTCAATAAGC Figure 28 RIES 71 RIES 70M STF2A EID 7 RSI MAQVINTNSZL TONNLNKSQSALGTAIERLSSGLRINSAKDDAA GOAIANRFTAI LTQASRNANDGISIAQTTEGALNEINNNLORV RELAVOSANSTNSQSDLDSIQABITORLNEIDRVSGQTOFNGVEVIL AQDNTLTIQVGANDGETIDIDLK SQTLGLDSLNVHGAPVDPAS PWTENPLOKI DAALAQVDALRSDLGAVONRFNSATTNLGNTVNNLS EARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLL REFCRYPAQWRPLMEKLQLKGTTYGVCSKAFKFLGTPADTGHGTVV LELOYTGIDGPCKVPISSVASLNDL
70. Soa E N lt EX Do od En riu E3 FJ E3 0 F3 Ed ET ET 42 JP 2008 527009 2008 7 24
71. _ ooo ooo E EXC _ ooo ooo Ex E _ Seo pg r3 r3 n n n ooo 00020 0 4 pb 2 Se c SS Ur Ed a En gt L3 rJ L1 LJ 41 pogjgoogunw n0004 L3 CJ CJ CJ EJ 2 2 L1E3 E E32 yy 20000 oOo X pb rr oo Ed Ed Ed Ed Ed 60 Ed EJ 0 lun Wila lun K 2 i tt 1H a 8 a E Nn N 30 HTT 1 160 100 100 100 i 3 1 SIE CM ie 3 o Tn smem i 4 L Fe smmm 4 33 34m STF2AEHF se 3 Fsmomm ie 4 5947 3 2 7 ip 3 ie 4 se 4 057 057 045 045 045 045 __ Lom eel
72. DEN1 DEN2 DEN3 DEN4 DEN 0 0000000 0 DEN 00000 DEN2 DEN3 DEN4 H D B 0600 Chang GJ et al Expert Rev Vaccine 3 199 2 004 DEN 00000 10 20 30 40 50 19 JP 2008 527009 2008 7 24 ENS oe ae ere n TD Hd S s ME ster PAM H 0 O 1000000000 00 0 0 0 Co
73. US 8 BRAS it lt 54 80 26 TRIE 275 1 0 305 08 57 0 000 ipBDpugugapnuugapnauaggnpnaugugppuuggpnuugpnagag ee ee ee ee ee ee ee ee ee ee 2 JP 2008 527009 2008 7 24 jiunmnuumiliuludgululdiuiliulWll nm HE 2 fli jiunmnuumiliuluduliuldiuililulWlkl oana L3 oa L3 L3
74. C N O Own Ol JP 2008 527009 2008 7 24 8 ID BU l 10 221 20 30 Den2 Den4 Den2 Den2 40 1 40 1 OFF
75. TGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGOGGTGCGGTA CAAAACCGTTTCAA TGCTATCACCAACCTGGGCAATACCGTAARCAATCTGTCTGAA GCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCG CAGATTCTGCAGCASGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAAC G7GCTGTCTCTGCTTACGTATGGAAAAATTGCAGTTGAAGGGAACAACCTATGGCGTCTGT TCARAGGCTTTCAAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTGTGZTGTTG GAATTGCAGTACACTGGCACGGATGGACCTTGCARAGTTCCTATCTCGTCAGTGGCTTCA TZGAACGACCTAACGCCAGTGGGCAGATTGGTCACTGTCAACCCTTTTGTTTCAGTGGCC ACGGCCARCGCTAAGGTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTG GTGGSCAGAGGAGAACAACAGATCAATCACCATTGGCACAAGTCTGGAAGCAGCATTGGC Figure 7 30 812148552900 fjB STE2 EHI 7 MAQVINTNSLSLLTONNLNKSQSALGTAIERLSSGLAINSAKDDAAGOAIANRETA NIKGLTOASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSI QAEITORL IRVSGOTOFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTL GLDSLNVQKAYDOVKDTAVTTKAYANNGTTLDVSGLDDAA KAATGGTNGTASVTGG AVKFDADNNKYFVTIG GDYEVNVATDGTVTLAAGATKTTMPAGATT KTEVOELKDT PAVVSADAKNALIAGGVDAT DANGAELVKMSYTDENGKTIBGGYAL KAGDKY YAADY DEATGAZ KAKTTSYTAADGTTKTAANOLGGVDGKTEVVT IDGKTY NASKAAGHDFRAQPSLAEAAAKT TEN P LOKI DAALAQVDALRS DLGAVQNRFENSAI TNLGNTVNNLSEARSRIEDS TEVSNMSRAQILQOQAGTSVLAQANQVPONVLSL LRMEKLOLKGTTYGVCSKAFKFLGTPADTGHGTVVLELQYTGTDGPCKVPISSVAS LNDLTPVGRLVTVNPEVSVATANAKVLIELEPPFGDSYCVVGRGEQOINHEWHKSG SSIGK Figure 8
76. 0DO0O000 0CO0OO0O000000000000000000 0000000000000 MEKLQLKGTTYGVCSKAF KF LGTPADTGHGTVVLELQYTGTDGPCKVPI SSVASLNDLTPVGRLVTVNPFVSVATANAKV 40 LI ELEPPFGDSYI VVGRGEQQ NHHAVHKSGSSIGK GITYGVCSKAF KFARTPADTGHGTVVL ELQYTGKDGPCKVPI SSVASLNDLTPVGRLVTVNPFVSVATANSKVLI FGDSYI VVGRGEQQ NHAWMKSG Stanford 5 8 GITYGVCSKAF KFLGTPADTGHGTVVLELQYTGTDGPCKVPI SSVASLNDLTPVGRLVTVNPFVSVATANAKVLI ELEPP FGDSYWGRGEQQ NHHVHKSG O 0 0 0000 0 NewYork NY 0000000 vEUDHUBD 900 0 0 0 sLEPPFGDsYI WGRGEQQ DOO O0 0 1000000000 700 50 21 JP 2008 527009 2008 7 24 ATGGAAAAAT TGCAGTTGAAGGGAACAACCT AT GGCGTCTGT TCAAAGGCTTT CAAGTTTCTTGGGACT CCCGCAGACAC AGGT CACGGCACT GT GGT GT TGGAAT TGCAGTACACT GGCACGGAT GGACCT T GCAAAGTT CCTAT CT CGT CAGT GGCTT CATTGAACGACCTAACGCCAGT GGGCAGATT GGT CACTGTCAACCCTTTTGTTTCAGT GGCCACGGCCAACGCT AAGGTC CTGATTGAATTGGAACCACCCTT TGGAGACT CATACAT AGT GGT GGGCAGAGGAGAACAACAGAT CAAT CACCAT T GGCA CAAGTCTGGAAGCAGCATTGGCAAA 0 O0 O0 3300 0 0 0 0 0 0 0 0 0 0 0 00 0 0 00 0
77. INTNSLSLL QNNLNKSOSALSTALERLS SGLRINSAKDDAAGOAIANRETA LTOASRNANDG c 252 GLDSLNVTENPLOKIDA LLAQVDALRSDLGAVQNRENSAIT LGNTVNNLSEZ IEDSOYATZVSNMSRAQILOQAGTSVLAQANQVPQNVLSLLRMEKLQLKGTTYGVC SKAFKFLGTPADTGBGTVVLELOYTGTDGPCKVPISSVASLNDLTPVGRLVTVNPF VSVATANARVLIELEPPFGDSYIVVGRGEOQINHHWEKSGSSIGK Figure 16 Bold 55 2 7 ZERLSSGLRINSAKDDAAGQAIANRFTANIKG INNLORVRELAVOSANSTNSQSDIDS 9 DAVSGQTQFNGVXV AQDNTLTIQVGANDGETIDIDLKOINSQTLG NNGTTLDVSGLDDAAI KAATGGTNGTASVTGGA GFTGADAAKNGDYEVNVET DGTVTLAAGATKTTMPASATTRKTSVQE SDTPAVVSADAEN ALIAGGVDATDANSAZLV YT DKNG EGSYALKAGDKY YAADYDEATGATRKAKTTS YIAADGTTKTAANOLGGVDGKTEVVTIDCKTYNASKAAGHDFKAQPZLAZAAAKTTENPi OKIDAALAQVDALRSDLGAVONRENS LGNTVNNLSEARSRIEDSLYATEVSNMSRA CILQOAGTSVLADOANQVPONVLSLLRKGNSKLEGQLEFPRTSMEKLOLKGTTYGVCSKAF RELGTPADTGHGTVVLELOYTGTDGPCKRVPISSVASLNDLTPVGRLVTVNPEVSVATANA KVLIELEPPFGDSYIVVGRGEQOINHHWEKSGSSIGK Figure 18 RIBS 55 HIERD muenchen 25 2 U v fliC 7 lt YATE SNMSRAQILQQAGTSVLAQANQVPONVL SL Figure 19 52 RATCGAGCGTCTGTCTICTGGTI CTGCGTATCAACAGC E CGGTATCTCCATTOCGCA XCGAARTCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCACTC
78. Weg iugggudagmgmggugagagugdutedgscgseczgeNEeg 0000 450 6500 TECA 50 PBS STF2 EQ Drosophila 000000 0000 0 0 25u STF2A ElllI 4400000 700 710 0000 25u g STF2A 114 25 0 5 2 9 541 55 25u g STF2 EIII H 0 OO 0 0 540 550 O0 0 25u g STF2 ED H 0 1580 159 3 350p 0000 0 ELIs 00 0 000000000000 000 00000 39000 60 51 00000000 0 5 2 000 700 71 5 2 HJ 0000 0 540 5500 000000030 000000 48 JP 2008 527009 2008 7 24
79. 275 2712 RAREN TCGCGGTGCACACATTTGGAGAACAGGGACTTTGTCACTGGTACTCAGGGAACCAC GAGAGTGACTCTGGTGTTGGAGCTGGGGGGATGTGTCACGATCACTGCTGAGGGGA AGCCCTCAATGGATGTGTGGCTCGATTCCATCTATCAGGAGAACCCTGCCAAGACA CGCGAGTACTGTCTGCATGCCAAGCTGTCGGACACCAAAGT TGCGGCCAGATGCCC AACAATGGGGCCTGCCACTCTGACTGAGGAGCATCAGAGTGGTACGGTGTGCAAGA GAGACCAGAGTGACCGAGGCTGGGGCAATCACTGCGGATTGTTTGGAAAGGGCAGT ATTGTGACCTGTGTCAAGGTGGCTTGTGAGGCAAAGAAGAAGGCCATTGGACATGT GTATGATGCCAACAAGATCGTGTACACCGTTAAGGTTGAGCCACACACGGGGGACT ATGTTGCCGCCAATGAAACCCACAGTGGGAGGAAGACGGCATCCTTCACGGTCTCC TCAGAAAAGACCATCTTGACTATGCGGGACTATGGAGATGTGCCCT TGTTGTGCAG AGTCGCCAGTGGCGTT GACTTGGCTCAGACTGTCATTCTTGAGCTTGACAAGACTC TGGAACACCTTCCAACAGCCTGGCAGGTCCATCGTGACTGGTTCAATGATCTGGCT CTACCGTGGAAACACGAAGGAGCGCAACAATGGAACAATGCTGAGCGACTGGTTGA ATI TGGAGCTCCGCATGCCGTTAAAATGGACGTGTATAACCTTGGAGATCAAACTG GGGTGTTCTTGAAGTCACTTGCTGGGCTTCCTGTGGCGCACATTGATCGAACAAAG TACCACCTAAAAAGCGGCCATGTAACATGCGAGGTTGGACTAGAAAAGCTCAAAAT GAAGGGTCTCACATACACAATGTGTGACAAAACGAAGTTCGCATGGAAGCGGACTC CAACAGACAGCGGACATGACACAGTGGTCATGGAGGTCACGTTCTCTGGAACAAAA CCTTGCAGGATCCCAGTGCGGGCAGTGGCACACGGCTCTCCAGATGTAAATGTGGC TGCAGCTACCCCCAGGGGATAACATCATCTATGTTGGGGAACTAAGCCATCAGTGG TTCCAGAAGGCGAGCAGCATCGGAAGGGTGTTTCAAAAGACCAGGAAGGGCATCGA GAGACTGACAGTGATAGGAGAACACGCCTCGGACTTCGGTTCCACTGGAGGTTTCT TGACTTCGGTAGCCAAAGCGCTGCACACACTCCTCGGCGGAGCCTTCAACAGCATC TTTGGGGGAGTGGGGTTTCTG
80. 426 50 LI C Ooo Anood C C L L3 oro zs ee e m e O OO O _ Ol OOO m O _ Ol Ooo f LE 2 No in ogo x L3 O LJ Lx C moo EJ 4 L3 C C oo no e k oon C r Lj oo O mE L L3 OW mel Lt C L L3 L3 O E c O A 3 lt Lt O O Ol C C L3 C _ O OL C L L3 5 EM n O o C 3 ooo O N L3 Oo Lt 1 OOO LA on Lt N N 31 m r3 C 2 c C 8 c __ PNE us do C gt c _ _ G C 1 Oooo 42 C C L3 L3 sf EI Lt I Ol o 1 N 4 G 1
81. 86 JP 2008 527009 2008 7 24 11 10 flj B STF2 20 20 Den2 Den2 Den2 Den4 Den4 Den4 30 fl aggel i 1 S muenchen fli Q Den1 1 40 PAMPO 50 Den3 Den3 fl
82. MAQVINTNSZ IERLSSGLRINSAKDDAAGOAIANRFTANIKG LORVRE VOSANSTE SQSDLDSIQAE CAGA T CAACICICAGACCCTGGGTETGGACTCRCT GART SATCCTGCTASCCCATGGACCGAAAACCCGCTGCAGAAAATTGATGC CGCGCTGGCGCAG PLORS DARLAQVDALRS DLGAVON GTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTAT CACC AACCTGGGCAATACCGTAAACAATCTGTCTGAAGCGCGTASCCGTA TCGAAGA TCCGAC TACGCGACCGAAGT TCCAACATG CGCGCAGATTTTGCAGCAGGCCGSTACTTCC CAGAACGTGCTGTCTCTGTTACGTGAATTCAGC AGATATCCAGCACAG GGCGSCCGCT CATGGACAAACTGGCTCTGAAAGGCACAACCTAT GGCATGTGTACAGAAAAATTCTCGTTCGCGAAAAATCCGGTGGACACTGGTCACGGAACA GITGTCATTGAACTCTCCTACTCT GGGAGTGATGGCCCCTGCAAAATTCCGATTGTTTCC GTTGCGAGCCTCAATGACATGACCCCCGTTGGGCGGCTGGTGACAGTGAACCCCTTCGTC GCGACTTCCAGTGCCAACTCAAAGGTGCTGGTCGAGATGGAACCCCCCTTCGGAGACTCC TACATCGTAGTTGGAAGGGGAGACAAGCAGATCAACCACCATTGGCACAAAGCTGGAAGC ACGCTGGGCAAGGCC Figure 33 RAQILOQAGTSVLA TOHGTVLVQVKYECT GENYIVVGAGEKALKLSWFEKK Figure 36 55 2008 527009 2008 7 24 BRI BOMBS 83 5 2 Eri BEALS ATG GTAATCAACACTARCAGTCTGTCGCTGCTGACCCAGARTAACCTGAACAAATCCCA STAR TCARCACTARCASTCTOTCGCTGCTGACCCAGAATAACCTGAACKAAT CTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGCGAAAGACG ACTGGGCACCGCTATCGAGCGTCTGTCTTCTSGTC GCGTATCAACAGCG ATGCGGCAGGTCAGGCGATTGCTARCCGTTTCACCGCGAACATCAAAGGTCTGACTCAGGCTTCC GCGSCAGGTCAGGCGATTGCTAACCGTTTC
83. 14 H D D 70 7 3D9 7 10000 1 0000000000009 000 49 O 5 2 1580 1590 STF2 540 55 STF2A Ellldg 0000 700 710 000 HR 000 0 19810 0 0000000000000 0 0 0 develop O D 450 6500 TECAN O0 Mageiliang 0o 000000000 4980 0 STF2 EQ 0 0 O 1580 1590 STF2 I1 0 540 55 0000 5 2 110 000 0 700 71 00 0 0 0 00 0 00 0 0 0 00 000 0 00000000 0 00000199 0000000000000 450 6500 TECAN 10 0 49d 0 STF2 ED 0 00 1580 1590 STF2 Ell 4 54 55 2 0000 0000 00 0 0 0 0 0 0 0 0 0 0 0 00 0 OD 450 6500 TECA log 000000 4901 5722 0 0 u 0 u 1580 1590 STF2 EL LI 4 540 55 5 2
84. 30 flj B STF2A EllI sd LU 10000 720 1000000 STF2A QD EIH 0000000000 100060 000000 17208 0000000000000 00000000000 00 III GO000 176 000 1100 UB ULBtlu 29 0000071 31 0 70000 100073 STF2A0 10 20 30 40 50 46 JP 2008 527009 2008 7 24
85. Den4 00 0000 fljB STF2Q OG fliqQ 00 000000 menchen fli 9 0 0 KLEKEVAET QHGTVLVQVKYEGT DAPCKI PFSTQDEKGVTONCGRLI TANPI VTDKEKPVNI VVGAGEKALKLSWFKK 210 960 Den2U 100000000 220 40 KGMBYSMCTGKF KVVKEI AETQHGTI VI RVQYEGDGSPCKTPFEI VDLEKRHVLGRLTTVNPI VTEKDSPVNI EAEPPFGDSYI GVEPGOLKLDWFKKT 97 Den3 010010000 230 KGMSYAMCLN TFVLKKEVSETQHGTI KVEYKGEDAPCKI PFSTEDGQGKAHNGRLI TANPVVTKKEEPVNI EAEPPF GESNI VI GD KALKI NWRKI 980 0 Den4 24 KGMSYTMCSGKFSI DKEMAETQHGTTVVKVKYEGAGAPCKVPI RDVNKEKVVCRI SPTPFAENTN SVTNI ELERPLDSYI VI GVGDsSALTLHWFRK O0 0 0 O 990 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 OD 00 000000000 Den3 4 iupndgbiudgdguiiildlisuutLutLl JP 2008 527009 2008 7 24 28
86. Wang et al J Immunol 167 5273 5277 2001 08 0 UU 0 0 00000060 C PBS 0 00000000 utt 10 37 2008 527009 2008 7 24
87. CHAPS TACCAAGTGCGCAACTCCACGGGGCTCTACCACGTCACCAATGATTGCC CTAACTCGAGTATTGTGTACGAGGCGGCCGATGCCATCCTGCACACTCCG GGGTGCGTCCCTTGCGTTCGCGAGGGCAACGCCTCGAGGTOTTIGOGTOG CGATGACCCCTACGGTGGCCACCAGGGATGOCAAACTCCCCGCGACGCA GCTTCGACGTCACATCGATCTGCTTGTCGGGAGCGCCACCCTCTGTTCOG CCCTCTACGTGGGGGACCTGTGCGGGICTGTCTTICTTGTCGGCCAACTG TTTACCTTCTCTCCCAGGCGCCACTGGACGACGCAAGGTTGCAATTGCTC TATCTATCCCGGCCATATAACGGGTCACCGCATGGCATGGGATATGATG ATGAACTGGTCCCCTACGACGGCGTTGGTAATGGCTCAGCTGCTCCGGAT CCCACAAGCCATCTTGGACATGATCGCTGGTGCTCACTGGGGAGTCCTO GCGGGCATAGCGTATTTCTCCATGGTGGGGAACTGGGCGA AGGTCCTGG TAGTGCTGCTGCTATTIGCCGGCGTCGACGCG Figure 24 EIES 69 iC BRE ATGGCACARAGTCATTARTACCAACAGCCTCTCGCTGATCACTCAAAATAATATCAR CAASAACCACTCTGCGCTGTCGAGTTCTATCGAGCGTCTGTCTTCTGGCTTGCGTA AASGATGACGCA GGTCAGSCGATTGCTAACCGTTTCACCTCT GGCCCGTAACGCCAACGACGGTATCTOCGTTGC AAGGCGCGCTGTCCGAAATCAACAACAACTTACAGCGTATCCGTG 2 CAGGCTTCTACCGGGACTAACTCCGATTCGGATCTGGACTCCATT CAGGACGAAATCAARTCCCGTCT AAATTGACCGCGTATCTGGCCAGACCCA GTTCAACGGCGTGAACGTACTGGCGAAAGACGGTTCAATGAAAATTCAGGTTGGTG CGAATGACGGCCAGACTAT CACGATT SATCTGAAGAABATT GACT CAGATACGOTG GCTGARTGGTTTTAACGTGAATGGTTCCGCTACGATAGCCAATAAACCGGCGAC SATTAGCGACCTGACAGCAGCGAAAATGGRTGCTGCAACTAATACTATAACTACAA CAAATARTGCGCTGATCTGCATCAANGGCGCTTGATCAACTGAAAGATGGTGACACT GTTACTATCAAAGCAGATGCTGCTCAAACTGCCACGGTTTATACATACAATGCATC AGCTGGTARCTTCTCATTCAGTAATGTATCGAATAATACTTCAGCAAAAGCAGGTG ATGTAGCAGCTAGCCTTCT GCCGGCTSGGC
88. 2008 7 24 MersOO0 0000 0 0 O CABI 1989997000000 Accelrys San Di California 00 000000000 0 ALIGN 0000 0 2 08 0000000000000 00000600 ALIGN 0000000000 0 0 200 0000000000000 0000 12 Juju nuna
89. 2008 7 24 STF2 E 1590000 0 45 500 000000000000 00 57060600 000 10 0 D Den 19 0000 Denig 000 160 160 000000000 1600000 10 20 00 Den 20 Den 20 00 0 0 Den2g H D 162 162 163 30 Den 30 De
90. AACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTA TCGGGTCTTGATGATG SERA A CAA TCT GICTGAAGCECGTASCOSTATCGANCAT CTATTARAGCGGCTACGGGTGGTACGAATGGTACGGCTTCTGTAACCGGTGGT SAAGTTTCCAACATGTCTOGCGOGCAGATy SAAGATTCCGACTACGCGAC CAGCTATTARAGCGGCTACGGGTGG G Teee Ae Aa eoo TGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGACGGTA CAGTAACCCTTGCGGCTGGCGCAACTAAAACCACAATGCCTGCTSGTGCGACAACT AAAACAGAAGTACAGGAGTTAAAAGATACACCGCCACTTGTTTCAGCAGATGCTAA AAMTGCCTTARTTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGG Figure 4 2 AAGACAATTGAAGGCGGTTATGCGCTT AAAGCT TTACCATGAAGCGACAGGAGCAATTAA AGCTAAAACTACAAGTTATACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACC STAGACGGTAAAACCGAACTCGTTACTATCCACGGTAAAACCTAC AGCAAAGCCGCTGGTCATGATTTCAAAGCACAACCAGAGCTGGCGGAAGC TAAARACCACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCASG TGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAAARACCGTTTCAACTCTGCTATC ACCAACCTGGGCAATACCGTAAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGA TTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCGCAGATTCTGCAGCAGG CCGGTACTTCCGTT AGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCT TIACGT CCGCAGAACGTSCTOTCTCTGTTACOTC Figure 2 1 5 29 MAES 29 5 2 ATGCCACAAGTAATCAACACTAACAGCTCTGTCGCTGCTGACCCAGAATAACCTGAACAAR ATCGCACAAGTARTCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCT
91. Dent EBE ELAI TORA ATS STARTCARCACTAACAGTCTGTCGCTSCTGACCCAGARTAACCTGAACAAAT CCGCACTGGGCACCGCTATCGAGCGICTGTCTTCTGGICTGCGTATCAACAGCGC CCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGC E 85 pET STF25 Den3 E CGATGCGGCAGGTCAGGCGATTGCTARCCGTTTCACCGCGAACATCAAAGGTCTC GAAAGACGATGCGGCAGCTCAGGOGRTTGCTAACOGTTTCACCGCGAACATCAAAGGTCTG C TTCCCGTARCGCTAACGACGSTATCTCCATTGCGCAGACCACTGAAGGCGCGC x CCGTARCGCTAACGACGOTATCTCCATTCCGORGACCACTCAAGSCCOG TGARCGAAATCARCAACARCCTGCAGCGTCTGCGTGAACTGGCGGTTCAGTCTGCTAACAG TERACGRARTCAACLACAACCTOCAGCETCTSCSTCRACTGCCGGTTCRGTCTGCTRRCAS GGCTGAARTCACCCAGCGCCTGAACOAA CACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGAR ACGGCGTGAAASGTCCIGGCGCAGGACRACA ATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCOTGAAAGTOCCTGGCGCAGGACAACA COCTGACCATCCAGGTTGGC CGACGGTGAAACTATCGATATCGATCTGAAGCAGAT CCCTGACCATCCAGGTTGSCGCCAACGACGGTGARACTATCGATATCGATCTGAAGCAGAT CRACTCTCAGACCCTGSETCIGSACT CACTGAACCTGCATGGAGCGCCGSTSGATECTGST CRACTCTCAGACCCTGGSTCTGGRCTCACTGRACGT SCAT SGAGCGLE ENSE CCGAAAARCCCGCTGCAGAAARTTGATGCCGCGCTGGCGCAGGTGOGATGCGC TGCGCTCTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAA CCGAAAACCCGCTGCAGARAATTGATGCCGCGCTGGCGCAGGTGGATGCGC CTGGGTGCGGTACAARACCGTCTCAACTCTGCTATCACCAACCTGGGCAA TGC TACCGTAAACA TCTETCTGAAGCGCGTACCOGTATCGAAGATTCCGACTACGCGACCGAA TACCGTAAACAATCTGTCTGAAGCGCCTAGCCOTATCGAACATTCOCACTACGOGACCGAA GTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCC
92. 0 0 0 0 0 45 5722 114 0000 0000000000 STF2A Elll HJ 0 0 0 d 700 710 STF2A 115 0 0 0 0 720 7310 0 STF2A JEII 10050 60 0000000000 STF2 1141 D D 5 2 0 U 0 D 540 550 000000 0 5M NaCl Sephar o se Q Amer sham Bi osci ences Piscataway NOOD DNA E HH 100m M Tri s pH8 10 10000 Sepharose B0 00000 BO 100nM Tri s CI 1M pH8 0 20 60 STF2 EL ILI 1000 Super dex 200 SD200 1 Na 100mM NaCl 100nM Tris HCl 1 pH8 0 502000 Sepharose 201 600 000000 0000060 Batch 0570 0 0 Extract Dr O Pierce Biotechnology Rockford 11 00000000 0000060 50nM Tri 50 100mM 80 CH 00 STF2A EIII 0 D STF2A Ell 00000 10 0 O Sorvall RO5Q 00 0 0 0 7000 71 0 0 8M 1001 Tri s HCI 5mM EDTAQ 0 560000 0 0 0000000 1M 0000000 Sepharose 9 0 0 000 0 100 1000 A 100 Tris HCl 5mM EDTA 1M pHs 0 10000 B 100m Tris Cl Q 5mM EDTAQ 1M NaC 1M pbs 8M 502000 100000000 O 10
93. 000000 0100000 1100000 000 00000000 000000000000 000 000000000000 88 1000 151 000 10 1 log De nl Den1 110 00 0 0 0 Den iiinnnnnnnpinnnn 00000 0000 T8000 TBIIO TBIII Den2 Den2 110 Den2 111000 0000000000000 E Era EP EDI EE 20 0 0 0 000100 PE B oi o 000 000000000000 EET od Ell l 111 0 000 UD ID In 11 11 00000000600 30 100 Deni 111 0000 Denl 111
94. 2 log STF2A 700 710 000000000 2 0000 mer 10000 4M STF2A 000 nag Tri s NaCl 0 0 0 0 0 1M S200 SDS PAGED D D 43kDan 0 000 nn nnnmn nn n n 10 STF2A Ellls STF2A El 1 72 2 720 730 STF2A 00000 0000 load 40 0 Triton x 1140 D D 0 0 0200 0 00000000000000 0 0 0 4 3kDa D D Triton 114 0 00 0015 20 E 2 0000 502 6000 0 50 Triton x 100 3 50 0 Source SSO00000000000 STF2A 00000000000000 sD02000 505 0 0000000 30 5 2N 3N NH 2 Ellls 0 H H O BLRO DE3Q plysSo 0
95. 40 0000000 010000000000 dull 00000 1 5 Comput Appl Biosci 10 30 5 1994 8 0 0 0 ADVANC ADAM 7 000 Pearson Lipman 00 0000000000000 00 00 Proc Natl Acad Sci USA 85 24440 2448 1988 0 0 0 0 J FASTA 00000 2 Baculovirus CHOU H 00 0 0 Pichia 1000000 0 Blossom 63 0 l PAM 00 1000000 120 109 80 6 4400000 3 44000 Accelrys San Diego Californi GAP 1000000000000 00010 10050 000000 30000 cca 000000 Accelrys San Diego California 0 0 0 O 10000060 n PAM 000 j Uu udguelululullui lWilWuiWuiiWiulillll 100 LU UL 1 5 20 58 000000 0 20 400 390 1600 1620 164 166 710 720 300 320 340 360 380 550 750 60 800 820 841 8600 0 0 0 0 0 0 0 Aubusel F M Current Protocols in Molecular Biology J
96. CT GT CGCT 510 BI pl Edi II GCATGCTCAGCTTATTAAGGGTT TGCCAATGCTGCTTCCCAGACTTGTG 520 11000 0 0 TACGTGAATTCAGCAGATATCCAGCAC 0 00 0O 530 2 ElI I1 O00000 fljb 20 00 H 5 20 0 0 0000 1 5kb 1 170 415 STF2 STF2A 4 30 00 TLR5 NH2 COOH 000000 GAPVDPASPW 560 PCR STF2 153 1000000000 152 5 28 1 5 1 0000000000 O sTF28WMF 2 O STF28bECR 2 5 00 00 0 0 0 270bpl OO00000 0 srF28BGF 1 0 5 2 210 00 0 0 D 0000000000 00 00 00 DNAD 000 0 77kb 0 III 00 0 0 3 ODO pM Bi P V5 His Invitrogen Carlsbad CAJ J UD D D 00000 0 InVitrogen Carlsbad 000 100000600 0 00000 00 TCAGTGCAACTAAA 1560 0 BGHREVJ 0 00 000000 O O TCGAGG 1577 0 0 B O PRO D D oO 100000600 5 2 STF2A El l pET STF2A 4 d 700 71110 100 1000006060 0 5 2
97. Den3 12 JP 2008 527009 2008 7 24
98. Diluent Buffer ADB BD Pharm ngen San Diego 0 00000000 0 0 0 5 1000600 PBs T0 0 0 0 0 00 0 ADB 1461 O Jackson cal West Grove 100000 1000 PBS T0 0 0 0 000 0 TM 3 3 5 5 G U U 0 0 Ultrag Pierce Biotechnol Rockford 11 100000 II 000 Aso0 Tecan 000000000000 10000 Pan3Cys Bachem Bi osci ence Inc King of Prussia PAU D H B B LU D O WNVOOT 10000000 00 0 0 Pan cys wvoolj7 0 000 010 0000 38 JP 2008 527009 2008 7 24
99. GCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT AACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG AACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTICC TGGCGCAG GACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTG AAGCAGATCAACTCTCAGACCCTGGGICTGGACTCACTGAACGTGCAGAAAGCGTATGAT GTGAAAGATACAGCAGTAACAACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTA TCGGGTCTTGATGATGCAGCTATTAAAGCGGUTACGGGTGGTACGAATGGTACGGCTTCT CTAACCGGTIGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGGT GGCTTTACTGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGAC GGTACAGTAACCCTTGCGGCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACT AAAACAGAAGTACAGGAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAAT GCCTTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATG TCTTATACCGATAAAAATCGTAACACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGAT AAGTATTACGCCGCAGATTACGATGAAGCGACAGGAGCAATTAAACCTAAAACCACAAGT TATACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AAAACCGAAGTCGTITACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCAT GATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAACCCGCTG CAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGA TCTGGCTGCGGTA CAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAA GCGCGTAGCCGTATCGAAGATTCCGACTACGUGACCGAAGTTTCCAACATGTCTCGCGCG CAGATTTTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAAC GTGCTGTCTCTGTTACGTCTCGAGGGCTCCATCGGCGCAGCAAGCATGGAATTTTGTTTT GATGTA
100. Hyg 3 90 18 1954 000 Boctor et al J Virol Methods 26 305 311 1989 0 1 0 000 George et al Bull WH O 62 8790 882 19 8 CDC Update V st Nile Virus Encephalitis New York 1999 MWR Morbid Mortal Wkly Rep 48 994 946 CDC Update V st Nile Virus Enc ephalitis New York 1999 MMR Morbid Mortal Wkly Rep 51 11350 11360 19991 2002 1 0000000000060 10001600 100000000060 0 0009000001000 Culex 0000 00 0 0 000000 10000 000 8 50 0000 00 10 000 0 0000000000000 000 00000 DEN 0 0 DEN 1 Den1 Den 10 000000 DEN 2 Den2 Den 20 0 0000000 N 30 000000 Den3 0000000000 0 DEN 4000 Den4 O Den 4 0 100060 0 Bu EE oe DD 100060 0000000 0000000000 0 300 0 0 0 0 EM 0000 00 000000 00 50 000 000 100 000 0 0 10000 Gubler D
101. KE LS SD SL SZ TZ UG ZM ZW EX AZ BY KG KZ M RU TJ TM EP AT BE BG CH CY CZ DK EE ES Fl FR GR HJ I E IS I T LT LU LV M PL PT RQ SE 51 55 TR OX BF B QM GA GQ GYM SN TD AE AG AL AM AT BA BG BR BWBY EZ CA CH CN O CR QJ CZ LE K EM LZ EG EG ES HGR HJ ID IL IN TS J P KE KG KM KN KP KR KZ LG LK L R LS LT LU LV LY M Ms M My WK MZ NG NZ QV PG PH PL PT RQ RU SG 50 SE SG SK SL SM SY 1 IM TN TR TT TZ UA UG UZ G W YU ZA 72 72 IUO U 72 72 U 00000 U 1000 00 48024 01 Avo 2 DX DO FA GIs GY7 AA02 A03 BAS 22 M6 M32 M35 M37 M52 M55 M60 M63 M66 ZA 5l 2 752 28331 28332 40085 7 62 92 11 907 052 Gl Galo 44045 ANI A0 086 EA20 22
102. ee foo Z oto E EE apa 2 L3 8 Py sa ES o gt OFF acere Lp unu ui i29 lt LJ L3 LJ L3 FJ c 1 0 s T E ll G CES eur a L3 Eye ES ES TUE 10000 300 290 0 50 Den3 flj B STF2 000 Den3 9 2008 527009 2008 7 24
103. fees were timely by the applicant Consequently this Intemational Search Report is restricted to the Invention first mentioned in the calms It is covered by claims Nos Remark on Protest 1 The additional search fees were accompanied by the applicant s protest x No protest accompanied the payment of additional search fees Form PCT ISA 210 continuation of first sheet 2 January 2004 70 JP 2008 527009 A 2008 7 24 Intemational Application No PCT US2006 001623 FURTHER INFORMATION CONTINUED FROM 210 This International Searching Authority found multiple groups of inventions in this international application as follows 1 claims 1 4 81 and 82 Concerns a composition particularly a fusion protein comprising at least a portion of at least one antigen and at least a portion of at least one flagellin wherein at least one of the flagellin lacks at least a portion of a hinge region and the use of said composition for stimulating an immune response 1n a subject 2 claims 5 13 partially 14 18 19 20 partially 24 36 partially 39 59 66 68 69 74 partially 75 and 77 both partially Concerns a composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one West Nile viral protein and the use of said composition for stimulating an immune response in a subject 3 claims 5 13 partially 19 20 partiall
104. pET STF2A DEN El I pET STF2A DEN2EI Q pET STF2A DENGEI I I pET STF2A I LT 800 821 841 8600 0 0 0 0 pET STF2A 7 UO Noti 100000 STF2 El I 4 5 2 dj STF2A EIIIs 5 2 JEIII pETSTF2 EllI 0 U 540 550 pETSTF2A 1110 00 O 700 710 pETSTF2A El II sd 0 720 730 0 0 O pETSTF2A JEI I I 00 50 60 BLR pLysS 0 D D 6L 1iugmguuguuuuuuuiza5sugmuiun uguuld 24u g m Woo 0 60 1nM PTG 37 3 O Sorvall RC5 7000rpm x 70 00000000 2xPBSO 10 DNAse 1 ing mr 0 33 JP 2008 527009 2008 7 24
105. 0 4 UU 10 0000000 14 0 0 0 0 0 0 0 0 0000000 300000 STF2 0 000000000 II 4 15 5 2 37 STFA D 0000000001060 16 EIL II 17 flj 5 2 119 00 00000 0 0 0 0 0000 0 0 540 000 STF2 000 gg D DDD DDD 000 000 0000 00 0000 18 0540 00 55 STF2 UU t STF20 00000000000 19 muenchen 58 000 0 20 58D 0 590 000 000 0 000000 21 000 630 0000 22 400000 23 100 20 000000000000 6500000 24 64 000000000000 660 0 0 00 25 65 26 27 68 690 00000600 28 flj B STF2A 11410 00000000000 0000 0000 0 70 10 00000000000 0 0 0 STF2A El 11 3 29 700 STF2A 0 0000000000000
106. 0 B P R PU PB CTD B n n n Dn D H 0 C sf Assay Dil uent Buffer ADB BD Pharm ngen 0000 100 0 PBS T mAb 6H11 lntotek O O 0 ance Road Rockville mbp 000 5 c50 7820 5H10 3D9 Beasley DW et al J Virol 76 13097 13100 2002 H C 0 PBS TO 0000000 ADB 0 0O O HRP 199 Jackson cal V st Grove H 000 TMB 3 3 5 5 100000 000 uUtrag Pierce Biotechnology Rockford IL Tecan Farcyter 0000000 0 0000000000000 0 00 00000000000 0060 100000060 10000000 0 0 T et al J I muno 167 5273 5277 200006 0 0000000000000000 ELISA ELISA 000 0 0000 0 0 PBSO 0 0 0 0 mAb 5059 7H2 5H10 3D9 Beasley DW et al J Viro 76 13097 13100 2002 Bi orel i ance Road Rockville MD H H D T G JJ DUH Assay
107. 000 LU Ul TLR2 UU Pan Cys PamBCys TLR50 0000000000 UU D 0 TLR 000 0 000 0000001000 Jun log TLR1 TLR2 5 Pan Cys 0 0 TLR3 TLR4 J 0000 li OOOG000000 0 TLRS 00000 TLR9 DNAD li TLR1O D 0 TLR120 00 00000000000 li U UULHUYBubWliIHBuuulL 10000 TLR20 0 00 0 0 0 Pan2Cys 0000 0 Pseudonona 5 aerugi nosa Opr O B ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACTCTGCTGGCAG GTTGCTCCAGCAACO 0 0 0 0 O 1800 0000 0 O MNNVEKFSALALAAVLATGCSSHI I 0 0 O ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAAT CCTGGGT TCTACTCTGCTGGCAGGTTGCTCCAGCAAQ 1820 0 0 0000 LGSTLLAGCSSN 0 0 O O 181 TL R2 1000000 TLR2 100000060 Onueti et at J Biol Chem 280 36616 36625 2005 180 lia2pnHuguuuggguguuuuuuuuuuuuudie iainrm 000 0 0 0000 TLR2 li 0 00 000 000 l
108. 0001000 30000000 1000 20 00000000 00 TLR20 0000 O Pan CysG 00000000000000000 0 00 0 0 0 0000 1 ys RS 2 3 0 GB 0000 00 0 0 0 00 0000000 0 0 0 000 l 2 0000 5 2 30 0 0 0 00 0 0 0 0 0 00 0 0 0 40 50 20 JP 2008 527009 2008 7 24
109. 0m Tri s pH8 09 100mM 1H 8 J 1 Na 0 000000000000 10 0000 Source 200 600 Bi 1 000006060 A 100nM Tri s HCl pH8 8M 5mM EDTA B 100nM Tri s CI p H8 5mM EDTA 8M 1M NaCl poli shi 9 0 SD200 J 1000 1000006060 100nM Tri s 8M O 100mM 502008 000000 2 5 D 0 0000000000000 100nM Tris HCl 100 058000 1d H 00 6M 4M 2 STF2A EI II STF2A Elll 70 71 1000000600 30 O STFA ElI 505 00 0000000000000 0 0 0 Triton X 114 s2000 rn 00 0 0 0 SDS 1 00000000 000000 34 JP 2008 527009 2008 7 24
110. 100 0 O Invitrogen Carlsbad CAD 000 50u pET24A STF2A U U O0 O 50 er O BERE O Novagenr 000000000000 0000000 0000000000 000000 pET24A STF2A JEIII 49 0 OJE EN H 000000000600 53 Qui Site Di rected Mutagenesis Kit Stratagene LaJolla CAD 0 0 0 O 5 2 94 0000000000000 1000000000000 0 0 0 5 TF2A J EI I I 000000 09 000000000000 0 0 srF2A Elll 0000000000 000000 000000000 000 710000 0 5 2 El 1151 0 000 72 5 2 000000 000000 120 39 1000000 000000 4 DE Den1 Den2 Den3 Den4 1600 167 Ing DEN T 1000 1001060 100000 0 Denig Den2 Den3 j De n 0000 01110 10005000600 l H 0 H E Si mons Am J Trop Med Hyg 65 159 2001 DE 295 1600 1620 1640 166 DEN O 10000000000000
111. 800000000000 11150 000000000 35 78 79 36 STF2A Den1 80 uH 0 0 0 0 STF2A 0 Den1 37 80 5 2 0 Den1 38 STF2A Den2 82 5 2 Den2 39 82 DLE 10 D STF2A Den2 EIIID D DD D 40 pET STF2A Den3 d RI 84 0000 STF2A 0 n3 41 840 D D 851 STF2A 0 Den3 EIIID I DD D D 0000042 pET STF2A Den4 EIIIT 86 STF2A Dena 43 86 0 8700000000 STF2A 0 Dena 000000 44 tp 18 00 1740 0000 45 Weg 00000 406 0 39 2920 406 2920 20 0000 100000000600 2980 406 E EC mpm a 5 d 67 47 JP 2008 527009 2008 7 24
112. 94 STF2A Eill 045 0861 coo d 0 00 001 01 1 16 100 1000 nmoies Figure 49C 050324 QC ELISA TH2E 7 2 1 804 1 60 i 4 40 1 20 STF2E 014 100 w STF2 EW 054 8 057 i 5 NI 5 241 57 2 045 9 20 4 0 00 0 001 0 01 0 1 1 10 100 1000 JUS nmoles Figure 49D WNV CER C3H HeN Y 2 Z O 20 COO OOOO Ree 904 Ed i 804 e a E 604 134 i ig 207 G Uus PBS gg U STE2AEUR ip i AH STF2A EUR sc 5 291 Steam ip aun STF2EN so 995995090000 1 0 2 6 8 0 i2 14 1 18 20 Figure 51 JP 2008 527009 2008 7 24 1 80 si DUE 1203 m EMI 957 5 2 0 90 7 CC STELE CM 060 030 4 i 040 16 100 1000 10000 100000 WARRE Figure 50 WNE 2M IgG ili pilli GB nt 35 H B NET i ess 284 5 PBS i e 5 2 045 igus 5 o STE2A EI 070 13 105 STF2A Elis 069 1 gs ip 2 ME oos 10 100 1000 10000 100000 1000000 MARRE Figure 52
113. AAACTGCTAGTGGTIGTTTATAAR GCAGCAAGCGGTGAAGTGAACTTTGATGTTGATGCGAATGSGTAAAATCACAATCGG AGTGATGGTAACTTAACTACAAACGATGCTGGTG CTGCGACTGCGGCTACGCTTGATGGTTTATTCAAGAAAGCTGOTGATGGTCAATCA RATCGGGTTTAAGAAGACTGCATCACTCACGATGGGGGGAACAACTTATAACTTTAA AACGGGTGCTGATGCTGATGCTGCAACTGCTAACGCAGGGGTATCGTTCACTGATA CAGCTAGCAAAGAAACCGTTTTAAATARAGTGGCTACAGCTAAACAAGGCAAAGCA GTTGCAGCTSACGGTGATACATC LCAATTACCTATAAATCTGGCGTTCAGAC SCTATCAGGCTGTATTTGCCGCAGGTGACGGTACTGCTAGCGCAAAATERTGCCGATA AAGCTGACGTTTCTAATGCAACAGCAACATACACTGATGCTGATGGTGAAATGACT ACAATTGGTTCATACACCACGARAGTATTCAATCGATGCTAACAACGGCAAGGTAAC TGTTGATTCTGGAACTGGTACGGGTAAATATGCCCCGAAAGTAGGGGCTGAAGTAT ATGTTAGTGCTARTGGTACTTTAACAACAGATGCAACTAGCGAAGGCACAGTAACA ATCCACTGAAAGCTCTGGATGAAGCTATCAGCTCCATCGACAAATTCCGTTC SGGTGCTATCCAGAACCGTCTGGATTCCGCAGTCACCAACCTGAACAACA ACCARCCTGTCCGARGCGCAGTCCCGTATTCAGGACGCCGACTATGCGACC CCARCATGTCGAAAGCGCAGATCATTCAGCAGGCCGGTAACTCCGTGCT CCAACCAGGTACCGCAGCAGGTTCTGTCTCTGCTGCAGGGTTAR Figure 27 53 EIES 67 CHAT EO AEH GAAACCCACGTCACCOGGGGAAGTOCCGGCCACACTGTGTCTGGATTTG TIAGCCTCCTCGCACCAGGCGCCAAGCAGAACGTCCAGCTGATCAACAC CAACGGCAGTTGGCACCTCAATAGCACGGCCCTGAACTGCAATGATAGC CTCAACACCGGCTGGTTGGCAGGGCTITTCTATCACCACAAGTTCAACTC TICAGGCTGTCCTGAGAGGCTAGCCAGCTGCCGACCCCTTACCGATTTTG ACCAGGGCTGGGGCCCTATCAGTTATGCCAACGGAAGCGGCCCCGACTA GCGCCCCTACTGCTGGCACTAC
114. ACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AAAACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCAT GATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAARACCCGCTG CAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTA CAAAACCGTTTCAACTCTGC TCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAA GCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCG CAGATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAAC 51 2008 527009 2008 7 24 S 52 ABS 31 jB STF2A ETIT 7 7 MAQV INTNSLSLLTONNLNKSOSALGTAIERLSSGLRINSAKDDAA GOAIANRZTTANIKGLTOASRNAND AQTTEGALNEINNNLORV ARELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVL AQDNTLTIQVGANDGETIDIDLKOQINSQTLGLOSLNVHGAPVDPAS PWIENPLOXTDAALAOVDALRS DLGAVONRENSAITNLGNTVNNLS ARSRIEDSDYATEVSNMSRAQ I LOQAGT SVLAQANOVPQNVLSLL RMEKLQLKGTTYGVCSKAPKFLGTPADTGHGTVVLELQYTGTDGPC RVPISSVASLNDLTPVGRLVTVNPFVSVATANAKVLTELEPPFGDS YIVVGRGEQOINHHWHKSGSSIGK Figure 10 00000 EIES 33 STF2A EI ESI 7GGGCACCGCTATCGAGCG CAGCGCGAAAGA GCGGCA CACCGCGAACATCAAASGTCTGA CTCAG TTCCCGTAACGCTAACGACGSTATCTCCATTGCGCAGAC GCTGAACGARATCAACAACAACCTGCAGCGTGTG CGTGAACTGGCGGTTCAGTCTGCTAACAGCACCAACTCOCAGTCTG ACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCT ARACTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGG TCTGGACTCACTGAACGTGCATGGAGCGCCGGTGGATCCTGOTAGC i SARAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGC AGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAAAACCGTTT CRACTCTGCT
115. ACCGCGAACATCAAAGGTCTG CCCGTAACGCTARCGACGGTATCTCCATTGCGCAGACCACTGAAGGCGOGC CAR GCCTGAACTGGCGETTCAGTCTGCTAACAGCACCAACTCCCAGTCTGACC TGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAG TCGAC TCACCCAGCGCCTGAACGAAATCGACCGTGTATCCGGCCAGACT ASCTCGACTOCAT CCAGGCTGAAATCACOCAGCGCOTGAACGAA CAGTTCAACGGCGTGAARAGTCCTGGCGCAGGACAACACCCTGACCATCOAGGTTGGCGCCAACOA ATCGACCGTGTATOCCGGCCAGACTCAGTTCAACGGCGTGAAAGTOCCTGGCGCAGGACAACA CGGTGARACTATCGATATCGATCTGAAGCACATCARCTCTCAGACCCTGGGTCTGGACTCACTGA CCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTGAAGOAGAT ACGTGCATGGAGCGCCGGTGGATCCTGOTAGCCCATGGACCGAAAACCCGCTGCAGAAAATTGAT CAACTCTCAGACCCTGGGTCTGGACTCACTGAACGIGCATGGAGCGOCGGTGGATCCT SCT GCCGCOCTGGCO ATGCGCTGCGCTCTOATCTGGGTGCGCTACRAAACCGTTTCAACTC AGCCCRTGGACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGC TGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAAGCGCGTAGCOGTATCGAAGATT TGCGCTCTGATCTGGGTGCGGTACARARCCGTTTCAACTCTGCTATCACCAACCTGGGCAR CCGACTACGCGACCGAACTTTCCARCATCTCTCGCGCGCAGATTTTGCAGCAGSCCOGTACTTCC TACCGTAAACAATCTGTCTGARGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAR GTTCTGGCGCAGGCTARCCAGGTCCCGCAGAACGTGCTGTCTCTCTTACGTGAATTCAGCAGATA GrTTCCAACATGTCTCGOGCGCAGATTTTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAOS CTAACCASGT CCCGCAGAACGT GCTGTCTCTGPTACGTGAATTCAGCAGATATCC
116. ACGGAACAGTTGTCATTGAACTCTCCTACTCTGGGAGTGATGGCCCCTGCAAAATT CCGATTGTTTCCGTTGCGAGCCTCAATGACATGACCCCCGTTGGGCGGCTGGTGAC AGTGAACCCCTTCGTCGCGACTTCCAGTGCCAACTCAAAGGTGCTGGTCGAGATGG AACCCCCCTTCGGAGACTCCTACATCGTAGTTGGAAGGGGAGACAAGCAGATCAAC CACCATTGGCACAAAGCTGGAAGCACGCTGGGCAAGGCC Figure 5 0000 6 pET STF2 JEZII 7 MAQVINTNSLSLLTQNNLNKSOSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTEGALNEINNNLORVRELAVOSANSTNSQSDLDSI QAEITQRL NEIDRVSGOTQFNGVEVLAQDNTI PPASP PLOKIDAZ Y NMSRAQILQQAGT TIQVGAND IDIDLKOINSQTLGLDSLN ATSSANSKVLVEMEPPFGDSYIVVGRGDKQINEHWHKAGSTLGKA Figure 6 XQVDALRSDLGAVONRENSAITNLGNTVNNLSEARSRIEDSD Y VLAQANQVPONVLSLLREFCRYPAQWRPLMDKLALKGTTY GMCTEKFSFAKNPVDIGHGTVVIELSYSGSDGPCKIPIVSVASLNDMTPVGRLVTVNEFV TCGGGTCTTGATGATGCAGCTATTAAAGCGGCTACGGGTGGTACGAATGCTACGGCTTCT GTAACCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTIGGT SGCTTTACTGGTGCTGATGCCSCTARAAATGGCGATTATGAAGTTAACGTTGCTACTGAC SGTACAGTAACCCTTGCGGTTGGTGCAACTAAAACCACAATGCCTGCTGGTGCGACAACT AAAACAGAAGTACAGGAGTTAAAAGATACACCGGCARCTTGTTTCAGCAGATGCTAAAAAT GCCTTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGACTTGGTCAAAATG TCTTATACCGATAAAAATGGTAAGACAATTGAACGCGGTTATGCGCTTAAAGCTGGCGAT AAGTATTACGCCGCAGATTACGATGAAGCGACAGGAGCARTTARAGCTARAACTACAAGT TATACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AARACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCAT GATTTCAAAGCACAACCAGAGCTGGCGSAAGCAGCCGCTAARACCACCGAAAACCCGCTG
117. AGCACA GTGGCGGCCGCTCAAAGGTATGAGCTATAGCATGTGTACCGGIAAATTTAAAGTTGTTAAA GCGCCATGTAAGATACCATTTTCCACTCAAGATGAGAAASGGGCGACTCAGAACGGAAGATTGAT GAAATTGCGGAAACCCAGCATGGTACCATTGTTACTCGTGTTCAGTATGAAGGTGATGS3TA AACCGCRAATCC CGTAACCGACAAGGAAAAGCCCGTGAATATTGAGGCAGAGCCTCCGTTTSO GCCCGTGTAAAATTCCGTTTGAAATTATGGATCTGGAAAAACGTCATGTTCTGGGTCCTCOT GGGAGTCGTATA STCGTTGGTGCTSESTCAAAAGGCTT TAAAGCTCAGTTGGTTCARAAAGGGG GATTACCGTTAATCCGATTSTTACCGABABAGATAGCCCGGTTAATAT TGAAGCGGAA TCG CCG7TTGGTGATAGCTATATTATT GTTGAACCGGGTCAGCTGAAACTGAATTGGT TTAAAAAAGGTAGCAGCATTGGTCAG Figure 39 Figure 37 BCDB m 84 DET str MAQVINTNSLSLLTOQNNLNKSOSALGTALERLSSGLRINSAKDDAAGQAIAI 82 ELIT Yom BRA LTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQS a NEIDRVSGQTQFNG 7 78827 MAQVZNTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANKETA DPASPXTENPLOKIDAALAQVDALRSDLGAVONRFNSAITNLGNTVNNLSEAR LTQASRNANDGISTAQCTEGALNEINNNLORVRELAVQSANSTNSQSDLDSIQAEI YATEVS 25118 KVEYKGEDAPCK GiGDKALXINWYRK NEIDRVSGQTOQFNGVKVLAQDNELT I QVGANDGETI DI DLKQINSQTLGLDSLNV FVLKKEVSE TENPLOK DAALAQVDALRSDLGAVONRFNSAITNLGNTVNNLSEARSRIEDSD NIE WIBAEPPFGDSYIIIGVEPGOLKLDWFKK Figure 40 Figure 38 10000 BRA BCA 87 pET STP24
118. AGTARTCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAA AGTCCGCACTGGG TATCGAGCCTCTGTCTTCTGGTCTGCGTA TCAACAGCGCGAAAZACGATGCGGCAGCTCAGGCGATTGCTAACCGTTTCACCGCG AACATCAAAGGTC CTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGC GCAGACCACTGAAGGCGCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTG AACAGCACCAACTCCCAGTCTGACCTCGACT TC AACGRAATCGACCGTCTATCCSGCCAGACTCA CAGGACAACACCCTGACCATCCAGGTTGGCG CGATCTGAAGCAGATCAACTCTCAGACCCTG GGTCTGGACTCACTGAACGTGC GAGCGCCGGTGGATCCTGCTAGCCCATSGAC CGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGG CGCTGCGCT CTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAAT ACCGTARACARTCTGTCTGAAGCGCGIAGCCGTATCGAAGATTCCGACTACGCGAC CGAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCO CTTCCGTTC TSGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTG TACGTATGGAAAAA TIGCAGTTGAAGGGAACAACCTATGGCGTCTGTICAAAGGCTTTCAAGTTTCTTGG GACTCCCGCAGACACAGGTCACGGCACTGTGGTGTTGGAATTGCAGTACACTGGCA CGGATGGACCTTGCAAAGTTCCTATCTCGTCAGTGGCTTCATTGAACGACCTAACG CCAGTGGGCAGATTGGTCACTGTCAACCCTT TTGTTTCAGTGGCCACGGCCAACGC TAAGGTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTGGTGGGCA GAGGAGAACAACAGATCAATCACCATTGGCACAAGTCTGGAAGCAGCATTGGCAAA GAAAGTCCTGGC CGACGGTGAAACTATCGATA AT G T G Figure 9 MIER 05195330 AB STF2A EMI S EMA MAQVINTNSLSLLTONNLNKSOSALGTAIERLSSGLRINSAKDDAA GOQAIANRPTANIKGLTOASRNANDGI QTTEGALNEINNNLORV RELAVOSANSTNSQSDLDS I QAEITORLNSI DRVSGOTOFNGVKVL AQDNTLTIQVGANDGETI DI DLKQINSOTLGLESLNVHGAPVDPAS PWTENPLOKI DAALA
119. AIVFKGLWEKAFKDEDTQAMPFRVTEQESKPVOMMY QIGLFRVASMASEKMKILELPFASCTMSMLVLLPDEVSGLEOLESIINFEKLTEWTSSNV MEERKIKVYLPRMKMEEKYNLTSVLMAMGITDVFSSSANLSGI SSAESLKISQAVHAAHA EINEAGREVVGSAEAGVDAASVSEEFRADHPFLFCIKHIATNAVLFFGRCVSPSKLEGKP IPNPLLGLDSTRTGHHHHHH Figure 62 00000 EIES 154 447 FS gt OVA 7 2 7 BEA GSIGAASMEFCFDVFKELKVHHANENI FY CPIAIMSALAMVYLGAKDSTRTOINKVVRED KLPGFGDSTEAQCGTSVNVHSSLRDILNQITKPNDVYSFSLASRLYARERYPILPEYLQC VKELYRGGLEPINFQTAADQARELINSWVESQTNGIIRNVLOPSSVDSQTAMVLVNAIVE KGLWEKAFKDEDTQAMPFRVTEQESKPVQMMYQIGLFRVASMASEKMKILELPFASGTMS MLVLLPDEVSGLEQLESIINFEKLTEWTSSNVMEERKIKVYLPRMKMEEKYNLTSVLMAM GITDVFSSSANLSCISSAESLKISQAVHAAHAEINEAGREVVGSAEAGVDAASVSEEFRA DHPFLFCIKHIATNAVLFFGRCVSP Figure 63 2008 527009 2008 7 24 BASS 155 OVA BEES GGGCTCCATCGGCGCAGCAAGCATGGAATTTTGT TTTGATGTATTCAAGGAGCTCAAAGT CCACCATGCCAATGAGAACATCTTCTACTGCCCCATTGCCATCATGTCAGCTCTAGCCAT GGTATACCTGGGTGCAAAAGACAGCACCAGGACACAAATAAATAAGGTTGTTCGCTTTGA TAAACTTCCAGGATTCGGAGACAGTATTGAAGCTCAGTGTGGCACATCTGTAAACGTTCA CTCTTCACTTAGAGACATCCTCAACCAAATCACCAAACCAAATGATGTTTATTCGTTCAG CCTTGCCAGTAGACTTTATGCTGAAGAGAGATACCCAATCCTGCCAGAATACTTGCAGTG TGTGAAGGAACTGTATAGAGGAGGCTTGGAACCTATCAACTTTCAAACAGCTGCAGATCA AGCCAGAGAGCTCATCAATTCCTGGGTAGAAAGT CAGACAAATGGAATTATCAGAAATGT CCTTCAGCCAAGCTCCGTGGATTCTCAAACTGCAATGGTTCTGGTTAATGCCATTGTCTT CAAAGGACTCTGGGAGAAAGCATTTAAGGATGAAGACACACAAGCAATGCCTTTCAGAGT GACTGAGCAAGAAAGCAAACCTGTGCAGATGATGTACCAGATTGGTTTATTTAGAGTGGC AT
120. ATCACCAACCTGGGCAATACCGTAAACAATCTGTZT GAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTT CCAACATGTCTCGCSCGCAGATTTT GCAGCAGGCCGGTACTTCCS TC GCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTA CGTCAATTCTGCAGATATCCAGZACACTGGCGGCCGCTCATGGAAA AATTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGGCTTT CAAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTGTGGTG TTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTTCCTA TCTCGTCAGTGGCTTCATTGAACGACCTAACGCCAGTGGGCAGATT GGTCACTGTCAACCCTTTTGTTTCAGTGGCCACGGCCAACGCTAAG GTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTGG TGGGCAGAGGAGAACAACAGATCAATCACCATTGGCACAAGTCTGG AAGCAGCATTGGCAAACCCTTAATAAGC EIES 36 MIESO 7 BACT MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGOAIA NRFTANIKGLTQASRNANDGISIADTTEGALNEINNNLORVRELAVQSANS TNSOSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDONTLTIQVGANDG ETIDIDLKZINSQTLGLDSLNVQKAYDVKDTAVTTKAYANNGTTLDVSGLD DRAIKARTGGTNGTASVTGGAVKFDADNNKYFVTIGGFTGADAAKNGDYEV NVATDGTVTLAASGATKTTMPAGATTKTEVQELEKDTPAVVSADAKNALTAGC DAT DANGAELVKMS YT DANGKTIEGSYALKAGDKY YAADY DEATGATKAK m TAADGTTKTAANQLGGVDGKTEVVTIDGKTYNASKAAGHDEKAQ EL AAKTTENPLOKIDAALAQVDALRSDLGAVONRFNSAITNLGNTVNNLS EARS SDYATEVSNMSRAOILOOASTSVLAQANQVPONVLSLLREECR XPAQWRPLMEKLOLKGTTYGVCSKAFKFLGTPADTGHGTVVLELOYTGOTDG PCKVPISSVASLNDLTPVGRLVTVNPFVSVATANAKVLIELEPPFGDSYIV VGRGEQQINHHWHKSGSSIGK Figure 14 IU D Du Bild 37 380 fliB STF2A EN HREJ ATGGCACAACTAATCAACACTAACAGTCTGTCGCTG
121. ATGTAAACAAGGAAAAAGTGGTTGGGCGTATCATCTCATCCACCCCTTTGG CTGAGAATACCAACAGTGTAACCAACATAGAATTAGAACCCCCCTTTGGGGACAGCTACATAGTGAT AGGTGTTGGAAACAGCGCATTAACACTCCATTGGTTCAGGAAAGGGAGTTCCATTGGCAAGATGTTT GAGTCCACATACAGAGGTGCAAAACGCAATGGCCATTCTAGGTGAAACAGCTTGGGATTTTGGTTCCG TTGGTGGATTGTIICACATCATTGGGAAAGGCTGTGCACCAGGTTTT GGAAGTGTGTATACAACCAT GTTTGGAGGAGICTCATCGATGATTAGAATCCTAATTGGGITCTTAGTGTTGTGGATTGGCACGAAC TCAAGGAACACTTCAATGGCTATGACGTGCATAGCTGTTGGAGGAATCACTCTGTTTOTGGGCTTC Figure 75 61 00000 MASS 164 Den 3 7 MRCVGVGNRDFVEGLSGATWVDVVLEHRGGCVTTMAKNKPTLDTELOKTEATOLATIRKICIFGKIT NITTDSRCPTOGEAILPEEODONYVCKHTYVDRGWGNGCGLEFGKGSLVICAKTQCLEPIEGKVVQH ENLKYTVIITVHTGDQHOVGNDTOGVTVEITPQASTVEAILPEYGTLGLECSPRTCLDFNEMILLT MKNKAWMVHRQWEFDLPLPWTSGATTETPTWNRKELLVTFKNAHARKQEVVVLGSQEGAMHTADTG ATEIQNSGGTSIFACHLKCRLKMDKLELKCMSYAMCLNTIVLKKEVSETOHGTILIKVEYKGEDAP CKIPPSTEDGQGKAHNGRLITANPVVTKKEEPVNIEAEPPFGESNIVIGIGDKALKINWYKKGSSI GKMFEATARGARRMAILGDTAWDEGSVGGVLNSLGKMVHOIFGSAYTALFSGVSWIMKIGIGVLLT WIGLNSKNTSMSFSCIAIGIITLYLGAVVOA Figure 72 BAS 165 3 ema ATGAGATGOGTGGGAGTACGAAACAGAGATTTTGTGGAAGGTCTGTCGGGAGCTACGTGGGTTGAT GTGGTCCYCGAGCACGGAGGGTGTGTGACCACCATGGCTAAGAACAAGCCTACGCTGGACATAGAG CTCCAGAACACCGAGGCCACCCAACTGGCGACCCTAAGAAAGTTATGCATTGAGGGARAAATTACC AACATAACAACTGACTCAAGGTGTCCTACCCAGGGGGAAGCGATTTTACCTGAGGAGCAGGACCAG AACTACGTATGTAAGCACACATACGTGGATAGAGGT T GGGGAAACGGTIGTGGTTTGTTTGGAAAA GGAAGCTTGGTGACATGCGCGAAATTTCAATGTCTAGAACCAATAGAGGGAAAACTGGTGCAACA
122. CAATGGCTTCTGAGAAAATGAAGATCCTGGAGCTTCCATTTGCCAGTGGGACAATGAG CATGTTGGTIGCTGTTGCCTGATGAAGTCTCAGGCCTTGAGCAGCTTGAGAGTATAATCAA CTTTGAAAAACTCACTGAATGGACCAGTTCTAATGTTATGGAAGAGAGGAAGATCAAAGT GTACTTACCTCGCATGAAGATGGAGGAAAAATACAACCTCACATCTGTCTTAATGGCTAT GGGCATTACTGACGTGTTTAGCTCTTCAGCCAATCTGTCTGGCATCTCCTCAGCAGAGAG CCTGAAGATATCTCAAGCTGTCCATGCAGCACATGCAGAAATCAATGAAGCAGGCAGAGA GGTGGTAGGGTCAGCAGAGGCTGGAGTGGATGCTGCAAGCGTCTCTGAAGAATTTAGCGGC TGACCATCCATTCCTCTTCTGTATCAAGCACATCGCAACCAACGCCGTTCTCTTCTTTGG CAGATGTGTTTCCCCT Figure 64 00000 159 5 2 7 MAQVINTNSLSLLTONNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTSGALNEINNNLORVRELAVOSANSTNSQSDLDSIQAEITORL NEIDRVSGQTOFNGVXVLAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVQKAYD VKDIAVTTKAYANNGTTLDVSGLDDAAI KAATGGTNGTASVTGGAVKFDADNNKYEVTIG GFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATTKTEVOELKDTPAVVSADAKN ALIAGGVDATDANGAELVKMSYTDKNGKTIEGGYALKAGDKYYAADYDEATGAIKAKTTS YTAADGTTKTAANQLGGVDGKTEVVT I DGKT YNASKAAGH DFKAQPELAEAAAKTTENPL QKIDAALAQVDALRS DLGAVONRFNSAI TNLGNT VNNLSEARSRIEDSDYATEVSNMSRA QILQQAGTSVLAQANQVPONVLSLLRENCLGMSNRDFLEGVSGATWVDLVLEGDSCVIIM SKDKPTIDVKMMNMEAANLAEVRSYCYLATVSDLSTKAACPTMGEAHNDKRADPAFVCRQ GVVDRGWGNGCGLFGKGSIDTCAKFACSTKAIGRTILKENIKYEVATFVHGPTTVESHGN YSTOVGATQAGRFSITPAAPSYTLKLGEYGEVTVDCEPRSGIDTNAYYVMTIVGTKTFLVH REWEMDLNLPWSSACSTVWRNRETLMEFEEPHATKOSVIALGSQEGALHQALAGAIPVEF SSNIVKLTSGHLKCRVKMEKLQLKGTTYGVCSKAFKFELGTPADTGHGTVVLELQYTGTDG PCKVPISSVASLNDLTPVGRLVTVNPFVSVATANAKVLIELE
123. CCCAAGCTCCTGTTGGGTGTGGCCTTAGCCTGGTT GGGCCTGAACATCAGGAACCCCACCATGTCCATGAGTTTCCTCTTGGCTGGGGGAC TGGTCCTGGCTATGACACTTGGAGTGGGTGCT Figure 78 BAS 178 EMH ATGGAAAAATTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAA GGCTITCAAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTG TGGTGTTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTT CCTATCTCGTCAGTGGCTTCATTGAACGACCTAACGCCAGTGGGCAG ATTGGTCACTGTCAACCCTTTTGTTTCAGTGGCCACGGCCAACGCTAA GGTCCTGATTGAATTGGAACCACCCTTIGGAGACTCATACATAGTGG TGGGCAGAGGAGAACAACAGATCAATCACCATTGGCACAAGTCTGG AAGCAGCATTGGCAAA Figure 79 00000 2008527009000001 62 00000 JP 2008 527009 2008 7 24 Figure 80 63 2008 527009 2008 7 24 INTERNATIONAL SEARCH REPORT Intemational application PCT US2006 001623 A61K39 12 A61P37 04 A CLASSIFICATION OF SUBJECT MATTER INV 07K14 00 07 14 18 A61K39 00 According to International Patent Classification IPC or to both national classification and IPG B FIELDS SEARCHED Minimum documentation searched classification system followed by classification symbols CO7K A61K Documentation searched other than minimum documentation to the extent that such documents are included In the flelds searched Electronic data base consulted during the International search name of data base and where practical search terms used EPO Interna BIOSIS MEDLINE EMBASE SCISEARCH WPI Data DOC
124. CCCCCAAAACCTTGCGGTATTGTGCCCG CGAAGAGTGTGTGTGGTCCGGTATATTGCTICACTCCCAGCCCCGTGGTG GTGGGAACGACCGACAGGTCGGGCGCGCCCACCTACAGCTGGGGTGAA AATGATACGGACGTCTICGTCCTTAACAATACCAGGCCACCGCTGGGCA ATTGGTTCGGTTGTACCTGGATGAACTCAACTGGATTCACCAAAGTGTGC GGAGCGCCTCCTTGTGTCATCGGAGGGGCGGGCAACAACACCCTGCACT GCCCCACTGATTGCTTCCGCAAGCATCCGGACGCCACATACTCTCGGTGC GGCTCCGGTCCCTGGATCACACCCAGGTGCCTGGTCGACTACCCGTATAG GCTTTGGCATTATCCTTGTACCATCAACTACACTATATITAAAATCAGGA TGTACGTGGGAGGGGTCGAGCACAGGCTGGAAGCTGCCTGCAACTGGAC GCGGGGCGAACGTTGCGATCTGGAAGATAGGGACAGGTCCGAGCTCAGC CCGTTACTGCTGACCACTACACAGTGGCAGGTCCTCCCGTGTICCTTCAC AACCCTGCCAGCCTTGTCCACCGGCCTCATCCACCTCCACCAGAACATTG TGGACGTGCAGTACTTGTACGGGGTGGGGTCAA GCATCGCGTCCTGGGC CATTAAGTGGGAGTACGTCGTCCTCCTGTTCCTTCTGCTTGCAGACGCGC GCGTCTGCTCCTGCTTGTGGATGATGCTACTCATATCCCAAGCGGAAGCG Figure 25 EWES 68 ARB HCT 5 C R FRESI MAQVINTNSLSLITONNINKNQSALSSSIERLSSGLRINSAKDDAAGQAIANRFTS NIKGLTCARRNANDGISVAQTTEGALSE NNNLORIRELTVOASTGTNSDSDL2SZ QDEL DEIDRVSGOTOFNGVNVLAKDGSMKIQVGANDGOTITIDLKKIDSDTL TIANKAATISDLTAAKMDAATNTITTTNNALTASKALDOLKDGDT CADAROTAT VY TYNASAGNES FSNVSNNTSAKAS DVAASLLPPAGOTASGVYK AASGEVNFDVDANGKITIGGQKAYLTSDGNLTTNDASGGATAATLDGLFKKAGDGQS IGPKKTASVTMGGTTYNFKTGADADAATANAGVSEFTDTASKETVLNKVATAKQGKA VAADGDTSATTTYKSGVQTYQAVFAASDGTASAKYADKXADVSNATATYTDADGEMT TIGSYTTEYSIDANNGKVTVDSGTGTGKYAPKVGAEVYVSANGTLTTDATSEGTVT KDPLKALDEATISSIDKFRSSLGAIONRLDSAVTNLNNTTTNLSEADSRIQDADYAT EVSNMSKAQIIQOAGNSVLAKANQVPQOVLSLLQG
125. CGCCAGTGGGCAGATTGGTCACTGTCAACCCTTTTGTTTCAGTGGCCACGGCCAACGCT AAGGTCCTGATTGAATTGGAACCACCCTTTIGGAGACTCATACATAGTGGTGGGCAGAGGA SAACAACAGATCARTCACCATTGGCACAAGTCTGGAAGCAGCATTGGCAAR Figure 17 EIES 59 HIERD muenchen 25 2 U v RBM FRE SI lt TGGCACAAGT CATTAATACAAACAGCCTSTCGCTGTTGACCCASAATAACCTGAA CAAATCCCAGTCCGCTCTGGGCACCGCTATCGAGCGTCTGTCTTCCGGTCTGCGTA TCAACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCG AACATCARAGGTCTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGC GCAGACCACTGAAGGCGCGCTGAACGAAATCAACAACAAC CAGCGTGTGCGTG AACTGGCGGTTCAGTCTGCTAACGGTACTAACTCCCAGTCTGACCTTGACTCTATC CAGGCTGAAATCACCCAGCGTCTGAACGAAATCGACCCTGTATCCGGTCAGACTCA GTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCTGACCATCCAGGTTGCTG CCAACGACGGTGAAACTATTGATATTGATTTAAAAGAAATTAGCTCTAAAACACTG GGACTTGATAAGCTTAATGTCCAGGATGCCTACACCCCGAAASGARLACTGCTGTAAC CGTTGATAAAACTACCTATAAAAATGGTACAGATACTATTACAGCCCAGAGCAATA CTGATATCCAAACTGCAATTGGCGGTGGTGCAACGGGGCTTACTGGGGCTGATATC AAATTITAAAGATGGTCAATACTATTTAGATGTTAAAGGCGGTGCTTCTGCTGGTGT TTATARAGCCACTTATGATGARACTACAAACAAAGTTAATATTGATACGACTGATA AAACTCCGTTAGCARACTG SCGGANGCTACAGCTATICOGGGEACGGCUACTATRAS CACAACCAAATTGCTGAAGCTAACAAAAGAGGGTGTTGATACGACCACAGTTGCG TCARCTTGCTGCTGCAGGGGTTACTOGTSCCGATAAGGACAATACTAGGOTTETAR AACTATCGTTTGAGGATAAAAACGGTAAGGTTATTGATGGTGGCTATGCACTGAAR TGGGCGACGATTTCTATGCCGCTACATATGATGAGAAAACAGGTACAATTACTGC TAAAACAACCACTTATACAGATGGTGCTGCGCGTTGCTCAAA
126. CGCGCAGATTTTGCAGCAGGCCGGTACTTCCGT TCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTA CGTGAATTCTCTAGATATCCAGCACAGTGGCGGCCGCTCATGGAAA AATTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGGCTTT CAAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTGTGGCTG TTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTTCCTA TCTCGTCAGTGGCTTCATTGAACGACCTAACGCCAGTGGGCAGAT T GGTCACTGTCAACCCTTTTGTTTCAGTGGCCACGGCCAACGCTAAG GTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTGG TGGGCAGAGGAGAACAACAGAT CAATCACCATTGGCACAAGTCTGG AAGCAGCATTGGCAAACCCTTAATAAGCTGA VLIELEPPFGDSYIVVGRGEQOINHHWHKSGSSIGKPLIS Figure 31 10000 BABS 78 5 76 pET STE2A gE311s Y amp RRI O R DRINSAKDDAAGQRIANRPTANIKG LAVQSANSTNSQSDLDST QAEITORL KV DIDLKOINSOTLGLDSLNVHGAPV Ps PETENPLOKI SRIEDSD YATEVSNMSRAQILQQAGTSVLAQANOVPQNVLSLZREFSRYPAQWAPLMDKLALKGTTY GMCTEKFSFAKNPVDTGEGTVVIELSYSGSDGPCKIPIVSVASLNDMTPVGRLVTYVNPFV ATSSANSKVLVEMEPPFGDSYIVVGRGDKQINEHWHKAGSTLGKA Figure 32 RIES 79 IEW 7 BBA MDKLALKGTTYGMCTEKFSFAKNPVDTGHGTVVIELSYSGSDGPCKIPIVSVASLND MIPVGRLVTVNPFVATSSANSKVLVEMEPPFGDSYIVVGRGDKQINHHWHKAGSTL GKA 5 77 pET STF2A JE311s EUER BOB U 7 5 RI 8 Cys ser Figure 35 CTAACAGTCTGTCGCTGCTGACCCAGAAT T TTCTGGTCTGC CCGTTTCACCGCGAAC 3T x CTCCATTGCGCAG 2 BABS 80 pET st al 7
127. CTGACCCAGARTAACCTGAA CAAATCCCAGTCCGCACTGGGCACCGCTATOGAGCCTCTGTCTTCTGSTCTGZGTA TCAACAGCGCGAAAGACGATGCGGCAGGTCAGSCGATTGCTAACCGTTTCAC AACATCARAGGTC CTCAGSCTTCCCETAACGCTAACGACGETATCTCCATTGC SCAGACCACTGAAGGCGCGCTGAACGAAATCAAC hACCTGCAGCGTGTGCGTG RAACTGGCGGTTCAGTCTGCTAACAGCACCAACTCCCAGTCTGACCTCGACTCCATC LTCACCCAGCGCCTGAACGAAATCGACCGTGTATCCGGCCAGACTCA GAAAATTGATGCCG CGCTGCGCTCTGATCTGGGTGCGGTACARAACCGTTTCAP ACCARCCTGGGCAATACCGTAAACAATCTGTCTGAAGCGCGTAGCCOT ATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCGCAGATTCT GCAGCAGGCCGZTACTTCCGTTCTGGCGCAGGCCAACCAGGTCCCGCAGAACGTGC TGTCTCTSGTTACGTATGGAAAAATTGCAGTTGAAGGGAACAACCTATGGCGTCTGT TCAAAGGCTTTCAAGTTTCTTGGGACTCCCGCAGACACAGGTCACGGCACTGTGGT GTTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTTCCTATCTCGTCAG TGGCTITCATTGAACGACCTAACGCCAGTGGGCAGATTGGTCACTGTCAACCCTTT GTTTCAGTGGCCACGGCCAACGCTAAGGTCCTGATTGAATTGGAACCACCCTTTGG AGACTCATACATAGTGGTGGGCAGAGGAGAACAACAGATCAATCACCATTGGCACA STGCTGTCTCTGTTACGTGAATTCTGCAGATATCCAGCACAGTGGCGGCCGCTCATGG AAAAATTGCACTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGGCTTTCAAGTTTCT TGGGACTCCCGCAGACACAGGTCACGGCACTGTGGTGTTGGAATTGCAGTACACTGGC ACGGATGGACCTTGCAAAGTTICCTATCTCGTCAGTGGCTTCATTGAACGACCTAACGC CAGTGGGCAGATTGGTCACTGTCAACCCTTTTGITTCAGTGGCCACGGCCAACGCTAA GGTCCTGATTGAATTGGAACCACCCTTTGGAGACTCATACATAGTGGTGGGCAGAGGA GAACAACAGATCAATCACCATTGGCACAAGTCTGGAAGCAGCATTGGCAAA Figure 13 AGTCTGGAAGCAGCATTGGCAAA ID MABS 38 370 fjB STF2AEII 7
128. CTGGAGCTGTGAART TTSGTGGCGCAARTGGTAARTCTGAAGCTTGTTACTGCTACCGATGGTAAAACTTAC TTAGCAAGCGACCTTGACAAACATARCTTCAGAACAGGCGGTGAGCTTAAAGAGGT TAATACAGATAAGACTGAARACCCACTGCAGAAAATTGATGCTGCCTTGGCACAGG TTGATACACTTCGTTCTGACCTGGGTGCGGTACAGAACCGTTTCAACTCCGCTATC ACCAACCTGGGCAATACCGTAAATAACCTGTCTTCTGCCCGTAGCCGTATCGAAGA TTCCGACTACGCGACCGAAGTCTCCAACATGTCTCGCGCGCAGATTCTGCAGCAGG CCGGTACCTCCGTTCTGGCGCAGGCTAACCAGGTTCCGCAAAACGTCCTCTCTTTA CTGCGTTAA Figure 20 EIES 63 YARRA AAGGGCAATTCGAAGCTIGAAGGTCAATTGGAATICCCTAGGACTAGTC CAGTGTGGTGGAATTCTGCAGATATCCAGCACAGTGGCGGCCGCCAGTG TGATGGATATCTGCAGAATTCGCCCTTGCGGCCGCTC Figure 21 2008 527009 2008 7 24 EIES 64 CHAT EL BACT YQVRNSTGL YH V TNDCPNSSIVYEAADAILHTPGCVPCVREGNASRCWVA MTPTVATRDGKLPATQLRRHIDLLVGS ATLCSALYVGDLCGSVFLVGQLET SPRRHWTTQGCNCSIYPGHITGHRMA WDMMMNWSPTTALVMAQLLRIPQ ALLDMIAGAHWGVLAGIA YFSMVGNW AK VLVVLLLEAGVDA Figure 22 BCP BS 65 CMAP 22 P ETHVTGGSAGHTVSGFVSLLAPGAKQNVQLINTNGSWHLNSTALNCNDSLN TGWLAGLFYHHKFNSSGCPERLASCRPLTDFDQGWGPISY ANGSGPDORPY CWHYPPKPCGIVPAKSVCGPVYCFTPSPVVVGTTDRSGAPTYSWGENDTDV FVLNNTRPPLGNWFGCTWMNSTGFTK VCGAPPCVIGGAGNNTLHCPTDCFR KHPDATYSRCGSGPWITPRCLVDYPYRLWHYPCTINYTIFKIRMYVGGVEH RLEAACNWTRGERCDLEDRDRSELSPLLLTTTQWQVLPCSFTTLPALSTGLI HLHQNIVDVQYLYGVGSSIASWAIK WEY VVLLFLLLADARVCSCLWMMLL ISQAEA Figure 23 BS 66
129. DCEPRSGIDFNEMIL MKMKKKTWLVHKQWFLDLPLPWTAGADTSEVH NYKERMVTFKVEHAKRODVTVLGSQEGAMHSAL AGATEVDSGDGNHMFAGHLKCBEVRMEKLRIKGMSYTMCSGKFSIDKEMAETQRGTTVVKVKYEGAG APCKVPIRIRDVNKERVVGRIISSTPLAENTNSVTNIELZPPFGDSYIVIGVGNSALTLHWFRKGS SIGKMFESTYRGAKRMAILGETAWDEGSVGGLFTSLGKAVHQVFGSVYTTMFGGVSWMIRILIGF LVLWIGINSRNTSMAMTCIAVGGITLFLGE Figure 74 BASS 167 Den 4 ATGCGATGCGTAGGAGTAGGARACAGAGACTTTGTGGAAGGAGTCTCAGGTGGAGCATGGGTCGACC TGGTGCTAGAACATGGAGGATGCGTCACAACCATGGCCCAGGGAAAACCAACCTTGGATTTTGAACT GACCAAGACAACAGCCAAGGAAGTGGCTCTGTTAAGAACCTATTGCA TTGAAGCCTCAATATCAAAC ATAACTACGGCAACAAGAT GICCAACGCAAGGAGAGCCTTATCTGAAAGAGGAACAGGACCAACAGT ACATTTGCCGGAGAGAT GI GGTAGACAGAGGGTGGGGCAATGGCTGTGGCTTGTTTGGAAAAGGAGG AGTTGTGACATGTGCGAAGTTTTCATGTTCGGGGAAGATAACAGGCAAT FTGGICCGAATTGAGAAC ATCATGGAGTTACAGCCATGATARCCCCCAGGTCACCATCGGTGGAAGTCAAATTGCCGGACTATGG AGAACTAACACTCGATTGTGAACCCAGGTCTGGAATTGACTTTAATGAGATGATTCTGATGAAAATG AAAAAGAAAACATGGCTCGTGCATAAGCAATGGTTTTTGGATCTGCCCCTTCCATGGACAGCAGGAG CAGACACATCAGAGGTTCACTCGAATTACAAAGAGAGAATGGTGACATTTAAGGTTCCTCATGCCAA GAGACAGGATGTGACAGTGCTGGGATCTCAGGAAGGAGCCATGCATTCTGCCCTCGCTGGAGCCACA GAAGTGGACTCCGGTGATGGAAATCACATGTTTGCAGGACATCTCAAGTGCGAAGTCCGTATGGAGA AATTGAGAATCAAGGGAATGTCATACACGATGTGTTCAGGAAAGTTTTCAATTGACAAAGAGATGGC AGAAACACAGCATGCGACAACAGTGGTGAAAGTCAAGTATGAAGGTGCTGGAGCTCCGTGTAAAGTC CCCATAGAGATAAGAG
130. E MASS NE I 7 STF2 Et pET STF2 Elli 0 01 04 10 100 1000 10000 ng ml T7 20 STF2A pET STF2AEIII Figure 47B Figure 46 VA 010 PIA EN 044 5 2 045 2 i 4 i fi M 1 NT de 1 10 100 1000 10000 i ng ml Figure 47A 1 STF2A Elll 044 050324 QC ELISA O WNE L2 0605 116 Hn i 1 20 4 i 144 i 1 00 4 L smeEQua i 1 i 424 gom j w STF2El 054 1 r1 9 080 STF2 ERI 057 11 5940 048 dos 5204 ooi 06 0 001 0 01 Oq 1 10 300 1000 0 4 4 RE nmoles 02 I oH 1 ES o S p Figure 49A 5 vw eu 7 00000 T3 4 050324 QC ELISA L2 2 2 z J 6H11 204 1204 STF2 E 014 54 oso 8 5 2 057 2 STF2A Elll 045 i 001 0 001 0 01 04 1 10 100 1000 Figure 48 nmoies Figure 49B 050324 QC ELISA 5C5 Z 7 D LIRA WNE 2 50 2 004 fex Ase ge ar STEZ Elbe 054 B 1003 1 5 2 057 D 4 1
131. ED BE RELEVANT Citation of document with indication where appropriate of the relevant passages SMITH K D ET AL Toll like receptor 5 recognizes a conserved site on flageTlin required for protofilament formation and bacterial motility NATURE IMMUNOLOGY NATURE PUBLISHING GROUP GB vol 4 no 12 December 2003 2003 12 pages 1247 1253 XP002999619 ISSN 1529 2908 the whole document INTERNATIONAL SEARCH REPORT Relevant to claim No AKIRA S ET AL Recognition of pathogen associated molecular patterns by TLR family IMMUNOLOGY LETTERS AMSTERDAM NL vol 85 2003 pages 85 95 002976689 ISSN 0165 2478 the whole document SINGH BHANU P ET AL Toll like receptors and their role in innate immunity CURRENT SCIENCE BANGALORE vol 85 no 8 25 October 2003 2003 10 25 pages 1156 1164 XP002425276 ISSN 0011 3891 the whole document OBERT M ET AL Protection of mice against 5 40 tumours by Pam3Cys and Pam3Cys conjugated with the SV40 T antigen derived peptide K 698 T 708 VACCINE BUTTERWORTH SCIENTIFIC GUILDFORD GB vol 16 no 2 3 2 January 1998 1998 01 02 pages 161 169 XP004098618 ISSN 0264 410 the whole document WO 01 40280 A INOTEK CORP 05 SALZMAN ANDREM L US MURTHY KANNEGANTI US SZABO 7 June 2001 2001 06 07 page 4 examples 1 2 WO 2005 042564 A SIDNEY KIMMEL CANCER CENT
132. ER LUSTGARTEN JOSEPH 12 May 2005 2005 05 12 pages 11 12 example II m WO 2006 040076 A JOHANNES GUTENBERG UNI MAINZ DE SCHILD HANSJOERG DE WARGER TOBIA 20 April 2006 2006 04 20 pages 11 33 Form 210 continuation of sacond shest April 2005 page 5 of 6 68 JP 2008 527009 2008 7 24 International application No PCT US2006 001623 Category Citation of document with Ctaton ot documen wita indtoston wiere appropriste ot he relevant passages where Ctaton ot documen wtmindcaton wiere appro ot he relevant passages of the relevant passages Relevant to claim No INTERNATIONAL SEARCH REPORT WO 2006 069262 A VAXINNATE CORP US POWELL THOMAS J US NAKAAR VALERIAN US SONG 29 June 2006 2006 06 29 pages 5 47 48 examples 2 4 WO 2005 077408 A VAXINNATE CORP US UNIV YALE US POWELL THOMAS J US MEDZHITOV R 25 August 2005 2005 08 25 pages 11 12 42 Form PCTASA 2i0 continuation of second sheet April 2005 page 6 of 6 69 2008 527009 2008 7 24 International application No INTERNATIONAL SEARCH REPORT PCT US2006 001623 Box Il 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 x Claims Nos because thoy relate
133. F2A EI II f 100060 1000100 TLR5 10000 000 10 000 sTF2A Elll4d 5792 Elli STF2 EL LI 1000000 VNV El STF2 EI I I STF2A EI I I STF2 EI II 39 STF2A 9 2008 527009 2008 7 24 STF2 El I LH OO Oaa a 0 L1 1 n n n gt IO UU El 1 STF2A EI LI ElI STF2A 10000 STF2 II 0010 11100 0 STF J moo
134. GAA TCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTSCTCTGCGTATCAACAGC CARATCCCAGTCCGCACTGGGCACCECTATCGAGCGTCTGTCTTCTGGTCTGCGTA GCGRAAGACGATGCGGCAGGTCAGGCGATTGCTARCCGTTTCACCGCGAACATCAARGGT TCAACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCSTTTCACCGCG CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC AACATCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGC GCGCTGAACGAAATCARCAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT GCAGACCACTGAAGGCGCGOTGAACGARATCAACAACAACCTGCAGCGTGTGZGTG RACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG ARCTGGCGGTTCAGTCTGCTAACAGCACCAACTCCCAGTCTGACCTCGACTCCATC BACGARATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGARAGTCCTGGCGCAG CAGSCTGAAATCACCCAGCGCCTGARCGAAATCGACCGTGTATCCGGCCAGACTCA GACARCACCCTGACCATCCAGGTTGGCGCCAACGACGGTGRARCTATCGATATCGATCTG GTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCTGACCATCCAGGTTGGCG RAGGA Gnt CRACTCTCRGACCCTGGGTCTGGACTCACTGAACGTGCAGARAGEGTATGAT CCAACGACGGTGARACTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTC SIGBARGATACAGG CARCERRAGCTTATGCCAATAATGGTACTACACTGGATGTA GGTCTGGACTCACTGAACGTGCATGGAGCGCCGGTGGATCCTSCTAGCCCATGGAC CGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCT CTGATCTGGCTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAAT AC AAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGAC CGAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCGTTC TGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGTGARTTCTGC AGATATCCAGCACAGTGGCGGCCGCTCATGGACAAACTGGCTCTGAAAGGCACAAC CTATGGCATGTGTACAGAAAAATTCTCGTTCGCGAAAAATCCGGTGGACACTGGTC
135. GGATTTTICGGGAAGGGAAGCATTGACACATGTGCAAAATTCTCCTGCACCAGTAA AGCGATTGGGAGAACAATCCAGCCAGAAAACATCAAATACAAAGTTGGCATTTTTGTGCATGGAACCACCACTT CGGAAAACCATGGGAATTATTCAGCGCAAGTTGGGGCGTCCCAGGCGGCAAAGTTTACAGTARCACCCAATGCT CCTTCGGTAGCCCTCAAACTTGGTGACTACGGAGAAGTCACACTGGACTGTGAGCCAAGGAGTGGACTGAACAC TGAAGCGTTTTACGTCATGACCGTGGGGTCAAAGTCATTTCTGGTCCATAGGGAGTGGTTTCATGACCTCGCTC TCCCCTGGACGTCCCCTTCGAGCACAGCGTGGAGAAACAGAGAACTCCTCATGGAAT TTGAAGGGGCGCACGCC ACAAAACAGTCCGTTGTTGCTCTTGGGTCACAGGAAGGAGGCCTCCATCATGCGTTGGCAGGAGCCATCGTGGT GGAGTACTCAAGCTCAGTGATGCTTAACATCAGGCCACCTGAAATGTAGGCTGAAAATGGACAAACTGGCTCTGA AAGGCACAACCTATGGCATGTGTACAGAAAAATTCTCGTTCGCGAAAAATCCGGTGGACACTGGTCACGGARACA GTTGTCATTGAACTCTCCTACICTGGGAGTGATGGCCCCTGCAAAATTCCGATTGTTTCCGTTGCGAGCCTCAA TGACATGACCCCCGTTGGGCGGCTGGTGACAGTGAACCCCTTCGTCGCGACTTCCAGTGCCAACTCARAGGTGC TGGTCGAGATGGAACCCCCCTTCGGAGACTCCTACATCGTAGTTGGAAGGGGAGACAAGCAGATCAACCACCAT TGGCACAAAGCTGGAAGCACGCTGGGCAAGGCC Figure 76 BABS 171 7 z BEN FNCLGMGNRDFIEGASGAAWVDLVLEGDSCLTIMANDKPTLDVRMINIEASOLAEVRSYCYHASVTDISTV ARCPTTGEAHNEKRADSSYVCKQGETDRGWGNGCGEFGKGSIDTCAKFSCTSKAIGRTIQPENIKYKXVGIF VHGTTTSENHGN YSAQVGASQAAKFTVT PNAPSVALKLGDYGEVT LDCE PRSGLNT EAFYVMTVGSKSELV HREWFHDLALPWTSPSSTAWRNRELLMEFEGAHATKOSVVALGSOEGGLHHALAGAIVVEYSSSVMLTSGR LKCRL MDKLALKGTTYGMCTEKFSFAKNPVDIGRGTVVIELSYSGSDGPCKIPIVSVASLNDMTPVGRLV TVNPFVATSSANSKVLVEMEPPFGDSYIVVGRGDKQINHHWHKAGSTLGKA Figure 77 2008 527009 A 2008 7 24 00000 BASS 175
136. GTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGC GCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCCTGTGCGTGAACTGGCGGTTCAGTCTGCT AACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG AACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTIGGCGCCAACGACGGTGAAACTATCGATATCGATCTG AAGCAGATCAACTCTCAGACCCTGGCTCTGGACTCACTGAACGTGCAGAAAGCGTATGAT GTGAAAGATACAGCAGTAACAACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTA TCGGGTCTTGATGATGCAGCTATTAAAGCGGCTACGGGTGGTACGAATGGTACGGCTTCT GTAACCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGGT GGCTTTACTGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGAC GGTACAGTAACCCTTGCGGCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACT AAAACAGAAGTACAGGAGTTAAAAGATACACCGGCAGTTGTITTCAGCAGATGCTAAAAAT GCCTTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATG TCTTATACCGATAAAAATGGTAAGACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGAT AAGTATTACGCCGCAGATTACGATGAAGCGACAGGACCAATTAAAGCTAAAACCACAAGT TATACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AAAACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCAT GATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAACCCGCTG CAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTA CAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAA GCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCG CAGATTTTGCAGCAGGCCGGTACTICCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAAC GTGCTGTCTCTGTTAC
137. GTITCAACTGCCTTGGAATGAGCAACAGAGACTTCTTGGAAGGA GTGTCTGGAGCAACATGGGTGGATTTGGTICTCGAAGGCGACAGCTGCGTGACTATCATG ICTAAGGACAAGCCTACCATCGATGTGAAGATGATGAATATGGAGGCGGCCAACCTGGCA GAGCTCCGCAGTTATTGCTA TTTGGCTACCGTCAGCGATCTCTCCACCAAAGCTGCGTGC CCGACCATGGGAGAAGCTCACAATGACAAACGTGCTGACCCAGCTTTTGTGTGCAGACAA CGAGTGGTGGACAGGGGCTGGGGCAACGGCTGCGGACTA TTGGCAAAGGAAGCATTGAC ACATGCGCCAAATTTGCCTGCTCTACCAAGGCAATAGGAAGAACCATCTTGAAAGAGAAT ATCAAGTACGAAGTGGCCATTTTTGTCCATGGACCAACTACTGTGGAGTCGCACGGAAAC TACTCCACACAGGTTGGAGCCACTCAGCCAGGGAGATTCAGCATCACTCCTGCAGCGCCT TCATACACACTAAAGCTTGGAGAATATGGAGAGGTGACAGTGGACTGTGAACCACGGTCA GGGATTGACACCAATGCATACTACGTGATGACTGTTGGAACAAAGACGTTCTTGGTCCAT CGTGAGTGGTTCATGGACCTCAACCTCCCTTGGAGCAGTGCTGGAAGTACTGTGTGGAGG AACAGAGAGACGTTAATGGAGTTTGAGGAACCACACGCCACGAAGCAGTCTGTGATAGCA TTGGGCTCACAAGAGGGAGCTCTGCATCAAGCTTTGGCTGGAGCCATTCCTGTGGAATTT TCAAGCAACACTGTCAAGTTGACGTCGGGTCATTTGAAGTGTAGAGTGAAGATGGAAAAA TTGCAGTTGAAGGGAACAACCTATGGCGTCTGTTCAAAGCCTTTCAAGTTTCTTGGGACT CCCGCAGACACAGGTCACGGCACTGTGGTGTTGGAATTGCAGTACACTGGCACGGATCGA CCTTGCAAAGTTCCTATCTCGTCAGTGGCTTCATTGAACGACCTAACCCCAGTGGGCAGA TTGGTCACTGTCAACCCTTTTGTTTCAGTGGCCACGGCCAACGCTAAGGTCCTGATTGAA TTGGAACCACCCTTTGCAGACTCATACATAGTGGTGGGCAGACGAGAACAACAGATCAAT CACCATTGGCACAAGTCTGGAAGCAGCATTGGCAAA Figure 65 RASS 160 Den 1 7 MRCVGIGNRDEVEGLSGATWVDVVLEHGSCVTTMAKNKPTDDIELDKTEVTNPAVLRKLCIEAKI SNTTTDSRCPTOGEATLVEEQDANFVCRRTFVDRGWGNGCGDFGKG
138. GTTCTGGCGCAGG GTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGC CTRACCASGTCCCGCAGAACGTGCTGTCTCTGT TACGTGARTTCAGCAGATATCCAGCACH CTAACCAGGTCCCGCAGAACCTGCTG TCICTCTTACGTGARTICAGCAGATATCCAGCACA GTGGCGGCCGCTCAAAGGAATGAGTTATGCAATGT ARATACATTIGTATTARAARAR STGGCGGCCGCTCAAGGGAATGTCATACACGATGTGTAGTGGTAAATTCTCTATAGACAAR AAGTGARACACAACATGGRACAATATTAATAARAGTAGAATATAAAGGAGAAGATG GAGATGGCAGAGACACAACACGGGACAACCGTCGTGAAGGTTAAGTATGAAGGAGCTGGCG CATSTAARATACCAT TASTACAGBAGAT GGACAAGGARAAGCACATARTGGAACATT CACCGTGCRAASTACCCATCGAAATTAGGGATGTAAACAAAGAGAAGGTCGTTGGSCGTAT I TTAGCTCAACCCCACTTGCGGAAAATACTAATTCTGTAACGAACATAGAGTTGGAACCA AACCACCATTTGGAGAAAGT CTAATAGGAATAGGAGATAAAGCATTAAAA CCCTTTGGTGATAGCTATATAGTTATTGGTGTGGGCAATAGTGCCTTAACTCTACATTGGT ATAAATTGGTATAGAAAAGGAAGTAGTATAGGCAAAA TIAGAARAGGATCCTCGATCGGGAAA Figure 41 Figure 43 00000 86 pET sTrF2a Den4 ELIZ PS BBS 174 74 27 MAQVINTNSLSLLTONNLNXSOSALGTAZERLSSGLRINSAKDDAAGQAIANRFTAN SACTHLENRDFVTCTQGTTRVTLVLELGCCVTZTAEGKPSMDVWLDSIYOENPAKTAEY LTQASRKANDGISIAQTTEGALNEINNNLORVRELAVOSANSTNSOSDLDSIQAEITQRAL CLEAKLSDTKVARRCPTMCPATLTEEHOSGTVCKRDQSDRGWGNHCGLECKGSiVTCVK NEIDRVSGOTQFNGVE WTLTIQVGANDGETIDIDLEQINSOTLGLDSLNVESAPV VACEAKKKAIGEVYDANKIVYTVKVEPHTGDYVAANETHSGRKTASFTVSSERTILTMG DPASPWTENPLORIDAALAQVDALRSDLGAVONRENSATTNLGNTVNNLSEARSRIEDSD DYGDVP
139. I QHSGGRQCDGY LQNSPL RPL 62 EFSRYPAQWRPL 75 mE 1000000 Pa nBCys Pan2Cys 000 000010060 lt Pan2Cys DB D D JP 2008 527009 2008 7 24 23 10 lt PANP 5 1110 20 PAMP PAMP
140. JP 2008 527009 2008 7 24 19 Fe 18 PT RRA 553 2008 527009 P2008 527009A 43 S36 SEHLOSETHI 248 2008 7 24 51 Int CI F va k 3 CO7K 14 18 20601 CO7K 14 18 ZNA 4BO24 C12N 15 09 2006 01 C12N 15 00 4C084 CO7K 19 00 206 01 CO7K 19 00 40085 CO7K 14 195 2006 01 CO7K 14 195 4HO45 A61K 39 00 2006 01 AGIK 39 00 BERK RAR 4 73 unum 882007 551469 P2007 551469 22 2006 1 19 mak H FR 194F8 A 31A 2007 8 31 ARER 52006 001623 BRAGS W02006 078657 EE EZ 184F7F 27H 2006 7 27 21 71 HERA 507203526 86 85 86 87 87 31 60 645 170 32 33 31 32 33 31 2 9 gt 97 08 512 v X Fry 2 247 3 TAREA 100095832 jf E 72 AOD A Vrd 0644 3 Kokyp 1 54 72 PAV NVUIPY 0651 4 gt 47 33 19 2005 1 19 US 60 653 405 2 3EBR177E2H 15 2005 2 15 9 5 60 704 160 32 29H 2005 7 29 33
141. KMEKLOLKGT BABS 131 E33 TSGHLKCRVKMEKLOLKGTT BABS 132 E34 SGHLKCRVKMEKLOLKGTTY BABS 133 B35 GHLKCRVKMEKLOLKGTTYG BABS 134 B36 HLKCRVKMEKLOLKGTTYGV BASS 135 E37 LKCRVKMEKLOLEGTTYGVC BABS 136 E38 KCRVKMEKLOLKGITYGVCS BABS 137 E39 CRVKMEKLOLKGTTYGVCSK BABS 138 E40 RVKMEKLQLKGTTYGVCSKA BABS 139 41 VKMEKLQLKGTTYGVCSKAF BABS 140 E42 KMEKLOLKGTTYGVCSKAFK BABS 141 E43 MEKLOLKGTTYGVCSKAFKE BAGS 142 B44 EKLOLKGTTYGVCSKAFKEL RAGS 143 E45 KLQLKGTTYGVCSKAFKFLG BAGS 144 E46 LOLKGTTYGVCSKAFKFLGT 145 E47 QLKCTTYGVCSKAFKFLGTP BABS 146 E48 LKGTTYGVCSKAFKFLGTPA RES 147 E49 KGTTYGVCSKAFKFLGTPAD RAGS 148 E50 GTTYGVCSKAPKFLGTPADT BABS 149 E51 TTYGVCSKAFKFLGTPADTG BASS 150 E52 TYGVCSKAFKFLGTPADTGH BABS 151 Figure 60 BASS 153 5 2 75 7 BEN MAQVINTNSLSLLTONNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITORE NEIDRVSGOTOFNGVKVLAQDNTLTiQVGANDGETIDIDLKQINSQTLGLDSLNVQXAYD VKDTAVTTKAYANNGTTLDVSGLDDAAIKAATGGTNGTASVTGGAVAKFDADNNKYFVTIG GFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATTKTEVOELKDTPAVVSADAKN ALIAGGVDATDANGAELVKMSYTDKNGKTIEGGYALKAGDKYYAADYDEATGAIKAKTTS YTAADGTTKTAANQLGGVDGKTEVVT I DEKTYNASKAAGHDFKAQPELAEAAAKTTENPL QKIDAALAQVDALRSDLGAVONRENSAITNLGNTVNNLSEARSRIEDSDYATEVSNMSRA QILOOAGTSVLAQANQVPONVLSLLRLEGSIGAASMEFCFDVFKELKVHHANENIFYCPI AIMSALAMVYLGAKDSTRTOINKVVRFDKLPGFGDSIEAOCGTSVNVHSSLRDILNQITK PNDVISFSLASRLYAEERYPILPEYLOCVKELYRGGLEPINFOTAADOARELINSWVESQ TNGIIRNVLOPSSVDSQTAMVLVN
142. LLCRVASGVDLAQTVILELOKTLEHLPTAWQVHRDWFNDLALPWKHEGAQOWN YATEZVSNMSRAQILQOAGTSVLAQANQVPONVLSLLREFSRYPAQWRPLKGMSYTMCSGK NAERLVEFGAPHAVKMDVYNLGDQTCVLLIKSLAGVPVAHIDGTKYHLKSGHVTCEVGLE FSID NIELES MAETQHGTTVUKVKYEGAGAPCKVPIEIRDVNKERVVGRIISPTPFAENTNSVT KLKMKGLTYTMCDKTKFAWKRTPTDSGHDTVVMEVTFSGTKPCRIPVRAVABGSPDVNV LDSYIVIGVGDSALTLEWFRK AMLITPNPTIENNGGGFIEMQLPPGDNIIYVGELSHQWFQKGSSIGRVFORTRKCIERL TVIGEHAWDPGSTGGFLTSVGKALHTVLGGAFNSIFGGVGFLPKLLLGVALAWLGLNMR NPTMSMS F LLAGGLVLAMTLGVGA Figure 42 Figure 44 56 2008 527009 2008 7 24 89 39 87 JLr2 4 JLZX T DLADB ZATAZSTS BEE GATWVDLVLEGDSC MSKDKPT I DVKMMND LAEVRSYC 60 3500 H ROGVVDRGWGNGCGLFGKGSIDTCAKFA 220 Ci GPTTVESHGNYSTQVGATQA AAPSYTLKL 180 3608 VMTVGTKTFLVHREWFMDLNLPWSSAGSTVWANRETLM 240 i TEE 5792 010 EFEEPEATKQSVIALGSQEGALHOALAGAIPVEFSSNTVKLTSGHLKCRVKMEKLOLXGT 300 8 054 TYSVCSKAFKFLGTPA TVVLELOYTGTDGPCKVPISSVAEZLNDLTEVGRLVTVNP 360 29003 57 FVSVATANAKVLIELEPPFGDSYIVVGRGEQOINEHWHKSSSSIGK 406 l 2000 4 y Ep 1500 Figure 45 oe 1 1000 4 800 4 M
143. MERLOLKOTTYGVCSK RASS 108 2 21 9 CRVKAEKLOLKGTTYGVCSK MABS 109 E2 21 10 CRVKMAKLQLKGTTYGVCSK MASS 110 E2 21 11 CRVKMEALOLKGTTYGVCSK BER 111 E2 21 12 CRVKMBKAQLKGTTYGVCSK RASS 112 E2 21 13 CRVKMEKLALKGITYGVCSK BASS 113 52 21 14 CRVKMEKLOAKGTTYGVCSK BABS 114 E2 21 15 CRVKMEXLOLAGTTYGVCSK BABS 115 E2 21 16 CRVKMEKLQLKATTYGVCSK BABS 116 E2 21 17 CRVKMEKLOLKGATYGVCSK BABS 117 E2 21 18 CRVKMEKLOLKGTAYGVCSK BABS 118 E2 21 19 CRVKMEKLOLKGTTAGVCSK EUER 119 E2 21 20 CRVKMEKLOLKGTTYAVCSK BABS 120 E2 21 21 CRVKMEKLOLKGTTYGACSK BABS 121 E2 21 22 CRVKMEKLQLKGTTYGVASK RASS 122 E2 21 23 CRVKMEKLQLKGTTYGVCAK RASS 123 E2 21 24 CRVKMEKLOLKGTTYGVCSA BABS 124 Figure 57 77 FR IgG 0 7 4 0 6 1 9 54 4 04 503 0 2 4 e e 9 1 J Pd e 8 s M 9 T PBS Pam3Cys WNVO0L RE Figure 58 FREUAWALYAA TFSAVAGEFALY I III F442 280 297 4 TII 298 406 281 307 WN LTSGHLKCRVKMEKLQLKGTTYGVCSK ENES 88 JE LTSGHLKCRLKMDKLALKGTTYGMCTE ENES 89 IFAGHLKCRLKMDKLTLKGMSYVMCTG ENES 90 D2 LFTGHLKCRLRMDKLOLKGMSYSMCTG ENES 91 D3 IFAGHLKCRLKMDKLKLKGMSYAMCLN 92 D4 MFAGHLKCKVRMBKLRIKGMSYTMCSG BAS 93 XXXGHLKCRxxMxKLxLKGxxYxxOxx BABS 94 GHLKCRMKLLKGYC 95 Figure 59 BABS 152 STF2 0VA HERI ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAA TCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCOGTATCAACAGC
144. PPFGDSYIVVGRGEQOIN HHWHKSGSSIGK Figure 66 RWS 57 1 12 ARREN TTCAACTGCCTTGGAATGAGCAACAGAGACTTCTTGGAAGGAGTGTCTGGAGCAACATGG GTGGATTTGGTTCTCGAAGGCGACAGCTGCGTGACTATCATGTCTAAGGACAAGCCTACC ATCGATGTGAAGATGATGAATATGGAGGCGGCCAACCTGGCAGAGGTCCGCAGTTATTGC TATTTGGCTACCGTCAGCGATCTCTCCACCAAAGCTGCGTGCCCGACCATGGGAGAAGCT CACAATGACAAACGTGCTGACCCAGCTTTTGTGTGCAGACAAGGAGTGGTGGACAGGGGC TGGGGCAACGGCTGCGGACTATTTGGCAAAGGAAGCATTGACACATGCGCCAAATTTGCC TGCTCTACCAAGGCAATAGGAAGAACCATCTTGAAAGAGAATATCAAGTACGAAGTGGCC ATTITTGTCCATGGACCAACTACTGTGGAGT CGCACGGAAACTACTCCACACAGGTTGGA GCCACTCAGGCAGGGAGATTCAGCATCACTCCTGCAGCGCCTTCATACACACTAAAGCTT GGAGAATATGGAGAGGTGACAGTGGACTGTGAACCACGGTCAGGGATTGACACCAATGCA TACTACGTGATGACTGTTGGAACAAAGACGTTCTTGGTCCATCGTGAGTGGTTCATGGAC CTCAACCTCCCTTGGAGCAGTGCTGGAAGTACTGTGTGGAGGAACAGAGAGACGTTAATG GAGTTIGAGGAACCACACGCCACGAAGCAGTCTGTGATAGCATTGGGCTCACAAGAGGGA GCTCTGCATCAAGCTTTGGCTGGAGCCATTCCTGTGGAATTTTCAAGCAACACTGTCAAG TTGACGTCGGGTCATTTGAAGTGTAGAGTGAAGATGGAAAAATTGCAGT TGAACGGAACA ACCTATGGCGTCTGTICAAAGGCTTTCAAGTTICTTGGGACTCCCGCAGACACAGGTCAC GGCACTGTGGTGTTGGAATTGCAGTACACTGGCACGGATGGACCTTGCAAAGTTCCTATC TCGTCAGTGGCTICATTGAACGACCTAACGCCAGTGGGCAGATTGGTCACTGTCAACCCT TTTGTTTCAGTGGCCACGGCCAACGCTAAGGTCCTGATTGAATTGGAACCACCCTTTGGA GACTCATACATAGTGGTGGGCAGAGGAGAACAACAGATCAATCACCATTGGCACAAGTCT GGAAGCAGCATTGGCAAA Figure 67 60 BABS 158 STF2 E BE ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAA TCCCA
145. QVDALRS DLGAVONRFNSAITNLGNTVNNLS E IEDSDYATEVSNMSRAQILOOAGTSVLAQANQOVPONVLSLL LMEKLOLKGTTYGVCSKAFKFLGTPADTGHGTVV LELQYTGTDGPCKVPISSVASLNDLTPVGRLVTVNPFVSVATANAK VLIELEPPFGDSYIVVGRGEQOINEBWHKSGSSIGKPLIS Figure 12 35 STF2 EHI STF2 HEA BTGGCACAAGTAATCAACACTAACAGTCTGTCECTGCTGACCCAGAATARCCTGAACAAR TCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGC GCGAAAGACGATGCGGCAGGTCAGGCG SCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT AACAGCACCAACTCCCACTCTGA CTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG AACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTG AAGCAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCAGAAAGCGTATGAT GTGAAAGATACAGCAGTAACAACGAAAGCTTATGCCAATAATGCGTACTACACTGGATGTA TCGGGTCTTGATGATGCAGCTATTAAAGCGGCTACGGGTGGTACGAATGGTACGGCTTCT GTAMCCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGOT GGCTTTACTGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCT LCTGAC GCTACAGTAACCCTTGCGGCTGGCGCAACTAARACCACAATGCCTGCTGGTGCGACAACT ARAACAGAACTACAGGAGTTAAAAGATACACCGGCAGTTCTTTCAGCAGATGCTAAAAAT GCCTTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATG TCTTATACCGATAAAAATGCTAAGACARTTGAAGGCGGTTATGCGCTTAAAGCTGGCGAT ATTACGCCGCAGATTACGATGARGCGACAGGAGCARTTAAAGCTAAAACTACAAGT TATACTGCTGCTGACGGCACTACCARA
146. SDLITCAKFKCVTKLEGKTA QYENLKYSVIVTVETGDQHQVGNETTEEGTTATITPQAPTSEIOLTDYCTLTLDCSPRTGLDENE MVLLTMKKKSWLVHKQWFLDLPLPWTSGALTSQETWNRODLLVTFKTAHAKKOEVVVLGSOEGAM ETALTGATEIOTSGTTTIFAGHLKCRLKMDKLTLKGMSYVMCTGSFKLEKEVAETQHUGTVLVQVK YEGTDAPCKIPFSTODEKGATONGRLITANPIVIDKEKPVNIZAEPPFGESYIVVGAGEKALKLS WFKKGSSIGKMPEATARGARRMAILGDTAWDFGSTGGVETSMGKLVHOVEGTAYGVLFSGVSWTM KIGIGILLTWLGLNSRNTSLSVMCIAVGMVTILYLGVMVQA Figure 68 BABS 161 1 HEEJ ATGCGATGCGTGGGAATAGGCCAACAGAGACTTCGTGGAAGGACTGTCAGGAGCAACATGGGTGGAT GTGGTACTGGAGCATGCAAGTTGCGTCACCACCATGGCAAAAAACAAACCAACACTGGACATTGAA CTCTTGAAGACGGAGGTCACAAACCCTGCAGTTCTGCGTAAATTGTGCATTGAAGCTAAAATATCA AACACCACCACCGATTCGACATGTCCAACACAAGGAGAAGCCACACTGGTGGAAGAACAAGACGOG AACTTTGTGTGCCGACCAACGTTCGTGGACAGAGGCTGGGGCAATGGCTGTGGGCTATTCGGAAAR GGTAGTCTAATAACGTGTGCCAAGTTTAAGTGTGTGACAAAACTAGAAGGAAAGATAGCTCAATAT GABARCCTAAAATATTCAGTGATAGTCACCGTCCACACTGGAGATCAGCACCAGGTGGGAAATGAG ACTACAGAACATGGAACAACTGCAACCATAACACCTCAAGCTCCTACGTCGGAAATACAGCTGACC GACTACGGAACCCT TACATTAGATTGTTCACCTAGGACAGGGCTAGATTT TAACGAGATGGTGTTG CTGACAATGAAAAAGAAATCATGGCTTGTCCACAAACAGTGGTTTCTAGACTTACCACTGCCTTGG ACCTCTGGGGCTTTAACATCCCAAGACACTTGGAACAGACAAGATTTACTGGTCACATTTAAGACA GCTCATGCAAAGAAGCAGGAAGTAGTCGTACTAGGATCACAAGAAGGAGCAATGCACACTGCGCTG ACTGGAGCGACAGAAATCCAAACGTCAGGAACGACAACAATTTTCGCAGGACACCTAAAATGCACA CTAAAAATGGACAAACTAACTTTAAAAGGGATGTCATATGTGATGTGCACAGGCTCATTCAACTTA GAGAAAGAAGTGGCTGAGACCCAGCATGGAACTGTTCTGCTGCAGGTTAAATATGAAGGAACAGAC GCACCATGCAAGATTCCCTTT
147. STF20 STF2A 000 STF2 II STF2A Ell 000 HEK293 11 8 STF2A STF2 El I TLR 50 000000 5 prtoeindoOooddo 2 AE DI TED GET Dd 5 2 4 TLR 50 0000000 BECHER 5 2 00000 0000 JE pe pe ew JE PES a 2 JEII4 0000 OJE 1 0000000000000 0 245 2 000000 pETSTF2A 10 20 30 40 50 43 JP 2008 527009 2008 7 24 JELILI PTG BLR D iuudgpmuaguuuululdgdagalulliuldsuuiuuiluliululbl lu lu
148. T GAGAACCTCAAATACACTGTCATCATCACAGTGCACACAGGAGACCAACACCAGGCTGGGAAATGAC ACGCAGGGAGTCACGGTTGAGATAACACCCCAGGCATCAACCGTTGAAGCTATCTTGCCTGAATAT GGAACCCTTGGGCTAGAATGTTCACCACGGACAGCGTTTGGATTTCAACGAAATGATTTTATTGACA ATGAAGAACAAAGCATGGATGGTACATAGGCAATGGTTCTTTGACCTACCCCTACCATGGACATCA GGAGCTACAACAGAGACACCAACTTGGAACAGGAAAGAGCTCCTTGTGACATTCAAGAATGCACAT GCAAAAAAGCAAGAAGTAGTTGTCCTTGGAT CGCAAGAGGGAGCAATGCACACAGCGCTGACAGGA GCTACAGAGATTCAAAACTCAGGAGGTACAAGCATTTTTGCGGGGCACTTGAAATGTAGACTTAAG ATGGACAAATTGGAACTCAAGGGGATGAGCTATGCAATGTGCTTGAATACCTTTGTGTTGAAGAAA GAAGTCTCTGAAACGCAGCATGGGACAATACTCATCAAGGTTGAGTACAAAGGGGAAGATGCACCT TGCAAGATTCCTTTCTCCACAGAGGATGGACAAGGGAAAGCTCACAATGGTAGACTGATCACAGCC AACCCAGTGGTGACCAACAAGGAGGAGCCTGTCAACATTGAGGCTGAACCTOCTTTTGGGGAAAGT AACATAGTGATTGGGATTGGAGACARAGCCTTGAAAATTAACTGGTACAAGAAGGGAAGCTCGATT GGAAAGATGTTCGAGGCT ACTGCCAGAGGTGCAAGGCGCATGGCCATCTTGGGAGACACAGCCTGG GATTTTGGTTCAGTGGGTGGTGTTCTGAATTCATTACGGAAARATGGYACACCAAATATTCGGAAGT GCTTACACAGCCCTGITTAGTGGAGTCTCATGGATAATGAARATTGGAATAGGTGTCCTCTTAACC TGGATAGGGTTGAATTCAAAAAACACTTCCATGTCATTTTCATGCATTGCGATACGAATTATTACA CTCTATCTGGGAGCCGTGGTACAAGCT Figure 73 BASS 170 JE REEN TTTAATTGTCTGGGAATGGGCAATCGTGACTTOATAGAAGGAGCCAGTGGAGCCGCTTGGGTGACTTGGTGCTA GAAGGAGACAGCTGCTTGACAATCATGGCAAACGACAAACCAACATTGGACGTCCGCATGATTAACATCGAAGC TAGCCAACTTGCTGAGGTCAGAAGTTACTGCTATCATGCTTCAGTCACTGACATCTCGACGGTGGCTCGGTGCC CCACGACTGGAGARGCCCACAACGAGAAGCGAGCTGATAGTAGCTATGTGTGCAAACAAGGCTTCACTGACCGCT GGGTGGGGCAACGGATGT
149. TCGACCCAAGATGAGAAAGGCAGCAACCCAGAATGGGAGATTAATA ACAGCCARCCCCATAGICACTGACAAAGAAAAACCAGTCAATATTGAGGCAGAACCACOCTTTGOGT GAGAGCTACATCGTGGTAGGAGCAGGTGAAAAAGCTTTGAAACTAAGCTCGTTCAAGAAAGGAAGC AGCATAGGGAAAATGTTTCAAGCAACTGCCCGAGGAGCACGAAGGATGGCCATTCTGGGAGACACC GCATGGGACTTCGGTTCTATAGGAGGAGTGTTCACGTCTATGGGAAAACTGGTACACCAGGTITTTT GGAACTGCATATGGAGTTTTGTTTAGCGGAGTTTCTTGGACCATGAAAATAGGAATAGGGATICTG CTGACATGGCTAGGATTAAATTCAAGGAACACGTCCCT TCGGTGATGTGCATCGCAGTTGGCATG G TCACACTGTACCTAGGAGTCATGGTTCAGGCA Figure 69 2008 527009 2008 7 24 BASS 162 Den 2 73 BEA MRCIGMSNRDEVEGVSGGSWVDIVLEHGS CVT TMAKNKPTLDFELIKTEAKQPATLRKYC IEAKLTNTTTESRCPTQGEPSLNEEQDKRFVCKHSMVDRGWGNGCGLFGKGGIVTCAMFR CKKNMEGKVVOPENLEYTIVITPHSGEEHAVGNDTGKHGKEIKITPQSSTTEAELTGYGT VIMECSPRTGLDFNEMVLLOMENKAWLVHROWFLDLPLPWLPGADTQGSNWIOKETLVTF KNPHAKKQDVVVLGSOEGAMHTALTGATEIQMSSCNLLFTGHLKCRLRMDKLOLKGMSYS MCTGKFKVVKEIAETOHGTIVIRVOYEGDGSPCKIPFEIMDLEKRHVLGRLITVNPIVTE KDSPVNIBAEPPFGDSYIIIGVEPGOLKLNWFKKGSSIGQMFETTMRGAKRMAILGDTAW DFGSLGGVFTSIGKALHQVFGATYGAAFSGVSWTMKILIGVIITWIGMNSRSTSLSVTLV LVGIVTLYLGVMVQA Figure 70 00000 BAS 163 2 HERH ATGCCTTGCATAGGAATGTCAAATAGAGACTTTGTGGAAGGGGTTTCAGGAGGAAGCTGGGTTGAC ATAGICTTAGAACATGGAAGCTGTGTGACGACGATGGCAARAAACAAACCAACATTGGATTTTGAA CTGATAAAAACAGAAGCCAAACAGCCTGCCACCCTAAGGAAGTACTGTATAGAGGCAAAGCTAACC AACACAACAACAGAATCTCGCTGCCCAACACAAGGGGAACCCAGCCTAAATGAAGACCAGGACAAA AGGITCGTCTGCAAACACTCCATGGTAGACAGAGGATGGGGAARATGGATGTGGACTATTTGGAAAG GGAGCCAT
150. TGTGACCIGTGCTATGTTCAGATGCAAAAAGAACATGGAAGGAAAAGTTGTGCAACCA GAAAACTTGGAATACACCAT TGTGATAACACCTCACTCAGGGGAAGAGCATGCAGTCGGAAATGAC ACAGGAAAACATGGCAAGGAAATCARAATAACACCACAGAGTTCCACCACAGAAGCAGAATTGACA CTGCAGATGGAAAA AA amp AGOTTGGCTGGTGCACAGGCAATGGTTCCTAGACCTGCCGTTACCATGG TTGCCCGGAGCGGACACACAAGGGTCAAATTGGATACAGAAAGAGACATTGGTCACTTTCAAAAAT CCCCATGCGAAGAAACAGGATGTTGTTGTTTTAGGATCCCAAGAAGGGGCCATGCACACAGCACTT ACAGGGGCCACAGAAATCCAAATGTCATCAGGAAACTTACTCTTCACAGGACATCTCAAGTGCAGG CTGAGAATGGACAAGCTACAGCTCAAAGGAATGTCATACTCTATGTGCACAGGAAACTTTAAAGTT GTGAAGGARATAGCAGAAACACAACATGGAACAATAGTTATCAGAGTGCAATATGAAGGGGACGCC TCTCCATGCAAGATCCCTTTTGAGATAATGGATTTGGAAAAAAGACATGTCTTAGGTCGCCTGATT ACAGTICAACCCAATTGTGACAGAAAAAGATAGOCCAGTCAACATAGAAGCAGAACCTCCATTCGGA GACAGCTACATCATCATAGGAGTAGAGCCGGGACAACTGAAGCTCAACTGGTTTAAGAAAGGAAGT TCTATCGGCCAAATGTTTGAGACAACAATGAGGGCGGCGAAGAGAATCGCCATTTTAGGTGACACA GCCTGGGATTTTGGATCCTTGGGAGGAGTGTTTACATCTATAGGAAACGCTCTCCACCAAGTCTTT GGAGCAATCTATGGAGCTGCCTICAGTGGGCTITCATGGACTATGAABATCCTCATAGGAGTCATT ATCACATGGATAGGAATGAATTCACGCAGCACCTCACTGTCTGTGACACTAGTATTGGTGGGAATT GTGACACTGTATTTGGGAGTCATGGTGCAGGCC Figure 71 00000 166 Den 4 7 7 MRCVGVGNRDFVEGVSGGAWVDLVLEHGGCVTTMAQGKPTLDFELTKTTAKEVALLRTYCIEASIS NITTATRCPTOGEPYLKEEQDOOYICRRDVVDRGWGNGCGILFGKGGVVTCAKFSCSGKITGNLVRI ENLEYTVVVTVHNGDTHAVGNDTSNHGVTAMITPRSPSVEVKLPDYGELTL
151. TH SCIENTIFIC GUILDFORD GB vol 20 no 21 22 21 June 2002 2002 06 21 pages 2772 2780 XP004357801 ISSN 0264 410X the whole document BEASLEY DAVID W C ET AL Identification of neutralizing epitopes within structural domain IIT of the West Nile virus envelope protein JOURNAL OF VIROLOGY vol 76 no 24 December 2002 2002 12 pages 13097 13100 XP002425273 ISSN 0022 538 the whole document CRILL W D ET AL Monoclonal antibodies 21 23 that bind to domain III of dengue virus E 37 38 glycoprotein arethe most efficient 63 65 blockers of virus adsorption to Vero 69 70 cells 72 73 JOURNAL OF VIROLOGY THE AMERICAN SOCIETY 76 78 80 FOR MICROBIOLOGY US vol 75 no 16 August 2001 2001 08 pages 7769 7773 XP002982315 ISSN 0022 538X the whole document Fom PCTASA 210 continuation of second sheet April 2005 page 3 of 6 66 JP 2008 527009 2008 7 24 International application No PCT US2006 001623 C Continustion DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with Indication where appropriate of the relevant passages WU S C ET AL The domain III fragment of Japanese encephalitis virus envelope protein mouse immunogenicity and liposome adjuvanticity VACCINE BUTTERWORTH SCIENTIFIC GUILDFORD GB vol 21 no 19 20 2 June 2003 2003 06 02 pages 2516 2522 XP004424163 ISSN 0264 410X the whole document BHARDWAJ S ET AL Biop
152. TPVGRLVTVNPFVSVATANAK VLIELEPPFGDSYIVVGRGEQOQINHHWHKSGSSIGKPLIS Figure 29 2008 527009 2008 7 24 54 2008 527009 A 2008 7 24 00000 00000 BCS 72 2 Cys Ser R F REJI IES 73 GBS 72 g STF2A EL Is Cys Ser 258 U VAIS FREES HRI 0 I F S lt MAOVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAA ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGA GOAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLORV ATAACCTGAACAAATCCCAGTCCGCACTGGGCACCGCTATCGAGCG RELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVEVL TCTGTCTTCTGGTCTGCGTATCAACAGCGCGAAAGACGATGCGGCA AQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVHGAPVDPAS GGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTGA EWTENPLOKIDAALAQVDALRSDLGAVONRFNSAITNLGNTVNNLS CTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGAC EARSRIEDSDYATEVSNMSRAQILOQAGTSVLAQANQVPQNVLSLL CACTGAAGGCGCGCTGAACGAAATCAACAACAACCTGCAGCGTGTG REFSRY PAQWRPLMEKLOLKGTTY GVCSKAFKFLGTPADTGHGTVV CGTGAACTGGCGGTTCAGTCTGCTAACAGCACCAACTCCCAGTCTG LELQYTGTDGPCKVPISSVASLNDLTPVGRLVTVNPFVSVATANAK ACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGAAAT CGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTG GCGCAGGACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTG AAACTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGG TCTGGACTCACTGAACGTGCATGGAGCGCCGGTGGATCCTGCTAGC CCATGGACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGC Figure 30 AGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAAAACCGTTT CAACTCTGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCT GAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTT CCAACATGTCTCG
153. TTCAAGGAGCTCAAAGTCCACCATGCCAATGAGAACATCTTCTACTGCCCCATT GCCATCATGTCAGCTCTAGCCATGGTATACCTGGGTGCAAAAGACAGCACCACGACACAA ATAAATAAGGTTGTTCGCTTTGATAAACTTCCAGGATTCGGAGACAGTATTGAAGCTCAC TGTGGCACATCTGTAAACGTTCACTCTTCACTTAGAGACATCCTCAACCAAATCACCAAA CCAAATGATGTTTATTCGTTCAGCCTTGCCAGTAGACTTTATGCTGAAGAGAGATACCCA ATCCTGCCAGAATACTTGCAGTGTGTGAAGGAACTGTATAGAGGAGGCTY GGAACCTATC AACTTTCAAACAGCTGCAGATCAAGCCAGAGAGCTCATCAATTCCTGGGTAGAAAGTCAG ACAAATGGAATTATCAGAAATGTCCTTCAGCCAAGCTCCGTGGATTCTCAAACTGCAATG GTTCTGGTTAATGCCATTGICTTCAAAGGACTGTGGGAGAAAGCATTTAAGGATGAAGAC ACACAAGCAATGCCTTTCAGAGTGACTGAGCAAGAAAGCAAACCTGTGCAGATGATGTAC CAGATIGGTTTATTTAGAGTGGCATCAATGGCTTCTGAGABAATGAAGATCCTGGAGCT T CCATTTGCCAGTGGGACAATGAGCATGTTGGTGCTGTTGCCTGATGAAGTCTCAGGCCTT GAGCAGCTTGAGAGTATAATCAACTTTGAAAAACTGACTGAATGGACCAGTTCTAATGTT ATGGAAGAGAGGAAGATCAAAGTGTACTTACCTCGCATGAAGATGGACGAAAAATACAAC CPCACATCTGTCTTAATGGCTATGGGCATTACTGACGTGTTTAGCTCTTCAGCCAATCTG TCTGGCATCTCCTCAGCAGAGAGCCTGAAGATATCTCAAGCTGTCCATGCAGCACATGCA GAAATCAATGAAGCAGGCAGAGAGGTGGTAGGGTCAGCAGAGGCTGGAGTGGATGCTGCA AGCGTCTCTGAAGAATTTAGGGCTGACCATCCATTCCTCTTCTGTATCAAGCACATCGCA ACCAACGCCGTTCTCTTCTTTGGCAGATGTGTTTCCCCTTCGAAGCTTGAAGGTAAGCCT ATCCCTAACCCTCTCCTCGGTCTCGATTCTACGCGTACCGGTCATCATCACCATCACCAT Figure 61 59 E2 21 CRVKMEKLQLKGTTYGVCSK BABS 125 E27 SNTVKLTSGHLKCRVKMEKT BABS 126 E28 NTVKLTSGHLKCRVKMEKLO BAGS 127 E29 TVKLTSGHLKCRVKMEKLQL BABS 128 B30 VELTSGHLKCRVKMEKLOLK BASS 129 E31 KLTSGELKCRVKMEKLOLKG BABS 130 E32 LTSGHLKCRV
154. U 50nM rris 0 1M 0 1 EDTA pH 8 00 0 00000000 Becknan Avanti J 20 XP JA 200000 0 40kxgQDOD0O00000000000000 50m Tris 0 1M InM EDTA 4M 0 8 00 00 0000000000000 00 0 0 Beckman Avanti J 20 XP JA 20 40kxgo0 0000000000000000 5 2 O O 50nM 10mM 8M0 0 O pH 4 1 5 30 0000000 0 Beckman Avanti J 20 XP JA 200000 00000 20kx g 000 0000000000000 body feedd 0 STF2A 115 D D iF FO Je GR PR 0 00 0 0 0 0 0 0 0 Advance Corporation Cel 65 0 0 0 0000 00 000000000 36 JP 2008 527009 2008 7 24
155. UMENTS CONSIDERED TO BE RELEVANT Citation of document with indication where appropriate of the relevant passages Relevant to clalm No X MCEWEN J ET AL SYNTHETIC RECOMBINANT VACCINE EXPRESSING INFLUENZA HEAMAGGLUTININ EPITOPE IN SALMONELLA FLAGELLIN LEADS TO PARTIAL PROTECTION IN ICE VACCINE BUTTERWORTH SCIENTIFIC GUILDFORD GB vol 10 no 6 1992 pages 405 411 XP001079342 ISSN 0264 410X page 405 page 407 figures 4 5 the whole document k See patent family annex x Further documents are listad in the continuallon of Box C catagorian olt T later document published after ihe Intemational fing daie A document defining the genera state of the art which is not or priority date and Not in cont with tha Hao but considered to be of particular relev inderstand the principle or theory undariying the earlier document but published on or after the international fling date L document which may throw doubts on priority clairn s which cited to establish the publication date of another citation or other special reason as specified document referring to an oral disclosure use exhibition or 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 search 16 March 2007 Name and mailing address of the ISA European Patent Office 5818 P
156. W STF2A Noti j U U LU D
157. atentlaan 2 NL 2280 HV Rilswilk 4 Tel 31 70 340 2040 Tx 31 651 epo nl Fax 181 70 340 3016 Form PCT ISA 210 second sheet April 2005 Invention X document of particular relevance the clalmed Invention cannot be considered novel or cannot be conside involve an Inventive step when the document Is taken alone Y document of particular relevance ihe clalmed invention cannot be considered to involve an inventive step when the document is combined with one or more other such ments such combination being obvious to a person skilled n the amp document member of the same patent family Date of mailing of the intemational search report 10 04 2007 Authorized officer Domingues Helena page 1 of 6 64 JP 2008 527009 2008 7 24 International application No PCT US2006 001623 C Continsetion DOCUMENTS CONSIDERED TO BE RELEVANT Citation of document with Indication where appropriate of the ralavant passages Relavant to claim US 6 130 082 A MAJARIAN ET AL 10 October 2000 2000 10 10 examples 1 5 the whole document INTERNATIONAL SEARCH REPORT WO 89 10967 A PRAXIS BIOLOGICS INC THE BOARD OF TRUSTEES OF THE LELAND STANDFORD J 16 November 1989 1989 11 16 pages 11 37 pages 60 61 pages 67 68 examples 1 4 DAS GRACAS LUNA MARIA ET AL Salmonella flageliin fused with a linear epitope of colonization factor antigen I CFA I can prime antibody
158. epi tope 1000000000 20 0 J T Adv Virus Res 59 141 20030 10000 450 689 709 721 740 0 0 77y07 000000000 D 390 1600 1620 1640 166 17 JP 2008 527009 2008 7 24
159. et al Nature 375 291 298 1995 Modis Y et al Nature 427 313 319 2004 1 1740 10 519 1370 1890 0 2859 3020 000000000 171740000000000 100000000 520 136 1900 28400 0 0 0 00 0 0 10 00000 1740 0 3030 395 Rey F A et al Nature 375 2911 298 1995 1741 0 440 000000 1750 78 10001000 2000000 1600 0 700000 19 520 1320 193 2800 296 100001 1600 0 00 0 530 1319 0 0 1940 279 110 0000 160 2971 49500 Modis Y et al Nature 427 3130 319 2004 3 4jgugudauguuutgti 1000000000 000000600 10000000000 20 1000000600 000000000000 1000000600 120 0000000000 1000000600 H E Z H 20 DEN3 O0 0 0 00 000 0 0 00 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 type specific contiguous critical domnant neutralizing
160. gugudgsuluuluduiliuuliluluuuli liiliLuiiililul l GITYGMCSKK FTFRPADTGHGTVVLELQY SGDGPCKI SVASKNDLTPVGRLVTVNPF VSSTANAKVLI EMEPPF GDSYI VVGGEQI NH
161. hysical characterization and vector specific antagonist activity of domain III of the tick borne flavivirus envelope protein JOURNAL OF VIROLOGY THE AMERICAN SOCIETY FOR MICROBIOLOGY US vol 75 no 8 Apri 2001 2001 04 pages 4002 4007 XP002375588 ISSN 0022 538X the whole document INTERNATIONAL SEARCH REPORT Relevant to claim No VLAYCHEVA L ET AL Yellow fever 17D virus pseudo revertant suppression of defective virus penetration and spread by mutations in domains II and III of the E protein VIROLOGY ACADEMIC PRESS ORLANDO US vol 327 no 1 15 September 2004 2004 09 15 pages 41 49 XP004527928 ISSN 0042 6822 the whole document HONKO N ET AL Mucosal administration of flagellin induces innate immunity in the mouse lung INFECTION AND IMMUNITY vol 72 no 11 November 2004 2004 11 pages 6676 6679 XP002425274 ISSN 0019 9567 the whole document MCQUISTON J R ET AL Sequencing and comparative analysis of flagellin genes fliC fljB and flpA from Salmonella JOURNAL OF CLINICAL MICROBIOLOGY MAY 2004 vol 42 no 5 May 2004 2004 05 pages 1923 1932 XP002425275 ISSN 0095 1137 the whole document Form PCT SA 210 continuation of second shast April 2005 page 4 of 6 67 JP 2008 527009 2008 7 24 International application No PCT US2006 001623 C Continuation DOCUMENTS CONSIDER
162. ion on patent family members cited In search report date member s US 6130082 10 10 2000 NONE Internatlonal application No PCT US2006 001623 Publication date WO 8910967 A 16 11 1989 AT 121782 T 15 05 1995 AU 637049 B2 20 05 1993 AU 3697989 A 29 11 1989 CA 1340817 C 09 11 1999 DE 68922394 D1 01 06 1995 68922394 2 05 10 1995 DK 263390 04 01 1991 EP 0419513 A1 03 04 1991 FI 104638 Bl 15 03 2000 JP 2793673 B2 03 09 1998 JP 4502402 T 07 05 1992 NO 904806 A 03 01 1991 WO 0140280 A 07 06 2001 AU 4709401 A 12 06 2001 WO 2005042564 A 12 05 2005 NONE WO 2006040076 20 04 2006 DE 102004049223 1 20 04 2006 2006069262 29 06 2006 2005077408 25 08 2005 2555253 1 25 08 2005 Form FCT ISA 210 patent family annex April 2005 73 JP 2008 527009 2008 7 24 5D1nt G 3912 20060 0000 3912 3012 2006 01 0000 380 2006 01 37 02 1 16 200601 1 16 37 04 200601 37 04 3929 2006 01 39 29 31 60 723 409 32 17 10 41 2005 10 4 30000 15 31 60 725 919 32 17 10 110 2005 10 11 33 00005 81 AP BIJGH GM
163. l 00000 1000000 0 PET STF2A ElIIHI 00 0000000000000 00100 Mach 10 InVitrogen Carlsbad 0 000000 00000000000 100 00000000000 5 2 JEIIIAI 0000060 5 14 14 21 Jai Chin Med J Eng 116 941 943 20030 0000000 O DNA 2 Inc Menlo Park NotI O O0 Bp In 000000 p 2 6015100 08000 0 1110000060 0 0 0 pET24A STF2A Elll 32 JP 2008 527009 2008 7 24
164. lls 720 730 E 210 100060 000600 100000 STF2A 0 000000 0 2 210 2 21 11 S E2 21 29 G 5 E2 21 2 S E2 21 4 E2 21 24 5 00 21 1000060 100060 50 2010 0000 100000 I Hutt 57 10000 57 Ell 0 1000060 1000000 log 01110000 1000 00000 1000 58 11100 0 0 001 1688 OU 140 28 PBS 22mg 0 VNV001 1680 PamBCys WWV001 357 00000 ELI SAT O00 VNV001 198 1000 59 114 El El 10001000 HI 880 95 2 114 00000000 0000 1000600 O 2 21 1250 0 60 2 2110 08 00000000 1250 151 00000 0000 0000000000000 0000000 0 1000000 61 5 2 vAp 0 0000 0000 1520000 0 5 2 100060 000000000000 300 00000 62 10000 252000000000000000 15300 0 5 2 154 1550 0 49 JP 2008 527009
165. n 0 O Den3 1000 164 164 16500000 4 Den 4 Den 40 0 0 0 0 Den4g 1000 166 166 00000 0000 0 167070000 170 20 0000170 000000000 000 000 00 1710000 44 174 175 0 450 0000000 700000000000 390 2920 406 178 50 JP 2008 527009 2008 7 24 0000 MBS 3 5 2 7 BBLS MISS 1 5 2 7 OIC TRESI MAQVINTNSLSLLTONNZNKSQSALGTAIERLSSGLRINSAKDDAAGQAiANRFTA NIKGLTQASRNANDCISIAQTTEGAL NNLORVRELAVQSANSTNSQSDLDSI QAEITORLNEIDRVSCQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTI GLDSLNVEGAPVDPAS PWIENPLOKI DAALAQVDALRSDLGAVQNRENSALTNLGN TVNNLSEARSRIEOSDYATEVSNMSRAQILQQAGTSVLAQANOVPONVLSLLR MAOVINTNSLSLLTONNENKSQSAL ERLSSGLRINSAKDDAAGQAIANRFTA NIKGLTOASRNANDGISIAQTTEGALNEINNNLORVRELAVQSANSTNSQSDLDS OAEITQRLNEIDRVSGQTQFNGVKVLAODNTLTIQVGANDGETIDIOLKQINSQTL CLDSLEVOKATYOVEDTAVITKATYANNGTTLDVSGLDOAAIKAATGGTNCTASVTGS AVKFDADNNKYEVIIGGFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATT KTEVQELKDTFAVVSADAKNAL LAGGVDAT DANGAELVKMS YT DKNGKTIEGGYAL TAADCTTKTAANOLGGVDGKTEVVTIDGKTY QKIDAALAQVDALRSDLGAVONRENSAI Figure 3 EVSNMSRAQILQQOAGTSVLAQANQVPONVLSL Figure
166. ohn Wley amp Sons N Y 2001 37 55 0 15M 0 9M 20 55 26 JP 2008 527009 2008 7 24
167. raceuti cal s 3 7 2 359 Biorel ance Road Rockville WAV Beverly MA Ud gd n n 5C5 5H MO O0 ELISA 10 10 20 30 40 50 40 JP 2008 527009 2008 7 24 5 0000 0 0 0 000 0 0 0 0 0 0 00 0 0 0 00 0 0 0 0 0 0 500 5H10 00 78920 I U U UD 0 0 0 0 0 O0 3DDJ 00000000000 00000 500 5H109 0 O 78920 0 0 0 0 0 00 0 0 00 0 0 000 00000 5 gt 2 STFA 11410 0000000
168. responses against homologous and heterologous fimbriae of enterotoxigenic Escherichia coli RESEARCH IN MICROBIOLOGY vol 151 no 7 September 2000 2000 09 pages 575 582 XP002392966 ISSN 0923 2508 page 575 page 577 page 579 the whole document CUADROS CAMILO ET AL Flagellin fusion proteins as adjuvants or vaccines induce specific immune responses INFECTION AND IMMUNITY vol 72 no 5 May 2004 2004 05 pages 2810 2816 002392967 ISSN 0019 9567 page 2810 figures 4 5 pages 2814 5 Form PCTASA 210 continuation of second shest April 2006 page 2 of 6 65 JP 2008 527009 2008 7 24 International application No PCT US2006 001623 C Continuation DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with Indication where appropriate of the relevant 5 Relevant to clalm No passag WU J Y ET AL EXPRESSION OF IMMUNOGENIC EPITOPES OF HEPATITIS B SURFACE ANTIGEN WITH HYBRID FLAGELLIN PROTEINS BY A VACCINE STRAIN OF SALMONELLA PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA NATIONAL ACADEMY OF SCIENCE WASHINGTON DC US vol 86 no 12 June 1989 1989 06 pages 4726 4730 XP002348920 ISSN 0027 8424 the whole document INTERNATIONAL SEARCH REPORT JEON S H ET AL Intranasal immunization with synthetic recombinant vaccine containing multiple epitopes of influenza virus VACCINE BUTTERWOR
169. rn PAMP and at least a portion of at least one Japanese encephalitis viral protein and the use of said composition for stimulating an immune response in a subject 7 claims 5 13 partially 19 20 partially 24 36 partially 69 74 partially 75 and 77 both partially Concerns composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one Tick borne encephalitis viral protein and the use of said composition for stimulating an immune response in a subject 8 claims 5 13 partially 19 20 partially 24 36 partially 69 74 partially 75 and 77 both partially Concerns a composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one Yellow fever viral protein and the use of said composition for stimulating an immune response in a subject 9 claims 21 23 37 38 63 65 69 70 partially 72 73 partially 76 78 80 Concerns a composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one Denl viral envelope protein Den2 viral envelope protein Den3 viral envelope protein or Den4 viral envelope protein and the use of said composition for stimulating an immune response in a subject 72 2008 527009 2008 7 24 INTERNATIONAL SEARCH REPORT Informat
170. to subject matter not required to be searched by this Authority namely Although claims 75 82 are directed to a method of treatment of the human animal body the search has been carried out and based on the alleged effects of the compound composition 2 L 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 s Claims nos because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6 4 8 Box Ill Observations where unity of invention Is lacking Continuation of item 3 of first sheet This Intemational Searching Authority found multiple Inventions in this international application as follows see additional sheet all required additional search fees were timely by the applicant this Intematlonal Search Report covers alll searchable clalms 2 fa As all searchable claims could be searched without effort Justifying an additional fee this Authority did not invite payment of any additional fee As only some of the required additional search fees were timely paid by the applicant thls International Search Report A covers only those claims for which fees were specifically claims Nos 1 82 parts corresponding to inventions 1 2 and 6 9 4 No required additional search
171. y 24 36 partially 69 74 partially 75 and 77 both partially Concerns a composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one Langat viral protein and the use of said composition for stimulating an immune response in a subject 4 claims 5 13 partially 19 20 partially 24 36 partially 69 74 partially 75 and 77 both partially Concerns a composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one Kunjin viral protein and the use of said composition for stimulating an immune response in a subject claims 5 13 partially 19 20 partially 24 36 partially 69 74 partially 75 and 77 both partially 71 JP 2008 527009 2008 7 24 International Application No PCT US2006 001623 FURTHER INFORMATION CONTINUED FROM 210 Concerns a composition comprising at least a portion of at least one pathogen associated molecular pattern PAMP and at least a portion of at least one Murray Valley encephalitis viral protein and the use of said composition for stimulating an immune response in a subject 6 claims 5 13 partially 19 20 24 36 1 11 60 62 69 74 partially 75 and 7 both partially Concerns a composition comprising at least a portion of at least one pathogen associated molecular patte

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