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請求項1 - Questel

1. 10 20 30 40 50 3 JP 4644486 B2 2011 3 2
2. 0000 000000000 00000000000000000 0000 1000000000000 10000000 100000000000000 1000000000000000000000 10000000 ng 6 000000000000000000000000000000 conserved pri CC43 uu ng kennel KAVAK DA Pi P69 Fort Do dge Fort Dodge
3. 0000 10000000000000000000000000000000 1000000000000000000000000000000 nnmnnnnm nn Better et 1988 Sci 240 1041 DO Skerraet al 0 0 0 0 Science 240 10 100000 Bird et al Sci ence 242 4230 Huston et al Proc Natl Acad Sci USA 85 10 et al Nature 341 544 100000000 Wnter amp MIstein 1991 Nature 349 293 299 100
4. 10 20 30 40 50 33 JP 4644486 B2 2011 3 2 IHHHHHHHHHHHHHHHHHHHHHHLai amp Cavanagh D nol bi ol of coronaviruses A
5. 100000000000000000000000000000 HHHHHHH re center 000000 U HHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 100000000000000000000000000000 HHHHHH HHHHHHHHHHHHHHHHHHH Binn et al 1967
6. bronchiseptica 1000000000000000000000000000 tl YU i ili ili li llt UU HHHHHHHHHHHHHHHHHHHHHHHHH 100 00000000000000000000 0 0000 0 000 10000000000000000000000000 EURI DHPPi jluu u iubBiublilil AU
7. 10 20 30 40 50 JP 4644486 B2 2011 3 2 4 10 100 100 100 100 100 20 100000 100 100 100 n n Bordetella bronchi septi ca B bronchi septi
8. 100000 5 ag 000000Spike20000 Spike3 000 HHHHHHSpike4HHHH gg 0000000 Hp pega med ggg mmm emp onu dno gms HHHHHHHHHHHHHHHH CHHHHHHHHHHHHHHHHHHH pM T easyg 0 0 0 10 Ther sequenase 7 dea EE 1000000000000000000000000000000000 0000000000000 000000000 Thonpson et al 1997 Phylip 3 6 senstei 1989 Fel senstein 19890 0 SeqbootH HHH 20 HHHHHHHHHHHHHHDNAparsHHHHHHHHHHHHHHHHH HHHHHHConsenseHHHHHHHHHHHHHHHHHHHHH Treevi 100000000 1996
9. LY 138 0600 00000000000 0430 0 000 0 0 00 0 0 0 0 0 0 0 100000000000000000000000000 00000000 00000000000000000000 000000 000000000000 000000000000 060 HHHHHHHHHHHHHHHHHHHHHHHHHHH Royal College Street London UK 23 St Machar Drive Aberdeen Scotl and AB24 3RY UK ET oana HHHHHHHHHHHHHHHHHH 0 00 0000000000 Genban 8 JP 4644486 B2 2011 3 2
10. bor 100000000 Beggs 1978 Nature 275 104 1090 0000000000 10 ano GV O ODO A Sg O RO Life Technol ogi es Gaithersburg MD 20877 100000000000000000000000 HHHHHHHHHHHHHHHHHHH Luchansky et al 1988 Ml Mcrobi ol 2 637 64 LHHHHHHHHHHHHHHHHHHHHHHH 20 0000 0000 10000 Becker amp Guarente 1990 hods Enzynol 194 182 40 EJ E oa E EE E ESI
11. 000 Genbank Genbank 0000 00000000 Genbank HHHHHHHHHHHHHHHHHHHHHHHHH JP 4644486 B2 2011 3 2 27 10
12. 30 JP 4644486 B2 2011 3 2 u r1
13. 50 JP 4644486 B2 2011 3 2 38 20 40 50 100 JP 4644486 B2 2011 3 2
14. JP 4644486 B2 2011 3 2 28 N n ELS Et ra
15. LY138 5894 CC43 L14643 Thompson et al 199700000 DI Spi ke 1 21 Spi 3 100000000000000000000 40 L3 ENI oa a EJ oa a L3 rrr 50 onanan LI 44 JP 4644486 B2 2011 3 2
16. PROGARH O KC PLUS bronchi septi 100 0000 1000000000000 PROGAR HHHHHHHHHHHHHH 000 1000000 PROGARD PI us 1000000000000 PROGARH 0 O O KC Pl us PROGARD O O O KC Pl us 0 O B bronchi septi 100000000000000000000000 Intrac B bronchiseptica HHHHHHHHHHHHHHHHHHHHHHHHHHHHHH vi 0008 bronchi septi car 0o 30 40
17. 100 Royal Veterinary College 0 C n 10 Tri Reagent HHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHIH 0 0 0 Random Hexaners 1 D 0 O 0 D Stephensen et al 1999 H Stephensen et al 199990 000000000000000 20 Conscoro5 5 ATG AAT TTG AAA TAT GC SEQ ID 3000 O Conscoro6 5 TCA CAC TTA GGA TAR TCC SEQID NO 32 000000 0 Conscoro5H O Conscoro 6060000 10000000000000000000000 0000000 G C C C nnnnnnn n n nn 30 H C Probe Conscoro TT GGY GGY TGG SEQ I
18. BP E DD PY ER DD Pearson 1990 Rapid and sensi ti ve sequence compari son with FASTP FASTA Methods Enzynol 183 63 98 1 Gap open 160 Gap extension penalty 40 0 1000000000000000000000000000000 Geneti cs Conputer Group 1991 Program Manual for the Package Version 7 1991 575 Science Dri ve Madison Wsconsin USA 537111 1000000000000000000000000 creation penalty 50 gap extensi on penalty 3 100000000 creation penalty 80 0 Gap extension penalty 2 00000000 Thomson et al 1997 100000000000000000000000000 Quebec 0000 000 G
19. Internati otechn New Haven CN ol ogi es Sai et al 198 8 Science 239 487 4911 10000000000000000000000 HHHHHHHHHHHHHHHHHHHH
20. HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 00 00000000000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 1000 1000 00 1000 1000 000000 Neuberger et al 1988 8th Interna tional Biotechnology Synposi um Part 2 792 7990 000000000000000 n H ERE m nnn Morri son 1984 Proc Acac Sci USA 81 685 1 6855 25 JP 4644486 B2 2011 3 2
21. 24 JP 4644486 B2 2011 3 2 100000 1000000000000 100000000000000000000000 1000 Monocl Anti bodi es manual of techni ques H Zola CRC Press 1 988 and in Hybri dona Anti bodi Techni ques and Applications Hurrell CRC Press 1982 0 00000000000
22. 100 100 40 50 U 100 5 JP 4644486 B2 2011
23. 100000000000000000000 50 JP 4644486 B2 2011 3 2 14
24. m 9 N FO 3 u L3 L3 L3 E DC S sin C DD L3 DD E E ES DI SEA m m ES E TEE 5 zt C L3 r3 L3 TEE rH z EIE Di TOE 5 Ai madi e EE Sa gt 2 65 Rm m m E gt pantang C EET Gi 3 i EI mm 3 m Star CO m ma DI CO gt m zm DI gt gt mi JP 4644486 B2 2011 3 2 15 Genbank
25. 16 JP 4644486 B2 2011 3 2 1000000000000000000000000000000000000000 1000000000000000000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 1000000000000 5 et al 2001 Molecular Cloning Laboratory Manual 379 edition et al eds Cold Spring Harbor Laboratory Press Cold Spring Harbor NY JP 4644486 B2 2011 3 2 17 10 100
26. 100 100 n 2001 Genbank LY138 40 100 100 50 IDO HH 100 Sanbr ook et
27. 8 UJ 10 20 30 40 50 JP 4644486 B2 2011 3 2 9 100 10000 100 U Genbank LY138 100 100 Genbank Genbank JP 4644486 B2 2011 3 2 10 BCV HCV HEV S CRCV S 1000 1 3 9 20 30 40 50
28. BEVspike TTGATGCTTCTCGCTTATATGCTATGTGTTTTGCTAGCATTTACTATTGACARGTTTGCTA BEVspike TAGCTGGTG CIGECACAGCAACTTGTCCTGTAGGCACCACTGTGCGCARGTGTTTTG m o 9 desea RN ECvspike TGACCTACAATTGGGCAATTIGGOCTATTTGCAGTCTTTTA Bevspike HCVspike TACCCABTGGTAGGAAGGTTGACCTACAATTOGGCAATTTGGGCTATTTGCACTCTTTTA HCVspike CAGGTACTAATTATTTAACTTGCCATAATGCTGCCCARTGTGATTGTTTGTGCACTCCCG CRCVspike TACCCAATGGTAGGRAQGTTGACCTACARATGGGCAATTTGGGCTATTTGCAGTCTTTTA CRCVspike CAGGTACTAATTATTTARCTTTGTTATANMTGCTAACCAATGNGATTGTTTGTGCACTCCAG BEVspike 1 HEVspike 6 AACGCTACTARGIGIACTTECTEGIETCAACCAG wawi AG R43 FO ARARR GE UN Wk xRRO A BCVspike BCTATBGRATTGATACTACTGCTACAAGTTGTCAGTTGTATTATAATTTACCTGCTGCTA BCVspike ACCCCATTACATCTAAATCTACAGGGCCTTATAAGTGCCCCCAAACTAAATATTTAGTTG HCVspike
29. Bor det el a bronchi septi bronchi septi bronchi septi 00000 100000000000000000 10 20 30 40 50 JP 4644486 B2 2011 3 2
30. CARAC TGGACTGTACCTGAATTGACAATTGACATTTTTAACGCARCCTATTTAARTCTG nm CARGATEARATGRATAGGITACACG AGGCAATARAZGIT TTAAATCATAGO BCTGGTGAAATTGATGACTTAGAATTTAGGTCAGARAAGCTACATAACACCACAGTAGAG de hk Ak dokRRA TACAT CAATCTCARGGACATTGGTACA C PTGCCATTCTCATTGACAATATTAACAATACATTAGTCARTCTTGRATGGCTCAATACA n add gt Oo TATGAATATTATGTAAARTGGCCTTGGTATGTATGGCTTTTAATTGGCCTTGCTGGCGTR ATTGAAACTTATGTGRARTGGCCTTGGTATGTGTGGCTACTAATAGGC TTAGTAGTAGT KAKARA RR E RE E RR GCTATGCTTGTT TTACTATTCTTCATATGCTGTTCTACAGGATG TGGGACTAGTTG GTTTTGCATACCGCTATTGCTATTTTGCTGTTGTAGTACAGGTTGCTGTGGATGCATAGG OR www FIGURE 8 Page 9 of 9 ERO ww dee 2 TITIAAGAAATGCGGTEGTIGTTCTGATGATTATACTEGACA TCAGGAGTTAGTAATC TTGTTTGGGAAGTTGTTGTCATTCTATTTGTAGTAGAAGACAATTTGARAATTACGAACC AREA ANTIGNAARAGTGCATGTCCACTAAA E dde wiara FIGURE 9 Page 2 of 12 TARTGTATAGTGAGTTTCCTGCTATAACTARTAGGTAGTACTTTTGTAAATACATCCTATA TAATGTATAGTGAGTTTCCTGCTATAACTATAGGTAGTACTTTTGTAAATACATCCTATA TAGTGTATAGTGAGTTTCCTGCTATAACTATAGGTAGTACTTTTGTARATACRTCCTATA TTATTTATAGTGAGTTTCCTGCTATTACTATAGGTAGTACTTTTGTAAATACTTCCTATA
31. 100000 HHHH 0000 LY138 0000 Genbank 100 05431 000000000 0430 00000 Genbank 00000000000 Genbank 0000 Genb FIGURE 1 X ctcagatgaa tttgaaatat gctattagtg ctaagaatag agcccgcact gttgctggtg tttocatact tagtactatg actggcagaa tgtttcatca aaaatgtttg aaaagtatag cagctacacg tggtgttcot gttgttatag gcaccactaa attttatggc sgctgggatg atatgttacg tcgccttatt aaagatgttg acaatcctgt acttatgggt tgggattatc ctaagtgtga FIGURE 2 QMNLKYAISA KWRARTVAGV SILSTMIGRM FHORCLKSIA ATRGVPVVIG TTKFYGGRDD MLRRLIKDVE NPVLMGNDYP acttotagtt tctacacaaa ccatttacto caaatacctt agagttacta ttggttgaat ctacttgaca actaagetta gattgtttag ttttotaaag ggtgccgaaa ccactgctct
32. HHHHHHHHHHHHHHHHHHHHHHHHIL LY138 LE EE 70 50 13 JP 4644486 B2 2011 3 2 r lt 197 20 LY138 30 1 LY138
33. CRCVspike ACTATAGAMTTGATACTACTGCTACAAGTTGTCAGTTGTATTATARATTTACCTGCTAGTA CRCVepike ACCOTATTITATOTARATCTACAGGECCI TATAAGIGCCOCCRAACTARATACTTAGTIG HEVspike ATTATAAGATTGACACTGCTGTTAGCAGTTETCAACTCTATTATAGTTTECCTGCAGCAR HEVspike ATCCIICCACATATARAGGTGTARATECCTEGACTTGICOGCARTCTARAGITTCTATAC Ak kk w BCVsptke ATGTITCPCTTACCAGGTTTARTCCTTCTACTTGGAATAGGAGATTTCCTTTTACAGAAC BCVspike GCATAGGTGAGCACTGTTCGGGTCTTGCTATTAAAAGTGATTATTOTGGAGGTARTCCTT HCVspike ATGT TTCTGTTAGCAGGTTTARTCCTTCTACTTGGAATAGGAGATTTGGTTTTACAGAAC ucvspike GCATAGGTGAGCACTGTTCGGETCTTGCTATTARARGTGATTATTGTGGAGGTARTCOTT CROVspike ATGTTTCTATTAGCRGOTTTANTCCTTCTATTTCCAATACGAGATTTGGTTTTACAGAAC CRCVspike GCATAGGTGAGCACTGTTCTGGTCTUGCTATTAAAAGTGATTATTGTGGAGGCARTCCTT HEVspike ACGTATCTGYTCACTCATTATAATCCTTCATCTTGGAACAGAAGGTATGGGTTTAT T BEVspike ARACCAGGTCAGCATIGCCCTGGCTTGGGIC TGTGGAGCATGATTCCTCTGGTAATCCTT se x Axio REA RR RR BCYspike GTACTTGCCARCCACAAGCATTTTTGGGTTGGTCTGTTGATTCTYGITTACAAGCGGATA HCVsptke BATCTGTTTTTAAGCCTCARCCTGTAGGTGTTTTTACTCATCATGATGTTGTTTATGCAC HCVspike GTACTTGCCAACCACARGCATTITTGGGTTGGTCTGTTGACTCTTGTTTACAAGGGGATA CROVspike ARTCTGTPTTTARGCCTCARCCTGTA
34. JP 4644486 B2 2011 3 2 Di tchfield et al 19620 U U 0 DD 0 D Bordetella bronchi septi et al 1977 et al 19988 00 00 0 0 0 000 0 0 0 0 0 0 0 0 0 0 0 0 10000
35. 10 20 30 40 50 53 JP 4644486 B2 2011 3 2 oa L3 oa 100 100 100 Genbank 100000 L1 100000000000000000000 HHHHHHHHHHHHHHHHHH 10 1000000000000000 1138 100000 0000 00 00000 0 0 00 0 0 0 0 0 0 0 0 0043 100000 Genban
36. 100000000000000000000000 10 000000000 00000000000 00000 1000000000000000000 prined ate 100000000 0000 pun E nnunnnn i e E ao 22 25 0100000 0000000 10000000000000000 SE 10000000 n 7 100000000000000000000 100000000000000000000 nuclei c aci d sequence based anplification 1991 Nature 350 91 92 AIDS 1993 Vol 7 Supp 20000000 strand di spl anplifi cati V l ker et a 2 Nucl Acids Res 20 1691 16960 00 0 0 00 0 0 0 0 0 0 00 0 0 0 0000 S naen 0000000000000000 20 JP 4644486 B2 2011 3 2 1000000000000000000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHH Balaguer et al 19 91 Quanti fi cati of DNA sequences obtained by ymerase chai n reaction us ing bi ol adsorbent Anal Biochem 195 105 1100 Dilesare et al 1993 A hi gh sensi ti vity el ectroche
37. HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 10 20 30 40 50 7 JP 4644486 B2 2011 3 2 0 1000000000000000000 US Patents Nos 6 057 436 6 372 224 1000000000000000000000000 1000000000000000000000000 1000000000000000000000000 1000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHH 1000000000000000000000000 Spaan et al 19881 0000 0 the chapter by Cavanagh et al entitled Coronviri dae 407 411 in Virus Taxonony 6th Report of the Internati onal Committee on Tax onony of Viruses pub Spri nger Verl ag V i n New York Eds Murphy et al
38. ke CTGCTAGTCTGTTTCCTCCTTGGTCAGCAGCAGCAGGTGTACCATTTTATTTAAATGTTC CROVspike AAGTAAATGAADTACTTGACRCTACACAGTTGCAAGTAGCTAATAGTTTAATGAATGGTG CRCVspike TTGCTAGTCTGTPTCCTCCITGGTCAGCAGCAGCAGCCGTACCATTTTATTTARATGTTC HEVspike BAGTARMTGAACTACTTGACACTACACAGTTGCAAGTAGOPAATAGPTTARTGARTGGAG HEVspike CTGCTAGCCTATTICCICCCTGGACAGCTGCAGChGCTGTACCATTTTATTTAAATGTTC RIA Rd RddobkAd dob AEE OO RH eo dne BCVspike TCACTCTTAGCACTAAGCTTAAAGATGGCGTTAATTTCAATGTAGACGACATCANTTTTT BCVspike HCVspike TCACTCTTPAGCACTAAGCTTARAGATGGCGTTARTTTCARTGTAGACGACATCANTTTTT ECVspike AGTATCGTATTARTGGGATTCGTGTTACCATGGATGTGTTAAGTCARARTCARARGCTTA CRCVspike VCACTCTTAGCACTAAGCTTAAAGATGGCTTTRATTTCARTGTAGATGACATCARTTTTT CRCVspike AGTATCGTATTARTGGTATTGCTGTTACCATGGATGTGCTAACTCAARATCAAAAGCTTA BEVspike TCACCCTTAGTACTAACATTARGGATGGGATTAATTTUAATGTTGACGATATCAACTTCT HEVspike AGTATCGTATARATGGGCTTGCCGTCACCATGGATGTGCTAAGCCARARCCABAAGCTTA PRI Punk FERRE RIETI ZAIRE RE Ek FREE ROERO b ERR BCVspike CCCCTGTATTAGGTTGTTTAGGAAGCGATTGTARTARAGTTTCCAGTAGATCTGCTATAG BCVspike TIGCIAATGCATTTARCARTGCCCTTGATGCTATTCAGGAAGGGTTTGATGCTACCARTT HCVspike CCOCTGTATTAGGTTICUITAGCARGCCCTTGTAATAAAGTTTCCAGCAGATCTGCTATAG HCVspike TTGCTARTCCATTTAGCAATGCTCTTGATGCTATTCAGGRA
39. DI 45 JP 4644486 B2 2011 000000000 HHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHH 0000 0 HHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHH 100000000000000000 LOU UH BU DBUZUBEHHLHBLDULULILILU 34 RT PCR sE dh 11 42 26 2 8 42 19 1 2 42 10 18 55 6 4 18 22 2 1 4 18 a 9 46 19 6 18 46 17 4 2 46 2 13 15 4 0 13 0 13 000000 000000000000 00000000000000000 LU Ut LU gl 000
40. 100000000000000000000000000 100000000000000000000000000 0000 0000 100000000000000000000000000 0 E 00000000 00 00 0000 1000000000 0000000000 000 0000 0000 0000 HH Genbank Genbank Genbank 26 JP 4644486 B2 2011 3 2 Genbank
41. 1985 Biotech JP 4644486 B2 2011 3 2 23 100 100 10 30 Bac BI ue 50 100 Invitrogen Sf9 Sf 21 Fi trogen
42. GTGTGGTAGTACAACCACATACTACCAATTTGGATAATAAATTACARGGTCTUTTAGAGA GIGTGGTAGTACAACCACATACTACTAATTTAGATAATAANTTACAAGGTCTCTTAGAGA GCRTAGTAGTARAGCCTCATACCTCATTTATTAATGGTAATTTACAAGGTTTTTTGCARA dO k ORA FERARO k FOE HORROR w RNO KOA TCTCTGTTTGCCAGTATACTATGTGOGAGT CCCACATACGATTTGTCATCOTAATTTGG TCTCTGTTTGCCAGTATACTA PGTCCGAGTACCCACATACGATTTGTCATCCTAATCTGG TCTCTGTTTGCCAGTATACTATGTGCGATTACCCACATACGATGTGTCATCCTARTCTGG TTTCTGTTTGTCARTATACTATGTGTGAATACCCACAGACTATTTGTCATCCTAATTTGG RG O GGI OR SIAE AGERE Aka URRA Ak GIRA do RR GTAATTICACATATGATETERATGCTCATTATITGIATTICCATTITTATCARGAAGGTG GTAATTICACATATGATGTGAATGCTGATTACTTGTATTTCCATTTTTATCARGARGGTG GTAATTTCACATATGATGTGAMTGCTGATTATTTGTATTCCCATTTTTATCARGARGGTG GTABTTTCACATATGATGTGAATGCTGATTATTTATATTTTCACTTTTATCACGAAGGTG n I GTACTTTTTATGCATATTTTACAGACACTGGTGTTGTTACTAAGTTTCTGTTTAA
43. Churchill Applied Bi osci ences Hunti ngd 100000000000000000000 C 30 200 0000000000000000000000 Si 9 0 20 0 0 1000000000000000000000 0 nHHnHH 1000000000000000000000000 40 Su Du T BOE z nn nnnnnnnH nnn NANANG nnnm n 50 43 JP 4644486 B2 2011 3 2 10 Conscoro5 Conscor o6 Pearson 1990 NUO lt HM UJ
44. CRCV BECV HEV CRCV BCV HECV HEV 18 ACCATTAACACTGGTTTTGATTTTAATTGTCATIATTTACTTTTACCCTCTGGTAATTAT ACCATTACCACTGGTTTTGATTTTAATTGTCATTATTTAGTTTTACCCTCTGGTAATTAT ACCATTACCACTGGTTTTGATCTTAATTGTTATTATTTACTTTTACCCTCTGGTAATTAT ACCATTACCACTGGTTTTGATTTTAATTGTCATTATTTAGTTCTACCCTCTGGCAATTAT ACCATTACCACTGCGTTTTGATTTTAATTGTCATTATTTAGTTCTACCCTCTGGTARTTAT KAKEAN KARANA KERA AIA GORGE RIACE E doble TTAGCCATTTCAABTGAGCTATTGTTAACTGTTCCTACGAAAGCAATCTGTCTTAATAAG TEES Page 2 of 2 CGTAAGGATTTTACGCCTGTACAGGTTGTTGACTCGCGGTGGAACABTGCCAGGCAGTCT CGTAAGGATTTTACGCCTGTACAGGTTGTTGACTCTCGGTGGAACAATGCCAGGCAGTCT CGTAAGGATTTTACGCCTGTACAGGTTIGTTGATTCGCGGTGGAACAATGCCAGGCAGTCT CGTAAGGATTTTACGCCYGTACAGGTTGTTGACTCGCGGTGGAACAATGCCAGGCAGTCT CGTAAGGTTTTTACGCCTGTACAGGTTGTTGATTCGCGGTGGBAACAATGCCAGGCAATCT ROIO RR IO RR ER ORIO O kk kk kaki A GATAACATGACGGCGGT GATAACATGACG
45. 00000000 1000000000000000 Fort Dodge Ani mal DA Pi P69 0000000000000 000 TD DD L Fort Dodge Animal Health KAVAK H EHE E DEU Intervet UK O NOBI DFPPi HHHHHHHHHHHHHHHHHHHHHHHUHHHHHHHHH ntervet UK NOBI VAC Bordetella bronchi septi cap Cornell 10000000000000000000000 0000000 06376 4026 Meri al Animal Health EUH 0 0000 0 0 0 000 00 000 0 0 VANGUARD7 SnyderH 115000000000 0 0 2 Mnhatta 10 50 0000000000000 35 00 0000 Leptospira cani col a Leptospi ra icterohaenorrhagi ae 00 00000000 000 Health QUANTUM 09670 10 20 30 40 50 36 JP 4644486
46. 12 JP 4644486 B2 2011 3 2 100000000000000000000000000 10 20 E HM HER n e E nnm nnnnnnnnmn UU AU TU UU D 30 LY138 0 Genbankl HHHHHHHHHHHHHH 40 LY138HHHHHHHHHHHHHHHH
47. HHHHHHHHHHHHHHHHHHHHHHHHHHHHH BoradH HHHHHHH pUC18 pUC19 pBR322 pBR329H 00000000000000 pTrc99A pKK223 3 pKK233 pDR540 T50 J HHHHHHHHHHHHHHHHHHHHHHH pBS Plagescript O 000 Bluescri pt O0 pNH8A pNH16A pNHI8A 1000000000000 pRS403 4060 pRS413 4160 pRS403 pRS404 pRS405 pRS406 I ntegrati ng 530 LEU2 pRS413 416 i medi ate early Hastin 21 JP 4644486 B2 2011 3 2 gs et al International Patent No 98 16643
48. D l D l 50 IDO HH 1000 n n JP 4644486 B2 2011 3 2 47 100 U F4 F4 F4 1999 Stephensen et al 20 30 0043 0043
49. DI DI DI x E ET DI DI DI QO 6 DI DI 9 s 9 DI 29 JP 4644486 B2 2011 000000000000000000000000000000 000000000000000000000000000000 10000000000000000000000 et Cell Biol HM o HM M m 09 HM 09 v 5 5 105 3087 3096 1987 0000
50. XA TGCNTATTTTACAGACACTGGTGTTGTTACTAAGTTTCTGTTTCATGTTTAT TTAGGCA TTACAAGTIAAATAACACCAATGGICTAA AAACCTATGAATTATGTGAAGATTATGAA OW oo EA k kok wk done CGGTGCTTT CBOATTATTA TGTCATGCCCTTGACTTGTAATAGTGCTATGACTTTA TATTGCACTGGCTACGCCACTAACATCTTTGCCCCARCTGTGGOGAGOTTACATACCTOAT Aat ak GAATACPGGGTTA __ CGATTTAGITTTAACAATIGGIITTTECITACARACAGCICCACTTTTETTAGIEGCAGA tak ox bo orir koia AGCCA ATTEGCAGATETTTACCGACGTATACCTAATCTTCCCE ATTETARTATAGACG ARTRACACAGTAGATGTCATTAGATTCAACCTTBATTTTACTGCAGATGTACAATCTGGC wakaka b gt Ah ERO x 55 JP 4644486 B2 2011 3 2 0000 CRCVspike CEPVspike CRCVspike CECVspike CRCVSpike CECVspike
51. 100 40 100 100 n 48 JP 4644486 B2 2011 3 2 229 EHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH C
52. CRCYspike AGRACCITTTATATGATTCIARTEGIARTCICIATESITTTAGGGACTACITAACARACA CRCVspike CPRATTTTGAGCCATTTACTETTAATCCAGTARATGAPAGITTACACCOTETAGGIEGIT HEVspike AGRATCITETTIATGATTCTAGTGGIARTCICTATEGCITTAGAGATTATITATCAARTA HEVspike Weak AWAKE PIO AA BCVspike GhACTTTTATGATTCGTAGTTGCTATAGCGCTCGTGTITCAGCGGCCTTTCATGCTARTT BCVspike TGTATGAARTTCAAATACCTTCAGAGTTTACTATAGGTARTATGGAGGAGT TTATTCAAR HCVspike GAACTTTTATGATTCGTAGTTGUTATAGCGGTCGTGTTTCAGCGGCCTTTCATGCTAACT HOVspike TGTATGARATTCARATACCTICAGAGTTTACTATAGGTAATATGGAGGAGTTTATTCAAR CRCVspike GAACTTTTATGATTCGTAGTTGCTATAGOGGTOGTGTTTCAGCGGGC TTCACTCTAACT CRCVspike TGIATGABATTCRAATACCTTCAGAGTTTACTATAGGTARTATGGAGGAGTTTATTCAAR HEVepike GAACCTTTCTTATTOGTAGCTGCTATAGTGGAAGAGITTCAGCAGTCTTTCATGCTARCT HEVspike TETATCARATACAGATACCTTCAGAGITTACCATIGGIZATITAGARGAATICATTCARA P w E AR BCVspike CTTCCCARCCAGCATTGCTATTTCGGARTATTAAATGCAATTACGTPPTTANTAATACTC TAAGCTCTCCTAARGTTACTATTGATTGTTCTGCTTTTGTCTGTGGTCATTATGCAGCAT HCVspike RCVspike CARGCTCTCCTAARGTTACTATTGATTGTTCTGCTTTTGTCTO
53. kik CRCVspike CRCVspike CECVspike CRCVsptke CECVspike CRCVspike CECVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CBCVspike CRCVspike BCVspike ACVspi ke CRCVspike BEVspike ECVspike CRCYspike HEVspike BCVspi ECVspike CROVspike HEVspike BCVspike HCVspike CRCVsptke HEVspike BCVspike BcYspike CROVspike HEVspike BCVspike HCVspke CRCVspixe BEVspike FIGURE 8 Page 8 of 9 GIA GCACTTTTGGACTTGTCGTTAAAGATGTTCAGTTGACGTTGTTTCGTARTCTAGATGACA ok A lt dee kak obk kR kak CTTEGATETTCACTEGIAGIEGITATTACTACCCIGARCOTATAACTGGARATRATGTGG AGTTICTATTTGACTCCCAGARCTATGTATCAGCCTAGAGCTGCAACTAGTTCTGATTTTG Rk kik ORSI E TTETTATCAGTACCIGIGCIETTARCTATACTARAGCACCEGGATEGTAATECTGRACATIT TICAGATIGAGGGOTGCGACGTGTTGTTTGTCAATGCAACTGTAATTGACTTGCCTAGTA TTATACCTGACTATATCGACATTAATCAGACTGTTCAAGRCATATTAGAARACTACAGAC E
54. 0 Ncol 10000000 D pMel Sp7 SpR Hi sTag Eco 0 1000 90 0 SpR Eco Hi 5 10000 BacB 10000 10 Spi MelBac HsTag 6xH 5 0 HH Ban 000 0 0 ABCD pSecTagA 0000000 Spi keSecTag BI ue 0000 Invitrogen O Spi ke Bach 0 5790 AcSpCRCV 1 1110000000000 IHHHHInvitrogenHHHHHHHHHHHHHHHHHH 20 SecTad Invitrogenl BHK 211000 Churchi Churchi
55. UU LL u n 1000 B n 1000 1000 3 HH n 10 Una 0 Pi 0 20 n ull n T 0000 DOO 30 40 1000006000000 20 JP 4644486 B2 2011 3 2 31 10 20 C 30 40 50 C C JP 4644486 B2 2011 3 2
56. GCACTCATACTETCGATGITACFARTEGITTAGGTACTTATTATETTITAGATCETETET GCACTGATATTGTCGATGTTACTAATGGTTTAGGTACTTATTATGTTTTAGATCGTGTGT GCACTGATGTTGTCGATGTTACTAATGGTTTAGGTACTTATTATGTTTTAGATCGTGTGT GCTCTGAAGTTGTTGATGTCACTAATGGTTTGGOGACTTTCTATGTTTTAGATCGTGTCT BER AR RE Rd e RIE Rh ATITAAATACTACGTTGPTGCTTAATGGTTACTACCCTACTTCAGGTTCTACATATCG A ATTTAANTACTACATTGTTGCTTIARTGGITATTATCCTACTTCAGGTTCTACATATCGTA ATITAARTACCACATTGTTGCTCAATGGTTATTACCCAATTTCAGGTGCTACATTTCGTA AadekkAdek dek AE GR AG ARR BATATGGCACTGAAGGGAACTTTACTATTGAGCACACTATGGTTTAAACCACCTTTTCTTT ATATGGCACTGRAGCGAACTTTACTATTGAGCAGACTATGGTTPAANCCACCTTTTCTTT BTATGGCACTGAAGGGAACTTTACTATTGAGCACACTATGGTTTABACCACCATTTCTTY ATGTGGCTCTGAAAGGAACTCGATTATTGAGCACCTTGTGGTTTAAGCCGCCTTTTTTAT Qd AAA ARRE RR O w RIA t CTGATTTTATTAATGCTATTTTTGCTAAGGTCAARAATACCAAGGTTATTARAAATGGTG CTGATTTTATTAATGGTATTTTTGCTAAGGTCAAABATACCAAGGTTATTARAAAGGGTG CTGA TTTATTGATGGTGTTTTTGCTAAGGTAAARARTACCAAGGTTATTARAGATGGTG CACCTTTTAATGATGGTATTTTTGCCAAGGTTAAAAACAGCAGATTTTCTAAACATGGTG OO k ERRORE GO AGRAR Ak FIGURE 9 Page 3 of 12 ATTTAGGCACGSTGCTTTCACATTATTATGTCATGCCTTTGACTTGTARTAGIGCTATGA APTTAGGCACGGTGCTTTCACATTATTATGTCCTGCCTTTGACTTGTAATAGTGCTATGA ATT
57. JP 4644486 B2 2011 3 2 19 H F JP 24 8 B2 11 4644486 P4644486 45 23 3 2 2011 3 2 24 22 12 10 2010 12 10 51 Int Cl FI C12N 15 09 2006 01 C12N 15 00 ZNAA COZ 14 165 2006 01 CO7K 14 165 CO7K 16 10 2006 01 CO7K 16 10 C12N 1 15 2006 01 C12N 1 15 C12N 1 19 2006 01 C12N 1 19 53 04 E 21 2004 523905 P2004 523905 73 505033743 86 22 15 7 1 2003 7 1 65 2005 533513 P2005 533513A 1 43 17 1 10 2005 11 10 O A 86 PCT GB2003 002832 n 87 w02004 011651 87 16 2 5 2
58. tm Lactovac Hoechst Roussel Vet he Veteri nary Data Sheet Conpendi un htt p ww ukvet co uk rot ovec scour h Veteri nary Formulary 5th Edition of t First Defense 100000 Scour Bos 4 Grand Laboraotri es Scour Guard 0 0000000000 000 00000000 0000 0000000 0000 0000 000 000 0000 0000 000 0 1000000000 1000000000000000 000 000 Bordetella bronchi septi ca B bro nchi septi
59. ARA 3 waw CRCVspike CRCVspike TTCTCAACAGCTTAGTGATTCTACACTAGTAAAATITAGTGCAGCACAACCTAIGGAGRA CECVspike TGTACAGGTGGTTATGACATAGCTGACTTAGTTTGTGCACAATATTACAATGGCATCATG CECVspike ATCTCAGACTCTARCCAGACAAGCGGAGCTTAGGGCTAGTAGACARCTTGCCARAGACAR AAA AAA PR AURA A REA ORE mnm COTE MER hh d CROVspike GTGTTGCCTC CACTGCTCTCAGAAARTCAGATCAGTGGATACACTTTGGCTGCCACCTT CRCVspike GGTTARTGAATGTGTCARARGCCAATCATCTAGGATAAATTTTTGTGGTAATGGTAATCA CECVspike GTTCTACCTGGTGCTTGCTAAT GATGACAAGATGACTATGTACACAGCCTCTCTTGCAGG CECVspike EGTTAATGAATETETTAGGTCTCAGTOTCAGAGATTTGGATTTTGISGTRATEGTACACA X t ak wana Sn CRCVspike TGCTAGTCTGTTTCCTCC TTGGTCAGCAGCA GCAGGCGTACCATTTTATTTAAATGT CRCVspike TATTATATCATTAGTGCAGARTGCTCCATATGGTTTGTATTTTATCCACTTTA GCTATG CECVspike TGGTATAGCATTAGGTGCACTAGGTGGTGGCGCOGTGGCTATACCTTTTGCAGTRGCAGT CECVspike TTTGTTTTCACTTGCAAATGCAGCACCAAATGGCATGGTTTTCTTTOACACAGTGCTAT pm Aa kk ok KOR MS wa a CREARE pa 5 92 saw harsa CRCVspike TCAGTATCGTATTARIGGTATTGGTGTTACCATGGATGTGCTARCTCARARTCAAAAGCT CRCVspike TCCCTACTAAGTATGTCACTGCGAAGGTTAGTCCCGGTCTGTGCATYGCAGETGATAGAG CECVspike TCAGGCTAGACTTANTTATGTTGCTCTACAARCTGATGTATTGAACAAAAACCAGCAGAT CECVspike TACCAACAGCTTATGAAACTGTARCAGCTTGGTCAGGTATTTGTGCTTCAGATGGCGATC mm
60. annnnnnnnnnnnnnnnnnnnm 10000 100 HHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHH HHHHHHHHHH HHHHHHHHH 00000 0043 0 D FE2H 00000 100 100 0000000000000000000000000000000000 000 2 No M84486 H CV O C 4 3 GenBank No M76373 L1 L3 L3 rJ EJ L L3 L3 EJ O oana a A ET oana rJ L3 L L3 L3 rJ L3 PCR HE1 HE 2 235 N Asn 242 TIE Phe 1000000000000000000000000000000000 100000000000000
61. ATTCTTAACT GTTCCTACGA AAGCAATCTG TCTTAATARG 420 CGTAAGGATT TTACGCCTGT ACAGGTTGTT GACTCGCGGT GGAACAATGC CAGGCAGICT 480 GATAACATGA CGGCGG 497 00000 500b FIGURE 14 400b YRSLTEVNVE YVYNGSAQST ALCKSGSLVL NNPAYIAREA NFGDYYYKVE ADFYLSGCDE 60 YIVPLCIFNG KFLSNIKYYD DSQYYENKDT TINTGFDENC HYLLLPSGNY 120 LAISNELLIT VPTKAICLNK REDETPVOVV DSRWNNARGS DNMTA 165 00000 812 100 80 60 40 Ue lt 20 0 n 77 43 HECV HEV CRCV BCV 0043 CRCV BCV OC43 CRCV BCV 0043 HECV HEV CRCV BCV OC43 HECV HEV FIGURE 15 1 of 2 TATCGCAGCCTTACTTTTGTTAATGTACCATATGTTTATAATGGCTCTGCACARTCTACA TATCGCAGCCTTACTTITTGTTAATGTACCATATGTTTATAATGGCTCTGCACAATCTACA RARE RA kkkkk kA GCTCTTTGTAAATCTCGTAGTTTAGTTCTTAATAACCCTGCATATATAGCTCGTGARGCT GCTCTTTGTAARTCTGOCTAGTTTAGTTCTTAATAACCCTGCATATATAGCTCGTGAAGCT GCTCTTTGTAAATCTGGT
62. HHHHHHHHHHHHHHHHHIH HHHHHHHHHHHHHHHHHIH 30 JP 4644486 B2 2011 3 2 51 10 20 30 40 093 1 32 3P1SIHX9 f 09 SIH HdS PEZ EN 4 Je4 10ux Jds DY LLYALI LLD AVD IDL VOI DOI DDOl VDI VOI VOI VDI VD l V VI LOIL LVV D LLI S 570 lt 6906 8565 6160 ON d OS LIYO ergy AG Z Yueguep 5700 YAUFGLOTYAINY 2 68904 ON egu 47 6 9 50 52 JP 4644486 B2 2011 3 2 0043 D HH
63. 00000000000000000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHUHHUHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHIH JP 4644486 B2 2011 3 2 11 10 20 100 30 40 50
64. 0C43 HEV CCV A ARRIA uuu protHCVpoly protHEVpoly protBCVpoly protCRCVpol protCECVpol protHcvpoly protHEVpoly protBCVpoly protCRCVpol protCECVpol CROVspike CECVspike CRCVspdke CECVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CROVspike FIGURE 7 MNLKYAISAKNRARTVAGVSILSTMTGRMFHOKCLKSIAATR MNLEKYAISAKNRARTVAGVSILSTMTGRMFHQKCLKSIAATR MNLAYAISAKNRARTVAGVSILSTMTGRMFHOKCLKSIAATR QMNLEYAISAKNRARTVAGVSILSTMTGRMFHOKCLKSIAATR MTOMNLKYAISGKARARTVGGVSLLSTMTTROYHOKHLKSIAATR k Ad k OR OR K DUO GVPVVIGITKFYGGWDDMLRRLIKDVDNPVLMGWDYPKC GVPVVIGTTKFYGGWDDMLRRLIKDVDNEVLMGWDYPKC GVPVVIGTTKFYGGWDDMLRRLIKDVDNPVLMGWDYPKC GVPVVIGTTKFYGGWDDMLRRLIKDVENPVLMGWDYPKC NATVVIGSTKFYGGWDNMLKNLMRDVDNGCLMGWDYPKC LU ido ARR FIGURE 8 Page 2 of 9 TGTGCGATTACCCACATA CGATGTGTC ATCCTARTCTGGGT AMTAAACG CATAG ATTTATGGTCTTGAGTGGAATGATGBAA TTTGTTACAGCGTACATTAGTGGTCGTTCTTAT ARCTATGGCATTGGGATACAGGTGTTGTTCCCTGT T TATATAAGCGTABTTTCACATAT ABTTGGARCATCAATARTAATTGGTTTAACARTGTCACGCTTCTSTATAGTCGCTCAAGC m ES UV ww w GATGTGA ATGCTGATTATTTGTATTCCCATTTTTATCAAGAAGGTGGTACTTT TTA ACTGCCACATGGCAACACAGTGC TGCATACGTTTACCRAGGTGTTTCTAACTTCACTTA
65. DER 3 I ox E E PENGEN y lt E QS s 3 _ Li Du 3 3 Ed CJ EB E B ES ESA M LINES CN 3 3 r3 3 3 3 3 Mii CO Og r3 D 6 3 rp EE gt 3 3 L3 ada DL 3 a o0 n ASW _ 3 Q nd cor d a g 3 r3 C3 a rt yea Do 3 Doo 3 g 3 r3 Cj E ES _ __ _ _ DI D ma mn DI C3 o g ENS Do Do 3 G g ga V o g T EJ EE
66. GaneSeg Uh Prot GeneSeq
67. 10 LY138 LY138 LY138 JUN N m muk m 585 um A DI E 22 m DI 65 6 EE 25 x c 5 gt 3
68. A72 190 191 TiO 7105 63 JP 4644486 B2 2011 3 2 10000 0004644486000001 64 JP 4644486 B2 2011 3 2 0000 2060 21 0000 50 20600 yo 000 0000 2 0 20060 21 02 0000 78 2060 0 128 0000 ve 2060 168 0000 Yn 2060 1 70 0000 3953 2060 33 53 0000 3759 20060 33 560 0000 325 2060 39 215 0000 1 0 20601 1 00 0000 20060 31 14 2000 0000000 10000 000 0000 Sa n 2000 10000 000 0000 D z nn nnnm SE 2000 00000 00000 10000 000 0000 D nnnnnn nn nnnm Duc pa m GT 100 590000 Mrdogy 1991 Vol 183 397 404 00000 0 183 397 404 58000000 1 0 0000 15 00 15 90 14 00 14 825 CN B Y MOI NY VA SIN SIA us us J ST7580 J D eanhi GenBank
69. 1000000000000000000000000000000 1000000000000000000000000000000 000 41 JP 4644486 B2 2011 3 2
70. 39 10 100 100 100 n 40 50 40 JP 4644486 B2 2011 3 2
71. HHHHHH 10000000000000000000000 1000 100 10000 Bethesda Research Laboratori es Bet hesda Aneri can Type Cul ture Collection ATCC of Rockvi 11 USA ATC C 31343 0 0 0 0000 0000000 0 0 YPHA99 YPH500 61 ATCQ CRL 16581 0000000 N 0 CRL1650 22 JP 4644486 B2 2011 3 2 00000000000000000000000000000000000 n HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 10000000000000000000000000000000000 Cohen et al 1972 Proc Natl Acad Sci USA 69 2110 and Sanbrook et 2001 Mlecular Cloning A Laboratory Manual 37 Ed Cold Spring Harbor Labo ratory Cold Spri ng Harbor EET EY EET B E DEVI EDT HESS het et al 1986 Methods n Yeast Genetics A Laboratory Manual Cold Spring
72. 100 100 100 20 LY138 LY138 Genbank 30 40 2 et 50 0011 18
73. B2 2011 3 2 1000000000000000000000000000000000 Leptospi ra col Leptospira icterohaenorr hagi L1 Vi r bac GEN DHPP 100000000000000 HHHHHHHHHHHHHHLH 1 Vi Meri al EURI CAN Herpes205 B bronchi septi B bronchi septi ca 1000000000000 DI DI bro
74. CTCABATGAATTTGAAATATGCTATTAGTGCTAAGAATAGAGCCCGCACTGTTGCTGGTG HEV CTCAAATGBATTTGAAATATGETATTAGTGCCAAGAATAGAGCCCGCACTGTTGCTGGTG CCV CTCAGATGAATTITGAAATATGCTATTTCTGGARAGGCTAGAGCTCGTACAGTAGGAGGAG AO AGR RR RA RAG kki kt E 101 TITCCATACTITAGTACTATGACTGGCAGAATGTTTCATCAAAAATGTTTGAAAAGTATAG TTICCATACTCAGTACTATGACTGGCAGAATGTTTCATCAAAAATGTTTGAAAAGTATAG 0043 TTTCCATACTTAGTACTATGACTGGCAGAATGTTTCATCARARATCTTTGAAAAGTATAG TPTCCATACTPTAGTACTATGACTGGCAGAATGTTTCATCAAAAATGCTTGAAAAGTATAG CCV TTTCACTTCTTICTACCATGACTACGAGACAATACCACCAGAAGCATTTGAAGTCAATTG da OX o Gun kkk X A gt T101 CAGCTACACGTGGTGTTICCTGTTGTTATAGGCACCACTAAATTTTATGGCGGCTGGGATG CAGCTACACGTGGTGTTCCTGTTGTTATAGGCACCACTAAGTTTTATGGCGGCTGGGATG 0 43 CAGCTACACGTGGTGTICCTGTAGTTATAGGCACCACTABATTTTATGGTGGCTGGGATG HEV CAGCTACACGTGGCGTITCCTGTGGTTATAGGCACCACTAAATTTTATOGCGGCTGGGATG CCV CTGCAACACGCAATGCCACTGTGGTTATTGGCTCAACCAAGTTTTATGGTGGTTGGGATA Ok RR kk IAA OA kk 1101 ATATGTTACGTCGCCTTATTABAGATGTTGACANTCCTGTACTTATGGGTTGGGATTATC ATATGTTACGTCGCCTTATTAAAGATGTTGCATAATCCTGTACTTATGGGTTGGGATTATC 0043 ATATGTTACGCCGCCTTATTAAAGATGTTGACAATCCTGTACTTATGGGTTGGGATTATC HEV ATATGTTACGCCGCCTTATTARAGATGTTGATAATCCTCTACTTATGGGTTGGGATTATC CCV ACATGCTTAAABATTTAATGCGTGATGTTGATAATGGTTGTTTGATGGGATGGGACTATC k k kakak kika 1101 CTAAGTCTGA
75. GATESGECCATACITOGACO TATEACITOCATTRATAGIGAACI CITAGGICTARCAC CECVspike G ATICGTTCTAACCAATT CTCAGTTTATCTTCACTCCACTTGCAAAAGTTCTTTATOG ae RE En e A Aw eka X gt da CRCVspike CROVepike ARARCTGATTATTGTGGAGGCAATCCTTGTACTTGCCARCCAAAAGCATTTTTGGG TT CECVSpike GACARCAATTITRATCAAGATTGCACAGATETTITATATECCACAGCIGTTATARARACT oe gt CRCVspike GGTTACTGGGGGGRTTACTCTACACARAGACGARGT CGTAGAACGATTACCACHTGG SRCVepike LL CECVspike ACA ACTCGTGGCACTGCARTCGACAGTAACCATGTAGATTGIGARCCTATCATAACCTA PIRA e WA ca mc wayt d CRCVspike ATCGGPTT ACTAATTTTGAGCCCATTTACTGTTAATCCAGTAAATGATAG A TARTE paipa E CECVspike TTCTARCATAGCTGTTTGTARARATGGTGCGTTGGTTTPTATTAACGTCACACATTCTEA CECVspike TIGICGTIGAATCCTACTGCTGCCAACTCTAAGTTTGATGTTGCTGCCOGTACARGAACC a Faina ge de La nes E s kawsas CRCVspike JTTTACACCCTGYAGGTGGTTTGTAT GABAT TCA AATA
76. JP 4644486 B2 2011 3 2 1000000000000000 000 HHHHHHHHHHHHHHHHH 1000000000000000 0000 5 et al 20011 00 0000 1000 0000 HHHHHHHHH 1000 00 0000 000 HHHHHHHHH 0000 0000
77. cactgatgtt tttaaatact tatggeactg tgattttatt agtgtatagt igtggtagta ctetgtttgc taatttcaca tactttttat tttaggcacg tttagastac tggtgttatt aacactatct aattgoagat tantgatsag ttttaatatg tgatgotget acccaatggt ctatagaatt tgtttctatt atctgttktt acatkgtttt aggragiggi aggtacteat ccctatttta cataggtgag tacttgccaa gtgtaatakt tgatttacaa tggtattaca gaacctttta aacttttatg ttccgaacca ttcacgacag tgataatagi VDVTNGLGTY YVLDRVYLNT DGVFAKVKNT KVIKDGVVYS QYTMCDYPHT MCHPNLGNKR AYPTDTGVVT KFLFAVYLGT FNAVDCKSDF MSEIKCKTLS SVPSPLNWER KTFSNCNFNM RKVDLOMGNL GYLOSFNYRI KPOPVGVETD HDVVYAQRCF YLTCYNANQC DCLCTEDFIL PKAFLGWSVD SCLOGDRCNI GOGIFVEVNA TYYNSWONLL ALLFRNIKCN YVENNTLSRQ STORRSRRTI KVTIDCPVEV CGDYAACKSG TELKDGFNEN VDDINFSEVL GAEIRDLICV QSYNGIKVLE NGIGVTMDVI TONQOKLISHA IBV SNKEGATSAS LQEILSRLDA EKVNECVKSQ SSRINFCGNG RGIAPKSGYF PDFKEEBDQW FKNOTLMAPD EYYVKHPWYV WLLIGLAGVA B2 2011 3 2 60 120 180 240 300 360 420 480 540 600 660 720 780 840 500 960 1020 1080 1240 1200 1260 1320 1380 1450 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2190 2160 2220 60 120 180 240 300 360 420 480 540 600 660 720 780 840 906 960 1020 1080 1140 1200 1260 1320 1363 uuu FIGURE 6 T101 CTCAGATGAATTTICAAATATGCTATTAGTGCTAAGAATAGAGCCCGCACTGTTGCTGGTG CICAMATGAATTTGAAATATGCTATTAGTGCTAAGAATAGAGCCCGCACTGTTGCTGGTG 0 43
78. tttcctcett aatggtattg tttaacaatg amp aaattcaag tctaataaat cttgaegcgc tatgtttctc gagaaggtta aatcstatta tatgtccota agaggtatag ggtagtggtt tgtgctgtta cctgatttta ttgtcacttg caggaggcaa gaatattatg atgcttgttt aaatgeggtg catgacgact ctgttcaaac gacgaagtcg ttaatecagt cagagtttac ttgattgtcc atggtagttt ctacacagtt aagatggctt gaagcgaatg taaagttato ttagggacct cagaaaatca dgtcagcagc gtgttaccat cocttgatgc ctgttgttaa ttggtgctat sagctcagat aacagettag atgaatgtgt tatcattagt ckaagtatgt ctcotaagag attactaccc actatactaa aggaagagtt attatataaa tasaagtttt taaaatggcc tactattctt gttgttgtga FIGURE 3 Page 2 of 2 atgtgatoto tagaacgatt asatgatagt tataggtaat tgtttttgte ttgtgacaat gcaagtagct taatttcaat taataaagtt tgatgttggt catttgtgtg gatcagtgga agcaggegta ggatgtgcta tattcaggsa tgoaaatgot aagtgcttet agacagactt tgattctaca caasagccaa gcagaatgct cactgcgaag tggttatttt tgaacctata agcaccggat ggatcaatgg tgttacatto aaatcatagc ttggtatgta catatgctgt tgattatact acagtaggta accactggti ttacaccetg atggaggagt tgtggtgatt attaatocta aatagtttaa gtagatgaca tecagtagat tttgttgatg caaadttata tacactttgg ccattttatt actcaaaatc gggtttgatg gaagctctta ttacaagaaa atcaatgggc ctagtaaaat teatetagga ccatatggtt gttagtcccg gttaatgtaa amp ctggaaata gtestgetga tttaasaacc ttggacctac tacatcaate tggcttttas tgtacaggat ggacatcagg gtggttactg atcggtttac taggtggttt ttattcaaao atgcagcatg tactcacaga tgaatggtgt t
79. 0000000000 HHHHHHHHHHHHHHHHHHHH HHHH 0000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 10 20 30 40 50 JP 4644486 B2 2011 3 2 46 100 1000 10 100 100 10000 n D 10000000 20 100 100 100 40 100 100 100
80. 00000000000000000000 Karpas et al 1968 Lou and V nner 1963 Randolph et al 1990000000 1000000000000000000000000 Bordete la bronchiseptica HHHHHHHHHHHHHHHHHHHHHHH 000000 0000000 HHHHHHHHHHHHHHHHHHHHH 000 100000 1000000000000 Makela et al 1998 Pensaert et al 1986 and Sapats 2000 HHHHHHHHHHHH Storz et al 2000 HHH 0000 Tennant et al 1993 Bi nn 197900000 000000 000 10000 ENS SEEN E iter Sa ES RES VR NEAR nn Leptospira cani col L icterohaenorrhagi ae 00000 r1 r1 r1 r1 u r1 r1 Bor det el bronchi septi Coyne MJ 5 1995 Consi derati ons in usi ng coro navirus vacci ne published as a Pfizer Technical Bulletin on the Internet at ht ww pfizer comah vet tref trbull ccv htm H
81. 004 2 5 74 100127052 SERRA 18 5 10 2006 5 10 31 0217434 0 74 100090033 32 14 7 27 2002 7 27 33 08 74 100093045 NCIMB 41146 54 CRCV 5 000000000 1000 0 00000000000000000000000000000000000000 HHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHH 1000 1000 1000 1000 1000 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 10000000 100000000000 1000 1000000 1000 1000 000 1000 100000 1000 100000000000000000000000 EP DLE EIE P ET SET EE EH 100000 10000000 000000 0000000000 0000000000000 00000000 00000 1000 10000000 0000 000000 10 20 2 JP 4644486 B2 2011 3 2
82. 1000 Sanbr ook 00111000000000000000000000000000000000 100 0000 0000 HHHHHHHHH 1000 DD DO 0000 Redi pri me random pri ner labelling kit 100000 Saiki et al 1988 Sci ence 239 487 4911 000 100000000000000000000000000000 100 100000000000000000000000000 00 00 19 JP 4644486 B2 2011 3 2
83. 2 2011 3 2 FIGURE 10 Page 4 of 5 FIGURE 10 Page 5 of 5 887 BCYspikepro INAILIEVNELLDITOLOVANSIMMGVII STRLRDGVAMNYDDIN BCUspikepro ECVKSOSSRINFCGNCNHIISLVORAPYGLYEIHFSYVPTKYVTAKVSPGLCTAGDRGIA HCVsplkepro INAILTEVNELLDTTOLOVANSLMNGVILSTKLKDGVNENVDDIN BCYspikepro ECVKSQSSRINFCGNGHHIISLVONAPYGLYFIHFSYVPTKYVTAKVSPGLCIAGDRGIA CRCVspikepr INAILTEVNELLDTTQLQVANSDMNGVTLSTELKDGENENVDDIR CRCVspikepr ECVKSQSSRINFCGNGNHIISLVONAPYGLYFIHFSYVPTKYVTAKVEPGLCIAGDRGIA HEVspikepro INAILIEVNELLDTTQLOVANSLMNGVTLSTKIKDGINENVDDIN BEVspikepro ECVKSOSSRTNFCGNGNBIISLVONAPYGLYFIHFSYYPTKYVTAKVSPGLCIAGDIGIS CECVspikepr IEDQALAMSASLENMEVDSMLFVSENABKDASVEAFNSTEHLDPIYKEWPNIGGSWLGGLK CECVspikepr ECVRSQSQREGFCGNGTHLISLANAAPNGMV PEHTVLLPTAYETVTAWSGICASDGDRTE m Bl brekk kgk i 933 ER p BCVspikepro GCLGSDCNKVSSRSAIEDLLFSKVKLSDVG FV AYNNCTGGAEIRDLICVOSYNGIKVL BCVspikepro PKSGYFVHVENTWMFTGSGYYYPEPITGNNVVVMSTCAVRYTKAPDVMLNISTP BCVspikepro GCLGSACNKVSSRSATEDLLFSKVKT SDVG FUTAYNNCTGGARIRDLICVOSYNGIKVL ACVspikepro PRSGYEVNVRNTWHFTGSGYYYPEPITGNRVVVMSTCANNYTKAPDVMLNISTP CRCVspikepr GCLGSECHKVSSRSAIEDLLFSKVKLSDVG FVDAYNNCTGGAEIRDLICVOSYNGIKVL CRCVspikepr 0 PKSGYZVNVNNTWMFTGSGYTYPEPITCHNVVVMSTCAVEYTKAPDVMLNISTP HEVspikepro SCLGSECNRASTRSRIEDLLFDKVKLSDVG FPVOAYNNCTGSAEIRDLICVQSYNGIKVL BEVspikepro PESGYFINVNNSWMFTGSGYYYPEPITONNVVVMSTCAVNYTKAPDLM
84. AFNOATGNITOAFGEYNDAIHOTSOGLATVAKALAKVODVVNTOGOALSHLTVOLQNSP CECVsplkepr LIDNINNTLVNLEWLNRIETYVKWEWYVRLLIGLVVVECIPLLLFCCCSTGCCG CIGCL SER ri Q8 CARATE ERE I CERA CIE BCVspikepro GAISSSLQEILSRLDALEAQAOXDRLINCRLTALNAYVSQOLSDSTLVKESAAQRMERVN BCVsptkepro BCVspikepro GAIGSSLOBILSRLDALEAQAQIDRLINGRLTALNAYVSQQNSDSTLVKFSAROAMERVN BCVspikepro GGCCDDYTGHOELVIKTSHDD CRCVspikepr GAISASLQEILSRLDALEAQAQIDRLINGRLTALNAYVSQQULSDSTLVKESARQAMEKVN CRCVspikepr GGCCDDYTGHOELVIKTSRDD BEVspikepro GAISASLOEILSRLDALEAKAQIDRLINGRLTALRAYVSOOLSDSTLVKTSAAOAJEKVN NEVspikepro GGCFDDYTGHOEFVIKTSEDD CECVEpikepr QAISSSISDIYNRLDELSADAQVDRLITGRLTALNAFVSQTLTRQAEVRASROLAKDKVN CECVspikepr GSCCESICSRRQFENYZPIEKVHVH ARA By Qr br E DW gt 00000 00000 FIGURE 11 FIGURE 13 TTACTTTTGT TAATGTACCA ATGGCTCTGC ACAATCTACA 60 GCTCTTTGTA AATAACCCTG CATATATAGC TCGTGAAGCT 120 ARTTTTGGGG GCTGATTTCT ATTTGTCAGG 180 10069 TITTARCEGC ANGITITISI CERATACARA 240 GATAGICAAT ATTATTITAA TARAGACACT GGTGTTATTT 300 72 15 18 12 113 T 121 ACCATTAACA CTGGTTTTGA TTTTAATTGT CATTATTTAC TITTACCCIC TGGTAATTAT 360 TTAGCCATT
85. AGTNYLTCY NANOCDCLCTPDPILSKSTGPYKCPOTKYLVGIGEBCSGLAIKS TCPVGTTVRKCEAAVTNATKCTCWCOPDPSTYKGVNAWTCPQSKVSIOPG BCPGLGLVE NITIDLGMKRSGYG QPIASTLSNITLPMODNNTDVYCIRSNOFSVYVHSTCKSSLVWDN 60 JP 4644486 B2 2011 3 2 00000 HOVspikepro CROVspikepr HEVspikepro CECVspikepr BCYspikepro HOVspikepro CRCVspikepr BEVspikepro CECVspikepr BCOVspikepro ECVspikepro CRCVspikepr HEYspikepro CECVepi kepr BCVspikepro CRCYSpikepr HEVspikepro CECYspikepr BCVspikepro HCVspikepro CREVspi kepr HEVspikepro CECVspikepr BCVspikepro HCVspikepro CRCVSpikepr HEVspikepro CECVspikepr BCVspikepro BCVspikepro CRCVspikepr HEVspikepro CECVspikepr BOVspikepro HCVspikepro CRCVspikepr HEVspikepro CECVspikepr BCVspikepro HCVspikepro CROVspikepr HEVspikepro CECVspikepr BCVspikepro HCVspikepro CRCVspikepr HEVspikepro CECVspikepr FIGURE 10 Page 1 of 5 HELILLISLPMALAVIGDLKCTTVSINDVDTGVPSVSTDTVDVTNGUGTYYVLDRV MFLILLISLPTAFAVIGDLKCTTVSINDIDTGAPSISTDIVDVTNGLGTYYVLDRV MFLIBLISDPMAFAVIGDDKCTTVSINDVDTGAPSISTDVVDVTNGLGTYYVDDRV MEPILLITLDPSVEAVIGDLKCNTSSINDVDTGVPSISSEVVDVTNGLGTFYVLDRV MIVLVTCILLLCSYHTASSTSNNDCRQVNVTOLDGNENLIRDELFONFKEEGTVVVGG 5 108 YLNTTLLLNGYYPTSGSTYRNMALKGTILLLSTLWFKPPFI S TREE YLNTTLLLNGYYPTSGSTYRNMALKGTLLLSRLWFKPPFLSDFINGIFAKVKNTKVIKKG YLNTTLLLNGYYPTSGSTYRNMALKGTLLLSTLWEKPPFLSDEIDGVFAKVKNTEVIKDG YLNTTLLLNGYYPISG
86. AGTTTAGTCCTTAATAACCCTGCATATATAGCTCCTCAAGCT GCTCTTTGTAAATCTGGTAGTTTAGTTCTTAATAACCCIGCATATATAGCTCGTGAAGCT GCACTTTGTAAGTCTGGCAGTTTAATTCTTAACAATCCTGCATATATAGCCCGTGAGGCT ERO ded FA ODE KE ER AE EA k AATTPIGGGGATTATTATTATAAGCTTGAAGCTGATTTCTATTTGTCAGGTTGTGACGAG AATTTTGGGGATTATTATTATAAGGTTGAAGCTGATTT TTATTTGTCAGGTTGTGACGAG BAACTCTGGGGATTATTATTATAAGGTTGAAGCTGATTTTTATTTGTCAGGTTGTGACGAG AATTTTGGGGATTATTATTATAAGGTTGAAGCTGATTTTTATTTGTCAGGTTGTGACGAG AATGTGGGTGATTATTATTATAAGTCTGAAGCAGATTTTTCTCTCTCAGGTTGTGACGAG AW AR RA ORO k TATATCGTACCACTTIGTATTTTTAACGGCAAGTITTTTGTCGAATACAAAGTATTATGAT TATATCGTACCACTTTGTATTTTTAACGGCAAGTTTTTGTCGAATACAAAGTATTATGAT TATATCGTACCACITTGTATTTTTAATGGCAAGTTTTTGTCGARTACAAAGTATTATGAT GORGE OR GATAGTCAATATTATTTTAATAAAGACACTGGTGTTATTTATGGTTTCAATTCTACTGRA GATAGTCAATATTATTTTAATARAGACACTGGTGTTATTTATGGICTCAATTCTACTGAA GATAGTCAATATTATTITAATARAGACACTGGTGITATITATEGICICAATICTACIGAR GATAGTCAATATTATTTTAATAAAGACACTGGTGTTATTTATGGTCTCAATTCTACTGAA Mu CRCV BCV BECV HEV CRCV
87. ATFRNVALKGTRLLSTLWFKPPFLSPFNDGIFAKVKNSRFSKHG YYPTEVWYNCSRTATTTAYEYFSNIHAFYFDMEAMENSTGNARGKPLLFHVIGEEVS V k 57 x To og 7l VMYSEFPAITIGSTFVNTSYSVVVOPSTTNLDNKLOGLLEISVCQYTMCEYPHTICHPNL VMYSEFPAITIGSTFVNTSYSVVVOPHTTNLONKLOGLDEISVCQYTMCEYPHTICHPNL VVYSEFPAITIGSTFVNTSYSVVVOPHTTKLONRLOGLLEISVCOYTMCDYPETMCBPNI VIYSEFPATTI GSIFVNTSYSIVVKPHTSEINGNLOGFLOISVCOYTMCEYPOTICHPNL IITISYRDDVQERPLLKHGLVCITESRNIDYN SFTSSQWNSICTGNDRKIPFSVIPTDN Ww ore Kausa AE LA gt 179 Da 20 GNRRIELWAWDTEVVSCLYKRNFTYDVN GNRRVELHHWDTGVVSCLYKRNFTYDVNW ri ADYLYFHFYQEGCTFYAYFTDYGVVT GNKRIELWBWDTGVVPCLYKRNETYDVN ADYLYSHFYOEGGTFYAYFTDTGVVT GNORTELWEHDTDVVSCLYRRNETYDVN ADYLIFAFYOBGGTTYAYFTDTGFVT GTKIYGLEWNDEFVTAYISGRSYNWNINNN WENNVTLLYSRSSTATROHSAAYVYOGVSN I e Pe PER 2 35 267 KFLFNVYLGTVLSEYYVMP LTCNSAMTLEYWVTELITSKQYULAFNODGVIF KFLENVYLGTVLSHYYVLP LTCNSAMTLEYWVTPLTSKOYLIATNODGVIF KFLFHVYLGTVLSHYYVMP LTCNSAMTLEYWVTPLTFKQYLLAFNQDGVIF KFLEKLYLGTVLSHYYVMP LTCDSALSLEYWVTPLTTROFLLAFDODCVLY FTYYKLENTNGLETYZLCEDYEYCTGYATNHIFAPTVGGYIPDGFSFNNWFLLTRSSTFVS pe ads E FIGURE 10 Page 3 of 5 592 608 DYCGGNPCTPCOP AFLGWSVDSCLOGDRCH IFANFILHDVNSGTTCSTDLOKGNTDII DYCGGNFPCTCQPQAFDGHSVDSCLOGDRCN IFANFILHDVNSGTTCSTDLORSNTDII DYCGCNPCTCQPKAFLGUSVDSCLOGDRCN IFARTILHGVNSGTTCSTDLOKSNTDI
88. ATGATCTTT RCVspike CTGATARTAGTACTTCTAGTCTTCTTCAAACATGUGATCICACAGTAGGTAGTCGTTACT CRCVspike CIGATTTACAARAATCARACACAGACATAATTCTTOGTGTITGTGTTANTTATGRTCTTT CRCVspike CTGATAATAGTACTTCTAGTTCTGTTCAABCATGTGATCTCACAGTAGGTAGTGGTTACT HEVspike CTGATTTACAACAGGGTAATACTAATATTACTACTGATGTTTGTGTTAATTATGACCTAT HEVspike CTTATARTARTACAGCTAGTCCTGTARGTACTTGTGATTTARCOGTTGGTAGCGGCTATT a RARA Gdd daade oh AR ERRARE XX ak BCVspike ATGGTATTACACGCCAAGGTATTTPTGTTGRGGTTARTGCGACTTATTATAATAGTTGGC BOVspike GCGTGGATTACTCTACAABANGACGAAGTCGTAGACCGATTACCACTGGTTATCGGTITA HCVsptke ATGGTATTACAGGCCAAGGTATTTTTGTTGAGGTTAATGCGCCTTATTATAATAGTTGGC HCVspike GTGTGGATTACTCTACARARAGACGARGTCGTAGAGCGATTACCACTGGTTATCGOTTTA CRCYspike CASGCCAACGTATTTTTCTTGAGGTTAATGOGACTTATTATANTAGTTOGC CRCVSpike GGGGGGATTACTCTACACAARCACGRAGTCGTAGARCOMTTACOACTGGTTATCGGTTTA HEVspike ATOGCATTACAGGCCAGEGCATACTTATAGAAGTTAATGCCACGTATTATAATAGTTGGC HEVspike GTGITGATTATGTTACAGCACTTAGATCACGTARGATCTTTTACTACAGGTTATCGCTTTA md k EcYspike BCVspike CTARTTTTGAGCCATTTACTGTTARTTCAGTAAMTGATAGTTTAGAACCTGTAGGTGOTT HCVspike RGARCCTTTTATATGATTCTAATGGTARTCTCTATGGTTTTAGAGACTACTTAACARACA
89. CCTTCAGAGTTTACTATAG CROVspike BARCACAGACATAATTCTTGGTGTTTGTGTTARTTATGATCTTTATGGTATTACAGGCCA C cVapiks POGAGATGTT CAACCAATTAGOACTGGCAATGTCACGATACCCACAAACTTTACCATAT CECVspike AR TGAGCAGGTTGTTAGARGTTTATATGTAATATATGAACAAGGAGACAACATAGTGGG X d ye dr ILE ERE QUON MER E w sakha CRCVspike GTAMTATGGACGAGTTTATTCAAACAAGATCTCCTARAGTTACTATTGATTGTCCTGTTT CRCVspike AGGTATTPTTGTTGA GGTTARTGCGACTTATTATAAMTACTTGGCAGAACCTTTTAT EUREN CEGTCCAAGTTGAATACATCCACGTTTACACTACACCGGTGTCRATAGATTGITCTAGAT CECVspike TGTACCGTCTGATARTAGTGGTCTTCACGATTTGTCAGTGTTACACTTAGACTCCTGTAC RG n TTGTCTGTGGTGATTATGCAGCATGTARATCACAGTTGGTTGAATATGGTAGTTTT GTG DASANE TANI G CECVspike ACGTTIGTANTGGTAACCCTAGATGTARTAAATTGTTARCACBATATGTSTCTGCATGTC CECVspike A GATTACARTATATATGGTAGAACTGGTGTT GGTATTATTAGACABACTAACAGCACA SRI RATIO ta n w wk FIGURE 8 6 of 9 FIGURE 8 Page 7 of 9 CRCVspike 4 CRCYspike TATTICTAATGCATTTAACARIGCOCITERTECTATI CAGGAAGGETT CECVspike AAACTATTGAGCAAGCGCTTGCAATGAGTGCCAGCCTTGAAAACATGGAAG TTGATTCCA CECVspike CCTGGCTAATGCTTTCAACCAAGCTATTGGTAACATTACACAGGCATTTGGTAAGGTTAA w waww p E wakan
90. CGGATGTAATGCTGAACATTTCAA CRCVspike CETCTTAATGCTTATGITICTCAACAGCTTAGTGATTCTACACTAGTAAAATTTAGTGCAG CRCVspike TTATGAGTACCTGTGCTGTTAACTATACTAAAGCACCGGATGTAATGCTGAACATTTCAA HEVspike CTCTTAATGCTUTATGTTTCTCAGCAGCTTAGTGATTCTACACTAGTAARATTTAGTIGCAG BEVspike TGNIGAGTACGTGTCCTCTTAATTATACTAAAGCACCGGATCTARTGCTGAACACATCGA mm M ode Adde ede KORR bt RIE ERE BOVspike BCVspike CACCCAACCTCCCTGATTTTAAGGARGRGTTGGATCAATGGTTTAARARCCARACATCAG BCVspike CACARGCTATGGAGAAGGTTAATGAATGTGTCAAARGOCAATCATCTAGGATAAATTTTT HCVspike CACCCAACCTCCATGATTTTAAGGAAGAGTTGGATCAATGGTTTAAARACCAAACATCAG CROVspike CACARGCTATEGAGBAGGI TARTGARTEGIGICRARAGCCRATCATCTAGGATARASTITI CRCVspike CACCCAACCTCCCTGATTTTAAGGAAGAGTTGGATCARTGGTTTAAAAACCARACATTAR HEVspike CACARGCTATTGAGAAAGTTABTGAATGTGTTARAAGCCARATCATCTAGGATAANTTTCT HEVspike CACCCAACCTICCTGATTTCAAGGAAGAATTGTATCAATGGTTTAAARACCARTC TPTCAT debba A RIAPRE RELA EIA RA RI RARE AREA k BCVspike GTGGTAATGGTAATCATATTATATCATTAGTGCAGAATGCTCCATATGGTTTGTATTTTA BCVspike TGGCACCAGATTTGTCACTTGATTATATARATGTTACATTCTTGGACCTACARGATGARAA HCVspike GTGGTAATGGTAATCATATTATATCATTAGTGCAGAATGCTCCATATGGTTTGTATTTTA HCV
91. CRCVspike CECVspike CRCVspike CECVspihe CRCVspike CECVepike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike CRCVspike CECVspike FIGURE 8 Page 1 of 9 ATGTTPTTGATACTTTTA ATGATTGTGCTCGTARCTTGCATTTTATIGTTATGTTCATACCACACTGCTTCCAGTACG GCTTTTGCTG TTATAGGBGATTTAAAGTG TACTACGGTTTC CATCAATGATGTTGACA SCARATAATGATTGTAGACAAGTTAR CGTAACACAATTAGATGGCAATGAARACCTCA E CCGGTG CICCTTCTATTAGCACTGATGTTGTCGATGTTACYAATGGTTTAGGTACTTAT TTAGAGACTTTTTGTTTCARARCTT TARAGAAGAAGGAACTGTAGTTGTTGGTGGTTAC ON TATGTTTTASA TCGTGTG TATTTAAATACTACA TTGTTGC TTAATGGTTA TACCCTACAGAGGTTIGGTATAACTGTTCTAGAACAGCAACAACTACTGCCTA TGAGTA AO Rx w uw wk ROBA ka TTATCCTACTTCAGGTTCTACATATCGTAATATGGCA CTGAAGGGAACT TTACTATTGA TTICAGTAATATACACGCATTCTATTTTGATATOGAAGCCATGGAGAATAGTACTGGTAA E ORO wakaka RESA LC GCACACTATGG TTTABACCBCCATTTCTTTCTGATTTTATTGATGGTGTTTTTGCTAA TGCACGTGGTARACCTTTATTATTTCATGTTCATGGTGAGCCTGTTAGTGTCATCATATA m GGTAARAAATACCARGGTIATTAAAGATGGTGTAGTGTATAG TGAGTTTCCTGCTAT CATATCTTA
92. D NO 33 00000 00000000000000000000000000 00000 058942 1146430000000 40 Spi Spi ke2 Spi ke3 Spi ke4 LU HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHl Spi kel 5 CTT ATA AGT GCC CCC AAA CTA 25291 25314 Spi ke2 5 CCT ACT GTG AGA TCA CAT GIT TG 25912 25890 Spi ke3 5 GTT GGC ATA GGT GAG CAC 25320 25339 Spi ke4 5 GCA ATG CTG GIT CGG AAG AG 25762 25742 50 42 JP 4644486 B2 2011 3 2
93. GCGGT GATAACATGACGGCGGT GATAACATGACEGCAGT GATAACATGACGGCAGT FIERE REIT sj a A x lt ac N spa AXhol SpF 62 CRCV BCY HECV HEV BCV 0043 CRCV 0043 1000 bp 750 500 bp ua 250 JP 4644486 B2 2011 3 2 FIGURE 16 YRSLTEVNVPYVYNGSAOSTALCKSGSIVLNNPAYIAREANFGDYYYKVEADFYLSGCDE YRSLTEVNVPYVYNGSAQSTALCKSGSLVLNNPAYIAREANFGDYYYKVEADFYLSGCDE YRSLTFVNVPYVYNGSAQSTALCKSGSLVLNNPAYIAPOANSGDYYYKVEADFYLSGCDE YRSLTFVNVPYVYNGSAQSTALCKSGSLVLNNPAYIAREANFGDYYYKVEADFYLSGCDE XRSLTLVNVPYVYNCSAOPTALCKSGSLILNNPAYIAREANVGDYYYKSEADFSLSGCDE khkk AIR YIVPLCIFNGKFLSNTKYYDDSOYYFNKDTGVIYGENSTETINIGFDFNCHYLLLPESGNY YIVPLCIFNGKFLSNTKYYDDSOYYFNKDIGVIYGLNSTETITTGFDENCHYLVIPSGNY YIVPLCIFNGKFLSNTKYYDDSQYYFNKDTGVIYGLNSTETITTGFDUNCYYLVLPSGNY YIVPLCIFNGKELSNTKYYDDSDYYFNKDTGVIYGLNSTETITTGFDFNCHYLVLPSGNY YIVPLCIFNGKELSNTKYYDDSQYYFNKDTGVIYGLNSTETITTGFDENCHYLVLPSGNY ORE IR III LAISNELLLTVPTKAICLNKRKDFTPVQVVDSRWNNARQS DNMTA LAISNELLLTVPTKAICLNKRKDFTPVQVVDSRWNNARQSDNMTA LAISNEULDLTVPTKAICLNKRKDFTPVQVVDSRWNNARQSDNMTA LAISNELLLTVPTKAICDNKRKDFTPVQVVDSRWNNARQSDNMTA LAISNELLLTVPTKAICLNKRKVFTPVQVVDSRENNAROSDNMTA PIA IO EA E RI OR KAKA KAKE ERRE AGO E FIGURE 17 1
94. GGGTTTGATGCTACCAATT CRCVsptke TTICTAMTGCATTTARCRATGCCCTTGATGCTATTCAGGAAGGGTTTGATGCTACCAATT HEVSpi CCTCTGTATTAGGTTCTTTAGGARGCGRATGTARCAGAGCTTCCACTAGATCTGOTATAG TTGCTAGTGCATTTARCARCCCTCTTGATTCTATCCAGGAAGGGTTCGACGCAACCAATT EE AREE AE AA KAKARANGAN BCVspike AGGATTSACTTTTTTCTRAAGTAAAGTTATCPGAYGTOGGTTTTGTTGAGGCTYATAATA BCVspike HCVspike AGGRTTTACTTTTTTCTARAGTARAGTTATCTGATGTCOGTTTCGTTGAGGCTTATAATA HCVspike CTGCTTTAGTTAARATTCAAGCTGTTGTTAATGCARATGCTGARGCTCTTARTARCTTAT CRCVspike AGGATTIACTITTTTCTARAGTAAAGTTATCTGATG TGGTTTTGTTGATGCTTATAATA CRCVspike CIGCTTTAGTTAAAATTCARGCTGTTGTTAATOCAAATGCTGAAGCTCTTARTAACTTAT ABVspike AGCATTTACTTTUTGRTAAAGTARARTTGTCTGATGTCGGTTTTGTACAGGCCUTATARTA CTGCTTTAGTTAARATTCAGGCTGTTGTTAATCCAAATGCTGAAGCACTTAATAACTTAT PRAIA IGO ki FREIRE RARE 8 RE KARAREHE GROSSA GA RO RIE BCVspike ATIGTACTGGAGGTGCCGARATTAGGGACCTCATTTGTGTGCAAACTTATAATGGTATCA BCVspike TGCAACARCTOTCTARTAGATTTGGTGCTATARGTTCTTC TTACARGAAATTOTATCTA HCVspike A PTGTACTGGAGGTG CGARATTACGGACCTCATTTGTGTGCAAAGTTATAATGGTATCA HCVspike TGCAACAACTCTCTANTAGATTTGGTGCTATAGGTTCTTCTTTACAAGABATTCTATCTA CROVspike ATI
95. GGTGTTTTTACTGATCATGATGTTGTTTATGCAC CRCVspike GThCTTGCCAACCABAAGCATTTTTGGGTTGGTCTGTGGACTCTTGTTTACAAGGGGATA HEVspike AGGC CTT CATGATGCTGTATATTCAC HEVspike GCACTIGTAAACCACAGGCTTTCATAGGCTGGAGTTCAGAAACTTGTTTGCAARATGGTA mo RARA aan FIGURE 9 6 of 12 FIGURE 9 Page 7 of 12 BCVspike BCVspike TTICACGACAGCTGCAACCTATTARCTATTTTGATAGTTATCTTGGTTGTCTTGTCAATG JHCVspike GGTGTARTATITTTGCTAATTTTATTTTGCATGATGTTAATAGTGGTACTACTTGTTCTA TTTCACGACAGCTGCAACCTATTARCTATTTTCATAGTTATCTTGGTTGTGTTGTCAATG CRCVspike GGTGTARTATTTTIGCTAATTTTATTTTGCATGGTGTTAATAGTGGTACTACTTGTTCTA TITCACGACAGCTGCAACCTATTAACTATTTTGATAGTTATCTTGGTTGTGTTGTCAATG HEVspike GGTGTANTATTTTTGCTARTTTTATTTPIGARTGATGTTARTAGCGGTACTACCTGTTCTA BEYspike TTTTAAGACARATACAGCTTGTTARTTATTTTCATAGTTACCTTGGTTGTGTTGTTARTG RIE RARA RA AA ER RR E FREIRE ARA dedit ts de kk k TC TRE TTIT TITTI BCVepi ke BCVspike HCVspike CTGATTTACAARAATCAAACACAGACATAATTCITGGTGTTTETGTTAATT
96. GTACTGGAGGTGCCGARATTAGGGACCTCATTTGTGTGCARBGTTATAATGGTATCA CRCVspike TGCRACAACTCTCTARTARATTTGGTGCTATAAGTGCTICTTTACARGAAATICTATCTA HEVspike ACTGCACTGGAGGAGCCGAAATTAGGGATCTCATTTGTGTGCAAAGTTATARTGGTATCA HEVspike dOdek KARAN KAKAK E KABAR GA n k AAAA A FIGURE 9 Page 10 of 12 FIGURE 9 Page 11 of 12 BCVspike GACTTGATGCTCTTGAAGCGChAGCTCRGATAGACAGACTTATTAATGSGCGTCTTACCG 1 BCVspiXe GACTGGATGCTCTTGAAGCGCAAGCTCAGATAGACACACTTATTAATGGGCGTCTTACCG HCVspike GGATGTTCACTGGTAGTGGTTATTACTACCCTGAACCCATARCTGGAAATAATGTTGTTG CACTTGATGCTCTTGARCCGCARGCTCAGATAGACAGACTTATCAATCOCCOTCTTACCG CRCVspike GGATGTTCACTGGTAGTGGTTATTACTACCCTGRACCTATARCTGGAAATAATCTGGTTG HEVspike GECTCEATECTCTTEAASCTAAAGCTCAGATAGACAGACTTATTAATGGGCGTCTCACCG HEVspike GGATGTTCACTGGTAGTGGCTATTACTACCCTGARCCTATARCCCAAANTAATOTTGTTG Geo a kak ORE AGRO eR de RR OE ERRE PEER RARE ROO nene dede dee BCVspike CTCTTAATGCTTATGTTTCTCARACAGCTTAGTGATTCTACACTAGTAAAATTTAGTGCAG BCVspike TYATGACYACCTGTGCTIGTTARTTACACTAAAGCACCGGATGTAATGCTGAACA TTTCAA HCVspike CTCTTAATGCTTATGTTTCTCAACAGCTTAGTGATTCTACACTAGTAAAATTTAGTGCAG BCVspike TTAIGAGTACCTGTGCTGTTARCTATACTAARGCGC
97. I DDCSCHPCTCKPOAFIGWSSETCLQNGRCN 1FAXFILNDVNSGTTCSTDLOQGNTNIT NEHODCTDVLYATAVIKTGTCPFSEDELNNY LTERKLCLSTNPTGANCKFDVAARTRTNE 40 di LDGVCVNYDLYGITGQGIFVEVNATYYNSHONLLYDSNCNLYGFRDYLTNRTFMIRSCYSG LGVCVUNYDLYGITGQOIFVEVNAPYYNSWOQNLLYDSNGNLYGFRDYLTNRTEMIRSCYSG LGVCVNYDLYGLITGQGIFVEVNATYYNSWONLLYDSNGNLYGFRDYLTNRTEMIRSCYSG TDVCVNYOLYGITGQGIDLIEVNATYYNSWONLLYDSSGNLYGFRDYLSHMRTFLIRSCYSG QVVRSLYVIYEECDNIVGVPSDRSGLEDLSVLHLDSCTDYN IYCRTGVGIIRQTNST Pac M M de 22 6 RVSAARFHANSSEPALLFRNIKCNYVERNTLSROLOPINYFDSYLGCVVNADNSTSSAVOT RVSARFHANSSEPBLLFRNIKCSYVFNNTLSROLQPINYFDSYLGCVVNADNSTSSVVOT RVSAGFHSNSSEPALLFRNIKCNYVENNTLSROLOPINYFDSYLGCVVNADNSTSSSVOT RVSAVFHANSSEPALMFRNLACSHVENYTILRQIOLVNYFDSYLGOVVNAYNNTASAVST ILSGLEYTSLSGDLLGFKNVSDGVVYSVTPCDVSAQAAViIDGATVGAMTSINSELLGLTH 757 759 763 ze9 COLTVESGYCVDYSTKRRSRRAITTEYRETNFEPFTVN CDLTVGSGYCVDYSTKRRSRRATYTGYREFTNEEPFTVNS CDLIVGSGYWGCDYSTORRSRRTITTGYRFTNFEPFTVNE CDLTVGSGYCVDYVTALRSRRSFTTCYRFTNFEPFAANL WITTPNFYYYSIYNTTNERTRGTAIDSNDVDCEPIITYSNIGVCKNGALVFINVTESDGD A24 4 vs 827 928 L PVGGLYEIQIPSEFTIGNMEEFIQISSPKVTIDCSAFVCGDYAACKSOLVEYGSFCDN LEPVCGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDCSAFVCGDYARCKSQLVEYGSFCONM LHPVGGLYEIQIPSEFTIGNMEEFIOTRSPKVTIDCPVTVCGDYARCKSQLVEYGSFCDN IEPVGGLYEIQIPSEFTIGNLEEFIQTSSPKVTIDCATFVCGDYARCRQOLAEYGSFCEN VOPIS TGNVTIPTNITISVOVEYIQVYTTPVSIDCSRYVONGNPRONKLLTOYVSACOT Ps pr O 919 p 2 ALS 61 JP 4644486 B
98. LNTSTP CECVspikepr DILPSHNSKRKYRSAIEDLLEDKVYTSCLETVDEDYKRCTGGYDIADLVCAQYYNGIMVL CECVspikepr GINVEDVOLTLERNLODKFYLTPRTMYOPRARTSSDFVQIEGCDVLFVNATVIDLESIIP z B o rr gt 257 BCVspikepro PPLLSENQISGYTLAATSASLFPPSS ARAGVPEYLNVOYRINGIGVTMDVLSQNOKLTA BCVspikepro n RLOE HCVspikepro PPLLSVNOTSCYTLAATSASLFPFNS AARGVPFYLNVOYRINGIGVTHDVLSONOKLIA BCVspikepro NLHDFKEBLDOWFKNOTS VAPDLSLDYINVIFLDLODEMN RLOR CRCVspikepr PPLLSENQISGYTLEATFASLFPPWS ARAGVPFYLNVOYRINGIGVTMDVLTQNOKLIS CRCVspikepr NEPDPKESLDOHWFKNQTL MAPDLSLDYINVTFLDLODEMN RLOE HEVSpiXepro PPLLSENQISGYTSAATAASLFPPWT ARAGVPFYLNVOYRINGLGVTMDVLSQNOKLIA HEYspikepro NLPDFKEELYQWFKHQSS LAPDLSEFDYINVTEFLDLQDEMN RLQE CECVspikepr PGVANDDEMTMYTASLAGGIALGALGGGAVAIPFAVAVORALNYVALQTDVLRKHOOILA CECVspikepr DYIDINOTVODILENYRPHWTVPELTIDIFRATYLNLTGEIDDLEFRSEKLHNTTVELAT TEM gt 1063 BCVspikepro EAFNNALDAIQEGFDATN SRLAKIQRVVHRNASALNNLLOOLON E BCVsp epro AIKVLNOSYINLAKDIGIYEYYVKWPWYVWLLIGLAGVAMLVDLFFICCCTGCGTSCEKKC BCVspikepro NAFSNBLDAIQEGFDATN SALVKIQAVVNANAEALNNLLQULSNRE ACVspikepro AIKVLNQSYINLKDIGTYEYYVKWPWYVWLLIGFAGVAMLVLLFFICCCTGCGTSCEKIC CRCVspikepr NAFNNALDAIOEGFDATN SALVKIORVVNAMAEALNNLLOOLSNKF CRCVspikepr AXKNLNESYTNCKDIGTYEYYVKWEWYVRLLIGLAGVAMLVLLFFICOCTGCGTSCEKKC SAFNNALDSIORGEDATN SALVKIQAVVRANAEALNNDLQOLSNRE HEVspikepro AXKVLNHSYINLKDIGTYEYYVKWPWIVRLLICLAGVVMLVLLFFICCCTGCGTSCFKKC CECVspikepr N
99. P FANFILUGVN YDSNGNLYGE LOPINYFDSY RETVNPVNDS TVEYGSFCDN GCLGSECHKV PLLSENQISG FNNALDAIQE LEAQAQIDRI NBLISLVONA GSGYYYPEPI LSLDYINVTF MLVLLFFICC HH MHV TGEV FIPV tacttttaat tttccatcaa ctastggttt ttaatggtta tactattgag ttgctaaggt ctataactat ctactaattt tgtgcgatta ggcattggga atgctgatta cagacactgg attattatgi ctcteacttt ttgattgtaa ctactggtgt gtatacctaa ctecattasa tgtcttttat gtatgtgttt acctacaaat ctacaagttg atccttotat ctgtaggtgt casatttotg atgctggtta gttataatgo cagggectta grottgotat ttttgggttg tattttgoa cagacataat tttttgttga atggtastct gctatagcgg ttcggaatat ttaactattt MAFAVIGDLK SGSTYRNMAL TCNSAMTLEY NGYTVOPiAD SETCNNIDAA YNLPASNVSI TNGSLCYGSG OTKYLVGIGE SGTICSTDLQ RDYLTNRTEM LGCVVNADNS LHPVGGLYEI TNALLTEVNE SSRSATEDLL YTLRATFASD GEDATNSALY INGRLTALNA PYGLYFIHES TGNNVVVMST LDLODEMNRL CTGCGTSCEK 4644486 FIGURE 3 1 of 2 ttecttacca tgatgttgac aggtacttat ttatcctact cacactatog aggtagtact agataataaa cccacatacg tacaggtgtt tttgtattcc tgttgttact catgcccttg taaacagtat gagtgatttt ttatgaatta tcttcecogat ttqggaacgt ccaggetgac tttoagcata gggcaatttg tcagttgtat ttggantagg ttttactgat tecgtgtana taaaaatagt taaccaatgt taagtgecce taaaagtgat gtctgtggac tggtgttaat tettggtgtt gottaatgcg ctatggtttt tegtgtktoa taaatgcaat tgatagttat FIGURE 4 CTTVSINDVD KGTLLLSTLW
100. QPRTTNLDNK YDVNADYLYS WVTPLTFKQY VYRRIPNLPD KIYGMCFFSI SRENFSIWNR FGIDAGYKNS ECSGLAIKSD KSNTDXILGV IRSCYSGRVS TSSSVOTCDL QIPSEFTIGN LLDTTOLOVA FSKVKLSDVG FPPRSAAAGV KIQRVVNANA YVSQOLSDST YVPTKYVTAK CAVNYTKAPD QEAINVLNRS KCGGCCDDYT atggcttttg accggtgotc tatgttttag tcaggtteta tttaaaccac aaggttatta tttgtaaata ttacaaggio atgtgtcato gtteoctgtt catttttatc aagtttctgt acttgtasta ttactcgctt atgagtgaga aacggttaca tgtaatatag aagacctttt tcgrttactt actatagata ggctatttoc tataatttac agatttggtt catgatgttg itgaatgggt ggtataggca gattgtttgt caaactaaat tattgtggeg tcttgtttac agtggtacta tgtgttaatt acttattsta agggactact gegagctttc tacgttttta cttggttgtg FIGURE 5 HEV TCV GAPSTSTDV FKPPFLSDFI LOGLLEISVC HFYQEGGTFY LIAFNQDGVI CHIEAWLNDK TIDKFATENG GIGTCPAGTN YCGGNPCTCQ CVNYDDYGIT AGFASNSSEP TVGSGYWGDY MEEFIQTRSP NSLMNGVTLS EVDAYNNCTG PEYLNUQYRI EALNNLLOOL VSPGLCIACD VMDNISTPNL YINLKOIGTY GHOELVIKTS HDD ctgttatagg cttctattag atcgtgtgta catatcgtaa catttotito aagatggtgt catcctatag tcttagagat tatataagog aagaaggtgg ttcatgttta gtgctatgac tcaatcaega ttaagtgtas ctgttcagcc aggettaget casattgtsa gtaataatat agtttgctat agtcttttaa ctgctagtaa ttacagaaca tttatgcaca etttgtgtgt cttgtcetgc gcactccaga acttagttgg geaatccttg aaggggatag citgttctac atgatcttta atagttggca taacazacag actctaactc ateatactct ttgtcaatge agatttaaag
101. RI Y eee TTAATGATAAGTCTGTGCCCTCTCCATTABATTGGGAACGTAAGRCCTTTTCARATTGTA TTAATGATAAGTCGGTGCCCTCTCCATTAAATTGGGAACGTARGRCCTTTTCARATTGTA TYTAATGATAAGTCGGTGCCTTCTCCATTAAATTGGCAACGTAAGACCTTTTCAAATTGTA TTAATICTAAGACCGTTTCTTCGCCTCTTARTTGGGAACGTARAATTTTTTCTAATTGTA mE 58 JP 4644486 B2 2011 3 2 FIGURE 9 Page 4 of 12 FIGURE 9 Page 5 of 12 BCVspike ATTTTARTATGAGCAGCCTGATGTCTTTYATTCAGGCAGACTCATTTACTTGTARTARTA ARCATTGUITIAAAGCTCCCACARATTTCIGTCCETETARATTEGATEGCICITTELETE HCVspike ASTTTTAATATGAGCAGCCTGATGTCTTUTATTCAGGCAGACTOATTTACTTGTAATAATA HCVspike ARCATTGTTTTABAGCTCCCACBARTTTCTGTCCGTGTAAATTGGATGGOTCTTTGTGTG CRCVspike ATTTPAATATGAGCASCCTGARTGTCTTTTATCCAGGCTGACTCGTTTACTPGTARTAATA CRCVspike ARCATTETTITARAGCTCCCACAARTITOTEGTOCETETARATIGAATEGETTITTETETE BEVspike ATTTTAACATGGGCAGGCTGATGTCTTTTATTCAGGCTGACTC T PTCGTTGTARCAATA AGCARTGTTTTARTACACCTARTACATATTGTCCTTGTA GAACAAGTC AATGCA Gd adde don ARAR FROG ROGO KERAN deiner oT BCVspike TTGATOCAGCTAAGRTATATGGTATGTGYTTTTCCAGCATARCTATAGATAAGTTTGCTA BCVspike TRGCTAGTGGTTCTGGTATAGATGCTGGTTATARARATAGTGGTATAGGCACTTGTCCTS HCVspike TUGATGCTGCTAAGRTATATGGTATGTGTTTTTCCAGCATAACTATACATAAGTTTGCTA ACVspike CROYspike TTGATGCTGCTARGRTATACGGTATCTGTTTTTTCAGCATARCTATACATAAGTTTCCTA CRCVspike
102. S Hyypia T Arstila P 1998 Viruses and bacteria in the eti ol ogy of the common cold J Clin Mcrobiol 36 539 42 Treeview An applicati on to di spl phyl ogeneti c trees on persona computers Computer Applications in the Bi osci ences 1996 12 357 358 Pearson VR Rapid and sensi ti ve sequence conpari son th FASTP FASTA Meth ods Enzynol 1990 183 63 98 Pensaert M Callebaut P Vergote J Isolation of a porci ne respiratory non e nteri c coronavirus rel ated to transnissi bl e gastroenteritis Vet 1986 8 3 257 61 Randol ph JF Mise NS Scarlett JM Shin SJ Blue JT Bookbi nder PR Preval en ce of nycopl asmal and ureapl asmal recovery fromtracheobronchi al avages and pre val ence of nycopl asmal recovery from pharyngeal swab speci mens in dogs wth or w ithout pul nonary disease Am Vet Res 1993 Mar 54 3 387 91 Spaan W Cavanagh D Horzi nek Coronaviruses structure and genone express ion J Gen Virol 1988 Dec 69 Pt 12 2939 52 Stephensen CB Casebolt DB Gangopadhyay NN Phylogenetic analysis of a hi ghl y conserved regi on of the gene from 11 coronaviruses and devel opnen t of a consensus ymerase chai n reacti on assay Virus Res 1999 Apr 60 2 18 1 9 Storz J Purdy CW Lin X Burrell M Truax RE Briggs RE Frank GH Loan RWIs olati on of respiratory coronavirus other cytoci dal viruses and Pasteure spp fromcattle i
103. TACGCACGGTGCTTTCACRTTATTATGTCATGCCCTTGACTTGTAATAGTGCTATGOA AUTTAGGCACTGTGCTGTCACACTATTATGTTATGCCATTGACTTGTGATAGCGCTTTAT KAKA KANAKA IUSR RUE RE debeo dae SODA A CTYTAGARTATTCGGITACACCICTCACTTCTARACAATATTTACTCGCTTTCAATCAAG CTTTAGAATACTGGGTTACACCTCTCACTTTTAAACAATATTTACTCGCTTTCAATCAAG CTTTAGAATATTGGGTTACACCTCTCACTACTAGACAATTTCTTCTAGCCTTTGACCAGG APR E AAA UE RA RAR AE RE ER EA RAR bk k b ATGGTGTTATTTTTARTGCTGTTCATTGTAAGAGTGAT TTTATGAGTGAGATTAAGTGTA ATYGGTGTTA TTTTTAATGCTGTTGATTGTAAGAGTGATITTATGAGTCAGATTAAGTOTA BTGGTGTTATTTTITAATGCTGTTGRTTGTARGAGTCATTTTATGAGTGAGATTAAGTGTA ATGGTGTTTTATACCATGCTGTTGATTGTGCTAGTCATTTTATGAGTGAGATTATGTGTA A kO FEAR PRO RIA E ABACACTATCTATAGCACCATCTACTGGTGTTTATGAATTAAACGGTTACACTGTTCAGC AARCACTATCTATAGCACCATCTACTGGTGTTTATGAATTARACGGTTACACTGTTCAGC ARACACTATCTATAGCACCATCTACTGGTGTTTATGARTTARACGGTTACACTGTTCAGC ARACTTCTTCAATTACACCACCTACTGGTGTTTATGAACTARACGGTTACACAGTTCAAC PERAE gt CAATTGCAGATETTTACCGACGIATACCTRATCTICCOGATTEGTAATATAGAGGCTTEGC CAATTGCAGATGTTTACCGACGTATACCTARTCTTCCCGATTGTAATATAGAGGCTTGGC CAATTGCAGATGTTITACCGACGTATACCTAATCTTCCCGATTGTAATATAGAGGCTTGGC CTGTTGCCACTGTGTATCGTAGAATACCTGACTTACCCAATTGCGATATCGAAGCTTGGC w
104. TAGAGAYGATGTGCARCATAGGCCACTTTTARAACACGGAT TAGTGTGCAT E w BACTATAGGIAGTACITTTG TA ARTACATCCTATAGTETGGTAGTACAACCACATAC RACTERRAGTCGCAACATTEACTATRACAGTTTCACCAGTA GCCAGTGGRATTCCATAT ek w TETTO TACTAATTTAGATAATAARTTACARGGTCTCTTAGAGATCTCTGTTTGCCAGTATACTA G TACGGGTAATGACAGAAABATTCCTT TCTCTGTCATACCCACGGACAATGGAACAAAA ww rn FIGURE 8 Page 3 of 9 CTTGGCTTAATGATAAGT CGGTGCCTICTCCATTAARTTGCGAACGTAAGACCTTTTCA ATGGGTGCTACAGTATTTTCACTGABTACAACAGGTGGTTGCATTCTTGCAGATTTCTT bowa ABTTGTAATTTTAATATGAGCAGCCTGATGTCTTTTATCCAGGCTORCTCGTTTACTTGT GTTATARTGATATAGTGAGCSAGTCAAGTTTCTACAGTTATGGTGA AATTCCCTIC ORO REA oe da RATAATATTGATGCTECTARGATATACGETATETETTTITTCA GCATAACTATAGATA CGCGTAACIGATGG ACCGCGTTAT TGTTATGTCCTCTATAATGGCACAGCTCTTAAGT AGTTTGCTA TACCCAATGGTAOGAAGGTTGACCTACAAATGGGCAATTTGGGCTATT ATTTCGCCACATTACCCCCTAGTGTCAAGG AAATTGCTATTAG TAAGTGGGGCCAAT w Wk GR k st A TGCAGTCTTTTAACTATAGARTTGATACTACTGCTACRAGTTGTCAGTTGTATTATAATT TTTATATTAATGGTTACAATTTCTTTAGCACTTTTCCTATTGATTGTATATCTTTTAACT ZU TACCTGCTAGTAATGTITCYATTAGCAGGTPTTAATCCTTCTATTTGGAATA GGAGATT TAACCACTGGTGATAGTGGAGCATTTTGGACABTTGCTTACARCATCGTACACTGARGCAT DO AK w o TGGTTTTA CAGAACAATCTGTTTTTAAGCCT CAACCTGTAGGTG
105. TGGTACATATGAGTATTATGTAAAATGGCCTTGGTATGTATGGCTTTTAATTGGCTTTG CRCVspike TYGCAGGTGATAGAGGTATAGCTCCTARGAGTGGTTATTTTGTTARTGTAAATAACACTT TIGGTACATATGAATATTATGTARAATGGCCTTGGTATGTATGCCTTTTAATTGGCCTTG BEVspike TTCCTGGCGATATAGGAATATCGCCTARGAGTOGTTATTTTATTARTGTARATAACTCTT BEVspike TUIGGTACATATGAGTATTATGTGAARTGGCCTTGGTATGTATGGCTTTTARTTTGCCTTG RI LITI nA SCSI dun M P IEEE HCVspike CRCVspike HEVspike BCVspike BCVspike CRCYspike BEVspike BCVspike BCVspike CRCVspike BEVSpike BCVspikepro HCVspikepro CRCVspikepr HEVspikepro CECVspikepr BCVspikepro CRCVspikepr HEVspikepro CECVspikepr BCVspikepro BCVspikepro CRCVspikepr BEVspikepro CECVspikepr BCVspikepro HCVspikepro CRCVspikepr HEVspikepro CECVspikepr BCVspikepro HCVspikepro CRCVspikepr HEVspikepro CECVspikepr FIGURE 9 Page 12 of 12 CTGGTGTACCTATGCTTGTTTTACTATTCTTCATATGCTGTTGTACAGGATGTGGGACTA CTGGTGTAGCTATGCTTGTTTTACTATTCTTCATATGCTGTTGTACAGGATGTGGGACTA CTGGCCTAGCTATGCTTCTTTTACTATTCTTCATATGCTGUTGTACAGGATGTGGGACTA CTGGTGTAGTTATGCTTGITTTACTATTCTTCATATGCTGCTGTACAGGATGTGGGACTA GTTGTTTTAAGAAATGTGGTGGTTGTTGTGATGATTATAC GTTGTTTTAAGATATGTGGTGGTTGTTGTGATGATTATACTGGACACCAGG GTIGTTTTRAGARATGCGGTGGITGTTGTGATGATTATACTGGACATCAGG GTIGTTTTRAGAAATGTGGOGGTTGTTTTGATGATTATACTGGACACCAGGAGTTTGTAR wkawkukkakakk d dk SUOI KAWA KANAAN TURARACTTCACATGACGATTARTTTCET FIGURE 10 Pag
106. TGGTGATTATGCAGCAT CRCVspike CTTCCGAACCAGCATTGCTATTTCGGABTATTAAATGCAATTACGTTTTTAATAATACTC CRCVspike CAAGATCTCCTAAAGTTACTATTGATTGTCCTGTTTTTGTCTGTGGTGATTATGCAGCAT HEVspike CTTCTGAACCAGCTTTGATGTTTCGTARTCTTAAATGCAGCCACGTTTTTARTTATACCA CGAGTTCCCCTAAGGTTACTATAGATTGTGCTACATITGTTTGTGGTGACTATGCTGCAT PA b KAKAK Kawak KAKE RAEE GIRA doe AG RA 59 JP 4644486 B2 2011 3 2 FIGURE 9 Page 8 of 12 FIGURE 9 Page 9 of 12 BCVspike GTAAATCACAGTTGGTTGRATATGGTAGTTTCTGTGACAATATTAATGCTATACTCACAG BCVspike ARGTCTTGCCTCCACTACTCTCAGAARATCAGRTCACTGGATACACTTIGGCTGCTACOT HCVspike GTAARTCACRGTTGGTTGAATATGGTAGCTTCTGTGACABTATTARTGCTATACTCACAG HCVspike CRCVspixe GTAAMTCACAGTIGGTTGARTATGGTAGTTTTTGTGACARTATTARTGCTATACTCACAG CRCVspike AAGTGTIGCCTCCACTGCTCTCAGAAABTCAGATCAGTCGATACACTTTGGCTGCCACCT BEVspie GTAGACAACAGTTAGCTGAGTATGGTAGTTTTTGTGAGARCATTAATGCTATACTCATAG BEVspike ARGIGIIGCCICCATIGITATCICARAATCAGATTAGIEGITACACITEGGCAGCCACCE ARPA k ARR FORIO kh de eR ERO Wo k RE REREERIRA AA AA Wu BCVspike ARGTARATGAACTACTIGACACTACACAGTTECAAGIAGCIARTAGITTARTERATEGIG BCVspike CTGCIAGTCTUTTTCCTPCCTTGGTCAGCAGCAGCAGGCOTACCATTTTATTTARATGT C ECVspike
107. TGTTT GTACTPTTTTATGCATATTTTACAGACACTGGTGTTGTTACTAAGTTTCTGTTTAATGTTT GTACTTTTTATGCATATTTTACAGACACTGGTGTTGTTACTAAGTTTCTGTTTCATGTTT GCACTTTTTATGCATRCTTTACAGATACTGGTTTTGTGACCAAGTTTCTGTTTAAGTTGT RU 57 4644486 2 2011 3 2 uuu BCVspike HCVspike CRCVepi HEVspike BCVspike CRCVspike HEVspike BCYspike HCVspike CRCVspike BCVspike CRCVspike BCVspike HCVspike CRCVspike HEVspike BCVspike HCVspike CRCVspike HEVspike BCYspike HEVspike BCVspike HCVspike CRCVspike HEVspike BCVspike Hcvspike CRCVspike HEVspike BCVspike HCVspike CRCVspike HEVspike BCVspike CRCVspike HEVsptke BCVspike HOVspike CRCVspike BEVspike FIGURE 9 Page 1 of 12 ATGTTTTTGATACTITTAATTTCCTTACCAATGGCICTTGCTGTTATAG ATGTTTTTGATACTTTTAATTTCCTTACCAACGGCTTTTGCTGTTATAG ATGTTTTTTATACTTTTAATCACCCTGCCTTCTGTTTTTGCAGTTATAG ARRA deiade A nnd GAGATTTAAAGTGTACTACGGTTTCCARTTAATGATGTTGACACCGGTGTTCCTYCTGTTA GAGATTTAAAGTOTACTACGGTTTCCATTARTGATATTGACACCGGTGCTCCTTCTATTA GAGATTTAAAGTGTACTACGGTTTCCATCAATGATGTTGACACCGGTGCTCCTTCTATTA GGGATTTARAGTOTAATACTTCATCAATTAATOACGTTGACACTGGTGTGCCATCTATTA RE k ki
108. TTTTTACTGATCAT Gk TETE o GATGTTGTTTATGCACAACATTGTTTTAAAGCTCCCACAAATTTCTGTCOG TGTA AACATCAAATGTTCTCAACTTACTGCTAATTTGCAAAATGGCTTTTATCCTGTTGCTTCA AA ARTTGABTGGGTCTTTGTGTGTAGGTAGTGGTTTTGGTA TAGATGCTGGTTATRAAA AGTGAAGTTGGTCTTGTCARTAAGAGTGTTGTGTTACTACCTACTTTCTATTCACATACC x dee kro 56 JP 4644486 B2 2011 3 2 E FIGURE 8 Page 5 of 9 FIGURE 8 Page 4 of 9 CRCVspike ATGATTCGTACTTGCTATAGCG GTCGTGTTTCAGCGGGCTTTCA CTCTAACTCTTC ABRTAGTCGTATAGGCACTTGTCCTGCAGGTACTAATTATTTARCTTGTTATAATGCTAAC GEN apik ATACITAGIEGCITACATTATACATCACIATCAGGIGATTIATTAGGITITARARATETT CECVspike AGTGTTAATATARCTATTGATCTTG GTATGAAGCGTAGTOGTTATGGTCRACCCA 3k dg WR DEI ded XO e de Ses dde e CRCVSpike CEARCCAGCATTG CTATTTCECARTATTARATGCARTIACGITTTIARTARTACTCITT CROVeplks CANIGTGNTTGITIGIGCRCTOCBGAC CECVspike AGTGATGGTGTTGTCTATTCTGTGACACCATGTGATGTAAGCGCACAAGCGGCTGTTATT CECVspike TAGCCTCARCACTARGTARCATCACACTACCAATGCAGGATAATARCACCGATGTGTACT 3 k m CRCVspike CBCG ACAGCTGOARCCTATTARCTATTTTCATAGTTATCTTGGTTG GTTGTCAA CRCVspike ARGTGCCCCCAAACTAAATACTTAGTTGGCATAGGTGAGCACTGTTCTGGTCTTGCTATT
109. caattttte ctgctataga cttataataa atggtatcaa ctgecacctt taaatgttca aasagottat ctaccaatte ataacttatt trcrarctag gtettaccgc ttagtgcagc taasttkttg tgtattttat gtctgtgcat ataacacttg atgtggttgt acatttcaac aaacattaat aagatgaaat teaaggacat ttggccttge gtgggactag agttagtaat gggggattac taattttgag gtatgaaatt aagatctect taaatcacag agtaaatgaa cactettagc cectgtatta ggatttactt ttgtactgga agtgttgect tgctagtctg gtatcgtatt ttctaatgca tgctttagtt geaacaacte acttgatgct tcttaatgct acaegctatd tggtaatggt ccactttagc yacaggtgat gatgttcact tatgagtacc acccaacctc ggcaccagat gaataggtta tggtacatat tggegtagct ttgttttaag caaaacgtca 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 080 4092 60 120 180 240 250 60 84 54 0000 atgtttttga tgtactacgg gtcegatgtta acattgttgc aagdgaactt gatggtgttt gagtttcctd caaccacsta cagtatacta atagaactat tatgatgtga gcatatttta gtgcttteac tgggttacac tttaatgetg atagcaccat gtttaccgac tcggtgectt agcagectga aagstatacg aggaaggttg gatactactg agcaggttta aagectcaac aaagctccca tttggtatag tatttaactt tctaaatcta cactgttctg ccaaaagcat tttgctaatt aastcasaca ggccaaggta tatgattcta attcgtagtt geettgctat ctgcaanccta MPLILLISLP TLLLNGYYPT RFPAITIGST IELWHWDTGV VLSHYYVMPL IAPSTGVYEL SSLMSFIOAD DTTATSCOLY SKSTGFYKC
110. dv Res 48 1 100 oaa 10 20 30 40 50 34 JP 4644486 B2 2011 3 2 00 US Patent No 5 750 112 00000 O O US 5 750 112 L3 Rotovec Corona 00000000
111. e 2 of 5 NAVDCKSDFMSEIRCKTLSTAPSTEVIELNGYTVOPIADVYRR IPRLEDCNIBANLNDK NAVDCKSDFMSEIKCKTLSIAPSTGVYELNGYTVOPIADVYRR IPNLPDCNIEAWLNDK NAVDCKSDEFMSEIKCKTLSIAPSTGVIELNGYTVQPIADVYRR IPNDPDCNIEAWLNDK HAVDCASDFMSETMCKTSSTTPPTGVYELNGYTVOPVATVYRR IPDLENCDIEAWLNSK GRFVTNOPLLVNCLNPVFPSFTGVAADEFCFEGAOFSQCNGVELNNTVDVIRTNLNETADVO X Vas on 2 388 SVPSPLNWERKTFSNCNFNHSSLMSFIQADSFICN NIDAAKIYGMCESSITIDK SVESPLNWERKTFSNCNENMSSLMSFIQADSETON NI DARKIYGMCFSSITIDK SVPSPLNWERKTFSNCNFNMSSLMSFIQADSETCN NIDAAKIYGMCFFSITIDK TVSSELNWERKIFSNCNFNMGRLMSFIQADSFGCN NIDASKLYGMCFGSITIDK SGMGAIVESLNTTGGCILEISCYNDIVSESSEFYSYGEIPFGVTOGPRYCYVLYNGTALKY 407 456 440 FRIPNGRKVDLOLGNLGYLOSENYRI RCA GEA FAIPNGREVDLOLGNLGYLQSFNYRIDTTATSCOLYYNLPAAN VSVSRENPSTWNRRFG FAIPNGRKVDLOMGNDGYLOSFNYRIDTTATSCOLYYNLPASR VSISRENPSIWNRREFG FAIPNSRKVDLOVGKSGYLOSFNYKIDTAVSSCOLYYSLPARN VSVTBHYNPSSWNRRYG FGTLPPSVKRIAISKHGOPYINGYNFFSTFPIDCISFMLTTGDSCAFWTIBYTSYTEALV QE FTEQSVFKPOPVGVETDHDVVYAORBCEKAPTNFCPCKLDGSLCVGSGSGCIBDAGYKNSGIG FTEQSVFKPQPVGVFTHHDVVYAQRCFKAPTNFCPCKLDGSLCVGNGPGIDAGYKNSGIG FTEOSVFKPOPVGVFTDHDVVYAQHCFKAPTNFCPCKLNGSLCVGSGFGIDAGYKNSGIG FINQS FGSRCLHDAVYSOOCENTPNTYCPCRT SQCIGC AGTIG QVENTAIKKVTYCNSHINNIKCSQLTANLQNGFYPVASSEVGLVNKSVVLLPSFYSHTSV En MES kO 528 lt o TCPAGTNYLTCH NABQCNCLCTPDPITSKSTGPYERCPQTKYLVGIGEBRCSGLATKS TCPAGIRYLTOCE NAAQCDCLCTPDPITSKSTGPYRCPQTKYLVGIGERCSGLAIKS TCP
112. ed froml aboratory dogs with respiratory disease Proc Soc Exp Bi ol Med 126 140 5 Chil vers M A M Rutnan A Mint S Silverman M and O Ca aghan C 2001 The effects of coronavirus on human nasal ciliated respirato ry epithelium Eur Respir 18 965 70 100000 Di tchfi el d Macpherson L W Zbitnew 1962 Association of a ca 10 20 30 40 50 49 JP 4644486 B2 2011 3 2 ni ne adenovi rus Toronto A 26 61 wth an outbreak of laryngotrachei ti s kennel cough Can Vet Jour 3 238 247 Fel senstein J 1989 PHYLI P Phyl ogeny Inference Package Versi on 3 2c di sti cs 5 164 166 I atovi J and Sapats S 2000 Avian infectious bronchitis virus Rev Sci Tech 19 493 508 Kar pas King Garcia F G Calvo F and Cross 1968 Canin e tracheobronchi ti s Isolation and characteri zati on of the agent wth experi nent al reproduction of the disease Proc Soc Exp Biol Med 127 45 52 Keil DJ and Fenw 1998 Role of Bordetella bronchiseptica in infec ti ous tracheobronchiti s in dogs Am Vet Med Assoc 15 200 7 Lou T Y and V nner HA 1963 Natural and experi mental infection of dogs w th reovirus typel pathogenicity of the strain for other animals 77 293 304 a MJ Puhakka T Ruuskanen O Leinonen M Saikku P Blonqvist
113. enbanki 0000000000000000000000000 LY138 00000 0 00 Genban 100000000000000000 Genbank 00000000000 8 oa 0000 LY138 0 0 Genbank 100000000000000000 100000000000000000 100 HHHHHHHHHHHHHHHHHHHH GenbankH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH GenbankH 0000000000000 0000000000 000
114. hi Ivers et 2001 000 HHHHHHHHHHHHHHHH apa RI e ERE anann Bordetella bronchi septi cap 08 000000000000 00 00000008000 00 1000000001000 0 HHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHH 1000000000000 Appel M L N 1987 Cani ne infectious tracheobronchiti s Short iew kennel cough In Virus infecti ons of carnivores M Appel Ed lst Editi on pp201 211 er Sci ence Publishers Amsterdam 5 D A Carmichael L E and Appel MJ 1977 Naturally occurri ng res piratory di sease in a kennel caused by Bordetella bronchi septi ca Cornell Vet 6 7 282 93 Binn L N Alford J P Marchwcki H Keefe T J Beattie J and 1979 Studies of respiratory disease in random source laboratory ogs viral infections in unconditioned dogs Lab Ani m Sci 29 48 52 Binn L N Eddy Lazar E J and T 1967 Vir uses recover
115. lt 00 100000000000000000 bronchiseptica VANGUARD 5 B bronchi septi car Ani NASAGUARD U S Vet Lic No 112 B br onchi septica Intervet ronchi septi cag PROGARD 10000 PROGARE J HHHH KQIHHHHHHHHHHHHHHHHHHB 37 JP 4644486 B2 2011 3 2 000 000000
116. m nescence based detection systemfor au tomated PCR product quanti tati on Bi oTechni ques 15 152 1570000 HHHHHHHHHHHHHHHUHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HH 0000000000000000000000000000000000 0 000000000000000000000000000 0000000 UU DU li ili
117. nchiseptica HHHHHHUHHHHHHHHHHHHHHHHHHIL Ani Heal th COUGHGUARD 0 ronchi septi cah I 0000000000000 B bronchi septi ca U S Vet Li c No 189 D B b 1000000000000000000000000000 COUGHGUARD B bronchiseptica B bronchiseptica 00000 Ani nal Heal VANGUARH 5B U S Vet Li c No 1890 00 100000000000000 00000 LU LU ULULHUgWuutiuuuLulu
118. nvolved in two natural outbreaks of shi ppi ng fever Am t Med Assoc 2000 May 15 216 10 1599 604 Tennant BJ Gaskell RM Jones RC Gaskell CJ Studies on the epi zooti ol of cani ne coronavirus Vet Rec 1993 Jan 2 132 1 7 11 Thonpson JD Gibson Plewni ak Higgins DG The Cl ustal X ows interface flexible strategies for multiple sequence i gnnent ai ded by qual ity anal ysis tool s Nucleic Aci ds Res 1997 Dec 15 25 24 4876 82 10 20 30 40 50 50 JP 4644486 B2 2011 3 2 5 5 Sp1 Sp8 0000 D BstXI pr7blue2 Novagenl 00 SpFXho Spe A Bst XI SpF Xho 10000 100 8000000
119. spike TGGCACCAGRTTTGTCACTTGATTATATAAATGTTACATTCTTGGACCTACAAGATGAAA CRCVSpike GTGGTAATGGTARTCATATTATATCATDIAGTGCAGAATGCTCCATATCGTTTGTATTTTA CRCVspike TGGCACCAGATTTGTCACTTGATTATATAARTGTTACATTUTTGGACCTACAAGATGARA HEVspike GTGGTARTGGTAATCATATTATATCATTAGTACAGAATGCTCCATATGGTTTGTATTTTA HEVspike TGGCACCAGATTTGTCATTTGATTATATTAATGTTACGTTCTTGGACCTACAAGATGARAA de TTI To tt dede dde EO e Oe eR dee de Xe joe deese DER HE Ri li ed dele BCVspike BCVspike HCVspike TCCACTTTAGCTATGTCCCTACTAAGTATGTCACTGCGAAGGTTAGTCCCGGTCTGTGCA HCVspike CRCVspike TCCACTTTAGCTATGTCCCTACTAAGTATGTCACTGCGAAGGTTAGTCCCGGTCTGTGCA CRCVspike TGBATAGGTTACAGGAGGCAATAAAAGTTTTAAATCATAGCTACATCAATCTCAAGGACA HEVsptke TCCATTTTAGCTATGICCCCACCAAGTATGTTACAGCAAAGGTTAGTCCTGGTTTGTGCA BEVsp3 ke TGRATAGGITACARGARGCTATARAAGITCTARATCATAGCTACATCRATCICAAGGACA ORSO A RI ORO AB ER AE SRR mE BCVspike TTGCTOGTGATACACGTATAGCCCCTARGAGTGGTTATTTTGTTAATGTAAATARCACTT BCVspike TTGGTACATATGAGTATTATGTARARTGGCCTTGGTATGTATGGCTTTTAATTGGCCTTC BOVspike TYGCTGGTGATAGAGGTATAGCCCCTARGAGTGGTTATTTTGTIAATGTARATAATACTT ECVspike T
120. ta 4x kkk 3 RE mn CRCVspike CACAGTTGCAAGTAGCTAATAGTT TAATGAATGGTGTCACTCTTAGCACTARGCTTAAAG CROYspike TGATGCTA CECVspike TGYTGTTTGTTTCAGAAARTGCCCTTA AATIGGCRTCTGTTGAGGCGTICARTAGTACA CECVspike TGATGCTATACATCABACATCACAAGETCTTGCCACTGTTGCTAAACCATTGGCAAAAGT ET mI SYS w CRCVspike ATGGCTTTARTTTCAATGTAGATGACAT CARTTT TTCCCCTGTATTAGGTTGT CRCVspike TCAAGCTGTTGTTAATGCAAATGCTGARGCTCTTARTARCTTATTGCAACAACTCTCTAA CECVspixe GAACATTTAGATCCTATTTACAAAGAATCGCCTAACATAGGTGCTTCTTGGCTAGGAGGT CECVspike GCBRAGATGTTGTTAACACACAAGGGCARGCTTTAAGCCACCTAACAGTACAACTGCAAAA mnm m P drei w t CRCVspike TTAGGAAGCGAAT GTAATAA AGTTTCCAGTA GATCTGCTATAGAGGAT CRCVspike TARATTTCGTGCTATAAGTGCTTCT TACARGAAATTCTATCTAGACTTGATGCTCTTGA CECVspike CTABRAGACATACTTOCGTCCCATAATAGCARACGTAAGTATCGTTCTGCTATAGAAGAC aw dae Mb m piena CRCVspike TTACTTTTTTCTARAGTAAAGTTATCTGATGTTGGTTTTGTTGATGC TTATAATART CRCVspike AGCGCAAGCTCAGATAGACAGACTTATCAATGGGCGTCTTACCOCTCTTAATGCTTATGT CECVspike TTGCTTTTTGRTAAAGTTGTAACTTCTGGTCTAGOTACAGTTGATGAAGATTATAAACOT CECVspike TGCTGATGCACAAGTTGATAGGCTGATTACAGGTAGACTTACRGCACTTARTGCATTTGT dAARAR d bkk AC dank nne

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