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抗体組成物のFc γ 受容体IIIaに対する結合活性を

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1. 7 JP VO2003 085119 Al 2003 10 16
2. 100000000 E e 22 00000070 1000000 n HHHHHHHHHHHHHHH JJ UU UD 1001000 HHHHHHHHHHHHHHH 10 20 30 50 JP VO2003 085119 A1 2003 10 16 4 10 20
3. 00 000004000 HHHHHHHHHHH HHHHHHHH 10000 HHHHHHHHHHHHHH 0000000000 000000 HHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHH CILE B IHHHHHHHHHHHHHH 0000000000000 0000000 0 HHHHHHHHHHHHHHH 10 20 30 50 3 JP VO2003 085119 A1 2003 10 16 0000000000 0000 00000000000 0000 HHHHHHHHHHHIH
4. 10 20 30 50 44 JP WO2003 085119 Al 2003 10 16 A ERE n N
5. 10 20 30 50 58 JP VO2003 085119 A1 2003 10 16 10 20 30 50 59 JP VO2003 085119 1 2003 10 16
6. 10 20 30 50 69 JP WO2003 085119 Al 2003 10 16 G poe Tj jo C 0 D C HHHH
7. Lane noo HHHHHHHHHHHIH 10 20 30 50 14 JP WO2003 085119 1 2003 10 25
8. 10 20 30 50 JP VO2003 085119 1 2003 10 16 21 10 20 30 50 HHHHHHHHHHHHHHHH 22 JP WO2003 085
9. 10 20 30 50 51 JP WO2003 085119 1 2003 10 C m 55 O 0000 O n Y Md ES HHHHYHHH Y HHHY D 10 20 30 50 52 JP VO2003 085119 A1 2003 10 16
10. Y H STA eee Y Y 000 Y zs n Y C E Ra e TIAE X 10 20 30 50 92 JP VO2003 085119 A1 2003 10 16 SA D C Y H H C O H H Y x 3 C
11. 42 JP WO2003 085119 Al 2003 10 16 10 20 30 50 43 JP WO2003 085119 1 2003 10
12. H 10 20 30 50 60 JP WO2003 085119 Al 2003 10 H D C u E
13. H C E C C C va S a H C ee H n ja Dun H B RE RENE Y C H C n no n n 10 20 30 50 75 JP WO2003 085119 A1 2003 10 16 B B H zi Hu HOO B B B HH B HHHHHHHH D nHHHHHHHHD H D 000 u C H C H B H C B
14. HHHHHHHHHHHHHHH HHHHHHHHHHHHH oana L3 LJ oana JD 1000000 000000 10 20 30 50 6 JP VO2003 085119 A1 2003 10 16
15. 87 JP WO2003 085119 2003 10 E a PE l U D 1000070 O O u D C C n n n n n 10 20 30 50 JP VO2003 085119 A1 2003 10 16 88 10 20 30 C
16. n O m MC a lt x C C n nnn An ee C mi u CH O C 000 C O O O O 10 20 30 50 79 JP WO2003 085119 A1 2003 10 16 5 2000 H C C C C T z 10 20 30 80 JP WO2003 085119 Al 2003 10 16 3 AK 1 288 488 5 DCHI01
17. 10 20 30 50 17 JP VO2003 085119 1 2003 10 16 10 20 30 50 18 JP WO2003 085119 Al 2003 10 16
18. _ 0000 0000000 10 20 30 50 10 JP WO2003 085119 Al 2003 10 16
19. a 5 GS ER m a 10 20 30 50 JP WO2003 085119 1 2003 10 10 20 30 50 34 JP VO2003 085119 Al 2003 10 16
20. 84 JP WO2003 085119 Al 2003 10 16 C H n n n m um u C C C n C n n n n n C C r3 r3 H H H n C C C C C n C n n n n n n an C C H C C n n H C n n non n n n log O 0 0 CHHHHH O 00000 a 10 20 30 50 85 JP WO2003 085119 A1 2003 10 16
21. 30 Y HHHHHHH HHHHHH HHHHHHH HHHHHHH 50 JP VO2003 085119 A1 2003 10 16
22. a a 10 20 30 50 35 JP WO2003 085119 Al 2003 10 16 a 10 20 30 50
23. 10 20 30 50 JP VO2003 085119 Al 2003 10 16 10 20 C 00000 IOB 100000 U D t 5 GMD FUTS CHO DG44 1 1 1 1 CHO DG44 bi CCR4 1 107 0 793 1 093 0 901 5 03 5 03 LCA 0 160 0 886 0 920 0 875 CHO CCR4 LCA HHHHH O 0000 0000
24. O O 000 a ji N SAS E a Ll O 000000 10 20 30 50 181 JP WO2003 085119 1 2003 10 n Y e YOO E ERRE upp ase ja E ADD NODUM x O HuHHHH HHHHHH Y HHHHHH 10 20 30 50 JP VO2003 085119 A1 20
25. a 2 N S ETS ERN Y a Do n n n n n uHHHHHHHHHHH Y H z Ned Ee S SE SE C A Y H C C r1 r1 r1 r1 r1 M 10 20 30 50 97 JP VO2003 085119 Al 2003 10 16 a lod lod D C C 00000 D 100 10 20
26. 10 20 30 50 8 JP WO2003 085119 Al 2003 10 16 Y Y O 0 D oes Y Y Y 0 O 0 DY O O O O Y Y a Ape EKKE KAN S mat ane SX E ENS 10 20 30 50 9 JP VO2003 085119 1 2003 10 16 BA HYHHHHH 0000 Y 0000 O OY Y
27. l o U l O 11 0UUUUUT O O O 00000 00070 s annn nnnnn ES SERVER GUESS Waste M Se n O 00000070 s a 10 20 30 50 28 JP VO2003 085119 Al 2003 10 16
28. 10 20 30 50 95 JP VO2003 085119 Al 2003 10 16 S Y i HHHHHHHHHY E a Y Y Y Y Y 10 20 30 50 96 JP WO2003 085119 2003 10
29. 5 nnnnnnnnnnnnnna a u x Em x SG n H SE 10 20 30 50 72 JP WO2003 085119 Al 2003 10 16 H C C G
30. 10 20 30 50 102 JP VO2003 085119 A1 2003 10 16 H 2 H 000000 0 000000 010 0000000000000 000 O 7 GFPP cDNA RACE PCR PCR 5 RACE PCR GFPPGSP1 1 UPM Univarsal primer mix ZEE GFPPGSP1 2 NUP Nested Univarsal primer 1100bp 3 RACE PCR GFPPGSP2 1 UPM Univ
31. KENT Kaia HHHHHHHHHHHHHHHHHHHHHHoeHHHHHHHH BAR w1 6 Yo 5 03 9 CHO CCR4 LCA 48 CHO CCR4 AAL 27 CHO CCR4 PHA 8 D JD U l a HHHHHHHHHHH a DJ JJ U l DJ DU DJ U 10 20 30 50 82 JP VO2003 085119 Al 2003 10 16
32. 10 20 30 50 2003 10 16 us nennn n nnnnnnnanmnn nnnhn a Eo 10 20 30 50 32 JP VO2003 085119 Al 2003 10 16
33. 10 20 30 50 JP WO2003 085119 1 2003 10 10 20 30 50 48 JP WO2003 085119 A1 2003 10 16
34. ud a 10 20 30 50 49 JP WO2003 085119 1 2003 10 sie N nak a RA ARA EE ATT gie PE CT _ 000 HHHHHHHHHHHH 10 20 30 50 50 JP WO2003 085119 Al 2003 10 16
35. 000 10 20 30 50 90 JP VO2003 085119 A1 2003 10 16 C C SC H O Y O C C C ae oE SRO H nn A 10 20 30 50 91 JP WO2003 085119 1 2003 10
36. E IH 0UUUUUT IH 0UUUUUT HHHHHHHLH Y 10 20 30 50 JP WO2003 085119 1 2003 10 10 20 30 50 57 JP VO2003 085119 A1 2003 10 16
37. 10 20 30 50 108 JP WO2003 085119 Al 2003 10 16 C C C Ll ec H A A a T H unn Sni ud H H y A Y 10 20 30 50 109 JP
38. 10 20 30 50 24 JP VO2003 085119 Al 2003 10 16 n n n n n n n a r1 a r1 10 20 30 50 25 JP WO2003 085119 A1 2003 10 16
39. 10 20 30 50 93 JP WO2003 085119 1 2003 10 a Y Y H LHHH o HHHHL Mom Lm am D PY ec 10 20 30 50 JP WO2003 085119 1 2003 10
40. 99 JP WO2003 085119 Al 2003 10 O O O H Y C s uHHHH C D D H C H 10 20 30 50 100 JP WO2003 085119 Al 2003 10 16 C C C C SG H O O D D O O 000060 E RE E ET 30 00
41. O HHHHHHHHHHHHHH JJ UU UU 9001000 HHHHHHHHHHHIH HHHHHHHHHHHHHHH nn Ka E n n Pieno A EN ASS S N nm ag RIE AKE S Saas a ya O 000 000000 HHHHH O O 000 000000070 10 20 30 50 IO UU HHHHHHHHHHHHHHHHHHHHHH HHHHHHHHH HHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHH
42. 10 20 30 50 40 JP WO2003 085119 1 2003 10 n mid Sorini to Sa ko A EN n v HN 10 20 30 50 JP VO2003 085119 A1 2003 10 16 41 10 20 30 50 HHHHHHH HHHHHH
43. Es E x HHHHHHHHHHH C 10 20 30 50 19 JP WO2003 085119 Al 2003 10 16 10 20 30 50 20 JP VO2003 085119 A1 2003 10 16
44. C H H E cnn B prs EXE JE O N ES B HHHHHHHH B m 10 20 30 50 76 JP WO2003 085119 Al 2003 10 8 00 B pO OT HHHHHHB HHHHHHL B 000 H H C C C C B MM 118 x 1 a uHH HHHHHHHHLHHH C C C C B O B O 10 20 30 77 JP VO2003 085119 A1 2003 10 16 1 PCR hp XT FUT8 F lt 5 GTCCATGGTGATCCTECAGTG
45. 64 JP VO2003 085119 Al 2003 10 16 HH g 0010 7 n n n n 000 O ER AKEN Sor ADCC 96 X100 1 Cr A Cr E no no pie rai KD aa im E papua kaga eje Pr C aa aS Ts oe ite H H H H i VAS 25 C H H H u m m eC n n nmmnmnnmnnmnnnmnumnnunn nm u C N N N N N o x
46. 10 20 30 50 61 JP VO2003 085119 1 2003 10 16 10 20 30 50 JP VO2003 085119 Al 2003 10 16 62 10 20 C 30 C C C
47. nnni C C C 0 i ES
48. 10 20 30 50 15 JP WO2003 085119 1 2003 10 E i E E wi i m a 10 20 30 50 16 JP WO2003 085119 A1 2003 10 16
49. 105 JP VO2003 085119 A1 2003 10 16 a x C H si C z C O C T E z C C SE RSS 5 ee ENO Kaka nn nnnnn W 10 20 30 50 JP VO2003 085119 1 2003 10 16 106 2 R m A L3 r3 E
50. 54 JP WO2003 085119 1 2003 10 10 20 30 50 55 JP VO2003 085119 1 2003 10 16
51. C JP VO2003 085119 A1 2003 10 16 63 10 20 000 50 C C C
52. A W O O 5 E CC PENNE HHHHHHHHHHHHH a O O 0 10 20 30 50 29 JP VO2003 085119 A1 2003 10 16 E DET E E na nnnnnnannn nnnn 10 20 30 50 30 JP VO2003 085119 2003 10
53. Y 10 20 30 50 JP VO2003 085119 1 2003 10 16 53 10 20 30 000000 HHHHHHHHHHHHHHH 50
54. 10 20 30 50 65 JP WO2003 085119 Al 2003 10 16 C 1 GIcNAcf 1 2Mang 1 6 Man B 1 4GIcNAcB 1 4GIcNAc PA GleNAcB 1 2 1 2 Gal 8 1 4GIcNAc B1 2Man N Man 8 1 4GicNAc 8 1 4GicNAc GlcNAc 8 1 2Man 01 3 GleNAcg 1 2Maa 1 6 Mang 1 4GIcNAc8 1 4GIcNAc PA JA Gal 1 4GIcNAcf 1 2Mang 1 10 20 30 66 JP WO2003 085119 Al 2003 10 16 4 Gal 1 4GleNAc 8 1 2Man Man 1 4GicNAc B1 4GIcNAc PA Gal 8 1 4GIcNAc A 1 2Man a A 5 GicNAc B1 2Man a N Fue amp 6 B 1 4GleNAc 1 4GIcNAc JE GlcNAc B1 2Man al 6 Gal 1 4GleNAc 1 2Man 1 GlcNAc 1 Man al jo g 1 N 6 1 4GIcNAc B1 4GleNAc PA 7 GleNAc 1 2 al Fuc a N 6 1 PA Gal 8 1 4GIcNAe 1 2Man al 8 Gal 1 4GlcNAc B 1 2Man g 1 mean 6 Man 8 1 4GIcNAc B 1 4GIicNAc PA Gal 1 4GlcNAc 8 1 2Man GIcNAc 8 1 2Man amp 1 N 4
55. 10 20 30 50 38 JP VO2003 085119 A1 2003 10 16 C a 10 20 30 50 39 JP WO2003 085119 1 2003 10 E
56. U D Hannn n r3 r3 10 20 30 50 26 JP VO2003 085119 Al 2003 10 16 a O Od O n D Ims ate I WS TP ND te z n Se e MIO TENE Va S Es TE 10 20 30 50 27 JP WO2003 085119 1 2003 10 16
57. C IE cnnnnnnnnnn H x U 00000000000 D D C ss capo C D 10 20 30 50 JP VO2003 085119 1 2003 10 16 86 10 20 C C 30 HHHHHHH C C 50
58. Y FUT8 979 bp 1000 185 n 1 1 CCR4 7 100 46 CCR4 25 39 is CCR4 27 60 CCR4 5 18 W 40 e CCR4 8 0 0 L 0 0001 0 001 0 01 0 1 1 10 Cz g ml 000 138 Dralll CHO YB2 0 cDNA pBluescript KS EcoRV PCR 3 0bp Y 8 792 ORF BE 1128 bp CHAc pBS YBAc pBS 4 1Kb TA Hindlll E FUTS Scal SEQ ID NO 8 CHFT8 pCR2 1 YBFT8 pCR2 1 4 9Kb PCR CHFT8d pCR2 1 YBFT8d pCR2 1 4 7Kb 186 JP WO2003 085119 Al 2003 10 16 15 Dralll 1 6 100 OO 5 8 a a 107 2 b ip p qa im 0 04 CHAcd pesi YBAcd pB 3 900 j ORF BARAK 10000 1 7 1 8 Z 5 03 E x CHO CCR4 LOA Ha 7 X CHO CCR4 AAL w CHO CCR4 PHA 0 0025 025 25 25 CCR4 ng mb 0 0025 0 25 25 25 CCR4
59. 10 20 30 50 45 JP VO2003 085119 Al 2003 10 16 10 20 30 50 46 JP WO2003 085119 1 2003 10 E
60. Gly Leu Ser 225 aca tgg aag gac cat aaa Trp 240 aga Thr Arg gac Asp Lys Asp His Lys gac aaa tga cag gat cc Asp Lys lt 210 gt 28 lt 211 gt 254 lt 212 gt PRT lt 213 gt Homo sapiens lt 400 gt 28 Met Trp Gin Leu Leu Leu Pro Thr 1 5 Gly Met Arg Thr Glu Asp Leu Pro 20 Gln Trp Tyr Arg Val Leu Glu Lys 35 40 132 aag tat Tyr 150 gac Lys aaa Lys Asp 165 gtg Val tct Ser tca acc Ser Thr ttg gtg Leu Val gtg Val aag Lys 230 ttt aaa Phe Lys 245 135 ttt Phe age Ser tea Ser atc Ile atg Met 215 aca Thr teg cat His Gly gag Glu tca Ser 200 gta Val aac Asn aga JP cat His tec Ser act Thr 185 tca Ser cte Leu att Ile aag Trp Arg Lys Ala Leu Leu Leu Leu 10 Lys Ala Val Val Phe 25 Asp Ser Val Thr Leu 45 WO2003 085119 A1 2003 10 16 140 gac 480 Asp aat tct Ser 155 ttc Phe Asn tec 528 Cys tac Tyr 170 gtg Val ate 576 Ile aac Asn ttt Phe cca 624 Pro tte Phe ctt Leu ttt Phe gca 672 Ala 220 tea 720 Ser cga age Ser 235 cot Arg caa 768 Gln gac Asp Pro 250 788 Val Ser Ala 15 Leu Glu Pro 30 Lys Cys Gln 10 20 30 Gly Ala Tyr 50 Ser Leu Ile 65 Val Asp Asp Ser Asp Pro Ala Pro Arg 115 His Ser Trp 130 Gly Lys Giy 145 Lys Ala Thr Gly Ser Lys Gly
61. DI DI DI I DI E DI 3 x DI 3 DI 8 DI I DI DI DI DI DI DI DI DI DI DI I DI DI DI oOo 3 DI DI DI DI DI DI DI I DI DI DI DI lt I O i DI DI DI DI 3 DI DI DI DI DI i lt lt 107 JP WO2003 085119 Al 2003 10 16 AE B C SE C SE C H C r1 H Lll H HHLH
62. cacgcagaat taaaggaggc ggtcagctgg tacactttct ttgcttatga atgacatcta aacctcgaac accattggga cetcctacaa aaaaatag cctcigccac tatttttgaa tgttatacat gggaaacata aatgtccagg cagtgctata tttatgaatt aagecccaaa cttcacctgt agaaaactcc tctiggaatg ttattacaac gccacatgca tgtgtttaga gtcaggtgaa ccatcctcgg aagagtocat tccagttatt ccccatcgag gcaagtggat aaagacaaag actacacaat ctcacaggct aatcatgcaa ctattttgga tgaagaggaa tggttattet agtccgagag cigagtgctg tattgtgata tttigcgtaa aagttataat aaataaatag taagttgtta attaaattga tetgttcatt tttagaacat tagaaaacaa tgttttcatg tggctgtigt gcttgtccti 180 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1728 60 120 180 240 300 360 420 480 540 600 660 720 780 10 20 30 atgattttat aaagttggct cccaceacct aatgatagat cagtagagtt agtagacaag atagtcagtg gtttetggta caataaaaat cagcttttct tagccttgta tctataatat tttcatatat tgattgagaa tttaaaatac ttagttcata tacatcatat ggtttgatoc ataaccttts gttgcaagtt ttcacttata tagccgaatt cacaacaatt aggtagaacc agctaattet ctatatctca gcacaggaca acagtatacc attttcctgt aagacagaag tatgctcatt agataatgac gcgcttaaaa aaatactcaa ctgttgaaaa tttttaaaag ttttgcatat attatgttta acttgtgtga attgtatgag ccagagtggt gEggatatca taacaacaac acattaaata agtataccce cattcttttg taaggttcag atttaatctc tatgtaaatg atgacttitc gttctttgtg atggcaaaca atagccaccc tagaaaaatg ccacctg
63. ng ml YB2 0 KM2760 58 35 16 5 03 CHO CCR4 LCA 187 JP WO2003 085119 Al 2003 10 16 19 8 20 j PCR 8 2 gt Stul BamHI E 7 Blue E td 5 600bp zz Fg 5 2 5 ESENE O 8 8 i 8 g E Ts E E x 5 5 mt C E 8 g Q O IDEATE HEERKE 2 1 i PCR Hindli EcoRI 150bp pT7 Blue R A NIAT kozak EcoRI E Sac C EcoRI SacI ATG WT N 23 EcoRI BamHI EcoRI BamHI fo pBluescript SK WT N EcoRIt BamHI C WT N in pBS 2 5 Hindi BamHI MoMLV LTR 7 It 4 BamHi HSV TK TORI cta ne pAGE249 WT in pBS BamHI C MoMLV LTR 7 0E 3 Kozak CHO GMD cDNA HSV TK 7 Ht 4 pAGE239GMD 188 JP WO2003 085119 Al 2003 10 16 O 2 4 Hindi EcoRI EcoRI ATG WT N in pBS HindIII EcoRI SS WT in pBS 268 140 _
64. 36 JP WO2003 085119 1 2003 10 10 20 30 50 37 JP WO2003 085119 2003 10 SC C nn ec Uu HHHHHHHHHHHH HHHHHHHHHHHHHH
65. 0 19 2 30 40 6 al 7an AWAK MORE 90 9 2 5 CCR4 7 46 is CCR4 7 39 E IT BELA 27 CCR4 3 18 CCR4 7 996 CCR4 7 8 0 001 0 01 0 1 1 gz g ml 184 8 B v P aosi atk Sci 896 vii IDR 40 60 80 6 2 ra DO e v Hi ji sas 27 vi 4 vii n 20 40 60 9 F G CCR4 y 46 no vi 40 60 a CCR4 v 39 wi vii vii 6 20 o 0 2 4 6 8 108 CCR4 5 100 46 39 m 60 27 a CCR4422 40 18 m 20 9 CCR4473 0 Ji 8 20 0 0001 0 001 0 01 0 1 1 10 Cz g ml JP VO2003 085119 A1 2003 10 16 JP VO2003 085119 A1 2003 10 16 CHO YB270 cDNA PCR 12
66. 0 20 40 60 80 100 w1 6 0 0000 E 3 4 GDS 42 GD3 12 80 70 60 gt m 50 40 ta 20 Fe RETE 10 0 0 001 0 01 1 0 BE g mL 00000 358 Bs 18 0 CH0 DG44 4 z w 1 5 P 1 0 5 0 0 001 0 01 0 1 1 10 ug ml 190 JP WO2003 085119 A1 2003 10 16 0D415 10000 E 33 CCR4 87 CCR4 98 CCR4 8 3 2 5 8 de 0 i 0 01 0 1 1 10 100 Cx J B nda z 36 YB2 0 1 4 x7 0 CHO D644 1 8 1 0 oo gg 9 001 0 01 0 1 H 10 ug mL 378 EcoRI EcoRI EcoRI EcoRI 22 8 34 2 EcoRI FeoRI CHO GMD 191 JP WO2003 085119 Al 2003 10 16 38 A PCR Apal Notl Not Apal Apal Nott A EcoRI AB Not if KM1334 VH Apal PCR EcoRI BsiWI Coat A 5G 6 A B EcoR BsiWI Nat 192 HHHHHHHH INTERNATIONAL SEARCH REPORT A CLASSIFICATION OF SUBJECT MATTER Int Cl
67. 10 20 30 173 JP WO2003 085119 A1 2003 10 16 130 135 140 Tyr Leu Leu Leu Lys Gln Thr Thr Ser Phe Tyr Ala Leu Leu Thr Cys 145 150 155 160 Ala Ile Ile Ile Gly Gly Phe Trp Leu Gly Ile Asp Gln Glu Gly Ala 165 170 175 Glu Gly Thr Leu Ser Leu Thr Gly Thr Ile Phe Gly Val Leu Ala Ser 180 185 190 Leu Cys Val Ser Leu Asn Ala Ile Tyr Thr Lys Lys Val Leu Pro Ala 195 200 I 205 Val Asp His Ser Tle Trp Arg Leu Thr Phe Tyr Asn Asn Val Asn Ala 210 215 220 Cys Val Leu Phe Leu Pro Leu Met Val Val Leu Gly Glu Leu His Ala 225 230 235 240 Leu Leu Ala Phe Ala His Leu Asn Ser Ala His Phe Trp Val Met Met 245 250 255 Thr Leu Gly Gly Leu Phe Gly Phe Ala Ile Gly Tyr Val Thr Gly Leu 260 265 270 Gln Ile Lys Phe Thr Ser Pro Leu Thr His Asn Val Ser Gly Thr Ala 215 280 285 Lys Ala Cys Ala Gln Thr Val Leu Ala Val Leu Tyr Tyr Glu Glu Ile 290 295 300 Lys Ser Phe Leu Trp Trp Thr Ser Asn Leu Met Val Leu Gly Gly Ser 305 310 315 320 Ser Ala Tyr Thr Trp Val Arg Gly Trp Glu Met Gln Lys Thr Gin Glu 325 330 335 Asp Pro Ser Ser Lys Glu Gly Glu Lys Ser Ala Gly Val 340 345 350 lt 210 gt 99 lt 211 gt 7752 lt 212 gt DNA lt 213 gt Mus musculus lt 400 gt 99 agcgttgcaa gttcagccga gggtggtgct gcaggtgcac ccgagggcac cgccgagggt 60 gagcaccagg tccctgcatc agocaggaca ccagagccca gtCgggtgga cggacggtac 120 gttctggaag ggaaagggcc cogggaaggg gatacagcat tgagaagctc agaggctttg 180 gtctgggcat gtgctgcttg Egtaggaaaa gagggaggtg tecctaagea agtctggtog gaaccttcca a
68. 190 Ala Ser Leu Pro Ala Val Asn Ala Cys 240 Arg Ala Leu 255 Met Met Thr 270 Gly Leu Gln Thr Ala Lys Giu Thr Lys 320 Gly Ser Ser 335 Gln Glu Asp 350 10 20 30 atgaataggg gaccectctg atcgcectgg tacctgctgg tgcctggtga gccgtggact tcggtggtct gectictaca ctgctcaagc ttctggcttg ttcggcgtgc ccggcggtgg ctcttcctgc ctgggcagtg ggctacgtga acggccaagg ticctcetggt 8gg8gCtggg gccatggggg lt 210 gt 94 lt 211 gt 364 212 PRT lt 213 gt Homo 400 94 Met Asn Arg Ala 1 Thr Gly Ala Ser Pro Phe Leu Leu 35 Trp Val Thr Ser 90 Ser Pro Ser Leu 65 Cys Leu Val Thr eccectctgaa cagaggcaga tggtctecct acagccocto ccacgctgct tocccagctt tcatcggcat atgtgggccg agaccacctc gtgtggacca iggctagcct acggcagcat ccctgctcct cecacttetg caggactgca CCtgtgccca ggacgagcaa agatgaagaa tgtga sapiens 20 gcggtccagg ctactgggtc cctgcggctg gtgcaaagge gcgcctggac gatcaccttc ctcactcacc cttctatgcc 8838888808 ctgtgtctcg ctggcgcctg gctgotcggg Sgggatgatg gatcaagtte gacagtgctg catgatggtg gactccggag 5 40 55 70 167 atcctgcaca gagaagccct acctocatct gacaceccca ctcagcgctc ctcagggtgg aataacctct accgtcttca ctgctcacct gaaggcacec ctcaacgoca actttctaca gagcttcagg acgctgggcg gcogtgotct ctgggcggct gagcccagcc 10 Asp Pro Ser Ala Glu Ala Glu Ala 25 75 JP VO2003 085119 A1 2003 10 16 tggcgctgac ttctgctgcg ccatggtgt
69. 30 50 98 JP WO2003 085119 1 2003 10 16 H C C n n PY n N g E C Y H C m r1 10 20 30 50
70. 480 528 624 672 120 768 816 10 20 30 Pro Glu Val Etc aag tte Val Lys Phe 275 aca aag ccg Thr Lys Pro 290 gtc cte acc Val Leu Thr 305 tgc gtc Cys Lys Val aaa gcc Ser Lys Ala cca tee cgg Pro Ser Arg 355 gtc aaa gge Val Lys Gly 370 888 Gly Gln Pro 385 gac gge tcc Asp Gly Ser tgg cag cag Trp Gln Gln cac aac cac His Asn His 435 lt 210 gt 90 Thr 260 aac Asn Arg gtc Val tcc Ser aaa Lys 340 gat sp ttc Phe gag Glu tte Phe Gly 420 tac Cys tgg Trp gag Glu ctg Leu aac Asn 325 EEE Gly gag Glu tat Tyr aac Asn tte Phe 405 aac Asn acg Val Val Val tac gtg gac Tyr Val Asp gag Glu cac His 310 aaa Lys cag Gln Leu CCC Pro aac Asn 390 ctc Leu gtc Val cag cag Gln 295 cag Gln gcc Ala cee Pro ace Thr age Ser 375 tac Tyr tac Tyr tic Phe aag Tyr Thr Gln Lys 280 tac Tyr gac Asp ctc Leu cga Arg aag Lys 360 gac Asp aag Lys age Ser tca Ser age Ser 440 162 Asp Val Ser 265 ggc Gly aac Asn tgg Trp cca Pro gaa Glu 345 aac Asn ate Ile acc Thr aag Lys tgc Cys 425 ctc gtg Val age Ser ctg Leu gee Ala 330 cca Pro cag Gin
71. C C 0 mnl O O B ET S nnnm nnnm B B B H eae E St D H C C C C 00000 0000 10 20 30 50 73 JP WO2003 085119 1 2003 10 H H lU C H C H C Te w C C H 10 20 30 50 74 JP VO2003 085119 1 2003 10 16
72. GIcNAc B1 2Man x 1 10 20 30 50 JP VO2003 085119 Al 2003 10 16 67 10 20 30 C HHHHHHHHHHHHHHH 50 68 JP VO2003 085119 1 2003 10 16
73. Thr Leu 180 Ile Thr 195 Val Cys Val Val Leu Glu Phe Arg 260 Gly His 275 Leu Pro Ala Val Pro Ala Gin Pro 340 Phe Lys 355 Gly Thr Glu Glu Arg Val Thr Lys 420 Ser Ala 435 Tle Leu Phe Ser His Pro 127 185 Tyr Leu Gln Asn Pro Lys Asn Tyr Ser 245 Pro Trp Tle Pro Val 325 Trp His Glu His Tyr 405 Tyr Gly Asp Ser Ile Asn 215 Cys Phe 230 Gln Asn Val Ser Ser Gly Val Asp 295 Glu Asp 310 Trp Trp Leu Glu Pro Val Ala Ala 375 Phe Gln 390 Leu Ala Ser Asn Leu His Ile His 455 Gln Val 470 200 Lys Met Trp Glu Glu 280 Ser Leu Val Arg Tle 360 Phe Leu Thr Tyr Asn 440 Phe Gly Cys Tle Ala Arg Tyr 250 Thr Cys 265 Val Lys Leu His Ala Asp Ser Gln 330 Glu Ile 345 Gly Val His Pro Leu Glu Asp Asp 410 Glu Phe 425 Arg Tyr Leu Ser JP VO2003 085119 1 2003 10 16 190 Asp Cys Ser Lys Ala Arg Gly Tyr 235 Ala Thr Asp Pro Arg 315 Phe Glu His Tle Arg 395 Pro Ile Thr Gin 205 Tyr Gly Cys Gln 220 Gly Thr Gin Thr Gly Gly Trp 255 Asp Arg Ser Gly 270 Lys Asn Val Gln 285 Arg Pro Pro Tyr 300 Leu Leu Arg Val Val Lys Tyr Leu 335 Glu Thr Thr Lys 350 Val Arg Arg Thr 365 Glu Glu Tyr Met 380 Arg Met Lys Val Ser Leu Leu Lys 415 Ser Asp Asn Ser 430 Glu
74. nnnm ES nnnm EM MM Y Y E Y NS fat Etta pi Y HHHHHHHHHHHHHH O O O Y 10 20 30 50 12 JP WO2003 085119 Al 2003 10 Y O HHHHHHHHHHH nnm a nnm E nnm nmn meme 10 20 30 50 13 JP WO2003 085119 1 2003 10 16
75. ug ml o g 4 724111250 00415 06 60 50 40 30 20 10 107 18 14 127 0 8 0 4 02 3 YB2 0 GD3 e CHO DG44 GD3 SP2 0 GD3 NS0 GD3 302 4 NS0 GD3 GT 107 g ml 5 0 01 01 1 TARE a g mL GD3 50 GD3 439 GD3 29 GD3 24 GD3 13 GD3 1 107 10 10 10 JP WO2003 085119 Al 2003 10 16 4 dn R m DX 0 40 60 80 6 A 50 N 0 0001 0001 001 01 1 10 B BURG 4 g mL 70 60 so 40 amp 20 10 9 0 0001 0 001 0 01 01 1 10 BRE g mL GD3 30 GD3 45 GD3 29 GD3 24 GD3 13 GD3 7 1000 7 I PESI a B 50 a sob
76. 30 lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 54 atgaagcctg gag 23 lt 210 gt 55 lt 211 gt 27 40 lt 212 gt DNA lt 213 gt Artificial Sequence 220 lt 223 gt Description of Artificial Sequence Synthetic DNA 145 JP WO2003 085119 Al 2003 10 16 lt 400 gt 55 tgccaccgtt tectccataa gcccagc 27 lt 210 gt 56 lt 211 gt 28 lt 212 gt DNA 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 56 atggctcaag cteccgctaa gtgcccga 28 lt 210 gt 57 lt 211 gt 27 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 57 tcaagcgttt gegttggtcc tcatgag 21 210 58 lt 211 gt 25 212 DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 58 10 20 30 146 JP WO2003 085119 Al 2003 10 16 tccggggatg gcgagatggg caagc 25 lt 210 gt 59 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 59 cttgacatgg ctctgggctc 24 lt 210 gt 60 lt 211 gt 25 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Seguence Synthetic DNA lt 400 gt 60 ccacttcagt
77. ctg Leu gtg aaa Lys ctt Leu 11 Phe got Ala 220 ett Leu gac Asp caa Gln agt Ser att Tle 300 acc Thr gaa Glu aac Asn caa gag Glu tat Tyr 805 Ala 205 aat Asn gga Gly tgg Trp aat Asn gtc Val 285 gtg Val SEC Gly gtg Val tgg Trp 149 Thr gec Ala 190 gtg Val ttt Phe caa Gln Gly gat Asp 270 cgt Arg tgg Trp aaa Lys gac Asp aag Lys 350 gat ace Thr 175 tat Tyr aac Asn gtt Val ctg Leu cat His 255 gaa Glu gaa Glu gaa Glu att Ile 335 Pro gtg 160 cct Pro teg Trp gge Gly act Thr gaa Glu 240 gcc Ala cca Pro ttt Phe gga Gly cat His 320 ctg Leu cgc Arg gag JP VO2003 085119 A1 2003 10 16 tte Phe att Ile att Ile Arg 220 tgt Cys aag Lys gag Glu gtt Val aag Lys 305 gtg Val cag Gln gtt Val cic tat Tyr gta Val ctc Leu 210 aaa Lys tte Phe gac Asp gac Asp gag Glu 290 aat Asn act Thr gga Gly gcc Ala atg cca Pro gtg Val 195 tte Phe att Ile agt Ser tat Tyr ttt Phe 275 aaa Lys gaa Glu gtg Val gac Asp ttt Phe 355 aga agg Arg 180 aac Asn aat Asn age Ser tig Leu gte Val 260
78. 085119 2003 10 16 100000000 52 Int d 21 02 50 72 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 79000 HH 100 0000000000 HHHHHH 0000000 O HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 100000 IHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHH IHHHHHHHHH HH HHHHHHHHHHHHHHHHHHH
79. 260 Ser Thr Lys Ser Asp Gly Gln Tyr 275 280 Leu Arg Ala Tyr Leu Pro Asp Phe 290 295 Val Lys Glu Thr Cys Ala Trp Phe 305 310 Lys lt 210 gt 20 lt 211 gt 590 lt 212 gt PRT lt 213 gt Cricetulus griseus lt 400 gt 20 Met Ala Ser Leu Arg Glu Ala Ser 1 5 Glu Met Arg Gly Lys Pro Val Ala 20 Val Ile Thr Ala Ala Asp Glu Lys 35 40 Leu Ser Glu Lys Leu Lys Arg Lys 50 55 His Val Phe Thr Asp Pro Pro Gly 65 70 Thr Leu Cys Ser Leu Gln Cys Leu 85 Asn Ser Phe Thr Val Leu Leu Ile 100 Leu Pro Asn Ala Ser Ala Leu Gly 123 JP VO2003 085119 A1 2003 10 16 Phe Ile Tyr Ser Leu Asp Leu Ala 220 Glu Tyr Asn Glu Val Glu Pro Ile 235 240 Glu Val Ser Ile Lys Glu Ala Ala 250 255 Phe Cys Gly Glu Val Thr Phe Asp 265 270 Lys Lys Thr Ala Ser Asn Gly Lys 285 Arg Phe Thr Pro Phe Lys Gln Ala 300 Thr Asp Asn Tyr Glu Gln Ala Arg 315 320 Leu Arg Lys Leu Arg Arg Phe Ser 10 15 Thr Gly Lys Phe Trp Asp Val Val 25 30 Gln Glu Leu Ala Tyr Lys Gln Gln 45 Glu Leu Pro Leu Gly Val Asn Tyr 60 Thr Lys Ile Gly Asn Gly Gly Ser 75 80 Glu Ser Leu Tyr Gly Asp Lys Trp 90 95 His Ser Gly Gly Tyr Ser Gin Arg 105 110 Lys Ile Phe Thr Ala Leu Pro Leu 10 20 30 Gly Asp 145 Asp Gln Thr Gly Ile 225 Gly Ser Ala Glu Thr 305 His Pro Thr Ala Pro 385 Ser Gly 115 Glu Pro fle 130 Phe Pro Ser Tle Glu Leu Pro Gly Phe 180 Thr His Gly 195 Asp Leu Glu 210 Glu Asn Met Gin Gin Asp Glu Tyr Val 260 Lys Lys Leu 275
80. 30 139 JP WO2003 085119 Al 2003 10 16 lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 40 cccaagcttg ccaccatggc gctagctgec cgagc lt 210 gt 41 lt 211 gt 31 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 41 ccggaattct gccaagtatg agccatcctg g lt 210 gt 42 lt 211 gt 17 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 42 gccatccaga aggtggt lt 210 gt 43 lt 211 gt 17 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Seguence Synthetic DNA 45 31 17 10 20 30 140 JP WO2003 085119 Al 2003 10 16 lt 400 gt 43 gtcttgtcag ggaagat 17 lt 210 gt 44 lt 211 gt 28 lt 212 gt DNA lt 213 gt Artificial Sequence 10 lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 44 ggcaggagac caccttgega gigoccac 28 lt 210 gt 45 20 lt 211 gt 28 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 45 30 gggtgggctg taccttctgg aacagege 28 lt 210 gt 46 lt 211 gt 28 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Syntheti
81. 90 Tle Asp Lys 135 ttt Phe age Ser tca Ser cat His Leu Val Val Gln Phe Thr Gly Pro Val JP cat cat His His tcc Gly Ser gag act Glu Thr 185 tga cag Leu Leu Val Phe Thr Leu 45 Trp Phe 60 Ile Asp Asn Leu Trp Leu Ile His 125 Thr Tyr WO2003 085119 Al 2003 10 16 aat tct Asn Ser 155 tac ttc Tyr Phe 170 gtg aac Val Asn gat cc Val Ser 15 Leu Glu 30 Lys Cys His Asn Ala Ala Ser Thr 95 Leu Leu 110 Leu Arg Leu Gln 140 gac Asp tgc Cys ate Tle Ala Pro Glu Thr 80 Leu Gln Cys Asn 480 528 576 620 10 20 30 136 JP WO2003 085119 A1 2003 10 16 130 135 140 Gly Lys Gly Arg Lys Tyr Phe His His Asn Ser Asp Phe Tyr Ile Pro 145 150 155 160 Lys Ala Thr Leu Lys Asp Ser Gly Ser Tyr Phe Cys Arg Gly Leu Phe 165 170 175 Gly Ser Lys Asn Val Ser Ser Glu Thr Val Asn Ile Thr Ile Thr Gln 180 185 190 Gly His His His His His His 195 210 gt 32 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 32 aggaaggtgg cectcatcac gggo 24 lt 210 gt 33 lt 211 gt 26 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 223 Description of Artificial Sequence Synthetic DNA lt 400 gt 33 taaggccaca agtcttaatt gcatcc 26 lt 210 gt 34 l
82. Gly get Gly aac Asn ada Lys cag Gln 115 gtt Ala Asp Val act Thr 145 gaa Glu 130 tet Cys ctg ggc Gly tat gac Asp acc Thr tac Tyr cga Arg atg Met 80 atc lle 100 agc Ser gat Asp ett Leu gga Leu Tyr Gly 48 96 144 192 240 288 336 384 432 480 10 20 30 aaa Lys 165 teg Ser ttt Phe cat His C8g Arg gga Gly 245 gag Glu ata Ile tte Phe gaa Glu ctg Leu 325 tcc Ser gag 150 gtg Val cee Pro Arg gag Glu tea Ser 230 aat Asn gct Ala gct Ala atg Met gtg Val 310 aaa caa Gln tat Tyr gag Glu agt Ser 215 gta Val ctg Leu atg Met act Thr tac gaa Glu gga Gly gct Ala 200 cct Pro gct Ala gac sp tgg Trp 555 Gly 280 att Tle aga Arg tac Lys Tyr Tyr aag ECE cag Lys Ala Gln ctg gtg agg ata Ile gca Ala 185 tat Tyr aga Arg aag Lys gee Ala ctg Leu 265 gaa Glu gga Gly igt Cys cga rg cag Gln 345 gag CCC Pro 170 gcc Ala aat Asn aga Arg att Ile aaa Lys 250 atg Met gtt Val aag Lys aaa Lys cca Pro 330 aaa Lys atg 155 cag Gin aaa Lys ctc Leu gga Gly tac Tyr 235 cga Arg tta Leu cat His acc Thr Bag Glu 315 act Thr
83. Gly Asp Ile Gly Val Asn Val Arg Glu Glu Lys Ile 575 Leu 15 560 Phe Val Arg Asp 30 Tle Leu Ala Arg Met Ala Thr Ala Thr Lys Lys 110 Leu Glu 95 Asp Trp Leu Lys His Leu Glu Gly Asn 140 Leu Leu Asp Leu Gly His His 80 Gin His Phe Glu Glu 10 20 30 145 Arg Ser Gly Asp Arg Lys His 225 Leu Thr Pro 305 Gly Leu Lys His 385 Lys Ala Ser Gly Arg Leu 210 His Val r Thr Glu 290 Leu Asp Pro Gly Val 370 Val Lys Lys Trp Val Ile Met Trp Arg 180 Ile Thr 195 Val Cys Val Val Leu Glu Phe Arg 260 Gly His 275 Leu Pro Ala Val Pro Ala Gln Pro 340 Phe Lys 355 Gly Thr Glu Glu Arg Val Thr Lys 420 Ser Ala 435 Ile Leu Thr 165 Glu Tyr Asn Tyr Ser 245 Pro Trp Tle Pro Val 325 Trp His Glu His Tyr 405 Tyr Gly Asp 150 Asp Leu Lys Glu Leu Gln Tle Asn 215 Cys Phe 230 Gln Asn Val Ser Ser Gly Val Asp 295 Glu Asp 310 Trp Trp Leu Glu Pro Val Ala Ala 375 Phe Gln 390 Leu Ala Ser Asn Leu His Tle His 129 155 Tyr Tyr Leu Ser 170 Ala Lys Asp Leu 185 Asn Pro Lys Asp 200 Lys Gly Cys Gly Met Ile Ala Tyr 235 Trp Arg Tyr Ala 250 Glu Thr Cys Thr 265 Glu Val Asn Asp 280 Ser Leu His Pro Leu Ala Asp Arg 315 Val Ser Gln Phe 330 Lys Glu Ile Glu 345 Ile Gly Val His 360 Ph
84. Thr Gln tac ttc Tyr Phe 75 cag aca Gin Thr ate Tle Gly gac ect Asp Pro aag gtc Lys Val ctt 48 Leu gtg 96 Val act 144 Thr tgg 192 Trp 60 att 240 Ile aac 288 Asn tgg 336 Trp att 384 Ile aca 432 Thr 10 20 30 125 tat Tyr ttc Phe Arg ace Thr lt 210 gt 31 tta Leu tac Tyr 888 Gly atc Ile 190 cag aat Gln Asn att cca Ile Pro 160 ett ttt Leu Phe 175 act caa Thr Gln lt 211 gt 199 lt 212 gt PRT lt 213 gt Homo sapiens lt 400 gt 31 Met Trp Gln Leu 1 Gly Met Arg Thr 20 Gln Trp Tyr Arg Gly Ser 65 Val Ser Ala His Ala 50 Leu Asp Asp Pro Ser 35 Tyr Ser Ile Ser Asp Ser Pro Val 100 Arg Trp 115 Trp Lys ggc Gly 145 aaa Lys ggg Gly ggt Gly Leu Glu Val Pro Ser Gly 85 Gln Val sn 130 aaa Lys gcc Ala agt Ser cat His Leu Asp Leu Glu Gln 70 Glu Leu Phe gge agg Gly Arg aca ctc Thr Leu aaa aat Lys Asn 180 cat cat His His 195 Pro Thr Leu Pro Glu Lys 40 Asp Asn 55 Ala Ser Tyr Arg Glu Val Lys Glu 120 aag Lys aaa Lys 165 gtg Val cat His Ala Lys 25 Asp Ser Ser Cys His 105 Glu Thr Ala Leu His 135 tat Tyr 150 gac Asp tct Ser cat His Leu 10 Ala Ser Thr Tyr Gln
85. Tle Asp Ala 290 Ala Glu Tyr Leu Leu Asp Leu Asn Val 340 Thr Glu Glu 355 Glu Leu Gly 370 Glu Asp Ser Gly Cys Cys Pro Glu Val Tyr Arg Tyr 165 Thr Val Tyr His Leu 245 Tyr Leu Tyr Thr Met 325 Val Tyr Leu His Val 405 Ser 124 120 JP VO2003 085119 A1 2003 10 16 Gln Met Leu Asp Leu Lys Leu 135 Met Lys Pro Gly Val Leu 150 Ser Ile Ala Leu Phe Val Arg Gln 215 His Phe 230 ser Gly Thr Asp Asp Phe Gly Asp 295 Lys Asn 310 Arg Gln Val Leu Leu Leu Gln Ser 375 Glu Lys 390 Ala Pro Ile Ser Gly Asp Ala His 185 Leu Asp 200 Cys His Asn Ala Gly Asp Ser Leu 265 Tyr Glu 280 Phe Leu Thr Ser Lys Ile Asn Asn 345 His Phe 360 Ile Ala Pro Cys Gly Ser Glu Asn Ser 170 Pro Ser Arg Val Thr 250 Phe Ser Gin His Phe 330 Ser Thr Phe Val Val 410 Cys 155 Glu Ser Ala Phe His 235 Thr Tyr Val Ala Val 315 His Arg Ser Ser Ile 395 Val Tle 140 Val Ser Ser Gly Leu 220 Arg Cys Met Gly Leu 300 Thr Leu Phe Asn Val 380 His Glu Ile 125 Ala Met Tyr Met Thr Cys Ala Asp 160 Ile Ala Phe Glu 175 Leu Ala Val Gly 190 Ser Leu Gln His 205 His Lys Pro Ser Leu Gly Ser Phe 240 His Pro Leu His 255 Asp His Lys Ser 270 Pro Leu Asn Cys
86. caagaaggag ctctgogtct atctggcgcc atagtgctgg tggctcatga cagatcaaat cagacagtgc aacctgatgg aagacccagg ccttcaggga gagcctactg gaagagccag cttctagtct gtctacctcc tgaagtgatg gaagggagct gctattaaca gagagagatg ggggtgactg tttacagatt ggcttetcit getatactct cetecatett 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 10 20 30 caggcaggaa catgaaggta ttatcccatc ttggcttata tttctgagga gcctcttgta agccttcaac ccagcaccac ccttttgtac atggggaaac ggcctgatgc lt 210 gt 96 lt 211 gt 360 212 PRT gtggggtcoa ggcttatgtt aggctectgt actgtictgg aacccctgtc taggagcact agaaggattc accctectat cctcatttoc catgtcagcc cctgagttgt 2192 Mus musculus 400 96 Met Ala Leu Thr 1 sn Lys Pro Phe Leu Tyr Trp Val 5 20 35 Leu Asp Ser Pro 50 Tyr Gln Cys Leu 65 Ala Thr Cys Cys Leu Lys Val Ala 85 100 ctcagectct ctctgaggct cacaaaatag cacatcctca agocotggga caacatgaat cctcagggta ttggcgtcat tctgcttccg atgtgattt Giy Val Ser Ala Leu Leu Arg Ala Thr Ser Ile Ser 40 Ser Leu Gin Leu 55 Val Thr Ser Leu 70 Pro Gly Met Val Arg Ser Val Leu 170 gttcccatct cctaggcogt geccacatca cttggtaaag gggCtccgcc ttggggacag gctgtcactg gtttgatgtc acttcecatg Val Ser Glu 10 Leu Gln Ile 25 Met Val
87. gCC Ala acg Thr ctc Leu 410 tcc Ser tcc gag Glu acg Thr aat Asn 315 cee Pro cag Gln gtc Val gtg Val ect Pro 395 acc Thr gtg Val ctg Leu Ser Leu His gig Val tac Tyr 300 ggc Gly atc lle gtg Val agc Ser gag Glu 380 ccc Pro gtg Val atg Met tet JP WO2003 085119 A1 2003 10 16 Glu Asp Pro Glu cat His 285 cgt Arg aag Lys gag Glu tac Tyr Leu 365 tgg Trp gtg Val gac Asp cat His 270 aat Asn gtg Val gag Glu aaa Lys acc Thr 350 acc Thr gag Glu ctg Leu agg Lys gag Glu 430 get gcc Ala gtc Val tac Tyr acc Thr 335 ctg Leu tge Cys age Ser gac Asp age Ser 415 get Ala aaa Ser Pro Gly Lys 445 aag Lys age Ser aag Lys 320 atc Ile ctg Leu aat Asn tec Ser 400 agg Arg ctg Leu 864 912 960 1008 1056 1104 1152 1200 1248 1296 1341 10 20 30 lt 211 gt 447 lt 212 gt protein lt 213 gt homo sapiens lt 400 gt 90 Met 1 Val Thr Arg Val 65 Asp Val Lys Phe Lys 145 Lys Arg Phe Thr Thr 225 Phe Pro Gly Ser Pro Leu Cys Leu 20 Gln His Val 35 Leu Ile Arg 50 Gln Val Leu Pro Phe Ala Arg Val Arg 100 Gly Lys Leu 115 Thr Glu Ile 130 Tyr Glu Gly Gly Ser Lys Leu Pro
88. geagtgaacc etttttacct aagtcaactt cagcatgtag atctttttgt tgttgaaaca ccaattcttt actggttcct ataggtggtc aagattcttg gagtetctce aggtataggg ttttaagtat tttacatagt atgcttatgt agtgctcatt tgctatgaat tctctcagat tctttatttg agaaggtaaa ttattaaagt ctttcaaata aataaatggt catttaaagt cccctttctt tcaaagtata ataattttat taagttacat ctaagcatac acatttggag ggaattttta ataatatatt ataatggtct gatggttatg aaaatgacag tagaaatgaa ctgaagtaca agaggtatta atttgttatc gatactgggt acgttgtatt agcccaggaa aagagtcatc acagaaactt gagctecgag ggcgttggat atttggttcg caaagctgga 8gtaggtttg tctcagtctg tgtagcagac tgcaatctta tgcatttaca aaattttttt B40 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 10 20 30 attctatgga tgatgaaaag teccatattt gaaagccaaa ttaacttgca tctaagaate tgcagatatg agatacagct tagagaggat cttttagaac aaatgtctat tectcggtgt agtcagggac cagggagggt gatttaggcc gtcatgggcc tettttcage aagattatac tecgaactct taaaagtete Ectcctgaat tecttttttc aatgtgaaat agagecteta ctgtcttaat caaggaaagg egatttccta geccaatcag gacttccccc taatttttat ttgtgctcat agagtttatt Cagaaatgtg gatgcatgca tgatgtcttt catotctcca aattgaattc aatgtaaata ctacaacaga caaaaattca ctagtctact gtctgattta gttactgagt atcatgtgta aagactttga gaatatatta gcettetggc tcagatgttt ggatgataat gagttg
89. gte Val tca Ser aat Asn tgc Cys 340 gac Asp acc 528 576 624 672 720 768 816 864 912 960 1008 1056 1104 10 20 30 150 JP WO2003 085119 Al 2003 10 16 Glu Leu Val Arg Glu Met Val Gln Ala Asp Val Glu Leu Met Arg Thr 360 365 370 aac ccc aac gcc tga gcacctctac aaaaaaattc gcgagacatg gactatggtg 1159 Asn Pro Asn Ala 375 cagagccagc caaccagagt ctgagaccat cgaccataaa ccctcgactg 1219 cotgtgtcgt ccccacagct gagagctggg ccacaggttt ggacggggac 1279 actecagage taaggccact tcgcttttgt caaaggctcc tctcaatgat tttgggaaat 1339 caagaagttt aaaatcacat actcattita cttgaaatta tgtcactaga caacttaaat 1399 ttttgagtct tgagattgtt tttotcttt cttattaaat gatctttcta tgacccagca 1459 aaaaaaaaaa aaaaaaggga tataaaaaaa aaaaaaaaaa 88888 1504 lt 210 gt 66 lt 211 gt 25 lt 212 gt DNA lt 213 gt Artificial Seguence 20 lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 66 atgaagttge actatggtga cetca 25 30 lt 210 gt 67 lt 211 gt 59 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 400 gt 67 ctgcctagta aaaatcatca atgaagtcaa acctacagag atctacaat 59 lt 210 gt 68 lt 211 gt 25 lt 212 gt DNA lt 213 gt Artificial Sequence 151 JP VO2003 085119 Al 2003 10 16 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 68 gacttagcag agtacactgo ag
90. tct Ser got Ala 880 Gly 20 gge Gly gga Gly tta Leu tat Tyr gtc Val att Ile 120 ace Thr gtg Val Pro aag Lys tca Ser att Ile tat Tyr ggt Gly aaa Lys 105 tec Ser ttg Leu aag gct Ala ccc Pro tac Tyr gta Val aag Lys 70 gac Asp 90 ect Pro ttt Phe CEE Arg tto age CCg Ser Cys Pro agg Arg ttg Leu Cgg Arg 55 aat Asn ctc Leu aca Thr gac Asp ctt Leu tac Lys Phe Tyr aag Lys gca Ala 40 cga Arg cca Pro ace Thr gag Glu tta Leu ctg Leu 140 cag Gln gtg Val 25 gaa Glu tcc Ser cag Gln gac Asp ate Ile goa Ala 125 gat sp gec Ala 148 age Ser 10 geg Ala tte Phe agt Ser gct Ala age Ser tac Tyr 110 gag Glu gca Ala tea Ser tee Ser cto Leu ctg Leu tca Ser cat His 75 acc Thr 95 aat Asn tac Tyr att Ile act Thr agg Arg ate Ile ctg Leu ttt Phe 60 att Ile tge Cys cit Leu act Thr aag Lys agt Ser JP VO2003 085119 Al 2003 10 16 aac Asn acg Thr gag Glu 45 aat Asn gaa Glu cta Leu get Gly tet Ser ggc Gly 30 aaa Lys aca Thr gga Gly gta Val Ala gat Gly 15 atc Ile gga
91. 1 AIC LARA BUS BRC SRT P RAER ORE 2207 na 23 06 03 oic 22 07 03 SHITE GEO SA Gas 935 ISA J P MEFS 100 8915 CS RRATAARBAB T H 4383 5 EMES 03 3581 1101 3448 RAPCT ISA 210 2 199 84474 196 JP WO2003 085119 A1 2003 10 16 PCT JP03 04504 X PX PX PX Shitara K et al A new vector for the high level expression of chimeric antibodies in myeloma cells J Immunol Methods 19 94 167 1 2 p 271 278 Davies J et al Expression of GnTIII in a recombinant anti C D20 CHO production cell line Expression of antibodies with altered glycoforms leads to an increase in ADCC through high er affinity for FC gamma Biotechnol Bioeng 2001 74
92. 20 0 75 0 73 0 99 1 81 1 36 61 33 0 16 0 19 0 24 0 30 0 10 L L3 L3 0 L L3 Ea L L L3 L3 L3 L L3 L3 L3 L E L L3 L3 L3 10 20 30 50 81 JP WO2003 085119 A1 2003 10 16
93. 22 taaatagaat tcggcatcat gtggoagotg ct lt 210 gt 23 lt 211 gt 575 lt 212 gt PRT lt 213 gt Cricetulus griseus lt 400 gt 23 Met Arg Ala Trp 1 Ala Trp Gly Thr 20 Asn Asp His Pro 35 Lys Leu Glu Arg 50 Glu Ser Leu Arg 65 Gly Arg Val Arg Tle Glu Asn Tyr 100 Glu Ile Leu Arg 115 Phe Leu Gln Ser 130 Leu Gln Arg His 145 Arg Ser Met Gly Glu Trp Arg Thr 5 Leu Asp Leu Ile Val 85 Lys Arg Glu Ala Thr 165 Glu Gly Ser Trp Leu Phe Tyr His Ser Ser 40 Lys Gln Gln 55 Pro Glu Gly 70 Leu Glu Glu Lys Gln Ala Arg Ile Glu 120 Leu Lys Lys 135 Asp Glu Ile 150 Asp Leu Tyr Lys Glu Ala Arg Trp Ile Met Leu Ile Leu 10 15 Ile Gly Gly His Leu Val Arg 25 30 Arg Glu Leu Ser Lys Ile Leu 45 Asn Glu Asp Leu Arg Arg Met 60 Pro Ile Asp Gln Gly Thr Ala 75 Gln Leu Val Lys Ala Lys Glu 90 95 Arg Asn Asp Leu Gly Lys Asp 105 110 Asn Gly Ala Lys Glu Leu Trp 125 Leu Lys Lys Leu Glu Gly Asn 140 Leu Leu Asp Leu Gly His His 155 Tyr Leu Ser Gln Thr Asp Gly 170 175 Lys Asp Leu Thr Glu Leu Val Phe Asp Ala Ala Thr 80 Gin His Phe Glu Glu 160 Ala Gln 10 20 30 Arg Lys His 225 Leu Thr Ser Val Pro 305 Gly Arg Leu Lys His 385 Lys Ala Ser Gly Cys 465 Thr Arg Leu 210 His Ile Val Thr Glu 290 Leu Asp Pro Gly Val 370 Val Lys Lys Trp Val 450
94. 285 Gly Pro Gly Ala Lys Glu Glu Ser 320 Leu Lys Gly Thr 335 Tyr His Ile Gly 350 Gly Ser Leu Gln 365 Phe Pro Asn Val Ser Ile Leu Asn 400 Tyr Ser Arg Leu 415 Ser Gly Ser Val 10 20 30 125 JP VO2003 085119 2003 10 16 420 425 430 Tle Glu Lys Ala Val Leu Pro Pro Cys Ser Phe Val Cys Ser Leu Ser 435 440 445 Val Glu Ile Asn Gly His Leu Glu Tyr Ser Thr Met Val Phe Gly Met 450 455 460 Glu Asp Asn Leu Lys Asn Ser Val Lys Thr Ile Ser Asp Ile Lys Met 465 470 475 480 Leu Gln Phe Phe Gly Val Cys Phe Leu Thr Cys Leu Asp Ile Trp Asn 485 490 495 Leu Lys Ala Met Glu Glu Leu Phe Ser Gly Ser Lys Thr Gln Leu Ser 500 505 510 Leu Trp Thr Ala Arg Ile Phe Pro Val Cys Ser Ser Leu Ser Glu Ser 515 520 525 Val Ala Ala Ser Leu Gly Met Leu Asn Ala Ile Arg Asn His Ser Pro 530 535 540 Phe Ser Leu Ser Asn Phe Lys Leu Leu Ser Ile Gln Glu Met Leu Leu 545 550 555 560 Cys Lys Asp Val Gly Asp Met Leu Ala Tyr Arg Glu Gln Leu Phe Leu 565 570 575 Glu Ile Ser Ser Lys Arg Lys Gln Ser Asp Ser Glu Lys Ser 580 585 590 lt 210 gt 21 lt 211 gt 25 lt 212 gt PRT lt 213 gt Homo sapiens lt 400 gt 21 Gln Val Thr Val Gln Ser Ser Pro Asn Phe Thr Gln His Val Arg Glu 1 5 10 15 Gln Ser Leu Val Thr Asp Gln Leu Cys 20 25 lt 210 gt 22 lt 211 gt 32 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 126 JP WO2003 085119 A1 2003 10 16 lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt
95. 3672800 A 9 31 33 34 36 39 4 3 45 48 5 8 17 2 0 30 32 35 37 38 4 4 46 47 26 28 Y Ripka J et al Two Chinese hamster ovary glycosylation 5 8 17 20 mutants affected in the conversion of GDP mannose to GDP 30 32 35 38 fucose Arch Biochem Biophys 1986 249 2 p 533 545 44 47 C A Y
96. Asn Ser Leu 445 Ala Asp Phe Leu 460 Cys Arg Val Ala Tyr Glu Ile Met Asp Ala Ser Ala Asn Phe 475 His Ser Leu Asp Asp Leu Thr 240 Glu Leu Val Leu His 320 Ile Lys Asp Val Asp 400 Glu Ile Arg Val Gln 480 Ile 10 20 30 485 Tyr Tyr Phe Gly Gly 500 His Gln Pro Arg Thr 515 Tle Gly Val Ala Gly 530 Arg Lys Leu Gly Lys 545 Lys Ile Glu Thr Val 565 lt 210 gt 24 lt 211 gt 575 lt 212 gt PRT lt 213 gt Mus musculus lt 400 gt 24 Met Arg Ala Trp Thr 1 5 Ala Trp Gly Thr Leu 20 Asn Asp His Pro Asp 35 Lys Leu Glu Arg Leu 50 Glu Ser Leu Arg Ile 65 Gly Arg Val Arg Val 85 Ile Glu Asn Tyr Lys 100 Glu Ile Leu Arg Arg 115 Phe Leu Gln Ser Glu 130 Leu Gln Arg His Ala 128 490 Gin Asn Ala His Asn Gln Ile Ala 505 Lys Glu Glu Ile Pro Met Glu Pro Asn His 535 Thr Gly 550 Lys Tyr Gly Ser Leu Phe His Ser Lys Gln 55 520 Trp Leu Pro Trp Tyr Ser 40 Gln 525 Asn Gly Tyr Ser Lys 540 Tyr Pro Ser Tyr Lys 555 Thr Tyr Pro Glu Ala 570 Arg Trp Ile Met Leu 10 Ile Gly Gly His Leu 25 Arg Glu Leu Ser Lys 45 Asn Glu Asp Leu Arg 60 Pro Glu Gly Pro Ile Asp Gln Gly 70 Leu Glu Glu 75 Gin Leu Val Lys Ala 90 Lys Gln Ala Arg Asn Gly Leu Gly Arg Ile Leu Lys 135 Asp Glu Glu 120 Lys Ile 105 Asn Gly Ala Lys Glu 125 495 JP WO2003 085119 Al 2003 10 16 Val Tyr Pro 510
97. C12P21 08 C12N15 09 C12N5 10 JP VO2003 085119 A1 2003 10 16 International application No PCT JP03 04504 07 16 18 GO1N33 50 07 16 46 61 39 395 A61P9 00 A61P29 00 A61P31 04 61 31 12 61 31 14 A61P35 00 A61P37 02 A61P37 04 According to International Patent Classification IPC or to both national classification and IPC B FIELDS SEARCHED Minimum documentation searched classification system followed by classification symbols Int Cl CO7K16 46 12 21 08 C12N15 09 C12N5 10 07 16 18 GO1N33 50 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Electronic data base consulted during the international search name of data base and where practicable search terms used BIOSIS MEDLINE WPIDS STN C DOCUMENTS CONSIDERED TO BE RELEVANT Category Wo 00 61739 Al 19 October 2000 amp EP 117619 Al X Y A 19 10 00 Ripka J et al Two Chinese hamster ovary glycosylation mutants affected in the conversion of GDP mannose to GDP fucose Biophys 1986 249 2 Citation of document with indication where appropriate of the relevant passages Kyowa Hakko Kogyo Co Ltd amp AU 3672800 A Arch Biochem pages 533 to 545 Relevant to claim No 1 4 9 16 21 25 27 29 31 33 34 36 39 43 45 48 5 8 17 20 30 32 35 37 38 44 46 47 26 28 5 8 17 20 30 32 35 38 44
98. DM DZ 74 100090343 EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN M W MX MZ NI NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW 54 F c y 1 1 1a 520000 HUHHHHHHHYHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH A HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHH 100D000D000000D0000D000D000000D000D000D ELE 00 N OBE D D 2 JP WO2003 085119 Al 2003 10 16
99. Phe Asp Thr Pro Leu Cys Lys 75 Asp Phe Pro 90 Pro Leu Ser 105 JP VO2003 085119 2003 10 16 gcttggacce gagcgcactg gtgtctaaga aggtactcat gcacagataa ecatgacctg aagcactcag tcctagtccc tttgtctctt ggttctaatg ctgagectct attctcggag acagtggagg agacccagta tctecctcag accacgatge ttctgtttgg tcgtgagaag aagttggtgg Glu Ser Glu Ser Gly 15 Ala Leu Val Val Ser 30 Leu Asn Lys Tyr Leu 45 Tie Phe Val Thr Phe 60 Gly Leu Ser Thr Leu 80 Thr Leu Asn Leu Asp 95 Val Val Phe Ile Gly 110 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2609 10 20 30 Met Ile Thr Phe Asn Asn Leu Cys Leu Lys Tyr Val Gly Val Pro Phe 115 120 125 Tyr Asn Val Gly Arg Ser Leu Thr Thr Val Phe Asn Val Leu Leu Ser 130 135 140 Tyr Leu Leu Leu Lys Gin Thr Thr Ser Phe Tyr Ala Leu Leu Thr Cys 145 Gly Val Ile Ile Thr Leu 180 Val Ser 195 His Ser Glu Gly Leu Cys Val Asp 210 Cys Val Leu Phe 225 Leu Leu Ala Phe Thr Leu Gly Gly 260 Lys Phe 275 Cys Ala Gln Ile Ala 290 Ser Lys Lys Phe Leu 305 Ser Ala Tyr Thr Ser Ser 340 Asp Pro lt 210 gt 97 lt 211 gt 1053 lt 212 gt DNA Gly 165 Ser Leu Ile Leu Thr 245 Leu Thr Gln Trp Trp 325 Lys 150 Gly Phe Trp Leu Thr Gly Asn Ala Ile 200 Trp Arg Leu 215 Pro Leu 230 His Leu Met Ser Phe Gly Phe Ser Pro Leu 280 Thr Val Leu 295 Trp Thr Ser 310 Val Arg Gly Asp Gly
100. VO2003 085119 A1 2003 10 16 10 20 30 lt 110 gt KYOWA KOGYO CO LTD lt 120 gt Method of enhancing of binding activity of antibody composition to Fcy receptor Illa lt 130 gt P044077 lt 150 gt P2002 106950 lt 151 gt 2002 04 09 lt 160 gt 100 110 SEOUENCE LISTING lt 170 gt Patentin Ver 2 1 lt 210 gt 1 lt 211 gt 2008 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 400 gt 1 aacagaaact teagctccga tggcgttgga catttggttc gcaaagctgg cgaataccag gaacagcttg ctgggaaagB ttttttetac catgcagatg tactacctca acagagctgg agaaagctgg gtttactgct tggcgctatg gacaggtctg tattttectg gaagacagaa ttatgcteat gagataatga agcgottaaa aaggccctat ttaaggccaa atcatgaaat aaagtgaatt aaattctttt gtcaaacaga iccagcggag tatgtaatat tcatgattgc ctactggagg gcctctccac tgtggctaac gggagttgaa tctttttgcc acaacaaaat tgatcagggg agaacagatt cttaaggagg gaagaaatta ggatttagga tggagcaggt aataacatat caacaaagge ttatggcacc atgggagact iggacactgg tagaaccaga actctgaaaa tgggggacct cattctagca gaagacttga acagctacag gaaaattaca aggattgaaa aagaaattag catcatgaaa gagtggcggg ctgcagaatc tgtggctatg cagcgaacac gtgtttagac icaggtgaag gtacaatgtt tgcgggcatg tattetttta gagaactetc ggagaatggc gaagagtccg agaaacaagc atggagctaa aaggaaacga ggtetatcat aaaaagaage CCaaggactg gatgtcaact tcatcttgga ctgtaagtga tgaaggacaa iccaattctt gactggttce tataggtggt caagattctt tgagtc
101. atccggaago tgaaggctgc Eccgtaaggt atccigcgca aagccatttc tecatttcca acccccattt agcactctgg aaggtggccc aacctotgcc gtgttcaacg ctcacctgcg agatcaatac gagaccigta aggtgaacat gctaagcati gttttatgga cactgacgta acacaccact ectctaccca aactaccttc attacacttg JP VO2003 085119 A1 2003 10 16 atggcttotc ctggaagcgg gtggcctgag ggtgaagatg gBgtggaggg cccttocctg gacttgccgg taagecgect cocgggacec gctccggtca tcccacgcgg ettectttct CCtCCCCCgC agaacttcat agccacagac gacccagctc tggcgctgac tgctccgggo tggtattcct ttgtcacctt ccacctgctg gaagtgtgct tcaagtacgt ttcttctctc ecetcatcat cacattactc gagaacaaat aataatgtta tgagccatet gagaaaccca gcagaaattt gttctcaaga ctgagccatt tcagatgtga tagcatcctc gcctctggaa tgaaaatagg ctcgagggac ggEgggggtc cacctgaccg gagaatgaca atctCCgggg ggagctcttg cgtaggcgtg gegtogctga ggCcoctgtc cectectttc tccgcgtccag ecctgcgact tagttaggcc cctagctgct ttctgccacc tggagtctct tctgcagatc caacaagtac ctaccaatgc ccccggcatg gccgctgtca aggggigece ctacetgctg tggtgagtgg attatctgtc aacttcctta ggcagacact taatgtaacg aggcacagag gcacataage ggtcaagggt tcagtggtcc ccataagtaa tttattgtac 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1146 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 10
102. cggtcggtag tattt 25 210 gt 61 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Seguence Synthetic DNA lt 400 gt 61 cgctcacccg cctgaggcga catg 24 147 JP VO2003 085119 A1 2003 10 16 lt 210 gt 62 lt 211 gt 32 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 62 ggcaggtgct gtcggtgagg tcaccatagt gc 32 lt 210 gt 63 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 63 gEEgCCatgc caaggactat gtcg 24 lt 210 gt 64 lt 211 gt 25 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 64 atgtggctga tgttacaaaa tgatg 25 lt 210 gt 65 10 20 30 lt 211 gt 1504 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 220 gt lt 221 gt CDS lt 222 gt 1 1119 lt 400 gt 65 atg Met 1 Gly ESC Gly gag Glu att Ile 65 aag Lys 85 ate Ile cat His gga Gly ata Ile get Ala gat Asp cag Gln gtt Val gaa Glu ttg Leu aat Asn gtc Val gtt Val aat Asn cac His aag Lys gat Asp 35 cat His cat His cac His gaa Glu aag Lys Gly 135
103. ctaccaggag tggggttggg tacacaaggg acatctctgg ttcagactac cctcttctgt acttcatatt atgaatgect ggccaccate tcccttcccc getgcacecg gagcccagtc ctgactggag cgggetetgc ttcctcaaca accttctacc tgctgccccg gtgctgccgc tacgtagggg ctctoctacc atcattgstg acgggcacca aagaaggtgc aatgcctgcg gecttcactc ggctttgcca aacgtgtcag gagattaaga tacacctggg ggtgagaaga gggCCtgccc tgtttacatc gaaagctgco tggcaccott gccagctgca agatgggttg ggecctggge ctttggaggc gtggatgggt ttcaacttta ctacagcecc ctgttcteca ttceccccoc 169 agggcaccgc gggtggacgg tetctgctgt agatcgcgct agtacctgct aatgoctggt gcatggtaga tgtcagtget tgcecttcta tgetgetcaa gtttctgget tettoggggt tecctgcagt tgctettett atctgagcag tcggctatgt gcacggccaa gcttcctgtg tcaggggctg gtgctatcag agcacggaag cttctcagaa aaatctectg cctgcctect cicttigggc tgaccctact aggtagcata agttgggage gaaaaggggg taaccccact acacctgacc cattagecte JP VO2003 085119 Al 2003 10 16 cgagggtgag acgggcgcet ctccgaggag ggtggtctct Bgacagcccc gacctcactg cttceecacc ctttatcggo caaecgtggga acagaccact gggtatagac gctggccagc agaccacagt gcocctgatg tgcccacttc gacaggactg ggcctgtgca gtggacaagc ggagatgcag ggtgtgagct gcttcccata gaccatctaa cctgccccat cctggggcct actggactga atagctagtt atagctaggt tgagccgaga aactgtccat agccacacet ttccctgcct cagetatctg ctecccaaca caccaggtec ctgaageggt tcagagagcg ctctactggg tccctgcagc ctgtgcaagg ctaaacctgg atgataacct cgctcgctca tecttctatg
104. etctatttct gatcctggat ggtctgtogg ecactcttta ttatcctcac tgtggctgga aggcttatat JP WO2003 085119 A1 2003 10 16 ggatgggaga actggacact gtagacagcc gatcgactog tatttgattc gecttcaaac gcagccttec gcacgcagaa ttaaaggagg tggtcagctg atacacttte gttgcttatg gatgacatct aaacctcgaa aaccattggg ecctectaca ctgtgtttag ggtcaggtga ttcatcctcg taagagtcca gtccacaacc atccagtcat atcccatcga tgcaagtgga caaagacaaa gactacacaa tctctcaggc aaatcatgca actattttgg ctgatgagga atggttattc aagtccgaga 2283 Description of Artificial Sequence Synthetic DNA lt 400 gt 8 aagtataagc ttacatggat gacgatatcg ctgcgctcgt 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 979 40 10 20 30 119 JP WO2003 085119 1 2003 10 16 2102 9 lt 211 gt 40 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 9 10 atttaactge aggaagcatt tecggtggac gatggagggg 40 lt 210 gt 10 lt 211 gt 40 2122 DNA lt 213 gt Artificial Sequence 20 lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 10 atttaaggta ccgaagcatt tgcggtgcac gatggagggg 40 lt 210 gt 11 30 lt 211 gt 23 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Deseription of Artificial Seguence Synthetic DNA lt 400 gt 11 40 ctccaattat gaatttatta gtg 23 lt 210 gt 12 120 JP VO2003 085
105. tgctacaggt ggtttctggc tgggtataga ccaagaggga 3480 gctgagggca ccctgtccct cataggcacc atcttcggge tgctggccag cctctgcgtc 3540 ccctcaatg ccatctatac caagaaggtg ctcecagcag tggacaacag CatctggCgo 3600 ctaaccttct ataacaatgt caatgcetgt gtgctottot tgcccctgat ggttetgctg 3660 ggtgagctcc gtgcectcet tgactttgct catctgtaca gtgcccactt ctggctcatg 3720 atgacgctgg gtggcotctt cggctttgcc attggctatg tgacaggact gcagatcaaa 3780 ttcaccagtc ccctgaccca caatgtatca ggcacagcca aggcctgtgc gcagacagtg 3840 ctggccgtgc tctactatga agagactaag agcttcctgt ggtggacaag caacctgatg 3900 gtgctgggtg gctcetcagc ctatacctgg gtcaggggct gggagatgca gaagacccaa 3960 gaggacccca gctccaaaga gggtgagaag agtgctattg gggtgtgagc ttettcaggg 4020 acctgggact gaacccaag 4039 180 JP VO2003 085119 Al 2003 10 16
106. 0 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 10 20 30 gttotcacca tcactttact gctattttat gtcacatctg tattggtgaa tccctttatc acacagaaac ctgttctaac tctttctctg acatggcctc cccgatgtcc aaccaatcag cocttgagat aggtgaatac tgggctccac tgaggtaagg tgtcctcatc tatagaccaa ggccagcctc ccacagtatc cctgatgata ccacttctgg aggactgcag ctgtgcacag gacaagcaac gatgcagaag gtgagctect tcccatagag catctaagaa ggggcctgtc ggactgatga gctagttgaa gctaggtgct gccgagagag tgtccatggg cacacgtttt cctgcctggc agggagccag ggecctcttc tttatagect tecttatata atttggggaa tgcagggcat ctggtatttt cctctaagct gcttgctctg tccacacttt catctgtact agatgatgga gettgeccet acagtacaca ECCCtCgEgCC gecatggaac gaaggagctg tgcgtctccc tggcgcctaa gtgctgggcg ctcatgatga atcaaattca acagtgctgg ctgatggtgc acccaggagg tcagggagcc cctactgggt gagccaggtt ctagtcttgg tacctccata agtgatgtct gggagctgtg attaacatca agagatggce gtgactgaca acagattaag ttetcttgge aaccaaggct ctttacagct tcattacaat ttccccctct gttataaccc ttctgtgcce cattaacaaa gctaatgccc ctccatgtgt tecttctece gtcctctccc aaaacagttt aacctgtact ggactgaccc ctttcttagt agtcagaacg gtgtcactct agggaacctt teaatgccat cettctataa agctccgtgc Cgctgggtgg ccagtcccct ccgtgctcta tgggtggctc accccagctc agggctgagc atggccctga ctttcctgat gaaagcccta tggtctctgg tactttctac taaccceaca ataacacttc attctgecct ectccacact tggagtgatg CCagaagggC 176 tagagccctg g
107. 00 H H C C C H Hod O O Hod O O O 10 20 30 FXcDNA RACE PCR 101 6 PCR JP WO2003 085119 A1 2003 10 16 5 RACE FX PCR FXGSP1 1 UPM Univarsal primer mix ZEE FXGSP1 2 NUP Nested Univarsal primer 300bp 3 RACE FX PCR FXGSP2 1 UPM Univarsal primer mix FXGSP2 2 NUP Nested Univarsal primer 1100bp H a u n nmnmnnnnnnnnunnnnnnnnnnunnnnm nn H H H 1 C C C C HHLHHHHHHHHH uHHHHH
108. 03 10 16 182 10 O O EL EEAET T8 OO O O O Qi OO Gp TUE O O Da E pal go BE DB R J O A R Ami a ngg ngg ngg ngg ngg a gg ngg ngg ngg ngg ngg ng ngga HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHWHHHHHHHHHHHHHHH HHHHHHHHHHH HHHHHHHHHHHHHHeWHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHH HHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHH UID OD LU EPA 9B ET i HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHH HHHHHHHUHHHHOHHHHHHHHHHHHHHHHHHHHHHHHH HHH HHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHH 00 000 O B Bug E HERE 2 HHHH 1 0000 1A 3 2 Kd YB2 0 GD3 e CHO DG44 GD3 0 SP2 0 GD3 NS0 GD3 302 NSO GD3 GIT N lt 6 6 S100 HESS 2 1 10 10
109. 119 Al 2003 10 16 a a a 10 20 30 50 23 JP VO2003 085119 A1 2003 10 16 E
110. 119 Al 2003 10 16 lt 211 gt 25 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 12 ggatgtttga agccaagctt cttgg 25 lt 210 gt 13 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 13 gtccatggtg atcctgcagt gtgg 24 lt 210 gt 14 lt 211 gt 23 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 14 caccaatgat atctccaggt tec 23 lt 210 gt 15 lt 211 gt 24 lt 212 gt DNA 10 20 30 121 JP VO2003 085119 A1 2003 10 16 lt 213 gt Artificial Sequence lt 220 gt 229 Description of Artificial Sequence Synthetic DNA lt 400 gt 15 gatatcgctg cgctcgtigt cgac 24 10 lt 210 gt 16 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA 20 lt 400 gt 16 caggaaggaa gectggaaaa gage 24 lt 210 gt 17 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence 30 lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 17 gatatcgotg cgctcgtcgt cgac 24 lt 210 gt 18 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 122 lt 223 gt Description of Artificial Se
111. 120 100 amp so ja 60 4 20 0 0 0 2 0 8 2 LCA mg ml 00000 2 7 KM2760 1 KM3060 pAGE249 CHO OGR4 LCA GMD CHO CCR4 LCA 25 25 HAREE ng ml 250 189 JP VO2003 085119 A1 2003 10 16 0 2 8 29 48 3 m IODD REPRE 3 0 3 1 GD3 4519 K N akena A 7 FGF 8 58 3T FGF 8 13 3 2 5 a 2 29 5 8 S X 2 gt 5 4n 44 15 ya 4 0 01 0 1 1 10 Cp g m 001 0 1 10 100 Cx g mL CCR4 87 CCR4 46 CCR4 39 CCR4 279 A CCR4 18 CCR4 9 CCR4 8 E 3 2 A 2 5 a 2 8 1 5 8 m 0 1 1 10 100 PUREE g mL 1 40 p mD 4 00415
112. 20 30 ccataagctc ttgccacagc ctcectggcc tgaaaaccaa gaagcatocg Ecccggcagt tttgecactt tcagagtcct tcttgtttgg tgtagggacc cctggatcca cactgceccoc cogtggggtc taggagaact gggacaagta gaaagtggag CCtcctgtgg cotgtogggc tctagactct accgtgggct agatagcatc cttgcctctc tcactccatc agttttaggg atgttgatgg 8Cagggagca ctgctecagt ccacaggaaa taacatagta agettaagta gatggctctg taaacctctg caggtttcta aggctgagta gaatggtgga ggggagctaa gaagcceggt gggggggtga tctgagtggc cecacaacta tgtgtttcaa cactatcact gccecttaac cacatggagc tgaatgaatt gaatgaacga cctatttaga aggccaacct gggttaaggg acatacatac ccacttceagt tacatgcagg ectgatagts ctctetgetg tcacageece agtggtaacc ctgctgagec ttgctatgtt tccagcttct cattgagcag tacaagtttg cagaaacgat tgtgggataa agtacaggct tatccactgt gcaaaaacgt acttctccca atgcctgtgc ccttgtggaa ccaactgggg ctggggggat gtccctggaa gtaggtggct gctgtggcct cccaggagte ggcatctctg agaagcagat gccagtctgc acagtctaaa ggcagcoact aaggecctct tagtggctgc aaagcaacct tgtccctggt gtactgtctt gtctgggcgg cctaagagat aagetacagt aggcagctga cceccactac tcictggaaa tctagggtct accaggaggt aagtgcctgt gccctcaagt tgaagacttg ctattagett agaaaggaag agttacacta cotgagcagg Eggaacacac agaaagatta Eggccccagtt agcagctcag tggteccact atgaggagtc gtggcaagga gaggaaggga agatgcagat tggggccatc agggagccat actgtaaaca 175 tgaaactgca agtctgggac tttgctectg tgtgctttta atgtcctgat tescttggac tgggttac
113. 4 p 288 294 Hackett J Jr et al Recombinant mouse human chimeric antibodies as calibrators in immunoassays that measure antibodies to Toxoplasma gondii J Clin Microbiol 1998 36 5 p 1277 1284 Elbashir SM et al Duplexes of 21 nucleotide RNAs mediate RN A interference in cultured mammalian cells Nature 2001 411 6836 p 494 498 WO 97 27303 A 1997 7 31 amp US 6054304 A EP 816503 Al amp JP 9 201191 A Shields RL et al High resolution mapping of the binding site on human 1861 for Fc gamma RI Fc gamma RII Fc gamma RIII and FcRn and design of IgGl variants with improved binding to the Fc gamma R J Biol Chem 2001 276 9 p 6591 6604 Shields RL et al Lack of fucose on human 1661 N linked oligo saccharide improves binding to human Fegamma RIII and antibody dependent cellular toxicity J Biol Chem 2002 Jul 277 30 p 26733 26740 Shinkawa T et al The absence of fucose but not the presence of galactose or bisecting N acetylglucosamine of human 1201 complex type oligosaccharides shows the critical role of enhancing antibody dependent cellular cytotoxicity J Biol Chem 2003 278 5 p 3466 3473 WO 02 31140 Al 2002 04 18 amp AU 9419801 A MRPCT ISA 210 2 1998475 1 25 30 45 47 48 1 27 29 37 46 5 8 17 20 30 32 35 38 44 47 1 48 1 48 1 48 1 48 1 48 197 JP VO2003
114. 400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 10 20 30 ctatctggct tggacccctg cgcactgatt tctaagaaca tactcataga cagataatct tgacctgatc cactcagacc tagtcectte gtctctttcg tctaatgaag ttttttaaaa lt 210 gt 100 lt 211 gt 4039 lt 212 gt DNA atactctctt ecatcttcag agectctcat ctcggagtta gtggaggttg cccagtattt ecctcaggce accccaaagc acgatgccca tgtttggcct tgagaagatg ttggtggggo ac tctgtactcc gcaggaagtg gaaggtaggc teccatcagg gcttataact ctgaggaaac tcttgtatag citcaacaga gcaccacacc tttgtaccct gggaaaccat ctgatgccct lt 213 gt Cricetulus griseus lt 400 gt 100 gaacttcacc gccctgtaga acagggccoc cctctgagga icgcgctggt acotgctgga gcctggtgac ccgttgactt cggtagtctt cettctacaa tgctcaaaca gBggCCCggg gtaggtacct tagaaaacaa ataatgttag caggtactca aaatatatec caagccatgt ccagggagtg tctgaagcgg ggcagatgaa cgtetctcte cageccctec ctctctgctg ecccaccctg cattggcatg cgtggggege gaccacttoc ggctgtggga ttacttactg ataacttect cagcaactac gatcyaagca gaattttaca gacaattgaa cttctggccg tecaggatcc gacagcagga tactgggtca ctgcagctgg tgcaagggcc aacctggacc ataagtttca tegctcacca ttctatgccc gcaggatggg tcccaggtcc tatggtcatt agcaaagatg ttggatccac gagggaaaac 177 etteccette gggtccactc ttatgttctc ctcctgtcac gttctggggg cectgtccac gagcactage aggattccaa ctcctatcct
115. 400 gt 30 gaa ttc ggc atc atg Met 1 cta Leu tte Phe ctg Leu 45 ttt Phe gac Asp ctc Leu ctg Leu cac His git tca gct ggc Val Ser Ala Gly 15 ctg gag cct caa Leu Glu Pro Gln 30 aag tgc cag gga Lys Cys Gin Gly cac aat gag age His Asn Glu Ser 65 get gcc gtc Ala Ala Thr Val 80 tec acc cte agt Ser Thr Leu Ser 95 ttg ctc cag gcc Leu Leu Gln Ala 110 ctg agg tgt cac Leu Arg Cys His tgg Trp atg Met tgg Trp gcc Ala 50 ete Leu gac Asp gac Asp ect Pro age Ser cag Gln CEE Arg tac Tyr 35 tac Tyr ate Ile gac Asp CCg Pro egg Arg 115 tgg ctg Leu act Thr 20 agg Arg tcc Ser tca Ser agt Ser gtg Val 100 tgg 134 ctc Leu 5 gaa Glu gtg Val ect Pro age Ser 884 Gly 85 cag Gin gtg ctc Leu gat Asp cte Leu gag Glu cag Gin 70 gag Glu cta Leu tte Trp Val Phe aag aac act cca Pro ctc Leu gag Glu gac Asp 55 gcc Ala tac Tyr gaa Glu aag Lys gct JP WO2003 085119 A1 2003 10 16 act get Thr Ala cca aag Pro Lys 25 aag gac Lys Asp 40 aat tcc Asn Ser tcg Ser Ser agg tgc Arg Cys gtc cat Val His 105 gag gaa Glu Glu 120 ctg cat Trp Lys Asn Thr Ala Leu His ctg cta Leu Leu 10 gct gtg Ala Val agt gtg Ser Val aca cag
116. 47 Further documents are listed in the continuation of Box C See patent family annex Special categories of cited documents A document defining the general state of the art which is not considered to be of particular relevance earlier document but published on or after the international filing date document which may throw doubts on priority claim s or which is cited to establish the publication date of another citation or other special reason as specified 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 pr later document published after the international filing date or priority date and not in conflict with the application but cited to understand the principle or theory underlying the invention document of particular relevance the claimed invention cannot be considered novel or cannot be considered to involve an inventive step when the document is taken alone document of particular relevance the claimed invention cannot be considered to involve an inventive step when the document is combined with onc or more other such documents such combination being obvious to a person skilled in the art document member of the same patent family Date of the actual completion of the international search 23 May 2003 23 05 03
117. 9 201191 A Shields RL et al High resolution mapping of the binding site on human IgGl for Fc gamma RI Fc gamma RII Fc gamma RITI and FcRn and design of IgGl variants with improved binding to the Fc gamma R J Biol Chem 2001 276 9 pages 6591 to 6604 Shields RL et al Lack of fucose on human 1461 N linked oligosaccharide improves binding to human Fc gamma RIII and antibody dependent celluiar toxicity J Biol Chem 2002 Jul 277 30 pages 26733 to 26740 SHINKAWA T et al The absence of fucose but not the presence of galactose or bisecting N acetylglucosamine of human IgGl complex type oligosaccharides shows the critical role of enhancing antibody dependent cellular cytotoxicity J Biol Chem 2003 278 5 pages 3466 to 3473 WO 02 31140 Al Kyowa Hakko Kogyo Co Ltd 18 April 2002 18 04 02 amp AU 9419801 A Form PCT ISA 210 continuation of second sheet July 1998 194 JP VO2003 085119 Al 2003 10 16 International application PCT JP03 04504 Continuation of A CLASSIFICATION OF SUBJECT MATTER International Patent Classification IPC INTERNATIONAL SEARCH REPORT Tnt C17 A61P37 08 61 43 00 GO1N33 15 C12P21 08 C12R1 91 C12N5 10 C12R1 91 According to International Patent Classification IPC or to both national classification and IPC Continuation of B FIELDS SEARCHED Minimum Documentation Searched International Patent Classificatio
118. Arg 180 Leu Asn Tyr 195 Trp Ala Pro 210 Cys Pro Pro Leu Phe Pro Glu Val Thr Arg Ser Ala Leu 5 Gln Ala Gln Val Arg Glu Gln Ser 40 Thr Tyr Gln Leu 55 Ala Asn Lys Arg 70 Lys Leu Ile Val 85 Gly Ala Glu Thr Ile Ala Lys Ser 120 Val Leu Glu Asn 135 Trp Tyr Met Ala 150 Thr Arg Gln His 165 Gly His His Thr Pro Pro Phe Thr 200 Glu Pro Arg Glu 215 Cys Pro Ala Pro 230 Pro Lys Pro Lys 245 Cys Val Val Val 163 Ser Cys Leu Leu 10 Thr Val Gln Ser 25 Leu Val Thr Asp Tyr Ser Arg Thr 60 Tle Asn Ala Met 75 Glu Thr Asp Thr 90 Gly Leu Tyr Ile 105 Asn Gly Lys Gly Asn Tyr Thr Ala 140 Phe Thr Arg Lys 155 Gln Arg Glu Val 170 Thr Glu Gln Ser 185 Arg Ser Leu Arg Pro Lys Ser Cys 220 Glu Leu Leu Gly 235 Asp Thr Leu Met 250 Asp Val Ser His JP VO2003 085119 A1 2003 10 16 Leu His Leu Leu 15 Ser Pro Asn Phe 30 Gln Leu Ser Arg Ser Gly Lys His Ala Glu Asp Gly 80 Phe Gly Ser Arg 95 Cys Met Asn Lys 110 Lys Asp Cys Val 125 Leu Gln Asn Ala Gly Arg Pro Arg 160 His Phe Met Lys 175 Leu Arg Phe Glu 190 Gly Ser Gln Arg 205 Asp Lys Thr His Gly Pro Ser Val 240 Ile Ser Arg Thr 255 Glu Asp Pro Glu 10 20 30 164 JP WO2003 085119 Al 2003 10 16 260 265 270 Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 275 280 285 Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 290 295 300 Val Leu Thr Val Leu His Gln A
119. Glu lt 213 gt Rattus norvegiucus lt 400 gt 97 171 155 Leu Gly Ile 170 Thr Ile Phe 185 Tyr Thr Lys Thr Phe Tyr Ile Val Leu 235 Ser Ala His 250 Ala Ile Gly 265 Thr His Asn Ala Val Leu Asn Leu Met 315 Glu Met 330 Ser Ala Trp Lys 345 JP VO2003 085119 Al 2003 10 16 Asp Gln Gly Val Val 205 Asn Lys Asn 220 Gly Glu Phe Trp Tyr Val Val Ser 285 Tyr Tyr 300 Val Leu Gln Lys Ile Arg 160 Glu Gly Ala 175 Leu Ala Ser 190 Leu Pro Ala Val Asn Ala Leu Arg Ala 240 Leu Met Met 255 Thr Gly Leu 270 Gly Thr Ala Glu Glu Ile Gly Gly Ser 320 Thr Gln Glu 335 Val 350 atggcectga ctggagcctc tgctgtctct gaggaggcag ctgctacggg ctctgcagat cgcgctggtg gtttctctct atggtattce tcaacaagta cctgctggac ttcgtcacct tctaccaatg cctggtgacc tcactgctgt gccacctgct gcoctggcat ggtagacttc CCCaCcctaa acagcgagaa caagccattt actgggtcac ctccatetcc tgcagctgga tacccccato gcaagggcct cagcactctg acctggacct caaggtggcc 10 20 30 40 60 120 180 240 300 cgaagtgtgo ctcaagtacg gtgcttctct gccatcatca tccctgacgg tacaccaaga aacgtcaacg ctcetggcct ctcttcggct acccataatg tatgaagaga tctgcctaca aaagagggtg 2102 98 lt 211 gt 350 2122 PRT tgcegctgtc tgggggtggc cctacctgct ttggtggttt gcaccatctt aggtgctcec ccigtgtgct tcgctcatct itgccattgg tgtegggcac ttaagagctt cctgggtcag agaagagtgc cgtggtettt cttctacaac gcttaaacag ctggctggga Cggggtgctg tgecg
120. Glu Glu Glu Ile Pro Met Glu 520 Asn His Trp Asp Gly Tyr Ser 535 540 Thr Gly Leu Tyr Pro Ser Tyr 550 555 Lys Tyr Pro Thr Tyr Pro Glu 570 10 JP VO2003 085119 A1 2003 10 16 Glu Ile Met Leu Asp Asp 495 Ala Val Tyr 510 Pro Gly Asp 525 Lys Gly Ile Lys Val Arg Ala Glu Lys 575 15 Gln 480 Ile Pro Ile Asn Glu 560 10 20 30 lt 210 gt 27 lt 211 gt 78 lt 212 gt lt 213 gt lt 220 gt lt 221 gt lt 222 gt lt 400 gt 27 gaa ttc ggc cta Leu ttc Phe ctg Leu 45 ttt Phe gac Asp ete Leu ctg Leu cac His ett Val ctg Leu 30 aag Lys cac His gct Ala tcc Ser ttg Leu 110 ctg Leu 8 DNA Homo sapiens CDS 19 tea Ser 15 gag Glu tgc Cys aat Asn gcc Ala acc Thr 95 cto Leu agg rg 774 atc get Ala cct Pro cag Gln gag Glu aca Thr 80 ctc Leu cag Gln tat Cys atg tgg cag Met Trp Gln 1 ggc atg cgg Gly Met Arg caa tgg tac Gln Trp Tyr 35 gga gcc tac Gly Ala Tyr 50 age ctc atc Ser Leu Ile 65 gtc gac gac Val Asp Asp agt gac ccg Ser Asp Pro gcc cct cgg Ala Pro Arg 115 cac agc tgg ctg Leu act Thr 20 agg Arg tcc Ser tca Ser agt Ser gtg Val 100 teg Trp aag ctc Leu 5 gaa Glu gtg Val cet Pro age Ser gga Gly 85 cag Gin gig Val aac 131 c
121. HHHHHHi C dmt nnn dein x x 10 20 30 50 JP WO2003 085119 A1 2003 10 16 70 10 20 30 50 C HHHHHHHHHHHHHHHHHHHHHH HHHH nnnnnnn C 71 JP WO2003 085119 Al 2003 10
122. JP WO2003 085119 2003 10 16 19 JP A1 1 WO2003 085119 17 8 11 2005 8 11 43 15 1 16 2003 10 16 51 Int C1 Fl CO7K 16 28 CO7K 16 28 ZNA C12N 1 15 C12N 1 15 C12N 1 19 C12N 1 19 C12N 1 21 C12N 1 21 C12N 5 10 C12P 21 02 C BARR RK 197 R 2003 582297 P2003 582297 71 000001029 21 PCT JP2003 004504 22 15 4 9 2003 4 9 1 6 1 3 31 2002 106950 P2002 106950 70 100105647 32 14 4 9 2002 4 9 BF 33 JP 74 100105474 81 AP GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW EA AM AZ BY KG KZ MD RU TJ TM AT 74 100108589 BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU NL PT RO SE SI SK TR OA BF BJ CF CG CI CM GA 74 100115107 GN GQ GW ML MR NE SN TD TG AG AL AM AT AU AZ if A BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK
123. JP WO2003 085119 Al 2003 10 16 ggatgggaga actggacact gtagacagcc gatcgactce tacttgatec ggettcaaac gcagccttcc gaacgcagaa ttaaaggagg tggtcagctg atacactttc gttgettatg gatgacatct caacctcgaa aaccattgga ecttectaca ctgtgtttag getcaggtga tccatcctcg tgagagtcca gtocacaace atccagttat atcccattga tgaaagtgga gactacacaa tctcccaggc aaatcatgea actattttgg ctaaagagga atggttacte aagtccgaga 25 24 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 979 10 20 30 lt 210 gt 7 lt 211 gt 979 lt 212 gt DNA lt 213 gt Rattus norvegicus lt 400 gt 7 actcatcttg acctgtaagt agtgaatgac ecctecttac tggtgatcct ttggctagaa tggagtccat agagtacatg taaaaaaaga gtactccaat teggiacaca igacttccta aaccctgcat aggccaaaat aattccaatg taaaggtgtc gaagatagaa lt 210 gt 8 lt 211 gt 40 lt 212 gt DNA gaatctcaga gagacatgca aaaaatatte ttaccactgg gcagtgtggt aaggaaatag gtcagacgca gtacatgtig gtatatctgg tatgaattta gaaaattcac gtgtgtactt cctgatgoct gcccacaace gaacctggag aacagaaaac acggtcaag attggcgeta cagacagatc aagiggtgga ctgttccaga gggtgtccca aagaagecac cagacaaagt aagaacattt ctaccgatga ttagtgataa ttcggggcgt tttcatccca ctgcaaactt agattgecgt atatcattgg ttggaaaaac lt 213 gt Artificial Sequence 220 118 igctactggt gctecccatt agaccttgca gttcgtcaaa caagaagctt teagctictc cectgctttg
124. Leu Ala 195 Val Ser Phe 210 Leu Tyr Phe 225 Lys Asp His lt 210 gt 29 lt 211 gt 51 lt 212 gt DNA Ser Ser Ser Val 100 Trp Lys Arg Leu Asn 180 Val Cys Ser Lys Pro Glu Asp Asn 55 Ser Gln Ala Ser 70 Gly Glu Tyr Arg 85 Gln Leu Glu Val Val Phe Lys Glu 120 Asn Thr Ala Leu 135 Lys Tyr Phe His 150 Lys Asp Ser Gly 165 Val Ser Ser Glu Ser Thr Ile Ser 200 Leu Val Met Val 215 Val Lys Thr Asn 230 Phe Lys Trp Arg 245 lt 213 gt Artificial Sequence lt 220 gt 133 Ser Thr Gln Ser Tyr Phe 75 Cys Gln Thr 90 His Ile Gly 105 Glu Asp Pro His Lys Val His Asn Ser 155 Ser Tyr Phe 170 Thr Val Asn 185 Ser Phe Phe Leu Leu Phe Ile Arg Ser 235 Lys Asp Pro 250 JP VO2003 085119 Al 2003 10 16 Trp Phe 60 Ile Asp Asn Leu Trp Leu Ile His 125 Thr Tyr 140 Asp Phe Cys Arg Thr Pro Pro 205 Ala Val 220 Ser Thr Gln Asp His Asn Glu Ala Ala Thr 80 Ser Thr Leu 95 Leu Leu Gln 110 Leu Arg Cys Leu Gln Asn Tyr Ile Pro 160 Gly Leu Phe 175 Ile Thr Gln 190 Gly Tyr Gln Asp Thr Gly Arg Asp Trp 240 Lys lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 29 tgttggatcc tgtcaatgat gatgatgatg atgaccttga gtgatggtga t 51 10 20 30 lt 210 gt 30 lt 211 gt 620 lt 212 gt DNA lt 213 gt Homo sapiens lt 220 gt lt 221 gt CDS lt 222 gt 13 609 lt
125. NA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence synthetic DNA lt 400 gt 85 atcgtacgtt ttatttccag cttggtco 28 lt 210 gt 86 lt 211 gt 57 lt 212 gt DNA lt 213 gt Artificial Sequence 220 223 Description of Artificial Sequence synthetic DNA 400 86 ttgttggtac cgaattcttt cagggcccog gagccccgag agcccaaatc ttgtgac 57 lt 210 gt 87 lt 211 gt 31 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 10 20 30 160 JP VO2003 085119 Al 2003 10 16 lt 223 gt Description of Artificial Sequence synthetic DNA lt 400 gt 87 gcgaattcca ccatgggcag cccccgctce g lt 210 gt 88 lt 211 gt 32 2122 DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence synthetic DNA lt 400 gt 88 cgggatccet atcgggectc cggggcccaa gt lt 210 gt 89 lt 211 gt 1341 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence synthetic DNA lt 400 gt 89 atg age Met Gly Ser 1 ett ctc tge Val Leu Cys aca cag cat Thr Gln His 35 cge ctc atc Arg Leu Ile ccc cgc gcg age Pro Arg Ser Ala Leu Ser 5 caa gcc cag gta act tec ctg ctg ttg cac ttg ctg Cys Leu Leu 10 gtt cag tec Leu Gln Gln Val Thr Val Gln Ser 20 25 gtg agg gag cag age ctg gig acg gat Val Arg Glu Gln Ser Leu 40 egg acc
126. Name and mailing address of the ISA Japanese Patent Office Facsimile No Form PCT ISA 210 second sheet July 1998 Date of mailing of the international search report 22 July 2003 22 07 03 Autborized officer Telephone No 193 JP WO2003 085119 Al 2003 10 16 INTERNATIONAL SEARCH REPORT International application No PCT JP03 04504 C Continuation DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with indication where appropriate of the relevant passages Relevant to claim No Shitara K et al A new vector for the high 1 25 30 45 level expression of chimeric antibodies in myeloma 47 48 celis J Immunol Methods 1994 167 1 2 pages 271 to 278 Davies J et al Expression of GnTIII in a recombinant anti CD20 CHO production cell line Expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FC gamma RIII Biotechnol Bioeng 2001 74 4 pages 288 to 294 Hackett J Jr et al Recombinant mouse human chimeric antibodies as calibrators in immunoassays that measure antibodies to Toxoplasma gondii J Clin Microbiol 1998 36 5 pages 1277 to 1284 Elbashir SM et al Duplexes of 21 nucleotide 5 8 17 20 RNAs mediate RNA interference in cultured 30 32 35 38 mammalian cells Nature 2001 411 6836 44 47 pages 494 to 498 WO 97 27303 A Toyobo Co Ltd 31 July 1997 31 07 97 amp US 6054304 A amp EP 816503 A1 amp JP
127. P VO2003 085119 1 2003 10 16 104 2 R m m eJ a DI I O Ol 5 a I O I p Ol DI I DIL DL 9 5 LI I I 5 N DL 5 C
128. Ser Glu tac gac Tyr sp tct aca Ser Thr 140 Leu Ser Gly Ala Ala Ser Arg Ser 60 Asp Ser 75 Ala Asp Ser Glu JP VO2003 085119 1 2003 10 16 95 tct gca Asp Ser Ala 110 gta agg ttt Val Arg Phe 125 Gly Thr Thr 15 Glu Val Ala 30 Gly Tyr Thr 45 Gly Gln Gly Ile Tyr Tyr Lys Ser Ser 95 gtc Val gtc Val Gly Arg Phe Leu Asn 80 Ser Asp Ser Ala Val 110 Tyr Asp Val Arg Phe Val Ser Thr 140 125 336 384 420 10 20 30 155 JP VO2003 085119 A1 2003 10 16 lt 210 gt 74 lt 211 gt 393 lt 212 gt DNA lt 213 gt Mus musculus lt 220 gt lt 221 gt CDS 222 1 393 400 74 atg aag ttg cct gtt agg ctg ttg gtg ctg atg ttc tgg att cct get 48 Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala 1 5 10 15 tcc agg agt gat ett ttg atg ace caa act cca cte tcc ctg cct gtc 96 Ser Arg Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val 20 25 30 agt ctt gga gat caa gcc tee atc tct tgc aga tet agt cag agt ctt 144 Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu 35 40 45 gta cat agt aat gga aga acc tat tta gaa tgg tac ctg cag aaa cet 192 Val His Ser Asn Gly Arg Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro 50 55 60 gec cag tca cca aag gtc ctg atc tac aaa gtt tcc aac att tct 240 Gly Gln Ser Pro Lys Val Leu Ile Tyr Lys Val Ser Asn Arg Ile Ser 65 70 75 80 ggg gtc cca gac agg ttc a
129. TGG 3 638 431 R 5 CACCAATGATATCTCCAGETICC 3 B actin F 5 GATATCGCTGCGCTCGTTGTCGAC 3 189 609 R 5 CAGGAAGGAAGGCTGGAAAAGAGC 3 10 G actin F 5 GATATCGCTGCGCTCGTCGTCGAC 3 789 609 R 5 CAGGAAGGAAGGCTGGAAGAGAGC 3 A nnn a F R H D D 20 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH na N B R 1 268 3 4 5 CHO 1 95 0 90 0 57 0 52 0 54 YB2 0 0 12 0 11 0 14 0 08 0 07 78 JP WO2003 085119 Al 2003 10 16
130. Val Asp 210 215 220 Gly Ser Ile Trp Arg Leu Thr Phe Tyr Asn Asn Val Asn Ala Cys Ile 225 230 235 240 Leu Phe Leu Pro Leu Leu Leu Leu Leu Gly Glu Leu Gln Ala Leu Arg 245 250 255 Asp Phe Ala Gln Leu Gly Ser Ala His Phe Trp Gly Met Met Thr Leu 260 265 270 Gly Gly Leu Phe Gly Phe Ala Ile Gly Tyr Val Thr Gly Leu Gln Ile 275 280 285 Lys Phe Thr Ser Pro Leu Thr His Asn Val Ser Gly Thr Ala Lys Ala 290 295 300 Cys Ala Gln Thr Val Leu Ala Val Leu Tyr Tyr Glu Glu Thr Lys Ser 305 310 315 320 Phe Leu Trp Trp Thr Ser Asn Met Met Val Leu Gly Gly Ser Ser Ala 325 330 335 Tyr Thr Trp Val Arg Gly Trp Glu Met Lys Lys Thr Pro Glu Glu Pro 340 345 350 Ser Pro Lys Asp Ser Glu Lys Ser Ala Met Gly Val 355 360 364 lt 210 gt 95 lt 211 gt 2609 lt 212 gt DNA lt 213 gt Mus musculus 400 95 ctgcatcagc ccaggatcct ggaacaagcc tcacctccat tggatacccc gcctcagcac acctcaaget teaataacct ccaccgtgtt ecctgctcac ctgagggaac ccctcaatge taaccttcta gcgagctccg tgacgctggg tcaccagtcc tggcogtgct tgctgggtgg aggaccccag gocagggctg ggtatggecc gttctttcct tgggaaagec atatggtcte tcttactttc gtgtaaccce teaataacac gecattctgc acacctccac aagtggagtg ggcccagaag ctttctgtac tggtgctgca caggacacca Bcgcatggcg atttetgete ttccatggta catttttgtc tctggccacoc ggccogaagt ctgcctcaag caacettctt ctgcggcgtc cttgtcoctg catctatacc taacaatgtc tgcectectg tggcctgttt cetgacocat ctactacgaa ctcctcogcc ctccaaagat agcicgggtg tgagcaataa gataatgtca
131. aa lt 210 gt 3 211 9196 lt 212 gt DNA aatctcagaa agacatgtac aaaacattca taccactggc cagtgtggtg aggaaataga tcagacgcac tacacgttga tatatctggc atgaatttat aaaattcact tgtgtacttt ctgatgecte aacctggaga acagaaaact cagtcaagta ttggcgctat agacagatct agtggtcgag tgttccagaa getetcccag agaagccacc agacaaagtg agaacatttt tactgatgat tagtgataac tcggggtgtg ttcateccag tgcgaacttc gattgctgtt tatcattggt tggaaaaaca teccacatat lt 213 gt Cricetulus griseus lt 400 gt 3 tctagaccag ggattaaagg atttacatta attattcttt ttttgtctat ggtatgtaat cagcaaagtg atecttaage etttctatat ggtccaagaa gatgagtctt ttccteccag tacitgtttc gctggtctog tgtgeaccac taattgtaag titgaaagtt gtatttgcat agettcaaca ttattaattc tgccagaact atgtggaaag tggagttatg gtgaccttag gtggatagga tatgtcttta aactcacaga CACCECCCEE taaaaatttt ttgttgteca atatatctat tgtggtatga atatgtccat agaattttat gtaggcetca taaggggaat tttetttaaa gtgagtttat tagaaaaaca 112 gctactggtg ggcctctcca ctccccattg gaccttgcag tttgtcaaat aagaagcttg ggaacagaag cagcttctcg cctactttgt tctatttctt atcctggata gtctgtcggg cattcttigg tatcctcaca gtggciggaa ggcttatatc cctgaagctg gaaccacctg cgtaaaatca cagcctattt taatagtcta ttaatctcct tagaattttt atttcaattt tttaatcagg ctaactgatt tacaagtetg aacacaaaat ttcagattat tatttttttt JP VO2003 085119 A1 2003 10 16 gatgggagac ctggacactg tagacagcct accgactcct acttgattcg gettcaaaca
132. ag tcatttgtac gtctctgagg ccctagaaac agagaggtca ctggtactec teccaacett ctctegagaa gccccatggc tggccccato ggCctcctag aggaccttga acagggtgct gaggctggag docagecaac tacctttctc gtggccaagt ggtggggtco gatgctaagg cctagctgaa atttgaatgt tttagttgta tttacagatg ctacaaaaat attecatett taaataaaga atgctgtgtt iccccaggag acacagagct atgtgacaga gtaggttctt acatcaggec JP WO2003 085119 1 2003 10 16 gctcggagag gcagtcccca acccttggga aatgaaagcc tccgocaaca agcatgtgtt agaccagggc ctgctctgga cccaggctgg attgccctgg gatagtggca tccttccagc agaggggatg cctgagecog ggectgecca tcttggctct acatgcggca gaatgaagaa ctgactgtgc agtctggtgc tggggctgca ctagcagtct attttccagg ttgctoctgg gctgtgggta aagtcattgc ttoctgaaga agacagagta aagggaattg cacagaacag getaattoct gaccatagca agcagcagga aggctgactt ctgtggatat Bgaagtcggg tgagcagggg atgagcagct gctgcgctce gttggtcata gttagcgcaa caggaacttt tcttttcagt agggaacatg atcttteccc ttttagttcg gtgctctaga ttggecagct ggatgcctcc ctacaagcta ggcctcctag ggtccecaaa agtggcacgg cecctccctt ctttgcaaag tggagtcact agggaaaccc ccttgttctg ggagcaccac ctatctgctc ccctgtactg tecgigaatg tctagaggga tggcatgaga cagttgggag gtagattggt gaactcagag gcaggggect gcagcagcag ttgecacaag agcigggaag tggocttgaa acagagaagt ctagatgcag 8CEEEEEEESE ctgacctaat 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 4080 414
133. agagtaggga tggctgcctg ggccatgBgg acatgggago gttaagtaac ctctctgatg gcctctacct tggtctggaa tatgagactc agccaaagec atagcacccg aacagggeca tgtaggtggc agctaataat ctatgaccac ctttaaagag agacatatgt agtgtatggg tgctgaggtc ttcactggtc gtectgctga tcgtctgcat cacaagtaag aagccagttt ctacaggeca tcaactgcag gtagctagag tgaattgagt aagcagcaat acttagtctc ccaatgcgca taaagggtct gggaactccc tttgtcctac gecatgagec gctcagatcc gcctgagtgg cttcctectg 8888888838 aggagtacag agccacggag arggacatgg ttctcccaaa cctgtgatgg tgtgggaatg agctatgcag aaagcaacat aagttagagt tettatctta cactgtectt tgsgggagtg cactgacata catgccactg gacaacacat tttaagtttt tggagataag tgaactcagg caatatatgt tcattatccc acaaatgggg ataggctggg actttgttcc aaagtgcttt gagttacaac gctcttggct gactgctggg gtgaccttca ctctggtgtc catctgccct acctgccccc aagecaccct tccttgtggg ccaaagtaac ctgaactctg tgagggaggg caatctaagc actgggaaca gaaaatcatt ceccaatttt tagctcaget tcctgccatt caggatctaa gctctttgag ecacccttaa ccigtgcttg tagecctcat 178 gcigggattt ttccttctca ctgacattgc attettrett Eggacaactt tcatcaggat gtecttttaa cttttacccg aaactgcaac ateccatcce tgcccattgg taaattaaag ctgattc gc aggacagcat tgacaaagac tttgtaccta tcagaggccc agaaatgtce ggagtcagat acacatccat gggatcccac gaatttagat cagtacctga cggectccgg cccatctctg ageccttact cccatttgaa ttagttacaa cattgatgaa tcataatcac ccatgttgct atgaaga
134. agtttttttt cagaagaggg ttgaactcag cccctgaagt ctectacctt ttcttttatc ttatataggc tggaatgggt agaagaaget gctaggaatc tetcttcaag tetagcacce cagagacagg 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9196 10 20 30 actcatcttg gaatctcaga atigg lt 210 gt 5 lt 211 gt 24 lt 212 gt DNA lt 213 gt Artificial Seguence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 5 cttgaccgtt tctatcttct ctcg lt 210 gt 6 lt 211 gt 979 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 400 gt 6 actcatcttg acctgtaagt agtgaaggac tectccttac tggtgatcct ttggctggaa tggagtecat ggaatacatg taaaaaaaga gtactccaat ccgatacaca tgacttcctt aacactgcat aggccaaaat aatccccatg taaaggtgtc gaagatagaa gaatctcaga gagacatgca aaaaatgtte ttacccttgg gcagtgtggt agggaaatag Btcagacgca gtacacgttg gtgtatctgg tatgaattta gaaaattcac gtgtgtactt cctgatgcct geccacaace gaacctggag aacagaaaac acggtcaag attggcgcta cagacaggtc aagtggtcga ctgtaccaga gggtatceca aagaaaccac ctgacaaagt aagaacattt ccactgatga ttagtgataa ttcggggcgt tttcatccca ctgeaaactt agattgcagt atatcattgg taggaaaaac 117 tgctactgga tggcctctcc gctccccatt agaccttgca gtttgtcaaa caagaagctt gggaacagaa tcagcttctc cccttctttg ctctatttct gatcctggat ggtctgtagg ccattcttta ttatcctcac tgtggotgga aggcctgtac
135. arsal primer mix GFPPGSP2 2 NUP Nested Univarsal primer 1400bp O HOO H byes Ao tat pia SN Ei ET DUO HOC AM a Be ede UE nga EAE NA 2245 58 IN Ka S O 000 O Od 10 20 30 50 103 JP WO2003 085119 A1 2003 10 16 H C C m n n n n C O 0000 000 10 20 30 50 J
136. atg 25 lt 210 gt 69 lt 211 gt 25 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 69 accttggata gaaaggggtg gtctc 25 lt 210 gt 70 lt 211 gt 125 lt 212 gt DNA f lt 213 gt Cricetulus griseus lt 400 gt 70 ttgatggagt tggcaccttg cggcttctgg atgcaattaa gacttgtggc ettataaatt 60 ctgtgaagtt ctaccaggcc tcaactagtg aactgtatgg aaaagtgcaa gaaataccce 120 agaaa 125 lt 210 gt 71 lt 211 gt 376 lt 212 gt PRT lt 213 gt Cricetulus griseus lt 400 gt 71 Met Ala His Ala Pro Ala Ser Cys Pro Ser Ser Arg Asn Ser Gly Asp 10 20 30 152 JP VO2003 085119 Al 2003 10 16 1 5 10 15 Gly Asp Lys Gly Lys Pro Arg Lys Val Ala Leu Ile Thr Gly Ile Thr 20 25 30 Gly Gln Asp Gly Ser Tyr Leu Ala Glu Phe Leu Leu Glu Lys Gly Tyr 35 40 45 Glu Val His Gly Ile Val Arg Arg Ser Ser Ser Phe Asn Thr Gly Arg 50 55 60 Ile Glu His Leu Tyr Lys Asn Pro Gln Ala His Ile Glu Gly Asn Met 65 70 75 80 Lys Leu His Tyr Gly Asp Leu Thr Asp Ser Thr Cys Leu Val Lys Ile 85 90 95 100 Iie Asn Glu Val Lys Pro Thr Glu Ile Tyr Asn Leu Gly Ala Gin Ser 105 110 115 His Val Lys Ile Ser Phe Asp Leu Ala Glu Tyr Thr Ala Asp Val Asp 120 125 130 Gly Val Gly Thr Leu Arg Leu Leu Asp Ala Ile Lys Thr Cys Gly Leu 135 140 145 Tle Asn Ser Val Lys Phe Tyr Gln Ala Ser Thr Ser Glu Leu Tyr Gly 150 155 160 Lys Val Gln Glu Ile Pro Gln Lys Glu Thr Thr Pro Phe Tyr Pro Arg 165 170 175 180 S
137. c DNA lt 400 gt 46 ggcgctgget tacccggaga ggaatggg 28 lt 210 gt 47 lt 211 gt 28 lt 212 gt DNA lt 213 gt Artificial Seguence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 47 ggaatgggtg tttgtctcctc caaagatge lt 210 gt 48 lt 211 gt 1316 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 400 gt 48 tggactggtg gatcctagtg tggcgctggc ggatgcagca tgctgeaatg gaatgtgcac ggtctcotgc aatgatccac gattgacgtg cectaccaat tggcctcatc tacagggaaa ggtcctgcgg agtctecatt cacttttgat togggcctac tgcctggttc ciceacctgg gaaccctgcg acagggggct ttacccggag caaacccaag gtaggaggcc atcaatgaca ctgtecacct aatggtccac cagaacaggg gtetttggac cataaggtgc ccacggagge gagtacaatg aaggaggcag tcaacaaagt ttgcctgatt accgacaact accgagagta caggtgcagc ctggactggt aggaatgggt cectgttcca ttttccggaa acgtcctgca Etatcttccc cccacagcag cctacttcca ctcatgacaa atciggccaa agttcatcta aagttgagcc ctgaggctgt cagatgggca tccgtttcac atgagcagge 141 gctggagaat aacaatgggt gggcagagct gtttgtctoo gaaggtacag tatcaaatac cteagcttto tgacaagacc caattttggg gcagcatggc cttcaacatt gagtaatggt ctcactggac catcatecto agtggaggcc gtataagaag acccttcaag coggaagtga JP WO2003 085119 2003 10 16 tgtgcaccgg atccagaagg tccaaagatg cccacecatg aacttggatt gaggtgggca acctatccta tactcgtatg tgcaccttca gaagatggcc tcagecttga ctagcccgge tcagtgggcg at
138. c ttc 144 Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe 35 40 45 act tac tat cta aac tgg gtg aag cag agg tct gga cag ggc ctt 192 Thr Asp Tyr Tyr Leu Asn Trp Val Lys Gln Arg Ser Gly Gln Gly Leu 50 55 60 gag tgg att gga gag att gat cct gga agt gat agt ata tat tat aat 240 Glu Trp Ile Gly Glu Ile Asp Pro Gly Ser Asp Ser Ile Tyr Tyr Asn 65 70 75 80 gaa aac ttg gag agg gcc ctg act gca aaa tec tcc age 288 Glu Asn Leu Glu Gly Arg Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser aca gcc Thr Ala tat ttc Tyr Phe tac tgg Tyr Trp 130 lt 210 gt 73 85 tac atg cag ctc Tyr Met Gln Leu 100 tgt gca aga tat Cys Ala Arg Tyr 115 ggc caa ggg act Gly Gln Gly Thr lt 211 gt 140 lt 212 gt PRT lt 213 gt Mus musculus lt 400 gt 73 Met Glu 1 Val Tyr Pro Gly Thr Asp 50 Glu Trp 65 Glu Asn Thr Ala Tyr Phe Tyr Trp 130 Trp Ile Trp Ile 5 Ser Gln Val Gln 20 Ala Ser Val Lys 35 Tyr Tyr Leu Asn Ile Gly Glu Ile 70 Leu Glu Gly Arg 85 Tyr Met Gln Leu 100 Cys Ala Arg Tyr 115 Gly Gln Gly Thr aac age Asn Ser ggg tat Gly Tyr 120 ctg gtc Leu Val 135 Phe Leu Leu Gln Leu Ser 40 Trp Val 55 Asp Pro Ala Thr Asn Ser Gly Tyr 120 Leu Val 135 154 90 ctg aca Leu Thr 105 tet aga Ser Arg act gtc Thr Val Phe Phe 10 Gln Ser 25 Cys Lys Lys Gln Gly Ser Leu Thr 90 Leu Thr 105 Ser Arg Thr Val tct gag
139. catttccttg gtcagectct gagttgtatg ggctgtaccc tggggtgaco tgcgcatggc acaagecgtt cotccatctc atacccctat tcagcactct ttaaggtggc ataacctctg cegtgttcaa tgctcacatg catcgaactg cttgcatcag caacaagtta gctctcgeca attaactcaa caaggcacag JP WO2003 085119 Al 2003 10 16 ecccecccat agcctctgtt tgaggctggg aaaatagect atcctcactt Cctgggaggg catgaatttg cagggtagct gegtcatgtt gcttccgact tgatttaata ccagacccta tagetettet ECtgactgga tctgctgcgg catggtattc ettcgtcact ggccacctge ccgcagcgtg cctcaagtac tgtgcttctg tggcatoatc aagccctaaa cagttacagg gggacccagc cttgcatgat ctaatcccta agaggctaag tagcctcctc cccatctgct 8ccggaggag aggccgtgtg cacatcaagg ggtaaaggca CtCCgCCCCa 888acagaag gtcactgtec tgatgtettt tcecatgggt aaaaaaaaat acatcttgga accaccatga ggctecactg ecectgcaga ctcaacaagt ttctaccaat tgccotggca ctgccactgt gtaggggtgg tcctacctgc attggtgagt ggtcaacact aagagccctg cagggtgaaa taaaatgige ttacaaggta tagcitgace 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7740 7752 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 10 20 30 aggatcacac atagatcaca gtccagttct aatagtgggt gggccaccac accacatggg actgagecat agatgtgaa atccctgtgg gccagggccc cctgtgctic aacacaataa CCagagctcc gtagtcatat ctgagatcat agtcciggge tgtttgacct caggatcagg ggactccatg ttgtttccte agggttagag gagaacctga gcagcagcct tctcctcttc
140. cggtagtctt cattggcatg ataagtttca ataacctctg cctcaagtac gtaggggtgg 540 ccttctacaa cgtggggcgc tcgctcacca ccgtgttcaa tgtgcttotg tcctacctgc 600 tgctcaaaca gaccacttcc ttctatgccc tgotcacatg tggcatcatc attggtggtt 660 tctggctggg tatagaccaa gagggagotg agggcaccct gtccctcata ggcaccatct 720 tcggggtgct ggccagcctc tgcgtctccc tcaatgccat ctataccaag aaggtgctcc 780 cagcagtgga caacagcatc tggcgcctaa ccttctataa caatgtcaat gcctgtgtgc 840 tottcttgcc cctgatggtt ctgctgggtg agctccgtgc cctocttgac tttgctcatc 900 tgtacagtgc ccacttctgg ctoatgatga cgctgggtgg cctcttcggc tttgccattg 960 gotatgtgac aggactgcag atcaaattca ccagtcccct gacccacaat gtatcaggca 1020 cagccaaggc ctgtgcgcag acagtgctgg ccgtgctcta ctatgaagag actaagagct 1080 tcctgtggtg gacaagcaac ctgatggtgc tgggtggctc ctcagectat acctgggtca 1140 ggggctggga gatgcagaag acccaagagg accccagctc caaagagggt gagaagagtg 1200 ctattggggt gtgagcttct tcagggacct gggactgaac 1245 lt 210 gt 92 lt 211 gt 365 lt 212 gt PRT 218 Cricetulus griseus 400 92 Met Asn Arg Ala Pro Leu Lys Arg Ser Arg Ile Leu Arg Met Ala Leu 1 5 10 15 Thr Gly Gly Ser Thr Ala Ser Glu Glu Ala Asp Glu Asp Ser Arg Asn 20 25 30 Lys Pro Phe Leu Leu Arg Ala Leu Gln Ile Ala Leu Val Val Ser Leu 35 40 45 Tyr Trp Val Thr Ser Ile Ser Met Val Phe Leu Asn Lys Tyr Leu Leu 50 55 60 Asp Ser Pro Ser Leu Gln Leu Asp Thr Pro Ile Phe Val Thr Phe Tyr 65 70 75 80 Gln Cys Leu Val Thr Ser Leu Leu Cys Lys Gly Leu Ser Tht Leu Ala 85 90 95 Thr Cys Cys Pro Gly Thr Val As
141. cgtc agagtccatg ccacaacctt ccagttattg cccattgagg aaagtggata aagacaaagt ctacacaace tcccaggctg atcatgcaaa tattttggag aaagaggaaa ggttactcta gtccgagaga tggagtgtaa cagactaaca agatgctgca attatgctca cgagataatg gaacgcttaa gaaggcccca gttaaggcca patcatgaaa caaagcgaac gaaaticttt agtcaaacag gtccagcgga gtgtgtaaca ticeatgattg JP WO2003 085119 Al 2003 10 16 ctecttactt gtgatectgc ggctggaaag gagtccatgt aatacatggt aaaaaagagt actccaatta gatacacaga acttccttgt cactgcatce gccaaaatgc tecccatgga aagetgtcaa agatagaaac gagattaaca tatggttcat otggtggaac ttctttttgc accaccctga aacagcaaaa ttgaccaggg aagaacagat totiaagaag tgaagaaatt tggatttagg atggagcagg gaataacata tcaataaagg cttatggcac acccttggct agtgtggtgg ggaaatagaa cagacgcact acacgttgaa gtatctggoc tgaatttatt aaattcactt gtgtactttt tgatgcotct acctggagat cagaaaacta agtcaaatac acagaattta tgacagacat gcctctttgt ctgggggacc tcactecage tgaagacttg gacagctaca tgaaaattac gaggattgaa aaagcattta acaccatgaa ggattggcgt tetecagaat ctgtggctat ccagcgaaca 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2008 60 120 180 240 300 360 420 480 540 600 660 720 10 20 30 ctcatcttgg cctgtaagtg gtaaatgaca cctecttact ggtgaccctg tggotggaaa ggagtccatg gagtacatgg aaaaaaagag tactecaatt cggtacacag gactttctag accctgcatc ggccaaaatg attccaatgg aaaggtatca aagataga
142. ctcecggaa acggccgcgg tcaggaaatg gccggaactt cgtgtccctc ggctctgcgg gttatttcct cacgtgtcoc ccttctccct agcaagatga ggggaccgat tgaagccctg atgaacaggg gctgtctcog gcgctggtgg ctgctggaca ctggtgacct gtagacttoc Etggtcttta ttctacaacg ctcaaacaga gactggggge ccaggtcttt ctgtgactca acagcaaagc gatccccatt aagctaagta agttacctoc gaactcaggt agtcaatatg ttaattaccg ccagaatgga gatctccggg aaggagagga caacggtggg gaaaggiggt atcigaagat gaaaatggga gaagagggca gaagtggcaa CECECagggc gaattcggct gagacgcctt gtgcttccgg cetccgctce ctgtcctcaa tccctgggtc ggagcggtgc aggtcatcec tagtccaggg CgCCtotgaa aggagtcaga tetctctcta gcccctccct cactgctgtg ccaccctaaa tcggcatgat tgggacgetc ccacttcctt gtegggagca tgcaccacca gtaagttagg cagccagaca acaaggtata gctgggatca ataggttaca catcacaatt tgtgtgcttt ataggagcgt ctttatctgg acttcatgtc cigcaacaag gagcc8ggcg attccatttt atcaggggaa gaggctatag ggtctgtggg cggcctgcga ccgccctgct cgtggcaacc cctgagcctc gggttcccgc gtecticctt actggcoatg ttgtttcgtg acctcggcaa atgtgacagt actgcttctg gcggtccagg gagcgggaac ctgggtcacc gcagctggat caagggcctc ectggacctc aaccttcaat getcaccace ctatgccotg ggaatcgtaa gtcataggga gatccagcca ctcagatcta atatagctgc cacaggtaat ctctigacca ggcacaagta aagaggcttt tgtgctgatc 174 aggaggtgac ctgactaggt gtcttcccga caagggctgg ctgggtagat aagatagtgc cacttgcaaa cataggtgca gctggccctt cggtaagtgg gcagggcctt ggtgatctcc agcccatgct gctgtcaaag acaccacctc
143. ctcttt Cgttcctccc eccttctctt tcttgtcctt tatcaggttt acatgtatce ttaaagattt cattcaaggt agaacagtca aagaggatag tttagccatt tcttccctgt ctgtttttac catgtatgtc ctgaaactgg tectctggaa caacttttaa atgcattgct gagctc tgtctaggct taggggtaaa otteeteett tecatgagca accectttge tagctgtggg ataaggtagt gcttagattg aaacctataa ctgactagat tettctaact attttagcaa attitggcta ttatatttag atttattttt ggttgtgagc gtgctcttaa cagtgcatca tatatgtaat ttgtctcate agtaagttat tgtgcaccat tattgtggat aagoagccac tggttaccag atatgggctt lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 4 116 gagagagtat tactgatcca cagggagtct accccttgtt tcatcacttc tgtctgcatoe catcagicto ttagttgggg tggctccctc cttcctgctc ccctctccGc aacctttttg gtatttgtat acacagattt tatgtettet caccatgtgg ccgctgagcc tttttecctt getgttacca tettattttt atcaaattaa gtgctgacct gttacgaact tgctctgagc tggataagag gtcacttcag JP VO2003 085119 Al 2003 10 16 ccetctatgt ctatcagtgg ggaacagttc caggtcagtt tccctctctg tgcttecatc attatcagag tcaaccttgt tgtggtggtag cotcatgtcc tccacccaCg gctataaaat gtgtttggtt aaatatttga gcctgcatgc ttgctgggaa atctctocag tgaccaatga getttacatt gtctgttgga aattatttta ggicttggcc gccatagggt cactgagtce tgcttgtatc cattgigtga ggagagggct ceccatagat tatgctggtt gtttctgtag caactggatt agctactgga aagggctttt aggtctctgg tcccttttct tcctctccco atececatta taattaattt agtgttttta
144. e Asp Pro Gly Ser Asp Ser Ile Tyr Tyr Asn Glu Asn Leu Glu 1 5 10 15 Gly 10 lt 210 gt 78 lt 211 gt 12 lt 212 gt PRT lt 213 gt Mus musculus lt 400 gt 78 Tyr Gly Tyr Ser Arg Tyr Asp Val Arg Phe Val Tyr 20 1 5 10 lt 210 gt 79 lt 211 gt 16 lt 212 gt PRT lt 213 gt Mus musculus 30 lt 400 gt 79 Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Arg Thr Tyr Leu Glu 1 5 10 15 lt 210 gt 80 Sali 7 lt 212 gt PRT 40 lt 213 gt Mus musculus 400 80 Lys Val Ser Asn Arg Ile Ser 1 5 lt 210 gt 81 lt 211 gt 9 lt 212 gt PRT lt 213 gt Mus musculus lt 400 gt 81 Phe Gln Gly Ser His Val Pro Tyr Thr 1 5 lt 210 gt 82 lt 211 gt 29 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 158 JP VO2003 085119 A1 2003 10 16 lt 223 gt Description of Artificial Sequence synthetic DNA lt 400 gt 82 ctgaattcgc ggcogctagt cc lt 210 gt 83 lt 211 gt 39 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 22 lt 223 gt Description of Artificial Sequence synthetic DNA lt 400 gt 83 atgegccctt ggtggaggct gtagagacag tgaccagag lt 210 gt 84 lt 211 gt 22 lt 212 gt DNA 39 10 20 30 159 JP WO2003 085119 A1 2003 10 16 lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Seguence synthetic DNA lt 400 gt 84 ctgaattcge ggccgctgct gt 22 lt 210 gt 85 lt 211 gt 28 lt 212 gt D
145. e His Pro Ile Leu Leu Ala Arg 395 Thr Asp Asp Pro 410 Tyr Glu Phe Ile 425 Asn Arg Tyr Thr 440 Phe Leu Ser Gln JP WO2003 085119 Al 2003 10 16 Gln Thr Asp Gly 175 Thr Glu Leu Val 190 Cys Ser Lys Ala 205 Tyr Gly Cys Gln 220 Gly Thr Gln Arg Thr Gly Gly Trp 255 Asp Arg Ser Gly 270 Lys Asn Ile Gln 285 Arg Pro Pro Tyr 300 Leu Leu Arg Val Val Lys Tyr Leu 335 Glu Ala Thr Lys 350 Val Arg Arg Thr 365 Glu Glu Tyr Met 380 Arg Met Gln Val Thr Leu Leu Lys 415 Ser Asp Asn Ser 430 Glu Asn Ser Leu 445 Ala Asp Phe Leu 160 Ala Gln Arg Leu Thr 240 Glu Leu Val Leu His 320 Ile Lys Asp Val Asp 400 Glu Tle Arg Val 10 20 30 Cys 465 Thr Tyr His 450 Thr Phe Ser Leu His Pro Tyr Phe Gly 500 Lys Pro Arg 515 Gly Val Ala 530 Lys Leu Gly Glu Thr lt 210 gt 25 lt 211 gt 18 lt 212 gt PRT lt 213 gt Homo sapiens lt 400 gt 25 Asp Glu Ser Ile Tyr Ser Asn Tyr Tyr Leu Tyr Glu Ser Ile Pro Lys 1 Pro Cys lt 210 gt 26 lt 211 gt 34 lt 212 gt DNA 213 Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 26 aataaaggat cotggggtca tttgtcttga gggt Ser Asp 485 Gly Thr Gly Lys Val 565 5 130 455 460 Gln Val Cys Arg Val Ala Tyr 470 475 Ala Ser Ala Asn Phe His Ser 490 Gln Asn Ala His Asn Gln fle 505
146. eattgcatt gcaccacaca agtacaggca atgccgtgca gtcatccatt cctatggtga cctcacacgt tcotcaaggg gaacaacgga gcttgcaatc cctgtgtcat aatattecag tcatagaaaa atggacactt ttaaaaccat tagatatttg ecctgtggac ccettgggat tgctgtccat agcaactctt tacaatggat gttettotit aaatggccac lt 210 gt 52 lt 211 gt 27 lt 212 gt DNA agcagctgac aaaggaattg tegaaatgga gtggaattcc tgcaagcgct gttggactta ggtcacctgt tgagcagcct tggagtattt atgccaccet tagactagga gcactctgag gctacttgat ctttctgcag cactaaagag aacaccoctg ggagtatctg catagctttc tcacagcatc attaggacct agctgttctg agaatattca atcagatata gaaccttaaa tgctegaatt gttaaatgce ccaggaaatg tctagaaatc tttgcctgga ctttctcccc ttctgatgga gaaaagcagg ccccttggag ggatcaacac ticacagtec ttaggaaaaa aaactagcca gcagatgata ggctttactg gtattggact ttcctccata agctttegtc tatgtetaca tictatgaaa gcactgggac gaatcacact aatgttgttg ctacatttca agtgtctttc ctgaattcag gaggtgtcca cccccatgtt actatggtgt aagatgctto gctatggaag ttccotgtot attcgaaacc cttctctgca agttcaaaga aacaggattg tetetecttt aaaaaaaaaa lt 213 gt Artificial Sequence 143 agcttgctta ttaactacca tttgttctct tgttaattca tcttcacggc tgtacatgga ttgaactata ccctagecca Ctgccggttc ageccagcat aacaggactt cagatagect gtgtaggcec ciggagcaac tgttggacat tecttaataa cttccaatgg caaatgtgcc gatgctgtgt tctcggaaaa ctttcgtgtg ttggcatgga agttct gg aactattttc gttcttctct attcgecatt aagatgtagg gaaaacagtc caaatgcag
147. er Pro Tyr Gly Ala Ala Lys Leu Tyr Ala Tyr Trp Ile Val Val Asn 185 190 195 Phe Arg Glu Ala Tyr Asn Leu Phe Ala Val Asn Gly Ile Leu Phe Asn 200 205 210 His Glu Ser Pro Arg Arg Gly Ala Asn Phe Val Thr Arg Lys Ile Ser 215 220 225 Arg Ser Val Ala Lys Ile Tyr Leu Gly Gln Leu Glu Cys Phe Ser Leu 230 235 240 Gly Asn Leu Asp Ala Lys Arg Asp Trp Gly His Ala Lys Asp Tyr Val 245 250 255 260 Glu Ala Met Trp Leu Met Leu Gln Asn Asp Glu Pro Glu Asp Phe Val 265 270 215 Ile Ala Thr Gly Glu Val His Ser Val Arg Glu Phe Val Glu Lys Ser 280 285 290 Phe Met His Ile Gly Lys Thr Ile Val Trp Glu Gly Lys Asn Glu Asn 295 300 305 Glu Val Gly Arg Cys Lys Glu Thr Gly Lys Ile His Val Thr Val Asp 153 JP WO2003 085119 Al 2003 10 16 310 315 320 Leu Lys Tyr Tyr Arg Pro Thr Glu Val Asp Phe Leu Gln Gly Asp Cys 325 330 335 340 Ser Lys Ala Gln Gln Lys Leu Asn Trp Lys Pro Arg Val Ala Phe Asp 345 350 365 Glu Leu Val Arg Glu Met Val Gln Ala Asp Val Glu Leu Met Arg Thr 360 365 370 Asn Pro Asn Ala 375 lt 210 gt 72 lt 211 gt 420 lt 212 gt DNA lt 213 gt Mus musculus 290 291 CDS 222 1 420 400 72 atg gaa tgg atc tgg atc ttt ctc ttc ttc ctc tca gga act aca ggt 48 Met Glu Trp Ile Trp Ile Phe Leu Phe Phe Leu Ser Gly Thr Thr Gly 1 5 10 15 gtc tac tcc cag gtt cag ctg cag cag tot gga got gag gtg agg 96 Val Tyr Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Ala Arg 20 25 30 ccc ggg gct tca gtg ctg tcc tgc aag got tct gge tac ac
148. g ectttccctt JP WO2003 085119 2003 10 16 caagcaacag tgttttcact tcagtgcctg ctctgglggc tttaccactt tttcccctea cagcattggg tecatctagt tttgcaacat tgaaaacatg gagtgggggt attttacatg actgaactgt tgcagagtac gaggcagaaa ctccaggttt ttegttacag tgaagactce ggcccctggc ctgcattato ctetttaagt agacaacttg agtctgtttc aggaagtaag gagtgagtcg CagCCtgagc apacatgett tgattcggag catattctat tgatgtaatg daaaa ttgtcggaga gatcctcctg gaaagcctct tacagtcaac ggtgagccca cgcatgaagc gactctgagt ctggctgtag ggtgacctag caccacttta gacaccacct gatcataaat gaaatagatg accaagaaca atattccacc tatcacattg gcagagctgg catgagaaac tcagtggtag ageggttctg gtggagataa aagaacagtg etgacttgtt acgcagctga gttgcagcat aacttcaagc gcttacaggg aaatcttaaa agatctctgg acaaaggtaa 180 240 300 360 420 480 540 600 660 120 180 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1965 10 20 30 144 JP WO2003 085119 Al 2003 10 16 lt 220 gt lt 223 gt Description of Artificial Seguence Synthetic DNA lt 400 gt 52 caggggtgtt cccttgagga ggtggaa 27 lt 210 gt 53 lt 211 gt 27 lt 212 gt DNA lt 213 gt Artificial Seguence 10 lt 220 gt lt 223 gt Description of Artificial Seguence Synthetic DNA lt 400 gt 53 cactgagcca ggggccacac agcatec 27 20 lt 210 gt 54 lt 211 gt 23 lt 212 gt DNA lt 213 gt Artificial Sequence 220
149. gacaaaga aggctagttc ggaatccagg atctaggtag ttetatatte ctgttagttt tttcttagca tgccecttat tttccatcaa gaaatctgaa tttgacaatg ttgatctett gctgttactt gtattatttt ttaagaaaaa aggtagttga gcttgttttg cattcatctc etgaattaac ttcagattac tgaagaagct catgcattce ggggaatagt gcacatccac agactgtgtc tgaaaatett agttectatt ttagtgttcc ccagtetttg tatttaaatt cetecectge aggecctcca tagggaagta catccacagg tagacttttt attcagataa gaaaacaaaa tacccaactt aatagcacat actagttgtg atgatttacg ctagcacaag tgtatttttt gatacttact agttcatatc ttgaaatgct gtttaccagc acttttagag teaaccttte atattttgat atctttatta agtttgaatt cgtgtggtct ttatgctggt ttgtctaaga ttcaagctgt cecttttcaa attttaaget aggcacatta tgtggtcagc gctaccacaa aggaaaaact aagttgacaa gattatcacc caagtccctg tgtctgtaaa gcttgtattt agaaacaaag tccccaccta tgggggaaat 115 tgtctcccca ggttttattt tecttactat atgtaatagt gcctgaaatg tccaaataca tttaaaatag tgtaaggtta tgtttggcca ttaaaggtgt tccictgtca ticttacact actgatttta tgggatcaga tgaatgtect tgataaagct attgttatoc ctgaccatat ttatttttgc ttactttgtg actgatatig cagattgtct acaaagtatg tttgtgtgtt agetttcttt gataatgtat catccacatg tcacttttcc tgggcatatc gatttagaca tiaaaactat ataattoatc ttecttectt tactttttta tcateccttc cigettttac agceccaatt cttcaatgtc JP WO2003 085119 Al 2003 10 16 ggctgttctc taaagctaag aattgagcta agetaatttc acagttttta atctgcagtt ctatttactc tggctgcaaa aaatcttgtt ggtagtattg tatatttgct ttctttggga aca
150. gag cagagagtga gcagctctaa cccaaggtca tacagtgatt ctgctagatt tgcagatttt JP WO2003 085119 1 2003 10 16 aaacataagc agagttccag taccttgagg tttatgygtg aagaattggt tggcacaaat gaggetttaa gaagecctct tcagagaaac agactggcca aagttageat tcagatgaac aaccatcttt gtgttaggaa caaggcatcc cteaggtict aggctgggta ecctggttga aaaaagctga cctaagagaa ttcagtctoc gcaagaaggt tagtgaggca aactggccco ataagtgctg gagaagtcct tgagtaaggt gacaaagagt ggaaattgga agaacagtca gatccctetg raagtectgg cccacaagtg ccaaatgctc ctttgectgg acaattataa gtagciggga cattctgggc agitacctcc gatcctgtct taacatttga tgtgtttggg ectttctece ecctttacce ctattttcce gggaggtgcc aaggctactt cactecctgg gttgcagtca ttttaaacat gcagtgcccg acatctggcc gttocctgag ttatctgtcc ctctggatgt gcagctcctg cagcaciggg ctggtattec CagCCttgcc acagtcacta gctgagaacc aactgttegg tggggactct tgctggcatg ttttcctgaa agattggtta actcrgagag gagtctagat gcatcagtaa ccccatgctg aatagagtcc acactgaggg cectectecti ttagagaggt tetactecct 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1600 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2080 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 10 20 30 179 JP VO2003 085119 A1 2003 10 16 cagccatttt ttggtgtggg agttagactt tggatatgtt gatgatgagg taagggccac 3360 agaacagtct gaactgtggt atcagaatcc tgtccctctc cetctctect catocctett 3420 caccttgtca ctcctctgtc
151. ggacttet caggctgtga agcatgggac aagtagctct gatccaggag tggtcgcaga cagatotgac tcatccatct tetggaggaa ctegcaaggt ttgatgaaac ccaagaggat ctgctgtcat atgtgctgcc ctgtttgggg tettcatctg aggaagatga gtggggaagt atggcaagct aggagacctg aagcgggtgc 28 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 10 20 30 142 JP VO2003 085119 Al 2003 10 16 tcagctggca atgeccagic agtaggctgc agtctcatca tttgcttgic aagaactgag 1140 gacagtatcc agcaacotga gccacatgct ggtctctctg ccagggggct tcatgcagcc 1200 atccagtagg gcccatgttt gtccatcctc gggggaaggc cagaccaaca ccttgtttgt 1260 ctgcttctge cccaacctca gtgcatccat gctggtcctg ctgtccocttg tctaga 1316 210 gt 49 lt 211 gt 23 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 49 gatcctgctg ggaccaaaat tgg 23 lt 210 gt 50 lt 211 gt 22 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 50 cttaacatcc caagggatgc tg 22 lt 210 gt 51 lt 211 gt 1965 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 400 gt 51 acgeggggct cccggaagcg gggaccatgg cgtctctgcg ogaagcgagc ctgcggaage 60 tgcggcgctt ttccgagatg agaggcaaac ctgtggcaac tgggaaattc tgggatgtag 120 10 20 30 ttgtaataac agctgaagag gaaccaaaat atggagacaa gacttcccaa tttatcagat otggagttit c
152. gt ggc agt gga tca ggg aca gat tte 288 Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 85 90 95 ctc aaa atc age aga gtg gag got gag gat ctg gga gtt tat tte tgc 336 Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys 100 105 110 ttt cag ggt cat git ccg tac tic gga ggg ggg acc aag ctg 384 Phe Gln Gly Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu 115 120 125 gaa ata aaa 393 Glu Ile Lys 130 156 JP WO2003 085119 A1 2003 10 16 lt 210 gt 75 lt 211 gt 131 lt 212 gt PRT lt 213 gt Mus musculus lt 400 gt 75 Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala 1 5 10 15 Ser Arg Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val 20 25 30 Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu 35 40 45 Val His Ser Asn Gly Arg Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro 50 55 60 Gly Gln Ser Pro Lys Val Leu Ile Tyr Lys Val Ser Asn Arg Ile Ser 65 70 75 80 Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 85 90 95 Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys 100 105 110 Phe Gin Gly Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu 115 120 125 Glu Ile Lys 130 lt 210 gt 76 lt 211 gt 5 lt 212 gt lt 213 gt Mus musculus lt 400 gt 76 Asp Tyr Tyr Leu Asn 1 5 lt 210 gt 77 157 JP VO2003 085119 1 2003 10 16 lt 211 gt 17 lt 212 gt PRT lt 213 gt Mus musculus lt 400 gt 77 Glu Il
153. gttgctt aactcagatt gatccaagaa tecetttaaa aatgagtgaa ttataaaatt ttattttcta gottagtaac gttctaatct tgagtttatg cttgctgtct gaatactaac tctttttttt gattigcaagg gagtcaagag tattcttaga cacttacttc acctctcatt cacacctgaa tgtatecctt aaaaacctgt aagttagata aatacatata atgtcagtct ccaactectt tgtcatatca tagattctac acatgaatga gtatttttgt tttgigataa agattcagaa ttcttgatat ttgatttttt catctttgac ccatictggg gaaggctctc ttetgtttta tttattttge cttttgtaat tgaacttttc tatgaaatct ttaatttgtg catattitca ttatttaatt gccaaatgaa tgccttttgt tatatagcat caaatgtaaa cctatcggtt tccgtactat tttaagggac ttatcaacat cagagagcag tagtctagga agttcatgca gagactcttc gccatcacta tgttattgta ittttagtta ttattttcaa tttttgtaat cagttcecte tettctcocc tttggagcag 9400 9460 5520 5580 5640 5700 8760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 10 20 30 ggectagacc cecaaagttc tgtecggacc tcccagatat gtttccccag ccagagttca tgagggctct aaggtagcct acagtgacag tgctctcatc tccccttctc gcttatgaga aatatgctta accttaattg tttttttttt caccagatct gacctctgga gtttctttta actgaattgt ttgctaaait ttttattitt gigtigacta gtcatattct aaaccecage caggtgatgc atgaaaattt aggatcccaa lt 210 gt 4 lt 211 gt 25 lt 212 gt DNA ctecccagtg atttgtgtac tccaaactga cagtctgggg CCCggtcttg gctcagtgtt aggatggcat cttgattatt aatt
154. hr age Ser 120 aac Asn Ecc Ala cat His aec Thr acg Thr 200 gag Glu cct Pro aag Lys gtg atc Ile gag Glu get Gly 105 aac Asn aac Asn ttt Phe cag Gln acc Thr 185 cgc Arg Pro gaa Glu gac Asp gac 161 aac Asn acc Thr 90 ctc Leu Gly tac Tyr acc Thr Arg 170 gag Glu age Ser aaa Lys cto Leu acc Thr 250 gtg gcc Ala 75 gat Asp tac Tyr aaa Lys acg Thr cag Gln ctg Leu tet Ser ctg Leu 235 ctc Leu 60 atg Met act Thr ate Ile ggC Gly gcg Ala 140 aag Lys gtg Val age Ser Arg tet Cys 220 ggg Gly atg Met cac JP WO2003 085119 Al 2003 10 16 gca Ala itt Phe tge Cys aag Lys 125 ctg Leu Gly cac His ctg Leu EEC Gly 205 gac Asp Gly ate Tle gaa gaa gac Glu Asp gga age Gly Ser 95 atg aac Met Asn 110 gac tge Asp Cys cag aac Gin Asn CRE CCC Arg Pro tte atg Phe Met 175 tte Arg Phe 190 age cag Ser Gln aaa act Lys Thr toa Pro Ser tee cgg Ser Arg 255 gac cct Gly 80 aga Arg aag Lys gta Val gcc Ala CgC Arg 160 aag Lys gag Glu agg rg cac His gtc Val 240 acc Thr gag 240 288 336 384 432
155. n IPC Int Cl Minimm documentation searched classification system followed by classification symbols Form PCT ISA 210 extra sheet July 1998 195 JP WO2003 085119 Al 2003 10 16 n PCT JP03 04504 I PC i Int CI C12P 21 08 CI2N 15 09 2 5 10 CO7K 16 18 GO1N33 50 C07K16 46 AGIK 39 395 AGIP 9 00 461 P 29 00 AGIP 31 04 AGIP 31 12 A61P31 14 AGIP 35 00 AGIP 37 02 AGIP 37 04 AGIP 37 08 AGIP 43 00 GO IN 33 15 C12P 21 08 C12R 1 91 CI2N 5 10 C12R 1 91 B 1 P C Int C12P 21 08 C12N 15 09 C12N 5 10 CO7K 16 18 GOIN33 50 CO7K16 46 BIOSIS MEDLINE WPIDS STN KAWA WO 00 61739 A1 2000 10 19 8 EP 117619 14 9 16 21 25 27 2 Al amp AU
156. p Phe Pro Thr Leu Asn Leu Asp Leu 100 105 110 Lys Val Ala Arg Ser Val Leu Pro Leu Ser Val Val Phe Ile Gly Met 115 120 125 Ile Ser Phe Asn 130 Asn Val Gly 145 Leu Leu Leu Tle Ile Ile Gly Thr Leu 195 Cys Val Ser 210 Asp Asn Ser 225 Val Leu Phe Leu Asp Phe Leu Gly Gly 275 Lys Phe 290 Ala Cys Ala 305 Ser Phe Leu Ala Tyr Thr Pro Ser Ser 355 lt 210 gt 93 2112 1095 212 DNA 135 166 Asn Leu Cys Leu Lys Tyr Val Gly 140 Arg Ser Leu Thr Thr Val Phe Asn Val Lys Gln 165 Gly Gly 180 Ser Leu Leu Asn Ile Trp Leu Pro 245 Ala His 260 Leu Phe Thr Ser Gln Thr Trp Trp 325 Trp Val 340 Lys Glu lt 213 gt Homo sapiens lt 400 gt 93 150 Thr Thr Ser Phe Trp Leu Ile Gly Thr 200 Phe Gly 185 Tle 155 Val Leu JP VO2003 085119 A1 2003 10 16 Ala Phe Tyr Leu Ser Tyr 160 Tyr Ala Leu Leu Thr Cys Gly 170 175 Ile Asp Gln Glu Gly Ala Glu Phe Gly Val Ala Ile Tyr Thr Lys Lys Val 215 Arg Leu Thr 230 Leu Met Val Leu Tyr Ser Gly Phe Ala 280 Pro Leu Thr 295 Val Leu Ala 310 Thr Ser Asn Arg Gly Trp Gly Glu Lys 360 Phe Leu Ala 265 Ile His Val Leu Glu 345 220 Tyr Asn Asn 235 Leu Gly Glu 250 His Phe Trp Gly Tyr Val Asn Val Ser 300 Leu Tyr Tyr 315 Met Val Leu 330 Met Gln Lys Leu 205 Leu Val Leu Leu Thr 285 Gly Glu Gly Thr Ser Ala Ile Gly Val 365
157. quence Synthetic DNA lt 400 gt 18 caggaaggaa ggCtggaaga gage lt 210 gt 19 lt 211 gt 321 lt 212 gt PRT lt 213 gt Cricetulus griseus lt 400 gt 19 Met Gly Glu Pro Gln Gly Ser Arg Arg 1 5 Gly Leu Val Gly Arg Ala Ile Gln Lys 20 25 Leu Pro Gly Glu Glu Trp Val Phe Val 35 40 Thr Asp Ala Ala Gln Thr Gln Ala Leu 50 55 His Val Ile His Leu Ala Ala Met Val 65 70 Lys Tyr Asn Leu Asp Phe Trp Arg Lys 85 Val Leu His Ser Ala Phe Glu Val Gly 100 105 Leu Ser Thr Cys Ile Phe Pro Asp Lys 115 120 Thr Met Ile His Asn Gly Pro Pro His 130 135 Tyr Ala Lys Arg Met Ile Asp Val Gln 145 150 His Gly Cys Thr Phe Thr Ala Val le 165 His Asp Asn Phe Asn Ile Glu Asp Gly 180 185 His Lys Val His Leu Ala Lys Ser Asn 195 200 Ile 10 Val Ser Phe Gly Asn 90 Thr Thr Ser Asn Pro 170 His Gly Leu Val Thr Gly Gly 15 Val Ala Asp Gly Ala 30 Ser Lys Asp Ala Asp 45 Gln Lys Val Gln Pro 60 Gly Leu Phe Arg Asn 75 Val His Ile Asn Asp 95 Arg Lys Val Val Ser 110 Thr Tyr Pro Ile Asp 125 Ser Asn Phe Gly Tyr 140 Arg Ala Tyr Phe Gln 155 Ser Gly Leu Thr 80 Asn Cys Glu Ser Gln 160 Thr Asn Val Phe Gly Pro 175 Val Leu Pro Gly Leu 190 Ser Ala Leu Thr Val 205 Ile Trp JP WO2003 085119 A1 2003 10 16 24 10 20 30 Gly Thr Gly Lys Pro Arg Arg Gin 210 215 Arg Leu Phe Ile Trp Val Leu Arg 225 230 Leu Ser Val Gly Glu Glu Asp 245 Glu Ala Val Val Glu Ala Met Asp
158. sp Trp Leu Asn Gly Lys Glu Tyr Lys 305 316 315 320 Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 325 330 335 Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 340 345 350 Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 355 360 365 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 370 375 380 Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 385 390 395 400 Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 405 410 415 Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 420 425 430 His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 435 440 445 lt 210 gt 91 lt 211 gt 1245 lt 212 gt DNA lt 213 gt Cricetulus griseus lt 400 gt 91 gaacttcace gcectgtaga cctotgagga tcgcgctggt acctgctgga gcctggtgac caagccatgt ccagggagtg tctgaagcgg ggcagatgaa cgtctctctc ctctctgctg gacaattgaa cttctggccg tccaggatce gacagcagga tactgggtca ctgcagctgg tgcaagggcc ggetgtacec tggggtgacc tgcgcatggc acaagccgtt ectccatctc atacccctat tcagcactet ccagacccta tagetettet gctgactgga tctgctgcgg catggtatte ettegtcact ggccacctgo acatcttgga accaccatga ggctecactg gogctgcaga ctcaacaagt ttctaccaat tgcectggca 60 120 180 240 300 360 420 165 JP WO2003 085119 A1 2003 10 16 10 20 30 ccgttgactt ccccaccctg aacctggacc ttaaggtggc ccgcagcgtg ctgccactgt 480
159. t tettcetcac tggocgcctg cecgcagcgt gcotcaagta acgtgctgct gcggtatcat tgtcgtggct tetacaccac acaacgtcaa ccctgogtga gectgtttgg tgacccacaa actacgagga ectecgccta ccaaagacag 30 Arg Ala Leu Gln Ile Ala Leu Val Val Ser 45 Ile Ser Met Val Phe Leu sn Lys Tyr Leu 60 Arg Leu Asp Thr Pro Ile Phe Val Thr Phe Thr Leu Leu Cys Lys Gly Leu Ser Ala Leu cggggcctca ggcattgcag ccttaataag cttctaccag ctgccctggt ectgeccctg cgtcggtgig ctcctacctg catcggggec gegcaccetc gaaggigctc cgcctgcatc ctttgcccag ctttgecatc tgtgtcgggc gaccaagage cacctgggtc cgagaagage Pro Leu Lys Arg Ser Arg Ile Leu His Met Ala Leu 15 Asn Gly Glu Lys Leu Tyr Leu Asp Tyr Gln 80 Ala Ala 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1095 10 20 30 168 JP WO2003 085119 A1 2003 10 16 85 90 95 Cys Cys Pro Gly Ala Val Asp Phe Pro Ser Leu Arg Leu Asp Leu Arg 100 105 110 Val Ala Arg Ser Val Leu Pro Leu Ser Val Val Phe Ile Gly Met Ile 115 120 125 Thr Phe Asn Asn Leu Cys Leu Lys Tyr Val Gly Val Ala Phe Tyr Asn 130 135 140 Val Gly Arg Ser Leu Thr Thr Val Phe Asn Val Leu Leu Ser Tyr Leu 145 150 155 160 Leu Leu Lys Gln Thr Thr Ser Phe Tyr Ala Leu Leu Thr Cys Gly Ile 165 170 175 Ile Ile Gly Gly Phe Trp Leu Gly Val Asp Gln Glu Gly Ala Glu Gly 180 185 190 Thr Leu Ser Trp Leu Gly Thr Val Phe Gly Val Leu Ala Ser Leu Cys 195 200 205 Val Ser Leu Asn Ala Ile Tyr Thr Thr Lys Val Leu Pro Ala
160. t 211 gt 27 10 20 30 137 JP WO2003 085119 2003 10 16 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 34 caggggtgtt cocttgagga ggtggaa lt 210 gt 35 lt 211 gt 23 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 35 CCCCtcaCgC atgaagcctg gag 210 36 lt 211 gt 28 lt 212 gt DNA lt 213 gt Artificial Sequence 220 223 Description of Artificial Sequence Synthetic DNA lt 400 gt 36 Egcaggagac caccttgcga gtgcccac lt 210 gt 37 lt 211 gt 28 212 DNA lt 213 gt Artificial Sequence 27 23 28 10 20 30 138 JP WO2003 085119 Al 2003 10 16 lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 37 ggcgctggct tacccggaga ggaatggg 28 210 38 lt 211 gt 28 212 DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 38 aaaaggcctc agttagtgaa ctgtatgg 28 lt 210 gt 39 lt 211 gt 29 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt lt 223 gt Description of Artificial Sequence Synthetic DNA lt 400 gt 39 cgeggatcct caagcgttgg ggttggtce 29 lt 210 gt 40 lt 211 gt 45 lt 212 gt DNA lt 213 gt Artificial Sequence lt 220 gt 10 20
161. taa atttgaacct cttctctaag aagtagtgag ctgagaactt gattaattat caagaaagat ctaacgtgtg ctttcagcct aacaactcag agaaagctgc agagagacta gtggctaact ggagttgaaa ctttttgcot caacaaaatg ggatttgatg atataatttc tcagtgatac gaatcagtat gacgaacaca ctettaactc acttcagecc aaacaacttg gatttatagg aaaaagtata ttecttggga tececeattc tagagaattt taatagaaaa ttaatgataa ttttaaccaa ttccatagct ggaggagata aaacacataa taagggttta gattttatcg ttattagtgt tttgatgttt gticaagtca atgacagcga gttttgcttt tcaaagatat agaattagac tggttgactt cctggccaaa ggtgtttctt etccttgtat attttgtctg agaaccagag ctctgaaaat gegegacctt attctagcag aagacttgag aaatactgtg tacaaaccgt atctatatag atagaagcag aactttatgt 113 tcagagtata acttcaatta aaccattaaa cacagggttt ctttgtaaac ttagigcttt tatattttag attttctttg aaaactctga tttaatttet ccigocttta ttagagttgc attttatttc ttaaagctga actgttgtta tgacatttce ttttaaatat ggtgtggttg gtttgagaat gatggagtga tagataatga aatcttttaa ttocagtatt aaagtgttta gataccatga actctttcca caccaggaag aagcatcatg tacaatgttt amp cgggcatgg attgttttat agaactctoc gagaatggct cttgacettt ctttetaaaa tcaatatagg tggcatttat gatttggatt JP WO2003 085119 A1 2003 10 16 aattetctga ttggcttcat cagactttag tgagaaaggg gtaaaactat ttgaattttg cagaaatcag Eggtttttgtg tttttggaat ggccatgtgg cagtaactat ccagtcactt taagagaatc taaagaacga gccttctttt atatatgtat atttgaaaaa ccaattggtt atgtectcta tgagaatttg acatattage tecctataaa
162. tac cag ctc tac Arg Thr Tyr Gln Leu Tyr Val Thr Asp age C amp C acc Ser Arg Thr Leu tea Ser cag Gln 45 age Ser His Leu Leu 15 ect aat ttt Pro Asn Phe 30 ctc age cgc Leu Ser Arg ggg aag cac Gly Lys His 31 32 48 96 144 192 10 20 30 gtg Val 65 gac Asp gtc Val aag Lys 145 aag Lys CEC Arg ttc Phe act Thr aca Thr 225 tte Phe CCt 50 cag Gln Pro cga Arg 555 Gly aca Thr 130 tac Tyr Gly ctg Leu ctc Leu tgg Trp 210 tgc Cys ctc Leu gag gte ctg gcc Val Leu Ala ttc Phe gtt Val aag Lys 115 Bag Glu gag Glu tec Ser ecg Pro aac Asn 195 gcc Ala cca Pro tie Phe gte 868 Ala cge Arg 100 cta Leu atc Ile Gly aag Lys CES rg 180 tac Tyr ceg Pro ceg Pro cec Pro aca aag Lys 85 BEC Gly att Ile gtg Val tgg Trp acg Thr 165 EEC Gly ccg Pro gag Glu tgc Cys cca Pro 245 tgc aac Asn 70 ctc Leu gca Ala gcc Ala ctg Leu tac Tyr 150 CgC Arg cac His CCC Pro ccc Pro cca Pro 330 aaa Lys gtg 55 aag Lys att Ile gag Glu aag Lys gag Glu 135 atg Met cag Gin cac His tte Phe cga Arg 215 gca Ala ccc Pro gtg Arg gtg Val aca T
163. tagac cttcttgccc gaacagcgcc ctatgtgaca agccaaggcc cctgtggtgg gggctgggag tatcggggtg lt 213 gt Rattus norvegiucus lt 400 gt 98 172 atcggcatga gtgggacgct accacttcct atagatcaag gCcagcotct cacagtatct ctgatgetag cacttctggg ggactgcaga tgtgcacaga acaagcaact atgcagaaga tga Met Ala Leu Thr Gly Ala Ser Ala Val Ser Glu 1 Asn Lys Pro Leu Tyr Trp 35 Leu Asp Ser 50 Tyr Gln Cys 65 Ala Thr Cys Leu Lys Val Met Ile Thr 115 5 10 Phe Leu Leu Arg Ala Leu Gln fle 20 25 Val Thr Ser Ile Ser Met Val Phe 40 Pro Ser Leu Gln Leu Asp Thr Pro 55 Leu Val Thr Ser Leu Leu Cys Lys 70 75 Cys Pro Gly Met Val Asp Phe Pro 85 90 Ala Arg Ser Val Leu Pro Leu Ser 100 105 Phe Asn Asn Leu Cys Leu Lys Tyr 120 JP WO2003 085119 Al 2003 10 16 taaccttcaa cgetcactac tttatgecct agggagctga gtgtctcact ggCgCctaac tgctgggcga tcatgatgac tcaaattcac cagtgctggc tgatggtgct cccaggagga taacctctgc egtgttcaat ectcacctgt gegcaccetg caatgccatc cttctataac gctccatgct gctgggtgga cagteccctg tetgctctac 8g8gtggctcc ccccagotec Glu Ala Asp Ser Glu 15 la Leu Val Val Ser 30 Leu sn Lys Tyr Leu 45 Ile Phe Val Thr Phe 60 Gly Leu Ser Thr Leu 80 Thr Leu Asn Leu Asp 95 Val Val Phe Ile Gly 110 Val Gly Val Ala Phe 125 Tyr Asn Val Gly Arg Ser Leu Thr Thr Val Phe Asn Val Leu Leu Ser 360 420 480 540 600 660 720 780 840 900 960 1020 1053
164. tc Leu gat sp ctc Leu gag Glu cag Gln 70 gag Glu cta Leu ttc Phe act His Ser Trp Lys Asn Thr cca Pro ctc Leu gag Glu gac Asp gcc Ala tac Tyr gaa Glu aag Lys get Ala act JP VO2003 085119 A1 2003 10 16 get ctg cta Thr Ala Leu Leu cca Pro aag Lys 40 aat sn Ser age Arg gtc Val Bag aag Lys 25 gac Asp tcc Ser age Ser tge Cys cat His 105 gaa 10 get gtg Ala Val agt gtg Ser Val aca cag Thr Gln tac tte Tyr Phe 75 cag aca Gln Thr 90 atc gge Ile Gly cet Glu Glu Asp Pro 120 ctg Leu cat His gte Lys Val ctt Leu gtg Val act Thr tgg Trp 60 att Ile aac Asn tgg Trp att Ile aca Thr 48 96 144 192 240 288 336 384 432 10 20 30 125 tat 130 aaa Lys Gly tta cag aat Gln ggc Gly 145 aaa agg Tyr Leu Asn Arg ttc Phe att Ile tac cca gcc aca ctc Pro Lys Ala Thr Leu 160 ttt Phe Tyr agg ctt agt aaa aat Arg Gly EEE Gly Asn 180 gtg Val Leu 175 act Thr Ser Lys atc Ile 190 EEE Gly ace Thr Gln ttg gca Leu Ala 195 tot ttc Ser Phe 210 tat tic Tyr Phe get Gly ect tac gto tgc Val caa Pro Tyr Gln Cys 205 gtg Val Asp aca cta tet Thr
165. tgat aagaagtggg tatgaaagtt tgctaatag agacagcetg cattttacag gttaacaaat tatcttcecta aggagagact aatcactgaa ttaccacaaa tetctgtcce ttaattatga tattaaacca gtccagggac tttgtctctg ccaatcagtg atcatgttat aaaaaattaa aagtagcatg cagattacat aagaagctgg ttcctgtgct gctgggaact gtcectcata ctaacaactg caatctagaa gacataaatt ttgttaaata aaaaattgtg aatggaaaac ttacaagttg cagtgettac cattagatgt ctttttgagg tctcecacac catatggtat gttgtatgtt ggtggtaatt cgatactttg gtggtctttg taactateat ttttactgaa ggtagaacct agctgaaaac teccatcctg ttttetecat gtatcttgtt tgcagggtcc aactgttget taactactat ctcttactcc ettattttct ttttattcat ttgtatgagt ttgtattgaa gagtgcagaa tttaagetga tcacattaca cagetcactt aactcaaage tggtctctta cattcaaatt catttttata 114 ttgaaaggct gaacagtgca gcataactgt ataaacaatg tetgacaact tgtcacttta ggtaattggc aacataatte cactgtttgc attgtgtaac aacactttta gtcacaatag ttggattaaa aactgaaatt ttatteggaa tttctagata ttaaaaaatg tetttgaatt agaaaaagca agaagatctc gttccatcta tttectgtat cacatccgce cagttggcta tgtaagtatt tctggcgtgt gattctgcte tagccaataa tettcagaaa aattatgtgt gagggaatca taatgtatga tccagagtca ttcctggagc caagttcaaa agacactttc acaaaatagt aataagcata JP VO2003 085119 A1 2003 10 16 tagttactct tccggaatgt tcaaagtcat atatctattt ttggattcte aaaaactgca actaccagca atgaatggaa atocattgca tcaccatcag caaaaacaaa gattattcag tcattttact atatetgatt tttgtcatat tctttatgag ttaaataa
166. totc igttttagaa taggaatgat agagctctgg actccaaaga gacagatcta caaagatctg ccatcatgtg atctcagaat gacatgcaca aaatgttcaa JP WO2003 085119 Al 2003 10 16 60 120 180 240 300 360 420 480 540 600 660 T20 180 840 900 960 10 20 30 gtggtogagc gtaccagaag gtatcccagt gaaaccacca gacaaagtgg gaacatttte actgatgacc agtgataact CggggCgtga tcatcccagg gcaaacttcc attgcagttt atcattggtg Bgaaaaacag cctacatatc gttcagacca gctccgcacc gaagggctgc lt 210 gt 2 lt 211 gt 1728 lt 212 gt DNA teeccattgt accttgcaga ttgtcaaata agaagcttgg gaacagaagc agcttctcga cttctttgtt ctatttcttg tectggatat tctgtagggt attetttaga atcctcacca tggctggaaa gcctgiaccc ctgaagctga tctcagocaa aagagcaagt tgtgccctca lt 213 gt Mus musculus lt 400 gt 2 atgcgggcat ttgttatttt agagaactct aggogaatgg ggaagagtec aagaaacaag aatggagcta gaaggaaatg aggtctatca gaaaaagagg cctaaggact gettgtcaac ggactggttc atataggtgg ccaagattct etgagtetct gtgttttaga ctagaaatgg aagagctctg aactccaaag tgacagatct ccaaagatct gcagcaaagc tccatcacgt agacagcctc tcgactcctg cttgatccgt cttcaaacat agccttecat acgcagaatg aaaggaggca gtcagctgga acactticte tecttatgaa tgacatctac acctcgaact ccattggaat ttectacaaa aaaatagaga gcagaagacc gegaacccto agCCCatg ctggcgttgg tcattiggtt tgcaaagctt cegaatacca agaacagett tetggggaag gttttttcta acatgcagat atactacctc gacagagctg caggaagctg ggtctactgt 111 catcct
167. tt ctggcagtat atgacccaga ttttccettt tagtactgtt gaaagaaaat tcaatcccaa gggcttotta tccatgtggt tggcagtgaa agctatgtca aagaaacatt atcatagtat atatgtgtct gatctttttt ttgcaaggtt agagtagaga tgagctgatt acctgttctt tttatattet ttttaaaage ttaactcagt taaattctta Eggtaattat cagttgtttg ctagatacct ttacttcata gggctagaca agtggtatta agtggagcat ittcacactg ttttatcttt tgaagecata caaggaacta ggaagttcat cattattctt gtgccaattt attctagtac tagtttgcoc ggctacacag aaattttatt tataatttag atttctgttt gtgttattgt ataaacacac ttggctagct cttatcttac saggagagag cttectgect tacacagaag cttttaatac gtgtgtcgat taagggacaa atcaacatgg gcaatgaatt gtaagccatc aagtataagc tgtacataga tgatataata aaaaataaat 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 10 20 30 gcatggttat tagtaatgct tggacatgct gctcagtttg aggcatataa caataatttt gtgataaatt tttcaaattt tcttggttag tttcttctct agetatatat ttgatttcta tgttctaaga atagactgaa ttttttaata gaaatgcttt ttctatattt atttttttet tgaatgttgt attatattct tggtgaatgc gttgtttgtt atatttagat etggtttttc cttgttttct aacaagttta gecagaaatg tgaattaatg tcataaacct atcaaccaag ccagatgatt gtaaatataa gattttgtga aataggtttt gtatgttctc ttattttttt teecteccct aggaagggtg tttecttcat gtttgtacac tgttagcatt atatctgtta attgaagttg caaaagcagt ta
168. ttggcccCc gactacaatt gctaagttct ccccacccct actttagccc ctgctggcac agatagatgc gacctcatgg ctctcictac acccagtcat ttacatagca gtatecagat ccaacagagg gcaggggtta gtggtgtcag tetgtctgtt gtccctgacg ctataccaag caatgtcaat cctcctggcc cctgtttggc gacccataac ctacgaagag ctcogcctac caaagatggt tcgggtgg8g gcaataatgt aatgtcagaa ccaggagtgg ggttggggcc acaagggaga tctctggggo agactacctt cttctgtgtg tcatattttc aatgcctcta caccatcctg JP VO2003 085119 Al 2003 10 16 tecettttta acaggccato gtaattagag gcotgggaga atatagctcc tctgctgggo cccaatgctt tgaatcctcc cagggaccct aggctgattg ctgaggatgg gtctgggcoo gggaacacag gactttgtat aatcctgtcc gcaggtggtt ggcaccatct aaggtgctec gCctgcgtgo ttcactcatc tttgccatcg gtgtcaggca attaagagct acctgggtca gagaagagtg cctgccecagc ttacatcctt agctgccaaa agctgcactc tgggttgtga CCtgggCagg tgsaggcagt gatgggtatg aactttagaa cageccctaa ttctccaaca gtgtccaagg aggcacctat agttgacagg atgtggaggg cctgctttgc caaataaatg aggttctgag gccatcegag tgatttcccc ctcactggga agtctttatt agatgcttga ccaaatcago gttctcactc gtgttgatga ctctccctcc tctggctggg tcggggtgct ctgoagtaga tettcttgce tgagcagtgc gctatgtgac cggccaaggc tcctgtggtg ggggctggga ctatcagggt acggaaggct ctcagaagac tetectgect gectoctect tttgggcact ccctactata tagcataata tsggagctga acagaccaac 8888888880 cctgacccag 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5

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