(57)【要約】 本発明は発現タンパク質を生成する能力を変化させるために
Contents
1.2. 10 20 30 50 JP 2005 521407 2005 7 21 61 10 20 30
3. 13 JP 2005 521407 A 2005 7 21
4. I LI LI II II II II II L II II II II II II m L a n nono a FT TW a PR n nono non II LI II ne fi noe 10 20 30 50 JP 2005 521407 A 2005 7 21 30 10
5. JP 2005 521407 A 2005 7 21 63 I LI II II II LI I LI LI I LI II II II II II II II 1 1I1II L LI I L LI LI II 1 1 I1 II L 10 20 30 50
6. I II II II II II II II II II II 10 20 30 50 JP 2005 521407 2005 7 21 4 LI II I LI II II II II L LI LI II II LI II II II II II II II II II II II II II II II II II I II II II II II II II II 10 20 000 I LI LI I LI LI 30
7. u 10 20 30 50 32 JP 2005 521407 2005 7 21
8. I G ATGAAAAAAGCTGTCATTGTAGAAAACAAAGGTTGTGCAACATGCTCGATCGGAGCC CTTGTCTAGTGGACGGTCCTATCCCTGATTTTGAAATTGCCGGTGCAACAGGTCTATTC GGTCTATGGGGG 1 I LI II II II II II II II II II II II II MKKAVIVENKGCATCSIGAACLVDGPIPDFEIAGATGLFGLWG 2 oa L3 E D L3 oa E E LI DI ATGATTGGAAGAATTATCCGTTTGTACCGTAAAAGAAAAGGCTATTCTATTAATCAGCTG GCTGTTGAGTCAGGCGTATCCAAATCCTATTTAAGCAAGATTGAAAGAGGCGTTCACAC GAATCCGTCCGTTCAATTTTTAAAAAAAGTTTCTGCCACACTGGAAGTTGAATTAACAGA ATTATTT
9. LI LI LI ODO LI II II II II II II II II II II II II II II II II II II II II 50 JP 2005 521407 2005 7 21 28 10 30 LI LI
10. LI LI II II II II II II II 10 20 30 50 JP 2005 521407 2005 7 21 16 10 20 30 50 I I II II II I II II II I LI II II II LI 000000 I LI LI LI LI 0010 L LI LI LI LI II II II II II LI II II II II II II II II II II II L LI
11. L3 L I D L3 L I L I L I D L3 L I L3 L I L3 L I Moo L3 L I L L3 L I L3 L I LI LI L I a LI L I L I D L3 L3 L3 D L3 L3 L3 L3 L I 50
12. 10 20 50 LI LI LI n I I LI LI I LI II II II II I II II I LI LI I II II LI LI n I LI LI 36 JP 2005 521407 A 2005 7 21
13. 10 20 30 50 71 JP 2005 521407 2005 7 21 u r1 10 20 30 72 JP 2005 521407 2005 7 21 Uu 1 755 4 PBSX UF Xbal CTACATTCTAGACGATTTGTTTGATCGATATGTGGAAGC 60 PBSX UR BamHI GGCTGAGGATCCATTCCTCAGCCCAGAAGAGAACCTA DF TCCCTCGGATCCGAAATAGGTTCTGCTTATTGTATTCG D Sad AGCGTTGAGCTCGCGCCATGCCATTATATTGGCTGCTG 7 1 Eco
14. 10 20 30 50 90 JP 2005 521407 A 2005 7 21 8 ily nnnnnn LI LI 7 7 U D U rn Y BamHI Y 59 2 BamHI 17 BamHI ie 1 REI 2 RE2 8 BamHI 0 U mi HAM ret 3 pJM102 4 gt y 5 2 XI 1 LI LI LI 1 2 3 4 5 gt Ex lt gt 727172 7 DA mud lt lt 6 7 8 12 ASSY o gt lt ZZ LLL ELL 554 Hours
15. 10 20 30 50 11 JP 2005 521407 2005 7 21 10 20 30 50 JP 2005 521407 2005 7 21 12 10 30
16. 50 L LI L LI LI LI II II II II II II II II II II II II I II II II II II II II II II II II II II II JP 2005 521407 2005 7 21 5 10 20 30 0010 II 1 1I1II L LI I LI LI I LI II II II II II II
17. 1000000 HHHHH I LI LI II LI II II II II II II II II II II II II I LI LI 50 00000000 JP 2005 521407 A 2005 7 21 62 10 20 30
18. 10 20 30 50 JP 2005 521407 2005 7 10 20 30 50 15 JP 2005 521407 A 2005 7 21
19. p96 CGGGTCCGATACTGACTGTAAGTTTGAC GCGCCCTTGATCCTAAGTCAGATGAAAC 10 GTACCATAACCATGCCTTGGTTAGGATGCATATGGCGGCCGC 101 spcF BstXI CCTTGTCTTCCATCTTGCTGGAGCTGGATCCATAACTTCGTATAATG au GAGAGCAAGGACATGACATTGACGC 197 mile m analt GATCTTCACCCTCTTCAACTTGTAAAG 198 anal PCR 20 HHHHHHH II 1 L I L 0 anal 000000 uuu 011 LI II II I II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II 00000000 00 00 I L II I 0 000000000000 HHHH 8 PcekA RE TTTGCTTCCTCCTGCACAAGGCCTC 199 Be CAATGGAAATGCACACACAATAACGTGACTGGCAA spc GAGA 201 40 pckA DFfus GTAATGGCCCTCTCGTATAAAAAAC GTTTTTTATACGAGAGGGCCATTACCAAT
20. 30 50 89 JP 2005 521407 2005 7 r1 nnmnnn n a a r1 a n n ne r1 r1 n u n n mn nono nono
21. LI II II II II II II II II II II II II II II II II II II II II II II II II II II 0 TTGATCATGACACAACCATCAAAAACTACGAAACTAACTAAAGATGAAGTCGATCGGCT 30 CATAAGCGATTACCAAACAAAGCAAGATGAACAAGCGCAGGAAACGCTTGTGCGGGTG TATACAAATCTGGTTGACATGCTTGCGAAAAAATACTCAAAAGGCAAAAGCTTCCACGA GGATCTCCGCCAGGTCGGCATGATCGGGCTGCTAGGCGCGATTAAGCGATACGATCC TGTTGTCGGCAAATCGTTTGAAGCTTTTGCAATCCCGACAATCATCGGTGAAATTAAAC GTTTCCTCAGAGATAAAACATGGAGCGTTCATGTGCCGAGACGAATTAAAGAACTCGGT CCAAGAATCAAAATGGCGGTTGATCAGCTGACCACTGAAACACAAAGATCGCCGAAAG TCGAAGAGATTGCCGAATTCCTCGATGTTTCTGAAGAAGAGGTTCTTGAAACGATGGAA ATGGGCAAAAGCTATCAAGCCTTATCCGTTGACCACAGCATTGAAGCGGATTCGGACG GAAGCACTGTCACGATTCTTGATATCGTCGGATCACAGGAGGACGGATATGAGCGGGT CAACCAGCAATTGATGCTGCAAAGCGTGCTTCATGTCCTTTCAGACCGTGAGAAACAAA TCATAGACCTTACGTATATTCAAAACAAAAGCCAAAAAGAAACTGGGGACATTCTCGGT 40 ATATCTCAAATGCACGTCTCGCGCTTGCAACGCAAAGCTGTGAAGAAGCTCAGAGAGG CCTTGATTGAAGATCCCTCGATGGAGTTAATG 9 LI LI LI HHHHHH I LI II I II II 38 JP 2005 521407 2005 7 21 MIMTQPSKTTKLTKDEVDRLISDYQTKQDEQAQETLVRVYTNLVDMLAKKYSKGKSFHED LRQVGMIGLLGAIKRYDPVVGKSFEAFAIPTIIGEIKRFLRDKTWSVHVPRRIKELGPRIKMA VDQLTTETORSPKVEEIAEFLDVSEEEVLETMEMGKSYQALSVDHSIEADSDGSTVTILDI VGSQEDGYERVNQQLMLQSVLHVLSDREKQIIDLTYIQNKSQKETGDILGISQMHVSRLQ
22. JP 2005 521407 2005 7 21 67 10 20 30 I L LI LI I LI LI 1000000000 000 LI I LI II II II II II II JP 2005 521407 A 2005 7 21 68 10 20
23. JP 2005 521407 2005 7 21 66 10 20 30 LI LI II LI I LI II LI I LI II 50 L
24. 8 730 2 CTGAACTCTAGACCTTCACCAGGCACAGAGGAGGTGA 137 Sir Uffus GCCAATAAGTTCTCTTTAGAGAACAGGATCC 138 GCTTACCGAAAGCCAGACTCAGCAA Sir Urfus TIGCTGAGTCTGGCTITCGGTAAGCGGATCCTIGTTCTCT 139 AAAGAGAACTTATTGGC Sir Dffus BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC 140 GGGCTAACGTTCGCATCTATAGGGG Sir Drfus CCCCTATAGATGCGAACGTTAGCCC GGATCC 141 TCATGGCTGTCATGGCGCATTAACG Sir DR TGAGACGAGCTCGATGCATAGGCGACGGCAGGGCGCC 142 CGAAATTCTAGATCCCGCGATTCCGCCCTTTGTGG 143 Sir DR 34374 V TICCAAGAGCTCGCGGAATACCGGAAGCAGCCCC 144 Xba CAATTCTCTAGAGCGGTCGGCGCAGGTATAGGAGGGG 145 YbcO UF GAAAAGAAACCAAAAAGAATGGGAAGGATCC GCTTACCGAAAGCCAGACTCAGCAA 142 143 144 145 146 TTCCCATTCTTTTTGGTTTCTTTTC GCTATTTAACATTTGAGAATAGGGA TCATGGCTGTCATGGCGCATTAACG snUF bal TAGGAATCTAGAGATCATTGCGGAAGTAGAAGTGGAR Csn UF TTTAGATTGAGTTCATCTGCAGCGGGGATCC 152 GCTTACCGAAAGCCAGACTCAGCAA Csn UR TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC 153 CCGCTGCAGATGAACTCAATCTAAA Csn DF CGTTAATGCGCCATGACAGCCATGAGGATCC 154 BamHI GTGAGAGGGGCTAAGGCTGATTGGCGGATCC TCATGGCTGTCATGGCGCATTAACG CsnDR Sal ATACTCGTCGACATACGTTGAATTGCCGAGAAGCCGC CTGGAGTACCTGGATCTGGATCTCC SigB UF Sacl CGGTTTGAGCTCGCGTCCTGATCTGCAGAAGCTCATT 159 SigB UF CTAA
25. LI E LI LI mm 1 L I ERI 10 20 30 42 JP 2005 521407 A 2005 7 21 ATGTTTAAAAATAATGTCATACTTTTAAATTCACCTTATCATGCACATGCTCATAAAGA GGGGTTTATTCTAAAAAGGGGATGGACGGTTTTGGAAAGCAAGTACCTAGATCTACT CGCACAAAAATACGATTGTGAAGAAAAAGTGGTAACAGAAATCATCAATTTGAAAGCG ATATTGAACCTGCCAAAAGGCACCGAGCATTTTGTCAGTGATCTGCACGGAGAGTAT CAGGCATTCCAGCACGTGTTGCGCAATGGTTCAGGACGAGTCAAAGAGAAGATACG CGACATCTTCAGCGGTGTCATTTACGATAGAGAAATTGATGAATTAGCAGCATTGGTC TATTATCCGGAAGACAAACTGAAATTAATCAAACATGACTTTGATGCGAAAGAAGCGT TAAACGAGTGGTATAAAGAAACGATTCATCGAATGATTAAGCTCGTTTCATATTGCTC CTCTAAGTATACCCGCTCCAAATTACGCAAAGCACTGCCTGCCCAATTTGCTTATATT ACGGAGGAGCTGTTATACAAAACAGAACAAGCTGGCAACAAGGAGCAATATTACTCC GAAATCATTGATCAGATCATTGAACTTGGCCAAGCCGATAAGCTGATCACCGGCCTT GCTTACAGCGTTCAGCGATTGGTGGTCGACCATCTGCATGTGGTCGGCGATATTTAT GACCGCGGCCCGCAGCCGGATAGAATTATGGAAGAACTGATCAACTATCATTCTGTC GATATTCAGTGGGGAAATCACGATGTCCTTTGGATCGGCGCCTATTCCGGTTCCAAA GTGTGCCTGGCCAATATTATCCGCATCTGTGCCCGCTACGACAACCTGGATATTATTG AGGACGTGTACGGCATCAACCTGAGACCGCTGCTGAACCTGGCCGAAAAATATTATG ATGATAATCCAGCGTTCCGTCCAAAAGCAGACGAAAACAGG CCAGAGGATGAGATTAAGCAAATCACAAAAATCCATCAAGCGATTGCCATGATCCAAT TCAAGCTTGAGAGCCCGATTATCAAGAGACGGCCGAACTTTAATATGGAAGAGCGGC TGTTATTAGAGAAAATAGACTATGACAAAAATGAAATCACGCTGAACGGAAAAACATA TCAACTGGAAAACACCTGCTTTGCGACGATTAATCCGGAGCAGCCAGATCAGCTATT AGAAGAAGAAGCAGAAGTCATAGACAAGCTGCTAT
26. n n LI II II II II II II II II 4 LI II II II II II II II II II II II II n n 10 20 30 50 JP 2005 521407 A 2005 7 21 33 10 20 30 I LI LI I LI LI L L LI II LI II II II II II II II II II
27. L LI II I LI LI n
28. 22 JP 2005 521407 2005 7 21 10 20 ATGAATTTTCAAACAATCGAGCTTGACACATGGTATAGAAAATCTTATTTTGACCATTA CATGAAGGAAGCGAAATGTTCTTTCAGCAT CACGGCAAACGTCAATGTGACAAATTTG CTCGCCGTGCTCAAGAAAAAGAAGCTCAAGCTGTATCCGGCTTTTATTTATATCGTAT CAAGGGTCATTCATTCGCGCCCTGAGTTTAGAACAACGTTTGATGACAAAGGAAGCT GGGTTATTGGGAACAAATG CATCCGTGCTATGCGATTTTTCATCAGGACGACCAAAC GTTTTCCGCCCTCTGGACGGAATACTCAGACGATTTTTCGCAGTTTTATCAT 30 CTTCTGGACGCCGAGCGCTTTGGAGACAAAAGGGGCCTTTGGGCTAAGCCGGACAT CCCGCCCAATACGTTTTCAGTTTCTTCTATTCCATGGGTGCGCTTTTCAACATTCAATT TAAACCTTGATAACAGCGAACACTTGCTGCCGATTATTACAAACGGGAAATACTTTTC AGAAGGCAGGGAAACATTTTTGCCCGTTTCCTGCAAGTTCACCATGCAGTGTGTGAC GGCTATCATGCCGGCGCTTTTATAA 58 LI LI II II II II II II 000 L LI LI LI II II LI II II II II II II II II II II II II II II II II II II II M
29. 64 JP 2005 521407 2005 7 21 I LI LI II II II II II II II II II II II II II II II II II LI LI LI II II II II II II II II II LU I LI II II II II II II LI LI LI LI II II II II II II II II II II II II II II II II II II II II II I LI LI II LI II I II II I II I II II I II II II II II II II II II II LI LI LI II II II II II II II II II II II II II II II LI LI LI II II II II II II II 900 91001000 I II II II II II II II II II II I I II II II II II II II II II LI LI LI II II II II II II II 000 II II II II II 0 I LI LI II II II II II II II II II II II II II II II II II II II II LI LI LI LI II II II II II II II II II II II II II II II II II II LI LI II II II lil I II II II II II II LI LI II II II I LI LI II II II I LI LI II II II I II LI II II II II II II II II II II II II II II II II II II II II II LI LI II II II I LI LI II II II I L LI LI LI LI I II II II II II I II II II II II II LI II II II II II II LI LI II II II II II II II II II II II II II II II II II II II II II II II
30. 0010 I LI II II II II II II II I LI II LI II II II II II II II II II I LI 50 JP 2005 521407 2005 7 21 8 L 10 I LI II LI I LI 20 30 I LI LI 50 I I II II II II 1 1I1II L
31. 30 LI LI 0000000 nnnnmn 50 I LI II II II II n nnnunnnnnnnnnnunnnnunnponnnnnnmnnn JP 2005 521407 A 2005 7 21 21 10 20 30
32. LI LI LI II II LI II II II II II II II II I LI II II II II II II LI LI LI II II LI II II II II II II II II II L LI LI LI LI II LI II II II II II II II II II II II II I LI LI I LI LI I LI LI LI 0010 50 29 JP 2005 521407 A 2005 7 21
33. 20 30 nnnnnnnnn L LI LI LI II II LI II II II II II II II II II II II II II II II II II II II II II II II II JP 2005 521407 A 2005 7 21 19 10 I LI LI I LI II II II II II II I LI LI L LI LI LI II LI II II II II LI II II II II II II II II II I
34. MOSLNYEDQVLWTRWKEWKDPKAGDDLMRRYMPLVTYHVGRISVGLPKSVHKDDLMS LGMLGLYDALEKFDPSRDLKFDTYASFRIRGAIIDGLRKEDWLPRTSREKTKKVEAAIEKL EQRYLRNVSPAEIAEELGMTVQDVVSTMNEGFFANLLSIDEKLHDQDDGENIQVM IRDDK NVPPEEKIMKDELIAQLAEKIHELSEKEQLVVSLFYKEELTLTEIGQVLNLSTSRISQIHSKA LFKLKNLLEKVIQ 57 L LI LI LI LI II II II II II II II II II II II II II II II II 000 L 10 20 30 50 58 JP 2005 521407 A 2005 7 21 u
35. 10000 MQSGKMKALMKKDGAFGAVLTEVPIPEIDKHEVLIKVKAASICGTDVHIYNWDQWARQRI KTPYVFGHEFSGIVEGVGENVSSVKVGEYVSAETHIVCGECVPCLTGKSHVCTNTAIIGV DTAGCFAEYVKVPADNIWRNPADMDPSIASIQEPLGNAVHTVLESQPAGGTTAVIGCGPI GLMAVAVAKAAGASQVIAIDKNEYRLRLAKQMGATCTVSIEKEDPLKIVSALTSGEGADLV CEMSGHPSAIAQGLAMAANGGRFHILSLPEHPVTIDLTNKVVFKGLTIQGITGRKMFSTW RQVSQLISSNMIDLAPVITHQFPLEEFEKGFELMRSGQCGKVILIP 38 000000 LI LI II II II LI II II II II II II II I II I II II II II II II II II LI 52 JP 2005 521407 2005 7 21 TAATACGATAAGAACAGCTTAGAAATACACAAGAGTGTGTATAAAGCAATTAGAATGA GTTGAGTTAGAGAATAGGGTAGCAGAGAATGAGT TTAGTTGAGCTGAGACATTATGTT TATTCTACCCAAAAGAAGTCTTTCTTTTGGGTTTATTTGTTATATAGTATTTTATCCTCT CATGCCATCTTCTCATTCTCCTTGCCATAAGGAGTGAGAGCAATGAATTTCCAATCAA ACATTTCCGCATTTTTAGAGGACAGCTTGTCCCACCACACGATACCGATTGTGGAGAC CTTCACAGTCGATACACTGACACCCATTCAAATGATAGAGAAGCTTGACAGGGAGATT ACGTATCTTCTTGAAAGCAAGGACGATACATCCACTTGGTCCAGATATTCGTTTATCG GCCTGAATCCATTTCTCACAATTAAAGAAGAGCAGGGCCGTTTTTCGGCCGCTGATC AGGACAGCAAATCTCTTTACACAGGAAATGAACTAAAAGAAGTGCTGAACTGGATGAA TACCACATACAAAATCAAAACACCTGAGCTT
36. HHHHHHHHHHHHHHHHHHHHHHHHHHHHH 0000 L LI L LI LI II II II II II II II II II II II II II II II II II II II II 50 JP 2005 521407 2005 7 21 7 10 20 30 L LI LI L II II II II II II II II II II II I L LI LI I LI LI I LI II II II LI
37. 20 30 50 00010 L 7 L LI LI L II II LI II II II II II II II II II II II II II II II II II II II II II II L LI LI LI II II LI II II II II II II II II II I II II II II II II II II II II II II II 00000 JP 2005 521407 A 2005 7 21 20 n 10 20
38. LI II I II II II MKISMQKADFWKKAAISLLVF TMFFTLMMSETVFAAGLNKDQKRRAEQLTSIFENGTTEIQ YGYVERLDDGRGYTCGRAGFTTATGDALEVVEVYTKAVPNNKLKKYLPELRRLAKEESD 20 DTSNLKGFASAWKSLANDKEFRAAQDKVNDHLYYQPAMKRSDNAGLKTALARAVMYDT VIQHGDGDDPDSFYALIKRTNKKAGGSPKDGIDEKKWLNKFLDVRYDDLMNPANHDTRD EWRESVARVDVLRSIAKENNYNLNGPIHVRSNEYGNFVIK 8 II I LI LI LI LI LI LI LI LI II II II II II II I II II II II II II II II II II II 1 1 30 ATGAAAAGAAACCAAAAAGAATGGGAATCTGTGAGTAAAAAAGGACTTATGAAGCCGG GAGGTACTTCGATTGTGAAAGCTGCTGGCTGCATGGGCTGTTGGGCCTCGAAGAGTAT TGCTATGACACGTGTTTGTGCACTTCCGCATCCTGCTATGAGAGCTATT 5 0000 LI MKRNQKEWESVSKKGLMKPGGTSIVKAAGCMGCWASKSIAMTRVCALPHPAMRAI 6 40 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH L LI LI LI II II I LI LI LI LI II II II II II II II II II II II II II 1 L3 LI L I
39. LI LI LI LU II IM III II II III L III III 1 II HHHHHHHHHH HHHHHHHHHHH I LI II II II II II II L LI L LI LI LI II II II II II II II II II I II II I II II II II II II II II II II II II II II L L LI L LI LI LI II II II II I II II II II II II II I II II II II II II II II II II II II II I II LI II II II II I II II I II I II II II II II II II II II II II I LI LI L LI L LI LI LI II II II II II II II I II II II II I II II II II II II II II II II II II II II 10 20 30 50 79 JP 2005 521407 2005 7 21 10 X5 tdh kbl 20 CTCAGTTCATCCATCAAATCACCAAGTCCG _ TACACGTTAGAAGACGGCTAGATGCGTCTGATTGTGACAGAC GGCG AACCTTCCAGTCCGGTTTACTGTCGC GTACCATAAGAAGACGGAGCTTGCCGTGTCCACTCCGATTAT AGCAG p98spcF Bbsl CCTTGTCTTGAAGACGGAGCTGGATC
40. 10 LI LI I LI II II II II II II I LI LI 20 30 C C 50 LI LI LI 0010 noe C LI ie m ASK TY C C C C C JP 2005 521407 A 2005 7 21 27 10 20 30
41. US 74 100122839 31 60 376 343 32 14 4 29 2002 4 29 74 100118647 33 US FR 54 570000 LI LI LI LI II II II II II II II II II II II II II II II II II II II II II II II II II II II II II 00 II II II II LI LI LI LI II II II II II II II II II I II II II II II II II II II II II II II II II II II II II II II II II II II II LI LI LI LI II II II II II II II II II I II II II II II II II II II II II II II II II II II II II II II II II II II II LI LI LI LI II II II II II II II II II I II II II II II II II II II II II II II II II II II II II II II II II II II II LI II LI LI II II II II II II II II II II II II II II II II II II II II II II II II I JP 2005 521407 2005 7 21 2 10 20 I LI LI
42. r1 r1 r1 r1 u n u n 10 20 30 50 70 JP 2005 521407 2005 7 21
43. LI 000000 n 8 C LL 1I XII II II II L 00 n o IL LI no 0000000000 OU g n L HHHHHHHHHHHHH u L LI LI LI II II LI II II II II II II II II 0000 II II II II II II 00000 eeu LI II II II II II II II II 86 JP 2005 521407 2005 7 C 10 20 30 50 87 JP 2005 521407 2005 7 21
44. 9 7 NaH2PO4 H20 0 896 56g KH2P04 0 8 56g MgSO4 7H20 0 28 19 6g 0 1 7g 12 2H2O 0 01 0 7g 7H2O 0 03 2 1g MnC12 4H2O 0 02 1 4g 100 x 1 70g 2 H2S04 0 16 11 25 60 1 29 90 Harwood and Cutting 5 4 9 8 r3 10 20 30 50 JP 2005 521407 2005 7 21 88 10 20
45. I LI LI II II II II II II II II I LI LI LI LI LI LI II LI II II II II II II I II II II II II II II II II II II II II II LI LI LI II II LI II II II I II II II II II II I II II II II II II II II II II II II II 0000000 JP 2005 521407 A 2005 7 21 9 I LI LI 10 HHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 20 30 I L LI LI n
46. JP 2005 521407 A 2005 7 21 25 000000 LI LI n L LI LI LI II II LI II II II II II II II II II 10 20 30 JP 2005 521407 A 2005 7 21 26
47. oa L3 F3 oa L3 F3 oa L3 F3 D L3 L3 F3 D L3 L3 F3 L3 L3 F3 10 20 30 50 75 JP 2005 521407 2005 21 4 3 i 10 76 JP 2005 521407 2005 7 21 3 5 UF 110 CGAGAATCTAGAACAGGATGAATCATCTGTGGCGGG DHB UFfus phieo CGACTGTCCAGCCGCTCGGCACATCGGATCCGCTTA CCGAAAGCCAGACTCAGCAA TTGCTGAGTCTGGCTTTCGGTAAGCGGATCCGATGTG CCGAGCGGCTGGACAGTCG DHB URfus phleo 10 112 CGTTAATGCGCCATGACAGCCATGAGGATCCCACAA GCCCGCACGCCTTGCCACAC DHB DRfus phleo GTGTGGCAAGGCGTGCGGGCTTGTGGGATCCTCATG GCTGTCATGGCGCATTAACG DHB DR Sacl GACTTCGTCGACGAGTGCGGACGGCCAGCATCACCA DHB UF 42741 GGCATATCTAGAGACATGAAGCGGGAAACAGATG DHB DR GGTGCGGAGCTCGACAGTATCACAGCCAGCGCTG YvfF yveK UF AAGCGTTCTAGACTGCGGATGCAGATCGATCTCGGG 118 YvfF yveK UF AACCTTCCGCTCACATGTGAGCAGGG
48. E 2 ae 8 H LI LI LI II II II II II II H II II II II II II 000 T SE Ne ne ARIE UE C 10 20 30 50 74 JP 2005 521407 A 2005 7 21 X2 BER IEEE ci m L L3 L3 F3 oa F3 oa L3 F3 L3 L3 F3
49. ATGCAGAGTG GAAAGATGAAAGCTCTAATGAAAAAGGACGGGGCGTTCGGTGCTGT GCTGACTGAAGTTCCCATTCCTGAGATTGATAAACATGAAGTCCTCATAAAAGTGAAA GCCGCTTCCATATGCGGCAC GGATGTCCACATTTATAATTGGGATCAATGGGCACGT CAGAGAATCAAAACACCCTATGTTTTCGGCCATGAGTTCAGCGG CATCGTAGAGGGC GTGGGAGAGAATGTCAGCAGTGTAAAAGTGGGAGAGTATGTGTCTGCG GAAACACA CATTGTCTGTG GTGAATGTGTCCCTTGCCTAACAGGAAAATCTCATGTGTGTACCAAT ACTGCTATAATCGGAGTGGACACGGCAGGCTGTTTTGCGGAGTATGTAAAAGTTCCA GCTGATAACATTTGGAGAAATCCCGCTGATATGGACCCGTCGATTGCTTCCATTCAAG AGCCTTTAG GAAATGCAGTTCATACCGTACTCGAGAGCCAGCCTGCAGGAGGAACGA CTG CAGTCATTGGATGCGGACCGATTGGTCTTATGGCTGTTGCGGTTGCAAAAGCAG CAGGAGCTTCTCAGGTGATAGCGATTGATAAGAATGAATACAGG CTGAGGCTTGCAA AACAAATGGGAGCGACTTGTACTGTTTCTATTGAAAAAGAAGACCCGCT CAAAATTGT AAGCGCTTTAACGAGTGGAGAAGGAGCAGATCTTGTTTGTGAGATGTCGGGCCATCC CTCAGCGATTGCCCAAGGTCTTGCGATGGCTGCGAATGGCGGAAGATTTCATATTCT CAGCTTG CCGGAACATCCGGTGACAATTGATTTGACGAATAAAGTGGTATTTAAAGG GCTTACCATCCAAGGAATCACAGGAAGAAAAATGTTTTCAACATGGCGCCAGGTGTC TCAGTTGATCAGTTCAAACATGATCGATCTTGCACCTGTTATTACCCATCAGTTTCCAT TAGAGGAGTTTGAAAAAGGTTTCGAACTGATGAGAAGCGGGCAGTGCGGAAAAGTAA TTTTAATTCCA 37 HHHHH I II II II II II II 10000 I II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II III III II II 10000 10 20 30 50 51 JP 2005 521407 2005 7 21
50. I LI LI I LI LI II II II II II II II II 50 I LI LI L LI LI LI LI II II II II II II II II II II II II II II II II II II II II II II II II II II JP 2005 521407 2005 7 21 6 I LI LI LI II 10 20 30 I LI LI I LI LI I LI LI I LI LI I LI LI
51. LI LI LI LI II II I MKRESNIQVLSRGQKDQPVSQIYQVSTMTSLLDGVYDGDFELSEIPKYGDFGIGTFNKLD GELIGFDGEFYRLRSDGTATPVQNGDRSPFCSFTFFTPDMTHKIDAKMTREDFEKEINSM LPSRNLFYAIRIDGLFKKVQTRTVELQEKPYVPMVEAVKTQPIFNFDNVRGTIVGFLTPAYA NGIAVSGYHLHFIDEGRNSGGHVFDYVLEDCTVTISQKMNMNLRLPNTADFFNANLDNPD FAKDIETTEGSPE 22 L LI LI II II II II II II II II II II I LI II LI II II II II II II II II LI LI LI LI II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II 44 JP 2005 521407 2005 7 21 ATGAAGGTAAAAGTAGCGATCAACGGGTTTGGAAGAATCGGAAGAATGGTTTTTAGA AAAGCGATGTTAGACGATCAAATTCAAGTAGTGGCCATTAACGCCAGCTATTCCGCA GAAACGCTGGCTCATTTAATAAAGTATGACACAATTCACGGCAGATACGACAAAGAG GTTGTGGCTGGTGAAGATAGCCTGATCGTAAATGGAAAGAAAGTGCTTTTGTTAAACA GCCGTGATCCAAAACAGCTGCCTTGGCGGGAATATGATATTGACATAGTCGTCGAAG CAACAGGGAAGTTTAATGCTAAAGATAAAGCGATGGGCCATATAGAAGCAGGTGCAA AAAAAGTGATTTTGACCGCTCCGGGAAAAAATGAAGACGTTACCATTGTGATGGGCG TAAATGAGGACCAATTCGACGCTGAGCGCCATGTCATTATTTCAAATGCGTCATGCAC GACAAATTGCCTTGCGCCTGTTGTAAAAGTGCTGGATGAAGAGTTTGGCATTGAGAG CGGTCTGATGACTACAGTTCATGCGTATACGAATGACCAAAAAAATATTGATAACCCG CACAAAGATTTGCGCCGGGCGCGGGCTTGCGGTGAATCCATCATTCCAACAACAACA GGAGCGGCAAA
52. I LI II II II II LI LI I II II II II II II II II I LI LI LI I LI LI LI LI 1 1 1 1 10 20 30 47 JP 2005 521407 2005 7 21 TTGTTAACAGCCTTAAAAACAGATACAGGAAAAATCCGCCAGCATAATGAAGATGATG CGGGGATATTCAAGGGGAAAGATGAATTTATATTAGCGGTTGTCGCTGATGGCATGG GCGGCCATCTTGCTGGAGATGTTGCGAGCAAGATGGCTGTGAAAGCCATGGGGGAG AAATGGAATGAAGCAGAGACGATTCCAACTGCGCCCTCGGAATGTGAAAAATGGCTC ATTGAACAGATTCTATCGGTAAACAGCAAAATATACGATCACGCTCAAGCCCACGAAG AATGCCAAGGCATGGGGACGACGATTGTATGTGCACTTTTTACGGGGAAAACGGTTT CTGTTGCCCATATCGGAGACAGCAGATGCTATTTGCTTCAGGACGATGATTTCGTTCA AGTGACAGAAGACCATTCGCTTGTAAATGAACTGGTTCGCACTGGAGAGATTTCCAG AGAAGACGCTGAACATCATCCGCGAAAAAATGTGTTGACGAAGGCGCTTGGAACAGA CCAGTTAGTCAGTATTGACACCCGTTCCTTTGATATAGAACCCGGAGACAAACTGCTT CTATGTTCTGACGGACTGACAAATAAAGTGGAAGGCACTGAGTTAAAAGACATCCTG CAAAGCGATTCAGCTCCTCAGGAAAAAGTAAACCTGCTTGTGGACAAAGCCAATCAG AATGGCGGAGAAGACAACATTACAGCAGTTTTGCTTGAGCTTGCTTTACAAGTTGAAG AGGGTGAAGATCAGTGC 29 L LI LI LI LI LI II II II II II II II II II II II II II I 10000 MLTALKTDTGKIRQHNEDDAGIFKGKDEFILAVVADGMGGHLAGDVASKMAVKAMGEKW NEAETIPTAPSECEKWLIEQILSVNSKIYDHAQAHEECQGMGTTIVCALFTGKTVSVAHIG DSRCYLLQDDDFVQVTEDHSLVNELVRTGEISREDAEHHPRKNVLTKALGTDQLVSIDTR SFDIE
53. E a OX SEN GE E 30 50 I LI LI LI I I LI LI LI LI I LI LI 69 JP 2005 521407 2005 7 21
54. JP 2005 521407 2005 7 21 91 7 D BamHI A E N lt a gt X 3 RAS 5 4 BamHI 1 4 EU L LI LI LI 92 24 Hours JP 2005 521407 2005 7 21 93 JP 2005 521407 2005 7 21 HHHHHHHH INTERNATIONAL SEARCH REPORT NO PCT US03 09585 CLASSIFICATION OF SUBJECT MATTER CI2P 21 06 CI2N 9 54 1 20 15 00 15 74 1 00 US CL 435 252 31 252 5 221 69 1 440 832 471 69 3 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 U S 435 252 31 252 5 221 69 1 440 832 471 69 3 Documentation searched other then 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 Please See Contimuation Sheet C DOCUMENTS CONSIDERED BE RELEVANT Citation of document with indication where appropriate of
55. n L LI LI LI II II II II II II II II II L II II I II II II II II 30 LI II 50 3 JP 2005 521407 2005 7 21
56. 82 I II II II II II II II II II II II II II II II II II II II II II II II II II II II II II II LI LI LI II II LI II II II I II II II II II II 0000000 LI LI II II II II II II II II II II 1 1 L3 rrr 1 LI LI LI LI LI LI sa LI LI 10 20 30 49 JP 2005 521407 2005 7 21 ATGACAGCTTTAT CTAAATCCAAAGAAATTATTGATCAGACGTCTCATTACGGAGCCA ACAATTATCACCCGCTCCCGATTGTTATTTCTGAAGCGCTGGGTGCTTGGGTAAAGS A CCCGGAAGGCAATGAATATATGGATATGCTGAGTGCTTACTCTGCGGTAAACCAGG AGCACAGACACCCGAAAATCATTCAGGCATTAAAGGATCAGGCT GATAAAATCAGCEE TCACGTCACGCG COTTTCATAACGATCAGCTTGGGCCGTTTTACGAAAAAACAGCT AA ACTGACAGGCAAAGAGATGATTCTGCCGATGAATACAGGAGCCGAAGCEGTTGAATC CGCGGTGAAAGCGGCGAGACGCTGGGCGTATGAAGTGAAGGGCGTAGCTGACAAT CAAGCGGAAATTATCGCATGTGTCGGGAACTTCCACGGCCGCACGATGCTGGOSGT ATCTCTTTCTTCTGAAGAG GAATATAAACGAGGATTCGGCCCGATGCTTCCAGGAATC AMACTCATTCCTTACGGCGATGTGGAAGCGCTTCGACAGGCCAT TACGCCGAATACA ACGGCATTCTTGTTTGAACCGATTCAAGGCGAAGCGGGCATTGTGATTCCGCC TO GGATTTTTACAGGAAGCGGCGGCGATTTGTAAGGAAGAGAATGT CTTGTTTATTGCG GATGAAATTCAGACGGGTCTCGGACGTACAGGCAAGACGTTTGCCTGTGACTGGGA GeGCATTGTTCCGGATATGTATATCTTGGGCAAAGCGCTTGGCGGCGGTGTGTTCGC GATCTCTTGCATTGCGGCGGACCGCGAGATCCTAGGCGTGTTTAACCCTGGCTCACA CGGCTCAACATTTGGTGGAAACCCGCTTGCATGTGCAGTGTCTATCGCTTCATTAGAA GTGCTG GAGGATGAAAAGCTGGC
57. I LI LI LI II II II II II II II II I 50 I LI II LI I LI LI LI II II II II II II II II II II II II II II II II II II II II n 34 JP 2005 521407 A 2005 7 21 u r1 n 10 20 30 50 JP 2005 521407 2005 7 21 35
58. 10 20 30 50 JP 2005 521407 A 2005 7 21 65 10 20 30 I LI LI 50 L LI LI LI II II LI II II II II II II II II LI LI LI II II II II II II II II II LI LI LI II II LI II II II II II II II II II I I LI LI nonno I LI LI LI II II II II II II II II
59. CssS DR Aspre GAGATCGGTACC CTITTGGGCCATATCGTGGATITC 103 GAGCC ARGENT CATTGACAGCARCONGGCAGATCIC __ 104 GCTTATAAGCTTGATACAAGAGAGGTCTCTOG ______ 106 Psi GOTTATAAGCTTCTGTGATGGCGOATTAACG Saci GAGCCGAGCTC CATGCCGATGAAGTCATCGTGGAGC_ 107 108 09 PhrC UF PhrC DF PhrC UR PhrC DR PhrC DR TCGCGGGATGTATGAATTTGATAAG 108 TGTAGGGAGCTC GATGCGCCACAATGTCGGTACAACG Xbal TCTAGA BamHI GGATCC GAGCTC Asp718 GGTACC PstI CTGCAG Hindli AAGCTT 7 I77 V PIS H H H H n H HuHH ES E eC C C LI II II II I 00000 CH 1 u M NUR ee E NES NIE C H H x H 0 H D LI LI L H
60. CCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTG GCGAAACCCGAC AGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGAC CCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGT GCGCTTTCTCAATG CTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTC GCTCCAAGCTGGGCTGTGTGCACG AACCCCCCGTTCAGCCCGACCGCT GCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCG GTAAGACACGACTTATCGCCACTGGCAG CAGCCACTGGTAACAGGATTAGCAGAGCGAGGTA TGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTG GCCTAACTACGGCTACACTAGAAGGACAGT ATTTGGTATCTGCG CTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAG CTCTTGATC CGGCAAACAAACCACCGCTGGTAG CGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAG AAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACG GGGTCTGACGCTCAGTGGAACGA AAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAG GATCTTCACCTAGATCCTTTTAA ATTAAAAATGAAGTTTTAAATCAAT CTAAAGTATATATGAGTAAACTTGGTCTGACAGTTACCAA TGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGT CTATTTCGTTCATCCATAGTTGCCTGAC TCCCCGTCGTGTAGATAACTACGATACG GGAGGGCTTACCATCTGGCCCCAGTGCTGCAATG ATACCGCGAGACCCACGCTCACCG GCTCCAGATTTATCAGCAATAAACCAGCCAGCCGGAAG GGCCGAGCGCAGAAGTGGTCCTGCAACTTTATCCGCCTC CATCCAGTCTATTAATTGTTGCCG GGAAGCTAGAGTAAGTAGTTCGCCAGTTAATAGTTTG CGCAACGTTGTTGCCATTGCTACAGG CATCGTGGTGTCACGCTCGTCGTTTG GTATGGCTTCATTCAGCTCCGGTTCCCAACGATCAAG GCGAGTTACATGATCCCCCATGTTGTGCAAAAAAGCGGTTAG CTCCTTCGGTCCTCCGATCGT TGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCATGGTTATGGCAG CACTGCATAATTCTCTT ACTGTCATGCCATCCGTAAGATGCTTTTCTGTG ACTGGTGAGTACTCAACCAAGTCATTCTGAG AATAGTGTATGCGGCGACCGAGTTG CTCTTGCCCGGCGTCAACACGGGATAATACCGCGCCA CATAGCAGAACTTTAAAAGTGCTCATCATTGG AAAACGTTCTTCGGGG
61. III UU III 9 20 9 26 9 42 9 54 9 88 9 90 1 21 1 125 1 21 1 07 9 12 1 125 9 12 1 07 9 16 1 125 9 16 1 07 9 18 1 125 9 18 1 07 9 20 1 125 9 20 1 07 9 26 1 125 9 26 1 07 9 42 1 125 9 42 1 07 9 54 1 125 9 54 1 07 9 88 1 125 9 88 1 07 9 90 1 125 990 1 07 97 JP 2005 521407 A 2005 7 21 9 20 926 42 954 9 88 9 90 1 21 1 125 1 1 07 9 12 1 125 9 12 1 07 9 16 1 125 9 16 1 07 918 1 125 9 18 1 07 9 20 1 125 9 20 1 07 9 26 1 125 9 26 1 07 42 1 125 42 1 07 954 1 125 954 1 07 9 88 1 125 9 88 1 07 9 90 1 125 9 90 1 07 98 JP 2005 521407 2005
62. MVLFFQIMVWCIVAGLGLYVYATWRFEAKVKEKMSAIRKTWYLLFVLGAMVYWTYEPTSL FTHWERYLIVAVSFALIDAFIFLSAYVKKLAGSELETDTREILEENNEMLHMYLNRLKTYQY LLKNEPIHVY YGSIDAYAEGIDKLLKT YADKMNLTASLCHYSTQADKDRLTEHMDDPADV QTRLDRKDVYYDQYGKVVLIPFTIETQNYVIKLTSDSIVTEFDYLLFTSLTSIYDLVLPIEEEG EG 12 OOOO OOO O OOO LI 10 20 30 39 JP 2005 521407 A 2005 7 21 ATGAAAATCAGTATGCAAAAAGCAGATTTTTGGAAAAAAGCAGCGATCTCATTACTTGTT TTCACCATGTTTTTTACCCTGATGATGAGCGAAACGGTTTTTGCGGCGGGACTGAATAA AGATCAAAAGCGCCGGGCGGAACAGCTGACAAGTATCTTTGAAAACGGCACAACGGA GATCCAATATGGATATGTAGAGCGATTGGATGACGGGCGAGGCTATACATGCGGACGG GCAGGCTTTACAACGGCTACCGGGGATGCATTGGAAGTAGTGGAAGTATACACAAAGG CAGTTCCGAATAACAAACTGAAAAAGTATCTGCCTGAATTGCGCCGTCTGGCCAAGGA AGAAAGCGATGATACAAGCAATCTCAAGGGATTCGCTTCTGCCTGGAAGTCGCTTGCA AATGATAAGGAATTTCGCGCCGCTCAAGACAAAGTAAATGACCATTTGTATTATCAGCC TGCCATGAAACGATCGGATAATGCCGGACTAAAAACAGCATTGGCAAGAGCTGTGATG TACGATACGGTTATTCAGCATGGCGATGGTGATGACCCTGACTCTTTTTATGCCTTGAT TAAACGTACGAACAAAAAAGCGGGCGGATCACCTAAAGACGGAATAGACGAGAAGAAG 10 TGGTTGAATAAATTCTTGGACGTACGCTATGACGATCTGATGAATCCGGCCAATCATGA CACCCGTGACGAATGGAGAGAATCAGTTGCCCGTGTGGACGTGCTTCGCTCTATCGCC AAGGAGAACAACTATAATCTAAACGGACCGATTCATGTTCGTTCAAACGAGTACGGTAA TTTTGTAATCAAA 7 I LI LI II II II II II II II II II II II
63. 19 JP 51 Int C1 C12N 15 09 C12N 1 21 C12N 9 12 C12N 9 16 C12N 9 8 22 C12N C12N C12N C12N C12N JP 2005 521407 A 2005 7 21 PT A 11 2005 521407 P2005 521407A 43 17 7 21 2005 7 21 15 00 ZNAA 48024 1 21 48050 9 12 4 65 9 16 B 9 18 BARR RAR PBA 08 882003 580558 2003 580558 15 3 28 2003 3 28 16 11 29 2004 11 29 PCT US2003 009585 W02003 083125 71 500284580 2 925 21 86 85 86 87 87 15 10 9 2003 10 9 74 100071010 31 60 368 949 32 14 29 2002 3 29 74 100121762 33 US 31 60 368 858 74 100126767 32 14 3 29 2002 3 29 33
64. 675 A ESTELL et al 10 May 1994 see entire document US 5 264 366 A FERRARI et al 23 November 1993 see entire document US 6 509 185 B1 VALLE et al 21 January 2003 see entire document Form PCT ISA 210 second sheet July 1998 95 JP 2005 521407 2005 7 21 INTERNATIONAL SEARCH REPORT i application No PCT US03 09585 Box I Observations where certain claims were found unsearchable Continuation of 1 of first sheet This international report has not been established in respect of certain claims under Article 17 2 for the following reasons Claim Nos because they relate to subject matter not required to be searched by this Authority namely Claim Nos because they relate to parts of the international application that do not comply with the prescribed requirements to such an extent that no meaningful international search can be carried out specifically Claim Nos because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule Box Observations where unity of invention is lacking Continuation of Item 2 of first sheet This International Searching Authority found multiple inventions in this international application as follows Please See Continuation Sheet As all required additional search fees were timely paid by the applicant this international search report covers ali searchable claims As all searchable claims could be searched without effort
65. LI LI 40 JP 2005 521407 2005 7 21 TTGAGGATGAAGCAGACGATTCCGTCCTCTTATGTCGGGCTTAAAATTAATGAATGGTA TACTCATATCCGGCAGTTCCACGTCGCTGAAGCCGAACGGGTCAAGCTCGAAGTAGAA AGAGAAATTGAGGATATGGAAGAAGACCAAGATTTGCTGCTGTATTATTCTTTAATGGA GTTCAGGCACCGTGTCATGCTGGATTACATTAAGCCTTTTGGAGAGGACACGTCGCAG CTAGAGTTTTCAGAATTGTTAGAAGACATCGAAGGGAATCAGTACAAGCTGACAGGGCT TCTCGAATATTACTTTAATTTTTTTCGAGGAATGTATGAATTTAAGCAGAAGATGTTTGTC AGTGCCATGATGTATTATAAACGGGCAGAAAAGAATCTTGCCCTCGTCTCGGATGATAT TGAGAAAGCAGAGTTTGCTTTTAAAATGGCTGAGATTTTTTACAATTTAAAACAAACCTA TGTTTCGATGAGCTACGCCGTTCAGGCATTAGAAACATACCAAATGTATGAAACGTACA CCGTCCGCAGAATCCAATGTGAATTCGTTATTGCAGGTAATTATGATGATATGCAGTAT CCAGAAAGAGCATTGCCCCACTTAGAACTGGCTTTAGATCTTGCAAAGAAAGAAGGCA ATCCCCGCCTGATCAGTTCTGCCCTATATAATCTCGGAAACTGCTATGAGAAAATGGGT GAACTGCAAAAGGCAGCCGAATACTTTGGGAAATCTGTTTCTATTTGCAAGTCGGAAAA GTTCGATAATCTTCCGCATTCTATCTACTCTTTAACACAAGTTCTGTATAAACAAAAAAAT GACGCCGAAGCGCAAAAAAAGTATCGTGAAGGATTGGAAATCGCCCGTCAATACAGTG ATGAATTATTTGTGGAGCTTTTTCAATTTTTACATGCGTTATACGGAAAAAACATTGACA CAGAATCAGTCTCACACACCTTTCAATTTCTTGAAGAACATATGCTGTATCCTTATATTG AAGAGCTGGCGCATGATGCTGCCCAATTCTATATAGAAAACGGACAGCCCGAAAAAGC ACTTTCATTTTATGAGAAAATGGTGCACGCACAAAAACAAATCCAGAGAGGAGATTGTT TATATGAAATC 15 I LI LI II II II II II II II II II II II MRMKQTIPSSYVGLKINEWY THIRQFHVAEAERVKLEVEREIEDMEEDQDLLLYYSLMEF RHRVMLDYIKPFGEDTSQLEFSELLEDIEGNQYKLTGLLEYYFNFFRG
66. TCTAGAATAATTCTACACAGCCCAGTCCAGACTATTCGGCACTGAAATTATGGGTGAAGTGGTC AAGACCTCACTAGGCACCTTAAAAATAG CGCACCCTGAAGAAGATTTATTTGAGGTAGCCCTT GCCTACCTAGCTT CCAAGAAAGATATCCTAACAGCACAAGAGCGGAAAGATGTTTTGTTCTACA TCCAGAACAAC CTCTGCTAAAATTCCTGAAAAATTTTGCAAAAAGTTGTTGACTTTATCTACAAG GTGTGGCATAATGTGTGGAATTGTGAGCGGATAACAATTAAGCTTAGGAGGGAGTGTTAAATG TCCAATTTACTGACCGTACACCAAAATTTGCCTGCATTACCGGTCGATGCAACGAGTGATGAG GTTCGCAAGAACCTGATGGACATGTTCAGGGATCGCCAGGCGTTTTCTGAGCATACCTGGAAA ATGCTTCTGTCCGTTTGCCGGTCGTGGGCGGCATGGTGCAAGTTGAATAACCGGAAATGGTTT CCCGCAGAACCTGAAGATGTTCGCGATTATCTTCTATATCTTCAGGCGCGCGGTCTGGCAGTA AAAACTATCCAGCAACATTTGGGCCAG CTAAACATGCTTCATCGTCGGTCCGGGCTGCCACGA CCAAGTGACAGCAATGCTGTTTCACTGGTTATGCGGCGGATCCGAAAAGAAAACGTTGATGCC GGTGAACGTGCAAAACAGGCTCTAGCGTTCGAACGCACTGATTI CGACCAGGTTCGTTCACTC ATGGAAAATAGCGATCGCTGCCAG GATATACGTAATCTGGCATTTCTGGGGATTGCTTATAACA CCCTGTTACGTATAGCCGAAATTGCCAGGATCAGGGTTAAAGATATCTCACGTACTGACGGTG GGAGAATGTTAATCCATATTGGCAGAACGAAAACGCTGGTTAGCACCG CAGGTGTAGAGAAG GCACTTAGCCTGGGGGTAACTAAACTGGTCGAGCGATGGATTTCCGTCTCTGGTGTAGCTGAT GATCCGAATAACTACCTGTTTTGCCGGGTCAGAAAAAATGGTGTTGCCGCGCCATCTGCCACC AGCCAGCTAT CAACTCGCGCCCTGGAAGGGATTTTTGAAGCAACTCATCGATTGATTTACGGC GCTAAGGATGACTCTGGTCAGAGATACCTGGCCTGGTCTGGACACAGTGCCCGTGTCGGAGC CGCGCGAGATATGGCCCGCGCTGGAGTTTCAATACCGGAGATCATGCAAG CTGGTGGCTGGA CCAATGTAAATATTGTCATGAACTATATCCGTAACCTGGATAGTGAAACAGGGGCAATGGTGC GCCTGCTGGAAGATGGCGATTAGGAG CTCGCATCACACGCAAAAAGGAAATTGGAATAAATGC GAAATTTGAGATGTTAATTAAAGACCTTTTTGAG GTCTTTTTTTCTTAGAT
67. justifying an additional fee this Authority did not invite payment of any additional fee As only some of the required additional search fees were timely paid by the applicant this international search report covers only those claims for which fees were paid specifically claims Nos 4 px No required additional search fees were timely paid by the applicant Consequently this international search report 5 restricted to the invention first mentioned in the claims it is covered by claims Nos 1 13 Remark on Protest The additional search fees were accompanied by the applicant s protest No protest accompanied the payment of additional search fees Form PCT ISA 210 continnation of first sheet 1 Guly 1998 96 JP 2005 521407 2005 7 21 PCT US03 09585 INTERNATIONAL SEARCH REPORT BOX OBSERVATIONS WHERE UNITY OF INVENTION IS LACKING Group I claims 1 13 drawn to altered Bacillus strain and method for enhancing expression of protein Group II claims 14 37 drawn to DNA construct Group IH claims 38 49 drawn to method for enhancing expression of a protease Group IV claims 50 60 drawn to an altered Bacillus strain Group V claims 61 64 drawn to protease producing Bacillus strain Group VI claims 65 72 drawn to method for expression of a protein of interest Group VII ciaims 73 80 drawn to method for obtaining a protein of interest from a Bacillus strain Group c
68. u n 10 20 30 50 JP 2005 521407 A 2005 7 21 59 10 20 30 LI LI I LI LI I LI LI II LI II II II II II II II II II II II II I LI LI II LI II II II II II II II II II II II LI LI L L 0000 60 JP 2005 521407 2005 7 21
69. 0 30 50 54 JP 2005 521407 A 2005 7 21 MFKLDLQPSEKLFIPFITAGDPVPEVSIELAKSLOKAGATALELGVAYSDPLADGPVIQR ASKRALDQGMNIVKAIELGGEMKKNGVNIPILFTYYNPVLQLNKEYFFALLRENHIDGL LVPDLPLEESNSLQEECKSHEVTYISLVAPTSESRLKTIIEQAEGFVYCVSSLGVTGVRN EFNSSVYPFIRTVKNLSTVPVAVGFGISNREQVIKMNEISDGVVVGSALVRKIEELKDRL ISAETRNQALQEFEDYAMAFSGLYSLK 41 L LI II II II II II LI II II II II II II II II II II II II II II II II I 8 I II II II II II II II II II II II II 000000 MYPYPNEIGRYGDFGGKFVPETLMQPLDEIQTAFKQIKDDPAFREEYYKLLKDYSGRPTA LTYADRVTEYLGGAKIYLKREDLNHTGSHKINNALGQALLAKKMGKTKIIAETGAGQHGVA AATVAAKFGFSCTVFMGEEDVARQSLNVFRMKLLGAEVVPVTSGNGTLKDATNEAIRYW VQHCEDHFYMIGSVVGPHPYPQVVREFQKMIGEEAKDQLKRIEGTMPDKVVACVGGGS NAMGMFQAFLNEDVELIGAEAAGKGIDTPLHAATISKGTVGVIHGSLTYLIQDEFGQIIEPY SISAGLDYPGIGPEHAYLHKSGRVTYDSITDEEAVDALKLLSEKEGILPAIESAHALAKAFKL AKGMDRGQLILVCLSGRGDKDVNTLMNVLEEEVKAHV 43 I LI LI LI LI II II II II II I II II II II II 0 00 II II I II II II II II II II II II II II II II II I II II II II III LI MLEKIIKQKKEEVKTLVLPVEQPFEKRSFKEAPASPNRFIGLIAEVKKASPSKGLIKEDF VPVQIAKDYEAAKADAISVLTDTPFFQGENSYLSDVKRAVSIPVLRKDFIIDSLQVEESR RIGADAILLIGEVLDPLHLHELYLEAGEKGMDVLVEVHDASTLEQILKVFTPDILGVNNR NLKTFETSVKQTEQIASLVPKESLL
70. 1 24 00000 LI LI LI LI II 1 1 I1 II LI LI I LI LI II LI II II II II II II II II II II II II LI n u 10 20 30 50 L LI LI LI II II LI II II II II II II II II LI LI LI II II II II II II II II II II II II nnnnnnn
71. 20 30 I LI LI n u 31 JP 2005 521407 2005 7
72. 50 LI LI LI I I LI LI 0010 10 JP 2005 521407 A 2005 7 21
73. 7 21 80000 AP G1 CM KE LS SD SL SZ TZ UG ZM ZW EX AM AZ BY KG KZ MD RJ TJ TM EP AT BE BG CH CY CZ LE DK ES Fl FR GR HJ I E I I LU PT SE SI SK TR OX BF B G3 G CM CA GY GQ M NE SN TD TG AE AG AL AM AT AU AZ BG BR BY EZ CA CH CN CL CE LX EC EE ES Fl Q GM FR HJ DIL I IV I 5 P KG KP KR KZ LG LK LR LS LT LU LV M M MK W M NZ NO NZ CM PH PL PT RU SG SD SE SG SK SL TM TN TR TT UG US UZ VG W YU ZA 74 100129713 72 LI LI 00000 72 0000000 79010 000 HHHHHH 2000 00000 48024 01 BAO7 BAIO BAIL BAIA DAS EAO4 48050 0002 LLO3 105 48065 AAI5X AAL5Y 17 AAL8X ANOX 2 1 20 BAo2 CM7 29 1 2
74. ACTCCAAGCATGGCCGGCCATCCGTCAGCCATTGTATTTTT GACGGCTGATGCCTTCGGAGTCCTGCCGCCGATCAGCAAACTAACGAAGGAGCAGG TGATGTACCATTTTTTGAGCGGTTACACGAGTAAGCTTGCCGGAACCGAACGTGGTG TCACGTCTCCTGAAACGACGTTTTCTACATGCTTCGGCTCACCGTTCCTGCCGCTTCC TGCTCACGTCTATGCTGAAATGCTCGGCAAAAAGAT CGATGAACACGGCGCAGACGT TTTCTTAGTCAATACCGGATGGACCGGGGGCGGCTACGGCACAG GCGAACGAATGA AGCTTTCTTACACTAGAGCAATGGTCAAAGCAGCGATTGAAGGCAAATTAGAGGATG CTGAAATGATAACTGACGATATTTTCGGCCTGCACATTCCGGCCCATGTTCCTGGCGT TCCTGATCATATCCTTCAGCCTGAAAACACGTGGACCAACAAGGAAGAATACAAAGAA AAAGCAGTCTACCTTGCAAATGAATTCAAAGAGAACTTTAAAAAGTTCGCACATACCG ATGCCATCGCCCAGGCAGGCGGCCCTCTCGTA 27 II II II II II II II II II II II II II II II LI LI LI LI II MNSVDLTADLQALLTCPNVRHNLSAAQLTEKVLSRNEGILTSTGAVRATTGAYTGRSPKD KFIVEEESTKNKIDWGPVNQPISEEAFERLYTKVVSYLKERDELFVFEGFAGADEKYRLPI TVVNEFAWHNLFARQLFIRPEGNDKKTVEQPFTILSAPHFKADPKTDGTHSETFIIVSF EKRTILIGGTEYAGEMKKSIFSIMNFLLPERDILSMHCSANVGEKGDVALFFGLSGTGKT TLSADADRKLIGDDEHGWSDTGVFNIEGGCYAKCIHLSEEKEPQIFNAIRFGSVLENVVV DEDTREANYDDSFYTENTRAAYPIHMINNIVTPSMAGHPSAIVFLTADAFGVLPPISKLT KEQVMYHFLSGYTSKLAGTERGVTSPETTFSTCFGSPFLPLPAHVYAEMLGKKIDEHGAD VFLVNTGWTGGGYGTGERMKLSYTRAMVKAAIEGKLEDAEMITDDIFGLHIPAHVPGVPD HILQPENTWTNKEEYKEKAVYLANEFKENFKKFAHTDAIAQAGGPLV 28 L LI LI LI LI LI II II II II II II II II II II II II II II II II II II II II II I LI II II II II
75. AGATGAAGTCGATCGGCTCATGGATCC 160 GCTTACCGAAAGCCAGACTCAGCAA SigB UR BamHi TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC 161 ATGAGCCGATCGACTTCATCTTTAG 10 20 30 i m 78 JP 2005 521407 A 2005 7 21 BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC 162 GAAGATCCCTCGATGGAGTTAATGT ACATTAACTCCATCGAGGGATCTTCGGATCC 163 TCATGGCTGTCATGGCGCATTAACG GCTTCGGTCGACTTTGCCGTCTGGATATGCGTCTCTCG GTCAAAGAGCTCTATGACAGCCTCCTCAAATTGCAGG 165 TTCCATGTCGACGCTGTGCAAAACCGCCGGCAGCGCC EcoRI ACATTCGAATTCAGCAGGTCAATCAGCTCGCTGACGC CCAGCACTGCGCTCCCTCACCCGAAGGATCC GCTTACCGAAAGCCAGACTCAGCAA TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC TTCGGGTGAGGGAGCGCAGTGCTGG CGTTAATGCGCCATGACAGCCATGAGGATCC 170 TCGAGAGATCCGGATGGTTTTCCTG IN CAGGAAAACCATCCGGATCTCTCGAGGATCC 169 TCATGGCTGTCATGGCGCATTAACG AGTCAT AAGCTTTCTGGCGTTTGATTTCATCAACGGG CAGCGCGACTTGTTAAGGGACAATA 173 GGCTGCTGTGATGAACTTTGTCGGA 174
76. AGGAAGC AATGCGATGGGTATGTTTCAGGCATTTTTAAATGAAGATGTTGAACTGATCGGCGCTG AAGCAGCAGGAAAAGGAATTGATACACCTCTTCATGCCGCCACTATTTCGAAAGGAA CCGTAGGGGTTATTCACGGTTCATTGACTTATCTCATTCAGGATGAGTTCGGGCAAAT TATTGAGCCCTACTCTATTTCAGCCGGTCTCGACTATCCTGGAATCGGTCCGGAGCA TGCATATTTGCATAAAAGCGGCCGTGTCACTTATGACAGTATAACCGATGAAGAAGC GGTGGATGCATTAAAGCTTTTGTCAGAAAAAGAGGGGATTTTGCCGGCAATCGAATC TGCCCATGCGTTAGCGAAAGCATTCAAACTCGCCAAAGGAATGGATCGCGGTCAACT CATTCTCGTCTGTTTATCAGGCCGGGGAGACAAGGATGTCAACACATTAATGAATGTA TTGGAAGAAGAGGTGAAAGCCCATGTTTAAATTGGATCTTCAACCATCAGAAAAATTG TTTATCCCGTTTATTACGGCGGGCGATCCAGTTCCTGAGGTTTCGATTGAACTGGCG AAGTCACTCCAAAAAGCAGGCGCCACAGCATTGGAGCTTGGTGTTGCATACTCTGAC CCGCTTGCAGACGGTCCGGTGATCCAGCGGGCTTCAAAGCGGGCGCTTGATCAAGG AATGAATATCGTAAAGGCAATCGAATTAGGCGGAGAAATGAAAAAAAACGGAGTGAA TATTCCGATTATCCTCTTTACGTATTATAATCCTGTGTTACAATTGAACAAAGAATACTT TTTCGCTTTACTGCGGGAAAATCATATTGACGGTCTGCTTGTTCCGGATCTGCCATTA GAAGAAAGCAACAGCCTTCAAGAGGAATGTAAAAGCCATGAGGTGACGTATATTTCTT TAGTTGCGCCGACAAGCGAAAGCCGTTTGAAAACCATTATTGAACAAGCCGAGGGGT TCGTCTACTGTGTATCTTCTCTGGGTGTGACCGGTGTCCGCAATGAGTTCAATTCATC CGTGTACCCGTTCATTCGTACTGTGAAGAATCTCAGCACTGTTCCGGTTGCTGTAGG GTTCGGTATATCAAACCGTGAACAGGTCATAAAGATGAATGAAATTAGTGACGGTGTC GTAGTGGGAAGTGCGCTCGTCAGAAAAATAGAAGAATTAAAGGACCGGCTCATCAGC GCTGAAACGAGAAATCAGGCGCTGCAGGAGTTTGAGGATTATGCAATGGCGTTTAGC GGCTTGTACAGTTTAAAA 89 10 2
77. ATTTA ACATTTGTCAATGAACATGGGGCGCGAGCTGTACTTATCGGTGAATCATTGATGAGA CAAACTTCTCAGCGTAAAGCAATCCATGCTTTGTTTAGGGAGTGAGGTTGTGAAGAAA CCGGCATTAAAATATTGCGGTATTCGGTCACTAAAGGATTTGCAGCTTGCGGCGGAA TCACAGGCTGATTACCTAGGATTTATTTTTGCTGAAAGCAAACGAAAAGTATCTCCGG AAGATGTGAAAAAATGGCTGAACCAAGTTCGTGTCGAAAAACAGGTTGCAGGTGTTTT TGTTAATGAATCAATAGAGACGATGTCACGTATTGCCAAGAGCTTGAAGCTCGACGTC ATTCAGCTTCACGGTGATGAAAAACCGGCGGATGTCGCTGCTCTTCGCAAGCTGACA GGCTGTGAAATATGGAAGGCGCTTCACCATCAAGATAACACAACTCAAGAAATAGCC CGCTTTAAAGATAATGTTGACGGCTTTGTGATTGATTCATCTGTAAAAGGGTCTAGAG GCGGAACTGGTGTTGCATTTTCTTGGGACTGTGTGCCGGAATATCAGCAGGCGGCTA TTGGTAAACGCTGCTTTATCGCTGGCGGCGTGAATCCGGATAGCATCACACGCCTAT TGAAATGGCAGCCAGAAGGAATTGACCTTGCCAGCGGAATTGAAAAAAACGGACAAA AAGATCAGAATCTGATGAGGCTTTTAGAAGAAAGGATGAACCGATATGTATCCATATC CGAATGAAATAGGCAGATACGGTGATTTTGGCGGAAAGTTTGTTCCGGAAACACTCA TGCAGCCGTTAGATGAAATACAAACAGCATTTAAACAAATCAAGGATGATCCCGCTTT TCGTGAAGAGTATTATAAGCTGTTAAAGGACTATTCCGGACGCCCGACTGCATTAACA TACGCTGATCGAGTCACTGAATACTTAGGCGGCGCGAAAAT CTATTTGAAACGAGAA GATTTAAACCATACAGGTTCTCATAAAATCAATAATGCGCTAGGTCAAGCGCTGCTTG CTAAAAAAATGGGCAAAACGAAAAT CATTGCTGAAACCGGTGCCGGCCAGCATGGTG TTGCCGCTGCAACAGTTGCAGCCAAATTCGGCTTTTCCTGTACTGTGTTTATGGGTGA AGAGGATGTTGCCCGCCAGTCTCTGAACGTTTTCCGCATGAAGCTTCTTGGAGCGGA GGTAGTGCCTGTAACAAGCGGAAACGGAACATTGAAGGATGCCACAAATGAGGCGA TCCGGTACTGGGT TCAGCATTGTGAGGATCACTTTTATATGATTGGATCAGTTGTCGGCCCGCATCCTTAT CCGCAAGTGGTCCGTGAATTTCAAAAAATGATCGGAGAGGAAGCGAAGGATCAGTTG AAACGTATTGAAGGCACTATGCCTGATAAAGTAGTGGCATGTGTAGGCGG
78. CAAAATATCTCTCATGA TTTAAAAACGCCGGTCATGGTCATCAGAGGCTATACACAATCAATTAAAGACGGGATT TTTCCTAAAGGAGACCTTGAAAACACTGTAGATGTTATTGAATGCGAAGCTCTTAAGC TGGAGAAAAAAATAAAGGATTTATTATATTTAACGAAGCTGGATTATTTAGCGAAGCAA AAAGTGCAGCACGACATGTTCAGTATTGTGGAAGTGACAGAAGAAGTCATCGAACGA TTGAAGTGGGCGCGGAAAGAACTATCGTGGGAAATTGATGTAGAAGAGGATATTTTG ATGCCGGGCGATCCGGAGCAATGGAACAAACTCCTCGAAAACATTTTGGAAAATCAA ATCCGCTATGCTGAGACAAAAATAGAAATCAGCATGAAACAAGATGATCGAAATATCG TGATCACCATTAAAAATGACGGTCCGCATATTGAAGATGAGATGCTCTCCAGCCTCTA TGAGCCTTTTAATAAAGGGAAGAAAGGCGAATTCGGCATTGGTCTAAGCATCGTAAAA CGAATTTTAACTCTTCATAAGGCATCTATCTCAATTGAAAATGACAAAACGGGTGTATC ATACCGCATAGCAGTGCCAAAA 17 LC LI LI LI II II II II II II II II II I I II II II II II II II II I II II II II II II II II II II II I 000 MKNKPLAFQI WVVISGILLAISILLLVLFSNTLRDFFTNETYTTIENEQHVLTEYRLPGSIE RRYYSEEATAPTTVRSVQ HVLLPENEEASSDKDLSILS SSFIHKVYKLADKQEAKKKR YSADVNGEKVFFVIKKGLSVNGQSAMMLSYALDSYRDDLAYTLFKQLLFIIAVVILLSWIPAI WLAKYLSRPLVSFEKHVKRISEQDWDDPVKVDRKDEIGKLGHTIEEMRQKLVQKDETER TLLQNISHDLKTPVMVIRGYTQSIKDGIFPKGDLENTVDVIECEALKLEKKIKDLLYLTKLDY LAKQKVQHDMFSIVEVTEEVIERLKWARKELSWEIVEEDILMPGDPEQWNKLLENILENQI RYAETKIEISMKQDDRNIVITIKNDGPHIEDEMLSSLYEPFNKGKKGEFGIGLSIVKRILTLHK ASISIENDKTGVSYRIAVPK 18
79. CATAACTTCGTATAATG 2106 R Bbsl p112UF gt p113DR 30 80 JP 2005 521407 2005 7 21 6 sigD 183 SigD UF ATATTGAAGTCGGCTGGATTGTGG SigD UR Bell GCGGCAGATCTCGGCGCATTAAGTCGTCA 184 SigpDF EcoRl GCGGCGAATTCTCTGCTGGAAAAAGTGATACA 185 10 SigD DR TICGCTGGGATAACAACAT Loxspc UF Bgll GCGGCAGATCTTAAGCTGGATCCATAACTTCG 187 Loxspc DR EcoRI GCGGCGAATTCATATGGCGGCCGCATAACTTC 188 SigD UO CAATTTACGCGGGGTGGTG 189 SigD DO GAATAGGTTACGCAGTIGTIG 190 Spc UR CTCCTGATCCAAACATGTAAG 191 Spc DF AACCCTTGCATATGTCTAG 20 81 JP 2005 521407 2005 7 21 RT prpC
80. CATCGAG CTGGGTAATAAGCGTTGGCAATT TAACCGCCAGTCAG GCTTTCTTTCACAGATGTGGATTGG CGATAAAAAACAACTGCTGACGCCGCTGCGCGATCAGT TCACCCGTGCACCGCT GGATAACGACATTGGCGTAAGTGAAGCGACCCG CATTGACCCTAAC GCCTGGGTCGAACGCTGGAAGGCG GCGGGCCATTACCAGGCCGAAGCAGCGTTGTTGCAGT GCACGGCAGATACACTTGCTGATGCGGT GCTGATTACGACCGCTCACGCGTGGCAGCATCAG GGGAAAACCTTATTTATCAGCCGGAAAACCTACCGGATTGATG GTAGTGGTCAAATGGCGATT ACCGTTGATGTTGAAGTGGCGAGCGATACACCGCATCCGGCGCGOATTGG CCTGAACTGCCA GCTGGCGCAGGTAGCAGAGCGG GTAAACTGGCTCGGATTAGGGCCGCAAGAAAACTATCCC GACCGCCTTACTGCCGCCTGTITTGACCGCTGGGATCTGCCATTGTCAGACATGTATAC TACGTCTTCCCGAGCGAAAACGGTCTG CGCTGCGGGACGCGCGAATTGAATTATGGCCCACA CCAGTG GCGCGGCGACTTCCAGTTCAACATCAGCCGCTACAGTCAACAGCAACTGATGGAAA CCAGCCATCGCCATCTGCTGCACGCG GAAGAAGGCACATGGCTGAATATCGACGGTTTCCAT ATGGGGATTGGTGGCGACGACT CCTGGAGCCCGTCAGTATCGGCGGAATTCCAG CTGAGCG CCGGTCG CTACCATTACCAGTTGGTCTGGTGTCAAAAATAATAATAACCG GGCAGGCCATGTC TGCCCGTATTTCGCGTAAGGAAATCCATTATGTACTATTTCAAGCTAATTCCGGTGGAAACGAG GTCATCATTTCCTTCCGAAAAAACGGTTGCATTTAAATCTTACATATGTAATACTTTCAAAGACT ACATTTGTAAGATTTGATGTTTGAGTCGG CTGAAAGATCGTACGTACCAATTATTGTTTCGTGAT TGTTCAAGC CATAACACTGTAGGGATAGTGGAAAG AGTGCTTCATCTGGTTACGATCAATCAAA TATTCAAACGGAGGGAGACGATTTTGATGAAACCAGTAACGTTATACGATGTCG CAGAGTATG CCGGTGTCTCTTATCAGACCGTTTCCCG CGTGGTGAACCAGGCCAGCCACGTTTCTGCGAAAA CGCGGGAAAAAGTGGAAGCGGCGATG CAACTGGCGGGCAAACAGTCGTTGCTGATTGG CGTTGCCACCTCCAGTCTGGCCCTGCACGC GCCGTCGCAAATTGTCGCGGCGAT
81. CGAAAACTCTCAAGG ATCTTACCGCTGTT GAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGCAT CTTTTACTTTCACCAGCGTTTCTGGGTGAGCAAAAACAG GAAGGCAAAATGCCGCAAAAAAGG GAATAAGGG CGACACGGAAATGTTGAATACTCATACTCTTCCTTTTTCAATATTATTGAAGCATT TATCAGGGTTATT GTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAG G GGTTCCGCGCACATTTCCCCGAAAAGTGCCACCTGACGTCCAATAGAC CGAGAGTCTAATAGAATGAGGTCGAAAAGTAAATCGC GTAATAAGGTAATAGATTTACATTAGA AAATGAAAGGG GATTTTATGCGTGAGAATGTTACAGTCTATCCCGGCATTG CCAGTCGGGGAT ATTAAAAAGAGTATAGGTTTTTATTGCGATAAACTAG GTTTCACTTTGGTTCACCATGAAGATGG ATTCGCAGTTCTAATGTGTAATGAGGTT CGGATTCATCTATGGGAGGCAAGTGATGAAGGCTG GCGCTCTCGTAGTAATGATTCACCGGTTTGTACAGGTG CGGAGTCGTTTATTGCTGGTACTGC TAGTTGCCGCATTGAAGTAGAG GGAATTGATGAATTATATCAACATATTAAGCCTTTGGGCATT TTGCACCCCAATACATCATTAAAAGATCAGTGGTGGGATGAACGAGACTTTGCAGTAATTGATC CCGACAACAATTTGATTACAAATAAAAAG CTAAAATCTATTATTAATCTGTTCCTGCAGGAGAGA CCG U II II II II II II II II II II II II II II II 0 LI LI LI LI II 000 0 0 L LI LI LI L HHHHH LI LI LI
82. CTGAAACCTGCGAGTGCT ACACCTGTTATTGCAGCAAAATTTGTTGAGGTGCTTGAAGAGTCCGGATTGCCAAAAG GCGTAGTCAACTTTGTTCCGGGAAGCGGATCGGAAGTAGGCGACTATCTTGTTGACC ATCCGAAAACAAGCCTTATCACATTTACGGGATCAAGAGAAGTTGGTACGAGAATTTT CGAACGCGCGGCGAAGGTTCAGCCGGGCCAGCAGCATTTAAAGCGTGTCATCGCTG AAATGGGCGGTAAAGATACGGTTGTTGTTGATGAGGATGCGGACATTGAATTAGCGG CTCAATCGATCTTTACTTCAGCATTCGGCTTTGCGGGACAAAAATGCTCTGCAGGTTC ACGTGCAGTAGTTCATGAAAAAGTGTATGATCAAGTATTAGAGCGTGTCATTGAAATT ACGGAATCAAAAGTAACAGCTAAACCTGACAGTGCAGATGTTTATATGGGACCTGTCA TTGACCAAGGTTCTTATGATAAAATTATGAGCTATATTGAGATCGGAAAACAGGAAGG GCGTTTAGTAAGCGGCGGTACTGGTGATGATTCGAAAGGATACTTCATCAAACCGAC GATCTTCGCTGACCTTGATCCGAAAGCAAGACTCATGCAGGAAGAAATTTTCGGACC TGTCGTTGCATTTTGTAAAGTGTCAGACTTTGATGAAGCTTTAGAAGTGGCAAACAAT ACTGAATATGGTTTGACAGGCGCGGTTATCACAAACAACCGCAAGCACATCGAGCGT GCGAAACAGGAATTCCATGTCGGAAACCTATACTTCAACCGCAACTGTACAGGTGCT ATCGTCGGCTACCATCCGTTTGGCGGCTTCAAAATGTCGGGAACGGATTCAAAAGCA GGCGGGCCGGATTACTTGGCTCTGCATATGCAAGCAAAAACAATCAGTGAAATGTTC 54 II II LI II II II II I LI LI II II 57 JP 2005 521407 2005 7 21 MTTPYKHEPFTNFQDQNYVEAFKKALATVSEYLGKDYPLVINGERVETEAKIVSIN PADK EEVVGRVSKASQEHAEQAIQAAAKAFEEWRYTSPEERAAVLFRAAAKVRRRKHEFSALL VKEAGKPWNEADADTAEAIDFMEYYARQMIELAKGKPVNSREGEKNQYVYTPTGVTVVI PPWNFLFAIMAGTTVAPIVTGNTVVLKPASATPVIAAKFVEVLEESGLPKGVVNFVPGSGS EVGDYLVDHPKTSLITFTGSREVGTRIFERAAKVQPGQQHLK
83. GACGCAGAAACAATGATGTATGAAAAAATCAGCGGCGGTGAAGAAGAATGGC GCGTACATTTAGTGCAAGCCGTACAAGCCGGGATGGAAAAGGAAGAATTGTTCACTTTT ACGAACAGACTCAAGAAAGAACAGCCTGAAACTGCCTCTTACCGCAACCGCAAACTGA CGGAATCCAATATAGAAGAATGGAAAGCGCTGATGGCGGAGGCAAGAGAAATCGGCTT GTCTGTCCATGAAGTCAAATCCTTTTTAAAAACAAAGGGAAGA 3 10 20 30 37 JP 2005 521407 2005 7 21 MIGRIIRLYRKRKGYSINQLAVESGVSKSYLSKIERGVHT NPSVQFLKKVSATLEVELTELF DAETMMYEKISGGEEEWRVHLVQAVQAGMEKEELFTFTNRLKKEQPETASYRNRKLTES NIEEWKALMAEAREIGLSVHEVKSFLKTKGR 4 LI LI LI LI II II II II II II II II II II II II II II II II ATGAAATTGAAATCTAAGTTGTTTGTTATTTGTTTGGCCGCAGCCGCGATTTTTACAGCG GCTGGCGTTTCTGCTAATGCGGAAGCACTCGACTTTCATGTGACAGAAAGAGGAATGA CG 13 LI LI LI LI II II II II II II II II II II II LI 20 MKLKSKLFVICLAAAAIFTAAGVSANAEALDFHVTERGMT 14 HHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHH LI II II
84. GATCC 119 phleo GCTTACCGAAAGCCAGACTCAGCAA YvfF yveK UR TTGCTGAGTCTGGCTTTCGGTAAGCGGATCC 120 phleo CCTGCTCACATGTGAGCGGAAGGTT YvfF yveK DF BamHI CGTTAATGCGCCATGACAGCCATGAGGATCC phleo GCCTTCAGCCTTCCCGCGGCTGGCT 121 YvfF yveK DR AGCCAGCCGCGGGAAGGCTGAAGGCGGATCC 122 phleo TCATGGCTGTCATGGCGCATTAACG DHB DFfus phleo 20 YviF yeK DR CAAGCACTGCAGCCCACACTTCAGGCGGCTCAGGTC GAGATATCTAGAATGGTATGAAGCGGAATTCCCG E YvfF yve DR _ Kpnl ATAAACGGTACCCCCCTATAGATGCGAACGTTAGCCC 7 077 7 UF EcoRI AAGGAGGAATTCCATCTTGAGGTATACAAACAGTCAT 7 07 T UF BamHi TCTCCGAGAAAGACAGGCAGGATCGGGATCC AAGGACGGTACCGGCTCATTACCCTCTTTTCAAGGGT pro7 UF ACCAAAGCCGGACTCCCCCGCGAGAGGATCC 130 phleo TCTCGCGGGGGAGTCCGGCTTTGGT 2 pro7 DF BamHI CGTTAATGCGCCATGACAGCCATGA u _ 132 2 pro7 DR TATGGTACATTGTGTACCCCGTATGGGATCC 133 phleo TCATGGCTGTCATGGCGCATTAACG pro7 DR ___ Psil GTCAACCTGCAGAGCGGCCCAGGTACAAGTTGGGGA pro7 UF GGATCAGAGCTCGCTTGTCCTCCTGGGAACAGCCGG 2 pro7 DR Ps TATATGCTGCAGGGCTCAGACGGTACCGGTTGTTCCT TCTAGA BamHI GGATCC SacI GAGCTC Asp718 GGTACC PstI CTGCAG Hindllli AAGCTT 77 JP 2005 521407 2005 7 21 4 POR
85. GCCGGATT TATGAGCGAGCTGCCAAAGTGCAGCCGGGCCAAAAATGGCTCAAACGGGTAATTGC AGAAATGGGCGGAAAAGACACAGTGCTTGTCGACAAGGACGCTGATCTTGACCTTGC TGCATCCTCTATCGTGTATTCAGCATTTGGATATTCAGGACAGAAGTGTTCTGCGGGC TCCCGCGCGGTCATTCATCAGGATGTGTATGATGAAGTGGTGGAAAAAGCTGTGGCG CTGACCAAAACGCTGACTGTCGGCAATCCAGAAGATCCTGATACGTATATGGGTCCC GTGATTCATGAAGCATCCTACAACAAAGTGATGAAATACATTGAAATCGGCAAATCTG AAGGCAAGCTATTGGCCGGCGGAGAAGGCGATGATTCAAAAGGCTACTTTATTCAGC CGACGATCTTTGCAGATGTTGATGAAAACGCCCGCTTGATGCAGGAAGAAATTTTCG GCCCGGTTGTTGCGATTTGCAAAGCGCGTGATTTCGATCATATGCTGGAGATTGCCA ATAACACGGAATACGGATTAACAGGTGCGCTTCTGACGAAAAACCGTGCGCACATTG AACGGGCGCGCGAGGATTTCCATGTCGGAAACCTATATTTTAACAGAGGATGTACCG GAGCAATTGTCGGCTATCAGCCGTTCGGCGGTTTTAATATGTCAGGAACAGACTCAA AAGCAGGCGGTCCCGATTACTTAATTCTTCATATGCAAGCCAAAACAACGTCCGAAG CTTTT 31 LI I II LI II II II II II II II II II II II II II II II I LI I LI LI II II MTVTYAHEPFTDFTEAKNKTAFGESLAFVNTQLGKHYPLVINGEKIETDRKIISINPANK EEHGYASTADQELAEKAMQAALQAFDSWKKQRPEHRANILFKAAAILRRRKHEFSSYLV KEAGKPWKEADADTAEAIDFLEFYARQMLKLKEGAPVKSRAGEVNQYHYEALGVGIVISP FNFPLAIMAGTAVAAIVTGNTILLKPADAAPVVAAKFVEVMEEAGLPNGVLNYIPGDGAEIG DFLVEHPKTRFVSFTGSRAVGCRIYERAAKVQPGQKWLKRVIAEMGGKDTVLVDKDADL DLAASSIVYSAFGYSGQKCSAGSRAVIHQDVYDEVVEKAVALTKTLTVGNPEDPDTYMG PVIHEASYNKVMKYIEIGKSEGKLLAGGEGDDSKGYFIQPTIFADVDENARLMQEEIFGPV VAICKARDFDHMLEIANNTEYGLTGALLTKNRAHIERAREDFHVGNLYFNRGCTGAIVGY QPFGGFNMSGTDSKAGGPDYLILHMQAKTTSEAF
86. GGATCGTTCTCTTGAACTTGGTGAATACTTTAAA AGCCAGCTTGAGAGTATTGACAGCCCTGTCATTAAAGAAGTCCGOGGCAGAGGGCI GTTTATCGGTGTGGAATTGACTGAAGCGGCACGT CCGTATTGTGAGCGTTTGAAGGA AGAGG GACTITTATGCAAGGAAACGCATGATACAGTCATTCGTTTTGCACCGCCATTA ATCATTTCCAAAGAGGACTTG GATTGGGCGATAGAGAAAATTAAGCACGTGCTGCGA AACGCA 33 I LI LI II II II II II II II II II II II II II II II II II 1 I II II 1 1 II II II MTALSKSKENDQTSHYGANNYHPLPIVISEALGAWVKDPEGNEYMDMLSAYSAVNQGHR HPKIIQALKDQADKITLTSRAFHNDQLGPFYEKTAKLTGKEMILPMNTGAEAVESAVKAAR RWAYEVKGVADNQAEIIACVGNFHGRTMLAVSLSSEEEYKRGFGPMLPGIKLIPYGDVEA LROAITPNTAAFLFEPIQGEAGIVIPPEGFLQEAAAICKEENVLFIADEIQTGLGRT GK TEACDWDGIVPDMYILGKALGGGVFPISCIAADREILGVFNPGSHGS TFGGNPLACAVS ASLEVLEDEKLADRSLELGEYFKSELESIDSPVIKEVRGRGLFIGVELTEAARPYCERLK EEGLLCKETHDTVIRFAPPLIISKEDLDWAIEKIKHVLRNA 84 HHHHHHHHHHHH II III II II III 1II I1 II 00000 I LI II II II II II II II II 10 20 30 50 JP 2005 521407 2005 7 21 ATGGATAAAACGATTTCGGTTATTGGAATGCCAATGGATTTAGGACAAGCACGACGC GGAGTGGATATGGGCCCGAGTGCCATCCGGTACGCTCATCTGATCGAGAGGCTGTC AGACATGGGGTATACGGTTGAAGATCTCGGTGACATTCCGATCAATCGCGAAAAAAT CAAAAATGACGAGGAACTGAAAAACCTGAATTCCGTTTT
87. GGCATTCCTTTTGTCGGCGGAGCTGTC GGGTACTTAAGCTATGATATGATCCCGCTGATTGAGCCTTCTGTTCCTTCGCATACCA AAGAAACAGACATGGAAAAGTGTATGCTGTTTGTTTGCCGGACATTAATTGCGTATGA TCATGAAACCAAAAACGTCCACTTTATCCAATATGCAAGGCTCACTGGAGAGGAAACA AAAAACGAAAAAATGGATGTATTCCATCAAAATCATCTGGAGCTTCAAAATCTCATTGA AAAAATGATGGACCAAAAAAACATAAAAGAGCTGTTTCTTTCTGCTGATTCATACAAGA CACCCAGCTTTGAGACAGTATCTTCTAATTATGAAAAATCGGCTTTTATGGCTGATGTA GAAAAAATCAAAAGCTATATAAAAGCAGGCGATATCTTCCAGGGTGTTTTATCACAAA AATTTGAGGTGCCGATAAAAGCAGATGCTTTTGAGTTATACCGAGTGCTTAGGATCGT CAATCCTTCGCCGTATATGTATTATATGAAACTGCTAGACAGAGAAATAGTCGGCAGC TCTCCGGAACGGTTAATACACGTTCAAGACGGGCACTTAGAAATCCATCCGATTGCC GGTACGAGAAAACGCGGTGCAGACAAAGCTGAAGATGAGAGACTGAAGGTTGAGCT CATGAAGGATGAAAAAGAAAAAGCGGAGCATTACATGCTCGTTGATCTTGCCCGAAA CGATATCGGCAGAGTAGCAGAGTATGGTTCTGTTTCTGTGCCGGAGTTCACAAAAAT TGTTTCCTTTTCACATGTCATGCACATTATCTCGGTGGTTACAGGCCGATTGAAAAAA GGGGTTCATCCTGTCGATGCACTGATGTCTGCTTTCCCGGCGGGGACTTTAACAGGC GCACCCAAAATCCGTGCCATGCAGCTTTTGCAAGAACTCGAGCCAACACCGAGAGAG ACATACGGAGGGTGTATTGCCTACATTGGGTTTGACGGGAATATCGACTCTTGTATTA CGATTCGCACGATGAGTGTAAAGAACGGTGTTGCATCGATACAGGCAGGTGCTGGC ATTGTTGCTGATTCTGTTCCGGAAGCCGAATACGAAGAAAGCTGTAATAAAGCCGGT GCGCTGCTGAAAACGATTCATATTGCAGAAGACATGTTTCATAGCAAGGAGGATAAA GCTGATGAACAGATTTCTACAATTGTGCGTTGACGGAAAAACCCTTACTGCCGGTGA GGCTGAAACGCTGATGAATATGATGATGGCAGCGGAAATGACTCCTTCTGAAATGGG GGGGATATTGTCAATTCTTGCTCATCGGGGGGAGACGCCAGAAGAGCTTGCGGGTT TTGTGAAGGCAATGCGGGCACACGCTCTTACAGTCGATGGACTTCCTGATATTGTTG ATACATGCGGAACAGGGGGAGACGGTATTTCCACTTTTAATATC
88. GGCGCTTTCGCTTGTGCTGCCGCATCTGAAAGGAAAACTTCACGG CCTCGCCTTGCGTGTCCCTGTTCCGAACGTCTCATTGGTTGATCTCGTTGTTGATCTG AAAACGGATGTTACGGCTGAAGAAGTAAACGAGGCATTTAAACGCGCTGCCAAAACG TCGATGTACGGTGTACTTGATTACTCAGATGAACCGCTC GTTTCGACTGATTATAATACGAATCCGCATTCAGCGGTCATTGACGGGCTTACAACAA TGGTAATGGAAGACAGGAAAGTAAAGGTGCTGGCGTGGTATGACAACGAATGGGGC TACTCCTGCAGAGTTGTTGATCTAATCCGCCATGTAGCGGCACGAATGAAACATCCG TCTGCTGTA 23 I LI LI II MI II II MKVKVAINGFGRIGRMVFRKAMLDDQIQVVAINASYSAETLAHLIKYDTIHGRYDKEVVA GEDSLIVNGKKVLLLNSRDPKQLPWREYDIDIVVEATGKFNAKDKAMGHIEAGAKKVILT APGKNEDVTIVMGVNEDQFDAERHVIISNASCTTNCLAPVVKVLDEEFGIESGLMTTVHAY TNDQKNIDNPHKDLRRARACGESIIPTTTGAAKALSLVLPHLKGKLHGLALRVPVPNVSLV DLVVDLKTDVTAEEVNEAFKRAAKTSMYGVLDYSDEPLVSTDYNTNPHSAVIDGLTTMVM EDRKVKVLAWYDNEWGYSCRVVDLIRHVAARMKHPSAV 24 1 1 L I 10 20 30 45 JP 2005 521407 A 2005 7 21 ATGACGAAGGAATTTGAGTTTTTAAAAGCAGAGCTTAATAGTATGAAAGAAAACCATA CATGGCAAGACATAAAACAGCTTGAATCTATGCAGGGCCCATCTGTCACAGTGAATC ACCAAAAAGTCATTCAGCTATCTTCTAATAATTACCTCGGATTCACTTCACATCCTAGA CTCA
89. GGCGGGAAATGAAAAACT CGCGCAAAAGGTCAACAAAGTCATTGAAGAGAAAAAATTCCCGCTTGTCCTGGGCGG TGACCACAGTATTGCGATCGGCACGCTTGCAGGCACAGCGAAGCATTACGATAATCT CGGCGTCATCTGGTATGACGCGCACGGCGATTTGAATACACTTGAAACTTCACCATC GGGCAATATTCACGGCATGCCGCTCGCGGTCAGCCTAGGCATTGGCCACGAGTCAC TGGTTAACCTTGAAGGCTACGCGCCTAAAATCAAACCGGAAAACGTCGTCATCATTG GCGCCCGGTCACTTGATGAAGGGGAGCGCAAGTACATTAAGGAAAGCGGCATGAAG GTGTACACAATGCACGAAATCGATCGTCTTGGCATGACAAAGGTCATTGAAGAAACC CTTGATTATTTATCAGCATGTGATGGCGTCCATCTGAGCCTTGATCTGGACGGACTTG ATCCGAACGACGCACCGGGTGTCGGAACCCCTGTCGTCGGCGGCATCAGCTACCGG GAGAGCCATTTGGCTATGGAAATGCTGTATGACGCAGGCATCATTACCTCAGCCGAA TTCGTTGAGGTTAACCCGATCCTTGATCACAAAAACAAAACGGGCAAAACAGCAGTA GAGCTCGTAGAATCCCTGTTAGGGAAGAAGCTGCTG 35 I LI II II LI II II II II II II II II II II II II II II II L II II II MDKTISVIGMPMDLGQARRGVDMGPSAIRYAHLIERLSDMGYTVEDLGDIPINREKIKND EELKNLNSVLAGNEKLAQKVNKVIEEKKFPLVLGGDHSIAIGTLAGTAKHYDNLGVIWYD AHGDLNTLETSPSGNIHGMPLAVSLGIGHESLVNLEGYAPKIKPENVVIIGARSLDEGER KYIKESGMKVYTMHEIDRLGMTKVIEETLDYLSACDGVHLSLDLDGLDPNDAPGVGTPVV GGISYRESHLAMEMLYDAGIITSAEFVEVNPILDHKNKTGKTAVELVESLLGKKLL 36 LI LI II II II II II II II II II II II II 000000000000 II II II II II II
90. GRPFLFSTSHPPAVTAACMEAIDVLLEEPEHMERLWEN TAYFKAMLVKMGLTLTKSETPILPILIGDEGVAKQFSDQLLSRGVFAQSIVFPTVAKGKARI RTIITAEHTKDELDQALDVIEKTAKELQLL 26 10 20 30 46 JP 2005 521407 2005 7 21 ATGAACTCAGTTGATTTGACCGCTGATTTACAAGCCTTATTAACATGTCCAAATGTGC GTCATAATTTATCAGCAGCACAGCTAACAGAAAAAGTCCTCTCCCGAAACGAAGGCAT TTTAACATCCACAGGTGCTGTTCGCGCGACAACAGGCGCTTACACAGGACGCTCACC TAAAGATAAATTCATCGTGGAGGAAGAAAGCACGAAAAATAAGATCGATTGGGGCCC GGTGAATCAGCCGATTTCAGAAGAAGCGTTTGAGCGGCTGTACACGAAAGTTGTCAG CTATTTAAAG GAGCGAGATGAACTGTTTGTTTTCGAAGGATTTGCCGGAGCAGACGA GAAATACAG GCTGCCGATCACTGTCGTAAATGAGTTCGCATGGCACAATTTATTTGCG CGGCAGCTGTTTATCCGTCCGGAAGGAAATGATAAGAAAACAGTTGAGCAGCCGTTC ACCATTCTTTCTGCTCCGCATTTCAAAGCGGATCCAAAAACAGACGGCACTCATTCCG AAACGTTTATTATTGTCTCTTTCGAAAAGCGGACAATTTTAATCGGCGGAACTGAGTA TGCCGGTGAAATGAAGAAGTCCATTTTCTCCATTATGAATTTCCTGCTGCCTGAAAGA GATATTTTATCTATGCACTGCTCCGCCAATGTCGGTGAAAAAGGCGATGTC GCCCTTT TCTTCGGACTGTCAGGAACAGGAAAGACCACCCTGTCGGCAGATGCTGACCGCAAG CTGATCGGTGACGATGAACATGGCTGGTCTGATACAGGCGTCTTTAATATTGAAGGC GGATGCTACGCTAAGTGTATTCATTTAAGCGAGGAAAAGGAGCCGCAAATCTTTAAC GCGATCCGCTTCGGGTCTGTTCTCGAAAATGTCGTTGTGGATGAAGATACACGCGAA GCCAATTATGATGATTCCTTCTATACTGAAAACACGCGGGCAGCTTACCCGATTCATA TGATTAATAACATCGTG
91. I II II II II II II II II 0010 n n LI II II MKKPALKYCGIRSLKDLQLAAESQADYLGFIFAESKRKVSPEDVKKWLNQVRVEKQVAG VFVNESIETMSRIAKSLKLDVIQLHGDEKPADVAALRKLTGCEIWKALHHQDNTTQEIARF KDNVDGFVIDSSVKGSRGGTGVAFSWDCVPEY QQAAIGKRCFIAGGVNPDSITRLLKWQ PEGIDLASGIEKNGQKDQNLMRLLEERMNRYVSISE 51 GTGATCACAAGAGATTTTTTCTTATTTTTATCCAAAAGCGGCTTTCTCAATAAAATGGC GAGGAACTGGGGAAGTCGGGTAGCAGCGGGTAAAATTATCGGCGGGAATGACTTTA ACAGTTCAATCCCGACCATTCGACAGCTTAACAGCCAAGGCTTGTCAGTTACTGTCGA TCATTTAGGCGAGTTTGTGAACAGCGCCGAGGTCGCACGGGAGCGTACGGAAGAGT 30 GCATTCAAACCATTGCGACCATCGCGGATCAGGAGCTGAACTCACACGTTTCTTTAAA AATGACGTCTTTAGGTTTGGATATAGATATGGATTTGGTGTATGAAAATATGACAAAAA TCCTTCAGACGGCCGAGAAACATAAAATCATGGTCACCATTGACATGGAGGACGAAG TCAGATGCCAGAAAACGCTTGATATTTTCAAAGATTTCAGAAAGAAATACGAGCATGT GAGCACAGTGCTGCAAGCCTATCTGTACCGGACGGAAAAAGACATTGACGATTTGGA TTCTTTAAACCCGTTCCTTCGCCTTGTAAAAGGAGCTTATAAAGAATCAGAAAAAGTA GCTTTCCCGGAGAAAAGCGATGTCGATGAAAATTACAAAAAAATCATCCGAAAGCAG CTCTTAAACGGTCACTATACAGCGATTGCCACACATGACGACAAAATGATCGACTTTA CAAAGCAGCTTGCCAAGGAACATGGCATTGCCAATGACAAGTTTGAATTTCAGATGCT GTACGGCATGCGGTCGCAAACCCAGCTCAGCCTCGTAAAAGAAGGTTATAACATGAG AGTCTACCTGCCATACGGCGAGGATTGGTACGGC
92. II LI II II II II II II II II II JP 2005 521407 2005 7 10 20 30 50 JP 2005 521407 A 2005 7 21 18 10
93. MYEFKQKMFVSA MMYYKRAEKNLALVSDDIEKAEFAFKMAEIFYNLKQTYVSMSYAVQALETYQMYETYTVR RIQCEFVIAGNYDDMQYPERALPHLELALDLAKKEGNPRLISSALYNLGNCYEKMGELQK AAEYFGKSVSICKSEKF DNLPHSIYSLTQVLYKQKNDAEAQKKYREGLEIARQYSDELFVE LFQFLHALYGKNIDTESVSHTFQFLEEHMLYPYIEELAHDAAQF YIENGQPEKALSFYEKM VHAQKQIQRGDCLYEI 16 L II LI II II II II II II II II II II LI II II II II I LI II II II II II II II II II II I LI II II II II LI LI LI LI II II II II I II II II II II II II II II I LI 10 20 30 41 JP 2005 521407 2005 7 21 ATGAAAAACAAGCCGCTCGCGTTTCAGATATGGGTTGTCATATCCGGCATCCTGTTAG CGATATCGATTTTACTGCTTGTGTTATTTTCAAACACGCTGCGAGATTTTTTCACTAAT GAAACGTATACGACGATTGAAAATGAGCAGCATGTTCTGACAGAGTACCGCCTGCCA GGTTCGATTGAAAGGCGCTATTACAGCGAGGAAGCGACGGCGCCGACAACTGTCCG CTCCGTACAGCACGTGCTCCTTCCTGAAAATGAAGAGGCTTCTTCAGACAAGGATTTA AGCATTCTGTCATCTTCATTTATCCACAAGGTGTACAAGCTGGCTGATAAGCAGGAAG CTAAAAAGAAACGTTACAGCGCCGACGTCAATGGAGAGAAAGTGTTTTTTGTCATTAA AAAGGGACTTTCCGTCAATGGACAATCAGCGATGATGCTCTCTTACGCGCTTGATTCT TATCGGGACGATTTGGCCTATACCTTGTTCAAACAGCTTCTGTTTATTATAGCTGTCGT CATTTTATTAAGCTGGATTCCGGCTATTTGGCTTGCAAAGTATTTATCAAGGCCTCTTG TATCATTTGAAAAACACGTCAAACGGATTTCTGAACAGGATTGGGATGACCCAGTAAA AGTGGACCGGAAAGATGAAATCGGCAAATTGGGCCATACCATCGAAGAGATGCGCC AAAAGCTTGTGCAAAAGGATGAAACAGAAAGAACTCTATTG
94. NFQTIELDTWYRKSYFDHYMKEAKCSFSITANVNVTNLLAVLKKKKLKLYPAFIYIVSRVI HSRPEFRTTFDDKGQLGYWEQMHPCYAIFHQDDQTFSALWTEYSDDFSQFYHQYLLDA ERFGDKRGLWAKPDIPPNTFSVSSIPWVRFSTFNLNLDNSEHLLPIITNGKYFSEGRETFL PVSCKFTMQCVTAIMPALL 59 50 23 JP 2005 521407 2005 7 21 a a n E n DE n m Eee r1 r1 u nn r1 r1 r1 noon 10 20 30 50 JP 2005 521407 A 2005 7 2
95. PGDKLLLCSDGLTNKVEGTELKDILQSDSAPQEKVNLLVDKANQNGGEDNITAVLL ELALQVEEGEDQC 30 II VU III DE UU DU DE VD VD GU DS UD VD VE DE UU DE PV LI LI II II II II II II 000 I II 1 I LI LI 10000 10 20 n 48 JP 2005 521407 2005 7 21 ATGACAGTCACATACGCGCACGAACCATTTACCGATTTTACGGAAGCAAAGAATAAAA CTGCATTTGGGGAGTCATTGGCCTTTGTAAACACTCAGCTCGGCAAGCATTATCCGC TTGTCATAAATGGAGAAAAAATTGAAACGGACCGCAAAATCATTTCTATTAACCCGGC AAATAAAGAAGAGATCATTGGGTACGCGTCTACAGCGGATCAAGAGCTTGCTGAAAA AGCGATGCAAGCCGCATTGCAGGCATTTGATTCCTGGAAAAAACAAAGACCGGAGCA CCGCGCAAATATTCTCTTTAAGGCAGCGGCTATTTTGCGCAGAAGAAAGCATGAATTT TCAAGCTATCTTGTGAAGGAAGCAGGAAAACCGTGGAAGGAAGCAGATGCGGACAC GGCTGAAGCGATAGACTTTTTAGAGTTCTACGCGCGCCAAATGTTAAAGCTCAAGGA AGGGGCTCCGGTGAAGAGCCGTGCTGGCGAGGTCAATCAATATCATTACGAAGCGC TTGGCGTCGGCATCGTCATTTCTCCATTTAACTTCCCGCTCGCGATTATGGCGGGAA CAGCGGTGGCAGCGATTGTGACAGGAAATACGATTCTCTTAAAACCGGCTGACGCAG CCCCGGTAGTGGCAGCAAAATTTGTCGAGGTCATGGAGGAAGCGGGTCTGCCAAAC GGCGTTCTGAATTACATTCCGGGAGATGGTGCGGAGATCGGTGATTTCTTAGTTGAG CATCCGAAGACACGGTTTGTCTCATTTACAGGTTCCCGTGCAGTCGGCT
96. RI GTGACGGAATTCCACGTGCGTCTTATATTGCTGAGCTT 64 CGTTTTGGATCCAAAAACACCCCTTTAGATAATCTTAT im x 79 x 1 2 1 2 7 1 ATCAAAGGATCCGCTATGCTCCAAATGTACACCTITCCGT 66 1 Pst ATATTTCTGCAGGCTGATATAAATAATACTGTGTGTICC CATCTTGAATTCAAAGGGTACAAGCACAGAGACAGAG 6800 TGACTIGGATCCGGTAAGTGGGCAGTITGTGGGCAGT 69 TAGATAGGATCCTATTGAAAACTGTTTAAGAAGAGGA COAGAACTGCAGGAGCGAGGCGTCTCGCTGCCTGAAA 75 PPS UF PPS UR PPS DF PPS DR Bambi BamHI GACAAGGGATCCTGCCGCTTACCGGAAACGGA ACTGATGAGCTCTGCCTAAACAGCAAACAGCAGAAC 89 _ mHi ACGAATGGATCCATCATAAAGOCGCAGCAGATTAAATAT 81 amHi bal ACTGATTCTAGAGCCTTTITCTCTTGATGCAATTCTTC 83 Xbal AGCCTCTAGAGCCCAT TGAATCATTTGTTT 84 t SPB UR SPp DF SPB D PKS UF PKS UR PKS DF G GAGCCGGATCCTTAAGGATGTCGTTTTTGTGTCT BamHI GAGCCGGATCCATTTCGGGGTTCTCAAAAAAA 2 8 C n AUF AJ UR BamA GAAGTGGATCCTTTCACCGATCATAAAAGCCG _____ 24y DF TGAAAGGATCCATTTTTCATTGATTGTTAAGTC 5 147 DR GAAGTTAGAGCTCGGGEGGGCATAAATITOGCS Prieo UF BamHI GTTATGGATCCGATACAAGAGAGGTCTCTCS Spec UF Spec DR BamHI ACTGATGGATCCOATATGCAAGGGTTTATTGTTTIO 8 _ CssSUF_ Xbal _____ GCACGTTCTAGACCAGCGTCCCOTETGTTGTATCCAG 95 TGACAAGGATCCTGTATCATACCGCATAGCAGTGCC 98 10 20 30 73 JP 2005 521407 2005 7 21
97. RKAVKKLREALIEDPSMELM 10 II LI LI II II II Ooo LI OOO LI ATGGTTTTATTCTTTCAGATCATGGTCTGGTGCATCGTGGCCGGACTGGGGTTATACGT GTATGCCACGTGGCGTTTCGAAGCGAAGGTCAAAGAAAAAATGTCCGCCATTCGGAAA ACTTGGTATTTGCTGTTTGTTCTGGGCGCTATGGTATACTGGACATATGAGCCCACTTC CCTATTTACCCACTGGGAACGGTATCTCATTGTCGCAGTCAGTTTTGCTTTGATTGATG CTTTTATCTTCTTAAGTGCATATGTCAAAAAACTGGCCGGCAGCGAGCTTGAAACAGAC ACAAGAGAAATTCTTGAAGAAAACAACGAAATGCTCCACATGTATCTCAATCGGCTGAA AACATACCAATACCTATTGAAAAACGAACCGATCCATGTTTATTATGGAAGTATAGATGC TTATGCTGAAGGTATTGATAAGCTGCTGAAAACCTATGCTGATAAAATGAACTTAACGG CTTCTCTTTGCCACTATTCGACACAGGCTGATAAAGACCGGTTAACCGAGCATATGGAT GATCCGGCAGATGTACAAACACGGCTCGATCGAAAGGATGTTTATTACGACCAATACG GAAAAGTGGTTCTCATCCCTTTTACCATCGAGACACAGAACTATGTCATCAAGCTGACG TCTGACAGCATTGTCACGGAATTTGATTATTTGCTATTTACGTCATTAACGAGCATATAT GATTTGGTGCTGCCAATTGAGGAGGAAGGTGAAGGA 11 LI II II II II II II II II II II II II I LI 000 0000
98. RVIAEMGGKDTVVVDEDA DIELAAQSIFTSAFGFAGQKCSAGSRAVVHEKVYDQVLERVIEIT ESKVTAKPDSADVYMG PVIDQGSYDKIMSYIEIGKQEGRLVSGGTGDDSKGYFIKPTIFADLDPKARLMQEEIFGPVV AFCKVSDFDEALEVAN NTEYGLTGAVITNNRKHIERAKQEFHVGNLYFNRNCTGAIVGYH PFGGFKMSGTDSKAGGPDYLALHMQAKTISEMF 55 II II II II II II I II II II II II II II II II II II II II II II II II II II II II II II II II II LI L LI LI LI II II II II II ATGCAATCCTTGAATTATGAAGATCAGGTGCTTTGGACGCGCTGGAAAGAGTGGAAA GATCCTAAAGCCGGTGACGACTTAATGCGCCGTTACATGCCGCTTGTCACATATCAT GTAGGCAGAATTTCTGTCGGACTGCCGAAATCAGTGCATAAAGACGATCTTATGAGC CTTGGTATGCTTGGTTTATATGATGCCCTTGAAAAATTTGACCCCAGCCGGGACTTAA AATTTGATACCTACGCCTCGTTTAGAATTCGCGGCGCAATCATAGACGGGCTTCGTAA AGAAGATTGGCTGCCCAGAACCTCGCGCGAAAAAACAAAAAAGGTTGAAGCAGCAAT TGAAAAGCTTGAACAGCGGTATCTTCGGAATGTATCGCCCGCGGAAATTGCAGAGGA ACTCGGAATGACGGTACAGGATGTCGTGTCAACAATGAATGAAGGTTTTTTTGCAAAT CTGCTGTCAATTGATGAAAAGCTCCATGATCAAGATGACGGGGAAAACATTCAAGTCA TGATCAGAGATGACAAAAATGTTCCGCCTGAAGAAAAGATTATGAAGGATGAACTGAT TGCACAGCTTGCGGAAAAAATTCACGAACTCTCTGAAAAAGAACAGCTGGTTGTCAG TTTGTTCTACAAAGAGGAGTTGACACTGACAGAAATCGGACAAGTATTAAATCTTTCT ACGTCCCGCATATCTCAGATCCATTCAAAGGCATTATTTAAATTAAAGAATCTGCTGG AAAAAGTGATACAA 56 LI II II II II II II II II II II II II II 0000
99. TAAATCTCGCG CCGATCAACTGGGTGCCAGCGTGGTGG TGTCGATGGTAGAACGAAGCG GCGTCGAAGCCTGTAAAGCGGCGGTGCACAATCTT CTCGCG CAACGCGTCAGTGGGCTGATCATTAACTATCCGCTGGATGACCAG GATGCCATTGCTGTGGAA GCTGCCTGCACTAATGTTCCGG CGTTATTTCTTGATGTCTCT GACCAGACACCCATCAACAGTA TTATTTTCTCCCATGAAGACGGTACGCGACTGGGCGTGGAG CATCTGGTCGCATTGGGTCACC AGCAAATCGCGCTGTTAGCGGG CCCATTAAGTTCTGTCTCGGCGCGTCTGCGTCTGG CTGGC TGGCATAAATATCTCACTCGCAATCAAATTCAG CCGATAGCGGAACGGGAAGGCGACTGGAGT GCCATGTC CGGTTTTCAACAAACCATGCAAATGCTGAATGAGGGCATCGTTCCCACT GCGATG CTGGTTGCCAACGATCAGATG GCGCTGGGCGCAATGCG CGCCATTACCGAGTCCGGGCTGC GCGTTGGTGCGGATATCTCG GTAGTGGGATACGACGATACCGAAGACAGCTCATGTTATATCC CGCCGTCAACCACCATCAAACAGGATTTTCGCCTGCTGG GGCAAACCAGCGTGGACCGCTTG CTGCAACTCTCTCAGGGCCAGG CGGTGAAGGGCAATCAG CTGTTGCCCGTCTCACTGGTGAA AAGAAAAACCACCCTGGCGCCCAATACGCAAAC CGCCTCTCCCCGCGCGTTGGCCGATTCAT TAATGCAGCTGGCACGACAGGTTTCCC GACTGGAAAGCGGGCAGTGAGCGCAACG CAATTAA TGTGAGTTAGGCATCGCATCCTGCCTCGCG CGTTTCGGTGATGACGGTGAAAACCTCTGACAC ATGCAG CTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATG CCGGGAGCAGACAAGCCC GTCAGGGCGCGTCAG CGGGTGTTGGCGGGTGTCGGGGCG CAGCCATGACCCAGTCACGTAG CGATAGCGGAGTGTATACTGGCTTAACTATG CGGCATCAGAGCAGATTGTACTGAGAGTGCAC CATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCTCTTCC GCTTCCTCGCTCACTGACTCG CTGCGCTCGGTCGTTCG GCTGCGGCGAGCGGTATCAGCTCA CTCAAAGGCG GTAATACGGTTATCCACAGAATCAGGGG ATAACGCAGGAAAGAACATGTGAG CAAAAGG CCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTG CTGGCGTTTTTCCATAGG 10 20 30 85 JP 2005 521407 2005 7 21
100. TACTTTATGAGACGCCTTGCAGA ACGTCCGTCAAACATTGCATTTGCTTTCAAAGGAATGACAAAGAAG 52 40 HHHHHHHHHHHHHHHHHH 0000 I II II II II 56 JP 2005 521407 2005 7 21 MITRDFFLFLSKSGFLNKMARNWGSRVAAGKIIGGNDFNSSIPTIRQLNSQGLSVTVDHL GEFVNSAEVARERTEECIQTIATIADQELNSHVSLKMTSLGLDIDMDLVYENMTKILQTA EKHKIMVTIDMEDEVRCQKTLDIFKDFRKKYEHVSTVLQAYLYRTEKDIDDLDSLNPFLR LVKGAYKESEKVAFPEKSDVDENYKKIIRKQLLNGHYTAIATHDDKMIDFTKQLAKEHGI ANDKFEFQMLYGMRSQTQLSLVKEGYNMRVYLPYGEDWYGYFMRRLAERPSNIAFAFK GMTKK 53 HHHHHHHHHHHHHHHHHHHHHH HHHH H HHHHHHHHH ATGACAACACCTTACAAACACGAGCCATTCACAAATTTCCAAGATCAAAACTACGTGG AAGCGTTTAAAAAAGCGCTTGCGACAGTAAGCGAATATTTAGGAAAAGACTATCCGCT TGTCATTAACGGCGAGAGAGTGGAAACGGAAGCGAAAATCGTTTCAATCAACCCAGC TGATAAAGAAGAAGTCGTCGGCCGAGTGTCAAAAGCGTCTCAAGAGCACGCTGAGC AAGCGATTCAAGCGGCTGCAAAAGCATTTGAAGAGTGGAGATACACGTCTCCTGAAG AGAGAGCGGCTGTCCTGTTCCGCGCTGCTGCCAAAGTCCGCAGAAGAAAACATGAA TTCTCAGCTTTGCTTGTGAAAGAAGCAGGAAAGCCTTGGAACGAGGCGGATGCCGAT ACGGCTGAAGCGATTGACTTCATGGAGTATTATGCACGCCAAATGATCGAACTGGCA AAAGGCAAACCGGTCAACAGCCGTGAAGGCGAGAAAAACCAATATGTATACACGCCG ACTGGAGTGACAGTCGTTATCCCGCCTTGGAACTTCTTGTTTGCGATCATGGCAGGC ACAACAGTGGCGCCGATCGTTACTGGAAACACAGTGGTT
101. TAGAAT spc rfus GAATATTTCCC 203 000000 WE I I I III 111 111 III A II II LI III II II III II III I I II II II III II II I III 0000000000000000000000000000000000000000 50 JP 2005 521407 A 2005 7 21 82 10 20 C C C C C 83 JP 2005 521407 A 2005 7 21 GGGGATCTCTGCAGTGAGATCTGGTAATGACTCTCTAGCTTGAGGCATCAAATAAAACGAAAG GCTCAGTCGAAAGACTGGGCCTTTCGTTTTATCTGTTGTTTGTCGGTGAACGCTCTCCTGAGTA GGACAAATCCGCCGCTCTAGCTAAGCAGAAGGCCATCCTGACGGATGGCCTTTTTGCGTTTCT ACAAACTCTIGTTAACTCTAGAG CTGCCTGCCGCGTTTCGGTGATGAAGATCTTCCCGATGATT AATTAATTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATGCAGCAATGGCAAGAACGTTGC
102. TCAACGCCGCACAGGAGGCCGTTCAGCAGTATGGAGCCGGCACCGGATCAGT GAGAACGATTGCGGGTACATTTACAATGCATCAAGAGCTTGAGAAAAAGCTGGCAGC CTTTAAAAAAACGGAGGCGGCACTTGTATTCCAATCAGGCTTCACAACAAACCAAGG CGTACTTTCAAGTATTCTATCAAAAGAGGACATTGTCATCTCAGATGAATTGAACCAT GCCTCTATTATTGACGGAATTCGACTGACAAAGGCGGATAAAAAGGTGTATCAGCAC GTCAATATGAGTGATTTAGAGCGGGTGCTGAGAAAGTCAATGAATTATCGGATGCGT CTGATTGTGACAGACGGCGTATTTTCCATGGATGGCAACATAGCTCCTCTGCCTGATA TTGTAGAGCTCGCTGAGAAATATGACGCATTTGTGATGGTGGATGACGCCCATGCAT CCGGAGTACTTGGCGAAAACGGCAGGGGAACGGTGAATCACTTCGGTCTTGACGGC AGAGTGCATATTCAGGTCGGAACATTAAGCAAGGCAATCGGAGTGCTCGGCGGCTA CGCTGCAGGTTCAAAGGTGCTGATCGATTATTTGCGCCATAAAGGCCGTCCATTTTTA TTCAGCACATCTCATCCGCCGGCAGTCACTGCAGCTTGTATGGAAGCGATTGATGTC TTGCTTGAAGAGCCGGAGCATATGGAGCGCTTGTGGGAGAATACTGCCTATTTTAAA GCAATGCTTGTGAAAATGGGTCTGACTCTCACGAAGAGTGAAACGCCGATTCTTCCT ATTTTAATAGGTGATGAAGGTGTGGCAAAGCAATTTTCAGATCAGCTCCTTTCTCGCG GTGTTTTTGCCCAAAGTATCGTTTTCCCGACTGTAGCAAAGGGAAAAGCCAGAATTCG CACGATTATAACAGCAGAGCACACCAAAGATGAACTGGATCAGGCGCTTGATGTCAT CGAAAAGACGGCAAAGGAGCTCCAGCTATTG 25 I LI LI II II II II II II II II II II II II II II II II I LI II LI TKEFEFLKAELNSMKENHTWQDIKQLESMQGPSVTVNHQKVIQLSSNNYLGFTSHPRLI EAVQQYGAGTGSVRTIAGTFTMHQELEKKLAAFKKTEAALVFQSGFTTNQGVLSSI LSKEDIVISDELNHASIIDGIRL TKADKKVYQHVNMSDLERVLRKSMNYRMRLIVTDGVFS MDGNIAPLPDIVELAEKYDAFVMVDDAHASGVLGENGRGTVNHFGLDGRVHIQVGTLSK AIGVLGGYAAGSKVLIDYLRHK
103. TCAACGGCCTCGG CAATTGTTGCCTCGGCAGCTGGTGCGAAAATCGCTAAGCATGGCAATCGCTCTGTCT CTTCTAAAAGCGGAAGCGCTGATGTTTTAGAGGAGCTAGAGGTTTCTATTCAAACCAC TCCCGAAAAGGTCAAAAGCAGCATTGAAACAAACAACATGGGATTTCTTTTTGCGCCG CTTTACCATTCGTCTATGAAACATGTAGCAGGTACTAGAAAAGAGCTAGGTTTCAGAA CGGTATTTAATCTGCTTGGGCCGCTCAGCAATCCTTTACAGGCGAAGCGTCAGGTGA TTGGGGTCTATTCTGTTGAAAAAGCTGGACTGATGGCAAGCGCACTGGAGACGTTTC AGCCGAAGCACGTTATGTTTGTATCAAGCCGTGACGGTTTAGATGAGCTTTCAATTAC AGCACCGACCGACGTGATTGAATTAAAGGACGGAGAGCGCCGGGAGTATACCGTTT CACCCGAAGATTTCGGTTTCACAAATGGCAGACTTGAAGATTTACAGGTGCAGTCTCC GAAAGAGAGCGCTTATCTCATTCAGAATATTTTTGAAAATAAAAGCAGCAGTTCCGCT TTATCTATTACGGCTTTTAATGCGGGTGCTGCGATTTACACGGCGGGAATTACCGCCT CACTGAAGGAAGGAACGGAGCTGGCGTTAGAGACGATTACAAGCGGAGGCGCTGCC GCGCAGCTTGAACGACTAAAGCAGAAAGAGGAAGAGATCTATGCTTGAAAAAATCAT CAAACAAAAGAAAGAAGAAGTGAAAACACTGGTTCTGCCGGTAGAGCAGCCTTTCGA GAAACGTTCATTTAAGGAGGCGCCGGCAAGCCCGAATCGGTTTATCGGGTTGATTGC CGAAGTGAAGAAAGCATCGCCGTCAAAAGGGCTTATTAAAGAGGATTTTGTACCTGT GCAGATTGCAAAAGACTATGAGGCTGCGAAGGCAGATGCGATTTCCGTTTTAACAGA CACCCCGTTTTTTCAAGGGGAAAACAGCTATTTATCAGACGTAAAGCGTGCTGTTTCG ATTCCTGTACTTAGAAAAGATTTTATTATTGATTCTCTTCAAGTAGAGGAATCAAGAAG AATCGGAGCGGATGCCATATTGTTAATCGGCGAGGTGCTTGATCCCTTACACCTTCAT GAATTATATCTTGAAGCAGGTGAAAAGGGGATGGACGTGTTAGTGGAGGTTCATGAT GCATCAACGCTAGAACAAATATTGAAAGTGTTCACACCCGACATTCTCGGCGTAAATA 10 20 30 53 JP 2005 521407 2005 7 21 ATCGAAACCTAAAAACGTTTGAAACATCTGTAAAGCAGACAGAACAAATCGCATCTCT CGTTCCGAAAGAATCCTTGCTTGTCAGCGAAAGCGGAATCGGTTCTTTAGAAC
104. TCTCTGTCCAGCATTCCGAAAA GCTGGGCCGCCATATGAATTTTATGATGAAAAAAGGCAGCCTTTATTTAAAATATAAC GGCAACCTGTTGATTCACGGCTGTATTCCAGTTGATGAAAACGGCAATATGGAAACG ATGATGATTGAGGATAAACCGTATGCGGGCCGTGAGCTGCTCGATGTATTTGAACGA TTCTTGCGGGAAGCCTTTGCCCACCCGGAAGAAACCGATGACCTGGCGACAGATATG GCTTGGTATTTATGGACAGGCGAATACTCCTCCCTCTTCGGAAAACGCGCCATGACG ACATTTGAGCGCTATTTCATCAAAGAGAAGGAAACGCATAAAGAGAAGAAAAACCCGT ATTATTATTTACGAGAAGACGAGGCAACCTGCCGAAACATCCTGGCAGAATTCGGCC TCAATCCAGATCACGGCCATATCATCAACGGCCATACACCTGTAAAAGAAATCGAAG GAGAAGACCCAATCAAAGCAAACGGAAAAATGATCGTCATCGACGGCGGCTTCTCCA AAGCCTACCAATCCACAACAGGCATCGCCGGCTACACGCTGCTATACAACTCCTACG GCATGCAGCTCGTCGCCCATAAACACTTCAATTCCAAGGCAGAAGTCCTAAGCACCG GAACCGACGTCTTAACGGTCAAACGATTAGTGGACAAAGAGCTTGAGCGGAAGAAAG TGAAGGAAACGAATGTGGGTGAGGAATTGTTGCAGGAAGTTGCGATTTTAGAGAGTT TGCGGGAGTATCGGTATATGAAG 19 HHHHHHHHHHHH I II LI II II II II IL LI MI LI MFKNNVILLNSPYHAHAHKEGFILKRGWTVLESKYLDLLAQKYDCEEKVVTEIINLKAILNL PKGTEHFVSDLHGEYQAFQHVLRNGSGRVKEKIRDIFSGVIYDREIDELAALVYYPED KLKLIKHDFDAKEALNEWYKETIHRMIKLVSYCSSKYTRSKLRKALPAQFAYITEELLYK TEQAGNKEQYYSEIIDQIIELGQADKLITGLAYSVQRLVVDHLHVVGDIYDRGPQPDRIM EELINYHSVDIQWGNHDVLWIGAYSGSKVCLANIIRICARYDNLDIIEDVYGINLRPLLN LAEKYYDDNPAFRPKADENRPEDEIKQITKIHQAIAMIQFKLESPIIKRRPNFNMEERLL LEKIDYDKNEITLNGKTYQLENTCFATINPEQPDQLLEEEAEVIDKLLFSVQHSEKLGRH MNFMMKKGSLYLKYNGNLLIHGCIPVDENGNMETMMIEDKPYAGRELLDVFERFLREAF AHPEETDDLATDMAWYLWTGEYSSLFGKRAMTTFERYFIKEKE
105. THKEKKNPYYYLREDE ATCRNILAEFGLNPDHGHIINGHTPVKEIEGEDPIKANGKMIVIDGGFSKAYQSTTGIAGYT LLYNSYGMQLVAHKHFNSKAEVLSTGTDVLTVKRLVDKELERKKVKETNVGEELLQEVAI LESLREYRYMK 20 L II LI II II II II II II II II II II II II II II LI I LI II LI II II II II II II II II 10 20 30 50 43 JP 2005 521407 2005 7 21 ATGAAACGAGAAAGCAACATTCAAGTGCTCAGCCGTGGTCAAAAAGATCAGCCTGTG AGCCAGATTTATCAAGTATCAACAATGACTTCTCTATTAGACGGAGTATATGACGGAG ATTTTGAACTGTCAGAGATTCCGAAATATGGAGACTTCGGTATCGGAACCTTTAACAA GCTTGACGGAGAGCTGATTGGGTTTGACGGCGAATTTTACCGTCTTCGCTCAGACGG AACCGCGACACCGGTCCAAAATGGAGACCGTTCACCGTTCTGTTCATTTACGTTCTTT ACACCGGACATGACGCACAAAATTGATGCGAAAATGACACGCGAAGACTTTGAAAAA GAGATCAACAGCATGCTGCCAAGCAGAAACTTATTTTATGCAATT CGCATTGACGGAT TGTTTAAAAAGGTGCAGACAAGAACAGTAGAACTTCAAGAAAAACCTTACGTGCCAAT GGTTGAAGCGGTCAAAACACAGCCGATTTTCAACTTCGACAACGTGAGAGGAACGAT TGTAGGTTTCTTGACACCAGCTTATGCAAACGGAATCGCCGTTTCTGGCTATCACCTG CACTTCATTGACGAAGGACGCAATTCAGGCGGACACGTTTTTGACTATGTGCTTGAG GATTGCACGGTTACGATTTCTCAAAAAATGAACATGAATCTCAGACTTCCGAACACAG CGGATTTCTTTAATGCGAATCTGGATAACCCTGATTTTGCGAAAGATATCGAAACAAC TGAAGGAAGCCCTGAA 21 I LI LI II II II II II II II II II II II II II II II II II II I
106. TTITGGGGTTATTTA GGGGAGAAAACATAGGGGGGTACTACGACCTCCCCCCTAGGTGTCCATTGTCCATTGTCCAA ACAAATAAATAAATATTGGGTTTTTAATGTTAAAAG GTTGTTTTTTATGTTAAAGTGAAAAAAACA GATGTTGGGAG GTACAGTGATAGTTGTAGATAGAAAAGAAGAGAAAAAAGTTG CTGTTACTTTA AGACTTACAACAGAAGAAAATGAGATATTAAATAGAATCAAAGAAAAATATAATATTAGCAAATC AGATGCAACCGGTATTCTAATAAAAAAATATG CAAAGGAGGAATACGGTGCATTTTAAACAAAA AAAGATAGACAG CACTGGCATGCTGCCTATCTATGACTAAATTTTGTTAAGTGTATTAGCACCG TTATTAT TCATGAGCGAAAATGTAATAAAAGAAACTGAAAACAAGAAAAATTCAAGAGGACGT 84 JP 2005 521407 2005 7 21 AATTGGACATTTGTTTTATATCCAG AATCAGCAAAAGCCGAGTGGTTAGAGTATTTAAAAGAGT TACACATTCAATTIGTAGTGTCTCCATTACATGATAGGGATACT GATACAGAAGG TAG GATGAA AAAAGAGCATTAT CATATTCTAGTGATGTATGAGGGTAATAAAT CTTATGAACAGATAAAAATAA TTAACAGAAGAATTGAATGCGACTATTCCGCAGATTG CAGGAAGTGTGAAAGGTCTTGTGAGA TATATGCTTCACATGGAC GATCCTAATAAATTTAAATATCAAAAAGAAGATATGATAGTTTATGG CGGTGTAGATGTIGATGAATT ATTAAAGAAAACAACAACAGATAGATATAAATTAATTAAAGAAA TGATTGAGTTTATTGATGAACAAGGAATCGTAGAATTTAAGAGTTTAATG GATTATGCAATGAAG GGTTCCCGCTTTTATGTGATAACTCGG CGTATGTTATICAAGAATATAT AAAATCAAATCGGTATAAATCTG ACCGATAGATTTTGAATTTAGGTGTCACAAGACACT CTTTTT TCGCACCAGCGAAAACTGGTTTAAGCCGACTGGAGCTCCTGCACTGGATGGTG GCGCTGGAT GGTAAGCCGCTGGCAAG CGGTGAAGTGCCTCTGGATGTCG CTCCACAAGGTAAACAGTTGAT TGAACTGCCTGAACTACCGCAGCCGGAGAG CGCCGGGCAACTCTGGCTCACAGTACGCGTAG TGCAACCGAACGCGACCGCATGGTCAGAAGCCGGG CACATCAGCGCCTGGCAGCAGTGGCG TCTGGCGGAAAACCTCAGTGTGACGCTCCCCGCCG CGTCCCACGCCATCCCGCATCTGACCA CCAGCGAAATGGATTTTTG
107. VSESGIGSLEHLTFVNEHGARAVLIGESLMRQTSQ RKAIHALFRE 45 LI I LI II LI LI II II I I II I II II II II I II II I II II II II II II II I I II I I II II II II I n D MNRFLQLCVDGKTLTAGEAETLMNMMMAAEMTPSEMGGILSILAHRGETPEELAGFVKA MRAHALTVDGLPDIVDTCGTGGDGISTFNISTASAIVASAAGAKIAKHGNRSVSSKSGSAD VLEELEVSIQTTPEKVKSSIETNNMGFLFAPLYHSSMKHVAGTRKELGFRTVFNLLGPLSN PLQAKRQVIGVYSVEKAGLMASALETFQPKHVMFVSSRDGLDELSITAPTDVIELKDGER REYTVSPEDFGFTNGRLEDLQVQSPKESAYLIQNIFENKSSSSALSITAFNAGAAIYTAGIT ASLKEGTELALETITSGGAAAQLERLKQKEEEIYA 47 10 20 30 55 JP 2005 521407 2005 7 21 MNFQSNISAFLEDSLSH HTIPIVETFTVDTLTPIQMIEKLDREITYLLESKDDTSTWSRY SFIGLNPFLTIKEEQGRFSAADQDSKSLYTGNELKEVLNWMNTTYKIKTPELGIPFVGGA VGYLSYDMIPLIEPSVPSHTKETDMEKCMLFVCRTLIAYDHETKNVH FIQYARLTGEETK NEKMDVFHQNHLELQNLIEKM MDQKNIKELFLSADSYKTPSFETVSSNYEKSAFMADVEK IKSYIKAGDIFQGVLSQKFEVPIKADAFELYRVLRIVNPSPYMYYMKLLDREIVGSSPERLIH VQDGHLEIHPIAGTRKRGADKAEDERLKVELMKDEKEKAEHYMLVDLARNDIGRVAEYG SVSVPEFTKIVSFSHVMHIISVVTGRLKKGVHPVDALMSAFPAGTLTGAPKIRAMQLLQEL EPTPRETYGGCIAYIGFDGNIDSCITIRTMSVKNGVASIQAGAGIVADSVPEAEYEESCNKA GALLKTIHIAEDMFHSKEDKADEQISTIVR 49 10 HHHHH I LI LI LI LI II II II II II II I II II II II II II I II II II II I
108. laims 81 83 drawn to method for enhancing expression of a protein of interest in Bacillus Group IX claims 84 85 drawn to method for enhancing expression of a protein of interest in Bacillus Group X claims 86 87 drawn to a nucleic acid sequence Group XI claim 88 drawn to an amino acid sequence The inventions listed as Groups I XI do not relate to a single general inventive concept under PCT Rule 13 1 because under PCT Rule 13 2 they lack the same or corresponding special technical features for the following reasons Groups I II IV X and XI are drawn to different products each defining different technical features that lack unity of invention The technical feature of Group I is not special in view of the teachings of Ferrari 5387521 Ferrari discloses an altered Bacillus strain that is capable of expressing proteins enzymes As such the various products and methods lack unity of invention because the technical feature of Group I is not special in that it does not define a novel contribution over the prior art As such the groups of inventions lack a corresponding special technical feature Continuation of FIELDS SEARCHED Item 3 WEST CABA BIOSIS MEDLINE JAPIO WPIDS BIOTECHDS LIFESCI CAPLUS AGRICOLA search terms inventor names bacillus strain alter mutant mutat gene heterologous protein express inactivat chromosomal gene recited genes in claim 1 Form PCT ISA 210 second sheet July 1998
109. relevant passages Relevant to claim No US 5 387 521 A FERRARI 07 February 1995 see entire document YANG et al Alanine scanning mutagenesis of Bacillus subtilis trp RNA binding attenuation protein TRAP reveals residues involved in tryptophan binding and RNA binding J Mol Biol 1997 Vol 270 pages 696 710 see entire document US 6 528 255 B1 ESTELL 04 March 2003 see entire document US 5 585 253 DOI et al 17 December 1996 see entire document WO 99 03984 A2 GENENCOR INTERNATIONAL INC 28 1999 see entire document YAKHNIN et al Expression of the Bacillus subtilis trpEDCFBA operon is influenced by translational coupling and Rho termination factor J Bacteriology October 2001 Vol 183 No 20 pages 5918 5926 see entire document EP 0246 678 AI GENENTECH INC 25 November 1987 see entire document Further documents are listed in the continuation of Box C C See patent family annex Special categories of cited documents later document published after the intemational filing date or priority date and not in conflict with the spplication but cited to understand the A document defining the general state of the art which is not considered to be principle or theory underlying the invention of particular relevance document of particular relevance the claimed invention cannot be E carlier application or patent published on or after the international filing date considered novel or cannot be con
110. sidered to involve an inventive step when the document is taken alone L document which may throw doubts on priority claim s or which js cited to establish the publication date of another citation or other special reason as document of particular relevance the claimed invention cannot be specificd considered to involve an inventive step when the document is combined with one or more other such documents such combination O document referring ta an oral disclosure use exhibition or other means being obvious to a person skilled in the art P document published prior to the international filing date but later than the document member of the same patent family priority date claimed Date of the actual completion of the international search tof mailing of the international search report 29 July 2003 29 07 2003 2003 Name and mailing address of the ISA US Fk 4 Stop ISA US Commissioner for Patents P O Box 1450 Alexandtia Virginia 22313 1450 elgphone No 703 308 0196 Facsimile No 703 305 3230 Form PCT ISA 210 second sheet July 1998 SUBSTITUTE SHEET RULE 26 94 JP 2005 521407 2005 7 21 PCT US03 09585 INTERNATIONAL SEARCH REPORT Continuation DOCUMENTS CONSIDERED TO BE RELEVANT Citation of document with indication where appropriate of the relevant passages WO 92 19721 Al GENENCOR INTERNATIONAL INC 12 November 1992 see entire document US 5 310
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