III III a IIOI DID IIO 1101 ID III DII IDI DID IID IID IIID II DI IIi
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- Vivien Daniela Dixon
- 8 years ago
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1 19) United States III III a IIOI DID IIO 1101 ID III DII IDI DID IID IID IIID II DI IIi US A1 (12) Patent Application Publication Al Powell et al. (43) Pub. Date: Jun. 25, (54) COMPOSITIONS OF INFLUENZA VIRAL PROTEINS AND METHODS OF USE THEREOF (76) Inventors: Thomas J. Powell, Madison, CT (US); James W. Huleatt, Nazareth, PA (US); Valerian Nakaar, Hamden, CT (US); Langzhou Song, Freehold, NJ (US); William F. McDonald, Madison, CT (US); Albert E. Price, New Haven, CT (US); Duane D. Hewitt, Hamilton (CA) Correspondence Address: HAMILTON, BROOK, SMITH & REYNOLDS, P.C. 530 VIRGINIA ROAD, P.O. BOX 9133 CONCORD, MA (US) (21) Appl. No.: 11/820,148 (22) Filed: Jun. 18, 2007 Related U.S. Application Data (63) Continuation-in-part of application No. PCT/U52005/ , filed on Dec. 21, 2005, Continuation-in-part of application No. 11/714,873, filed on Mar. 6, (60) Provisional application No. 60/638,254, filed on Dec. 21, 2004, provisional application No. 60/638,350, filed on Dec. 21, 2004, provisional application No. 60/645,067, filed on Jan. 19, 2005, provisional application No. 60/653,207, filed on Feb. 15, 2005, provisional application No. 60/666,878, filed on Mar. 31, 2005, provisional application No. 60/682,077, filed on May 18, 2005, provisional application No. 60/741, 202, filed on Nov. 30, 2005, provisional application No. 60/779,854, filed on Mar. 7, 2006, provisional application No. 60/784,497, filed on Mar. 20, 2006, provisional application No. 60/790,457, filed on Apr. 7, 2006, provisional application No. 60/814,292, filed on Jun. 16, 2006, provisional application No. 60/830, 881, filed on Jul. 14, 2006, provisional application No. 60/838,007, filed on Aug. 16, 2006, provisional application No. 60/856,451, filed on Nov. 3, 2006, provisional application No. 60/933,554, filed on Jun. 6, Publication Classification (51) Int. Cl. A61K 39/145 ( ) A61P 37/04 ( ) (52) U.S. Cl /210.1 (57) ABSTRACT Compositions, fusion proteins and polypeptides comprise at least one pathogen-associated molecular pattern and at least a portion of at least one integral membrane protein of an influenza viral antigen. The compositions, fusion proteins and polypeptides are used to stimulate an immune response in a subject.
2 Patent Application Publication Jun. 25, 2009 Sheet 1 of 85 US 2009/ Al SEQ ID NO: 1 flib/stf2 amino acid sequence (hinge region underlined) MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRL NEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVQKAYD VKDTAVTTKAYANNGTTLDVSGLDDAAIKAATGGTNGTASVTGGAVKFDADNNKYFVTIG GFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATTKTEVQELKDTPAVVSADAKN ALIAGGVDATDANGAELVKMSYTDKNGKTIEGGYALKAGDKYYAADYDEATGAIKAKTTS YTAADGTTKTAANQLGGVDGKTEVVTIDGKTYNASKAAGHDFKAQPELAEAAAKTTENPL QKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSDYATEVSNMSRA QILQQAGTSVLAQANQVPQNVLSLLR Figure 1
3 Patent Application Publication Jun. 25, 2009 Sheet 2 of 85 US 2009/ Al SEQ ID NO: 2 fljb/stf2 nucleic acid sequence (hinge region underlined) ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAA TCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGC GCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT AACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG AACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTG AAGCAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCAGAAAGCGTATGAT GTGAAAGATACAGCAGTAACAACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTA TCGGGTCTTGATGATGCAGCTATTAAAGCGGCTACGGGTGGTACGAATGGTACGGCTTCT GTAACCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGGT GGCTTTACTGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGAC GGTACAGTAACCCTTGCGGCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACT AAAACAGAAGTACAGGAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAAT GCCTTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATG TCTTATACCGATAAAAATGGTAAGACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGAT AAGTATTACGCCGCAGATTACGATGAAGCGACAGGAGCAATTAAAGCTAAAACTACAAGT TATACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AAAACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCAT GATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACC ACCGAAAACCCGCTG CAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTA CAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAA GCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCG CAGATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAAC GTGCTGTCTCTGTTACGT Figure 2
4 Patent Application Publication Jun. 25, 2009 Sheet 3 of 85 US 2009/ Al SEQ ID NO: 3 fljb/stf20 amino acid sequence MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKGLT QASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEID RVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVHGAPVDPASPW TENPLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSDYATEVSNM SRAQILQQAGTSVLAQANQVPQNVLSLLR Figure 3
5 Patent Application Publication Jun. 25, 2009 Sheet 4 of 85 US 2009/ Al SEQ ID NO: 4 flib/stf2a nucleic acid sequence ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAATC CCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGCGA AAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTGACT CAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAA CGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAGCACCA ACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGAAATCGAC CGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCTGAC CATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTGAAGCAGATCAACTCTC AGACCCTGGGTCTGGACTCACTGAACGTGCATGGAGCGCCGGTGGATCCTGCTAGCCCATGG ACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGA TCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAACA ATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATG TCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCC GCAGAACGTGCTGTCTCTGTTACGTG Figure 4
6 Patent Application Publication Jun. 25, 2009 Sheet 5 of 85 US 2009/ Al SEQ ID NO: 5 E. coli flic amino acid sequence (hinge region underlined) MAQVINTNSLSLITQNNINKNQSALSSSIERLSSGLRINSAKDDAAGQAIANRFTSNIKG LTQAARNANDGISVAQTTEGALSEINNNLQRIRELTVQASTGTNSDSDLDSIQDEIKSRL DEIDRVSGQTQFNGVNVLAKDGSMKIQVGANDGQTITIDLKKIDSDTLGLNGFNVNGSGT IANKAATI SDLTAAKMDAATNTI TTTNNALTASKALDQLKDGDTVTIKADAAQTATVYTY NASAGNFSLSNVSNNTSEKAGDVAASLLPPAGQTASGVYKAASGEVNFDVDANGKITIGG QKAYLTSDGNLTTNDAGGATAATLDGLFKKAGDGQSIGFKKTASVTMGGTTYNFKTGADA DAATANAGVSFTDTASKETVLNKVATAKQGKAAAADGDTSATITYKSGVQTYQAVFAAGD GTASAKYADKADVSNATATYTDADGEMTTIGSYTTKYSIDANNGKVTVDSGTGTGKYAPK VGAEVYVSANGTLTTDATSEGTVTKDPLKALDEAISSIDKFRSSLGAIQNRLDSAVTNLN NTTTNLSEAQSRIQDADYATEVSNMSKAQIIQQAGNSVLAKANQVPQQVLSLLQG Figure 5
7 Patent Application Publication Jun. 25, 2009 Sheet 6 of 85 US 2009/ Al SEQ ID NO: 6 E. coli flic -nucleic acid sequence (hinge region underlined) ATGGCACAAGTCATTAATACCAACAGCCTCTCGCTGATCACTCAAAATAATATCAACAAG AACCAGTCTGCGCTGTCGAGTTCTATCGAGCGTCTGTCTTCTGGCTTGCGTATTAACAGC GCGAAGGATGACGCCGCAGGTCAGGCGATTGCTAACCGTTTTACTTCTAACATTAAAGGC CTGACTCAGGCTGCACGTAACGCCAACGACGGTATTTCCGTTGCGCAGACCACCGAAGGC GCGCTGTCCGAAATCAACAACAACTTACAGCGTATCCGTGAACTGACGGTTCAGGCTTCT ACCGGGACTAACTCCGATTCAGATCTGGACTCCATTCAGGACGAAATCAAATCCCGTCTG GACGAAATTGACCGCGTATCTGGCCAGACCCAGTTCAACGGCGTGAACGTACTGGCGAAA GACGGTTCAATGAAAATTCAGGTTGGTGCGAATGACGGCCAGACTATCACGATTGATCTG AAGAAAATTGACTCAGATACGCTGGGGCTGAATGGTTTTAACGTGAATGGTTCCGGTACG ATAGCCAATAAAGCGGCGACCATTAGCGACCTGACAGCAGCGAAAATGGATGCTGCAACT AATACTATAACTACAACAAATAATGCGCTGACTGCATCAAAGGCGCTTGATCAACTGAAA GATGGTGACACTGTTACTATCAAAGCAGATGCTGCTCAAACTGCCACGGTTTATACATAC AATGCATCAGCTGGTAACTTCTCACTCAGTAATGTATCGAATAATACTTCAGAAAAAGCA GGTGATGTAGCAGCTAGCCTTCTCCCGCCGGCTGGGCAAACTGCTAGTGGTGTTTATAAA GCAGCAAGCGGTGAAGTGAACTTTGATGTTGATGCGAATGGTAAAATCACAATCGGAGGA CAGAAAGCATATTTAACTAGTGATGGTAACTTAACTACAAACGATGCTGGTGGTGCGACT GCGGCTACGCTTGATGGTTTATTCAAGAAAGCTGGTGATGGTCAATCAATCGGGTTTAAG AAGACTGCATCAGTCACGATGGGGGGAACAACTTATAACTTTAAAACGGGTGCTGATGCT GATGCTGCAACTGCTAACGCAGGGGTATCGTTCACTGATACAGCTAGCAAAGAAACCGTT TTAAATAAAGTGGCTACAGCTAAACAAGGCAAAGCAGCTGCAGCTGACGGTGATACATCC GCAACAATTACCTATAAATCTGGCGTTCAGACGTATCAGGCTGTATTTGCCGCAGGTGAC GGTACTGCTAGCGCAAAATATGCCGATAAAGCTGACGTTTCTAATGCAACAGCAACATAC ACTGATGCTGATGGTGAAATGACTACAATTGGTTCATACACCACGAAGTATTCAATCGAT GCTAACAACGGCAAGGTAACTGTTGATTCTGGAACTGGTACGGGTAAATATGCGCCGAAA GTAGGGGCTGAAGTATATGTTAGTGCTAATGGTACTTTAACAACAGATGCAACTAGCGAA GGCACAGTAACAAAAGATCCACTGAAAGCTCTGGATGAAGCTATCAGCTCCATCGACAAA TTCCGTTCTTCCCTGGGTGCTATCCAGAACCGTCTGGATTCCGCAGTCACCAACCTGAAC AACACCACTACCAACCTGTCCGAAGCGCAGTCCCGTATTCAGGACGCCGACTATGCGACC GAAGTGTCCAACATGTCGAAAGCGCAGATCATTCAGCAGGCCGGTAACTCCGTGCTGGCA AAAGCCAACCAGGTACCGCAGCAGGTTCTGTCTCTGCTGCAGGGTTAG Figure 6
8 Patent Application Publication Jun. 25, 2009 Sheet 7 of 85 US 2009/ Al SEQ ID NO: 7 Salmonella muenchen flagellin flic amino acid sequence (hinge region under1ined) MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKGLT QASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANGTNSQSDLDSIQAEITQRLNEID RVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKEISSKTLGLDKLNVQDAYTPKETAV TVDKTTYKNGTDTITAQSNTDIQTAIGGGATGVTGADIKFKDGQYYLDVKGGASAGVYKATY DETTKKVNIDTTDKTPLATAEATAIRGTATITHNQIAEVTKEGVDTTTVAAQLAAAGVTGAD KDNTSLVKLSFEDKNGKVIDGGYAVKMGDDFYAATYDEKTGTITAKTTTYTDGAGVAQTGAV KFGGANGKSEVVTATDGKTYLASDLDKHNFRTGGELKEVNTDKTENPLQKIDAALAQVDTLR SDLGAVQNRFNSAITNLGNTVNNLSSARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQ VPQNVLSLLR Figure 7
9 Patent Application Publication Jun. 25, 2009 Sheet 8 of 85 US 2009/ Al SEQ ID NO: 8 Salmonella muenchen flagellin flic nucleic acid sequence (hinge region underlined) AATGGCACAAGTCATTAATACAAACAGCCTGTCGCTGTTGACCCAGAATAACCTGAACAAAT CCCAGTCCGCTCTGGGCACCGCTATCGAGCGTCTGTCTTCCGGTCTGCGTATCAACAGCGCG AAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTGAC TCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGA ACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACGGTACT AACTCCCAGTCTGACCTTGACTCTATCCAGGCTGAAATCACCCAGCGTCTGAACGAAATCGA CCGTGTATCCGGTCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCTGA CCATCCAGGTTGGTGCCAACGACGGTGAAACTATTGATATTGATTTAAAAGAAATTAGCTCT AAAACACTGGGACTTGATAAGCTTAATGTCCAGGATGCCTACACCCCGAAAGAA ACTGCTGT AACCGTTGATAAAACTACCTATAAAAATGGTACAGATACTATTACAGCCCAGAGCAATACTG ATATCCAAACTGCAATTGGCGGTGGTGCAACGGGGGTTACTGGGGCTGATATCAAATTTAAA GATGGTCAATACTATTTAGATGTTAAAGGCGGTGCTTCTGCTGGTGTTTATAAAGCCACTTA TGATGAAACTACAAAGAAAGTTAATATTGATACGACTGATAAAACTCCGTTAGCAACTGCGG AAGCTACAGCTATTCGGGGAACGGCCACTATAACCCACAACCAAATTGCTGAAGTAACAAAA GAGGGTGTTGATACGACCACAGTTGCGGCTCAACTTGCTGCTGCAGGGGTTACTGGTGCCGA TAAGGACAATACTAGCCTTGTAAAACTATCGTTTGAGGATAAAAACGGTAAGGTTATTGATG GTGGCTATGCAGTGAAAATGGGCGACGATTTCTATGCCGCTACATATGATGAGAAAACAGGT ACAATTACTGCTAAAACAACCACTTATACAGATGGTGCTGGCGTTGCTCAAACTGGAGCTGT GAAATTTGGTGGCGCAAATGGTAAATCTGAAGTTGTTACTGCTACCGATGGTAAAACTTACT TAGCAAGCGACCTTGACAAACATAACTTCAGAACAGGCGGTGAGCTTAAAGAGGTTAAT ACA GATAAGACTGAAAACCCACTGCAGAAAATTGATGCTGCCTTGGCACAGGTTGATACACTTCG TTCTGACCTGGGTGCGGTACAGAACCGTTTCAACTCCGCTATCACCAACCTGGGCAATACCG TAAATAACCTGTCTTCTGCCCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTCTCC AACATGTCTCGCGCGCAGATTCTGCAGCAGGCCGGTACCTCCGTTCTGGCGCAGGCTAACCA GGTTCCGCAAAACGTCCTCTCTTTACTGCGTTAA Figure 8
10 Patent Application Publication Jun. 25, 2009 Sheet 9 of 85 US 2009/ Al SEQ ID:9 Amino acid sequence of pmt/stf2 (Linker underlined) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRI NSAKDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVREL AVQSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGAND GETIDIDLKQINSQTLGLDSLNVQKAYDVKDTAVTTKAYANNGTTLDVSGLDDAAIK AATGGTNGTASVTGGAVKFDADNNKYFVTIGGFTGADAAKNGDYEVNVATDGTVTLA AGATKTTMPAGATTKTEVQELKDTPAVVSADAKNALIAGGVDATDANGAELVKMSYT DKNGKTIEGGYALKAGDKYYAADYDEATGAIKAKTTSYTAADGTTKTAANQLGGVDG KTEVVTIDGKTYNASKAAGHDFKAQPELAEAAAKTTENPLQKIDAALAQVDALRSDL GAVQNRFNSAITNLGNTVNNLSEARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQA NQVPQNVLSLLRKGNSKLEGQLEFPRTSPVWWNSADIQHSGGRSSLEGPRFEGKPIP NPLLGLDSTRTGHHHHHH Figure 9
11 Patent Application Publication Jun. 25, 2009 Sheet 10 of 85 US 2009/ Al SEQ ID: 10 Amino acid sequence of pmt/stf2 (Linker underlined) ATGAAGTTATGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGATCT GCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAATCC CAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGCG AAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTG ACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCG CTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAAC AGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAAC GAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGAC AACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTGAAG CAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCAGAAAGCGTATGATGTG AAAGATACAGCAGTAACAACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTATCG GGTCTTGATGATGCAGCTATTAAAGCGGCTACGGGTGGTACGAATGGTACGGCTTCTGTA ACCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGGTGGC TTTACTGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGACGGT ACAGTAACCCTTGCGGCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACTAAA ACAGAAGTACAGGAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAATGCC TTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATGTCT TATACCGATAP,AAATGGTAAGACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGATAAG TATTACGCCGCAGATTACGATGAAGCGACAGGAGCAATTAAAGCTAAAACTACAAGTTAT ACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGTAAA ACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCATGAT TTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAACCCGCTGCAG AAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAA AACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAAGCG CGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCGCAG ATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTG CTGTCTCTGTTACGTAAGGGCAATTCGAAGCTTGAAGGTCAATTGGAATTCCCTAGGACT AGTCCAGTGTGGTGGAATTCTGCAGATATCCAGCACAGTGGCGGCCGCTCGAGTCTAGAG GGCCCGCGGTTCGAAGGTAAGCCTATCCCTAACCCTCTCCTCGGTCTCGATTCTACGCGT ACCGGTCATCATCACCATCACCAT Figure 10
12 Patent Application Publication Jun. 25, 2009 Sheet 11 of 85 US 2009/ Al SEO ID NO: 17 4xM2e AGCTTGCTGACTGAGGTTGAGACCCCGATTCGCAACGAATGGGGTTCCCGTTCCAACGATTC TTCCGACCCGCTCGAGAGCCTGTTGACCGAGGTTGAAACCCCTATCCGTAATGAATGGGGCT CCCGTAGCAACGACTCTTCTGACCCAGGATCCTCCCTCTTGACCGAAGTGGAAACGCCTATT CGTAATGAGTGGGGTTCTCGTAGCAATGACAGCTCGGACCCGGAGCTCTCGCTGCTGACGGA AGTGGAGACTCCGATCCGTAACGAGTGGGGCTCTCGCTCTAACGATAGCTCAGACCCGTCTA GATAA Figure 11
13 Patent Application Publication Jun. 25, 2009 Sheet 12 of 85 US 2009/ Al SEQ ID NO: 18 4xM2e SLLTEVETPIRNEWGSRSNDSSDPLESLLTEVETPIRNEWGSRSNDSSDPGSSLLTEVET PIRNEWGSRSNDSSDPELSLLTEVETPIRNEWGSRSNDSSDPSR Figure 12
14 Patent Application Publication Jun. 25, 2009 Sheet 13 of 85 US 2009/ Al SEQ ID NO.: 31 flib/stf2-4xm2e MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKGLT QASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEID RVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVQKAYDVKDTAV TTKAYANNGTTLDVSGLDDAAIKAATGGTNGTASVTGGAVKFDADNNKYFVTIGGFTGADAA KNGDYEVNVATDGTVTLAAGATKTTMPAGATTKTEVQELKDTPAVVSADAKNALIAGGVDAT DANGAELVKMSYTDKNGKTIEGGYALKAGDKYYAADYDEATGAIKAKTTSYTAADGTTKTAA NQLGGVDGKTEVVTIDGKTYNASKAAGHDFKAQPELAEAAAKTTENPLQKIDAALAQVDALR SDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQ VPQNVLSLLRLSLLTEVETPIRNEWGSRSNDSSDPLESLLTEVETPIRNEWGSRSNDSSDPG SSLLTEVETPIRNEWGSRSNDSSDPELSLLTEVETPIRNEWGSRSNDSSDPSR Figure 13
15 Patent Application Publication Jun. 25, 2009 Sheet 14 of 85 US 2009/ Al SEQ ID NO: 32 STF2-4xM2e ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAATC CCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGCGA AAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTGACT CAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAA CGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAGCACCA ACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGAAATCGAC CGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACCCTGAC CATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTGAAGCAGATCAACTCTC AGACCCTGGGTCTGGACTCACTGAACGTGCAGAAAGCGTATGATGTGAAAGATACAGCAGTA ACAACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTATCGGGTCTTGATGATGCAGC TATTAAAGCGGCTACGGGTGGTACGAATGGTACGGCTTCTGTAACCGGTGGTGCGGTTAAAT TTGACGCAGATAATAACAAGTACTTTGTTACTATTGGTGGCTTTACTGGTGCTGATGCCGCC AAAAATGGCGATTATGAAGTTAACGTTGCTACTGACGGTACAGTAACCCTTGCGGCTGGCGC AACTAAAACCACAATGCCTGCTGGTGCGACAACTAAAACAGAAGTACAGGAGTTAAAAGATA CACCGGCAGTTGTTTCAGCAGATGCTAAAAATGCCTTAATTGCTGGCGGCGTTGACGCTACC GATGCTAATGGCGCTGAGTTGGTCAAAATGTCTTATACCGATAAAAATGGTAAGACAATTGA AGGCGGTTATGCGCTTAAAGCTGGCGATAAGTATTACGCCGCAGATTACGATGAAGCGACAG GAGCAATTAAAGCTAAAACCACAAGTTATACTGCTGCTGACGGCACTACCAAAACAGCGGCT AACCAACTGGGTGGCGTAGACGGTAAAACCGAAGTCGTTACTATCGACGGTAAAACCTACAA TGCCAGCAAAGCCGCTGGTCATGATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTA AAACCACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGC TCTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGT AAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCA ACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAG GTCCCGCAGAACGTGCTGTCTCTGTTACGTCTGAGCTTGCTGACTGAGGTTGAGACCCCGAT TCGCAACGAATGGGGTTCCCGTTCCAACGATTCTTCCGACCCGCTCGAGAGCCTGTTGACCG AGGTTGAAACCCCTATCCGTAATGAATGGGGCTCCCGTAGCAACGACTCTTCTGACCCAGGA TCCTCCCTCTTGACCGAAGTGGAAACGCCTATTCGTAATGAGTGGGGTTCTCGTAGCAATGA CAGCTCGGACCCGGAGCTCTCGCTGCTGACGGAAGTGGAGACTCCGATCCGTAACGAGTGGG GCTCTCGCTCTAACGATAGCTCAGACCCGTCTAGATAA Figure 14
16 Patent Application Publication Jun. 25, 2009 Sheet 15 of 85 US 2009/ Al H O H 14 0 ^`"-SLLTEVETPIRNEWGSRSNDSSDP s 14 0 O Figure 15
17 Patent Application Publication Jun. 25, 2009 Sheet 16 of 85 US 2009/ Al.S^ ^^ "....., ^\::;: i :.^'}::":2 ^k.; : ^ '!. is ^
18 Patent Application Publication Jun. 25, 2009 Sheet 17 of 85 US 2009/ Al MCS STF2 pmt/stf2 STF2 STF2.4xM2e(H1). STF2 STF2.4xM2e(H5) STF2 rc!p-i STF2.4 xm2 e (H 1H5) Figure 17A
19 Patent Application Publication Jun. 25, 2009 Sheet 18 of 85 US 2009/ Al MCS STF2A! pmt/stf A smpu11uij STF2t STF20.4xM2e (Hl)!1^\ STF2 STF2A. 4xM2e (H5) STF2A via- cu ^ STF2Lt.4xM2e(H1H5) Figure 17B
20 Patent Application Publication Jun. 25, 2009 Sheet 19 of 85 US 2009/ Al STF2A MCS 1 PICZa/STF2L STF2L.HAPRB STF2i.HAH5 Figure 18
21 Patent Application Publication Jun. 25, 2009 Sheet 20 of 85 US 2009/ Al SEQ ID NO: 60 MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRL NEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVHGAPV DPASPWTENPLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSD YATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLREFSRYPAQWRPLDQICIGYHANN STEQVDTIMEKNVTVTHAQDILEKKHNGKLCDLDGVKPLILRDCSVAGWLLGNPMCDEFI NVPEWSYIVEKANPVNDLCYPGDFNDYEELKHLLSRINHFEKIQIIPKSSWSSHEASLGV SSACPYQGKSSFFRNVVWLIKKNSTYPTIKRSYNNTNQEDLLVLWGIHHPNDAAEQTKLY QNPTTYISVGTSTLNQRLVPRIATRSKVNGQSGRMEFFWTILKPNDAINFESNGNFIAPE YAYKIVKKGDSTIMKSELEYGNCNTKCQTPMGAINSSMPFHNIHPLTIGECPKYVKSNRL VLATGLRNSPQRERRRKKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKEST QKAIDGVTNKVNSIIDKMNTQFEAVGREFNNLERRIENLNKKMEDGFLDVWTYNAELLVL MENERTLDFHDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNECMESVRNGTYDYPQ YSEEARLKREEISGVKLESIGIYQILSIYST Figure 19
22 Patent Application Publication Jun. 25, 2009 Sheet 21 of 85 US 2009/ Al SEQ ID NO: 61 ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAA TCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGC GCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT AACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG AACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTG AAGCAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCATGGAGCGCCGGTG GATCCTGCTAGCCCATGGACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAG GTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACC AACCTGGGCAATACCGTAAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGAC TACGCGACCGAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCC GTTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGT GAATTCTCT AGATATCCAGCACAGTGGCGGCCGCTC GACCAGATCTGTATCGGTTATCATGCTAACAAT TCTACTGAACAAGTAGATACTATCATGGAGAAGAACGTTACAGTTACACATGCACAAGAT ATCCTGGAAAAGAAGCATAATGGAAAACTGTGTGACCTTGATGGTGTTAAACCACTAATA TTGCGTGACTGCTCAGTTGCTGGGTGGTTGTTGGGGAATCCAATGTGCGACGAATTTATC AACGTTCCAGAATGGAGTTACATTGTTGAAAAAGCTAACCCTGTTAACGACTTGTGTTAC CCAGGCGATTTTAATGACTACGAGGAACTTAAGCATTTGTTGTCAAGAATTAACCACTTC GAGAAAATTCAAATTATTCCAAAGTCATCTTGGTCCTCCCATGAAGCATCCCTAGGAGTC TCTTCCGCTTGCCCTTACCAAGGCAAGAGTTCCTTTTTTCGTAATGTCGTCTGGCTGATC AAAAAGAACTCCACCTATCCAACTATAAAGAGATCATACAACAACACAAATCAGGAGGAT CTGCTAGTTCTGTGGGGCATTCACCACCCCAATGACGCAGCTGAGCAGACTAAATTGTAC CAAAACCCAACTACCTATATATCAGTTGGTACCTCAACTCTTAACCAGCGACTAGTCCCC CGTATTGCTACTAGGTCAAAGGTTAATGGTCAAAGTGGACGAATGGAGTTTTTCTGGACT ATTTTGAAGCCCAACGATGCCATCAACTTCGAAAGTAATGGAAATTTCATAGCCCCTGAG TACGCTTACAAAATCGTTAAAAAGGGTGATTCCACTATCATGAAATCTGAACTGGAATAC GGAAACTGTAACACCAAATGCCAGACGCCAATGGGTGCCATCAACTCTTCTATGCCTTTT CACAACATTCATCCTTTGACTATTGGTGAATGCCCAAAGTACGTCAAATCTAACCGTTTG GTGTTGGCTACTGGTCTAAGGAACTCCCCTCAGCGTGAAAGAAGAAGAAAGAAGAGGGGA TTATTCGGTGCTATCGCTGGATTTATTGAGGGAGGATGGCAGGGAATGGTCGATGGCTGG TATGGTTACCATCACTCAAATGAACAGGGAAGTGGATACGCAGCTGATAAAGAATCTACT CAAAAGGCTATCGACGGTGTTACAAACAAGGTCAATTCTATTATCGATAAGATGAATACA CAGTTTGAGGCTGTTGGTAGAGAGTTCAATAATCTTGAGAGAAGAATCGAAAACCTGAAC AAGAAAATGGAAGACGGATTTTTAGATGTATGGACTTACAATGCTGAGTTGTTGGTCTTG ATGGAGAATGAACGAACGTTGGACTTCCATGACTCCAATGTGAAGAACCTATATGACAAA GTGAGGCTGCAACTTAGAGACAACGCCAAGGAATTGGGAAACGGGTGCTTCGAGTTTTAC CACAAATGCGACAACGAATGTATGGAATCAGTGAGAAACGGTACCTATGATTACCCCCAA TATTCCGAGGAGGCAAGACTGAAGAGAGAAGAGATATCTGGTGTAAAGTTGGAATCCATC GGTATTTATCAGATTCTATCTATATATTCTACCTAATAG Figure 20
23 Patent Application Publication Jun. 25, 2009 Sheet 22 of 85 US 2009/ Al SEQ ID NO: 62 MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRL NE IDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVHGAPV DPASPWTENPLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSD YATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLREFSRYPAQWRPLDTICIGYHANN STDTVDTVLEKNVTVTHSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGWLLGNPECDPLL PVRSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIFPKESSWPNHNTNGV TAACSHEGKSSFYRNLLWLTEKEGSYPKLKNSYVNKKGKEVLVLWGIHHPPNSKEQQNLY QNENAYVSVVTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTIIFEANGNLIAPM YAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSLPYQNIHPVTIGECPKYVRSAKL RMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGMIDGWYGYHHQNEQGSGYAADQKSTQNAI NGITNKVNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTYNAELLVLLENE RTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRNGTYDYPKYSEE SKLNREKVDGVKLESMGIYQ Figure 21
24 Patent Application Publication Jun. 25, 2009 Sheet 23 of 85 US 2009/ Al SEQ ID NO: 63 ATGGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAA TCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGC GCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT AACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTG AACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTG AAGCAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCATGGAGCGCCGGTG GATCCTGCTAGCCCATGGACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAG GTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACC AACCTGGGCAATACCGTAAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGAC TACGCGACCGAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCC GTTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGTGAATTCTCT AGATATCCAGCACAGTGGCGGCCGCTCGACCAGATCTGTATCGGTTATCATGCTAACAAT TCTACTGAACAAGTAGATACTATCATGGAGAAGAACGTTACAGTTACACATGCACAAGAT ATCCTGGAAAAGAAGCATAATGGAAAACTGTGTGACCTTGATGGTGTTAAACCACTAATA TTGCGTGACTGCTCAGTTGCTGGGTGGTTGTTGGGGAATCCAATGTGCGACGAATTTATC AACGTTCCAGAATGGAGTTACATTGTTGAAAAAGCTAACCCTGTTAACGACTTGTGTTAC CCAGGCGATTTTAATGACTACGAGGAACTTAAGCATTTGTTGTCAAGAATTAACCACTTC GAGAAAATTCAAATTATTCCAAAGTCATCTTGGTCCTCCCATGAAGCATCCCTAGGAGTC TCTTCCGCTTGCCCTTACCAAGGCAAGAGTTCCTTTTTTCGTAATGTCGTCTGGCTGATC AAAAAGAACTCCACCTATCCAACTATAAAGAGATCATACAACAACACAAATCAGGAGGAT CTGCTAGTTCTGTGGGGCATTCACCACCCCAATGACGCAGCTGAGCAGACTAAATTGTAC CAAAACCCAACTACCTATATATCAGTTGGTACCTCAACTCTTAACCAGCGACTAGTCCCC CGTATTGCTACTAGGTCAAAGGTTAATGGTCAAAGTGGACGAATGGAGTTTTTCTGGACT ATTTTGAAGCCCAACGATGCCATCAACTTCGAAAGTAATGGAAATTTCATAGCCCCTGAG TACGCTTACAAAATCGTTAAAAAGGGTGATTCCACTATCATGAAATCTGAACTGGAATAC GGAAACTGTAACACCAAATGCCAGACGCCAATGGGTGCCATCAACTCTTCTATGCCTTTT CACAACATTCATCCTTTGACTATTGGTGAATGCCCAAAGTACGTCAAATCTAACCGTTTG GTGTTGGCTACTGGTCTAAGGAACTCCCCTCAGCGTGAAAGAAGAAGAAAGAAGAGGGGA TTATTCGGTGCTATCGCTGGATTTATTGAGGGAGGATGGCAGGGAATGGTCGATGGCTGG TATGGTTACCATCACTCAAATGAACAGGGAAGTGGATACGCAGCTGATAAAGAATCTACT CAAAAGGCTATCGACGGTGTTACAAACAAGGTCAATTCTATTATCGATAAGATGAATACA CAGTTTGAGGCTGTTGGTAGAGAGTTCAATAATCTTGAGAGAAGAATCGAAAACCTGAAC AAGAAAATGGAAGACGGATTTTTAGATGTATGGACTTACAATGCTGAGTTGTTGGTCTTG ATGGAGAATGAACGAACGTTGGACTTCCATGACTCCAATGTGAAGAACCTATATGACAAA GTGAGGCTGCAACTTAGAGACAACGCCAAGGAATTGGGAAACGGGTGCTTCGAGTTTTAC CACAAATGCGACAACGAATGTATGGAATCAGTGAGAAACGGTACCTATGATTACCCCCAA TATTCCGAGGAGGCAAGACTGAAGAGAGAAGAGATATCTGGTGTAAAGTTGGAATCCATC GGTATTTATCAGATTCTATCTATATATTCTACCTAATAG Figure 22
25 Patent Application Publication Jun. 25, 2009 Sheet 24 of 85 US 2009/ Al SEQ ID NO: 64 DTI CIGYHANNSTDTVDTVLEKNVTVTHSVNLLEDSHNGKLCRLKGIAPLQLGKCNIAGW LLGNPECDPLLPVRSWSYIVETPNSENGICYPGDFIDYEELREQLSSVSSFERFEIFPKE SSWPNHNTNGVTAACSHEGKSSFYRNLLWLTEKEGSYPKLKNSYVNKKGKEVLVLWGIHH PPNSKEQQNLYQNENAYVSVVTSNYNRRFTPEIAERPKVRDQAGRMNYYWTLLKPGDTII FEANGNLIAPMYAFALSRGFGSGIITSNASMHECNTKCQTPLGAINSSLPYQNIHPVTIG ECPKYVRSAKLRMVTGLRNIPSIQSRGLFGAIAGFIEGGWTGMIDGWYGYHHQNEQGSGY AADQKSTQNAINGITNKVNTVIEKMNIQFTAVGKEFNKLEKRMENLNKKVDDGFLDIWTY NAELLVLLENERTLDFHDSNVKNLYEKVKSQLKNNAKEIGNGCFEFYHKCDNECMESVRN GTYDYPKYSEESKLNREKVDGVKLESMGIYQ Figure 23
26 Patent Application Publication Jun. 25, 2009 Sheet 25 of 85 US 2009/ Al SEQ ID NO: 65 GACCAGATCTGTATCGGTTATCATGCTAACAATTCTACTGAACAAGTAGATACTATCATG GAGAAGAACGTTACAGTTACACATGCACAAGATATCCTGGAAAAGAAGCATAATGGAAAA CTGTGTGACCTTGATGGTGTTAAACCACTAATATTGCGTGACTGCTCAGTTGCTGGGTGG TTGTTGGGGAATCCAATGTGCGACGAATTTATCAACGTTCCAGAATGGAGTTACATTGTT GAAAAAGCTAACCCTGTTAACGACTTGTGTTACCCAGGCGATTTTAATGACTACGAGGAA CTTAAGCATTTGTTGTCAAGAATTAACCACTTCGAGAAAATTCAAATTATTCCAAAGTCA TCTTGGTCCTCCCATGAAGCATCCCTAGGAGTCTCTTCCGCTTGCCCTTACCAAGGCAAG AGTTCCTTTTTTCGTAATGTCGTCTGGCTGATCAAAAAGAACTCCACCTATCCAACTATA AAGAGATCATACAACAACACAAATCAGGAGGATCTGCTAGTTCTGTGGGGCATTCACCAC CCCAATGACGCAGCTGAGCAGACTAAATTGTACCAAAACCCAACTACCTATATATCAGTT GGTACCTCAACTCTTAACCAGCGACTAGTCCCCCGTATTGCTACTAGGTCAAAGGTTAAT GGTCAAAGTGGACGAATGGAGTTTTTCTGGACTATTTTGAAGCCCAACGATGCCATCAAC TTCGAAAGTAATGGAAATTTCATAGCCCCTGAGTACGCTTACAAAATCGTTAAAAAGGGT GATTCCACTATCATGAAATCTGAACTGGAATACGGAAACTGTAACACCAAATGCCAGACG CCAATGGGTGCCATCAACTCTTCTATGCCTTTTCACAACATTCATCCTTTGACTATTGGT GAATGCCCAAAGTACGTCAAATCTAACCGTTTGGTGTTGGCTACTGGTCTAAGGAACTCC CCTCAGCGTGAAAGAAGAAGAAAGAAGAGGGGATTATTCGGTGCTATCGCTGGATTTATT GAGGGAGGATGGCAGGGAATGGTCGATGGCTGGTATGGTTACCATCACTCAAATGAACAG GGAAGTGGATACGCAGCTGATAAAGAATCTACTCAAAAGGCTATCGACGGTGTTACAAAC AAGGTCAATTCTATTATCGATAAGATGAATACACAGTTTGAGGCTGTTGGTAGAGAGTTC AATAATCTTGAGAGAAGAATCGAAAACCTGAACAAGAAAATGGAAGACGGATTTTTAGAT GTATGGACTTACAATGCTGAGTTGTTGGTCTTGATGGAGAATGAACGAACGTTGGACTTC CATGACTCCAATGTGAAGAACCTATATGACAAAGTGAGGCTGCAACTTAGAGACAACGCC AAGGAATTGGGAAACGGGTGCTTCGAGTTTTACCACAAATGCGACAACGAATGTATGGAA TCAGTGAGAAACGGTACCTATGATTACCCCCAATATTCCGAGGAGGCAAGACTGAAGAGA GAAGAGATATCTGGTGTAAAGTTGGAATCCATCGGTATTTATCAGATTCTATCTATATAT TCTACCTAATAG Figure 24
27 Patent Application Publication Jun. 25, 2009 Sheet 26 of 85 US 2009/ Al SEQ ID NO: 66 E. coli flic Amino Acid sequence (without hinge region) MAQVINTNSLSLITQNNINKNQSALSSSIERLSSGLRINSAKDDAAGQAIANRFTSNIKG LTQAARNANDGISVAQTTEGALSEINNNLQRIRELTVQASTGTNSDSDLDSIQDEIKSRL DEIDRVSGQTQFNGVNVLAKDGSMKIQVGANDGQTITIDLKKIDSDTLGTKDPLKALDEA ISSIDKFRSSLGAIQNRLDSAVTNLNNTTTNLSEAQSRIQDADYATEVSNMSKAQIIQQA GNSVLAKANQVPQQVLSLLQG Figure 25
28 Patent Application Publication Jun. 25, 2009 Sheet 27 of 85 US 2009/ Al SEQ ID No: 67 Amino Acid sequence of H5NI HA DQICIGYHANNSTEQVDTIMEKNVTVTHAQDILEKKHNGKLCDLDGVKPLILRDCSVAGWLLGNPMC DEFINVPEWSYIVEKANPVNDLCYPGDFNDYEELKHLLSRINHFEKIQIIPKSSWSSHEASLGVSSA CPYQGKSSFFRNVVWLIKKNSTYPTIKRSYNNTNQEDLLVLWGIHHPNDAAEQTKLYQNPTTYISVG TSTLNQRLVPRIATRSKVNGQSGRMEFFWTILKPNDAINFESNGNFIAPEYAYKIVKKGDSTIMKSE LEYGNCNTKCQTPMGAINSSMPFHNIHPLTIGECPKYVKSNRLVLATGLRNSPQRERRRKKRGLFGA IAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKESTQKAIDGVTNKVNSIIDKMNTQFEAVGREFNN LERRIENLNKKMEDGFLDVWTYNAELLVLMENERTLDFHDSNVKNLYDKVRLQLRDNAKELGNGCFE FYHKCDNECMESVRNGTYDYPQYSEEARLKREEISGVKLESIGIYQILSIYST Figure 26
29 Patent Application Publication Jun. 25, 2009 Sheet 28 of 85 US 2009/ Al SEQ ID No: 68 Nucleic acid sequence of H5N1 HA GACCAGATCTGTATCGGTTATCATGCTAACAATTCTACTGAACAAGTAGATACTATCATG GAGAAGAACGTTACAGTTACACATGCACAAGATATCCTGGAAAAGAAGCATAATGGAAAA CTGTGTGACCTTGATGGTGTTAAACCACTAATATTGCGTGACTGCTCAGTTGCTGGGTGG TTGTTGGGGAATCCAATGTGCGACGAATTTATCAACGTTCCAGAATGGAGTTACATTGTT GAAAAAGCTAACCCTGTTAACGACTTGTGTTACCCAGGCGATTTTAATGACTACGAGGAA CTTAAGCATTTGTTGTCAAGAATTAACCACTTCGAGAAAATTCAAATTATTCCAAAGTCA TCTTGGTCCTCCCATGAAGCATCCCTAGGAGTCTCTTCCGCTTGCCCTTACCAAGGCAAG AGTTCCTTTTTTCGTAATGTCGTCTGGCTGATCAAAAAGAACTCCACCTATCCAACTATA AAGAGATCATACAACAACACAAATCAGGAGGATCTGCTAGTTCTGTGGGGCATTCACCAC CCCAATGACGCAGCTGAGCAGACTAAATTGTACCAAAACCCAACTACCTATATATCAGTT GGTACCTCAACTCTTAACCAGCGACTAGTCCCCCGTATTGCTACTAGGTCAAAGGTTAAT GGTCAAAGTGGACGAATGGAGTTTTTCTGGACTATTTTGAAGCCCAACGATGCCATCAAC TTCGAAAGTAATGGAAATTTCATAGCCCCTGAGTACGCTTACAAAATCGTTAAAAAGGGT GATTCCACTATCATGAAATCTGAACTGGAATACGGAAACTGTAACACCAAATGCCAGACG CCAATGGGTGCCATCAACTCTTCTATGCCTTTTCACAACATTCATCCTTTGACTATTGGT GAATGCCCAAAGTACGTCAAATCTAACCGTTTGGTGTTGGCTACTGGTCTAAGGAACTCC CCTCAGCGTGAAAGAAGAAGAAAGAAGAGGGGATTATTCGGTGCTATCGCTGGATTTATT GAGGGAGGATGGCAGGGAATGGTCGATGGCTGGTATGGTTACCATCACTCAAATGAACAG GGAAGTGGATACGCAGCTGATAAAGAATCTACTCAAAAGGCTATCGACGGTGTTACAAAC AAGGTCAATTCTATTATCGATAAGATGAATACACAGTTTGAGGCTGTTGGTAGAGAGTTC AATAATCTTGAGAGAAGAATCGAAAACCTGAACAAGAAAATGGAAGACGGATTTTTAGAT GTATGGACTTACAATGCTGAGTTGTTGGTCTTGATGGAGAATGAACGAACGTTGGACTTC CATGACTCCAATGTGAAGAACCTATATGACAAAGTGAGGCTGCAACTTAGAGACAACGCC AAGGAATTGGGAAACGGGTGCTTCGAGTTTTACCACAAATGCGACAACGAATGTATGGAA TCAGTGAGAAACGGTACCTATGATTACCCCCAATATTCCGAGGAGGCAAGACTGAAGAGA GAAGAGATATCTGGTGTAAAGTTGGAATCCATCGGTATTTATCAGATTCTATCTATATAT TCTACCTAATAG Figure 27
30 Patent Application Publication Jun. 25, 2009 Sheet 29 of 85 US 2009/ Al SEQ ID: 82 Amino acid sequence of pmt/stf2.4xm2e (HI) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKD DAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANSTNS QSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKQINSQT LGLDSLNVQKAYDVKDTAVTTKAYANNGTTLDVSGLDDAAIKAATGGTNGTASVTGGAVKFD ADNNKYFVTIGGFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATTKTEVQELKDTP AVVSADAKNALIAGGVDATDANGAELVKMSYTDKNGKTIEGGYALKAGDKYYAADYDEATGA IKAKTTSYTAADGTTKTAANQLGGVDGKTEVVTIDGKTYNASKAAGHDFKAQPELAEAAAKT TENPLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSDYATEVSNM SRAQILQQAGTSVLAQANQVPQNVLSLLRKGNSKLEGQLEFSLLTEVETPIRNEWGSRSNDS SDPLESLLTEVETPIRNEWGSRSNDSSDPGSSLLTEVETPIRNEWGSRSNDSSDPELSLLTE VETPIRNEWGSRSNDSSDPSR Figure 28
31 Patent Application Publication Jun. 25, 2009 Sheet 30 of 85 US 2009/ Al SEQ ID: 83 Nucleic acid sequence of pmt/stf2.4xm2e (Hi) ATGAAGTTATGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGATCT GCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAATCC CAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGCG AAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTG ACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCG CTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAAC AGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAAC GAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGAC AACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTGAAG CAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCAGAAAGCGTATGATGTG AAAGATACAGCAGTAACAACGAAAGCTTATGCCAATAATGGTACTACACTGGATGTATCG GGTCTTGATGATGCAGCTATTAAAGCGGCTACGGGTGGTACGAATGGTACGGCTTCTGTA ACCGGTGGTGCGGTTAAATTTGACGCAGATAATAACAAGTACTTTGTTACTATTGGTGGC TTTACTGGTGCTGATGCCGCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGACGGT ACAGTAACCCTTGCGGCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACTAAA ACAGAAGTACAGGAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAATGCC TTAATTGCTGGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATGTCT TATACCGATAAAAATGGTAAGACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGATAAG TATTACGCCGCAGATTACGATGAAGCGACAGGAGCAATTAAAGCTAAAACTACAAGTTAT ACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGTAAA ACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGTCATGAT TTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAACCCGCTGCAG AAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGGGTGCGGTACAA AACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAACAATCTGTCTGAAGCG CGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCCAACATGTCTCGCGCGCAG ATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTG CTGTCTCTGTTACGTAAGGGCAATTCGAAGCTTGAAGGTCAATTGGAATTC AGCTTGCTG ACTGAGGTTGAGACCCCGATTCGCAACGAATGGGGTTCCCGTTCCAACGATTCTTCCGAC CCGCTCGAGAGCCTGTTGACCGAGGTTGAAACCCCTATCCGTAATGAATGGGGCTCCCGT AGCAACGACTCTTCTGACCCAGGATCCTCCCTCTTGACCGAAGTGGAAACGCCTATTCGT AATGAGTGGGGTTCTCGTAGCAATGACAGCTCGGACCCGGAGCTCTCGCTGCTGACGGAA GTGGAGACTCCGATCCGTAACGAGTGGGGCTCTCGCTCTAACGATAGCTCAGACCCGTCT AGATAA Figure 29
32 Patent Application Publication Jun. 25, 2009 Sheet 31 of 85 US 2009/ Al SEQ ID: 84 Amino acid sequence of pmt/stf2.4xm2e (H5) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSA KDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSAN STNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLK QINSQTLGLDSLNVQKAYDVKDTAVTTKAYANNGTTLDVSGLDDAAIKAATGGTNGTASV TGGAVKFDADNNKYFVTIGGFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATTK TEVQELKDTPAVVSADAKNALIAGGVDATDANGAELVKMSYTDKNGKTIEGGYALKAGDK YYAADYDEATGAIKAKTTSYTAADGTTKTAANQLGGVDGKTEVVTIDGKTYNASKAAGHD FKAQPELAEAAAKTTENPLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEA RSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLR KGNSKLEGQLEF SLL TEVETPTRNEWESRSSDSSDPLESLLTEVETPTRNEWESRSSDSSDPESSLLTEVETPTR NEWESRSSDSSDPGSSLLTEVETPTRNEWESRSSDSSDPSR Figure 30
33 Patent Application Publication Jun. 25, 2009 Sheet 32 of 85 US 2009/ Al SEQ ID: 85 Nucleic acid sequence of pmt/stf2.4xm2e (H5) ATGAAGTTATGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGA TCTGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAAC AAATCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATC AACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAAC ATCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAG ACCACTGAAGGCGCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTG GCGGTTCAGTCTGCTAACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCT GAAATCACCCAGCGCCTGAACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAAC GGCGTGAAAGTCCTGGCGCAGGACAACACCCTGACCATCCAGGTTGGCGCCAACGAC GGTGAAACTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGGTCTGGAC TCACTGAACGTGCAGAAAGCGTATGATGTGAAAGATACAGCAGTAACAACGAAAGCT TATGCCAATAATGGTACTACACTGGATGTATCGGGTCTTGATGATGCAGCTATTAAA GCGGCTACGGGTGGTACGAATGGTACGGCTTCTGTAACCGGTGGTGCGGTTAAATTT GACGCAGATAATAACAAGTACTTTGTTACTATTGGTGGCTTTACTGGTGCTGATGCC GCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGACGGTACAGTAACCCTTGCG GCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACTAAAACAGAAGTACAG GAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAATGCCTTAATTGCT GGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATGTCTTATACC GATAAAAATGGTAAGACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGATAAGTAT TACGCCGCAGATTACGATGAAGCGACAGGAGCAATTAAAGCTAAAACTACAAGTTAT ACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AAAACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGT CATGATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAAC CCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTG GGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAAC AATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCC AACATGTCTCGCGCGCAGATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCT AACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGTAAGGGCAATTCGAAGCTTGAA GGTCAATTGGAATTC TCTCTGCTGACTGAAGTAGAAACTCCAACGCGTAATGAATGG GAATCCCGTTCTAGCGACTCCTCTGATCCTCTCGAGTCCCTGCTGACGGAGGTTGAA ACCCCGACCCGCAACGAGTGGGAAAGCCGTTCCTCCGATTCCTCTGATCCGGAGAGC AGCCTGCTGACCGAGGTAGAAACCCCGACCCGTAATGAGTGGGAATCTCGCTCCTCT GATTCTTCTGACCCGGGATCCTCTCTGCTGACCGAAGTGGAGACTCCGACTCGCAAC GAATGGGAGAGCCGTTCTTCTGACTCCTCTGACCCGTCTAGATAAT Figure 31
34 Patent Application Publication Jun. 25, 2009 Sheet 33 of 85 US 2009/ Al SEQ ID: 86 Amino acid sequence of pmt/stf2.4xm2e (H1H5) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSA KDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSAN STNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLK QINSQTLGLDSLNVQKAYDVKDTAVTTKAYANNGTTLDVSGLDDAAIKAATGGTNGTASV TGGAVKFDADNNKYFVTIGGFTGADAAKNGDYEVNVATDGTVTLAAGATKTTMPAGATTK TEVQELKDTPAVVSADAKNALIAGGVDATDANGAELVKMSYTDKNGKTIEGGYALKAGDK YYAADYDEATGAIKAKTTSYTAADGTTKTAANQLGGVDGKTEVVTIDGKTYNASKAAGHD FKAQPELAEAAAKTTENPLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEA RSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLRKGNSKLEGQLEFSLL TEVETPIRNEWGSRSNDSSDPLESLLTEVETPIRNEWGSRSNDSSDPGSSLLTEVETPIR NEWGSRSNDSSDPELSLLTEVETPIRNEWGSRSNDSSDPSRSREFSLLTEVETPTRNEWE SRSSDSSDPLESLLTEVETPTRNEWESRSSDSSDPESSLLTEVETPTRNEWESRSSDSSD PGSSLLTEVETPTRNEWESRSSDSSDPSR Figure 32
35 Patent Application Publication Jun. 25, 2009 Sheet 34 of 85 US 2009/ Al SEQ ID: 87 Nucleic acid sequence of pmt/stf2.4xm2e (H1H5) ATGAAGTTATGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGA TCTGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAAC AAATCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATC AACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAAC ATCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAG ACCACTGAAGGCGCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTG GCGGTTCAGTCTGCTAACAGCACCAACTCCCAGTCTGACCTCGACTCCATCCAGGCT GAAATCACCCAGCGCCTGAACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAAC GGCGTGAAAGTCCTGGCGCAGGACAACACCCTGACCATCCAGGTTGGCGCCAACGAC GGTGAAACTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGGTCTGGAC TCACTGAACGTGCAGAAAGCGTATGATGTGAAAGATACAGCAGTAACAACGAAAGCT TATGCCAATAATGGTACTACACTGGATGTATCGGGTCTTGATGATGCAGCTATTAAA GCGGCTACGGGTGGTACGAATGGTACGGCTTCTGTAACCGGTGGTGCGGTTAAATTT GACGCAGATAATAACAAGTACTTTGTTACTATTGGTGGCTTTACTGGTGCTGATGCC GCCAAAAATGGCGATTATGAAGTTAACGTTGCTACTGACGGTACAGTAACCCTTGCG GCTGGCGCAACTAAAACCACAATGCCTGCTGGTGCGACAACTAAAACAGAAGTACAG GAGTTAAAAGATACACCGGCAGTTGTTTCAGCAGATGCTAAAAATGCCTTAATTGCT GGCGGCGTTGACGCTACCGATGCTAATGGCGCTGAGTTGGTCAAAATGTCTTATACC GATAAAAATGGTAAGACAATTGAAGGCGGTTATGCGCTTAAAGCTGGCGATAAGTAT TACGCCGCAGATTACGATGAAGCGACAGGAGCAATTAAAGCTAAAACTACAAGTTAT ACTGCTGCTGACGGCACTACCAAAACAGCGGCTAACCAACTGGGTGGCGTAGACGGT AAAACCGAAGTCGTTACTATCGACGGTAAAACCTACAATGCCAGCAAAGCCGCTGGT CATGATTTCAAAGCACAACCAGAGCTGGCGGAAGCAGCCGCTAAAACCACCGAAAAC CCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTG GGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGTAAAC AATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACCGAAGTTTCC AACATGTCTCGCGCGCAGATTCTGCAGCAGGCCGGTACTTCCGTTCTGGCGCAGGCT AACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGTAAGGGCAATTCGAAGCTTGAA GGTCAATTGGAATTCAGCTTGCTGACTGAGGTTGAGACCCCGATTCGCAACGAATGG GGTTCCCGTTCCAACGATTCTTCCGACCCGCTCGAGAGCCTGTTGACCGAGGTTGAA ACCCCTATCCGTAATGAATGGGGCTCCCGTAGCAACGACTCTTCTGACCCAGGATCC TCCCTCTTGACCGAAGTGGAAACGCCTATTCGTAATGAGTGGGGTTCTCGTAGCAAT GACAGCTCGGACCCGGAGCTCTCGCTGCTGACGGAAGTGGAGACTCCGATCCGTAAC GAGTGGGGCTCTCGCTCTAACGATAGCTCAGACCCGTCTAGATCTAGAGAATTCTCT CTGCTGACTGAAGTAGAAACTCCAACGCGTAATGAATGGGAATCCCGTTCTAGCGAC TCCTCTGATCCTCTCGAGTCCCTGCTGACGGAGGTTGAAACCCCGACCCGCAACGAG TGGGAAAGCCGTTCCTCCGATTCCTCTGATCCGGAGAGCAGCCTGCTGACCGAGGTA GAAACCCCGACCCGTAATGAGTGGGAATCTCGCTCCTCTGATTCTTCTGACCCGGGA TCCTCTCTGCTGACCGAAGTGGAGACTCCGACTCGCAACGAATGGGAGAGCCGTTCT TCTGACTCCTCTGACCCGTCTAGATAA Figure 33
36 Patent Application Publication Jun. 25, 2009 Sheet 35 of 85 US 2009/ Al SEQ ID: 88 Amino acid sequence of pmt/stf2r MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLS SGLRINSAKDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEI NNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKV LAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVHGAPVDPASPWTEN PLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSDY ATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLREFSRYPAQWRPLTRTG HHHHHH. Figure 34
37 Patent Application Publication Jun. 25, 2009 Sheet 36 of 85 US 2009/ Al SEQ ID: 89 Nucleic acid sequence of pmt/stf20 ATGAAGTTATGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCG GGAGATCTGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAA TAACCTGAACAAATCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCT TCTGGTCTGCGTATCAACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTG CTAACCGTTTCACCGCGAACATCAAAGGTCTGACTCAGGCTTCCCGTAACGC TAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAACGAAATC AACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAGCA CCAACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCT GAACGAAATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTC CTGGCGCAGGACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAA CTATCGATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGGTCTGGACTC ACTGAACGTGCATGGAGCGCCGGTGGATCCTGCTAGCCCATGGACCGAAAAC CCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTG ATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAA TACCGTAAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTAC GCGACCGAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTA CTTCCGTTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTT ACGTGAATTCTCTAGATATCCAGCACAGTGGCGGCCGCTCACGCGTACCGGT CATCATCACCATCACCATTGA Figure 35
38 Patent Application Publication Jun. 25, 2009 Sheet 37 of 85 US 2009/ Al SEQ ID: 90 Amino acid sequence of pmt/stf2n.4xm2e(h1) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLS SGLRINSAKDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEI NNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKV LAQDNTLTIQVGANDGETIDIDLKQINSQTLGLDSLNVHGAPVDPASPWTEN PLQKIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDSDY ATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLREFSLLTEVETPIRNEW GSRSNDSSDPLESLLTEVETPIRNEWGSRSNDSSDPGSSLLTEVETPIRNEW GSRSNDSSDPELSLLTEVETPIRNEWGSRSNDSSDPSR Figure 36
39 Patent Application Publication Jun. 25, 2009 Sheet 38 of 85 US 2009/ Al SEQ ID: 91 Nucleic acid sequence of pmt/stf2l.4xm2e(h1) ATGTGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGAT CTGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCT GAACAAATCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGT CTGCGTATCAACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACC GTTTCACCGCGAACATCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGA CGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAACGAAATCAACAAC AACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAGCACCAACT CCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGA AATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCG CAGGACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCG ATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAA CGTGCATGGAGCGCCGGTGGATCCTGCTAGCCCATGGACCGAAAACCCGCTG CAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGG GTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGT AAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACC GAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCG TTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGT GA ATTCAGCTTGCTGACTGAGGTTGAGACCCCGATTCGCAACGAATGGGGTTCC CGTTCCAACGATTCTTCCGACCCGCTCGAGAGCCTGTTGACCGAGGTTGAAA CCCCTATCCGTAATGAATGGGGCTCCCGTAGCAACGACTCTTCTGACCCAGG ATCCTCCCTCTTGACCGAAGTGGAAACGCCTATTCGTAATGAGTGGGGTTCT CGTAGCAATGACAGCTCGGACCCGGAGCTCTCGCTGCTGACGGAAGTGGAGA CTCCGATCCGTAACGAGTGGGGCTCTCGCTCTAACGATAGCTCAGACCCGTC TAGATAA Figure 37
40 Patent Application Publication Jun. 25, 2009 Sheet 39 of 85 US 2009/ Al SEQ ID: 92 amino acid sequence of pmt/stf2a.4xm2e(h5) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRIN SAKDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQS ANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDID LKQINSQTLGLDSLNVHGAPVDPASPWTENPLQKIDAALAQVDALRSDLGAVQNRFNSAI TNLGNTVNNLSEARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLREF SLLTEVETPTRNEWESRSSDSSDPLESLLTEVETPTRNEWESRSSDSSDPESSLLTEVET ^I^I^^3f.'^.^a^'^^^X^^^^X'^^^fl^ali^^^l^^^^^ ' C 1!?f ^^.Y.^^^f ^ ' Figure 38
41 Patent Application Publication Jun. 25, 2009 Sheet 40 of 85 US 2009/ Al SEQ ID: 93 Nucleic acid sequence of pmt/stf2a.4xm2e(h5) (Linker underlined) ATGTGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGAT CTGCACAAGTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCT GAACAAATCCCAGTCCGCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGT CTGCGTATCAACAGCGCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACC GTTTCACCGCGAACATCAAAGGTCTGACTCAGGCTTCCCGTAACGCTAACGA CGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAACGAAATCAACAAC AACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAGCACCAACT CCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGA AATCGACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCG CAGGACAACACCCTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCG ATATCGATCTGAAGCAGATCAACTCTCAGACCCTGGGTCTGGACTCACTGAA CGTGCATGGAGCGCCGGTGGATCCTGCTAGCCCATGGACCGAAAACCCGCTG CAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCGCTGCGCTCTGATCTGG GTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGCAATACCGT AAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACC GAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCG TTCTGGCGCAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGTGA ATTCTCTCTGCTGACTGAAGTAGAAACTCCAACGCGTAATGAATGGGAATCC CGTTCTAGCGACTCCTCTGATCCTCTCGAGTCCCTGCTGACGGAGGTTGAAA CCCCGACCCGCAACGAGTGGGAAAGCCGTTCCTCCGATTCCTCTGATCCGGA GAGCAGCCTGCTGACCGAGGTAGAAACCCCGACCCGTAATGAGTGGGAATCT CGCTCCTCTGATTCTTCTGACCCGGGATCCTCTCTGCTGACCGAAGTGGAGA CTCCGACTCGCAACGAATGGGAGAGCCGTTCTTCTGACTCCTCTGACCCGTC TAGATAATAA Figure 39
42 Patent Application Publication Jun. 25, 2009 Sheet 41 of 85 US 2009/ Al SEQ ID: 94 Amino acid sequence of pmt/stf2l.4xm2e(h1h5) MKLCILLAVVAFVGLSLGRSAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRIN SAKDDAAGQAIANRFTANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQS ANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDID LKQINSQTLGLDSLNVHGAPVDPASPWTENPLQKIDAALAQVDALRSDLGAVQNRFNSAI TNLGNTVNNLSEARSRIEDSDYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLR EF SLLTEVETPIRNEWGSRSNDSSDPLESLLTEVETPIRNEWGSRSNDSSDPGSSLLTEVET PIRNEWGSRSNDSSDPELSLLTEVETPIRNEWGSRSNDSSDPSRQFSLLTEVETPTRNEW ESRSSDSSDPLESLLTEVETPTRNEWESRSSDSSDPESSLLTEVETPTRNEWESRSSDSS DPGSSLLTEVETPTRNEWESRSSDSSDPSR Figure 40
43 Patent Application Publication Jun. 25, 2009 Sheet 42 of 85 US 2009/ Al SEQ ID: 95 Nucleic acid sequence of pmt/stf2l.4xm2e(h1h5) ATGTGCATATTACTGGCCGTCGTGGCCTTTGTTGGCCTCTCGCTCGGGAGATCTGCACAA GTAATCAACACTAACAGTCTGTCGCTGCTGACCCAGAATAACCTGAACAAATCCCAGTCC GCACTGGGCACCGCTATCGAGCGTCTGTCTTCTGGTCTGCGTATCAACAGCGCGAAAGAC GATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGTCTGACTCAG GCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGCGCGCTGAAC GAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCTAACAGCACC AACTCCCAGTCTGACCTCGACTCCATCCAGGCTGAAATCACCCAGCGCCTGAACGAAATC GACCGTGTATCCGGCCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAGGACAACACC CTGACCATCCAGGTTGGCGCCAACGACGGTGAAACTATCGATATCGATCTGAAGCAGATC AACTCTCAGACCCTGGGTCTGGACTCACTGAACGTGCATGGAGCGCCGGTGGATCCTGCT AGCCCATGGACCGAAAACCCGCTGCAGAAAATTGATGCCGCGCTGGCGCAGGTGGATGCG CTGCGCTCTGATCTGGGTGCGGTACAAAACCGTTTCAACTCTGCTATCACCAACCTGGGC AATACCGTAAACAATCTGTCTGAAGCGCGTAGCCGTATCGAAGATTCCGACTACGCGACC GAAGTTTCCAACATGTCTCGCGCGCAGATTTTGCAGCAGGCCGGTACTTCCGTTCTGGCG CAGGCTAACCAGGTCCCGCAGAACGTGCTGTCTCTGTTACGT GAATTCAGCTTGCTGACT GAGGTTGAGACCCCGATTCGCAACGAATGGGGTTCCCGTTCCAACGATTCTTCCGACCCG CTCGAGAGCCTGTTGACCGAGGTTGAAACCCCTATCCGTAATGAATGGGGCTCCCGTAGC AACGACTCTTCTGACCCAGGATCCTCCCTCTTGACCGAAGTGGAAACGCCTATTCGTAAT GAGTGGGGTTCTCGTAGCAATGACAGCTCGGACCCGGAGCTCTCGCTGCTGACGGAAGTG GAGACTCCGATCCGTAACGAGTGGGGCTCTCGCTCTAACGATAGCTCAGACCCGTCTAGA TCTAGAGAATTCTCTCTGCTGACTGAAGTAGAAACTCCAACGCGTAATGAATGGGAATCC CGTTCTAGCGACTCCTCTGATCCTCTCGAGTCCCTGCTGACGGAGGTTGAAACCCCGACC CGCAACGAGTGGGAAAGCCGTTCCTCCGATTCCTCTGATCCGGAGAGCAGCCTGCTGACC GAGGTAGAAACCCCGACCCGTAATGAGTGGGAATCTCGCTCCTCTGATTCTTCTGACCCG GGATCCTCTCTGCTGACCGAAGTGGAGACTCCGACTCGCAACGAATGGGAGAGCCGTTCT TCTGACTCCTCTGACCCGTCTAGATAA Figure 41
44 Patent Application Publication Jun. 25, 2009 Sheet 43 of 85 US 2009/ Al SEQ ID NO: 98 Salmonella muenchen flic Amino Acid Sequence (Hinge region deleted) MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANRFTANIKG LTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQSANGTNSQSDLDSIQAEITQRL NEIDRVSGQTQFNGVKVLAQDNTLTIQVGANDGETIDIDLKEISSKTLDKHNFRTGGELK EVNTDKTENPLQKIDAALAQVDTLRSDLGAVQNRFNSAITNLGNTVNNLSSARSRIEDSD YATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLR Figure 42
45 Patent Application Publication Jun. 25, 2009 Sheet 44 of 85 US 2009/ Al SEQ ID NO: 99 Salmonella Muenchen flic Nucleic Acid Sequence (Hinge region deleted) ATGGCACAAGTCATTAATACAAACAGCCTGTCGCTGTTGACCCAGAATAACCTGAACAAA TCCCAGTCCGCTCTGGGCACCGCTATCGAGCGTCTGTCTTCCGGTCTGCGTATCAACAGC GCGAAAGACGATGCGGCAGGTCAGGCGATTGCTAACCGTTTCACCGCGAACATCAAAGGT CTGACTCAGGCTTCCCGTAACGCTAACGACGGTATCTCCATTGCGCAGACCACTGAAGGC GCGCTGAACGAAATCAACAACAACCTGCAGCGTGTGCGTGAACTGGCGGTTCAGTCTGCT AACGGTACTAACTCCCAGTCTGACCTTGACTCTATCCAGGCTGAAATCACCCAGCGTCTG AACGAAATCGACCGTGTATCCGGTCAGACTCAGTTCAACGGCGTGAAAGTCCTGGCGCAG GACAACACCCTGACCATCCAGGTTGGTGCCAACGACGGTGAAACTATTGATATTGATTTA AAAGAAATTAGCTCTAAAACACTGACAGATAAGACTGAAAACCCACTGCAGAAAATTGAT GCTGCCTTGGCACAGGTTGATACACTTCGTTCTGACCTGGGTGCGGTACAGAACCGTTTC AACTCCGCTATCACCAACCTGGGCAATACCGTAAATAACCTGTCTTCTGCCCGTAGCCGT ATCGAAGATTCCGACTACGCGACCGAAGTCTCCAACATGTCTCGCGCGCAGATTCTGCAG CAGGCCGGTACCTCCGTTCTGGCGCAGGCTAACCAGGTTCCGCAAAACGTCCTCTCTTTA CTGCGTTAA Figure 43
46 Patent Application Publication Jun. 25, 2009 Sheet 45 of 85 US 2009/ Al 6000 IL-8 Secretion Following Stimulation of TLR5+ Cells 0 STF2.OVA 5000 _ STF2.4xM2E QO cs concentration, ng/ml Figure 44
47 Patent Application Publication Jun. 25, 2009 Sheet 46 of 85 US 2009/ Al 300 TNF Secretion Following Stimulation of TLR2+ Cells z 250 ALPS 200 a LPS+PMB I Pam3Cys Pam3Cys+PM B + Pam3Cys.M2e 100 $ Pam3Cys.M2e+PMB concentration, ng/ml Figure 45
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