RU2773273C2 - Neoantigens and their application methods - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to the field of biotechnology, specifically to a pharmaceutical composition containing neoantigen peptide for use in the treatment of mammary gland cancer. The obtained pharmaceutical composition contains neoantigen peptide containing tumor-specific neoepitope containing one or several adjacent mutant amino acids encoded by a sequence obtained by a mutation of a reading frame shift in GATA3 gene, where tumor-specific neoepitope is encoded by GATA3 gene of subject’s cancer cells or expressed by subject’s cancer cells.

EFFECT: invention can be used for the effective treatment of mammary gland cancer.

23 cl, 9 dwg, 3 tbl, 9 ex

Description

CROSS REFERENCES

[1] This application claims priority of U.S. Provisional Application No. 62/316530 filed March 31, 2016, U.S. Provisional Application No. 62/316533 filed March 31, 2016, U.S. Provisional Application No. 62/316547 filed March 31, 2016, U.S. Provisional Application No. 62/316552 filed March 31, 2016, U.S. Provisional Application No. 62/316567 filed April 1, 2016, and U.S. Provisional Application No. 62/316571 filed April 1, 2016, each of which is incorporated herein in its entirety description by reference.

FIELD OF TECHNOLOGY TO WHICH THE INVENTION RELATES

[2] The present invention relates to the field of immunotherapeutic peptides, peptide-encoding nucleic acids, peptide-binding agents, and their use, for example, in cancer immunotherapy. In one aspect, the invention relates to neoantigenic peptides useful alone or in combination with other tumor-associated peptides, anti-cancer agents, or immunomodulatory agents for the treatment of cancer.

BACKGROUND OF THE INVENTION

[3] Cancer vaccines typically consist of tumor antigens and immunostimulatory molecules (eg, adjuvants, cytokines, or TLR ligands) that work together to induce antigen-specific cytotoxic T cells (CTLs) that recognize and lyse tumor cells. Such vaccines contain general tissue-specific tumor antigens or a mixture of general and patient-specific antigens in the form of preparations based on whole tumor cells. Common tissue-specific tumor antigens are ideally immunogenic proteins that are selectively expressed in tumors in many individuals and are usually delivered to patients as synthetic peptides or recombinant proteins. In contrast, whole tumor cell preparations are delivered to patients as autologous irradiated cells, cell lysates, cell fusions, heat shock protein preparations, or total mRNA. Because whole tumor cells are isolated from an autologous patient, the cells may contain patient-specific tumor antigens as well as general tumor antigens. Finally, there is a third class of tumor antigens, neoantigens, which are rarely used in vaccines, which consist of proteins with tumor-specific mutations (which may be patient-specific or general) that result in altered amino acid sequences. Such mutant proteins: (a) are unique to the tumor cell, since the mutation and its corresponding protein are present only in the tumor; (b) avoid central tolerance and are therefore more likely to be immunogenic; (c) provide an excellent target for immunological recognition, including humoral and cellular immunity. However, for the use of personalized neoantigens, it is necessary to sequence the genome of each patient, and then obtain a composition with patient-specific neoantigens. Thus, there is still a need to develop additional therapeutic agents against malignant tumors.

BRIEF DESCRIPTION OF THE INVENTION

[4] Provided herein is an isolated neoantigenic peptide comprising a tumor-specific neoepitope, wherein the isolated neoantigenic peptide is not a native polypeptide, wherein the neoepitope contains at least 8 contiguous amino acid sequences represented by: A _x B _y C _z , where each of A and C is an amino acid corresponding to the native polypeptide, y is at least 1, and B is an amino acid substitution or insertion of the native polypeptide, x+y+z is at least 8, at least 8 contiguous amino acids contain By, and native полипептид кодируется геном, выбранным из группы, состоящей из: (a) ABL1, где A _x B _y C _z представляет собой (i) VADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGKVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVC, (ii) VADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGVVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVC, (iii) LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSATEY LEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF, (iv) SLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIIEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLA или (v) STVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQHGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLG; (b) ALK, where A _x B _y C _z is (i) SSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIADFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLL or (ii) QVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILMELMAGGDLKSFLELETRPSYQ; (c) BRAF where A _x B _y C _z is MIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATEKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELM; (d) BTK where A _x B _y C _z is MIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGSLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVND; (e) EEF1B2, where A _x B _y C _z is MGFGDLKSPAGLQVLNDYLADKSYIEGYVPSQADVAVFEAVSGPPPADLCHALRWYNHIKSYEKEKASLPGVKKALGKYGPADVEDTTGSGAT; (f) EGFR where A _x B _y C _z is (i) SLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIIRNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLL or (ii) IPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLIMQLMPFGCLLDYVREHK; (g) ERBB3 where A _x B _y C _z is ERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRMVRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDK; (h) ESR1, где A _x B _y C _z представляет собой (i) HLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYGLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEA, (ii) NQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLPSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSH, (iii) IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLCDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, (iv) IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLNDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE или (v) IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLSDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE; (i) FGFR3 where A _x B _y C _z is HRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERCPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVG; (j) FRG1B where A _x B _y C _z is AVKLSDSRIALKSGYGKYLGINSDELVGHSDAIGPREQWEPVFQNGKMALSASNSCFIRCNEAGDIEAKSKTAGEEEMIKIRSCAEKETKKKDDIPEEDKG; (k) HER2, where A _x B _y C _z is GSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGLGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM; (l) IDH1, где A _x B _y C _z представляет собой (i) RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGHHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM, (ii) RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGCHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM, (iii) RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGGHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM, или (iv) RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGSHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM; (m) SET, where A _x B _y C _z is (i) VEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIANLLGACTIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYK, or (ii) VEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIANLLGCCACTIGGPTTLVITEKLYK, or (ii) VEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIANLLGCCACTIGGPTTLVITEKLYK; (n) MEK, где A _x B _y C _z представляет собой (i) ISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHESNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSI или (ii) LGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSLYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVI; (o) MYC, где A _x B _y C _z представляет собой (i) MPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSDLQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGG, (ii) FTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLSTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLG или (iii) TNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPIPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGG; (p) PDGFRa where A _x B _y C _z is VAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIIIEYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSYVILS; (q) PIK3CA, где A _x B _y C _z представляет собой (i) IEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLSKITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPP, (ii) HANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLSEITKQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKP, или (iii) LFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDARHGGWTTKMDWIFHTIKQHALN; (r) POLE, where A _x B _y C _z is QRGGVITDEEETSKKIADQLDNIVDMREYDVPYHIRLSIDIETTKLPLKFRDAETDQIMMISYMIDGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCVFN; (s) PTEN where A _x B _y C _z is KFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGQTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY; (t) RAC1 where A _x B _y C _z is MQAIKCVVVGDGAVGKTCLLISYTTNAFSGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTVGET; и (u) TP53, где A _x B _y C _z представляет собой (i) IRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGSMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEP, (ii) TYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRHCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEV, (iii) EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNQRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE, (iv) EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNWRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE или (v) PEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVCVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPL.

[5] In embodiments, the native polypeptide is encoded by the EGFR, ERBB3, or FGFR3 gene and at least one By is extracellularly expressed.

[6] Provided herein is an isolated neoantigenic peptide comprising a tumor-specific neoepitope, wherein the isolated neoantigenic peptide is not a native polypeptide, wherein the neoepitope comprises at least 8 contiguous amino acid sequences represented by: A _x B _y C _z , where each A is amino acid corresponding to the native polypeptide; By is absent; each C is an amino acid encoded by a frameshift of the native polypeptide coding sequence; x+y+z is at least 8; at least 8 contiguous amino acids contain at least one Cz; и нативный полипептид кодируется геном, выбранным из группы, состоящей из: (a) APC, где Cz представляет собой (i) AKFQQCHSTLEPNPADCRVLVYLQNQPGTKLLNFLQERNLPPKVVLRHPKVHLNTMFRRPHSCLADVLLSVHLIVLRVVRLPAPFRVNHAVEW, (ii) APVIFQIALDKPCHQAEVKHLHHLLKQLKPSEKYLKIKHLLLKRERVDLSKLQ или (iii) MLQFRGSRFFQMLILYYILPRKVLQMDFLVHPA; (b) ARID1A, где Cz представляет собой (i) ALGPHSRISCLPTQTRGCILLAATPRSSSSSSSNDMIPMAISSPPKAPLLAAPSPASRLQCINSNSRITSGQWMAHMALLPSGTKGRCTACHTALGRGSLSSSSCPQPSPSLPASNKLPSLPLSKMYTTSMAMPILPLPQLLLSADQQAAPRTNFHSSLAETVSLHPLAPMPSKTCHHK, (ii) AHQGFPAAKESRVIQLSLLSLLIPPLTCLASEALPRPLLALPPVLLSLAQDHSRLLQCQATRCHLGHPVASRTASCILP, (iii) PILAATGTSVRTAARTWVPRAAIRVPDPAAVPDDHAGPGAECHGRPLLYTADSSLWTTRPQRVWSTGPDSILQPAKSSPSAAAATLLPATTVPDPSCPTFVSAAATVSTTTAPVLSASILPAAIPASTSAVPGSIPLPAVDDTAAPPEPAPLLTATGSVSLPAAATSAASTLDALPAGCVSSAPVSAVPANCLFPAALPSTAGAISRFIWVSGILSPLNDLQ, (iv) PCRAGRRVPWAASLIHSRFLLMDNKAPAGMVNRARLHITTSKVLTLSSSSHPTPSNHRPRPLMPNLRISSSHSLNHHSSSPLSLHTPSSHPSLHISSPRLHTPPSSRRHSSTPRASPPTHSHRLSLLTSSSNLSSQHPRRSPSRLRILSPSLSSPSKLPIPSSASLHRRSYLKIHLGLRHPQPPQ, (v) RTNPTVRMRPHCVPFWTGRILLPSAASVCPIPFEACHLCQAMTLRCPNTQGCCSSWAS или (vi) TNQALPKIEVICRGTPRCPSTVPPSPAQPYLRVSLPEDRYTQAWAPTSRTPWGAMVPRGVSMAHKVATPGSQTIMPCPMPTTPVQAWLEA; (c) β2M, where Cz is (i) RMERELKKWSIQTCLSARTGLSISCTTLNSPPLKKMSMPAV or (ii) LCSRYSLFLAWRLSSVLQRFRFTHVIQQRMESQIS; (d) CDH1, где Cz представляет собой (i) RSACVTVKGPLASVGRHSLSKQDCKFLPFWGFLEEFLLC, (ii) IQWGTTTAPRPIRPPFLESKQNCSHFPTPLLASEDRRETGLFLPSAAQKMKKAHFLKTWFRSNPTKTKKARFSTASLAKELTHPLLVSLLLKEKQDG, (iii) PTDPFLGLRLGLHLQKVFHQSHAEYSGAPPPPPAPSGLRFWNPSRIAHISQLLSWPQKTEERLGYSSHQLPRK, (iv) FCCSCCFFGGERWSKSPYCPQRMTPGTTFITMMKKEAEKRTRTLT или (v) WRRNCKAPVSLRKSVQTPARSSPARPDRTRRLPSLGVPGQPWALGAAASRRCCCCCRSPLGSARSRSPATLALTPRATRSRCPGATWREAASWAE; (e) GATA3, where Cz is (i) PGRPLQTHVLPEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHRHGLEPCSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLKAESKIMFATLQRSSLWCLCSNH; or (ii) PRPRRCTRHPACPLDHTTPPAWSPPWVRALLDAHRAPSESPCSPFRLAFLQEQYHEA; (f) MLL2, где Cz представляет собой TRRCHCCPHLRSHPCPHHLRNHPRPHHLRHHACHHHLRNCPHPHFLRHCTCPGRWRNRPSLRRLRSLLCLPHLNHHLFLHWRSRPCLHRKSHPHLLHLRRLYPHHLKHRPCPHHLKNLLCPRHLRNCPLPRHLKHLACLHHLRSHPCPLHLKSHPCLHHRRHLVCSHHLKSLLCPLHLRSLPFPHHLRHHACPHHLRTRLCPHHLKNHLCPPHLRYRAYPPCLWCHACLHRLRNLPCPHRLRSLPRPLHLRLHASPHHLRTPPHPHHLRTHLLPHHRRTRSCPCRWRSHPCCHYLRSRNSAPGPRGRTCHPGLRSRTCPPGLRSHTYLRRLRSHTCPPSLRSHAYALCLRSHTCPPRLRDHICPLSLRNCTCPPRLRSRTCLLCLRSHACPPNLRNHTCPPSLRSHACPPGLRNRICPLSLRSHPCPLGLKSPLRSQANALHLRSCPCSLPLGNHPYLPCLESQPCLSLGNHLCPLCPRSCRCPHLGSHPCRLS; (g) PTEN, где Cz представляет собой (i) SWKGTNWCNDMCIFITSGQIFKGTRGPRFLWGSKDQRQKGSNYSQSEALCVLL, (ii) KRTKCFTFG, (iii) PIFIQTLLLWDFLQKDLKAYTGTILMM, (iv) QKMILTKQIKTKPTDTFLQILR, (v) GFWIQSIKTITRYTIFVLKDIMTPPNLIAELHNILLKTITHHS, (vi) NYSNVQWRNLQSSVCGLPAKGEDIFLQFRTHTTGRQVHVL или (vii) YQSRVLPQTEQDAKKGQNVSLLGKYILHTRTRGNLRKSRKWKSM; (h) TP53, где Cz представляет собой (i) SSQNARGCSPRGPCTSSSYTGGPCTSPLLAPVIFCPFPENLPGQLRFPSGLLAFWDSQVCDLHVLPCPQQDVLPTGQDLPCAAVG, (ii) GAAPTMSAAQIAMVWPLLSILSEWKEICVWSIWMTETLFDIVWWCPMSRLRLALTVPPSTTTTCVTVPAWAA, (iii) TGGPSSPSSHWKTPVVIYWDGTALRCVFVPVLGETGAQRKRISARKGSLTTSCPQGALSEHCPTTPAPLPSQRRNHWMENISPFRSVGVSASRCSES, (iv) FHTPARHPRPRHGHLQAVTAHDGGCEALPPP, (v) CCPRTILNNGSLKTQVQMKLPECQRLLPPWPLHQQLLHRRPLHQPPPGPCHLLSLPRKPTRAATVSVWASCILGQPSL, (vi) VRKHFQTYGNYFLKTTFCPPCRPKQWMI, или (vii) LARTPLPSTRCFANWPRPALCSCGLIPHPRPAPASAPWPSTSSHST; или (i) VHL, где Cz представляет собой (i) ELQETGHRQVALRRSGRPPKCAERPGAADTGAHCTSTDGRLKISVETYTVSSQLLMVLMSLDLDTGLVPSLVSKCLILRVK, (ii) KSDASRLSGA, (iii) RTAYFCQYHTASVYSERAMPPGCPEPSQA, (iv) TRASPPRSSSAIAVRASCCPYGSTSTASRSPTQRCRLARAAASTATEVTFGSSEMQGHTMGFWLTKLNYLCHLSMLTDSLFLPISHCQCIL, (v) SSLRITGDWTSSGRSTKIWKTTQMCRKTWSG, или (vi) RRRRGGVGRRGVRPGRVRPGGTGRRGGDGGRAAAARAALGELARALPGHLLQSQSARRAARMAQLRRRAAALPNAAAWHGPPHPQLPRSPLALQRCRDTRWASG; (j) ACVR2A, where A _x B _y C _z is (i) GVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDDINCYDRTDCVEKKRQP, or (ii) GVEEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDINCYDRTDCVEKKTALKYIFVAVRAICVMKSFLIFRRWKSHSPLQIQLHLSHPITTSCSIPWCHLC; (k) C15ORF40 where A _x B _y C _z is TAEAVNVAIAAPPSEGEANAELCRYLSKVLELRRKSDVVLDKVGLALFFFFFETKSCSVAQAGVQWRSLGSLQPPPPGFKLFSCLSFLSSWDYRRMPPCLANFCIFNRDGVSPCWSGWS; (l) CNOT1, where A _x B _y C _z is (i) LSVIIFFFVYIWHWALPLILNNHHICLMSSIILDCNSVRQSIMSVCFFFFSVIFSTRCLTDSRYPNICWFK, or (ii) LSVIIFFFVYIWHWALPLILNNHHICLMSSIILDCNSVRQSIMSVCFFFFCYILNTMFDR; (m) EIF2B3, where A _x B _y C _z or Cz is VLVLSCDLITDVALHEVVDLFRAYDASLAMLMRKGQDSIEPVPGQKGKKKQWSSVTSLEWTAQERGCSSWLMKQTWMKSWSLRDPSYRSILEYVSTRVLWMPTSTV; (n) EPHB2, where A _x B _y C _z or Cz is SIQVMRAQMNQIQSVEGQPLARRPRATGRTKRCQPRDVTKKTCNSNDGKKREWEKRKQILGGGGKYKEYFLKRILIRKAMTVLAGDKKGLGRFMRCVQSETKAVSLQLPLGR; (o) ESRP1 where A _x B _y C _z is (i) LDFLGEFATDIRTHGVHMVLNHQGRPSGDAFIQMKSADRAFMAAQKCHKKKHEGQIC, or (ii) LDFLGEFATDIRTHGVHMVLNHQGRPSGDAFIQMKSADRAFMAAQKCHKKT; (p) FAM11B, where A _x B _y C _z is GALCKDGRFRSDIGEFEWKLKEGHKKIYGKQSMVDEVSGKVLEMDISKKKHYNRKISIKKLNRMKVPLMKLITRV; (q) GBP3, where A _x B _y C _z is RERAQLLEEQEKTLTSKLQEQARVLKERCQGESTQLQNEIQKLQKTLKKKPRDICRIS; (r) JAK1 where A _x B _y C _z is (i) VNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFEALLKTSN or (ii) CRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEEQNPDIVSEKNQQLKWTPHILKSAS; (s) LMAN1 where A _x B _y C _z is (i) DDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQQELDKKKRGIPEGPPRPPRAACGGNI, or (ii) DDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQQELDKKKRNSRRATPTSKGSLRRKYLRV; (t) MSH3, where A _x B _y C _z is (i) TKSTLIGEDVNPLIKLDDAVNVDEIMTDTSYLLCISENKENVRDKKKGQHFYWHCGSAACHRRGCV, or (ii) LYTKSTLIGEDVNPLIKLDDAVNVDEIMTDTSTSYLLCISENKENVRDKKRATFLLALWECSLPQARLCLIVSRTLLLVQS; (u) NDUFC2, where A _x B _y C _z is (i) LPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQLLYITAFFFCWILSCKT, or (ii) SLPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQLLYITAFFLLDIIL; (v) RBM27, where A _x B _y C _z is NQSGGAGEDCQIFSTPGHPKMIYSSSNLKTPSKLCSGSKSHDVQEVLKKKTGSNEVTTRYEEKKTGSVRKANRMPKDVNIQVRKKQKHETRRKSKYNEDFERAWREDLTIKR; (w) RPL22, where A _x B _y C _z is (i) MAPVKKLVVKGGKKKEASSEVHS, or (ii) MAPVKKLVVKGGKKRSKF; (x) SEC31A, where A _x B _y C _z is (i) MPSHQGAEQQQQQHHVFISQVVTEKEFLSRSDQLQQAVQSQGFINYCQKKN or (ii) MPSHQGAEQQQQQHHVFISQVVTEKEFLSRSDQLQQAVQSQGFINYCQKKLMLLRLNLRKMCGPF; (y) SEC63 where A _x B _y C _z is (i) AEVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKKKETFKKKTYTCAITTVKATETKAGKWSRWE, or (ii) MAEVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKKRNL; (z) SLC35F5 where A _x B _y C _z is NIMEIRQLPSSHALEAKLSRMSYPVKEQESILKTVGKLTATQVAKISFFFALCGFWQICHIKKHFQTHKLL; (aa) SMAP1 where A _x B _y C _z is (i) YEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKKKGREKERKGARKAGKTTYS, or (ii) KYEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKKRKRKRKREKRSQKSRQNHLQLKSCRRKISNWSLKWALK; (bb) TFAM where A _x B _y C _z is (i) IYQDAYRAEWQVYKEEISRFKEQLTPSQIMSLEKEIMDKHLKRKAMTKKKRVNTAWKTKKTSFSL, or (ii) IYQDAYRAEWQVYKEEISRFKEQLTPSQIMSLEKEIMDKHLKRKAMTKKKS; (cc) TGFBR2 where A _x B _y C _z is (i) KPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKAW, or (ii) EKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKSLVRLSSCVPVALMSAMTTSSSQKNITPAILTCC; (dd) THAP5 where A _x B _y C _z is VPSKYQFLCSDHFTPDSLDIRWGIRYLKQTAVPTIFSLPEDNQGKDPSKKNPRRKTWKMRKKYAQKPSQKNHLY; (ee) TTK where A _x B _y C _z is GTTEEMKYVLGQLVGLNSPNSILKAAKTLYEHYSGGESHNSSSSKTFEKKGEKNDLQLFVMSDTTYKIYWTVILLNPCGNLHLKTTSL; and (ff) XPOT where A _x B _y C _z is QQLIRETLISWLQAQMLNPQPEKTFIRNKAAQVFALLFVTEYLTKWPKFFLTFSQ.

[7] Provided herein is an isolated neoantigenic peptide comprising a tumor-specific neoepitope, wherein the isolated neoantigenic peptide is not a native polypeptide, wherein the neoepitope comprises at least 8 contiguous amino acid sequences represented by: A _x B _y C _z , where each A is an amino acid corresponding to the first native polypeptide; each C is an amino acid corresponding to the second native polypeptide or a cryptic exon or splice variant exon of the first native polypeptide, each B is an amino acid that is not an amino acid corresponding to the first native polypeptide, the second native polypeptide or the cryptic exon of the first native polypeptide, and x +y+z is at least 8 where y is absent and at least 8 contiguous amino acids contain at least one Ax and at least one Cz, or y is at least 1 and at least 8 contiguous amino acids contain at least one By, where: (a) the first native polypeptide is encoded by the BCR gene, the second native polypeptide is encoded by the ABL gene, and (i) y is 0 and A _x B _y C _z is ERAEWRENIREQQKKCFRSFSLTSVELQMLTNSCVKLQTVHSIPLTINKEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASG, or (ii) y is 1 and A _x B _y C _z is ELQM LTNSCVKLQTVHSIPLTINKEDDESPGLYGFLNVIVHSATGFKQSSKALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGD; (b) the first native polypeptide is encoded by the C11orf95 gene, the second native polypeptide is encoded by the RELA gene, y is 1, and A _x B _y C _z is ISNSWDAHLGLGACGEAEGLGVQGAEEEEEEEEEEEEEGAGVPACPPKGPELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTD; (c) the first native polypeptide is encoded by the CBFB gene and the second native polypeptide is encoded by the MYH11 gene, y is 0 and A _x B _y C _z is LQRLDGMGCLEFDEERAQQEDALAQQAFEEARRRTREFEDRDRSHREEMEVHELEKSKRALETQMEEMKTQLEELEDELQATEDAKLRLEVNMQALKGQF; (d) the first native polypeptide is encoded by the CD74 gene and the second native polypeptide is encoded by the ROS1 gene, y is 0 and A _x B _y C _z is KGSFPENLRHLKNTMETIDWKVFESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQ; (e) the first native polypeptide is encoded by the EGFR gene and the second native polypeptide is encoded by (i) the SEPT14 gene, y is 0 and A _x B _y C _z is LPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQLQDKFEHLKMIQQEEIRKLEEEKKQLEGEIIDFYKMKAASEALQTQLSTD; or (ii) EGFR genome, y is 1 and A _x B _y C _z is MRPSGTAGAALLAALCPASRALEEKKGNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPRCRKVCNGIGIGEFKD; (f) первый нативный полипептид кодируется геном EML4, второй нативный полипептид кодируется геном ALK, y представляет собой 1, и A _x B _y C _z представляет собой SWENSDDSRNKLSKIPSTPKLIPKVTKTADKHKDVIINQAKMSTREKNSQVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDL, (g) первый нативный полипептид кодируется геном FGFR3, второй нативный полипептид кодируется геном TACC3, y is 0 and A _x B _y C _z is _{EGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDVKATQEENRELRSRCEELHGKNLELGKIMDRFEEVVYQAMEEVQKQKELS} , (h) the first native polypeptide is encoded by the NAB gene, the second native polypeptide is encoded by the STAT6 gene, y is at least 1, and Az y is at least 1, and _{Az is} B RDNTLLLRRVELFSLSSRQVARESTYLSSLKGSRLHPEELGGPPLKKLKQEATSKSQIMSLWGLVSKMPPEKVQRLYVDFPQHLRHLLGDWLESQPWEFLVGSDAFCC; (i) the second native polypeptide is encoded by ERG, y is 0, and (i) the first native polypeptide is encoded by the NDRG1 gene, and A _x B _y C _z is MSREMQDVDLAEVKPLVEKGETITGLLQEFDVQEALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDW, or (ii) the first native polypeptide is encoded by the TMPRSS2 gene, and A _x B _y C _z is MALNSEALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDW; (j) первый нативный полипептид кодируется геном PML, второй нативный полипептид кодируется геном RARA, y представляет собой 1, и A _x B _y C _z представляет собой (i) VLDMHGFLRQALCRLRQEEPQSLQAAVRTDGFDEFKVRLQDLSSCITQGKAIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKG, или (ii) RSSPEQPRPSTSKAVSPPHLDGPPSPRSPVIGSEVFLPNSNHVASGAGEAAIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKG; (k) the first native polypeptide is encoded by the RUNX1 gene, the second native polypeptide is encoded by the CBFA2T1 gene (RUNX1T1), y is 1, and A _x B _y C _z is VARFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKITVDGPREPRNRTEKHSTMPDSPVDVKTQSRLTPPTMPPPPTTQGAPRTSSFTPTTLTNGT; (l) the first native polypeptide is encoded by the AR-v7 gene, the cryptic or splicing variant exon is encoded by the AR-v7 gene, y is 0, and A _x B _y C _z is SCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGEKFRVGNCKHLKMTRP.

[8] Provided herein is an isolated neoantigenic peptide comprising a tumor-specific neoepitope, wherein the isolated neoantigenic peptide is not a native polypeptide, wherein the neoepitope contains at least 8 contiguous amino acid sequences represented by: A _x B _y C _z , where each A is an amino acid corresponding to the first native polypeptide; each B is an amino acid that is not an amino acid corresponding to the first native polypeptide or the second native polypeptide, each C is an amino acid encoded by a frameshift of the sequence encoding the second native polypeptide; x+y+z is at least 8 where y is absent and at least 8 contiguous amino acids contain at least one Cz, or y is at least 1 and at least 8 contiguous amino acids contain at least one By and/or at least one Cz; and (a) the first native polypeptide is encoded by the AC011997.1 gene, the second native polypeptide is encoded by the LRRC69 gene, y is 1, and A _x B _y C _z is MAGAPPPASLPPCSLISDCCASNQRDSVGVGPSEPGNNIKICNESASRK, (b) the first native polypeptide is encoded by the EEF1DP3 gene, the second native polypeptide is encoded by FRY gene, y is 1 and A _x B _y C _z is HGWRPFLPVRARSRWNRRLDVTVANGRSWKYGWSLLRVPQVNGIQVLNVSLKSSSSNVISY, (c) the first native polypeptide is encoded by the MAD1L1 gene, the second native polypeptide is encoded by the MAFK gene, y is 0, and A _x B _y C _z is RLKEVFQTKIQEFRKACYTLTGYQIDITTENQYRLTSLYAEHPGDCLIFKLRVPGSSVLVTVPGL, или (d) первый нативный полипептид кодируется геном PPP1R1B, второй нативный полипептид кодируется геном STARD3, y представляет собой 1, и A _x B _y C _z представляет собой AEVLKVIRQSAGQKTTCGQGLEGPWERPPPLDESERDGGSEDQVEDPALSALLLRPRPPRPEVGAHQDEQAAQGADPRLGAQPACRGLPGLLTVPQPEPLLAPPSAA.

[9] In embodiments, the isolated neoantigenic peptide contains the sequence of Table 1. In embodiments, x+y+z is at most 500, at most 250, at most 150, at most 125, or at most 100. In embodiments, x+y +z is at least 8, at least 50, at least 100, at least 200, or at least 300. In embodiments, z is at most 500, at most 250, at most 150, at most 125, or at least greater than 100. In embodiments, z is at least 8, at least 50, at least 100, at least 200, or at least 300. In embodiments, the isolated neoantigenic peptide is about 8 to about 500 amino acids long. In embodiments, the isolated length of the isolated neoantigenic peptide is from about 8 to about 100 amino acids. In embodiments, the isolated neoantigenic peptide is about 8 to about 50 amino acids in length. In embodiments, the isolated neoantigenic peptide is about 15 to about 35 amino acids in length. In embodiments, the isolated neoantigenic peptide is between about 8 and about 15 amino acids in length. In embodiments, the isolated neoantigenic peptide is between about 8 and about 11 amino acids in length. In embodiments, the isolated neoantigenic peptide is 9 or 10 amino acids long. In embodiments, the isolated neoantigenic peptide binds a class I major histocompatibility complex (MHC). In embodiments, the isolated neoantigenic peptide binds class I MHCs with a binding affinity of about 500 nM or less. In embodiments, the isolated neoantigenic peptide binds MHC class I with a binding affinity of about 250 nM or less. In embodiments, the isolated neoantigenic peptide binds MHC class I with a binding affinity of about 50 nM or less. In embodiments, the isolated neoantigenic peptide is between about 8 and about 30 amino acids in length. In embodiments, the isolated neoantigenic peptide is about 8 to about 25 amino acids in length. In embodiments, the isolated neoantigenic peptide is about 15 to about 24 amino acids in length. In embodiments, the isolated neoantigenic peptide is about 9 to about 15 amino acids in length. In embodiments, the isolated neoantigenic peptide binds MHC class II. In embodiments, the isolated neoantigenic peptide binds MHC class II with a binding affinity of 1000 nM or less. In embodiments, the isolated neoantigenic peptide binds class I MHCs with a binding affinity of about 500 nM or less. In embodiments, the isolated neoantigenic peptide further comprises flanking amino acids. In embodiments, the flanking amino acids are not naturally occurring flanking amino acids. In embodiments, the total length of the isolated neoantigenic peptide is at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450, or at least 500 amino acids . In embodiments, the total length of the isolated neoantigenic peptide is no more than 8, no more than 9, no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more than 17, no more more than 18, no more than 19, no more than 20, no more than 21, no more than 22, no more than 23, no more than 24, no more than 25, no more than 26, no more than 27, no more than 28, no more than 29, no more than 30 , no more than 40, no more than 50, no more than 60, no more than 70, no more than 80, no more than 90, no more than 100, no more than 150, no more than 200, no more than 250, no more than 300, no more than 350, no more than 400, not more than 450 or not more than 500 amino acids. In embodiments, the isolated neoantigenic peptide is a first neoantigenic peptide linked to at least a second neoantigenic peptide. In embodiments, the isolated neoantigenic peptide is linked to at least a second neoantigenic peptide via a polyglycine or polyserine linker. In embodiments, the second neoantigenic peptide binds class I or class II MHCs with a binding affinity of less than about 1000 nM. In embodiments, the second neoantigenic peptide binds class I or class II MHCs with a binding affinity of less than about 500 nM. In embodiments, the isolated neoantigenic peptide and the second neoantigenic peptide bind human leukocyte antigen (HLA) -A, -B, -C, -DP, -DQ, or -DR. In embodiments, an isolated neoantigenic peptide binds HLA class I and a second neoantigenic peptide binds HLA class II. In embodiments, the isolated neoantigenic peptide binds HLA class II and the second neoantigenic peptide binds HLA class I. In embodiments, the isolated neoantigenic peptide further comprises a modification that increases in vivo half-life, cell targeting, antigen uptake, antigen processing, MHC affinity, MHC stability, antigen presentation, or a combination thereof. In embodiments, the modification is carrier protein conjugation, ligand conjugation, antibody conjugation, pegylation, polysialylation, hesylation, recombinant PEG mimetics, Fc fusion, albumin fusion, attachment of nanoparticles, nanoparticle envelope encapsulation, cholesterol fusion , iron fusion, acylation, amidation, glycosylation, side chain oxidation, phosphorylation, biotinylation, addition of a surfactant, addition of amino acid mimetics, or addition of unnatural amino acids. In embodiments, the isolated neoantigenic peptide further comprises a modification that increases cell targeting of antigen-presenting cells. In embodiments, the antigen presenting cells are dendritic cells. In embodiments, dendritic cells are targeted with the marker DEC205, XCR1, CD197, CD80, CD86, CD123, CD209, CD273, CD283, CD289, CD184, CD85h, CD85j, CD85k, CD85d, CD85g, CD85a, CD141, CD11c, CD83, receptor TSLP, Clec9a or CD1a. In embodiments, dendritic cells are targeted with the CD141, DEC205, Clec9a, or XCR1 marker. In embodiments, the dendritic cells are autologous cells. In embodiments, one or more dendritic cells are associated with a T cell. In embodiments, the T cell is an autologous T cell. In embodiments, the isolated neoantigenic peptide is not the isolated neoantigenic peptide shown in Table 2. In embodiments, the isolated neoantigenic peptide is fused to at least one additional neoantigenic peptide shown in Table 1 or 2.

[10] Provided herein is an in vivo delivery system comprising the isolated neoantigenic peptide described herein. In embodiments, the delivery system includes cell-penetrating peptides, nanoparticle encapsulation, virus-like particles, liposomes, or any combination thereof. In embodiments, the cell-penetrating peptide is a TAT peptide, herpes simplex virus VP22, transportan, Antp, or any combination thereof.

[11] Provided herein is a cell containing the isolated neoantigenic peptide described herein. In embodiments, the cell is an antigen presenting cell. In embodiments, the cell is a dendritic cell. In embodiments, the cell is an autologous cell. In embodiments, the cell is associated with a T cell. In embodiments, the T cell is an autologous T cell.

[12] Provided herein is a composition comprising the isolated neoantigenic peptide described herein.

[13] In embodiments, the composition comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, or at least 100 isolated neoantigenic peptides containing a tumor-specific neoepitope according to Table 1, or 2. In embodiments, the composition contains from about 2 to about 20 neoantigenic peptides, or about flax from 2 to about 30 neoantigenic peptides. In embodiments, a neoantigen specific for an individual's tumor. In embodiments, the composition further comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 , at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19 , at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, or at least 100 additional neoantigenic peptides. In embodiments, the composition contains from about 4 to about 20 additional neoantigenic peptides, from about 4 to about 30 additional neoantigenic peptides. In embodiments, at least one of the additional neoantigenic peptides is specific for a particular individual's tumor. In embodiments, a specific neoantigenic peptide from an individual is selected by identifying sequence differences between the genome, exome, and/or transcriptome of the individual's tumor sample and the genome, exome, and/or transcriptome of the non-tumor sample. In embodiments, the samples are fresh or formalin-fixed, paraffin-embedded tumor tissues, fresh isolated cells, or circulating tumor cells. In embodiments, sequence differences are determined by next generation sequencing.

[14] Provided herein is an isolated polynucleotide encoding the isolated neoantigenic peptide described herein. In embodiments, the polynucleotide is DNA. In embodiments, the polynucleotide is RNA. In embodiments, the RNA is a self-amplifying RNA. In embodiments, the RNA is modified to increase stability, increase cell targeting, increase translation efficiency, adjuvant, cytosolic accessibility, and/or reduce cytotoxicity. In embodiments, the modification is carrier protein conjugation, ligand conjugation, antibody conjugation, codon optimization, increased GC content, introduction of modified nucleosides, introduction of a 5' cap or cap analog, and/or introduction of an unmasked poly-A sequence.

[15] Provided herein is a cell containing the polynucleotide described herein.

[16] Provided herein is a vector containing the polynucleotide described herein. In embodiments, the polynucleotide is operably linked to a promoter. In embodiments, the vector is a self-amplifying RNA replicon, plasmid, phage, transposon, cosmid, virus, or virion. In embodiments, the vector is derived from an adeno-associated virus, a herpes virus, a lentivirus, or a pseudotype thereof.

[17] Provided herein is an in vivo delivery system comprising the isolated polynucleotide described herein. In embodiments, the delivery system comprises spherical nucleic acids, viruses, virus-like particles, plasmids, bacterial plasmids, or nanoparticles.

[18] Provided herein is a cell containing the vector or delivery system described herein. In embodiments, the cell is an antigen presenting cell. In embodiments, the cell is a dendritic cell. In embodiments, the cell is an immature dendritic cell.

[19] Provided herein is a composition comprising at least one polynucleotide as described herein. In embodiments, the composition contains at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90 or at least 100 isolated polynucleotides. In embodiments, the composition contains from about 2 to about 20 isolated polynucleotides, or from about 2 to about 30 isolated polynucleotides. In embodiments, the neoantigenic peptides are encoded by a vector containing one or more isolated polynucleotides. In embodiments, the composition further comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 , at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19 , at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29 , at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, or at least 100 additional neoantigenic polynucleotides encoding additional neoantigenic peptides. In embodiments, one or more additional neoantigenic peptides are encoded by a vector containing one or more additional neoantigenic polynucleotides. In embodiments, the composition contains from about 4 to about 20 additional neoantigenic polynucleotides, or from about 4 to about 30 additional neoantigenic polynucleotides. In embodiments, the isolated polynucleotides and additional neoantigenic polynucleotides are linked. In embodiments, the polynucleotides are linked using nucleic acids that encode a poly-glycine or poly-serine linker. In embodiments, at least one of the additional neoantigenic peptides is specific to a particular individual's tumor. In embodiments, the individual specific neoantigenic peptide from the individual is selected by identifying sequence differences between the genome, exome and/or transcriptome of the individual's tumor sample and the genome, exome and/or transcriptome of the non-tumor sample. In embodiments, the samples are fresh or formalin-fixed, paraffin-embedded tumor tissues, fresh isolated cells, or circulating tumor cells. In embodiments, sequence differences are determined by next generation sequencing.

[20] Provided herein is a T cell receptor (TCR) capable of binding at least one neoantigenic peptide as described herein or an MHC-peptide complex comprising at least one neoantigenic peptide as described herein. In embodiments, the MHC from the MHC peptide is a class I or class II MHC. In embodiments, the TCR is a bispecific TCR further comprising a domain containing an antibody or antibody fragment capable of binding an antigen. In embodiments, the antigen is a T cell specific antigen. In embodiments, the antigen is CD3. In embodiments, the antibody or antibody fragment is an anti-CD3 scFv.

[21] Provided herein is a chimeric antigen receptor comprising: (i) a T-cell activating molecule; (ii) a transmembrane region; and (iii) an antigen recognition fragment capable of binding at least one neoantigenic peptide as described herein or an MHC-peptide complex comprising at least one neoantigenic peptide as described herein. In embodiments, CD3-zeta is a T-cell activating molecule. In embodiments, the chimeric antigen receptor further comprises at least one costimulatory signaling domain. In embodiments, the signaling domain is CD28, 4-1BB, ICOS, OX40, ITAM, or Fc-epsilon-RI-gamma. In embodiments, the antigen recognition fragment is capable of binding an isolated neoantigenic peptide within a class I or class II MHC. In embodiments CD3-zeta, transmembrane region CD28, CTLA-4, ICOS, BTLA, KIR, LAG3, CD137, OX40, CD27, CD40L, Tim-3, A2aR, or PD-1. In embodiments, the neoantigenic peptide is located in the extracellular domain of a tumor-associated polypeptide. In embodiments, the MHC from the MHC peptide is a class I or class II MHC.

[22] Provided herein is a T cell comprising a T cell receptor or a chimeric antigen receptor as described herein, optionally wherein the T cell is a helper or cytotoxic T cell. In embodiments, the T cell is a T cell of an individual.

[23] Provided herein is a T cell comprising a T cell receptor (TCR) capable of binding at least one neoantigenic peptide as described herein, or an MHC-peptide complex comprising at least one neoantigenic peptide as described in the present description, where the T cell is a T cell isolated from a population of T cells from an individual, which was incubated with antigen presenting cells and one or more of at least one neoantigenic peptide described in the present description, for a period of time sufficient to activate T cells. In embodiments, the T cell is a CD8+ T cell, a helper T cell, or a cytotoxic T cell. In embodiments, the population of T cells from an individual is a population of CD8+ T cells from an individual. In embodiments, one or more of the at least one neoantigenic peptide described herein is an individual-specific neoantigenic peptide. In embodiments, the individual-specific neoantigenic peptide comprises a distinct tumor neoepitope, which is an epitope specific to the individual's tumor. In embodiments, the individual-specific neoantigenic peptide is the expression product of a tumor-specific emerging mutation that is not present in a non-tumor sample from the individual. In embodiments, the individual-specific neoantigenic peptide binds to the individual's HLA protein. In embodiments, the individual-specific neoantigenic peptide binds to the individual's HLA protein with an IC _{50 of} less than 500 nM. In embodiments, activated CD8+ T cells are separated from antigen presenting cells. In embodiments, the antigen presenting cells are dendritic cells or expanded CD40L B cells. In embodiments, the antigen-presenting cells are non-transformed cells. In embodiments, the antigen-presenting cells are uninfected cells. In embodiments, the antigen presenting cells are autologous. In embodiments, antigen-presenting cells have been treated to remove endogenous MHC-associated peptides from their surface. In embodiments, the treatment to remove endogenous MHC-associated peptides comprises culturing the cells at about 26°C. In embodiments, the treatment to remove endogenous MHC-associated peptides comprises treating the cells with a mild acid solution. In embodiments, antigen-presenting cells are loaded with at least one neoantigenic peptide described herein. In embodiments, loading comprises incubating antigen-presenting cells in the presence of at least about 2 μg/ml of each of the at least one neoantigenic peptide described herein. In embodiments, the ratio of isolated T cells to antigen presenting cells is between about 30:1 and 300:1. In embodiments, the isolated population of T cells is incubated in the presence of IL-2 and IL-7. In embodiments, the MHC of the MHC peptide is a class I or class II MHC.

[24] Provided herein is a method for activating tumor-specific T cells, comprising: isolating a population of T cells from an individual and incubating the isolated population of T cells with antigen-presenting cells and at least one neoantigenic peptide described herein for a period of time sufficient to activate T cells. In embodiments, the T cell is a CD8+ T cell, a helper T cell, or a cytotoxic T cell. In embodiments, the population of T cells from an individual is a population of CD8+ T cells from an individual. In embodiments, one or more of the at least one neoantigenic peptide described herein is an individual-specific neoantigenic peptide. In embodiments, the individual-specific neoantigenic peptide comprises a distinct tumor neoepitope, which is an epitope specific to the individual's tumor. In embodiments, the individual-specific neoantigenic peptide is the expression product of a tumor-specific emerging mutation that is not present in a non-tumor sample of the individual. In embodiments, the individual-specific neoantigenic peptide binds to the individual's HLA protein. In embodiments, the individual-specific neoantigenic peptide binds to the individual's HLA protein with an IC _{50 of} less than 500 nM. In embodiments, the method further comprises separating activated T cells from antigen presenting cells. In embodiments, the method further comprises testing activated T cells for evidence of reactivity against at least one neoantigenic peptide described herein. In embodiments, the antigen presenting cells are dendritic cells or expanded CD40L B cells. In embodiments, the antigen-presenting cells are non-transformed cells. In embodiments, the antigen-presenting cells are uninfected cells. In embodiments, the antigen presenting cells are autologous. In embodiments, antigen-presenting cells have been treated to remove endogenous MHC-associated peptides from their surface. In embodiments, the treatment to remove endogenous MHC-associated peptides comprises culturing the cells at about 26°C. In embodiments, the treatment to remove endogenous MHC-associated peptides comprises treating the cells with a mild acid solution. In embodiments, antigen-presenting cells are loaded with at least one neoantigenic peptide described herein. In embodiments, loading comprises incubating antigen-presenting cells in the presence of at least about 2 μg/ml of each of the at least one neoantigenic peptide described herein. In embodiments, the ratio of isolated T cells to antigen presenting cells is between about 30:1 and 300:1. In embodiments, the isolated population of T cells is incubated in the presence of IL-2 and IL-7. In embodiments, the MHC of the MHC peptide is a class I or class II MHC.

[25] Provided herein is a composition comprising activated tumor-specific T cells obtainable by the method described herein.

[26] Provided herein is a method for treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of an activated tumor-specific T cell as described herein or produced by a method as described herein. In embodiments, administration includes administration of about 10 ⁶ to 10 ¹² , about 10 ⁸ to 10 ¹¹ , or about 10 ⁹ to 10 ¹⁰ activated tumor-specific T cells.

[27] Provided herein is a nucleic acid containing a promoter operably linked to a polynucleotide encoding a T cell receptor as described herein. In embodiments, the TCR is capable of binding at least one neoantigenic peptide within a class I or class II major histocompatibility complex (MHC).

[28] Provided herein is a nucleic acid containing a promoter operably linked to a polynucleotide encoding the chimeric antigen receptor described herein. In embodiments, the antigen recognition fragment is capable of binding at least one neoantigenic peptide within a class I or class II major histocompatibility complex (MHC). In embodiments, the neoantigenic peptide is located in the extracellular domain of a tumor-associated polypeptide. In embodiments, the nucleic acid comprises a CD3-zeta, CD28, CTLA-4, ICOS, BTLA, KIR, LAG3, CD137, OX40, CD27, CD40L, Tim-3, A2aR, or PD-1 transmembrane region.

[29] Provided herein is an antibody or antibody fragment capable of binding at least one neoantigenic peptide as described herein, or an MHC-peptide complex comprising at least one neoantigenic peptide as described herein, optionally wherein the antibody fragment is a T-cell-attracting bispecific activator (BiTE). In embodiments, the antibody or antibody fragment binds to the extracellular region of at least one neoantigenic peptide. In embodiments, the native polypeptide is encoded by a gene selected from the group consisting of: β2M, where Cz is RMERELKKWSIQTCLSARTGLSISCTTLNSPPLKKMSMPAV, or LCSRYSLFLAWRLSSVLQRFRFTHVIQQRMESQIS; EGFR where A _x B _y C _z is IPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLIMQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA; BTK, where A _x B _y C _z is MIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGSLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVND; или ESR1, где A _x B _y C _z представляет собой HLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYGLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEA, NQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLPSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSH, IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLCDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLNDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, или IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLSDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE; or HER2, where A _x B _y C _z is GSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGLGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM. In embodiments, the antibody or antibody fragment is a bispecific antibody or antibody fragment. In embodiments, one antigen-binding domain of the bispecific antibody or antibody fragment is an anti-CD3 binding domain.

[30] Provided herein is a modified cell transfected or transduced with the nucleic acid described herein. In embodiments, the modified cell is a T cell, a tumor infiltrating lymphocyte, a TCR expressing NK-T cell, a CD4+ T cell, a CD8+ T cell, or an NK cell.

[31] Provided herein is a composition comprising a T cell receptor or chimeric antigen receptor as described herein.

[32] Provided herein is a composition comprising autologous T cells from an individual containing the T cell receptor or chimeric antigen receptor described herein. In embodiments, the composition further comprises an immune checkpoint inhibitor. In embodiments, the composition further comprises at least two immune checkpoint inhibitors. In embodiments, each of the immune checkpoint inhibitors inhibits a checkpoint protein selected from the group consisting of the ligand family CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof. In embodiments, each of the immune checkpoint inhibitors interacts with a checkpoint protein ligand selected from the group consisting of the ligand family CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof. In embodiments, the T cells are PD-1 and/or CTLA4 knockout T cells, optionally wherein the PD-1 and/or CTLA4 knockout T cells are generated using a CRISPR system. In embodiments, the composition further comprises an immunomodulator or adjuvant. In embodiments, the immunomodulator is a costimulatory ligand, TNF ligand, Ig superfamily ligand, CD28, CD80, CD86, ICOS, CD40L, OX40, CD27, GITR, CD30, DR3, CD69, or 4-1BB. In embodiments, the immunomodulator is at least one cancer cell or cancer cell extract. In embodiments, the cancerous cell is autologous to the individual in need of the composition. In embodiments, the cancer cell is lysed or exposed to UV radiation. In embodiments, the composition further comprises an adjuvant. In embodiments, the adjuvant is selected from the group consisting of: poly(I:C), poly-ICLC, STING agonist, 1018 ISS, aluminum salts, Amplivax, AS15, BCG, CP-870.893, CpG7909, CyaA, dSLIM, GM-CSF , IC30, IC31, imiquimod, ImuFact IMP321, IS Patch, ISS, ISCOMATRIX, JuvImmune, LipoVac, MF59, monophosphoryl lipid A, Montanide IMS 1312 VG, Montanide ISA 206 VG, Montanide ISA 50 V2, Montanide ISA 51 VG, OK-432, OM-174, OM-197-MP-EC, ISA-TLR2 agonist, ONTAK, PepTel®, vector system, PLG microparticles, resiquimod, SRL172, virosomes and other virus-like particles, YF-17D, VEGF-Trap, R848, beta- glucan, Pam3Cys, Pam3CSK4, acrylic or methacrylic polymers, maleic anhydride copolymers, and QS21 stimulon. In embodiments, the composition elicits a humoral response when administered to an individual. In embodiments, the composition induces T-helper cell type 1 when administered to an individual.

[33] Provided herein is a method for inhibiting the growth of a tumor cell expressing a tumor-specific neoepitope, comprising contacting the tumor cell with a peptide, polynucleotide, delivery system, vector, composition, antibody, or cells described herein.

[34] Provided herein is a method of prophylaxis in an individual, comprising contacting a cell of the individual with a peptide, polynucleotide, delivery system, vector, composition, antibody, or cells described herein. In embodiments, the native polypeptide is encoded by a gene selected from the group consisting of: β2M, where Cz is RMERELKKWSIQTCLSARTGLSISCTTLNSPPLKKMSMPAV or LCSRYSLFLAWRLSSVLQRFRFTHVIQQRMESQIS; EGFR where A _x B _y C _z is IPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLIMQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA; BTK, где A _x B _y C _z представляет собой MIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGSLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVND или ESR1, где A _x B _y C _z представляет собой HLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYGLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEA, NQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLPSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSH, IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLCDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLNDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, или IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLSDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, и HER2, где A _x B _y C _z представляет собой GSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGLGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM.

[35] Provided herein is a method of treating cancer or stimulating, enhancing, or prolonging an antitumor response in an individual in need thereof, comprising administering to the individual a peptide, polynucleotide, vector, composition, antibody, or cell described herein. In embodiments, the individual is a human. In embodiments, the subject is suffering from a cancer. In embodiments, the cancer is selected from the group consisting of genitourinary cancer, gynecological cancer, lung cancer, gastrointestinal cancer, head and neck cancer, glioblastoma cancer, mesothelioma cancer, non-metastatic or metastatic breast cancer, melanoma cancer, carcinoma from Merkel cell or bone and soft tissue sarcoma, hematologic neoplasia, multiple myeloma, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia, non-small cell lung cancer (NSCLC), breast cancer, metastatic colorectal cancer, hormone-sensitive or hormone-resistant prostate cancer cancer, colorectal cancer, ovarian cancer, hepatocellular cancer, hepatocellular cancer, pancreatic cancer, gastric cancer, esophageal cancer, hepatocellular cancer types, cholangiogenic cancer types, squamous cell carcinoma you and neck, soft tissue sarcomas and small cell lung cancer. In embodiments, the peptide, polynucleotide, vector, composition, antibody, or cells described herein are for use in the treatment of an appropriate cancer according to Table 1 or Table 2. In embodiments, the peptide, polynucleotide, vector, composition, antibody, or the cells described herein are for use in the treatment of an individual with an HLA type that corresponds to an HLA type according to Table 1 or Table 2. In embodiments, the individual has undergone surgical removal of a tumor. In embodiments, the peptide, polynucleotide, vector, composition, or cells are administered via intravenous, intraperitoneal, intratumoral, intradermal, or subcutaneous administration. In embodiments, the peptide, polynucleotide, vector, composition, or cells are administered to an anatomic site that empties into a lymphatic manifold. In embodiments, the administration is carried out in several lymphatic collectors. In embodiments, administration is by subcutaneous or intradermal route. In embodiments, a peptide is administered. In embodiments, the introduction is carried out inside the tumor. In embodiments, the polynucleotide is optionally administered with RNA. In embodiments, the polynucleotide is administered intravenously. In embodiments, the cell is a T cell or a dendritic cell. In embodiments, the peptide or polynucleotide contains a fragment directed to antigen-presenting cells. In embodiments, the cell is an autologous cell. In embodiments, the method further comprises administering at least one immune checkpoint inhibitor to the individual. In embodiments, the checkpoint inhibitor is a biological therapeutic agent or a small molecule compound. In embodiments, the checkpoint inhibitor is selected from the group consisting of a monoclonal antibody, a humanized antibody, a wholly human antibody, and a fusion protein, or a combination thereof. In embodiments, the checkpoint inhibitors are an anti-PD-1 antibody or an anti-PD-L1 antibody. In embodiments, the checkpoint inhibitor is selected from the group consisting of ipilimumab, tremelimumab, nivolumab, avelumab, durvalumab, atezolizumab, pemobrolizumab, and any combination thereof. In embodiments, the checkpoint inhibitor inhibits a checkpoint protein selected from the group consisting of the CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR ligand family , 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, and any combination thereof. In embodiments, the checkpoint inhibitor interacts with a checkpoint protein ligand selected from the group consisting of the ligand family CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA , KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof. In embodiments, two or more checkpoint inhibitors are administered. In embodiments, at least one of the two or more checkpoint inhibitors is an anti-PD-1 antibody or an anti-PD-L1 antibody. In embodiments, at least one of the two or more checkpoint inhibitors is selected from the group consisting of ipilimumab, tremelimumab, nivolumab, avelumab, durvalumab, atezolizumab, and pemobrolizumab. In embodiments, the checkpoint inhibitor and the composition are administered simultaneously or sequentially in any order. In embodiments, the peptide, polynucleotide, vector, composition, or cells are administered prior to the checkpoint inhibitor. In embodiments, the peptide, polynucleotide, vector, composition, or cells are administered after the checkpoint inhibitor. In embodiments, checkpoint inhibitor administration is continued throughout neoantigenic peptide, polynucleotide, vector, composition, or cell therapy. In embodiments, neoantigenic peptide, polynucleotide, vector, composition, or cell therapy is administered to individuals who are partially responsive or non-responsive to checkpoint inhibitor therapy. In embodiments, the composition is administered intravenously or subcutaneously. In embodiments, the checkpoint inhibitor is administered intravenously or subcutaneously. In embodiments, the checkpoint inhibitor is administered subcutaneously approximately 2 cm from the site of administration of the composition. In embodiments, the composition is administered to the same draining lymph node as the checkpoint inhibitor. In embodiments, the method further comprises administering the additional therapeutic agent to the individual prior to, concurrently with, or after treatment with the peptide, polynucleotide, vector, composition, or cells. In embodiments, the additional agent is a chemotherapeutic agent, an immunomodulatory drug, an immune metabolism modifying drug, targeted therapy, radiation, an anti-angiogenic agent, or an agent that reduces immune suppression. In embodiments, the chemotherapeutic agent is an alkylating agent, a topoisomerase inhibitor, an antimetabolite, or an antimitotic agent. In embodiments, the additional agent is a glucocorticoid-induced tumor necrosis factor receptor (GITR) family agonist antibody or fragment, ibrutinib, docetaxel, cisplatin, an anti-CD40 agonist antibody or antibody fragment, an IDO inhibitor, or cyclophosphamide. In embodiments, the method elicits a CD4+ T cell immune response or a CD8+ T cell immune response. In embodiments, the method elicits a CD4+ T cell immune response and a CD8+ T cell immune response.

[36] Provided herein is a method for stimulating an immune response in an individual, comprising administering an effective amount of modified cells or a composition as described herein. In embodiments, the immune response is a cytotoxic and/or humoral immune response. In embodiments, the method stimulates a T cell mediated immune response in an individual. In embodiments, the T-cell mediated immune response is directed to a target cell. In embodiments, the target cell is a tumor cell. In embodiments, the modified cells are transfected or transduced in vivo . In embodiments, the modified cells are transfected or transduced ex vivo . In embodiments, the modified cells are autologous T cells from the individual. In embodiments, the individual's autologous T cells are obtained from an individual who has received a neoantigenic peptide or nucleic acid vaccine. In embodiments, the neoantigenic peptide or nucleic acid vaccine comprises at least one personalized neoantigen. In embodiments, the neoantigenic peptide or nucleic acid vaccine comprises at least one additional neoantigenic peptide shown in Table 1 or 2. and/or after receiving a vaccine based on neoantigenic peptide or nucleic acid. In embodiments, the individual is receiving treatment with at least one checkpoint inhibitor. In embodiments, autologous T cells are obtained from an individual who has already received at least one cycle of T cell therapy comprising a neoantigen. In embodiments, the method further comprises adoptive T cell therapy. In embodiments, adoptive T cell therapy comprises autologous T cells. In embodiments, autologous T cells are directed against tumor antigens. In embodiments, the adoptive T cell therapy further comprises allogeneic T cells. In embodiments, allogeneic T cells are directed against tumor antigens. In embodiments, the adoptive T cell therapy is administered before the checkpoint inhibitor, after the checkpoint inhibitor, or concurrently with the checkpoint inhibitor.

[37] Provided herein is a method for evaluating the efficacy of any of the cells described herein, comprising: (i) determining the number or concentration of target cells in a first sample obtained from an individual prior to administration of the modified cell, (ii) determining the number or concentration of cells -targets in the second sample obtained from the individual after the introduction of the modified cell, and (iii) determining an increase or decrease in the number or concentration of target cells in the second sample compared to the number or concentration of target cells in the first sample. In embodiments, the effectiveness of treatment is determined by monitoring clinical outcome; increase, amplification or prolongation of antitumor activity by T-cells; an increase in the number of antitumor T-cells or activated T-cells compared to the number before treatment; B-cell activity; CD4+ T cell activity, or combinations thereof. In embodiments, the effectiveness of treatment is determined by monitoring the biomarker. In embodiments, the biomarker is selected from the group consisting of CEA, Her-2/neu, bladder tumor antigen, thyroglobulin, alpha-fetoprotein, PSA, CA 125, CA19.9, CA 15.3, leptin, prolactin, osteopontin, IGF-II , CD98, fascina, sPIgR, 14-3-3-eta, troponin I, tumor cell circulating RNA or DNA, and type b natriuretic peptide. In embodiments, the clinical outcome is selected from the group consisting of tumor regression; reducing the size of the tumor; tumor necrosis; antitumor response by the immune system; spread, recurrence or metastasis of the tumor, or a combination thereof. In embodiments, the effect of treatment is predicted based on the presence of T cells or the presence of a gene signature indicative of T cell inflammation, or a combination thereof.

[38] Provided herein is a method of treating cancer or stimulating, enhancing, or prolonging an antitumor response in an individual in need thereof, comprising administering to the individual: a peptide, polynucleotide, vector, composition, antibody, or cell described herein; and at least one checkpoint inhibitor. In embodiments, the method further comprises administering an immunomodulator or adjuvant. In embodiments, the immunomodulator or adjuvant is selected from the group consisting of poly(I:C), poly-ICLC, STING agonist, 1018 ISS, aluminum salts, Amplivax, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, GM- CSF, IC30, IC31, imiquimod, ImuFact IMP321, IS Patch, ISS, ISCOMATRIX, JuvImmune, LipoVac, MF59, Monophosphoryl lipid A, Montanide IMS 1312 VG, Montanide ISA 206 VG, Montanide ISA 50 V2, Montanide ISA 51 VG, OK-432 , OM-174, OM-197-MP-EC, ISA-TLR2 agonist, ONTAK, PepTel® vector system, PLG microparticles, resiquimod, SRL172, virosomes and other virus-like particles, YF-17D, VEGF-Trap, R848, beta- glucan, Pam3Cys, Pam3CSK4, acrylic or methacrylic polymers, copolymers of maleic anhydride and stimulant QS21, costimulatory ligand, TNF ligand, Ig superfamily ligand, CD28, CD80, CD86, ICOS, CD40L, OX40, CD27, GITR, CD30, DR3, CD69, or 4-1BB. In embodiments, the immunomodulator or adjuvant is a poly-ICLC. In embodiments, the checkpoint inhibitor is an anti-PDl antibody or fragment. In embodiments, the anti-PDl antibody or fragment is nivolumab or pembolizumab. In embodiments, the checkpoint inhibitor is an anti-PD-L1 antibody or fragment. In embodiments, the anti-PD-L1 antibody or fragment is velumab, durvalumab, or atezolizumab. In embodiments, the checkpoint inhibitor is an anti-CTLA4 antibody or fragment. In embodiments, the anti-CTLA4 antibody is ipilimumab or tremelimumab. In embodiments, the method includes administering an anti-PD1 antibody and an anti-CTLA4 antibody. In embodiments, administration of the checkpoint inhibitor is started prior to administration of the peptide, polynucleotide, vector, composition, antibody, or cell. In embodiments, administration of the checkpoint inhibitor is initiated after administration of the peptide, polynucleotide, vector, composition, antibody, or cell has begun. In embodiments, administration of the checkpoint inhibitor is started concurrently with the initiation of administration of the peptide, polynucleotide, vector, composition, antibody, or cell. In embodiments, the peptide, polynucleotide, vector, composition, antibody, or cell is administered intravenously or subcutaneously. In embodiments, the checkpoint inhibitor is administered intravenously or subcutaneously. In embodiments, the checkpoint inhibitor is administered subcutaneously approximately 2 cm from the site of administration of the peptide, polynucleotide, vector, composition, antibody, or cell. In embodiments, the peptide, polynucleotide, vector, composition, antibody, or cell is administered to the same draining lymph node as the checkpoint inhibitor.

[39] Provided herein is a kit containing a peptide, polynucleotide, vector, composition, antibody, cell, or composition as described herein. In embodiments, the cancer is selected from the group consisting of: adrenal cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, gliobalstoma, head and neck cancer, chromophobic kidney cancer, clear cell kidney cancer, papillary kidney cancer, cancer liver, adenocarcinoma of the lung, squamous cell lung cancer, ovarian cancer, pancreatic cancer, melanoma, gastric cancer, endometrial cancer of the body of the uterus and carcinosarcoma of the uterus. In embodiments, the cancer is selected from the group consisting of: prostate cancer, bladder cancer, squamous cell lung cancer, NSCLC, breast cancer, head and neck cancer, lung adenocarcinoma, GBM, glioma, CML, AML, supratentorial ependymoma, acute promyelocytic leukemia, solitary fibroids, and crizotinib-resistant cancer. In embodiments, the cancer is selected from the group consisting of: CRC, head and neck cancer, stomach cancer, squamous cell lung cancer, lung adenocarcinoma, prostate cancer, bladder cancer, gastric cancer, renal cell carcinoma, and uterine cancer. In embodiments, the cancer is selected from the group consisting of: melanoma, squamous cell lung cancer, DLBCL, uterine cancer, head and neck cancer, uterine cancer, liver cancer, and CRC. In embodiments, the cancer is selected from the group consisting of: cancer of the lymphatic system; Burkitt's lymphoma, neuroblastoma, prostate adenocarcinoma, colorectal adenocarcinoma; adenocarcinoma of the uterus/endometrium; MSI+; serous carcinoma of the endometrium; carcinosarcoma of the uterus - a malignant mixed mesodermal tumor; gliomas; astrocytomas; GBM, acute myeloid leukemia. associated with MDS; chronic lymphocytic leccosis - small cell lymphoma; myelodysplastic syndrome; acute myeloid leukemia; breast carcinomas of the luminal type NS; chronic myeloid leukemia; ductal carcinoma of the pancreas; chronic myelomonocytic leukemia; myelofibrosis; myelodysplastic syndrome; adenocarcinoma of the prostate; essential thrombocythemia and medullomyoblastoma. In embodiments, the cancer is selected from the group consisting of: colorectal cancer, uterine cancer, endometrial cancer, and gastric cancer. In embodiments, the cancer is selected from the group consisting of: cervical cancer, head and neck cancer, anal cancer, gastric cancer, Burkitt's lymphoma, and nasopharyngeal carcinoma. In embodiments, the cancer is selected from the group consisting of: bladder cancer, colorectal cancer, and stomach cancer. In embodiments, the cancer is selected from the group consisting of: lung cancer, CRC, melanoma, breast cancer, NSCLC, and CLL. In embodiments, the subject is partially responsive or non-responsive to checkpoint inhibitor therapy. In embodiments, the cancer is selected from the group consisting of: bladder urothelial carcinoma (BLCA), invasive breast carcinoma (BRCA), breast cancer, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), chronic lymphocytic leukemia (CLL), colorectal cancer (CRC), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), kidney papillary cell carcinoma (KIRP), hepatic cell carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), adenocarcinoma pancreatic cancer (PAAD), prostate cancer, skin melanoma (SKCM), gastric adenocarcinoma (STAD), thyroid adenocarcinoma (THCA), and endometrioid carcinoma of the uterine corpus (UCEC). In embodiments, the cancer is selected from the group consisting of: colorectal cancer, uterine cancer, endometrial cancer, gastric cancer, and Lynch syndrome. In embodiments, the cancer is an MSI+ cancer.

[40] The present invention provides an isolated neoantigenic peptide comprising a tumor-specific neoepitope as defined in Table 1, wherein the isolated neoantigenic peptide is not a native polypeptide. The present invention also relates to an isolated neoantigenic peptide that contains a tumor-specific neoepitope and is defined in Table 1.

[41] In certain embodiments, the isolated neoantigenic peptide is about 8 to about 50 amino acids in length. In another embodiment, the isolated neoantigenic peptide is about 15 to about 35 amino acids in length. In another embodiment, the isolated neoantigenic peptide is about 15 amino acids or less in length. In another embodiment, the isolated neoantigenic peptide is between about 8 and about 11 amino acids in length. In another embodiment, the isolated neoantigenic peptide is 9 or 10 amino acids long. In another embodiment, the isolated neoantigenic peptide binds a class I major histocompatibility complex (MHC). In another embodiment, the isolated neoantigenic peptide binds class I MHCs with a binding affinity of less than about 500 nM.

[42] In certain embodiments, the isolated neoantigenic peptide is about 30 amino acids or less in length. In another embodiment, the isolated neoantigenic peptide is between about 6 and about 25 amino acids in length. In another embodiment, the isolated neoantigenic peptide is between about 15 and about 24 amino acids in length. In another embodiment, the isolated neoantigenic peptide is between about 9 and about 15 amino acids long. In another embodiment, the isolated neoantigenic peptide binds MHC class II. In another embodiment, the isolated neoantigenic peptide binds class II MHCs with a binding affinity of less than about 1000 nM.

[43] In certain embodiments, the isolated neoantigenic peptide further comprises flanking amino acids. In another embodiment, the flanking amino acids are not native flanking amino acids. In another embodiment, the isolated neoantigenic peptide is linked to at least a second neoantigenic peptide. In another embodiment, the peptides are linked using a polyglycine or polyserine linker. In another embodiment, the second neoantigenic peptide binds class I or class II MHCs with a binding affinity of less than about 1000 nM. In another embodiment, the second neoantigenic peptide binds class I or class II MHCs with a binding affinity of less than about 500 nM. In another embodiment, both neoepitopes bind human leukocyte antigen (HLA) -A, -B, -C, -DP, -DQ, or -DR. In another embodiment, the isolated neoantigenic peptide binds HLA class I and the second neoantigenic peptide binds HLA class II. In another embodiment, the isolated neoantigenic peptide binds HLA class II and the second neoantigenic peptide binds HLA class I.

[44] In certain embodiments, the isolated neoantigenic peptide further comprises modifications that increase in vivo half-life, cell targeting, antigen uptake, antigen processing, MHC affinity, MHC stability, or antigen presentation. In another embodiment, the modification is carrier protein conjugation, ligand conjugation, antibody conjugation, pegylation, polysialylation, hesylation, recombinant PEG mimetics, Fc fusion, albumin fusion, nanoparticle attachment, nanoparticle envelope encapsulation, fusion with cholesterol, iron fusion, acylation, amidation, glycosylation, side chain oxidation, phosphorylation, biotinylation, addition of a surfactant, addition of amino acid mimetics, or addition of unnatural amino acids. In another embodiment, the cells that are targeted are antigen-presenting cells. In another embodiment, the antigen presenting cells are dendritic cells. In another embodiment, the dendritic cells are targeted using the marker DEC205, XCR1, CD197, CD80, CD86, CD123, CD209, CD273, CD283, CD289, CD184, CD85h, CD85j, CD85k, CD85d, CD85g, CD85a, CD141, CD11c, CD83, TSLP receptor, Clec9a or CD1a. In another embodiment, the dendritic cells are targeted using the CD141, DEC205, or XCR1 marker.

[45] In certain embodiments, the invention provides an in vivo delivery system comprising the isolated neoantigenic peptide described herein. In another embodiment, the delivery system includes cell-penetrating peptides, nanoparticle encapsulation, virus-like particles, or liposomes. In another embodiment, the cell-penetrating peptide is a TAT peptide, herpes simplex virus VP22, transportan, or Antp.

[46] In certain embodiments, the implementation of the invention relates to a cell containing the selected neoantigenic peptide described in the present description. In another embodiment, the cell is an antigen presenting cell. In another embodiment, the cell is a dendritic cell.

[47] In certain embodiments, the invention relates to a composition containing the selected neoantigenic peptide described in the present description. In another embodiment, the composition contains at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 , at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 , at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 isolated neoantigenic peptides comprising a tumor-specific neoepitope as defined in Table 1 or 2. In another embodiment, the composition comprises 2 to 20 neoantigenic peptides. In another embodiment, the composition further comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25, at least 26, at least 27, at least 28, at least at least 29 or at least 30 additional neoantigenic peptides. In another embodiment, the composition contains from about 4 and from about 20 additional neoantigenic peptides. In another embodiment, the additional neoantigenic peptide is specific to a particular patient's tumor. In another embodiment, the patient specific neoantigenic peptide is selected by identifying sequence differences between the gene, exome and/or transcriptome of the patient's tumor sample and the gene, exome and/or transcriptome of the non-tumor sample. In another embodiment, the samples are fresh or formalin-fixed, paraffin-embedded tumor tissues, freshly isolated cells, or circulating tumor cells. In another embodiment, sequence differences are determined by next generation sequencing.

[48] In certain embodiments, the invention provides an isolated polynucleotide encoding an isolated neoantigenic peptide as described herein. In another embodiment, the isolated polynucleotide is an RNA, optionally a self-amplifying RNA. In another embodiment, the RNA is modified to increase stability, increase cell targeting, increase translation efficiency, adjuvant, cytosolic accessibility, and/or reduce cytotoxicity. In another embodiment, the modification is carrier protein conjugation, ligand conjugation, antibody conjugation, codon optimization, increased GC content, introduction of modified nucleosides, introduction of a 5' cap or cap analog, and/or introduction of an unmasked poly-A sequence.

[49] In certain embodiments, the invention relates to a cell containing the polynucleotide described in the present description.

[50] In certain embodiments, the implementation of the invention relates to a vector containing a polynucleotide described in the present description. In another embodiment, the polynucleotide is operably linked to a promoter. In another embodiment, the vector contains a self-amplifying RNA replicon, plasmid, phage, transposon, cosmid, virus, or virion. In another embodiment, the vector is an adeno-associated virus, herpesvirus, lentivirus, or pseudotypes thereof.

[51] In certain embodiments, the invention provides an in vivo delivery system comprising an isolated polynucleotide as described herein. In another embodiment, the delivery system includes spherical nucleic acids, viruses, virus-like particles, plasmids, bacterial plasmids, or nanoparticles.

[52] In certain embodiments, the invention relates to a cell containing the vector or delivery system described in the present description. In another embodiment, the cell is an antigen presenting cell. In another embodiment, the cell is a dendritic cell. In another embodiment, the cell is an immature dendritic cell.

[53] In certain embodiments, the invention relates to a composition containing at least one polynucleotide described in the present description. In another embodiment, the composition contains at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 , at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20 , at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, or at least 30 isolated polynucleotides. In another embodiment, the composition contains between about 2 and about 20 polynucleotides that encode neoantigenic peptides. In another embodiment, the composition further comprises at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29 or at least 30 additional neoantigenic polynucleotides encoding additional neoantigenic peptides. In certain embodiments, the composition contains from about 4 and from about 20 additional neoantigenic polynucleotides. In certain embodiments, the isolated polynucleotides and additional neoantigenic polynucleotides are linked. In certain embodiments, the polynucleotides are linked using a nucleic acid that encodes a polyglycine or polyserine linker. In certain embodiments, at least one of the additional neoantigenic peptides is specific to a particular patient's tumor. In certain embodiments, the patient-specific neoantigenic peptide is selected by identifying sequence differences between the gene, exome, and/or transcriptome of the patient's tumor sample and the gene, exome, and/or transcriptome of the non-tumor sample. In certain embodiments, the samples are fresh or formalin-fixed, paraffin-embedded tumor tissues, freshly isolated cells, or circulating tumor cells. In certain embodiments, sequence differences are determined by next generation sequencing.

[54] In certain embodiments, the invention provides a T cell receptor (TCR) capable of binding at least one neoantigenic peptide described herein. In certain embodiments, the TCR is capable of binding an isolated neoantigenic peptide within a class I or class II MHC.

[55] In certain embodiments, the invention provides a chimeric antigen receptor comprising: (i) a T-cell activating molecule; (ii) a transmembrane region; and (iii) an antigen recognition fragment capable of binding the isolated neoantigenic peptide described herein. In certain embodiments, the chimeric antigen receptor contains CD3-zeta as a T-cell activating molecule. In certain embodiments, the chimeric antigen receptor further comprises at least one costimulatory signaling domain. In certain embodiments, the signaling domain is CD28, 4-1BB, ICOS, OX40, ITAM, or Fc epsilon RI-gamma. In certain embodiments, the antigen recognition fragment is capable of binding an isolated neoantigenic peptide within a class I or class II MHC. In certain embodiments, the chimeric antigen receptor comprises a CD3-zeta, CD28, CTLA-4, ICOS, BTLA, KIR, LAG3, CD137, OX40, CD27, CD40L, Tim-3, A2aR, or PD-1 transmembrane region. In certain embodiments, the tumor-specific epitope is located in the extracellular domain of a tumor-associated polypeptide.

[56] In certain embodiments, the invention relates to a T-cell containing a T-cell receptor or chimeric antigen receptor described in the present description. In certain embodiments, the T cell is a helper or cytotoxic T cell.

[57] In certain embodiments, the invention provides a nucleic acid containing a promoter operably linked to a polynucleotide encoding a T-cell receptor as described herein. In certain embodiments, the TCR is capable of binding at least one neoantigenic peptide within a class I or class II major histocompatibility complex (MHC). In another embodiment, the nucleic acid contains a promoter operably linked to a polynucleotide encoding a chimeric antigen receptor as described herein. In another embodiment, the antigen recognition fragment is capable of binding at least one neoantigenic peptide within a class I or class II major histocompatibility complex (MHC). In certain embodiments, the tumor-specific epitope is located in the extracellular domain of a tumor-associated polypeptide. In certain embodiments, the nucleic acid comprises a CD3-zeta, CD28, CTLA-4, ICOS, BTLA, KIR, LAG3, CD137, OX40, CD27, CD40L, Tim-3, A2aR, or PD-1 transmembrane region.

[58] In certain embodiments, the invention provides an antibody capable of binding at least one neoantigenic peptide described herein.

[59] In certain embodiments, the invention provides a modified cell transfected or transduced with the nucleic acid described herein. In certain embodiments, the modified cell is a T cell, a tumor infiltrating lymphocyte, a TCR expressing NK-T cell, a CD4 ⁺ T cell, a CD8 ⁺ T cell, or an NK cell.

[60] In certain embodiments, the implementation of the invention relates to compositions containing T-cell receptor or chimeric antigen receptor described in the present description. In certain embodiments, the composition comprises a patient's autologous T cells containing a T cell receptor or a chimeric antigen receptor. In certain embodiments, the composition further comprises an immune checkpoint inhibitor. In certain embodiments, the composition further comprises at least two immune checkpoint inhibitors. In certain embodiments, each of the immune checkpoint inhibitors inhibits a checkpoint protein selected from the group consisting of the CTLA-4 ligand family, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3 , VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof. In certain embodiments, each of the immune checkpoint inhibitors interacts with a checkpoint protein ligand selected from the group consisting of the CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9 family of ligands. , LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof.

[61] In certain embodiments, the composition further comprises an immunomodulator or an adjuvant. In another embodiment, the immunomodulator is a costimulatory ligand, TNF ligand, Ig superfamily ligand, CD28, CD80, CD86, ICOS, CD40L, OX40, CD27, GITR, CD30, DR3, CD69, or 4-1BB. In another embodiment, the immunomodulator is at least one cancer cell or cancer cell extract. In another embodiment, the cancer cell is autologous to the individual in need of the composition. In another embodiment, the cancer cell is lysed or exposed to UV radiation. In another embodiment, the adjuvant induces a humoral response when administered to an individual. In another embodiment, the adjuvant induces type 1 T helper cells when administered to an individual.

[62] In certain embodiments, the invention provides a method for inhibiting the growth of a tumor cell expressing a tumor-specific neoepitope as described herein, comprising contacting the tumor cell with a peptide, polynucleotide, delivery system, vector, composition, antibody, or cells of the invention.

[63] In certain embodiments, the invention relates to a method of treating cancer or stimulating, enhancing or prolonging an antitumor response in an individual in need thereof, comprising administering to the individual a peptide, polynucleotide, vector, composition, antibody, or cell described herein.

[64] In certain embodiments, the cancer is selected from adrenal cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, glioblastoma, head and neck cancer, chromophobic kidney cancer, clear cell kidney cancer, papillary kidney cancer, liver cancer. , adenocarcinoma of the lung, squamous cell lung cancer, ovarian cancer, pancreatic cancer, melanoma, gastric cancer, endometrial cancer of the body of the uterus and carcinosarcoma of the uterus.

[65] In certain embodiments, the cancer is selected from the group of: prostate cancer, bladder cancer, squamous cell lung cancer, NSCLC, breast cancer, head and neck cancer, lung adenocarcinoma, GBM, glioma, CML, AML, supratentorial ependymoma , acute promyelocytic leukemia, solitary fibroids, and crizotinib-resistant cancer.

[66] In certain embodiments, the cancer is selected from the group consisting of CRC, head and neck cancer, gastric cancer, squamous cell lung cancer, lung adenocarcinoma, prostate cancer, bladder cancer, gastric cancer, renal cell carcinoma, and uterine cancer.

[67] In certain embodiments, the cancer is selected from the group consisting of melanoma, squamous cell lung cancer, DLBCL, uterine cancer, head and neck cancer, uterine cancer, liver cancer, and CRC.

[68] In certain embodiments, the cancer is selected from the group consisting of cancer of the lymphatic system; Burkitt's lymphoma, neuroblastoma, prostate adenocarcinoma, colorectal adenocarcinoma; adenocarcinoma of the uterus / endometrium; MSI ⁺ ; serous carcinoma of the endometrium; uterine carcinosarcoma - a malignant mixed mesodermal tumor; gliomas; astrocytomas; GBM, acute myeloid leukemia associated with MDS; chronic lymphocytic leukemia - small cell lymphoma; myelodysplastic syndrome; acute myeloid leukemia; breast carcinomas of the luminal type NS; chronic myeloid leukemia; ductal carcinoma of the pancreas; chronic myelomonocytic leukemia; myelofibrosis; myelodysplastic syndrome; adenocarcinoma of the prostate; essential thrombocythemia and medullomyoblastoma.

[69] In certain embodiments, the cancer is selected from the group consisting of colorectal cancer, uterine cancer, endometrial cancer, and gastric cancer.

[70] In certain embodiments, the cancer is selected from the group consisting of cervical cancer, head and neck cancer, anal cancer, gastric cancer, Burkitt's lymphoma, and nasopharyngeal carcinoma.

[71] In certain embodiments, the cancer is selected from the group consisting of bladder cancer, colorectal cancer, and gastric cancer.

[72] In certain embodiments, the cancer is selected from the group consisting of lung cancer, CRC, melanoma, breast cancer, NSCLC, and CLL.

[73] In certain embodiments, the cancer is selected from the group consisting of adrenocortical carcinoma (ACC), acute promyelocytic leukemia, acute myeloid leukemia (AML), AML associated with myelodysplastic syndromes (MDS), anal cancer, astrocytoma, bladder cancer , urothelial carcinoma of the bladder (BLCA), breast cancer, invasive breast carcinoma (BRCA), Burkitt's lymphoma, castration-resistant prostate cancer, cervical cancer, squamous cell carcinoma of the cervix and endocervical adenocarcinoma (CESC), chronic lymphocytic leukemia- small cell lymphoma, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia, colorectal adenocarcinoma, colorectal cancer (CRC), crizotinib-resistant non-small cell lung cancer (NSCLC), diffuse large B-cell lymphoma (DLBCL), pancreatic ductal carcinoma uterine carcinosarcoma - malignant mixed mesodermal tumor, endometrial serous carcinoma, essential thrombocythemia, glioblastoma multiforme (GBM), glioma, head and neck cancer, head and neck squamous cell carcinoma (HNSC), invasive lobular carcinoma (ILC) LumA of the breast , chromophobic kidney cancer (KICH), renal clear cell carcinoma (KIRC), papillary cell carcinoma of the kidney (KIRP), acute myeloid leukemia (LAML), hepatic cell carcinoma (LIHC), liver cancer, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) ), luminal type breast carcinoma NS, lung cancer, cancer of the lymphatic system, medullomyoblastoma, melanoma, colorectal cancer (CRC) with microsatellite instability (MSI) ⁺ , MSI ⁺ endometrioid carcinoma, MSI ⁺ gastric cancer, MSI ⁺ uterine/endometrial cancer, myelodysplastic syndrome, myelofibrosis, nasopharyngeal carcinoma, neuroblastoma, non-small cell lung cancer (NSCLC), serous qi ovarian stadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), prostate cancer, renal cell carcinoma, skin melanoma (SKCM), solitary fibroid tumors, gastric adenocarcinoma (STAD), gastric cancer, supratentorial ependymoma, adenocarcinoma thyroid gland (THCA), endometrioid carcinoma of the uterine corpus (UCEC) or uterine carcinosarcoma (UCS), uterine cancer and uterine/endometrial adenocarcinoma.

[74] In certain embodiments, the cancer is selected from the group consisting of bladder urothelial carcinoma (BLCA), invasive breast carcinoma (BRCA), breast cancer, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), chronic lymphocytic leukemia ( CLL), colorectal cancer (CRC), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), renal papillary cell carcinoma (KIRP), hepatic cell carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) ), pancreatic adenocarcinoma (PAAD), prostate cancer, skin melanoma (SKCM), gastric adenocarcinoma (STAD), thyroid adenocarcinoma (THCA) and endometrioid carcinoma of the uterus (UCEC).

[75] In certain embodiments, the individual is a human. In another embodiment, the individual suffers from a malignant tumor. In another embodiment, the cancer is selected from the group consisting of genitourinary cancer, gynecological cancer, lung cancer, gastrointestinal cancer, head and neck cancer, malignant glioblastoma, malignant mesothelioma, non-metastatic or metastatic breast cancer, malignant melanoma, Merkel cell or bone and soft tissue sarcoma, hematologic neoplasia, multiple myeloma, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia, non-small cell lung cancer (NSCLC), breast cancer, metastatic colorectal cancer, hormone-sensitive or hormone-resistant prostate cancer cancer, colorectal cancer, ovarian cancer, hepatocellular cancer, hepatocellular cancer, pancreatic cancer, gastric cancer, esophageal cancer, hepatocellular cancer, cholangiogenic cancer, head and neck squamous cell carcinoma, soft tissue sarcoma tissue and small cell lung cancer. In another embodiment, the subject has undergone surgical removal of a tumor. In another embodiment, the peptide, polynucleotide, vector, composition, or cells are administered via intravenous, intraperitoneal, intratumoral, intradermal, or subcutaneous administration. In another embodiment, the peptide, polynucleotide, vector, composition, or cells is administered to an anatomical site that empties into a lymphatic manifold. In another embodiment, the introduction is carried out in several lymphatic collectors. In another embodiment, administration is by subcutaneous or intradermal route.

[76] In certain embodiments of the method, a peptide is administered. In another embodiment, the introduction is carried out inside the tumor. In another embodiment of the method, a polynucleotide, optionally RNA, is administered. In another embodiment, the polynucleotide is administered intravenously. In certain embodiments of the method, a cell is introduced. In another embodiment, the cell is a T cell or a dendritic cell. In another embodiment, the peptide or polynucleotide contains a fragment directed to antigen-presenting cells.

[77] In another embodiment of the method, at least one immune checkpoint inhibitor is also administered to the individual. In another embodiment, the checkpoint inhibitor is a biological therapeutic or small molecule compound. In another embodiment, the checkpoint inhibitor is selected from the group consisting of a monoclonal antibody, a humanized antibody, a wholly human antibody, and a fusion protein, or a combination thereof. In another embodiment, the checkpoint inhibitor inhibits a checkpoint protein selected from the group consisting of the ligand family CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof. In another embodiment, the checkpoint inhibitor interacts with a checkpoint protein ligand selected from the group consisting of the ligand family CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and B-7, or combinations thereof. In another embodiment, two or more checkpoint inhibitors are administered. In another embodiment, the checkpoint inhibitors are: (i) ipilimumab or tremelimumab and (ii) nivolumab. In another embodiment, the checkpoint inhibitor and the composition are administered simultaneously or sequentially in any order. In another embodiment, the neoantigenic peptide, polynucleotide, vector, composition, or cells is administered prior to the checkpoint inhibitor. In another embodiment, the peptide, polynucleotide, vector, composition, or cells are administered after the checkpoint inhibitor. In another embodiment, the checkpoint inhibitor continues to be administered throughout neoantigenic peptide, polynucleotide, vector, composition, or cell therapy. In another embodiment, neoantigenic peptide, polynucleotide, vector, composition, or cell therapy is administered to individuals who have partially responded or not responded to checkpoint inhibitor therapy. In another embodiment, the composition is administered intravenously or subcutaneously. In another embodiment, the checkpoint inhibitor is administered intravenously or subcutaneously. In another embodiment, the checkpoint inhibitor is administered subcutaneously approximately 2 cm from the injection site of the composition. In another embodiment, the composition is administered to the same draining lymph node as the checkpoint inhibitor.

[78] In certain embodiments of the method, an additional agent is administered. In another embodiment, the agent is a chemotherapeutic agent, an immunomodulatory drug, an immune metabolism modifying drug, targeted therapy, radiation, an anti-angiogenic agent, or an agent that reduces immune suppression. In another embodiment, the chemotherapeutic agent is an alkylating agent, a topoisomerase inhibitor, an antimetabolite, or an antimitotic agent. In another embodiment, the additional agent is a glucocorticoid-induced tumor necrosis factor receptor family agonist antibody or fragment, ibrutinib, docetaxel, cisplatin, or cyclophosphamide. In another embodiment, the introduction causes a CD4 ⁺ T-cell immune response. In another embodiment, the administration elicits a CD4 ⁺ T cell immune response and a CD8+ T cell immune response.

[79] In certain embodiments, the invention relates to a method of stimulating an immune response in an individual, comprising the introduction of an effective amount of the modified cells or composition described in the present description. In another embodiment, the immune response is a cytotoxic and/or humoral immune response. In another embodiment, the method stimulates a T-cell mediated immune response in an individual. In another embodiment, the T-cell mediated immune response is directed against a target cell. In another embodiment, the target cell is a tumor cell. In another embodiment, the modified cells are transfected or transduced in vivo . In another embodiment, the modified cells are transfected or transduced ex vivo . In another embodiment, the modified cells are autologous T cells from the patient. In another embodiment, autologous patient T cells are obtained from a patient who has received a neoantigenic peptide or nucleic acid vaccine. In another embodiment, the neoantigenic peptide or nucleic acid vaccine contains at least one personalized neoantigen. In another embodiment, the neoantigenic peptide or nucleic acid vaccine comprises at least one additional neoantigenic peptide as described herein. In another embodiment, the patient received a chemotherapeutic agent, an immunomodulatory drug, an immune metabolism modifying drug, targeted therapy, or radiation prior to and/or during the preparation of a neoantigenic peptide or nucleic acid vaccine. In another embodiment, the patient is receiving treatment with at least one checkpoint inhibitor. In another embodiment, autologous T cells are obtained from a patient who has already received at least one cycle of T cell therapy comprising a neoantigen. In another embodiment, the method further comprises adoptive T cell therapy. In another embodiment, the adoptive T cell therapy comprises autologous T cells. In another embodiment, autologous T cells are directed against tumor antigens. In another embodiment, the adoptive T cell therapy further comprises allogeneic T cells. In another embodiment, allogeneic T cells are directed against tumor antigens. In another embodiment, the adoptive T cell therapy is administered prior to the administration of the checkpoint inhibitor.

[80] In certain embodiments, the invention relates to a method for evaluating the effectiveness of treatment, including: (i) determining the number or concentration of target cells in the first sample obtained from the individual prior to the introduction of the modified cell, (ii) determining the number or concentration of target cells in a second sample obtained from the individual after administration of the modified cell, and (iii) determining an increase or decrease in the number or concentration of target cells in the second sample compared to the number or concentration of target cells in the first sample. In another embodiment, the effectiveness of treatment is determined by monitoring clinical outcome; increase, amplification or prolongation of antitumor activity by T-cells; an increase in the number of antitumor T-cells or activated T-cells compared to the number before treatment; B-cell activity; CD4 T cell activity or combinations thereof. In another embodiment, the effectiveness of the treatment is determined by monitoring the biomarker. In another embodiment, the biomarker is selected from the group consisting of CEA, Her-2/neu, bladder tumor antigen, thyroglobulin, alpha-fetoprotein, PSA, CA 125, CA19.9, CA 15.3, leptin, prolactin, osteopontin, IGF- II, CD98, fascina, sPIgR, 14-3-3-eta, troponin I and type b natriuretic peptide. In another embodiment, the clinical outcome is selected from the group consisting of tumor regression; reducing the size of the tumor; tumor necrosis; antitumor response by the immune system; spread, recurrence or metastasis of the tumor, or a combination thereof. In another embodiment, the effect of treatment is predicted based on the presence of T cells or the presence of a gene signature indicative of T cell inflammation, or a combination thereof.

[81] In certain embodiments, the invention relates to a method of treating cancer or stimulating, enhancing or prolonging an antitumor response in an individual in need thereof, comprising administering to the individual: (a) a peptide, polynucleotide, vector, composition, antibody, or cells described herein description, and (b) at least one checkpoint inhibitor. In another embodiment, the method further comprises administering an immunomodulator or adjuvant. In another embodiment, the immunomodulator or adjuvant is selected from the group consisting of poly(I:C), poly-ICLC, STING agonist, 1018 ISS, aluminum salts, Amplivax, AS15, BCG, CP-870,893, CpG7909, CyaA, dSLIM, GM -CSF, IC30, IC31, Imichimod, ImuFact IMP321, IS Patch, ISS, ISCOMATRIX, JuvImmune, LipoVac, MF59, Monophosphoryl lipid A, Montanide IMS 1312 VG, Montanide ISA 206 VG, Montanide ISA 50 V2, Montanide ISA 51 VG, OK- 432, OM-174, OM-197-MP-EC, ISA-TLR2 agonist, ONTAK, PepTel® vector system, PLG microparticles, resiquimod, SRL172, virosomes and other virus-like particles, YF-17D, VEGF-Trap, R848, beta -glucan, Pam3Cys, Pam3CSK4, acrylic or methacrylic polymers, copolymers of maleic anhydride and stimulant QS21, costimulatory ligand, TNF ligand, Ig superfamily ligand, CD28, CD80, CD86, ICOS, CD40L, OX40, CD27, GITR, CD30, DR3, CD69 or 4-1BB. In another embodiment, the immunomodulator or adjuvant is a poly-ICLC. In another embodiment, the checkpoint inhibitor is an anti-PDl antibody or fragment. In another embodiment, the PD-1 pathway inhibitor is nivolumab. In another embodiment, the checkpoint inhibitor is an anti-CTLA4 antibody or fragment. In another embodiment, the anti-CTLA4 antibody is ipilimumab or tremelimumab. In another embodiment, the method includes administering an anti-PD1 antibody and an anti-CTLA4 antibody. In another embodiment, administration of the checkpoint inhibitor is initiated after administration of the peptide, polynucleotide, vector, composition, antibody, or cell has begun. In another embodiment, administration of the checkpoint inhibitor is initiated after administration of the peptide, polynucleotide, vector, composition, antibody, or cell has begun. In another embodiment, administration of the checkpoint inhibitor is initiated simultaneously with the initiation of administration of the peptide, polynucleotide, vector, composition, antibody, or cell. In another embodiment, the peptide, polynucleotide, vector, composition, antibody, or cell is administered intravenously or subcutaneously. In another embodiment, the checkpoint inhibitor is administered intravenously or subcutaneously. In another embodiment, the checkpoint inhibitor is administered subcutaneously approximately 2 cm from the site of administration of the peptide, polynucleotide, vector, composition, antibody, or cell. In another embodiment, the peptide, polynucleotide, vector, composition, antibody, or cell is administered to the same draining lymph node as the checkpoint inhibitor.

[82] In certain embodiments of the therapeutic methods, the additional therapeutic agent is, for example, a chemotherapeutic or biotherapeutic agent, radiation, or immunotherapy. Any suitable therapeutic treatment for a particular cancer can be carried out. Examples of chemotherapeutic and biotherapeutic agents include, but are not limited to, an angiogenesis inhibitor such as hydroxyangiostatin K l-3, DL-a-difluoromethylornithine, endostat III, fumagillin, genistein, minocycline, staurosporine, and thalidomide; a DNA intercalator/crosslinker such as bleomycin, carboplatin, carrmistem, chlorambucil, cyclophosphamide, cis-diaminplatinum (D) dichloride (cisplatin), melphalan, mitoxantrone, and oxaliplatin; DNA synthesis inhibitor such as (B±)-ametopterin (methotrexate), 3-amino-1,2,4-benzotriazine-1,4-dioxide, aminopterin, cytosine β-D-arabinofuranoside, 5-fromo-5'- deoxyuridine, 5-fluorouracil, ganciclovir, hydroxyurea, and mitomycin C; DNA-RNA transcription regulators such as actinomycin D, dow orubicin, doxorubicin, homogarringtonin and idarubicin; οη/.γηκ inhibitor such as S(-i-)-camptotecm, curcumin, (-)-deguelm ((-)-Deguelm), 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside, etoposide, formestane, fostriecine , hispidin, 2-immo-1-imidazolidineacetic acid (cyclocreatine), mevmoline, trichostatin A, tyrphostin AG 34 and tyrphostin AG 879; regulator gene such as 5-aza-2'-deoxycytidine, 5-azacytidine, cholecalciferol (vitamin D3), 4-hydroxy tamoxifen, melatonin, mifepristone, raloxifene, all-trans retinal (vitamin A aldehyde), all-trans retinoic acid (vitamin A acid), 9-cis-retinoic acid, 13-cis-retinoic acid, retinol (vitamin A), tamoxifen and troglitazone; a microtubule inhibitor such as colchicine, docetaxel, dolastathirs 15, nocodazole, paclitaxel, podophyllotoxin, rizoxin, vinblastine, vincristine, vindesin, and vinorelbine (navelbin); and an unclassified therapeutic agent such as 17-(allylamino)-1 7-demethoxygeldamycin, 4-amino-1,8-naphthalimide, apigenin, brefeldin A, cimetidine, dichloromethylenediphosphonic acid, leuprolide (leuprorelin), a hormone that stimulates the release of luteinizing hormone, pifitrin-a, rapamycin, sex hormone-binding globulin, thapsigargin, and a urinary trypsin inhibitor fragment (bicunin). The therapeutic agent may be altretamine, amifostine, asparaginase, capecitabine, cladribine, cisapride, cilaragirs, dacarbazine (DT1C), dactinomycin, dronabinol, epoetin alfa, filgrastim, fludarabine, gemcitabine, granisetron, ifosfamide, irinotecan, lansoprazole, levamisole, leucovorin, mesovorin , mesna, methochloramide, mitotane, omeprazole, ondansetron, pilocarpine, prochlorperazine, or topotecan hydrochloride. The therapeutic agent may be a monoclonal antibody such as rituximab (Rituxan®), alemtuzumab (Campath®), bevacizumab (Avastin®), cetuximab (Erbitux®), panitumumab (Vectibix®), and trastuzumab (Herceptin®), vemurafenib (Zelboraf ®), imatinib mesylate (Gleevec®), erlotinib (Tarceva®), gefitinib (Iressa®), vismodegib (Erivedge™), 90Y-ibritumomab tiuxetan, 1311-tositumomab, adotrastuzumab emtansine, lapatinib (Tykerb®), pertuzumab (Perjeta™) ), adotrastuzumab emtansine (adcyla™), regorafenib (Stivarga®), sunitinib (Sutent®), denomumab (Xgeva®), sorafenib (Nexavar®), pazopanib (Votrient®), axitinib (Inita®), dasatinib (Sprycel®) , nilotinib (Tasigna®), bosutinib (Bosulif®), ofatumumab (Arzerra®), obinutuzumab (Gazyva™), ibrutinib (Imbruvica™), idelicib (Zydelig®), crizotinib (Xalkori®), erlotinib (Tarceva®), afatinib dimaleate (Giiotrif®), ceritinib (LDK378/Zykadia), tositumomab and 1311-tositumomab (Bexxar®), ibritumomab tiuxetan (Zevalin®), brentuximab vedotin (Adc etris®), bortezomib (Velcade®), siltuximab (Sylvant™), trametinib (ekinist®), dabrafenib (Tafmlar®), pembrolizimiab (Keytruda®), carfilzomib (Kyprolis®), ramucirumab (Cyramza™), cabozantinib (Cometriq™) ), vandetanib (Caprelsa®). Optionally, the therapeutic agent is a neoantigen. The therapeutic agent may be a cytokine such as interferons (INF), interleukins (IL) or hematopoietic growth factors. The therapeutic agent may be INF-α, IL-2, aldesleukin, IL-2, erythropoietin, granulocyte-monocyte colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor. The therapeutic agent may be a targeted therapy such as toremifene (Fareston®), fulvestrant (Faslodex®), anastrozole (Arimidex®), exemestane (Aromasin®), letrozole (Femara®), ziv-aflibercept (Zaltrap®), alitretinoin ( Panretin®), temsirolimus (Torisel®), tretinoin (Vesanoid®), denileukin diftitox (Ontak®), vorinostat (Zoiinza®), romidepsin (Istodax®), bexarotene (Targretin®), pralatrexate (Foiotyn®), lenaliomide (Revlimid ®), belinostat (Beleodaq™), lenaliomide (Revlimid®), pomalidomide (Pomalyst®), cabazitaxel (Jevtana®), enzalutamide (Xtandi®), abiraterone acetate (Zytiga®), radium chloride 223 (Xofigo®), or everolimus (Afiniior ®). Additionally, the therapeutic agent may be an epigenetically targeted drug such as HDAC inhibitors, kinase inhibitors, DNA methyltransferase inhibitors, histone demethylase inhibitors, or histone methylation inhibitors. Epigenetic drugs can be azacitidine (Vidaza), decitabine (Dacogen), vorinostat (Zolinza), romidepsin (Istodax), or ruxolitinib (Jakafi). For prostate cancer, the treatment, preferably a chemotherapeutic agent with which an anti-CTLA-4 antibody can be combined, is paclitaxel (Taxol).

[83] In certain embodiments, the invention provides a kit containing any of the neoantigen therapeutics described herein.

[84] In the case where aspects or embodiments of the invention are described in relation to the Markush group or other groups of alternatives, the present invention applies not only to the group given as a whole, but also to each member of the group separately and all possible subgroups of the main group, as well as the absence of one or more members of the group in the main group. The present invention also provides for the explicit exclusion of one or more of any group members in the invention described in the application.

INCLUDED IN THE DESCRIPTION BY REFERENCE

[85] All publications, patents, and patent applications referred to in this specification are incorporated herein by reference in their entirety for all purposes, to the same extent as if each individual publication, patent, or patent application were specifically and separately identified by reference. For example, all publications and patents referred to in this specification are incorporated herein by reference in their entirety for the purpose of describing and disclosing the kits, compositions, and methodologies that are described in the publications that can be used in relation to the methods, kits, and compositions described herein. description. The documents discussed in this specification are provided for disclosure only prior to the filing date of this application. Nothing in this specification should be construed as an admission that the inventors of the invention described herein are not entitled to date such disclosure by virtue of prior invention or for any other reason.

BRIEF DESCRIPTION OF THE DRAWINGS

[86] Figure 1 is an illustrative graph of 562 peptides with theoretically calculated affinities for a selected HLA class I molecule from 1 nM to 100,000 nM (plotted on the x-axis) that were synthesized. Actual affinity (IC ₅₀ (nM)) was measured as described (y-axis). Thick vertical and horizontal lines represent the 500 nM threshold between weak and very weak theoretically calculated and observed binding agents, respectively. The diagonal dotted line means the line of best fit (Graphpad Prism) with R ² 0.45.

[87] Figure 2 is an illustrative graph of the 275 peptides from Figure 1 that were tested for stability (T _1/2 , hours) with their respective HLA class I molecules. The peptides were grouped according to the observed affinity in Figure 1. The median and interquartile range are presented for each group.

[88] Figure 3A is an illustrative graph of HLA-A02: ⁰¹⁺ T cells co-cultured with monocytic dendritic cells loaded with a neoepitope fused to MPRSS2::ERG (ALNSEALSV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity to neoepitope fused to TMPRSS2::ERG using multimers (original: BV421 and PE).

[89] Figure 3B is an illustrative graph of HLA-A02:01 ⁺ T cells co-cultured with monocyte dendritic cells loaded with a neoepitope fused to TMPRSS2::ERG (ALNSEALSV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for neoepitope fused to TMPRSS2::ERG using multimers (confirmation: APC and BUV396).

[90] Figure 4A is an illustrative graph of HLA-A02: ⁰¹⁺ T cells co-cultured with monocytic dendritic cells loaded with GATA3 frameshift neoepitope (SMLTGPPARV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the GATA3 frameshift neoepitope using multimers (original: APC and BUV396).

[91] Figure 4B is an illustrative graph of HLA-A02:01 ⁺ T cells co-cultured with monocytic dendritic cells loaded with GATA3 frameshift neoepitope (SMLTGPPARV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the GATA3 frameshift neoepitope using multimers (confirmation: PE and BV421).

[92] Figure 5A is an illustrative graph of HLA-A02:01 ⁺ T cells co-cultured with monocytic dendritic cells loaded with β2M frameshift neoepitope (LLCVWVSSI; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the β2M frameshift neoepitope using multimers (initial: PE and APC).

[93] Figure 5B is an illustrative graph of HLA-A02: ⁰¹⁺ T cells co-cultured with monocytic dendritic cells loaded with frameshift neoepitope β2M (LLCVWVSSI; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the β2M frameshift neoepitope using multimers (confirmation: PE and BV421).

[94] Figure 6A is an illustrative graph of HLA-A02: ⁰¹⁺ T cells co-cultured with KRAS G12C neoepitope-loaded monocyte dendritic cells (KLVVVGACGV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the frameshifted KRAS G12C neoepitope using multimers (original: BUV396 and BV421).

[95] Figure 6B is an illustrative graph of HLA-A02: ⁰¹⁺ T cells co-cultured with KRAS G12C neoepitope-loaded monocytic dendritic cells (KLVVVGACGV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the frameshifted KRAS G12C neoepitope using multimers (confirmation: APC and BUV396).

[96] Figure 7 is an illustrative graph of T cells co-cultured with monocytic dendritic cells loaded with β2M frameshift neoepitopes for 20 days (re-stimulation with fresh monocytic dendritic cells on day 20). CD4 ⁺ T cells were analyzed for antigen specificity by intracellular staining for cytokines after re-stimulation with monocytic dendritic cells loaded with β2M frameshift peptide for 24 hours (right) compared to controls without peptide (left).

[97] Figure 8 is an exemplary graph of T cells co-cultured with monocytic dendritic cells loaded with neopeptide BTK C481S for 20 days (re-stimulation with fresh monocytic dendritic cells on day 20). CD4 ⁺ T cells were analyzed for antigen specificity by intracellular staining for cytokines after re-stimulation with monocytic dendritic cells loaded with neopeptide BTK C481S for 24 hours (right) compared to control wild-type BTK peptide (left).

[98] Figure 9 is an illustrative graph of T cells co-cultured with monocytic dendritic cells loaded with GATA3 frameshift neopeptides for 20 days (re-stimulation with fresh monocytic dendritic cells on day 20). CD4 ⁺ T cells were analyzed for antigen specificity by intracellular staining for cytokines after re-stimulation with monocytic dendritic cells loaded with GATA3 frameshift peptide for 24 hours (right) compared to controls without peptide (left).

DETAILED DESCRIPTION OF THE INVENTION

[99] The present description describes new immunotherapeutic agents and their use based on the discovery of neoantigens resulting from mutational events unique to the individual's tumor. Thus, the invention described herein relates to peptides, peptide-encoding polynucleotides, and peptide-binding agents that can be used, for example, to stimulate an immune response to a tumor-associated antigen, to create an immunogenic composition or cancer vaccine for use in treatment of the disease.

I. Definitions

[100] The terminology used in the present description is for the purpose of describing specific cases only and is not intended to be limiting. As used herein, the singular forms are also intended to include the plural forms, unless the context clearly dictates otherwise. In addition, to the extent that the terms "comprising", "includes", "having", "has", "with", or variations thereof are used in any detailed description and/or claims, such terms are intended to be inclusive in a manner analogous to the term "containing".

[101] The term "approximately" can mean within an acceptable error range for a particular value, as determined by one skilled in the art, which depends in part on how the value is measured or determined, ie. measurement system limitations. For example, "about" can mean within 1 or more than 1 standard deviation, according to practice in this field. Alternatively, "about" can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly in relation to biological systems or processes, the term may mean in order of magnitude, a change of 5 times, and more preferably 2 times the value. In the case where specific values are described in the application and claims, unless otherwise indicated, the term "about" should be assumed to mean within the allowable error range for a particular value.

[102] To facilitate understanding of the present invention, a number of terms and phrases are defined below.

[103] "Neoantigen" means a class of tumor antigens that result from tumor-specific changes in proteins. Neoantigens include, but are not limited to, tumor antigens that result from, for example, a substitution in a protein sequence, a frameshift mutation, a fusion polypeptide, a deletion, an in-frame insertion, expression of endogenous retroviral polypeptides, and tumor-specific overexpression of polypeptides.

[104] "Tumor-specific neoepitope" refers to an epitope that is not present in a reference, such as a normal non-cancerous or germline cell, but occurs in malignant cells. This includes in particular situations where a corresponding epitope occurs in a normal non-cancerous or germline cell, however, as a result of one or more mutations in the cancer cell, the sequence of the epitope is altered, thus resulting in a neo-epitope.

[105] "Reference" can be used to correlate and compare the results obtained in the methods of the invention from a tumor sample. Typically, a "reference" can be derived from one or more normal samples, in particular samples that are not affected by a malignant disease, or that are obtained from a patient or one or more different individuals, for example healthy individuals, in particular from individuals of the same species. . "Reference" can be determined empirically by testing a sufficiently large number of normal samples.

[106] The term "mutation" refers to a change or difference in a nucleic acid sequence (substitution, addition or deletion of a nucleotide) compared to a reference. A "somatic mutation" can occur in any of the body's cells with the exception of germ cells (sperm and egg) and thus is not passed on to children. These changes can (but not always) cause cancer or other diseases. In certain embodiments, the mutation is a non-synonymous mutation. The term "non-synonymous mutation" refers to a mutation, eg a nucleotide change, that results in an amino acid change, such as an amino acid change in a translation product. A "frameshift" occurs when a mutation disrupts the normal phase of a gene's codon periodicity (also known as "reading frame"), resulting in the translation of a non-native protein sequence. It is possible that different mutations in a gene result in the same altered reading frame.

[107] As used herein, the term "affinity" refers to a measure of the binding strength between two members of a binding pair, eg, an HLA binding peptide and HLA class I or II. K _D is the dissociation constant and has the units of molarity. The affinity constant is the opposite of the dissociation constant. Affinity constant is sometimes used as a general term to describe this chemical compound. It is a direct measure of the binding energy. Affinity can be determined experimentally, for example by surface plasmon resonance (SPR) using commercially available Biacore SPR devices. Affinity can also be expressed as an inhibitory concentration 50 (IC ₅₀ ), the concentration at which 50% of the peptide is displaced. Similarly, ln(IC ₅₀ ) refers to the natural log IC ₅₀ . K _off refers to the rate constant of the reverse reaction, for example, for the dissociation of an HLA binding peptide and HLA class I or II.

[108] Throughout this description, the results of "binding data" can be expressed in terms of "IC ₅₀ ". The IC ₅₀ is the concentration of the test peptide in the binding assay at which 50% inhibition of binding of the labeled reference peptide is observed. Considering the conditions under which the assays are performed (ie, limiting concentrations of HLA protein and labeled reference peptide), these values approach the K _D values. Binding assays are well known in the art and are described in detail in, for example, PCT publications WO 94/20127 and WO 94/03205, and other publications such as Sidney et al., Current Protocols in Immunology 18.3.1 (1998); Sidney et al., J. Immunol. 154:247 (1995); and Sette et al., Mol. Immunol. 31:813 (1994). Alternatively, binding may be expressed relative to binding to a reference standard peptide. For example, may be based on an IC ₅₀ relative to the IC ₅₀ of a reference standard peptide.

[109] Binding can also be determined using other assay systems, including assay systems using: live cells (eg, Ceppellini et al., Nature 339:392 (1989); Christnick et al., Nature 352:67 (1991); Busch et al., Int. Immunol. 2:443 (1990); Hill et al., J. Immunol. 147:189 (1991); del Guercio et al., J. Immunol. 154:685 (1995)), cell-free systems using lysates after detergent treatment (eg, Cerundolo et al., J. Immunol. 21:2069 (1991)), immobilized purified MHC (eg, Hill et al., J. Immunol. 152, 2890 (1994); Marshall et al., J. Immunol. 152:4946 (1994)), ELISA systems (e.g. Reay et al., EMBO J. 11:2829 (1992)), surface plasmon resonance (e.g. Khilko et al., J Biol Chem 268:15425 (1993)); high density soluble phase assays (Hammer et al., J. Exp. Med. 180:2353 (1994)) and MHC class I stabilization or assembly measurements (e.g., Ljunggren et al., Nature 346:476 (1990); Schumacher et al., Cell 62:563 (1990); Townsend et al., Cell 62:285 (1990); Parker et al., J. Immunol. 149:1896 (1992)).

[110] "Cross-linking" indicates that the peptide is bound by more than one HLA molecule; synonymy is degenerate binding.

[111] The term "obtainable" when used to describe an epitope is synonymous with "prepared". The resulting epitope may be isolated from a natural source, or it may be synthesized according to standard protocols in the art. Synthetic epitopes may contain artificial amino acid residues "amino acid mimetics", such as D-isomers of natural L-amino acid residues, or non-natural amino acid residues, such as cyclohexylalanine. The resulting or prepared epitope may be analogous to the native epitope.

[112] "Diluent" includes sterile liquids such as water and oils, including petroleum, animal, vegetable or synthetic oils such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water is also a diluent for pharmaceutical compositions. Salt solutions and aqueous solutions of dextrose and glycerol can also be used as diluents, for example in injectable solutions.

[113] An "epitope" is a general characteristic of a molecule, such as the primary, secondary, and tertiary peptide structure and charge, which together form a site recognized by, for example, an immunoglobulin, a T-cell receptor, an HLA molecule, or a chimeric antigen receptor. Alternatively, an epitope can be defined as a set of amino acid residues that is involved in recognition by a particular immunoglobulin, or in relation to T cells, those residues that are required for recognition by the T cell receptor of proteins, chimeric antigen receptors and/or major histocompatibility complex (MHC) receptors. . Epitopes may be obtained by isolation from a natural source, or they may be synthesized according to standard protocols in the art. Synthetic epitopes may contain artificial amino acid residues, "amino acid mimetics" such as D-isomers of natural L-amino acid residues, or non-natural amino acid residues such as cyclohexylalanine. Throughout this description, epitopes may be referred to in some instances as peptides or peptide epitopes.

[114] It should be understood that proteins or peptides that contain the epitope or analog described in the present description, as well as additional amino acid(s) do not yet go beyond the scope of the invention. In certain embodiments, the implementation of the peptide contains a fragment of the antigen.

[115] In certain embodiments, there is a limitation on the length of the peptide of the invention. An embodiment that is limited in length occurs when a protein or peptide containing an epitope as described herein contains a region (ie, contiguous series of amino acid residues) with 100% native sequence identity. To avoid reading out the definition of an epitope, such as whole natural molecules, there is a length limit on any region that is 100% identical to the native peptide sequence. Thus, for a peptide containing an epitope as described herein and a region with 100% identity to the native peptide sequence, the length of the region with 100% identity to the native sequence is typically: less than or equal to 600 amino acid residues, less than or equal to 500 amino acid residues less than or equal to 400 amino acid residues less than or equal to 250 amino acid residues less than or equal to 100 amino acid residues less than or equal to 85 amino acid residues less than or equal to 75 amino acid residues less than or equal to 65 amino acid residues residues, and less than or equal to 50 amino acid residues. In certain embodiments, an "epitope" as described herein consists of a peptide containing a region of less than 51 amino acid residues that is 100% identical to the native peptide sequence, at any increment of less than 5 amino acid residues; e.g. 50, 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residue.

[116] A "human leukocyte antigen" or "HLA" is a class I or class II major histocompatibility complex (MHC) protein (see, for example, Stites, et al., IMMUNOLOGY, 8TH ED., Lange Publishing, Los Altos, Calif. (1994).

[117] "HLA supertype or HLA family" as used herein describes groups of HLA molecules grouped based on common peptide binding specificity. Class I HLA molecules that have something similar to binding affinity for peptides bearing certain amino acid motifs are grouped into such HLA supertypes. The terms HLA superfamily, HLA supertype family, HLA family, and HLA xx-like molecules (where "xx" denotes a specific type of HLA) are synonymous.

[118] The terms "identical" or percent "identity" in relation to two or more peptide sequences or antigen fragments means two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues that are the same when compared and aligned for maximum consistency throughout the comparison window, as measured using a sequence comparison algorithm or through manual alignment and visual observation.

[119] An "immunogenic" peptide or "immunogenic" epitope or "peptide epitope" is a peptide that contains an allele-specific motif such that the peptide binds to an HLA molecule and induces a cell-mediated or humoral response, e.g., a cytotoxic T-lymphocyte (CTL), T-lymphocyte helper (HTL) and/or B-lymphocyte response. Thus, the immunogenic peptides described herein are capable of binding to an appropriate HLA molecule and thus inducing a CTL (cytotoxic) response, or an HTL (and humoral) response to the peptide.

[120] As used herein, "chimeric antigen receptor" or "CAR" refers to an antigen-binding protein that contains an immunoglobulin antigen-binding domain (eg, an immunoglobulin variable domain) and a T-cell receptor (TCR) constant domain. As used herein, a "constant domain" of a TCR polypeptide comprises a TCR constant domain proximal to the membrane and may also contain a TCR transmembrane domain and/or a TCR cytoplasmic tail. For example, in certain embodiments, a CAR is a dimer that comprises a first polypeptide comprising an immunoglobulin heavy chain variable domain linked to a TCR.beta constant domain and a second polypeptide comprising an immunoglobulin light chain variable domain (e.g., a κ- or λ- chains) associated with the TCRα constant domain. In certain embodiments, the CAR is a dimer that contains a first polypeptide containing an immunoglobulin heavy chain variable domain linked to a TCRα constant domain and a second polypeptide containing an immunoglobulin light chain variable domain (e.g., a κ- or λ-chain variable domain) linked with a constant TCRβ domain.

[121] The phrase "isolated" or "biologically pure" refers to a substance that is largely or essentially free of components that are normally present in the substance, in the form in which it occurs in its native state. Thus, the isolated peptides described herein do not contain certain or all of the substances normally associated with peptides in their in situ environment. An "isolated" epitope refers to an epitope that does not contain the complete antigen sequence from which the epitope was derived. Typically, no additional amino acid residues are added to an "isolated" epitope that results in a sequence that has 100% identity over the entire length of the native sequence. The native sequence may be the sequence, such as a tumor associated antigen, from which the epitope is derived. Thus, the term "isolated" means that the substance is removed from its primary environment (eg, the natural environment, if it is natural). For example, a naturally occurring polynucleotide or peptide present in a living animal is not isolated, but the same polynucleotide or peptide separated from certain or all of the concomitants in the natural system is isolated. Such a polynucleotide may be part of a vector, and/or such a polynucleotide or peptide may be part of a composition, and still be "isolated", since such a vector or composition is not part of its natural environment. Isolated RNA molecules include in vivo or in vitro RNA transcripts of the DNA molecules described herein and further include such synthetically produced molecules.

[122] "Major histocompatibility complex" or "MHC" is a cluster of genes that play a role in the regulation of cellular interactions involved in physiological immune responses. In humans, the MHC complex is also known as the human leukocyte antigen (HLA) complex. For a detailed description of the MHC and HLA complexes, see Paul, FUNDAMENTAL IMMUNOLOGY, 3.sup.RD ED., Raven Press, New York (1993).

[123] A "native" or "wild-type" sequence refers to a naturally occurring sequence. Such a sequence may contain a longer sequence in nature.

[124] "T-cell epitope" is to be understood as meaning a peptide sequence that can be bound by MHC class I or II molecules in the form of a peptide-presenting MHC molecule or MHC complex, and then can be recognized and bound by cytotoxic T lymphocytes in that form. or T-helper cells, respectively.

[125] It should be understood that "receptor" means a biological molecule or group of molecules capable of binding a ligand. A receptor can serve to transmit information in a cell, the formation of a cell or an organism. The receptor contains at least one receptor unit, for example, where each receptor unit may consist of a protein molecule. The receptor has a structure that is complementary to that of the ligand and can form a complex with the ligand as a binding partner. Information is transmitted, in particular, as a result of conformational changes in the receptor after the formation of a complex with a ligand on the cell surface. In certain embodiments, receptor is to be understood as specifically MHC class I and II proteins capable of forming a receptor/ligand complex with a ligand, in particular a peptide or peptide fragment of suitable length.

[126] It should be understood that "ligand" means a molecule that has a structure complementary to that of a receptor and is capable of complexing with such a receptor. In certain embodiments, a ligand is to be understood as a peptide or peptide fragment that is of suitable length and contains suitable binding motifs in its amino acid sequence such that the peptide or peptide fragment is capable of complexing with MHC class I or MHC class II proteins.

[127] In certain embodiments, "receptor/ligand complex" should also be understood to mean "receptor/peptide complex" or "receptor/peptide fragment complex" containing a class I or class II MHC molecule presenting a peptide or peptide fragment.

[128] "Major histocompatibility complex (MHC) proteins or molecules", "MHC molecules", "MHC proteins", or "HLA proteins" should be understood to mean proteins capable of binding peptides resulting from proteolytic cleavage of protein antigens and representing possible lymphocytic epitopes (eg, T-cell epitope and B-cell epitope), transporting them to the cell surface and presenting them there to specific cells, in particular cytotoxic T-lymphocytes, T-helper cells or B-cells. The major histocompatibility complex in the genome includes a genetic region whose gene products, expressed on the cell surface, are important for the binding and presentation of endogenous and/or foreign antigens and thus for the regulation of immunological processes. The major histocompatibility complex is classified into two groups of genes encoding different proteins, namely MHC class I molecules and MHC class II molecules. The cell biology and expression profiles of the two MHC classes are tailored to these different roles.

[129] The terms "peptide" and "peptide epitope" are used interchangeably with "oligopeptide" in the present description to describe a series of residues connected to each other, usually by peptide bonds between the amino groups of the variable domain and the carboxyl groups of adjacent amino acid residues.

[130] "Synthetic peptide" refers to a peptide that is obtained from a non-natural source, for example, obtained artificially. Such peptides can be obtained using methods such as chemical synthesis or recombinant DNA technology. "Synthetic peptides" includes "fusion proteins".

[131] A "PanDR binding" peptide, a "PanDR epitope binding" is a member of a family of molecules that bind more than one HLA class II DR molecule.

[132] "Pharmaceutical acceptable" refers to a generally non-toxic, inert and/or physiologically compatible composition or composition component.

[133] A "pharmaceutical excipient" or "excipient" includes a substance such as an adjuvant, a carrier, pH modifying and buffering agents, tonicity agents, wetting agents, preservatives, and the like. A "pharmaceutical excipient" is an excipient that is pharmaceutically acceptable.

[134] The term "motif" refers to a pattern of residues in an amino acid sequence of a certain length, e.g., a peptide less than about 15 amino acid residues long, or less than about 13 amino acid residues long, for example, from about 8 to about 13 amino acid residues (e.g., 8, 9 , 10, 11, 12, or 13) for an HLA class I motif and from about 6 to about 25 amino acid residues (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25) for an HLA class II motif that is recognized by a particular HLA molecule. The motifs are generally different for each HLA protein encoded by a given human HLA allele. The pattern of these motifs is distinguished by primary and secondary anchor residues. In certain embodiments, an MHC class I motif identifies a 9, 10, or 11 amino acid residue long peptide.

[135] "Supermotif" defines the binding specificity of a peptide shared by HLA molecules encoded by two or more HLA alleles. In certain embodiments, the supermotif-bearing peptide described herein is recognized with high or moderate affinity (as defined herein) by two or more HLA antigens.

[136] The term "natural" as used herein refers to the fact that an object can be found in nature. For example, a peptide or nucleic acid that is present in the body (including viruses) and that can be isolated from a source in nature, and that has not been intentionally altered in a laboratory, is natural.

[137] According to the invention, the term "vaccine" refers to a pharmaceutical preparation (pharmaceutical composition) or product that, when administered, induces an immune response, for example, a cellular or humoral immune response that recognizes and attacks a pathogenic or diseased cell, such as a malignant cell. The vaccine can be used to prevent or treat a disease. The term "personalized cancer vaccine" or "personalized cancer vaccine" refers to a specific cancer patient and means that the cancer vaccine is tailored to the needs or special circumstances of the individual cancer patient.

[138] A "protective immune response" or "therapeutic immune response" refers to a CTL and/or HTL response to an antigen derived from a pathogenic antigen (e.g., a tumor antigen) that, in some cases, prevents or at least partially eliminates the symptoms of a disease, side effects or progression. The immune response may also include an antibody response facilitated by stimulation with helper T cells.

[139] "Antigen processing" or "processing" refers to the degradation of a polypeptide or antigen to processing products that are fragments of said polypeptide or antigen (e.g., degradation of the polypeptide to peptides) and the formation of an association of one or more such fragments (e.g., via binding ) with MHC molecules for presentation by cells, eg antigen-presenting cells, to specific T cells.

[140] "Antigen presenting cells" (APCs) are cells that present peptide fragments of protein antigens in association with MHC molecules on their cell surface. Certain APCs can activate antigen-specific T cells. Professional antigen-presenting cells are very efficient at internalizing antigen, either through phagocytosis or receptor-mediated endocytosis, and then presenting an antigen fragment bound to an MHC class II molecule on their membrane. The T cell recognizes and interacts with the MHC class II antigen-molecule complex on the membrane of the antigen-presenting cell. The antigen presenting cell then produces an additional costimulatory signal leading to T cell activation. Expression of co-stimulatory molecules is a defining feature of professional antigen-presenting cells.

[141] The main types of professional antigen presenting cells are dendritic cells, which have the widest range of antigen presentation and are probably the most important antigen presenting cells, macrophages, B cells, and certain activated epithelial cells.

[142] Dendritic cells (DC) are populations of leukocytes that present antigens captured in peripheral tissues to T cells by both MHC class II and class I antigen presentation pathways. It is well known that dendritic cells are potent stimulators of immune responses, and the activation of these cells is a critical step in the induction of antitumor immunity.

[143] Dendritic cells are conveniently divided into "immature" and "mature" cells, which can be used as a simple way to distinguish between two well-characterized phenotypes. However, this nomenclature should not be considered as excluding all possible intermediate stages of differentiation.

[144] Immature dendritic cells are characterized as antigen-presenting cells with a high ability to capture and process antigen, which correlates with high expression of the Fey receptor and the mannose receptor. The mature phenotype is typically characterized by lower expression of these markers, but higher expression of cell surface molecules responsible for T cell activation, such as MHC class I and class II, adhesion molecules (e.g., CD54 and CD1 1 ), and costimulatory molecules ( eg CD40, CD80, CD86 and 4-1 BB).

[145] The term "residue" refers to an amino acid residue or an amino acid mimetic residue incorporated into a peptide or protein via an amide bond or an amide bond mimetic, or a nucleic acid (DNA or RNA) encoding an amino acid or amino acid mimic.

[146] The nomenclature used to describe peptides or proteins follows common practice, where the amino group is on the left (amino or N-terminus) and the carboxyl group on the right (carboxy or C-terminus) of each amino acid residue. When amino acid residue positions are designated as in a peptide epitope, they are numbered from amino to carboxy terminus, where position 1 is occupied by the residue located at the N-terminus of the epitope or of the peptide or protein of which it may be a part.

[147] In the formulas representing selected specific embodiments of the present invention, the amino and carboxyl terminal groups, although not specifically shown, are in the form they will take at physiological pH values, unless otherwise indicated. In amino acid structure formulas, each residue is usually represented by standard three-letter or one-letter designations. The L-form of an amino acid residue is represented by a single capital letter or the first capital letter of a three-letter symbol, and the D-form for such amino acid residues having D-forms is represented by a single lowercase letter or a lowercase three-letter symbol. However, when three-letter symbols or full names are used without capital letters, they may refer to L-amino acid residues. Glycine does not contain an asymmetric carbon atom and is simply referred to as "Gly" or "G". The amino acid sequences of the peptides referred to in the present description, as a rule, are designated using a standard one-letter symbol. (A, Alanine; C, Cysteine; D, Aspartic Acid; E, Glutamic Acid; F, Phenylalanine; G, Glycine; H, Histidine; I, Isoleucine; K, Lysine; L, Leucine; M, Methionine; N, Asparagine ; P, Proline; Q, Glutamine; R, Arginine; S, Serine; T, Threonine; V, Valine; W, Tryptophan and Y, Tyrosine.)

[148] The terms "polynucleotide" and "nucleic acid" are used interchangeably herein and refer to polymers of nucleotides of any length, and include DNA and RNA, eg, mRNA. Nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases and/or analogs thereof, or any substrate that can be introduced into the polymer by a DNA or RNA polymerase. In certain embodiments, the polynucleotide and nucleic acid may be an in vitro transcribable mRNA. In certain embodiments, the polynucleotide that is administered using the methods of the invention is an mRNA.

[149] The terms "identical" or percent "identity" in relation to two or more nucleic acids or polypeptides refers to two or more sequences or subsequences that are the same or contain a certain percentage of nucleotides or amino acid residues that are the same when compared and aligned (with the introduction of gaps, if necessary) for maximum matching, without considering any conservative amino acid substitutions as part of the sequence identity. Percent identity can be measured using software or sequence alignment algorithms or by visual analysis. Various algorithms and software are well known in the art that can be used to obtain amino acid or nucleotide sequence alignments. These include, but are not limited to, BLAST, ALIGN, Megalign, BestFit, GCG Wisconsin Package and variations thereof. In certain embodiments, two nucleic acids or polypeptides described herein are substantially identical, meaning that they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in certain embodiments, at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity when compared and aligned for maximum match, as measured using a sequence comparison algorithm or by visual analysis. In certain embodiments, identity exists over the entire length of a region of sequences that is at least about 10, at least about 20, at least about 40-60 residues, at least about 60-80 residues in length, or any integer value between them. In certain embodiments, identity exists over a longer region than 60-80 residues, such as at least about 80-100 residues, and in certain embodiments, the sequences are substantially identical throughout the sequences being compared, such as the coding region of the nucleotide sequences.

[150] A "conservative amino acid substitution" is a substitution in which one amino acid residue is replaced with another amino acid residue containing a similar side chain. Families of amino acid residues containing similar side chains have been identified in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), non-polar side chains (eg, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (eg, threonine, valine, isoleucine) and aromatic side chains (eg tyrosine, phenylalanine, tryptophan, histidine). For example, replacing phenylalanine with tyrosine is a conservative substitution. Methods for identifying conservative nucleotide and amino acid substitutions that do not interfere with the function of a peptide are well known in the art.

[151] The term "vector" as used herein means a construct that is capable of delivering and typically expressing one or more genes or sequences of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors, naked DNA or RNA expression vectors, plasmid, cosmid or phage vectors, DNA or RNA expression vectors coupled with cationic condensing agents, and DNA or RNA expression vectors encapsulated in liposomes.

[152] A polypeptide, antibody, polynucleotide, vector, cell, or composition that is "isolated" is a polypeptide, antibody, polynucleotide, vector, cell, or composition that is in a form that is not naturally occurring. Isolated polypeptides, antibodies, polynucleotides, vectors, cells, or compositions include those that have been purified to the extent that they are no longer in the form in which they occur naturally. In certain embodiments, the polypeptide, antibody, polynucleotide, vector, cell, or composition that is isolated is substantially pure. In certain embodiments, an "isolated polynucleotide" includes a PCR or quantitative PCR reaction containing a polynucleotide amplified in a PCR or quantitative PCR reaction.

[153] The term "substantially pure" as used herein refers to a substance that is at least 50% pure (i.e. free of contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.

[154] The term "individual" refers to any animal (eg, mammal), including, but not limited to, humans, non-human primates, dogs, cats, rodents, and the like, that will receive a particular treatment. As a general rule, the terms "individual" and "patient" are used interchangeably herein with respect to a human individual.

[155] The terms "effective amount" or "therapeutically effective amount" or "therapeutic effect" refers to the amount of a therapeutic agent effective to "treat" a disease or disorder in an individual or mammal. A therapeutically effective amount of a drug has a therapeutic effect and thus may prevent the development of a disease or disorder; slow the progression of a disease or disorder; slow the progression of a disease or disorder; alleviate to some extent one or more of the symptoms associated with the disease or disorder; reduce morbidity and mortality; improve quality of life or a combination of these effects.

[156] The terms "treatment" or "treatment" or "treat" or "attenuation" or "attenuate" refers to 1) therapeutic measures that treat, slow the development, alleviate the symptoms and/or stop the progression of the diagnosed pathological condition or disorder, and 2) prophylactic or preventive measures that prevent or slow down the development of the pathological condition or disorder of interest. Thus, those in need of treatment include those already suffering from a disorder; those who are susceptible to the disorder and those who need to be prevented from the disorder.

[157] As used in the present specification and claims, singular forms include plural forms unless the context clearly dictates otherwise.

[158] It should be understood that terms such as "comprises", "comprised", "comprising", and the like. may have the meaning ascribed to them in US patent law; for example, they may mean "includes", "included", "including", etc.; and such terms, since "consisting in substance" and "consisting in substance" have the meaning assigned to them by U.S. Patent Law, for example, they allow elements not expressly stated, but exclude elements that occur in the prior art, or that violate fundamental or new characteristics of the invention. Nothing in this description should be construed as a promise.

[159] The term "and/or" as used in a phrase such as "A and/or B" in the present specification is intended to include A and B; A or B; A (separate) and B (separate). Similarly, the term "and/or" as used in a phrase such as "A, B, and/or C" is intended to include each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (separately); B (separate) and C (separate).

II. Neoantigens

[160] One of the critical barriers in the development of therapeutic and tumor-specific immunotherapy is the identification and selection of highly specific and restricted tumor antigens to rule out autoimmunity. Tumor neoantigens that result from a genetic change (eg, inversions, translocations, deletions, sense change mutations, splice site mutations, etc.) in malignant cells that present the most tumor-specific class of antigens. Neoantigens have very rarely been used in cancer vaccines or immunogenic compositions due to technical difficulties in identifying them, selecting optimized antigens, and producing neoantigens for use in a vaccine or immunogenic composition. These problems can be addressed by: identifying mutations in neoplasia/tumors that are present at the DNA level in the tumor but not in comparable germline samples in a significant proportion of individuals suffering from cancer; analysis of identified mutations using one or more peptide-MHC binding prediction algorithms to obtain a population of T-cell epitopes of neoantigens that are expressed in neoplasia/tumor and that bind to a high proportion of HLA alleles of patients, and the synthesis of a population of neoantigenic peptides selected from the set of all neoantigenic peptides; and theoretical binding peptides, for use in a cancer vaccine or immunogenic composition suitable for the treatment of a significant proportion of individuals suffering from cancer.

[161] For example, translating peptide sequencing information to the level of a therapeutic vaccine may involve predicting mutant peptides that can bind to HLA molecules in a significant proportion of individuals. To effectively select which particular mutations to use as an immunogen, it is essential to be able to predict which mutant peptides will effectively bind to a high proportion of a patient's HLA alleles. Recently, neural network-based approaches with validated binder and non-binding peptides have improved the accuracy of prediction algorithms for major HLA-A and -B alleles. However, even with the use of current neural network-based algorithms to encode HLA peptide binding rules, several factors limit the ability to predict peptides presented on HLA alleles.

[162] For example, translating peptide sequencing information into a therapeutic vaccine level may involve formulating the drug as a long peptide multi-epitope vaccine. Targeting as many mutant epitopes as practicable takes advantage of the vast capacity of the immune system, prevents immune response evasion by reducing the expression of the gene product targeted by the immune response, and compensates for the known error of epitope prediction approaches. Synthetic peptides provide a useful means to efficiently produce many immunogens and to quickly translate the identification of mutant epitopes into an effective vaccine. Peptides can be easily synthesized chemically and easily purified using reagents that do not contain contaminating bacteria or animal substances. The small size allows a clear focus on the mutant region of the protein, and also reduces the competition of irrelevant antigens with other components (raw protein or viral vector antigens).

[163] For example, translating peptide sequencing information into a therapeutic vaccine may include combination with a strong vaccine adjuvant. Effective vaccines may require a strong adjuvant to elicit an immune response. For example, poly-ICLC, a TLR3 agonist, and MDA5 and RIG3 helicase RNA domains showed some desirable properties for a vaccine adjuvant. These properties include induction of local and systemic activation of immune cells in vivo , production of excitatory chemokines and cytokines, and stimulation of DC antigen presentation. In addition, poly-ICLCs can induce sustained CD4+ and CD8+ responses in humans. Of note, strong similarities in upregulation of the transcriptional pathway and signal transduction pathway were observed in individuals vaccinated with poly-ICLC and in volunteers who received a highly potent vaccine based on replication-competent yellow fever virus. In addition, >90% of patients with ovarian carcinoma immunized with poly-ICLC vaccine in combination with NYESO-1 peptide (in addition to montanide) showed induction of CD4+ and CD8+ T cells, as well as antibody responses to the peptide in a recent study 1 phase. At the same time, poly-ICLC has been extensively tested in more than 25 clinical trials to date and has a relatively poor toxicity profile.

[164] Applicants have found mutational events in the following genes:

[165] ABL1, AC011997, ACVR2A, AFP, AKT1, ALK, ALPPL2, ANAPC1, APC, ARID1A, AR, AR-v7, ASCL2, β2M, BRAF, BTK, C15ORF40, CDH1, CLDN6, CNOT1, CT45A5, CTAG1B, DCT , DKK4, EEF1B2, EEF1DP3, EGFR, EIF2B3, env, EPHB2, ERBB3, ESR1, ESRP1, FAM111B, FGFR3, FRG1B, GAGE1, GAGE10, GATA3, GBP3, HER2, IDH1, JAK1, SET, KRAS, LMAN1, MABEB16, MAGEA1 , MAGEA10, MAGEA4, MAGEA8, MAGEB17, MAGEB4, MAGEC1, MEK, MLANA, MLL2, MMP13, MSH3, MSH6, MYC, NDUFC2, NRAS, PAGE2, PAGE5, PDGFRa, PIK3CA, PMEL, pol protein, POLE, PTEN, RAC1, RBM27, RNF43, RPL22, RUNX1, SEC31A, SEC63, SF3B1, SLC35F5, SLC45A2, SMAP1, SMAP1, SPOP, TFAM, TGFBR2, THAP5, TP53, TTK, TYR, UBR5, VHL, XPOT EEF1DP3:FRY fusion polypeptide, EGFR fusion polypeptide :SEPT14, EGFRVIII deletion polypeptide, EML4:ALK fusion polypeptide, NDRG1:ERG fusion polypeptide, AC011997.1:LRRC69 fusion polypeptide, RUNX1(ex5)-RUNX1T1 fusion polypeptide, TMPRSS2:ERG fusion polypeptide, NAB:STAT6 fusion polypeptide, fusion NDRG1:ERG polypeptide, PML:RARA fusion polypeptide, gender fusion PPP1R1B:STARD3 ipeptide, MAD1L1:MAFK fusion polypeptide, FGFR3:TAC fusion polypeptide, FGFR3:TACC3 fusion polypeptide, BCR:ABL fusion polypeptide, C11orf95:RELA fusion polypeptide, CBFB:MYH11 fusion polypeptide, CBFB:MYH11 fusion polypeptide, CD74 fusion polypeptide :ROS1, CD74:ROS1 fusion polypeptide, ERVE-4: protease, ERVE-4: reverse transcriptase, ERVE-4: reverse transcriptase, ERVE-4: unknown, ERVH-2 matrix protein, ERVH-2: gag, ERVH-2 : retroviral matrix, ERVH48-1: envelope protein, ERVH48-1: syncytin, ERVI-1 envelope protein, ERVK-5 gag, ERVK-5 env, ERVK-5 pol, EBV A73, EBV BALF3, EBV BALF4, EBV BALF5, EBV BARF0, EBV LF2, EBV RPMS1, HPV-16, HPV-16 E7 and HPV-16 E6.

[166] In certain embodiments, the neoantigen described herein is the result of a mutational event in β2M, BTK, EGFR, GATA3, KRAS, MLL2, a TMPRSS2:ERG fusion polypeptide, or TP53.

Neoantigenic polypeptides

[167] In some aspects, the invention provides isolated peptides that contain a tumor-specific mutation from Table 1 or 2. These peptides and polypeptides are referred to herein as "neoantigenic peptides" or "neoantigenic polypeptides". The term "peptide" is used interchangeably herein with "mutant peptide" and "neoantigenic peptide" to refer to a series of residues, typically L-amino acids, linked to each other, typically by peptide bonds between α-amino and carboxyl groups of adjacent amino acids. Similarly, the term "polypeptide" is used interchangeably herein with "mutant polypeptide" and "neoantigenic polypeptide" to refer to a series of residues, e.g., L-amino acids linked to each other, typically by peptide bonds between α-amino and carboxyl groups of contiguous amino acids. Polypeptides or peptides can be of various lengths, be in neutral (uncharged) forms or in forms that are salts, and contain no modifications such as glycosylation, side chain oxidation, or phosphorylation, or contain such modifications, provided that the modification is not violates the biological activity of polypeptides, as described in the present description.

[168] In certain embodiments, sequencing methods are used to identify tumor-specific mutations. Any suitable sequencing method can be used according to the invention, such as next generation sequencing (NGS) technologies. Third generation sequencing methods may be replaced in the future by NGS technology, which will increase the speed of the sequencing step of the method. For clarification: the terms "next generation sequencing" or "NGS" in the context of the present invention are all new high-throughput sequencing technologies that, in contrast to the "conventional" sequencing methodology known as Sanger chemistry, read nucleic acid arrays randomly throughout the genome in parallel by breaking the genome into small pieces. Such NGS technologies (also known as massively parallel sequencing technologies) are capable of delivering whole genome, exome, transcriptome (all transcribed genome sequences), or methylome (all methylated genome sequences) nucleic acid sequence information in very short periods of time, for example, within 1- 2 weeks, for example, within 1-7 days or less than 24 hours, and provide overall single cell sequencing approaches. Many NGS platforms that are commercially available or that are mentioned in the literature can be used within the scope of the invention, such as those detailed in WO 2012/159643, for example.

[169] In certain embodiments of the neoantigenic peptide described herein, the molecule may contain, but is not limited to, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13 , approximately 14, approximately 15, approximately 16, approximately 17, approximately 18, approximately 19, approximately 20, approximately 21, approximately 22, approximately 23, approximately 24, approximately 25, approximately 26, approximately 27, approximately 28, approximately 29, approximately 30, approximately 31, approximately 32, approximately 33, approximately 34, approximately 35, approximately 36, approximately 37, approximately 38, approximately 39, approximately 40, approximately 41, approximately 42, approximately 43, approximately 44, approximately 45, approximately 46, about 47, about 48, about about 49, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120 or more amino acid residues, and any range that can be deduced from them. In specific embodiments of the neoantigenic peptide, the molecule is equal to or less than 100 amino acids.

[170] In certain embodiments, the neoantigenic peptides and polypeptides described herein are 13 residues or less for MHC class I, and typically consist of about 8 to about 11 residues, in particular 9 or 10 leftovers. In certain embodiments, the neoantigenic peptides and polypeptides described herein are 9-24 residues long for MHC class II.

[171] The longer neoantigenic peptide can be constructed in several ways. In certain embodiments, when HLA binding peptides are theoretically calculated or known, the longer neoantigenic peptide may consist of (1) individual binding peptides with 2-5 amino acid extensions towards the N- and C-terminus of each respective gene product; or (2) connecting as a chain of some or all of the binding peptides with extended sequences for each. In other embodiments, when sequencing reveals a long (>10 residue) neoepitope sequence present in a tumor (e.g., due to frameshift, pass-through, or intron insertion resulting in a new peptide sequence), the longer neoantigenic peptide may consist of the whole plot of new tumor-specific amino acids in the form of a single longer peptide or multiple overlapping longer peptides. In certain embodiments, it is contemplated that the use of a longer peptide allows for endogenous processing by the patient's cells and may result in more efficient antigen presentation and induction of T cell responses. In certain embodiments, two or more peptides can be used, where the peptides overlap and follow each other along the entire length of the long neoantigenic peptide.

[172] In certain embodiments, neoantigenic peptides and polypeptides bind to an HLA protein (eg, HLA class I or HLA class II). In specific embodiments, the neoantigenic peptides and polypeptides bind to the HLA protein with greater affinity than the corresponding wild-type peptide. In specific embodiments, the neoantigenic peptide or polypeptide has an IC ₅₀ of at least less than 5000 nM, at least less than 500 nM, at least less than 100 nM, at least less than 50 nM, or less.

[173] In certain embodiments, the neoantigenic peptides can be about 8 to about 50 amino acid residues in length, or about 8 to about 30, about 8 to about 20, about 8 to about 18, about 8 to about 15, or about 8 to about 12 amino acid residues. In certain embodiments, neoantigenic peptides can be from about 8 to about 500 amino acid residues in length, or from about 8 to about 450, about 8 to about 400, about 8 to about 350, about 8 to about 300, about 8 about up to 250, from about 8 to about 200, from about 8 to about 150, from about 8 to about 100, from about 8 to about 50, or from about 8 to about 30 amino acid residues.

[174] In certain embodiments, the length of the neoantigenic peptides may be at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 , 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or more amino acid residues. In certain embodiments, the neoantigenic peptides may be at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500 or more amino acid residues. In certain embodiments, the neoantigenic peptides may be no more than 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 , 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or less amino acid residues . In certain embodiments, the neoantigenic peptides may be no more than 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 , 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60 , 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500 or less amino acid residues.

[175] In certain embodiments, the total length of the neoantigenic peptides is at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 450, or at least 500 amino acids.

[176] In certain embodiments, the total length of the neoantigenic peptides is no more than 8, no more than 9, no more than 10, no more than 11, no more than 12, no more than 13, no more than 14, no more than 15, no more than 16, no more 17, max 18, max 19, max 20, max 21, max 22, max 23, max 24, max 25, max 26, max 27, max 28, max 29, no more than 30, no more than 40, no more than 50, no more than 60, no more than 70, no more than 80, no more than 90, no more than 100, no more than 150, no more than 200, no more than 250, no more than 300, no more 350, not more than 400, not more than 450 or not more than 500 amino acids.

[177] In certain embodiments, the pI value of the neoantigenic peptides is about 0.5 and about 12, about 2 and about 10, or about 4 and about 8. In certain embodiments, the pI value of the neoantigenic peptides is at least 4.5, 5 , 5.5, 6, 6.5, 7, 7.5 or more. In certain embodiments, the pI value of the neoantigenic peptides is no more than 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or less.

[178] In certain embodiments, the HLA binding affinity of neoantigenic peptides can be between about 1 pM and about 1 mM, about 100 pM and up to about 500 μM, about 500 pM and up to about 10 μM, about 1 nM and up to about 1 µM, or up to about 10 nM and up to about 1 µM. In certain embodiments, the HLA binding affinity of neoantigenic peptides can be at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 or more In certain embodiments, the HLA binding affinity of the neoantigenic peptides may be no more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900 μM.

[179] In certain embodiments, the neoantigenic peptide described herein may contain carriers such as carriers well known in the art, e.g. thyroglobulin, albumins such as human serum albumin, tetanus toxin, polyamino acid residues such as poly L-lysine, poly-L-glutamic acid, influenza virus proteins, hepatitis B core protein, and the like.

[180] In certain embodiments, the neoantigenic peptide described herein can be modified by acylation of the NH ₂ terminus, e.g., via alkanoyl (C ₁ -C ₂₀ ) or thioglycolyl acetylation, amidation of the carboxyl end, e.g., with ammonia, methylamine, etc. d. In certain embodiments, these modifications may provide sites for binding to a substrate or other molecule.

[181] In certain embodiments, the neoantigenic peptide described herein may contain modifications such as, but not limited to, glycosylation, side chain oxidation, biotinylation, phosphorylation, the addition of a surfactant, e.g., a lipid, or can be chemically modified, for example, by acetylation, etc. In addition, the bonds in a peptide may be other than peptide bonds, such as covalent bonds, ester or ester bonds, disulfide bonds, hydrogen bonds, ionic bonds, and so on.

[182] In certain embodiments, the neoantigenic peptide described herein may contain substitutions to modify a physical property (eg, stability or solubility) of the resulting peptide. For example, neoantigenic peptides can be modified by replacing cysteine (C) with α-aminobutyric acid ("B"). Due to its chemical structure, cysteine tends to form disulfide bridges and sufficiently alter the structure of the peptide, thus reducing the binding ability. The replacement of α-aminobutyric acid C not only alleviates this problem, but actually improves the binding and crosslinking ability under certain circumstances. The replacement of a cysteine with an α-aminobutyric acid can occur at any residue of the neoantigenic peptide, for example, at anchor or non-anchor positions of an epitope or analog in the peptide, or at other positions on the peptide.

[183] In certain embodiments, the neoantigenic peptide described herein may contain amino acid mimetics or non-natural amino acid residues, for example, D- or L-nafilalanine; D- or L-phenylglycine; D- or L-2-thienylalanine; D- or L-1, -2, 3- or 4-pyrenylalanine; D- or L-3 thienylalanine; D- or L-(2-pyridinyl)alanine; D- or L-(3-pyridinyl)alanine; D- or L-(2-pyrazinyl)alanine; D- or L-(4-isopropyl)phenylglycine; D-(trifluoromethyl)phenylglycine; D-(trifluoromethyl)phenylalanine; D-.rho.-fluorophenylalanine; D- or L-.rho.-biphenylphenylalanine; D- or L-.rho.-methoxybiphenylphenylalanine; D- or L-2-indole(allyl)alanines and D- or L-alkylalanines, where the alkyl group may be substituted or unsubstituted with methyl, ethyl, propyl, hexyl, butyl, pentyl, isopropyl, isobutyl, sec-isotyl, isopentyl, or non-acidic amino acid residues. Non-natural amino acid aromatic rings include, for example, thiazolyl, thiophenyl, pyrazolyl, benzimidazolyl, naphthyl, furanyl, pyrrolyl, and pyridyl aromatic rings. Modified peptides that contain different amino acid mimetics or unnatural amino acid residues are particularly useful because they tend to show increased in vivo stability. Such peptides may also have improved storage or manufacturing properties.

[184] the Stability of the peptide can be assessed in various ways. For example, peptidases and various biological media such as human plasma and serum have been used for stability testing. See, for example, Verhoef et al., Eur. J. Drug Metab. Pharmacokinetics 11:291 (1986). The half-life of the peptides described herein is, for convenience, determined using a 25% human serum (v/v) assay. The protocol is as follows: pooled human serum (type AB, non-heat-inactivated) is destroyed by centrifugation prior to use. The serum is then diluted to 25% using RPMI-1640 or other suitable tissue culture medium. At certain time intervals, a small amount of the reaction solution was removed and 6% aqueous trichloroacetic acid (TCA) or ethanol was added. The cloudy reaction sample is cooled (4°C) for 15 minutes and then centrifuged to precipitate the settled whey proteins. The peptide content is then determined by reverse phase HPLC using chromatographic stability conditions.

[185] In certain embodiments, the neoantigenic peptide described herein may be in solution, in lyophilized form, or may be in crystalline form.

[186] In certain embodiments, the neoantigenic peptide described herein can be produced synthetically, by recombinant DNA technology, or by chemical synthesis, or can be isolated from natural sources such as native tumors or pathogenic organisms. Epitopes can be synthesized individually or attached directly or indirectly to the peptide. Although the neoantigenic peptide described herein is substantially free of other naturally occurring host cell proteins and fragments thereof, in certain embodiments, the peptide can be synthetically conjugated to be attached to native fragments or particles.

[187] In certain embodiments, the implementation of the neoantigenic peptide described in the present description, you can get a wide range of methods. In certain embodiments, the implementation of the peptides can be synthesized in solution or on a solid support in accordance with conventional methods. Various automatic synthesizers are commercially available and can be used according to known protocols. (See, for example, Stewart & Young, SOLID PHASE PEPTIDE SYNTHESIS, 2D. ED., Pierce Chemical Co., 1984). In addition, individual peptides can be attached using chemical ligation to produce larger peptides that are still within the scope of the invention.

[188] Alternatively, recombinant DNA technology can be used where the nucleotide sequence that encodes the peptide is introduced into an expression vector, transformed or transfected into a suitable host cell, and cultured under suitable expression conditions. These methods are generally known in the art, as described generally in Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989). Thus, recombinant peptides that contain or consist of one or more of the epitopes described herein can be used to provide a suitable T cell epitope.

[189] In one aspect, the invention described in the present description also relates to compositions containing one, at least two or more than two neoantigenic peptides. In certain embodiments, the implementation of the composition described in the present description contains at least two different peptides. In certain embodiments, at least two different peptides are derived from the same polypeptide. By different polypeptides is meant that the peptide differs in length, amino acid sequence, or both. The peptides are derived from any polypeptide known or found to carry a tumor-specific mutation.

[190] In certain embodiments, the isolated neoantigenic peptide is encoded by a gene with a point mutation resulting in an amino acid substitution of the native peptide.

[191] In certain embodiments, the isolated neoantigenic peptide is encoded by the ABL gene. В родственных вариантах осуществления A _x B _y C _z представляет собой VADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGKVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVC, VADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYGVVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVC, LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSATEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF, SLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIIIEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLA или STVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQHGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLG.

[192] In certain embodiments, the isolated neoantigenic peptide is encoded by the ALK gene. In related embodiments, A _x B _y C _z is SSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIADFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLL or QVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILMELMAGGDLKSFLRETRPRPSQPSSLAMLDLLH.

[193] In certain embodiments, the isolated neoantigenic peptide is encoded by the BRAF gene. In related embodiments, A _x B _y C _z is MIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATEKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELM. In some related embodiments, the neoantigenic peptide is not DFGLATEKSR or FGLATEKSRW.

[194] In certain embodiments, the isolated neoantigenic peptide is encoded by the BTK gene. In related embodiments, A _x B _y C _z is MIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGSLLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVND.

[195] In certain embodiments, the isolated neoantigenic peptide is encoded by the EEF1B2 gene. In related embodiments, A _x B _y C _z is MGFGDLKSPAGLQVLNDYLADKSYIEGYVPSQADVAVFEAVSGPPPADLCHALRWYNHIKSYEKASLPGVKKALGKYGPADVEDTTGSGAT. In some related embodiments, the neoantigenic peptide is not EAVSGPPPA, FEAVSGPPP, or FEAVSGPPPA.

[196] In certain embodiments, the isolated neoantigenic peptide is encoded by the EGFR gene. In related embodiments, A _x B _y C _z is MSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKIIRNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLL or IPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRRLGICLTSTVQLIMQLMPFGCLLDYVREHKTKIIGSQYLLNWLED.

[197] In certain embodiments, the isolated neoantigenic peptide is encoded by the ERBB3 gene. In related embodiments, A _x B _y C _z is EFSTLPLPNLRMVRGTQVYDGKF. In some related embodiments, the neoantigenic peptide is not RMVRGTQVY, LPLPNLRMV, LRMVRGTQV, TLPLPNLRMV, NLRMVRGTQV, or LRMVRGTQVY.

[198] In certain embodiments, the isolated neoantigenic peptide is encoded by the ESR1 gene. В родственных вариантах осуществления A _x B _y C _z представляет собой HLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYGLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEA, NQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLPSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSH, IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLCDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE, IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLNDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE или IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLSDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE.

[199] In certain embodiments, the isolated neoantigenic peptide is encoded by the FGFR3 gene. In related embodiments, A _x B _y C _z is HRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERCPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVG. In some related embodiments, the neoantigenic peptide is not DVLERCPHR, LERCPHRPI, CPHRPILQA, or LERPHRPIL.

[200] In certain embodiments, the isolated neoantigenic peptide is encoded by the FRG1B gene. In related embodiments, A _x B _y C _z is AVKLSDSRIALKSGYGKYLGINSDELVGHSDAIGPREQWEPVFQNGKMALSASNSCFIRCNEAGDIEAKSKTAGEEEMIKIRSCAEKETKKKDDIPEEDKG. In some related embodiments, the neoantigenic peptide is not SASNSCFIR, LSASNSCFI, ALSASNSCF, or FQNGKMALSA.

[201] In certain embodiments, the isolated neoantigenic peptide is encoded by the HER2 gene. In related embodiments, A _x B _y C _z is GSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGLGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM.

[202] In certain embodiments, the isolated neoantigenic peptide is encoded by the IDH1 gene. В родственных вариантах осуществления A _x B _y C _z представляет собой RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGHHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM, RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGCHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM, RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGGHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM или RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIGSHAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM. In some related embodiments, the neoantigenic peptide is not PIIIGHHAY, GHHAYGDQY, KPIIIGHHAY, IGHHAYGDQY, PIIIGCHAY, GCHAYGDQY, KPIIIGCHAY, IGCHAYGDQY, PIIIGGHAY, GGHAYGDQY, KPIIIGGHAY, or IGGHAYGDQY.

[203] In certain embodiments, the isolated neoantigenic peptide is encoded by the KIT gene. In related embodiments, A _x B _y C _z is VEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIANLLGACTIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYK or VEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIANLLGACTIGGPTLVITEYCCYSFICLSNFEDK.

[204] In certain embodiments, the isolated neoantigenic peptide is encoded by the MEK gene. В родственных вариантах осуществления A _x B _y C _z представляет собой ISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHESNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSI или LGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSLYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVI.

[205] In certain embodiments, the isolated neoantigenic peptide is encoded by the MYC gene. В родственных вариантах осуществления A _x B _y C _z представляет собой MPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSDLQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGG, FTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLSTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLG или TNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLPIPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGG.

[206] In certain embodiments, the isolated neoantigenic peptide is encoded by the PDGFRa gene. In related embodiments, A _x B _y C _z is VAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIIIEYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSYVILS.

[207] In certain embodiments, the isolated neoantigenic peptide is encoded by the PIK3CA gene. В родственных вариантах осуществления A _x B _y C _z представляет собой IEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLSKITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPP, HANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLSEITKQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKP или LFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDARHGGWTTKMDWIFHTIKQHALN. In some related embodiments, the neoantigenic peptide is not ISTRDPLSK, STRDPLSKI, LSKITEQEK, AISTRDPLSK, SKITEQEKDF, SEITKQEKDF, KQEKDFLWSH, FMKQMNDAR, KQMNDARHG, RHGGWTTKM, YFMKQMNDAR, FMKQMNDARH, KQMNDARHGG, QMNDARHGGW, or ARMHGGWTTK.

[208] In certain embodiments, the isolated neoantigenic peptide is encoded by the POLE gene. In related embodiments, A _x B _y C _z is QRGGVITDEEETSKKIADQLDNIVDMREYDVPYHIRLSIDIETTKLPLKFRDAETDQIMMISYMIDGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCVFN. In some related embodiments, the neoantigenic peptide is not TTKLPLKFR, RDAETDQIM, KFRDAETDQI, ETTKLPLKFR, or RDAETDQIMM.

[209] In certain embodiments, the isolated neoantigenic peptide is encoded by the PTEN gene. In related embodiments, A _x B _y C _z is KFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGQTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY. In some related embodiments, the neoantigenic peptide is not QTGVMICAY, GKGQTGVMI, GQTGVMICAY, or KAGKGQTGVM.

[210] In certain embodiments, the isolated neoantigenic peptide is encoded by the RAC1 gene. In related embodiments, A _x B _y C _z is MQAIKCVVVGDGAVGKTCLLISYTTNAFSGEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTVGET. In some related embodiments, the neoantigenic peptide is not TTNAFSGEY, FSGEYIPTV, SGEYIPTVF, YTTNAFSGEY, TTNAFSGEYI, or FSGEYIPTVF.

[211] In certain embodiments, the isolated neoantigenic peptide is encoded by the TP53 gene. В родственных вариантах осуществления A _x B _y C _z представляет собой IRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGSMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEP, TYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRHCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEV, EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNQRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE, EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNWRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE или PEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVCVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPL. В некоторых родственных вариантах осуществления неоантигенный пептид не является SSCMGSMNR, GSMNRRPIL, MGSMNRRPI, CNSSCMGSM, SMNRRPILTI, SSCMGSMNRR, NSSCMGSMNR, MGSMNRRPIL, MCNSSCMGSM, CMGSMNRRPI, TEVVRHCPH, VVRHCPHHER, SQHMTEVVRH, MNQRPILTI, NQRPILTII, CMGGMNQRPI, GMNQRPILTI, SSCMGGMNQR, NQRPILTIIT, NWRPILTII, SSCMGGMNW , MGGMNWRPI, MNWRPILTI, CMGGMNWRPI, GMNWRPILTI, SSCMGGMNWR, MNWRPILTII, NSSCMGGMNW, NSFEVCVCA, EVCVCACPGR, or FEVCVCACPG.

[212] In certain embodiments, the isolated neoantigenic peptide is encoded by a gene with a frameshift mutation.

[213] In certain embodiments, the isolated neoantigenic peptide is encoded by the ACVR2A gene. In related embodiments, A _x B _y C _z is GVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDDINCYDRTDCVEKKRQP or GVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDINCYDRTDCVEKKTALKYIFVAVRAICVMKSFLIFRRWKSHSPLQIQLHLSHPITTSCSIPWCHLC.

[214] In certain embodiments, the isolated neoantigenic peptide is encoded by the C15ORF40 gene. In related embodiments, A _x B _y C _z is TAEAVNVAIAAPPSEGEANAELCRYLSKVLELRRKSDVVLDKVGLALFFFFFETKSCSVAQAGVQWRSLGSLQPPPPGFKLFSCLSFLSSWDYRRMPPCLANFCIFNRDGVSPCWSGWS.

[215] In certain embodiments, the isolated neoantigenic peptide is encoded by the CNOT1 gene. In related embodiments, A _x B _y C _z is LSVIIFFFVYIWHWALPLILNNHHICLMSSIILDCNSVRQSIMSVCFFFFSVIFSTRCLTDSRYPNICWFK or LSVIIFFFVYIWHWALPLILNNHHICLMSSIILDCNSVRQSIMSVCFFFFCYILNTMFDR.

[216] In certain embodiments, the isolated neoantigenic peptide is encoded by the EIF2B3 gene. In related embodiments, A _x B _y C _z is VLVLSCDLITDVALHEVVDLFRAYDASLAMLMRKGQDSIEPVPGQKGKKKQWSSVTSLEWTAQERGCSSWLMKQTWMKSWSLRDPSYRSILEYVSTRVLWMPTSTV.

[217] In certain embodiments, the isolated neoantigenic peptide is encoded by the EPHB2 gene. In related embodiments, A _x B _y C _z is SIQVMRAQMNQIQSVEGQPLARRPRATGRTKRCQPRDVTKKTCNSNDGKKREWEKRKQILGGGGKYKEYFLKRILIRKAMTVLAGDKKGLGRFMRCVQSETKAVSLQLPLGR.

[218] In certain embodiments, the isolated neoantigenic peptide is encoded by the ESRP1 gene. In related embodiments, A _x B _y C _z is LDFLGEFATDIRTHGVHMVLNHQGRPSGDAFIQMKSADRAFMAAQKCHKKKHEGQIC or LDFLGEFATDIRTHGVHMVLNHQGRPSGDAFIQMKSADRAFMAAQKCHKKT.

[219] In certain embodiments, the isolated neoantigenic peptide is encoded by the FAM11B gene. In related embodiments, A _x B _y C _z is GALCKDGRFRSDIGEFEWKLKEGHKKIYGKQSMVDEVSGKVLEMDISKKKHYNRKISIKKLNRMKVPLMKLITRV. В некоторых родственных вариантах осуществления неоантигенный пептид не является KLNRMKVPL, PLMKLITRV, RMKVPLMKL, ISKKKHYNR, SKKKHYNRK, KHYNRKISI, HYNRKISIK, YNRKISIKK, KISIKKLNR, SIKKLNRMK, LNRMKVPLM, ISIKKLNRM, MKVPLMKLI, KLNRMKVPLM, RMKVPLMKLI, ISIKKLNRMK, ISKKKHYNRK, KHYNRKISIK, HYNRKISIKK, KISIKKLNRM, SIKKLNRMKV , LNRMKVPLMK, KVPLMKLITR, DISKKKHYNR, KKHYNRKISI, KKLNRMKVPL or VPLMKLITRV.

[220] In certain embodiments, the isolated neoantigenic peptide is encoded by the GBP3 gene. In related embodiments, A _x B _y C _z is RERAQLLEEQEKTLTSKLQEQARVLKERCQGESTQLQNEIQKLQKTLKKKPRDICRIS.

[221] In certain embodiments, the isolated neoantigenic peptide is encoded by the JAK1 gene. In related embodiments, A _x B _y C _z is VNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFEALLKTSN or CRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEEQNPDIVSEKNQQLKWTPHILKSAS.

[222] In certain embodiments, the isolated neoantigenic peptide is encoded by the LMAN1 gene. In related embodiments, A _x B _y C _z is DDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQELDKKKRGIPEGPPRPPRAACGGNI or DDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQQELDKKKRNSRRATPTSKGSLRRKYLRV.

[223] In certain embodiments, the isolated neoantigenic peptide is encoded by the MSH3 gene. In related embodiments, A _x B _y C _z is TKSTLIGEDVNPLIKLDDAVNVDEIMTDTSYLLCISENKENVRDKKKGQHFYWHCGSAACHRRGCV or LYTKSTLIGEDVNPLIKLDDAVNVDEIMTDTSTSYLLCISENKENVRDKKRATFLLALWECSLPQARLCLIVSRTLLLVQS.

[224] In certain embodiments, the isolated neoantigenic peptide is encoded by the NDUFC2 gene. In related embodiments, A _x B _y C _z is LPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQLLYITAFFFCWILSCKT or SLPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQLLYITAFFLLDIIL.

[225] In certain embodiments, the isolated neoantigenic peptide is encoded by the RBM27 gene. In related embodiments, A _x B _y C _z is NQSGGAGEDCQIFSTPGHPKMIYSSSNLKTPSKLCSGSKSHDVQEVLKKKTGSNEVTTRYEEKKTGSVRKANRMPKDVNIQVRKKQKHETRRKSKYNEDFERAWREDLTIKR.

[226] In certain embodiments, the isolated neoantigenic peptide is encoded by the RPL22 gene. In related embodiments, A _x B _y C _z is MAPVKKLVVKGGKKKEASSEVHS or MAPVKKLVVKGGKKRSKF. In some related embodiments, the neoantigenic peptide is not VVKGGKKRSK or VKGGKKRSK

[227] In certain embodiments, the isolated neoantigenic peptide is encoded by the SEC31A gene. In related embodiments, A _x B _y C _z is MPSHQGAEQQQQQHHVFISQVVTEKEFLSRSDQLQQAVQSQGFINYCQKKN or MPSHQGAEQQQQHHVFISQVVTEKEFLSRSDQLQAVQSQGFINYCQKKLMLLRLNLRKMCGPF.

[228] In certain embodiments, the isolated neoantigenic peptide is encoded by the SEC63 gene. In related embodiments, A _x B _y C _z is AEVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKKKETFKKKTYTCAITTVKATETKAGKWSRWE or MAEVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKKRNL.

[229] In certain embodiments, the isolated neoantigenic peptide is encoded by the SLC35F5 gene. In related embodiments, A _x B _y C _z is NIMEIRQLPSSHALEAKLSRMSYPVKEQESILKTVGKLTATQVAKISFFFALCGFWQICHIKKHFQTHKLL.

[230] In certain embodiments, the isolated neoantigenic peptide is encoded by the SMAP1 gene. In related embodiments, A _x B _y C _z is YEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKKKGREKERKGARKAGKTTYS or KYEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKKRKRKREKRSQKSRQNHLQLKSCRRKISNWSLKKVPALKKLRSPLWIF. В некоторых родственных вариантах осуществления неоантигенный пептид не является ALKKLRSPL, KISNWSLKK, SLKKVPALK, KLRSPLWIF, KKRKRKREK, RKREKRSQK, RSQKSRQNH, SQKSRQNHL, KSRQNHLQL, RRKISNWSL, RKISNWSLK, KVPALKKLR, HLQLKSCRR, WSLKKVPAL, RQNHLQLKS, KKVPALKKL, LKKLRSPLW, KKLRSPLWI, KISNWSLKKV, KSRQNHLQLK, SLKKVPALKK , WSLKKVPALK, KRKREKRSQK, RSQKSRQNHL, HLQLKSCRRK, RRKISNWSLK, CRRKISNWSL, NWSLKKVPAL, QKSRQNHLQL, RQNHLQLKSC, LQLKSCRRKI, ALKKLRSPLW, or KKLRSPLWI

[231] In certain embodiments, the isolated neoantigenic peptide is encoded by the TFAM gene. In related embodiments, A _x B _y C _z is IYQDAYRAEWQVYKEEISRFKEQLTPSQIMSLEKEIMDKHLKRKAMTKKKRVNTAWKTKKTSFSL or IYQDAYRAEWQVYKEEISRFKEQLTPSQIMSLEKEIMDKHLKRKAMTKKKS.

[232] In certain embodiments, the isolated neoantigenic peptide is encoded by the TGFBR2 gene. In related embodiments, A _x B _y C _z is KPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKAW or EKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKSLVRLSSCVPVALMSAMTTSSSQKNITPAILTCC.

[233] In certain embodiments, the isolated neoantigenic peptide is encoded by the THAP5 gene. In related embodiments, A _x B _y C _z is VPSKYQFLCSDHFTPDSLDIRWGIRYLKQTAVPTIFSLPEDNQGKDPSKKNPRRKTWKMRKKYAQKPSQKNHLY.

[234] In certain embodiments, the isolated neoantigenic peptide is encoded by the TTK gene. In related embodiments, A _x B _y C _z is GTTEEMKYVLGQLVGLNSPNSILKAAKTLYEHYSGGESHNSSSSKTFEKKGEKNDLQLFVMSDTTYKIYWTVILLNPCGNLHLKTTSL

[235] In certain embodiments, the isolated neoantigenic peptide is encoded by the XPOT gene. In related embodiments, A _x B _y C _z is QQLIRETLISWLQAQMLNPQPEKTFIRNKAAQVFALLFVTEYLTKWPKFFLTFSQ.

[236] In certain embodiments, the isolated neoantigenic peptide is encoded by the APC gene. In related embodiments, C _z is AKFQQCHSTLEPNPADCRVLVYLQNQPGTKLLNFLQERNLPPKVVLRHPKVHLNTMFRRPHSCLADVLLSVHLIVLRVVRLPAPFRVNHAVEW, APVIFQIALDKPCHQAEVKHLHHLLKQLKPSEKYLKIKHLLLKRERVDLSKLQ, or MLQPAFRGSRFFQVMLILYYILPRKQQ. В некоторых родственных вариантах осуществления неоантигенный пептид не является ADVLLSVHL, ADVLLSVHLI, APFRVNHAV, ARHKAVEFL, CLADVLLSV, CLADVLLSVH, DVLLSVHLI, DVLLSVHLIV, FLQERNLPPK, FRVNHAVEW, HLIVLRVVR, HLIVLRVVRL, HLNTMFRRPH, HPKVHLNTM, HPKVHLNTMF, KAVEFLQER, KVHLNTMFR, KVHLNTMFRR, KVVLRHPKV, LLSVHLIVL, LLSVHLIVLR , LPAPFRVNH, LPAPFRVNHA, LQERNLPPKV, LRVVRLPAPF, LSVHLIVLR, LSVHLIVLRV, MFRRPHSCL, MFRRPHSCLA, NLPPKVVLR, NTMFRRPHSC, QERNLPPKV, RHPKVHLNTM, RNLPPKVVL, RNLPPKVVLR, RPHSCLADV, RPHSCLADVL, RVVRLPAPF, RVVRLPAPFR, SARHKAVEFL, SVHLIVLRV, SVHLIVLRVV, TMFRRPHSC, TMFRRPHSCL, VEFLQERNL, VLLSVHLIV , VLLSVHLIVL, VLRHPKVHL, VLRVVRLPA, VVRLPAPFR, or VVRLPAPFRV.

[237] In certain embodiments, the isolated neoantigenic peptide is encoded by the ARID1A gene. В родственных вариантах осуществления C _z представляет собой ALGPHSRISCLPTQTRGCILLAATPRSSSSSSSNDMIPMAISSPPKAPLLAAPSPASRLQCINSNSRITSGQWMAHMALLPSGTKGRCTACHTALGRGSLSSSSCPQPSPSLPASNKLPSLPLSKMYTTSMAMPILPLPQLLLSADQQAAPRTNFHSSLAETVSLHPLAPMPSKTCHHK, AHQGFPAAKESRVIQLSLLSLLIPPLTCLASEALPRPLLALPPVLLSLAQDHSRLLQCQATRCHLGHPVASRTASCILP, PILAATGTSVRTAARTWVPRAAIRVPDPAAVPDDHAGPGAECHGRPLLYTADSSLWTTRPQRVWSTGPDSILQPAKSSPSAAAATLLPATTVPDPSCPTFVSAAATVSTTTAPVLSASILPAAIPASTSAVPGSIPLPAVDDTAAPPEPAPLLTATGSVSLPAAATSAASTLDALPAGCVSSAPVSAVPANCLFPAALPSTAGAISRFIWVSGILSPLNDLQ, PCRAGRRVPWAASLIHSRFLLMDNKAPAGMVNRARLHITTSKVLTLSSSSHPTPSNHRPRPLMPNLRISSSHSLNHHSSSPLSLHTPSSHPSLHISSPRLHTPPSSRRHSSTPRASPPTHSHRLSLLTSSSNLSSQHPRRSPSRLRILSPSLSSPSKLPIPSSASLHRRSYLKIHLGLRHPQPPQ, RTNPTVRMRPHCVPFWTGRILLPSAASVCPIPFEACHLCQAMTLRCPNTQGCCSSWAS или TNQALPKIEVICRGTPRCPSTVPPSPAQPYLRVSLPEDRYTQAWAPTSRTPWGAMVPRGVSMAHKVATPGSQTIMPCPMPTTPVQAWLEA. В некоторых родственных вариантах осуществления неоантигенный пептид не является AAWRSCIAL, AAWRSCIALW, AETVSLHPL, AETVSLHPLA, AHMALLPSG, ALWCASSVT, AMPILPLPQL, APLLAAPSPA, APRTNFHSS, APRTNFHSSL, ASNKLPSLPL, AWRSCIALW, CAGRWLWYCW, CIALWCASSV, CPQPSPSLPA, CRRAVSATSW, CTACHTALGR, DQQAAPRTNF, ETVSLHPLA, FHSSLAETV, GMYSPSRYPR , GQWMAHMAL, GQWMAHMALL, GRCTACHTAL, GTAWQLVPL, HMALLPSGT, HMALLPSGTK, HPLAPMPSK, HSSLAETVSL, HTALGRGSL, IALWCASSV, ILATPPSAA, ILATPPSAAW, IPMAISSPP, IPMAISSPPK, ISSPPKAPL, ISSPPKAPLL, ITSGQWMAHM, KGRCTACHT, KGRCTACHTA, KLPSLPLSK, KLPSLPLSKM, KMYTTSMAM, KMYTTSMAMP, LAAPSPASR, LAAPSPASRL , LAETVSLHPL, LATPPSAAW, LATPPSAAWR, LLAAPSPASR, LLLSADQQAA, LLSADQQAA, LPASNKLPS, LPASNKLPSL, LPLPQLLLS, LPLPQLLLSA, LPSLPLSKM, LPSLPLSKMY, LQCINSNSRI, LQCRRAVSA, LQCRRAVSAT, LSADQQAAPR, LSKMYTTSM, LSKMYTTSMA, LWCASSVTER, LWYCWPTWL, LWYCWPTWLR, MAHMALLPS, MALLPSGTK, MPILPLPQL, MPILPLPQLL , MYSPSRYPR, MYTTSMAMPI, PMAISSPPK, QLVPLQCRR, QQAAPRTNF, QQAAPRTNFH, QWMAHMALL, RAVSATSWA, RAVSATSWA S, RCAGRWLWY, RCTACHTAL, RGTAWQLVPL, RLQCINSNSR, RRAVSATSW, RTNFHSSLA, RTNFHSSLAE, RTRCAGRWL, RTRCAGRWLW, RWLWYCWPT, RWLWYCWPTW, SAAWRSCIA, SAAWRSCIAL, SGQWMAHMAL, SKMYTTSMA, SKMYTTSMAM, SMAMPILPL, SNKLPSLPL, SPASRLQCI, SPPKAPLLAA, SPSLPASNKL, SRITSGQWM, SSCPQPSPSL, SSLAETVSL, SSNDMIPMAI, SSSNDMIPM, SSSSNDMIPM, SSSSSSNDM, SSSSSSSNDM, TACHTALGR, TERTRCAGRW, TSMAMPILPL, TTSMAMPIL, TVSLHPLAPM, TWLRGTAWQL, VPLQCRRAV, VSLHPLAPM, VTERTRCAGR, WLRGTAWQL, WLRGTAWQLV, WLWYCWPTW, WLWYCWPTWL, WMAHMALLPS, WPTWLRGTA, WPTWLRGTAW, WYCWPTWLR, YPRSSSSSS, YPRSSSSSSS, YTTSMAMPI или YTTSMAMPIL.

[238] In certain embodiments, the isolated neoantigenic peptide is encoded by the β2M gene. In related embodiments, C _z is RMERELKKWSIQTCLSARTGLSISCTTLNSPPLKKMSMPAV or LCSRYSLFLAWRLSSVLQRFRFTHVIQQRMESQIS. В некоторых родственных вариантах осуществления неоантигенный пептид не является ALAVLALLSF, ALLSFWPGGY, DSGLLTSSSR, ELLCVWVSSI, EWKVKFPEL, FPELLCVWV, FWPGGYPAY, GLLTSSSREW, KFPELLCVW, KFPELLCVWV, KVKFPELLC, KVKFPELLCV, LAVLALLSF, LAVLALLSFW, LLCVWVSSI, LLCVWVSSIR, LLSFWPGGY, LLTSSSREW, LLTSSSREWK, LSFWPGGYPA, LTSSSREWK or YPAYSKDSGL.

[239] In certain embodiments, the isolated neoantigenic peptide is encoded by the CDH1 gene. В родственных вариантах осуществления C _z представляет собой RSACVTVKGPLASVGRHSLSKQDCKFLPFWGFLEEFLLC, IQWGTTTAPRPIRPPFLESKQNCSHFPTPLLASEDRRETGLFLPSAAQKMKKAHFLKTWFRSNPTKTKKARFSTASLAKELTHPLLVSLLLKEKQDG, PTDPFLGLRLGLHLQKVFHQSHAEYSGAPPPPPAPSGLRFWNPSRIAHISQLLSWPQKTEERLGYSSHQLPRK, FCCSCCFFGGERWSKSPYCPQRMTPGTTFITMMKKEAEKRTRTLT или WRRNCKAPVSLRKSVQTPARSSPARPDRTRRLPSLGVPGQPWALGAAASRRCCCCCRSPLGSARSRSPATLALTPRATRSRCPGATWREAASWAE.

[240] In certain embodiments, the isolated neoantigenic peptide is encoded by the GATA3 gene. In related embodiments, C _z is PGRPLQTHVLPEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHRHGLEPCSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLKAESKIMFATLQRSSLWCLCSNH or PRPRRCTRHPACPLDHTTPPAWSPPWVRALLDAHRAPSESPCSPFRLAFLQEQYHEA. В некоторых родственных вариантах осуществления неоантигенный пептид не является AALSRHNVL, ADAPAIQPV, ADAPAIQPVL, AESKIMFAT, AESKIMFATL, AIQPVLWTT, ALQPLQPHA, APAIQPVLW, ARVPAVPFDL, ATLQRSSLW, AVPFDLHFCR, CSMLTGPPA, CSMLTGPPAR, DLHFCRSSI, DLHFCRSSIM, EPHLALQPL, ESKIMFATL, FATLQRSSL, FATLQRSSLW, FCRSSIMKPK, FDLHFCRSSI , FLKAESKIM, FLKAESKIMF, GPPARVPAV, GYMFLKAESK, HADAPAIQPV, HAHADAPAI, HFCRSSIMK, HLALQPLQPH, HMSSLSHISA, HPLQHGHRH, HPPSSLSFW, HRHGLEPCSM, IMFATLQRS, IMFATLQRSS, IMKPKRDGY, IMKPKRDGYM, KAESKIMFA, KIMFATLQR, KPKRDGYMF, KPKRDGYMFL, LALQPLQPH, LHFCRSSIM, LHFCRSSIMK, LKAESKIMF, LQHGHRHGL , LQPHADHAH, LQRSSLWCL, LQRSSLWCLC, LSFGPHHPL, LSFGPHPPL, LSFWTTPPL, LSHISALQPL, MFATLQRSSL, MFLKAESKI, MFLKAESKIM, MHPPSSLSFW, MKPKRDGYMF, MLTGPPARV, MSSLSHISA, MSSLSHISAL, NPAALSRHNV, PARVPAVPF, PAVPFDLHF, PEPHLALQPL, PPARVPAVPF, QPVLWTTPPL, RHGLEPCSM, RHNVLPEPHL, RSSIMKPKR, SALQPLQPH , SHISALQPL, SIMKPKRDGY, SLSFGPHHPL, SLSFGPHPPL, SLSFWTTPPL, SMLTGPPAR, SMLTGPPARV, SSLSHISAL, TLQRSSLWCL, TT PPLQHGHR, VLPEPHLAL, VPAVPFDLHF, VPFDLHFCR, YMFLKAESK, or YMFLKAESKI.

[241] In certain embodiments, the isolated neoantigenic peptide is encoded by the MLL2 gene. В родственных вариантах осуществления C _z представляет собой TRRCHCCPHLRSHPCPHHLRNHPRPHHLRHHACHHHLRNCPHPHFLRHCTCPGRWRNRPSLRRLRSLLCLPHLNHHLFLHWRSRPCLHRKSHPHLLHLRRLYPHHLKHRPCPHHLKNLLCPRHLRNCPLPRHLKHLACLHHLRSHPCPLHLKSHPCLHHRRHLVCSHHLKSLLCPLHLRSLPFPHHLRHHACPHHLRTRLCPHHLKNHLCPPHLRYRAYPPCLWCHACLHRLRNLPCPHRLRSLPRPLHLRLHASPHHLRTPPHPHHLRTHLLPHHRRTRSCPCRWRSHPCCHYLRSRNSAPGPRGRTCHPGLRSRTCPPGLRSHTYLRRLRSHTCPPSLRSHAYALCLRSHTCPPRLRDHICPLSLRNCTCPPRLRSRTCLLCLRSHACPPNLRNHTCPPSLRSHACPPGLRNRICPLSLRSHPCPLGLKSPLRSQANALHLRSCPCSLPLGNHPYLPCLESQPCLSLGNHLCPLCPRSCRCPHLGSHPCRLS. В некоторых родственных вариантах осуществления неоантигенный пептид не является APGPRGRTC, CHYLRSRNSA, CLRSHTCPPR, CLWCHACLHR, CPHLGSHPC, CPHRLRSLPR, CPLGLKSPL, CPPGLRNRI, CPPGLRSHTY, CPPRLRDHI, CPPSLRSHAY, CPRSCRCPH, CPRSCRCPHL, CSLPLGNHPY, CTCPPRLRSR, DHICPLSLR, EESPMSPHL, ESPMSPHLR, ESPMSPHLRY, EVSRLSPCL, GLKSPLRSQA , GLRNRICPL, GLRNRICPLS, GLRSHTYLR, GLRSHTYLRR, GLRSRTCPPG, HACPPGLRNR, HAYALCLRSH, HHLRTHLLPH, HLGSHPCRL, HLLPHHRRTR, HLRLHASPH, HLRLHASPHH, HLRSCPCSL, HLRTHLLPH, HLRTHLLPHH, HLRTPPHPH, HLRTPPHPHH, HLRYRAYPP, HLRYRAYPPC, HPCCHYLRSR, HPHHLRTHL, HPHHLRTHLL, HRLRSLPRPL, HTYLRRLRS, HTYLRRLRSH , HYLRSRNSA, KSPLRSQANA, LESQPCLSL, LHLRLHASPH, LHLRSCPCSL, LLPHHRRTR, LPCPHRLRSL, LPHHRRTRS, LPHHRRTRSC, LPLGNHPYL, LPRPLHLRL, LRLHASPHHL, LRNCTCPPRL, LRNHTCPPSL, LRNRICPLSL, LRSCPCSLPL, LRSHACPPGL, LRSHACPPNL, LRSHAYALCL, LRSHTCPPRL, LRSHTCPPSL, LRSHTYLRRL, LRSLPRPLHL, LRSQANALHL, LRTPPHPHHL , LRYRAYPPCL, LSLGNHLCPL, LSLRSHPCPL, LWCHACLHRL, MSPHLRYRA, MSPHLRYRAY, NLPCPHRLR, NLRNHTCPP, PMSPHLRYR, PPRLRSRTCL, PPSLRSHAY, RAYPPCLWCH, RDHICPLSL, RGRTCHPGL, RGRTCHPGLR, RLHASPHHL, RLHASPHHLR, RLRDHICPL, RLRDHICPLS, RLRNLPCPH, RLRNLPCPHR, RLRSHTCPP, RLRSHTCPPS, RLRSLPRPL, RLRSLPRPLH, RLRSRTCLL, RLRSRTCLLC, RLSPCLWCHA, RNHTCPPSL, RNHTCPPSLR, RNLPCPHRLR, RNRICPLSL, RNRICPLSLR, RPLHLRLHA, RPLHLRLHAS, RSCPCRWRSH, RSCPCSLPL, RSHACPPGL, RSHACPPGLR, RSHACPPNL, RSHACPPNLR, RSHAYALCL, RSHAYALCLR, RSHPCCHYL, RSHPCCHYLR, RSHPCPLGL, RSHPCPLGLK, RSHTCPPRL, RSHTCPPRLR, RSHTCPPSL, RSHTCPPSLR, RSHTYLRRL, RSHTYLRRLR, RSLPRPLHL, RSLPRPLHLR, RSQANALHL, RSQANALHLR, RSRNSAPGP, RSRNSAPGPR, RSRTCLLCL, RSRTCLLCLR, RSRTCPPGL, RSRTCPPGLR, RTCHPGLRSR, RTHLLPHHR, RTHLLPHHRR, RTPPHPHHL, RTPPHPHHLR, RTRSCPCRW, RTRSCPCRWR, RWRSHPCCH, RWRSHPCCHY, RYRAYPPCL, RYRAYPPCLW, SHAYALCLR, SLGNHLCPL, SLPLGNHPY, SLPLGNHPYL, SLPRPLHLR, SLPRPLHLRL, SLRNCTCPPR, SLRSHACPPG, SLRSHAYAL, SLRSHAYALC, SLRSHPCPL, SLRSHPCPLG, SPHHLRTPP, SPHHLRTPPH, SPHLRYRAY, SPLRSQANAL, SPMSPHLRY, SPMSPHLRYR, SQANALHLR, SQANALHLRS, VSRLSPCLW, WRSHPCCHY, WRSHPCCHYL, YLPCLESQPC, YLRRLRSHTC, YLRSRNSAP, or YLRSRNSAPG.

[242] In certain embodiments, the isolated neoantigenic peptide is encoded by the PTEN gene. В родственных вариантах осуществления C _z представляет собой SWKGTNWCNDMCIFITSGQIFKGTRGPRFLWGSKDQRQKGSNYSQSEALCVLL, KRTKCFTFG, PIFIQTLLLWDFLQKDLKAYTGTILMM, QKMILTKQIKTKPTDTFLQILR, GFWIQSIKTITRYTIFVLKDIMTPPNLIAELHNILLKTITHHS, NYSNVQWRNLQSSVCGLPAKGEDIFLQFRTHTTGRQVHVL или YQSRVLPQTEQDAKKGQNVSLLGKYILHTRTRGNLRKSRKWKSM. In some related embodiments, the neoantigenic peptide is not KMLKRTKCF, MLKRTKCFT, LKRTKCFTF, MLKRTKCFTF, KQNKMLKRTK, KMLKRTKCFT, or NKMLKRTKCM.

[243] In certain embodiments, the isolated neoantigenic peptide is encoded by the TP53 gene. В родственных вариантах осуществления C _z представляет собой SSQNARGCSPRGPCTSSSYTGGPCTSPLLAPVIFCPFPENLPGQLRFPSGLLAFWDSQVCDLHVLPCPQQDVLPTGQDLPCAAVG, GAAPTMSAAQIAMVWPLLSILSEWKEICVWSIWMTETLFDIVWWCPMSRLRLALTVPPSTTTTCVTVPAWAA, TGGPSSPSSHWKTPVVIYWDGTALRCVFVPVLGETGAQRKRISARKGSLTTSCPQGALSEHCPTTPAPLPSQRRNHWMENISPFRSVGVSASRCSES, FHTPARHPRPRHGHLQAVTAHDGGCEALPPP, CCPRTILNNGSLKTQVQMKLPECQRLLPPWPLHQQLLHRRPLHQPPPGPCHLLSLPRKPTRAATVSVWASCILGQPSL, VRKHFQTYGNYFLKTTFCPPCRPKQWMI или LARTPLPSTRCFANWPRPALCSCGLIPHPRPAPASAPWPSTSSHST. В некоторых родственных вариантах осуществления неоантигенный пептид не является APASAPWPST, APPWPLHQQL, APWPSTSSH, ASCILGQPSL, ATVSVWASCI, CQRLLPPWPL, HQPPPGPCHL, HQQLLHRRPL, IEQWFTEDQV, KLPECQRLL, KPTRAATVSV, KTYQGSYGFV, KTYQGSYVS, KTYQGSYVSV, LLSLPRKPTR, LPPWPLHQQL, LPRKPTRAA, LPRKPTRAAT, LSLPRKPTR, MKLPECQRL, MKLPECQRLL , MPEAAPPWPL, PEAAPPWPL, PTRAATVSV, QMKLPECQR, QQLLHRRPL, QQLLHRRPLH, QRLLPPWPL, QWFTEDQVQM, RAATVSVWA, RLLPPWPLH, RMPEAAPPW, RPAPASAPW, SLPRKPTRA, SLPRKPTRAA, SQKTYQGSYV, STPRPAPASA, SYGFVWASC, SYGFVWASCI, SYVSVWASC, SYVSVWASCI, TEDQVQMKL, TPRPAPASA, TPRPAPASAP, TRAATVSVW, TVSVWASCI , TVSVWASCIL, TYQGSYGFV, TYQGSYGFVW, TYQGSYVSV, TYQGSYVSVW, VSVWASCIL, WPLHQQLLH, WPSTSSHST, YGFVWASCI, YGFVWASCIL, YQGSYGFVW, YQGSYGFVWA, YQGSYVSVW, YQGSYVSVWA, YVSVWASCI or YVVWASCIL.

[244] In certain embodiments, the isolated neoantigenic peptide is encoded by the VHL gene. В родственных вариантах осуществления C _z представляет собой ELQETGHRQVALRRSGRPPKCAERPGAADTGAHCTSTDGRLKISVETYTVSSQLLMVLMSLDLDTGLVPSLVSKCLILRVK, KSDASRLSGA, RTAYFCQYHTASVYSERAMPPGCPEPSQA, TRASPPRSSSAIAVRASCCPYGSTSTASRSPTQRCRLARAAASTATEVTFGSSEMQGHTMGFWLTKLNYLCHLSMLTDSLFLPISHCQCIL, SSLRITGDWTSSGRSTKIWKTTQMCRKTWSG или RRRRGGVGRRGVRPGRVRPGGTGRRGGDGGRAAAARAALGELARALPGHLLQSQSARRAARMAQLRRRAAALPNAAAWHGPPHPQLPRSPLALQRCRDTRWASG. В некоторых родственных вариантах осуществления неоантигенный пептид не является CHLSMLTDSL, EMQGHTMGF, FLPISHCQC, FLPISHCQCI, FRDAGHTMGF, FWLTKLNYL, GFWLTKLNY, GFWLTKLNYL, GSSEMQGHTM, HLSMLTDSL, HLSMLTDSLF, HSYRGHLGSS, HTMGFWLTK, HTMGFWLTKL, KERCLQLSGA, KLNYLCHLSM, LFRDAGHTM, LNYLCHLSM, LNYLCHLSML, LPISHCQCI, LPISHCQCIL , LSMLTDSLF, LSMLTDSLFL, LTDSLFLPI, LTKLNYLCHL, MGFWLTKLNY, MLTDSLFLPI, MQGHTMGFW, MQGHTMGFWL, NYLCHLSML, RDAGHTMGF, RDAGHTMGFW, RGHLGSSEM, RIHSYRGHLG, SEMQGHTMG, SEMQGHTMGF, SLFLPISHC, SMLTDSLFL, SSEMQGHTM, TKLNYLCHL, TLKERCLQL, TMGFWLTKL, WLFRDAGHT, WLFRDAGHTM, YLCHLSMLT или YRGHLGSSEM .

[245] In certain embodiments, the isolated neoantigenic peptide is encoded by the fusion of a first gene with a second gene. In certain embodiments, the isolated neoantigenic peptide is encoded by an in-frame fusion of a first gene with a second gene.

[246] In certain embodiments, the isolated neoantigenic peptide is encoded by the BCR gene and the ABL gene. In related embodiments, A _x B _y C _z is ERAEWRENIREQQKKCFRSFSLTSVELQMLTNSCVKLQTVHSIPLTINKEEALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASG or ELQMLTNSCVKLQTVHSIPLTINKEDDESPGLYGFLNVIVHSATGFSGQSSKALQRPVASDFEPQGLSEAARWNSKENL.

[247] In certain embodiments, the isolated neoantigenic peptide is encoded by the C11orf95 gene and the RELA gene. In related embodiments, A _x B _y C _z is ISNSWDAHLGLGACGEAEGLGVQGAEEEEEEEEEEEEEGAGVPACPPKGPELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTD.

[248] In certain embodiments, the isolated neoantigenic peptide is encoded by the CBFB gene and the MYH11 gene. LQRLDGMGCLEFDEERAQQEDALAQQAFEEARRRRTREFEDRDRSHREEMEVHELEKSKRALETQMEEMKTQLEELEDELQATEDAKLRLEVNMQALKGQF.

[249] In certain embodiments, the isolated neoantigenic peptide is encoded by the CD74 gene and the ROS1 gene. In related embodiments, AxByCz is KGSFPENLRHLKNTMETIDWKVFESWMHHWLLFEMSRHSLEQKPTDAPPKAGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQ.

[250] In certain embodiments, the isolated neoantigenic peptide is encoded by the EGFR gene and the SEPT14 gene. In related embodiments, A _x B _y C _z is the first native polypeptide encoded by the gene and the second native polypeptide is encoded by LPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQLQDKFEHLKMIQQEEIRKLEEEKKQLEGEIIDFYKMKAASEALQTQLSTD.

[251] In certain embodiments, the isolated neoantigenic peptide is encoded by the EGFR gene and the EGFR gene. In related embodiments, A _x B _y C _z is MRPSGTAGAALLALLAALCPASRALEEKKGNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKD.

[252] In certain embodiments, the isolated neoantigenic peptide is encoded by the EML4 gene and the ALK gene. In related embodiments, A _x B _y C _z is SWENSDDSRNKLSKIPSTPKLIPKVTKTADKHKDVIINQAKMSTREKNSQVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDL.

[253] In certain embodiments, the isolated neoantigenic peptide is encoded by the FGFR3 gene and the TACC3 gene. In related embodiments, A _x B _y C _z is EGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDVKATQEENRELRSRCEELHGKNLELGKIMDRFEEVVYQAMEEVQKQKELS,

[254] In certain embodiments, the isolated neoantigenic peptide is encoded by the NAB gene and the STAT6 gene. In related embodiments, A _x B _y C _z is RDNTLLLRRVELFSLSSRQVARESTYLSSLKGSRLHPEELGGPPLKKLKQEATSKSQIMSLWGLVSKMPEKVQRLYVDFPQHLRHLLGDWLESQPWEFLVGSDAFCC.

[255] In certain embodiments, the isolated neoantigenic peptide is encoded by the NDRG1 gene and the ERG gene. In related embodiments, A _x B _y C _z is MSREMQDVDLAEVKPLVEKGETITGLLQEFDVQEALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDW.

[256] In certain embodiments, the isolated neoantigenic peptide is encoded by the TMPRSS2 gene and the ERG gene. In related embodiments, A _x B _y C _z is MALNSEALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDW.

[257] In certain embodiments, the isolated neoantigenic peptide is encoded by the PML gene and the RARA gene. In related embodiments, A _x B _y C _z is VLDMHGFLRQALCRLRQEEPQSLQAAVRTDGFDEFKVRLQDLSSCITQGKAIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKG or RSSPEQPRPSTSKAAVSPPHLDGPPSPRSPVIGSEVFLPNNSNHVASGAGEAAIETQSSSSEEIVPSPPSPGPLPRIYKPCFVCGQDACEG.

[258] In certain embodiments, the isolated neoantigenic peptide is encoded by the RUNX1 gene and the CBFA2T1 (RUNX1T1) gene. In related embodiments, A _x B _y C _z is VARFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKITVDGPREPRNRTEKHSTMPDSPVDVKTQSRLTPPTMPPPPTTQGAPRTSSFTPTTLTNGT

[259] In certain embodiments, the isolated neoantigenic peptide is encoded by fusion of the first gene with an exon splicing variant of the first gene. In certain embodiments, the isolated neoantigenic peptide is encoded by the fusion of the first gene to the cryptic exon of the first gene.

[260] In certain embodiments, the isolated neoantigenic peptide is encoded by the AR-v7 gene and the cryptic exon encoded by the AR-v7 gene. In certain embodiments, the isolated neoantigenic peptide is encoded by an AR-v7 gene containing an exon splicing variant of the AR gene. In related embodiments, A _x B _y C _z is SCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLGEKFRVGNCKHLKMTRP.

[261] In certain embodiments, the isolated neoantigenic peptide is encoded by a fusion of a first gene to a second gene, wherein the peptide contains an amino acid sequence encoded by an out-of-frame sequence resulting from the fusion.

[262] In certain embodiments, the isolated neoantigenic peptide is encoded by the AC011997.1 gene and the LRRC69 gene. In related embodiments, y is 1. In related embodiments, A _x B _y C _z is MAGAPPPASLPPCSLISDCCASNQRDSVGVGPSEPGNNIKICNESASRK.

[263] In certain embodiments, the isolated neoantigenic peptide is encoded by the EEF1DP3 gene and the FRY gene. In related embodiments, y is 1. In related embodiments, A _x B _y C _z is HGWRPFLPVRARSRWNRRLDVTVANGRSWKYGWSLLRVPQVNGIQVLNVSLKSSSNVISY.

[264] In certain embodiments, the isolated neoantigenic peptide is encoded by the MAD1L1 gene and the MAFK gene. In related embodiments, y is 0. In related embodiments, A _x B _y C _z is RLKEVFQTKIQEFRKACYTLTGYQIDITTENQYRLTSLYAEHPGDCLIFKLRVPGSSVLVTVPGL.

[265] In certain embodiments, the isolated neoantigenic peptide is encoded by the PPP1R1B gene and the STARD3 gene. In related embodiments, y is 1. In related embodiments, A _x B _y C _z is AEVLKVIRQSAGQKTTCGQGLEGPWERPPPLDESERDGGSEDQVEDPALSALLLRPRPPRPEVGAHQDEQAAQGADPRLGAQPACRGLPGLLTVPQPEPLLAPPSAA.

[266] In certain embodiments, the isolated neoantigenic peptide comprises one or more of the peptide sequences illustrated in Table 1. In certain embodiments, the isolated neoantigenic peptide comprises one or more of the peptide sequences illustrated in Table 1A, Table 1B, Table 1C, Table 1D, Table 1E and/or Table 1F. In certain embodiments, the isolated neoantigenic peptide does not contain one or more of the peptide sequences illustrated in Table 2. In certain embodiments, the isolated neoantigenic peptide does not contain one or more of the peptide sequences illustrated in Table 2A, Table 2B, Table 2C, and/or Table 2D .

Neoantigenic polynucleotides

[267] The polynucleotides encoding each of the peptides described herein are also part of the invention. As one skilled in the art will understand, different nucleic acid sequences can encode the same peptide due to the degeneracy of the genetic code. Each of these nucleic acids is within the scope of the present invention. Nucleic acids encoding peptides may be DNA or RNA, such as mRNA, or a combination of DNA and RNA. In certain embodiments, the nucleic acid encoding the peptide is a self-amplifying mRNA. (Brito et al., Adv. Genet. 2015; 89:179-233). Any suitable polynucleotide encoding the peptide described in the present description, is included in the scope of the present invention.

[268] The term "RNA" includes and in certain embodiments refers to "mRNA". The term "mRNA" means "messenger RNA" and refers to a "transcript", which is obtained using a DNA template, and which encodes a peptide or polypeptide. Typically, an mRNA contains a 5'UTR, a protein coding region, and a 3'UTR. mRNAs have only a limited half-life in cells and in vitro . In certain embodiments, the mRNA is a self-amplifying mRNA. In the context of the present invention, mRNA can be obtained by in vitro transcription from a DNA template. The in vitro transcription method is known to the skilled person. For example, there are a number of commercially available in vitro transcription kits.

[269] The stability and efficiency of RNA translation can be modified as needed. For example, RNA can be stabilized and its translation can be increased by one or more modifications that have stabilizing effects and/or increase the efficiency of RNA translation. Such modifications are described, for example, in PCT/EP2006/009448, incorporated herein by reference. To increase the expression of the RNA used in the present invention, it can be modified in the coding region, i. sequence encoding an expressed peptide or protein without changing the sequence of an expressed peptide or protein, thus it is possible to increase the content of GC to increase mRNA stability and carry out codon optimization and thus enhance translation in cells.

[270] the Term "modification" in relation to the RNA used in the present invention refers to any modification of the RNA, which does not occur naturally in the specified RNA. In certain embodiments of the invention, the RNA used according to the invention does not contain uncapped 5'-triphosphates. Removal of such uncapped 5'-triphosphates can be obtained by treating the RNA with phosphatase. The RNA of the invention may contain modified ribonucleotides to increase its stability and/or reduce cytotoxicity. For example, in certain embodiments, in the RNA used according to the invention, 5-methylcytidine is partially or completely replaced, for example, completely with cytidine. Alternatively or additionally, in certain embodiments, pseudouridine is partially or completely replaced in the RNA used according to the invention, for example, completely with uridine.

[271] In certain embodiments, the term "modification" refers to providing RNA with a 5'-cap or 5'-cap analog. The term "5'cap" refers to the cap structure found at the 5' end of the mRNA molecule and typically consists of a guanosine nucleotide linked to the mRNA by a conventional 5'-5' triphosphate bond. In certain embodiments, such guanosine is 7-methylated. The term "conventional 5'-cap" refers to the natural 5'-cap of RNA, the 7-methylguanosine cap (mG). In the context of the present invention, the term "5'-cap" refers to a 5'-cap analog that is similar to the RNA cap structure and is modified to have the ability to stabilize RNA and/or enhance RNA translation, if attached, in vivo and /or in a cage.

[272] In certain embodiments, an mRNA encoding a neoantigenic peptide of the invention is administered to an individual in need thereof. In certain embodiments, the invention relates to RNA, oligoribonucleotide and polyribonucleotide molecules containing a modified nucleoside, gene therapy vectors containing the neoantigenic peptide of the invention, gene therapy methods, and methods for transcriptionally silencing genes containing the neoantigenic peptide of the invention. In certain embodiments, the mRNA to be administered contains at least one modified nucleoside.

[273] Polynucleotides encoding the peptides described herein can be synthesized by chemical methods, for example, the phosphotriester method according to Matteucci, et al., J. Am. Chem. soc. 103:3185 (1981). Polynucleotides encoding peptides containing or consisting of an analog can simply be easily prepared by substituting the appropriate and desired nucleic acid base(s) with a base that encodes a native epitope.

[274] A large number of vectors and host systems suitable for the production and administration of the neoantigenic peptide described herein are known to those skilled in the art and are commercially available. The following vectors are given as an example. Bacterial: pQE70, pQE60, pQE-9 (Qiagen), pBS, pD10, PhageScript, psiX174, pBlueScript SK, pbsks, pNH8A, pNH16a, pNH18A, pNH46A (Stratagene); ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 (Pharmacia); pCR (Invitrogen). Eukaryotic: pWLNEO, pSV2CAT, pOG44, pXT1, pSG (Stratagene) pSVK3, pBPV, pMSG, pSVL (Pharmacia); p75.6 (Valentis); pCEP (Invitrogen); pCEI (Epimmune). However, any other plasmid or vector may be used, provided it is replicable and viable in the host.

[275] As representative examples of suitable hosts, mention may be made of: bacterial cells such as E. coli , Bacillus subtilis, Salmonella typhimurium , and various species of the genus Pseudomonas , Streptomyces , and Staphylococcus ; fungal cells such as yeast; insect cells such as Drosophila and Sf9; animal cells such as the monkey kidney fibroblast line COS-7 described by Gluzman, Cell 23:175 (1981), and other cell lines capable of expressing a compatible vector, such as C127, 3T3, CHO, HeLa and BHK cell lines or Bowes melanoma ; plant cells, etc. Based on the indications in the present description, specialists in this field are able to select a suitable host.

[276] Thus, the present invention also relates to vectors and expression vectors suitable for the production and administration of the neoantigenic peptides described herein, and to host cells containing such vectors.

[277] Host cells are genetically engineered (transduced or transformed or transfected) with vectors, which may be, for example, a cloning vector or an expression vector. The vector may be in the form of a plasmid, virus particle, phage, etc., for example. The engineered host cells can be cultured in conventional nutrient media modified as necessary to activate promoters, select transformants, or amplify polynucleotides. Culture conditions such as temperature, pH, and the like are those previously used for the host cell selected for expression, and will generally be apparent to one skilled in the art.

[278] For expression of the neoantigenic peptides described herein, a coding sequence is provided operably linked to the strat and stop codons, promoter and terminator regions, and in certain embodiments, a replication system to provide an expression vector for expression in the desired cellular host. For example, promoter sequences compatible with bacterial hosts are provided in plasmids containing suitable restriction sites to insert the desired coding sequence. The resulting expression vectors are transformed into suitable bacterial hosts.

[279] Typically, recombinant expression vectors contain origins of replication and selectable markers that allow transformation of the host cell, such as the E. coli ampicillin resistance gene and the S. cerevisiae TRP1 gene, and a promoter derived from a highly expressed gene for direction of transcription of the subsequent structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in an appropriate phase with translation initiation and termination sequences and, in certain embodiments, a leader sequence capable of directing the secretion of the translated protein into the periplasmic space or extracellular environment. Optionally, the heterologous sequence may encode a fusion protein, including a signal peptide at the N-terminus, conferring the desired characteristics, such as stabilization or easier purification of the expressed recombinant product.

[280] Yeast, insect, or mammalian host cells can also be used using suitable vectors and regulatory sequences. Examples of mammalian expression systems include the COS-7 monkey kidney fibroblast lines described by Gluzman, Cell 23:175 (1981), and other cell lines capable of expressing a compatible vector, such as C127, 3T3, CHO, HeLa, and BHK cell lines. Mammalian expression vectors contain an origin of replication, a suitable promoter and enhancer, and any necessary ribosome binding sites, polyadenylation site, splicing donor and acceptor sites, transcription termination sequences, and 5' flanking non-transcribed sequences. Such promoters can also be obtained from viral sources such as, for example, human cytomegalovirus (CMV-IE promoter) or herpes simplex virus type 1 (HSV TK promoter). Nucleic acid sequences derived from SV40 splicing and polyadenylation sites can be used to provide the necessary non-transcribed genetic elements.

[281] The polynucleotides encoding the neoantigenic peptides described herein may also contain a ubiquitinylation signal sequence and/or a targeting sequence, such as an endoplasmic reticulum (ER) signal sequence, to facilitate movement of the resulting peptide into the endoplasmic reticulum.

[282] The polynucleotides described herein can be administered and expressed in human cells (eg, immune cells, including dendritic cells). A human codon frequency table can be used as a guide to codon selection for each amino acid. Such polynucleotides contain spacer amino acid residues between epitopes and/or analogs, such as analogs described above, or may contain natural flanking sequences adjacent to epitopes and/or analogs (and/or CTL, HTL and B-cell epitopes).

[283] In certain embodiments, the neoantigenic peptide described herein can also be administered/expressed via viral or bacterial vectors. Examples of expression vectors include attenuated host viruses such as vaccinia virus or fowl pox virus. As an example of such an approach, vaccinia virus is used as a vector for the expression of nucleotide sequences that encode the neoantigenic peptides described herein. Ospavaccinia vectors and methods useful in immunization protocols are described, for example, in US Pat. No. 4,722,848. Another vector is BCG (Bacille Calmette Guerin). BCG vectors are described by Stover et al., Nature 351:456-460 (1991). From the description provided herein, those skilled in the art will appreciate a wide range of other vectors suitable for therapeutic administration or immunization with the neoantigenic polypeptides described herein, for example, adenovirus and adeno-associated virus vectors, retrovirus vectors, vectors based on Salmonella typhi , detoxified anthrax vectors, Sendai virus vectors, poxvirus vectors, canarypox vectors and chickenpox vectors, and the like. In certain embodiments, the vector is a modified Ankara (VA) vaccinia virus (eg, Bavarian Noridic (MVA-BN)).

[284] Standard regulatory sequences well known to those skilled in the art can be introduced into the vector to promote expression in human target cells. Some elements of the vector are necessary: a promoter with a downstream site for cloning the polynucleotide in the 5'-3' direction, eg a minigene insert; polyadenylation signal for efficient transcription termination; an E. coli origin of replication; and an E. coli selectable marker (eg, ampicillin or kanamycin resistance gene). Various promoters can be used for this purpose, for example the human cytomegalovirus (hCMV) promoter. See, for example, US Pat. Nos. 5,580,859 and 5,589,466 for other suitable promoter sequences. In certain embodiments, the promoter is the CMV-IE promoter.

[285] The polynucleotides described herein may contain one or more synthetic or natural introns in the transcribed region. The introduction of stabilizing RNA sequences and sequences for replication in mammalian cells can also be considered to increase the expression of polynucleotides.

[286] In addition, the polynucleotide described in the present description may contain immunostimulatory sequences (ISS or CpG). These sequences can be introduced into the vector outside the polynucleotide coding sequence to increase immunogenicity.

[287] In certain embodiments, the size of at least one antigenic peptide molecule can be, but not limited to, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31, about 32, about 33 , approximately 34, approximately 35, approximately 36, approximately 37, approximately 38, approximately 39, approximately 40, approximately 41, approximately 42, approximately 43, approximately 44, approximately 45, approximately 46, approximately 47, approximately 48, approximately 49, approximately 50, about 60, about 70, p about 80, about 90, about 100, about 110, about 120 or more molecules of amino acid residues, and any range derived therefrom.

[288] In certain embodiments, the antigenic peptide molecules are equal to or less than 50 amino acids in length. In certain embodiments, the antigenic peptide molecules are about 20 to about 30 amino acids in length. A longer peptide can be designed in several ways. For example, when the HLA binding regions are theoretically calculated or known, the longer peptide may consist of: individual binding peptides with a 0-10 amino acid extension to the N- and C-terminus of each respective gene product. The longer peptide may also consist of a sequential chain of some or all of the binding peptides with extended sequences for each. Alternatively, when sequencing reveals a long (>10 residue) epitope sequence present in diseased tissue (e.g., due to a frameshift, passthrough, or intron insertion resulting in a new peptide sequence), the longer peptide may be composed along its entire length. from new disease-specific amino acids. In both cases, the use of a longer peptide requires endogenous processing by professional antigen-presenting cells, such as dendritic cells, and may result in more efficient antigen presentation and induction of T cell responses. In certain embodiments, the extended sequence is altered to improve the biochemical properties of the polypeptide (properties such as solubility or stability) or to increase the likelihood of efficient proteasome processing of the peptide.

[289] Antigenic peptides and polypeptides can bind the HLA protein. In certain embodiments, the antigenic peptides can bind the HLA protein with greater affinity than the corresponding native/wild type peptide. The IC _{50 of} an antigenic peptide can be less than about 1000 nM, less than about 500 nM, less than about 250 nM, less than about 200 nM, less than about 150 nM, less than about 100 nM, or less than about 50 nM. In certain embodiments, the antigenic peptides do not induce an autoimmune response and/or induce immunological tolerance when administered to an individual.

[290] The invention also relates to compositions containing a set of antigenic peptides. Reference to antigenic peptides includes any suitable delivery method that may result in the introduction of a peptide into a cell of an individual (eg, a nucleic acid). In certain embodiments, the implementation of the composition contains at least 2 or more antigenic peptides. In certain embodiments, the composition contains at least about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 individual peptides. In certain embodiments, the composition contains at least one peptide from Table 1. In certain embodiments, the composition contains at least one peptide from Table 1 and at least one other peptide from Table 1. In certain embodiments, the composition contains at least one a peptide from Table 1; and at least one other peptide from Table 2. In certain embodiments, the composition contains at least 20 different peptides. In certain embodiments, the implementation of the composition contains no more than 20 different peptides. According to the invention, 2 or more different peptides can be obtained from the same polypeptide. For example, if a mutation in an antigen encodes a polypeptide, two or more antigenic peptides can be derived from the polypeptide. In certain embodiments, two or more antigenic peptides derived from a polypeptide may comprise a block matrix that extends over the entire polypeptide (eg, antigenic peptides may comprise a series of overlapping antigenic peptides that span a region or the entire polypeptide). Antigenic peptides can be obtained from any gene encoding a protein. Antigenic peptides can be obtained from mutations in a human cancer or from an infectious agent or an autoimmune disease.

[291] Antigenic peptides, polypeptides, and analogs can be further modified to contain additional chemical molecules not normally part of a protein. Such derivatized molecules may improve solubility, biological half-life, protein absorption, or binding affinity. The molecules can also reduce or eliminate any desired side effects of proteins and the like. A review of such molecules can be found in Remington's Pharmaceutical Sciences, 20th ed., Mack Publishing Co., Easton, PA (2000). For example, antigenic peptides and polypeptides with the desired activity can be modified as needed to provide certain desirable qualities, such as improved pharmacological characteristics, while increasing or at least maintaining essentially the full biological activity of the unmodified peptide, bind the desired MHC molecule and activate the corresponding T -cell. For example, antigenic peptides and polypeptides may be subject to various changes, such as substitutions, conservative or non-conservative, where such changes may provide certain advantages in their use, such as improved binding of MHC. Such conservative substitutions may include replacing an amino acid residue with another amino acid residue that is biologically and/or chemically similar, for example, one hydrophobic residue with another, or one polar residue with another. The effect of single amino acid substitutions can also be investigated using D-amino acids. Such modifications can be made using well known peptide synthesis techniques as described in, for example, Merrifield, Science 232:341-347 (1986), Barany & Merrifield, The Peptides, Gross & Meienhofer, eds. (N.Y., Academic Press), pp. 1-284 (1979) and Stewart & Young, Solid Phase Peptide Synthesis, (Rockford, III., Pierce), 2d Ed. (1984).

[292] The antigenic peptide can also be modified by lengthening or shortening the amino acid sequence of the compound, for example by adding or deleting amino acids. Antigenic peptides, polypeptides or analogs can also be modified by changing the order or composition of certain residues. One skilled in the art will appreciate that certain amino acid residues essential to biological activity, such as amino acid residues at critical contact sites or conservative residues, generally cannot be altered without adversely affecting biological activity. Non-critical amino acids should not be limited to natural amino acids in proteins, such as L-a-amino acids, or their D-isomers, but may also include non-natural amino acids, such as β-γ-δ-amino acids, as well as many derivatives of L-a-amino acids.

[293] An antigenic peptide can be optimized using a series of peptides with single amino acid substitutions to determine the effect of electrostatic charge, hydrophobicity, etc. for MHC binding. For example, a series of positively charged (eg, Lys or Arg) or negatively charged (eg, Glu) amino acid substitutions can be made throughout the length of the peptide, revealing different patterns of sensitivity to different MHC molecules and T-cell receptors. In addition, multiple substitutions can be applied using small, relatively neutral molecules such as Ala, Gly, Pro or similar residues. The substitutions may be homo-oligomers or hetero-oligomers. The amount and types of residues that are replaced or added depend on the distance required between the main points of contact and certain functional characteristics required (eg, hydrophobicity versus hydrophilicity). Also, by such substitutions, an increased binding affinity for the MHC molecule or T-cell receptor can be obtained compared to the affinity of the original peptide. In any case, such substitutions should use amino acid residues or other molecular moieties chosen to eliminate, for example, steric and charge interference that can interfere with binding. Amino acid substitutions are usually single residues. Substitutions, deletions, insertions, or any combination thereof can be combined to produce the final peptide.

[294] The antigenic peptide can be modified to obtain the desired characteristics. For example, the ability of peptides to induce CTL activity can be enhanced by binding to a sequence that contains at least one epitope that is capable of inducing a helper T cell response. In certain embodiments, the immunogenic peptide/T-helper conjugates are linked via a spacer molecule. In certain embodiments, the spacer contains relatively small, neutral molecules, such as amino acids or amino acid mimetics, that are substantially uncharged under physiological conditions. The spacers can be selected, for example, from Ala, Gly or other neutral non-polar amino acid spacers or neutral polar amino acids. It should be understood that an optionally present spacer need not contain the same residues and thus may be a hetero- or homo-oligomer. The antigenic peptide can be coupled to the T-heper peptide directly or via a spacer to the N- or C-terminus of the peptide. The N-terminus of the antigenic peptide or T-helper peptide may be acetylated. Exemplary T-helper peptides include tetanus toxin 830-843, influenza 307-319, malaria sporozoite 382-398 and 378-389.

[295] The present invention is based at least in part on the ability to present one or more disease-specific antigens to the patient's immune system. One of skill in the art will appreciate from this description and knowledge in the art that there are a number of ways in which disease-specific antigens can be obtained. In general, such disease-specific antigens can be obtained in vitro or in vivo . Disease-specific antigens can be produced in vitro as peptides or polypeptides, which can then be formulated into a vaccine or immunogenic composition and administered to an individual. As detailed hereinafter, such in vitro production can be carried out by various methods known to the person skilled in the art, such as, for example, peptide synthesis or expression of a peptide/polypeptide from a DNA or RNA molecule in any of a number of bacterial, eukaryotic or viral recombinant expression systems, followed by purification of the expressed peptide/polypeptide. Alternatively, disease-specific antigens can be produced in vivo by introducing molecules (eg, DNA, RNA, viral expression systems, etc.) that encode disease-specific antigens to an individual, whereupon the encoded disease-specific antigens are expressed. Methods for obtaining in vitro and in vivo antigens are also further described in the present description, since. they relate to pharmaceutical compositions and methods for delivering therapy.

[296] In certain embodiments, the present invention relates to modified antigenic peptides. The modification may include a covalent chemical modification that does not change the primary amino acid sequence of the antigenic peptide itself. Modifications can produce peptides with desired properties, such as increased in vivo half-life, increased stability, reduced clearance, altered immunogenicity or allergenicity, ability to induce specific antibodies, cell targeting, antigen uptake, antigen processing, MHC affinity, MHC stability, or presentation. antigen. Modification of the antigenic peptide that can be performed includes, but is not limited to, carrier protein conjugation, ligand conjugation, antibody conjugation, pegylation, polysialylation, hesylation, recombinant PEG mimetics, Fc fusion, albumin fusion, nanoparticle attachment, encapsulation in nanoparticle shell, cholesterol fusion, iron fusion, acylation, amidation, glycosylation, side chain oxidation, phosphorylation, biotinylation, addition of a surfactant, addition of amino acid mimetics, or addition of unnatural amino acids.

[297] Problems associated with short plasma half-life or susceptibility to degradation by proteases can be addressed through various modifications, including conjugation or linking of the polypeptide sequence to any of a number of non-protein polymers, such as polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes (see, for example, typically through a binding moiety covalently linked to another protein and a non-protein polymer, such as PEG). Such PEG-conjugated biomolecules have been shown to have clinically useful properties, including better physical stability and thermal stability, protection from susceptibility to enzymatic degradation, increased solubility, longer in vivo circulating half-life and reduced clearance, reduced immunogenicity and antigenicity, and reduced toxicity.

[298] PEGs suitable for conjugation to a polypeptide sequence are generally highly soluble in water at room temperature and have the general formula R(0-CH2-CH2)nO-R, where R is hydrogen or a protecting group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000. When R is a protecting group, it generally contains from 1 to 8 carbon atoms. The PEG conjugated to the polypeptide sequence may be linear or branched. The present invention provides branched derivatives of PEG, "star-PEG" and multipath PEG.

[299] The present disclosure also contemplates compositions of conjugates wherein the PEG has a different value of n, and thus a number of different PEGs are contained in specific ratios. For example, some compositions contain a mixture of conjugates where n=l, 2, 3 and 4. In some compositions, the percentage of conjugates when n=1 is 18-25%, the percentage of conjugates when n=2 is 50-66%, the percentage of conjugates when n=3 is 12-16%, and the percentage of conjugates when n=4 is up to 5%. Such compositions can be prepared using reaction conditions and purification methods known in the art. For example, cation exchange chromatography can be used to separate conjugates and then identify fractions that contain a conjugate containing, for example, the desired number of attached PEG molecules, purify from unmodified protein sequences, and from conjugates with other amounts of attached PEG molecules.

[300] PEG may be associated with the polypeptide of the present invention through the terminal reactive group ("spacer"). A spacer is, for example, a terminal reactive group that mediates a bond between the free amino or carboxyl groups of one or more polypeptide sequences and the polyethylene glycol. PEG containing a spacer that can be coupled to a free amino group includes N-hydroxysuccinylimide polyethylene glycol, which can be obtained by adding a succinic acid ester of polyethylene glycol with N-hydroxysuccinylimide. Another activated polyethylene glycol that can be coupled to a free amino group is 2,4-bis(0-methoxypolyethylene glycol)-6-chloro-s-triazine, which can be prepared by reacting polyethylene glycol mono-methyl ether with cyanuric chloride. Activated polyethylene glycol, which is associated with a free carboxyl group, includes polyoxyethylenediamine.

[301] Conjugation of one or more polypeptide sequences of the present invention with a PEG containing a spacer can be carried out in various conventional ways. For example, the conjugation reaction can be carried out in solution at a pH of 5 to 10, at a temperature of 4°C to room temperature, over a period of 30 minutes to 20 hours using a reactant to protein molar ratio of 4:1 to 30:1. You can choose the reaction conditions to direct the reaction to obtain predominantly the desired degree of substitution. In general, low temperature, low pH (e.g. pH=5) and short reaction time tend to reduce the amount of PEG added, while high temperature, neutral to high pH (e.g. pH>7) and longer reaction time tend to increase the number of attached PEGs. Various means known in the art can be used to stop the reaction. In certain embodiments, the implementation of the reaction is stopped by acidifying the reaction mixture and freezing, for example, at -20°C.

[302] The disclosure also contemplates the use of PEG mimetics. Recombinant PEG mimetics have been developed that retain the characteristics of PEG (eg, increased serum half-life) while providing various additional advantageous properties. As an example, simple polypeptide chains (comprising, for example, Ala, Glu, Gly, Pro, Ser, and Thr) capable of forming an extended conformation similar to PEG can be made recombinantly already fused to a peptide or protein-based drug of interest (e.g. , Amunix' XTEN technology; Mountain View, CA). This eliminates the need for an additional conjugation step during the manufacturing process. In addition, established molecular biology techniques are capable of controlling the side chain composition of polypeptide chains, which provides immunogenicity and manufacturing properties.

[303] Glycosylation can alter the physical properties of proteins and may also be important for protein stability, secretion, and subcellular localization. Proper glycosylation may be important for biological activity. In fact, some genes from eukaryotic organisms, when expressed in bacteria (for example, E. coli ), which lack cellular protein glycosylation processes, produce proteins that are isolated with little or no activity due to their lack of glycosylation. The addition of glycosylation sites can be done by changing the amino acid sequence. Modification of the polypeptide can be carried out, for example, by adding or replacing one or more serine or threonine residues (for O-linked glycosylation sites) or asparagine residues (for N-linked glycosylation sites). The structure of N-linked and O-linked oligosaccharide and sugar residues found in each type may differ. One type of sugar that is often found in each type is N-acetylneuraminic acid (hereinafter referred to as sialic acid). Sialic acid is generally the terminal residue of N-linked and O-linked oligosaccharides and, due to its negative charge, can impart acidic properties to the glycoprotein. Embodiments of the present invention include the preparation and use of N-glycosylated variants.

[304] The polypeptide sequences of the present invention can optionally be altered by changes at the DNA level, in particular by mutating the DNA encoding the polypeptide at preselected bases so that codons are obtained that will be translated into the desired amino acids. Another way to increase the number of carbohydrate groups on a polypeptide is to chemically or enzymatically link glycosides to the polypeptide. Removal of carbohydrates can be carried out chemically or enzymatically, or by changing codons encoding amino acid residues that are glycosylated. Chemical methods of deglycosylation are known and enzymatic cleavage of carbohydrate groups on polypeptides can be carried out using various endo- and exoglycosidases.

[305] Additional suitable components and molecules for conjugation include, for example, molecules for targeting the lymphatic system, thyroglobulin; albumins such as human serum albumin (HAS); tetanus toxin; diphtheria toxoid; polyamino acids such as poly(D-lysine:D-glutamic acid); rotavirus VP6 polypeptides; influenza virus hemagglutinin, influenza virus nucleoprotein; saucer hemocyanin (KLH) and core protein and hepatitis B surface antigen, or any combination of the above.

[306] The fusion of albumin with one or more polypeptides of the present invention can be obtained, for example, through genetic manipulation, such that DNA encoding HSA or a fragment thereof, is connected to DNA encoding one or more polypeptide sequences. A suitable host can then be transformed or transfected with the fused nucleotide sequences in the form of, for example, a suitable plasmid, to express the fusion polypeptide. Expression can be carried out in vitro , eg from prokaryotic or eukaryotic cells, or in vivo , eg from a transgenic organism. In certain embodiments of the present invention, expression of the fusion protein is carried out in mammalian cell lines, for example, CHO cell lines. Transformation is widely used herein to refer to a genetic change in a cell caused by the direct uptake, incorporation and expression of exogenous genetic material (exogenous DNA) from its environment and absorbed through the cell membrane(s). Transformation occurs naturally in some types of bacteria, but it can also be done artificially in other cells. In addition, albumin itself can be modified to extend its circulating half-life. Fusion of the modified albumin with one or more polypeptides can be carried out by the genetic manipulation techniques described above, or by chemical conjugation; the resulting fusion molecule has a half-life that is greater than that of fusions with unmodified albumin. (See WO2011/051489). Several albumin binding strategies have been developed as alternatives to direct fusion, including binding of albumin via a conjugated fatty acid chain (acylation). Because serum albumin is a fatty acid transport protein, these natural ligands with albumin binding activity have been used to extend the half-life of small protein therapeutics. For example, insulin detemir (LEVEMIR), an approved anti-diabetic product, contains a myristine chain conjugated to genetically engineered insulin, resulting in a long-acting insulin analogue.

[307] Another type of modification is the conjugation (e.g., linking) of one or more additional components or molecules at the N- and/or C-terminus of a polypeptide sequence, such as another protein (e.g., a protein containing an amino acid sequence that is heterologous to protein under study) or a carrier molecule. Thus, an exemplary exemplary polypeptide sequence may be provided as a conjugate to another component or molecule.

[308] Modification of the conjugate can result in a polypeptide sequence that retains activity with an additional or complementary function or activity of a second molecule. For example, a polypeptide sequence can be conjugated to a molecule, such as to facilitate solubility, storage, in vivo half-life or storage or stability, reduce immunogenicity, delayed or controlled release in vivo , etc. Other functions or activities include a conjugate that reduces toxicity relative to the unconjugated polypeptide sequence, a conjugate that targets a cell or organ type more effectively than the unconjugated polypeptide sequence, or a drug to further combat the causes or effects associated with a disorder or disease as defined herein (e.g., diabetes) .

[309] The polypeptide can also be conjugated to large, slowly metabolized macromolecules such as proteins; polysaccharides such as sepharose, agarose, cellulose, cellulose granules; polymeric amino acids such as polyglutamic acid, polylysine; amino acid copolymers; inactivated viral particles; inactivated bacterial toxins such as toxoid from diphtheria, tetanus, cholera, leukotoxin molecules; inactivated bacteria and dendritic cells.

[310] Additional candidate components and molecules for conjugation include molecules suitable for isolation or purification. Specific non-limiting examples include binding molecules such as biotin (biotin-avidin binding pair), antibody, receptor, ligand, lectin, or molecules that contain a solid support, including, for example, plastic or polystyrene beads, plates or beads, magnetic beads, test - strips and membranes. Purification methods such as cation exchange chromatography can be used to separate conjugates by means of a charge difference that effectively separates the conjugates into their different molecular weights. The content of fractions obtained by cation exchange chromatography can be identified by molecular weight using conventional methods, such as mass spectroscopy, SDS-PAGE or other known methods for separating molecular structures by molecular weight.

[311] In certain embodiments, the amino or carboxyl terminus of a polypeptide sequence of the present invention can be fused to an immunoglobulin Fc region (eg, human Fc) to form a fusion conjugate (or fusion molecule). Fc fusion conjugates have been shown to increase the overall half-life of biopharmaceuticals and thus the biopharmaceutical may require less frequent administration.

[312] Fc binds to the neonatal Fc receptor (FcRn) in endothelial cells that line blood vessels, and once bound, the Fc fusion molecule is protected from degradation and re-released into the bloodstream, keeping the molecule in the bloodstream for a longer period of time. This Fc binding is believed to be the mechanism by which endogenous IgG maintains its long plasma half-life. More recent Fc-fusion technology couples a single copy of a biopharmaceutical to the Fc region of an antibody to optimize the pharmacokinetic and pharmacodynamic properties of the biopharmaceutical compared to traditional Fc-fusion conjugates.

[313] The present description contemplates the use of other modifications, currently known or developed in the future, polypeptides to improve one or more properties. One such method of extending the half-life in the cow's duct, increasing stability, decreasing clearance, or altering the immunogenicity or allergenicity of a polypeptide of the present invention involves modifying polypeptide sequences by hesylation, which uses hydroxyethyl starch derivatives bound to other molecules to modify the characteristics of the molecule. Various aspects of hesylation are described, for example, in US patent applications No. 2007/0134197 and 2006/0258607.

[314] Proteins or peptides can be produced by any method known to those skilled in the art, including expression of proteins, polypeptides, or peptides by standard molecular biological methods, isolation of proteins or peptides from natural sources, in vitro translation, or chemical synthesis of proteins or peptides.

[315] Peptides can be easily synthesized chemically using reagents that do not contain contaminants of bacterial or animal origin (Merrifield RB: Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc.85:2149- 54, 1963). In certain embodiments, antigenic peptides are produced by (1) parallel solid phase synthesis on multichannel devices using uniform synthesis and digestion conditions; (2) purification on a RP-HPLC column with a distillation column; and rewashing, but not swapping, between peptides; followed by (3) analysis with a limited set of the most informative analyses. The scope of Good Manufacturing Practice (GMP) can be defined for a set of peptides for an individual patient, such that a switching procedure is required to change between peptide syntheses for different patients only.

[316] Alternatively, a nucleic acid (eg, a polynucleotide) encoding an antigenic peptide of the invention can be used to produce an antigenic peptide in vitro . The polynucleotide may be, for example, DNA, cDNA, PNA, CNA, RNA, single- and/or double-stranded, native or stabilized forms of polynucleotides such as, for example, phosphorus backbone polynucleotides, or combinations thereof, and may or may not contain introns, provided that it codes for a peptide. In certain embodiments, in vitro translation is used to produce the peptide. It is also possible to obtain an expression vector capable of expressing the polypeptide. Expression vectors for different cell types are well known in the art and can be selected without undue experimentation. Typically, DNA is introduced into an expression vector, such as a plasmid, in the correct orientation and in the correct reading frame for expression. If desired, the DNA can be linked to appropriate transcriptional and translational regulatory control nucleotide sequences recognized by the desired host (eg, bacteria), although such regulatory sequences are usually available in an expression vector. The vector is then introduced into host bacteria for cloning by standard methods (see, for example, Sambrook et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY).

[317] Also provided are expression vectors containing isolated polynucleotides, as well as host cells containing expression vectors. The antigenic peptides can be provided in the form of RNA or cDNA molecules encoding the desired antigenic peptides. One or more antigenic peptides of the invention may be encoded by a single expression vector.

[318] In certain embodiments, the polynucleotides may comprise a coding sequence for a disease-specific antigenic peptide fused in-frame to a polynucleotide that aids in, for example, expression and/or secretion of the polypeptide from a host cell (e.g., a leader sequence, which functions as a secretory sequence to direct the transport of the polypeptide out of the cell). A polypeptide containing a leader sequence is a preprotein and may contain a leader sequence that is cleaved by the host cell to form the mature form of the polypeptide.

[319] In certain embodiments, the polynucleotides may comprise a coding sequence for a disease-specific antigenic peptide fused in the same reading frame to a marker sequence, which allows, for example, to purify the encoded polypeptide, which can then be incorporated into a personalized disease vaccine or immunogenic composition. . For example, the marker sequence may be a hexahistidine tag delivered by the pQE-9 vector to allow purification of the mature polypeptide fused to the marker in the case of a bacterial host, or the marker sequence may be a haemagglutinin (HA) tag derived from influenza hemagglutinin protein when used. a mammalian host (eg, COS-7 cells). Additional tags include, but are not limited to, calmodulin tags, FLAG tags, Myc tags, S tags, SBP tags, Softag 1, Softag 3, V5 tag, Xpress tag, Isopepeptag tags, SpyTag, Biotin Carboxyl Carrier Protein (BCCP) GST tags , fluorescent protein tags (eg, green fluorescent protein tags), maltose-binding protein tags, Nus tags, Strep tags, thioredoxin tag, TC tag, Ty tag, and the like.

[320] In certain embodiments, the polynucleotides may comprise a coding sequence for one or more disease-specific antigen-specific peptides fused in the same reading frame to form a single concatemerized antigenic peptide construct capable of producing multiple antigenic peptides.

[321] In certain embodiments, isolated nucleic acid molecules can be provided comprising a nucleotide sequence that is at least 60% identical, at least 65% identical, at least 70% identical, at least 75% identical, at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, or at least 96%, 97%, 98% or 99% identical a polynucleotide encoding a disease-specific antigenic peptide of the present invention.

[322] The isolated disease-specific antigenic peptides described herein can be produced in vitro (eg, in a laboratory) by any suitable method known in the art. Such methods range from direct methods of protein synthesis to the construction of a DNA sequence encoding isolated polypeptide sequences and the expression of these sequences in a suitable transformed host. In certain embodiments, a DNA sequence is constructed using recombinant technology by isolating or synthesizing a DNA sequence encoding a wild-type protein of interest. Optionally, the sequence can be subjected to mutagenesis by site-directed mutagenesis to provide its functional analogues. See, for example, Zoeller et al., Proc. Nat'l. Acad. sci. USA 81:5662-5066 (1984) and US Pat. No. 4,588,585.

[323] In certain embodiments, a DNA sequence encoding a polypeptide of interest is constructed by chemical synthesis using an oligonucleotide synthesizer. Such oligonucleotides can be designed based on the amino acid sequence of the desired polypeptide and selection of those codons that are appropriate in the host cell in which the recombinant polypeptide of interest is being produced. Standard methods can be used to synthesize an isolated polynucleotide sequence encoding an isolated polypeptide of interest. For example, the complete amino acid sequence can be used to construct a reverse translated gene. In addition, a DNA oligomer containing a nucleotide sequence encoding a particular isolated polypeptide can be synthesized. For example, several small oligonucleotides encoding portions of the desired polypeptide can be synthesized and then ligated. Individual oligonucleotides typically contain 5' or 3' overhangs for complementary assembly.

[324] Once assembled (e.g., by synthesis, site-directed mutagenesis, or other method), the polynucleotide sequences encoding the particular isolated polypeptide of interest are inserted into an expression vector and optionally operably linked to an expression control sequence suitable for expression of the protein in the desired host. Correct assembly can be confirmed by nucleotide sequencing, restriction mapping, and expression of the biologically active polypeptide in a suitable host. As is well known in the art, to obtain high levels of expression of a transfected gene in a host, the gene can be operatively linked to transcriptional and translational control sequences that are functional in the host of choice for expression.

[325] Recombinant expression vectors can be used to amplify and express DNA encoding disease-specific antigenic peptides. Recombinant expression vectors are replicable DNA constructs that contain synthetic or cDNA-derived DNA fragments encoding a disease-specific antigenic peptide, or a bioequivalent analogue, operably linked to suitable transcriptional or translational regulatory elements derived from genes of mammals, microorganisms, viruses, or insects. A transcription unit typically contains a collection of (1) a genetic element or elements that have a regulatory role in gene expression, such as transcriptional promoters or enhancers, (2) a structural or coding sequence that is transcribed into mRNA and translated into protein, and (3 ) the corresponding sequences of initiation and termination of transcription and translation, as detailed in the present description. Such regulatory elements may include an operator sequence to control transcription. Additionally, you can enter the ability to replicate in the host, usually provided by the origin of replication, and a selection gene to facilitate the recognition of transformants. Regions of DNA are operably linked when they are operably linked to each other. For example, DNA for a signal peptide (secretory leader) is operably linked to DNA for a polypeptide if it is expressed as a precursor that is involved in the secretion of the polypeptide; a promoter is operably linked to a coding sequence if it controls the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is located to allow translation. As a general rule, operably linked means adjacent, and in the case of secretory leaders, means adjacent and in reading frame. Structural elements for use in yeast expression systems include a leader sequence that allows extracellular secretion of the translated protein by the host cell. Alternatively, when the recombinant protein is expressed without a leader or transport sequence, it may contain an N-terminal methionine residue. This residue may optionally then be cleaved from the expressed recombinant protein to obtain the final product.

[326] Suitable expression vectors for eukaryotic hosts, especially mammals or humans, include, for example, vectors containing expression control sequences from SV40, bovine papillomavirus, adenovirus, and cytomegalovirus. Suitable expression vectors for bacterial hosts include known bacterial plasmids such as plasmids from Escherichia coli including pCR 1, pBR322, pMB9 and their derivatives, wider host range plasmids such as M13 and filamentous single stranded DNA phages.

[327] Suitable host cells for polypeptide expression include prokaryotes, yeasts, insects, or higher eukaryotic cells under the control of appropriate promoters. Prokaryotes include gram-negative or gram-positive organisms such as E. coli or bacilli. Higher eukaryotic cells include established mammalian cell lines. Cell-free translation systems can also be used. Appropriate cloning and expression vectors for use with bacterial, fungal, yeast and mammalian host cells are well known in the art (see Pouwels et al., Cloning Vectors: A Laboratory Manual, Elsevier, NY, 1985).

[328] Various mammalian or insect cell culture systems are also advantageously used to express the recombinant protein. It is possible to carry out the expression of recombinant proteins in mammalian cells, since such proteins, as a rule, are correctly folded, suitably modified and fully functional. Examples of suitable mammalian host cell lines include the COS-7 monkey kidney cell line described by Gluzman (Cell 23: 175, 1981) and other cell lines capable of expressing the appropriate vector, including, for example, L cells, C127, 3T3 cell lines. , Chinese hamster ovary (CHO), 293, HeLa and BHK. Mammalian expression vectors may contain non-transcribed elements such as an origin of replication, an appropriate promoter and enhancer associated with the gene to be expressed, and other 5' or 3' flanking non-transcribed sequences and 5' or 3' non-translated sequences such as those required. ribosome binding sites, polyadenylation site, donor and acceptor splicing sites, and transcription termination sequences. For a review of baculovirus systems for producing heterologous proteins in insect cells, see Luckow and Summers, Bio/Technology 6:47 (1988).

[329] Proteins produced by the transformed host can be purified by any suitable method. Such standard methods include chromatography (eg, ion exchange, affinity and size distribution column chromatography, etc.), centrifugation, differential solubility, or any other standard protein purification method. Affinity tags such as hexahistidine, a maltose binding domain, an influenza envelope sequence, and glutathione S-transferase can be attached to the protein to allow for easy purification by passing through an appropriate affinity column. Isolated proteins can also be physically characterized using methods such as proteolysis, nuclear magnetic resonance, and X-ray crystallography. For example, supernatants from systems secreting recombinant protein into culture media can first be concentrated using a commercially available protein concentration filter, such as an Amicon or Millipore Pellicon ultrafiltration device. After the concentration step, the concentrate can be applied to a suitable purification matrix. Alternatively, an anion exchange resin, such as a matrix or substrate, having diethylaminoethyl (DEAE) overhanging groups can be used. The matrices may be acrylamide, agarose, dextran, cellulose, or other types commonly used for protein purification. Alternatively, a cation exchange step may be used. Suitable cation exchangers include various insoluble matrices containing sulfopropyl or carboxymethyl groups. Finally, one or more reverse phase high performance liquid chromatography (RP-HPLC) steps, including a hydrophobic RP-HPLC medium, such as silica gel having methyl or other aliphatic overhangs, can be used to further purify the cancer stem cell protein-Fc composition. Some or all of the above purification steps in various combinations can also be used to obtain a homogeneous recombinant protein.

[330] The recombinant protein produced in bacterial culture can be isolated, for example, by initial separation from cell pellets followed by one or more steps of concentration, salting out, aqueous ion exchange, or size exclusion chromatography. High performance liquid chromatography (HPLC) can be used for final purification steps. The microbial cells used to express the recombinant protein can be disrupted by any suitable method, including freeze and thaw cycles, sonication, mechanical disruption, or the use of cell lysis agents.

[331] The present invention also provides for the use of nucleic acid molecules as carriers for delivering antigenic peptides/polypeptides to an individual in need in vivo , in the form of, for example, DNA/RNA vaccines (see, for example, WO2012/159643 and WO2012/159754 incorporated in its entirety, thus by reference).

[332] In certain embodiments, antigens can be administered to a patient in need using a plasmid. Such plasmids are plasmids that typically consist of a strong viral promoter to promote in vivo transcription and translation of the gene (or complementary DNA) of interest (Mor, et al., 1995). Journal of Immunology 155 (4): 2039-2046). In some cases, intron A can be introduced to improve mRNA stability and thus increase protein expression (Leitner et al., 1997). Journal of Immunology 159 (12): 6112-6119). The plasmids also include a strong polyadenylation/transcriptional termination signal, such as the polyadenylation signal of the bovine growth hormone or rabbit beta-globulin sequence (Alarcon et al., (1999). Adv. Parasitol. Advances in Parasitology 42: 343-410; Robinson et al. , (2000) Adv. Virus Res. Advances in Virus Research 55: 1-74, Böhmet al., (1996) Journal of Immunological Methods 193(1): 29-40.). In some cases, multicistronic vectors are constructed to express more than one immunogen, or to express an immunogen and an immunostimulatory protein (Lewis et al., 1999). Advances in Virus Research (Academic Press) 54: 129-88).

[333] Plasmids can be introduced into animal tissues in several different ways. The two most popular approaches are injection of DNA in saline using a standard hypodermic needle and gene gun delivery. A schematic outline for the construction of a DNA vaccine plasmid and its subsequent delivery by these two methods to a host is illustrated in Scientific American (Weiner et al., (1999) Scientific American 281 (1): 34-41). Injection in saline is typically administered intramuscularly (IM) into skeletal muscle or intradermally (ID) where the DNA is delivered to the extracellular spaces. This can be facilitated by electroporation by temporarily damaging muscle fibers with myotoxins such as bupivacaine; or using hypertonic saline or sucrose solutions (Alarcon et al., (1999) Adv Advs in Parasitology 42: 343-410). Many factors can influence immune responses to this mode of delivery, including needle type, needle alignment, injection rate, injection volume, muscle type, and the age, sex, and physiology of the injected animal (Alarcon et al., (1999). Adv Parasitol Advances in Parasitology 42: 343-410).

[334] Gene gun delivery, another widely used delivery method, ballistically accelerates plasmid DNA (pDNA) that is adsorbed on gold or tungsten microparticles into target cells using pressurized helium as an accelerator (Alarcon et al., (1999). Adv. Parasitol, Advances in Parasitology 42: 343-410, Lewis et al., (1999) Advances in Virus Research (Academic Press) 54: 129-88).

[335] Alternative methods of delivery may include inhalation of naked DNA aerosols on mucosal surfaces, such as the nasal and lung mucosa (Lewis et al., 1999). Advances in Virus Research (Academic Press) 54: 129-88) and topical application of pDNA to the ocular and vaginal mucosa (Lewis et al., (1999) Advances in Virus Research (Academic Press) 54: 129-88). Delivery to the mucosal surface was also performed using cationic liposome-DNA preparations, biodegradable microspheres, attenuated Shigella or Listeria vectors for oral administration to the intestinal mucosa, and recombinant adenovirus vectors. DNA or RNA can also be delivered to cells after mild mechanical disruption of the cell membrane, temporarily permeabilizing the cell. This gentle mechanical disruption of the membrane can be done by gently forcing the cells through a small hole (Ex Vivo Cytosolic Delivery of Functional Macromolecules to Immune Cells, Sharei et al, PLOS ONE | DOI:10.1371/journal.pone.0118803 April 13, 2015).

[336] In certain embodiments, the disease-specific vaccine or immunogenic composition may contain separate DNA plasmids encoding, for example, one or more antigenic peptides/polypeptides. As described herein, the exact choice of expression vectors may depend on the peptide/polypeptide to be expressed and is known to those skilled in the art. The expected persistence of the DNA constructs (eg, in episomal, non-replicating, non-integrated form in muscle cells) is expected to provide longer-term protection.

[337] One or more antigenic peptides of the invention may be encoded and expressed in vivo using a virus-based system (eg, an adenovirus, adeno-associated virus (AAV), poxvirus, or lentivirus system). In certain embodiments, a vaccine or immunogenic composition against a disease may comprise a virus-based vector for use in a human patient in need, such as, for example, an adenovirus. Plasmids that can be used to deliver viruses, adenoviruses and lentiviruses have been previously described (see, for example, US Pat.

[338] The peptides and polypeptides of the invention may also be expressed via a vector, such as a nucleic acid molecule as discussed herein, such as an RNA or DNA plasmid, a viral vector such as a poxvirus, such as orthopoxvirus, avian pox virus, or adenovirus. , AAV or lentivirus. This approach involves the use of a vector to express the nucleotide sequences that encode the peptide of the invention. When introduced into a host with an acute or chronic infection, or into an uninfected host, the vector expresses the immunogenic peptide and thereby elicits a host CTL response.

[339] Among the vectors that can be used in the practice of the invention, integration into the genome of the host cell can be carried out by retroviral gene transfer methods, which often results in long-term expression of the introduced transgene. In certain embodiments, the retrovirus is a lentivirus. In addition, high transduction efficiency has been observed in many different cell types and target tissues. Retrovirus tropism can be altered by incorporating foreign envelope proteins, which expands the possible target population of target cells. A retrovirus can also be engineered to conditionally express the introduced transgene so that only certain cell types are infected with the lentivirus. You can use cell-specific promoters to direct expression in specific cell types. Lentiviral vectors are retroviral vectors (and thus both lentiviral and retroviral vectors can be used in the practice of the invention). In addition, lentiviral vectors are capable of transducing or infecting non-dividing cells and typically produce high titers of viruses. Thus, the choice of retroviral gene transfer system may depend on the target tissue. Retroviral vectors consist of cis-acting long terminal repeats with a packaging capacity of up to 6-10 kb. for an alien sequence. Minimal cis-acting LTRs are sufficient to replicate and package the vectors, which are then used to integrate the desired nucleic acid into the target cell to ensure consistent expression. Commonly used retroviral vectors that can be used in the practice of the invention include those based on mouse leukemia virus (MuLV), gibbon leukemia virus (GaLV), simian immunodeficiency virus (SIV), human immunodeficiency virus (HIV), and combinations thereof ( see for example Buchscher et al., (1992) J. Virol.66: 2731-2739; Johann et al., (1992) J. Virol.66: 1635-1640; Sommnerfelt et al., (1990)) Virol. 176: 58-59, Wilson et al., (1998) J. Virol. 63: 2374-2378; Miller et al., (1991) J. Virol. 65: 2220-2224; PCT/US94/05700).

[340] Also useful in the practice of the invention is a minimal non-primate lentiviral vector, such as the equine infectious anemia virus (EIAV) lentiviral vector. The vectors may contain a cytomegalovirus (CMV) promoter that directs expression of the target gene. Thus, the invention relates to vector(s) useful in the practice of the invention: viral vectors, including retroviral vectors and lentiviral vectors.

[341] In this embodiment, delivery is via a lentivirus. Doses of, for example, 10 μl of recombinant lentivirus with a titer of 1×10 ⁹ transducing units (TEu)/ml can be adapted or extrapolated to use a retroviral or lentiviral vector in the present invention. For transduction in tissues such as the brain, very small volumes must be used, so the virus preparation is concentrated by ultracentrifugation. You can use other methods of concentration, such as ultrafiltration or binding and elution from the matrix. In other embodiments, the amount of lentivirus administered may be 1x10 ^{5 or about 1x10 5 plaque formation units (PFU), 5x10 5 or about} 5x10 ⁵ PFU, 1x10 ⁶ or about 1x10 ⁶ PFU, 5×10 ⁶ or approximately 5×10 ⁶ PFU, 1×10 ⁷ or approximately 1×10 ⁷ PFU, 5×10 ⁷ or approximately 5×10 ⁷ PFU, 1×10 ⁸ or approximately 1×10 ⁸ PFU, 5× 10 ⁸ or approximately 5×10 ⁸ PFU, 1×10 ⁹ or approximately 1×10 ⁹ PFU, 5×10 ⁹ or approximately 5×10 ⁹ PFU, 1×10 ¹⁰ or approximately 1×10 ¹⁰ PFU or 5×10 ¹⁰ or approximately 5×10 ¹⁰ PFU as a total single dose for an average 75 kg human or adjusted for the weight and size and species of the individual. A person skilled in the art can determine the appropriate dosage. Suitable doses for the virus can be determined empirically.

[342] Also useful in the practice of the invention is an adenovirus vector. One advantage is the ability of recombinant adenoviruses to efficiently transfer and express recombinant genes in various mammalian cells and tissues in vitro and in vivo , resulting in high expression of transferred nucleic acids. In addition, the ability to productively infect quiescent cells extends the utility of recombinant adenoviral vectors. In addition, high expression levels ensure that nucleic acid products will be expressed at sufficient levels to elicit an immune response (see, for example, US Pat. No. 0,729,848, incorporated herein by reference). With regard to adenovirus vectors useful in the practice of the invention, mention should be made of US Pat. No. 6,558,080. The adenovirus vector used may be selected from the group consisting of Ad5, Ad35, Ad11, C6 and C7 vectors. The genome sequence of adenovirus 5 ("Ad5") has been published. (Chroboczek, J., Bieber, F., and Jacrot, B. (1992) The Sequence of the Genome of Adenovirus Type 5 and Its Comparison with the Genome of Adenovirus Type 2, Virology 186, 280-285; the full contents of which, thus incorporated by reference). Ad35 vectors are described in US Pat. Nos. 6,974,695, 6,913,922 and 6,869,794. US Pat. No. 6,277,558. Adenovirus vectors that are E1 deficient or E1 deleted, E3 deficient or E3 deleted, and/or E4 deficient or E4 deleted can also be used. Certain adenoviruses with mutations in the E1 region have an increased safety record, because. E1-defective adenovirus mutants are replication-defective in non-permissive cells, or at most highly attenuated. Adenoviruses with mutations in the E3 region may have increased immunogenicity as a result of disruption of the mechanism by which adenovirus suppresses MHC class I molecules. Adenoviruses with E4 mutations may have reduced adenoviral vector immunogenicity due to suppression of late gene expression. Such vectors may be particularly useful when re-vaccination using the same vector is desired. In accordance with the present invention, adenoviral vectors that have been deleted or mutated at E1, E3, E4, E1 and E3 and E1 and E4 can be used. In addition, "gutted" adenovirus vectors in which all viral genes have been removed can also be used in accordance with the present invention. Such vectors require a helper virus for their replication and require a specific human cell line 293 expressing E1a and Cre, a condition that does not exist in the natural environment. Such "gutted" vectors are not immunogenic, and thus the vectors can be inoculated several times for re-vaccination. Gutted adenoviral vectors can be used to introduce heterologous inserts/genes, such as the transgenes of the present invention, and can even be used to co-deliver a large number of heterologous inserts/genes. In certain embodiments, delivery is via adenovirus, which may be in a single boosted dose. In certain embodiments, the adenovirus is delivered via multiple doses. With respect to in vivo delivery, AAV is more efficient than other viral vectors due to low toxicity and low insertional mutagenesis, since it does not integrate into the host genome. AAV has a packaging limit of 4.5 or 4.75 tons. Contractions greater than 4.5 or 4.75 t. lead to significantly reduced virus production. There are many promoters that can be used to direct the expression of a nucleic acid molecule. The AAV ITR can serve as a promoter and is preferred to eliminate the need for an additional promoter element. The following promoters can be used for ubiquitous expression: CMV, CAG, CBh, PGK, SV40, ferritin heavy or light chains, etc. The following promoters can be used for expression in the brain: synapsin I for all neurons, CaMKII alpha for excitatory neurons, GAD67 or GAD65 or VGAT for GABAergic neurons, etc. Promoters used to direct RNA synthesis may include: Pol III promoters such as U6 or H1. The use of a Pol II promoter and an intron cassette can be used to express guide RNA (gRNA). With regard to AAV vectors useful in the practice of the invention, US Pat. Nos. 5,658,785; 7,115,391; 7,172,893; With regard to AAV, AAV may be AAV1, AAV2, AAV5, or any combination thereof. You can choose AAV depending on the target cells; for example, AAV serotypes 1, 2, 5 or hybrid capsid AAV1, AAV2, AAV5 or any combination of these can be selected to target brain or nerve cells; and AAV4 can be selected to target cardiac tissue. AAV8 is suitable for liver delivery. In certain embodiments, delivery is via AAV. The dose may be adjusted to balance the therapeutic benefit against any side effects.

[343] In certain embodiments, effective activation of a cellular immune response to a vaccine or immunogenic composition against a disease can be obtained by expression of relevant antigens in the vaccine or immunogenic composition in a non-pathogenic microorganism. Known examples of such microorganisms are Mycobacterium bovis BCG, Salmonella and Pseudomona (see US patent No. 6,991,797, which is fully incorporated into the present description by reference).

[344] In certain embodiments, a poxvirus is used in a vaccine or immunogenic composition against a disease. These include orthopoxvirus, fowlpox virus, vaccine poxvirus, MVA, NYVAC, canarypox virus, ALVAC, chickenpox virus, TROVAC, etc. (See, for example, Verardiet al., Hum Vaccin Immunother, 2012 Jul, 8 (7): 961-70, and Moss, Vaccine 2013, 31 (39): 4220-4222). Expression vectors for poxvirus were described in 1982 and quickly became widely used for vaccine development, as well as for research in many areas. The advantages of vectors include simple construction, the ability to accommodate large amounts of foreign DNA, and high levels of expression. Information regarding poxviruses that may be used in the practice of the invention, such as the Chordopoxvirinae subfamily of poxviruses (vertebrate poxviruses), e.g. orthopoxviruses and avipoxviruses, e.g. , strain Copenhagen, NYVAC, NYVAC.1, NYVAC.2, MVA, MVA-BN), canarypox virus (e.g. strain Wheatley C93, ALVAC), chickenpox virus (e.g. strain FP9, strain Webster, TROVAC), virus pigeon pox virus, quail pox virus and raccoon pox virus, among others, their synthetic or non-natural recombinants, their use and methods of preparation using such recombinants, can be found in the scientific and patent literature.

[345] In certain embodiments, the vaccinia virus is used in a vaccine or immunogenic composition against a disease to express an antigen. (Rolph et al., Recombinant viruses as vaccines and immunological tools. Curr Opin Immunol 9:517-524, 1997). The recombinant vaccinia virus is able to replicate in the cytoplasm of an infected host cell, and thus the polypeptide of interest can induce an immune response. In addition, poxviruses have been widely used as vaccine vectors or immunogenic composition vectors due to their ability to target encoded antigens for processing along the class I major histocompatibility complex pathway through direct infection of immune cells, in particular antigen presenting cells, and also due to their ability to be adjuvant.

[346] In certain embodiments, ALVAC is used as a vector in a vaccine or immunogenic composition against a disease. ALVAC is a canarypox virus that can be modified to express foreign transgenes and has been widely used as a method of vaccination against both prokaryotic and eukaryotic antigens (Horig H, Lee DS, Conkright W, et al. Phase I clinical trial of a recombinant canarypoxvirus (ALVAC) vaccine expressing human carcinoembryonic antigen and the B7.1 co-stimulatory molecule Cancer Immunol Immunother 2000;49:504-14;von Mehren M, Arlen P, Tsang KY, et al. avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas Clin Cancer Res 2000;6:2219-28; Musey L, Ding Y, Elizaga M, et al. HIV-1 vaccination administered intramuscularly can induce both systemic and mucosal T cell immunity in HIV-1-uninfected individuals J Immunol 2003;171:1094-101; Paoletti E. Applications of pox virus vectors to vaccination: an update. Proc Natl Acad Sci U S A 1996;93:11349-53; US patent No. 7255862). In a phase I clinical trial, ALVAC virus expressing the CEA tumor antigen had an excellent safety record and resulted in increased CEA-specific T cell responses in selected patients; however, no objective clinical responses were observed (Marshall JL, Hawkins MJ, Tsang KY, et al. Phase I study in cancer patients of a replication-defective avipox recombinant vaccine that expresses human carcinoembryonic antigen. J Clin Oncol 1999;17:332 -7).

[347] In certain embodiments, the modified vaccinia virus Ankara (MVA) can be used as a viral vector for an antigenic vaccine or immunogenic composition. MVA is a member of the orthopoxvirus family and was formed by approximately 570 serial passages of chick embryo fibroblasts of the Ankara strain of ospavaccinia virus (CVA) (for a review, see Mayr, A., et al., Infection 3, 6-14, 1975). As a result of these passages, the resulting MVA virus contains 31 kb less genomic information compared to CVA and is largely restricted to the host cell (Meyer H. et al., J. Gen. Virol., 72, 1031-1038, 1991 ). MVA is characterized by its strong attenuation, ie reduced virulence or infectivity, yet excellent immunogenicity. When tested in various animal models, MVA has been shown to be avirulent, even in immunocompromised individuals. In addition, MVA-BN®-HER2 is a candidate immunotherapy for the treatment of HER-2 positive breast cancer and is currently in clinical trials. (Mandl et al., Cancer Immunol Immunother. Jan 2012; 61 (1): 19-29). Methods for making and using recombinant MVA are described (eg, see US Pat. Nos. 8,309,098 and 5,185,146, fully incorporated).

[348] In certain embodiments, the recombinant viral particles of the vaccine or immunogenic composition are administered to patients in need thereof.

Neoantigen binding peptides

[349] In certain embodiments, the present invention provides a binding protein (e.g., an antibody or antigen-binding fragment thereof) or a T cell receptor (TCR) or a chimeric antigen receptor (CAR) capable of binding with high affinity to a neoantigenic peptide complex. : human leukocyte antigen (HLA). In certain embodiments, the present invention provides a CAR that is capable of binding with high affinity to a neoantigenic peptide derived from the extracellular domain of a protein. In certain embodiments, a neoantigen-specific binding protein, or TCR, or CAR, as described herein, includes polypeptide variant species that have one or more amino acid substitutions, insertions, or deletions in the native amino acid sequence, provided that the binding protein retains or essentially retains its specific binding function. Conservative amino acid substitutions are well known and may occur naturally or may be introduced upon receipt of a recombinant synthetic protein or TCR. Amino acid substitutions, deletions, and additions can be introduced into a protein using mutagenesis techniques known in the art (see, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual, 3rd ed., Cold Spring Harbor Laboratory Press, NY, 2001). Oligonucleotide-targeted site-specific (or segment-specific) mutagenesis methods can be used to provide an altered polynucleotide that has certain codons altered in accordance with the desired substitution, deletion, or insertion. Alternatively, random mutagenesis or saturation mutagenesis methods such as alanine scanning mutagenesis, error prone polymerase chain reaction mutagenesis, and site-directed mutagenesis can be used to generate variants of an immunogenic polypeptide (see, for example, Sambrook et al., supra).

[350] Various criteria known to those skilled in the art indicate whether an amino acid that is substituted at a particular position in a peptide or polypeptide is conservative (or similar). For example, a similar amino acid or conservative amino acid substitution is an amino acid in which an amino acid residue is replaced with an amino acid residue with a similar side chain. Similar amino acids can be divided into the following categories: amino acids with basic side chains (eg, lysine, arginine, histidine); amino acids with acidic side chains (eg aspartic acid, glutamic acid); amino acids with uncharged polar side chains (eg, glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, histidine); amino acids with non-polar side chains (eg, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan); amino acids with beta-branched side chains (eg threonine, valine, isoleucine); and amino acids with aromatic side chains (eg tyrosine, phenylalanine, tryptophan). Proline, which is considered more difficult to classify, shares properties with amino acids that have aliphatic side chains (eg, leucine, valine, isoleucine, and alanine). In some cases, the substitution of glutamine for glutamic acid or asparagine for aspartic acid can be considered a similar substitution, in that glutamine and asparagine are amide derivatives of glutamic acid and aspartic acid, respectively. As understood in the art, "similarity" between two polypeptides is determined by comparing the amino acid sequence and conservative amino acid substitutions of its polypeptide with that of a second polypeptide (e.g., using GENEWORKS, Align, the BLAST algorithm, or other algorithms described herein and practiced in the art). ).

[351] In certain embodiments, a neoantigen-specific binding protein, TCR or CAR, is capable of (a) specifically binding to a neoantigen:HLA complex on the cell surface, independently or in the absence of CD8. In certain embodiments, the neoantigen-specific binding protein is a T cell receptor (TCR), a chimeric antigen receptor, or a TCR antigen-binding fragment, any of which may be chimeric, humanized, or human. In additional embodiments, the implementation of the antigen-binding fragment of the TCR contains a single-stranded TCR (scTCR).

[352] In certain embodiments, a composition is provided comprising a neoantigen specific binding protein or high affinity recombinant TCR according to any of the above embodiments and a pharmaceutically acceptable carrier, diluent, or excipient.

[353] Methods used to isolate and purify recombinantly produced soluble TCR, by way of example, may include obtaining supernatants from suitable host cell/vector systems that secrete recombinant soluble TCR into the culture medium, and then concentrating the medium using a commercially available filter . After concentration, the concentrate can be applied to one suitable purification matrix or to a number of suitable matrices such as an affinity matrix or an ion exchange resin. For further purification of the recombinant polypeptide, one or more reverse phase HPLC steps can be used. These purification methods can also be used to isolate an immunogen from its natural environment. Methods for large-scale production of one or more isolated/recombinant soluble TCRs described herein include fed-batch culture of cells that is monitored and controlled to maintain appropriate culture conditions. Purification of soluble TCR can be carried out in accordance with the methods, which can be carried out by the methods described in the present description and known in this field.

III. Immunogenic and vaccine compositions

[354] In certain embodiments, the present invention provides an immunogenic composition, eg, a vaccine composition, capable of eliciting a neoantigen-specific response (eg, a humoral or cell-mediated immune response). In certain embodiments, the immunogenic composition comprises neoantigen-based therapeutic agents (e.g., peptides, polynucleotides, TCRs, CARs, TCR or CAR-containing cells, polypeptide-containing dendritic cell, polynucleotide-containing dendritic cell, antibody, etc.), described in the present description corresponding to the tumor-specific neoantigen identified in the present description.

[355] In certain embodiments, the immunogenic peptides are identified from one or more individuals with a disease or condition. In certain embodiments, the immunogenic peptides are specific for one or more individuals with a disease or condition. In certain embodiments, the immunogenic peptides can bind to an HLA that matches the HLA haplotype of one or more individuals with the disease or condition.

[356] A person skilled in the art will be able to select neoantigenic therapeutics by testing, for example, in vitro production of T cells, as well as their effectiveness and overall presence, proliferation, affinity and expansion of certain T cells for certain peptides and functionality of T cells, for example, by assaying IFN-γ production or tumor killing by T cells. The most effective peptides can then be combined as an immunogenic composition.

[357] In certain embodiments, the various neoantigenic peptides and/or polypeptides are selected such that one immunogenic composition contains neoantigenic peptides and/or polypeptides capable of binding to different MHC molecules, such as another class I MHC molecule. In certain embodiments, the immunogenic composition comprises neoantigenic peptides and/or polypeptides capable of binding to the most commonly occurring class I MHC molecules. Thus, the immunogenic compositions described herein comprise various peptides capable of binding to at least 2, at least 3, or at least 4 MHC class I or class II molecules.

[358] In certain embodiments, the immunogenic composition described herein is capable of inducing a specific cytotoxic T cell response, a specific helper T cell response, or a B cell response.

[359] In certain embodiments, the implementation of the immunogenic composition described in the present description may additionally contain an adjuvant and/or carrier. Examples of suitable adjuvants and carriers are given below. The polypeptides and/or polynucleotides in the composition may be linked to a carrier such as, for example, a protein or an antigen-presenting cell, such as, for example, a dendritic cell (DC) capable of presenting the peptide to a T cell or B cell. In additional embodiments, DC binding peptides are used as vehicles for targeted delivery of neoantigenic peptides and polynucleotides encoding neoantigenic peptides to dendritic cells (Sioud et al., FASEB J 27: 3272-3283 (2013)).

[360] In embodiments, neoantigenic polypeptides or polynucleotides can be provided as antigen-presenting cells (eg, dendritic cells) containing such polypeptides or polynucleotides. In other embodiments, such antigen presenting cells are used to stimulate T cells for use in patients.

[361] In certain embodiments, the antigen-presenting cells are dendritic cells. In related embodiments, the dendritic cells are autologous, which are primed with a neoantigenic peptide or nucleic acid. The neoantigenic peptide may be any suitable peptide that results in an appropriate T cell response. T cell therapy using autologous dendritic cells loaded with peptides from a tumor associated antigen is described in Murphy et al. (1996) The Prostate 29, 371-380 and Tjua et al. (1997) The Prostate 32, 272-278. In certain embodiments, the T cell is a CTL. In certain embodiments, the T cell is an HTL.

[362] Thus, in one embodiment of the present invention, an immunogenic composition comprising at least one antigen presenting cell (e.g., dendritic cell) that is primed or loaded with one or more neoantigenic polypeptides or polynucleotides described herein. In embodiments, such APCs are autologous (eg, autologous dendritic cells). Alternatively, peripheral blood mononuclear cells (PBMCs) isolated from a patient can be loaded with ex vivo neoantigenic peptides or polynucleotides. In appropriate embodiments, such APCs or PBMCs are back-injected into the patient.

[363] The polynucleotide can be any suitable polynucleotide that is capable of transducing a dendritic cell, thereby leading to presentation of the neoantigenic peptide and induction of immunity. In certain embodiments, the implementation of the polynucleotide may be naked DNA, which is taken up by cells through passive loading. In another embodiment, the polynucleotide is part of a delivery vehicle, such as a liposome, viral particle, plasmid, or expression vector. In another embodiment, the polynucleotide is delivered via a vectorless delivery system, such as high efficiency electroporation and high speed cell strain). In embodiments, such antigen-presenting cells (APCs) (eg, dendritic cells) or peripheral blood mononuclear cells (PBMCs) are used to stimulate a T cell (eg, an autologous T cell). In related embodiments, the T cell is a CTL. In other appropriate embodiments, the T cell is HTL. Such T cells are then administered to the patient. In certain embodiments, the CTL is administered to a patient. In certain embodiments, the HTL is administered to a patient. In certain embodiments, the CTL and HTL are administered to the patient. The introduction of any therapeutic agent can be carried out simultaneously or sequentially and in any order.

[364] Pharmaceutical compositions (eg, immunogenic compositions) described herein for therapeutic treatment are intended for parenteral, topical, nasal, oral, or topical administration. In certain embodiments, the pharmaceutical compositions described herein are administered parenterally, such as intravenously, subcutaneously, intradermally, or intramuscularly. In embodiments, the composition may be administered intramuscularly. The compositions can be administered at the site of surgical removal to induce a local immune response to the tumor. In certain embodiments described herein, compositions for parenteral administration are provided that contain a solution of neoantigenic peptides and the immunogenic compositions are dissolved or suspended in a suitable vehicle, eg, an aqueous vehicle. Various aqueous vehicles can be used, such as water, buffered water, 0.9% saline, 0.3% glycine, hyaluronic acid, and the like. These compositions may be sterilized by conventional well known sterilization techniques or may be sterile filtered. The resulting aqueous solutions can be packaged for use as is or lyophilized, where the lyophilized preparation is combined with a sterile solution prior to administration. The compositions may contain pharmaceutically acceptable excipients as necessary to approximate physiological conditions, such as pH adjusters and buffering agents, tonicity adjusters, wetting agents, and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc.

[365] The concentration of the neoantigenic peptides and polynucleotides described herein in pharmaceutical formulations can vary widely, i. e. from less than about 0.1%, typically, or at least 2% to 20-50% or more, by weight, and will be selected depending on liquid volumes, viscosity, etc., in accordance with the particular chosen method of administration.

[366] The neoantigenic peptides and polynucleotides described herein can also be administered via liposomes that target the peptides to specific cellular tissue, such as lymphoid tissue. Liposomes are also useful for extending the half-life of peptides. Liposomes include emulsions, foams, micelles, insoluble monolayers, liquid crystals, phospholipid dispersions, laminar layers, and the like. In these preparations, the peptide to be delivered is administered as part of a liposome, alone or in combination with a molecule that binds, for example, to a receptor predominant among lymphoid cells, such as monoclonal antibodies that bind to the DEC205 antigen, or to other therapeutic or immunogenic compositions. Thus, liposomes loaded with the desired peptide or polynucleotide as described herein can be targeted to the site of lymphoid cells, where the liposomes then deliver selected therapeutic/immunogenic polypeptide/polynucleotide compositions. Liposomes can be formed from standard vesicle-forming lipids, which typically include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The choice of lipids is generally made by considering, for example, the size of the liposomes, acid lability and the stability of the liposomes in the blood stream. Various methods are available for preparing liposomes, as described, for example, in Szoka et al., Ann. Rev. Biophys. Bioeng. 9; 467 (1980), US Pat. Nos. 4,235,871; 4,501,728; 4,501,728;

[367] To target immune cells, neoantigenic polypeptides or polynucleotides need to be liposome-captured for cell surface determinants of desired immune system cells. The liposomal suspension containing the peptide can be administered intravenously, topically, topically, etc. at a dose that varies depending on, inter alia, the route of administration, the polypeptide or polynucleotide delivered, and the stage of the disease being treated.

[368] In certain embodiments, the neoantigenic polypeptides and polynucleotides are directed to dendritic cells. In certain embodiments, the neoantigenic polypeptides and polynucleotides are directed to dendritic cells using the markers DEC205, XCR1, CD197, CD80, CD86, CD123, CD209, CD273, CD283, CD289, CD184, CD85h, CD85j, CD85k, CD85k, CD85d, CD85g, CD85a, receptor TSLP, Clec9a or CD1a.

[369] For solid compositions, conventional or nanoparticle-based non-toxic solid carriers can be used, which include, for example, mannitol, lactose, starch, magnesium stearate, sodium saccharin, talc, cellulose, glucose, sucrose, pharmaceutical grade magnesium carbonate, etc. P. For oral administration, a pharmaceutically acceptable non-toxic composition is prepared by administering any of the commonly used excipients, such as the previously listed carriers, and typically 10-95% of the active ingredient, i.e. one or more neoantigenic polypeptides or polynucleotides described herein at a concentration of 25%-75%.

[370] For aerosol administration, the neoantigenic polypeptides or polynucleotides can be supplied in a highly dispersed form along with a surfactant and a propellant. Representatives of such agents are esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. You can use mixed esters, such as mixed or natural glycerides. The surfactant may be 0.1-20% by weight of the composition, or 0.25-5%. The balance of the composition may be the propellant. A carrier may also be administered if desired, such as with lecithin for intranasal delivery.

[371] Additional delivery methods for the neoantigenic polynucleotides described herein are also known in the art. For example, the nucleic acid can be delivered directly as "naked DNA". Such an approach is described, for example, in Wolff et al., Science 247: 1465-1468 (1990), as well as US Pat. Nos. 5,580,859 and 5,589,466. No. 5204253. You can enter the particles, consisting only of DNA. Alternatively, DNA can be attached to particles such as gold particles.

[372] For therapeutic or immunization purposes, mRNA encoding neoantigenic peptides or peptide-binding agents can also be administered to a patient. In certain embodiments, the mRNA is a self-amplifying RNA. In a further embodiment, the self-amplifying RNA is part of a synthetic composition of the lipid nanoparticle (Geall et al., Proc Natl Acad Sci U S A. 109: 14604-14609 (2012)).

[373] Nucleic acids can also be delivered complexed with cationic compounds, such as cationic lipids. Lipid-mediated gene delivery methods are described, for example, in WO 96/18372, WO 93/24640; Mannino & Gould-Fogerite, BioTechniques 6(7): 682-691 (1988); US patent No. 5279833; WO 91/06309 and Felgner et al., Proc. Natl. Acad. sci. USA 84: 7413-7414 (1987).

[374] The neoantigenic peptides and polypeptides described herein can also be expressed by attenuated viruses such as vaccinia virus or fowl pox virus. This approach includes the use of vaccinia virus as a vector for the expression of nucleotide sequences that encode the peptide described in the present description. When administered to an acutely or chronically infected host or an uninfected host, the recombinant vaccinia virus expresses an immunogenic peptide and thus induces a CTL response in the host. Ospavaccine vectors and methods useful in immunization protocols are described, for example, in US Pat. No. 4,722,848. Another vector is BCG (Bacille Calmette Guerin). BCG vectors are described in Stover et al. (Nature 351: 456-460 (1991)). Those skilled in the art will recognize from the description provided herein that a wide range of other vectors suitable for therapeutic administration or immunization of the peptides described herein will be apparent.

[375] Adjuvants are any substance whose addition to an immunogenic composition enhances or otherwise modifies the immune response to a therapeutic agent. Carriers are framework structures, for example a polypeptide or polysaccharide, to which a neoantigenic polypeptide or polynucleotide can be attached. Optionally, the adjuvants are covalently or non-covalently conjugated to the polypeptides or polynucleotides described herein.

[376] The ability of an adjuvant to increase the immune response to an antigen is typically manifested in a significant increase in the immune-mediated response or a decrease in the symptoms of the disease. For example, an increase in humoral immunity may be manifested in a significant increase in the titer of antibodies induced against the antigen, and an increase in T cell activity may be manifested in increased cell proliferation or cellular cytotoxicity, or secretion of cytokines. The adjuvant can also alter the immune response, for example by changing primarily the humoral or T-helper 2 response to a predominantly cellular or T-helper 1 response.

[377] Suitable adjuvants are known in the art (see WO 2015/095811) and include, but are not limited to, poly(I:C), poly-ICLC, STING agonist, 1018 ISS, aluminum salts, Amplivax, AS15, BCG, CP-870,893 CpG7909 CyaA dSLIM GM-CSF IC30 IC31 , Montanide ISA-51, OK-432, OM-174, OM-197-MP-EC, ONTAK, PepTel®. vector system, PLG microparticles, resiquimod, SRL172, virosomes and other virus-like particles, YF-17D, VEGF-Trap, R848, beta-glucan, Pam3Cys, Pam3CSK4, Aquila's stimulol QS21 (Aquila Biotech, Worcester, Mass., USA), which derived from saponin, mycobacterial extracts and synthetic bacterial cell wall mimetics and other branded adjuvants such as Ribi's Detox. Quil or Superfos. Adjuvants also include incomplete Freund's adjuvant or GM-CSF. Some immunological adjuvants (e.g., MF59) specific for dendritic cells, as well as their preparation, have previously been disclosed (Dupuis M, et al., Cell Immunol. 1998; 186(1):18-27; Allison A C; Dev Biol Stand. 1998; 92:3-11) (Mosca et al. Frontiers in Bioscience, 2007; 12:4050-4060) (Gamvrellis et al. Immunol & Cell Biol. 2004; 82: 506-516). In addition, cytokines can be used. Some cytokines have been directly associated with influencing migration of dendritic cells into lymphoid tissue (eg, TNF-alpha), increased maturation of dendritic cells into effective antigen-presenting cells for T-lymphocytes (eg, GM-CSF, PGE1, PGE2, IL-1, IL -1b, IL-4, IL-6 and CD40L) (U.S. Patent No. 5,849,589 incorporated herein by reference in its entirety) and acting as immunoadjuvants (e.g., IL-12) (Gabrilovich D I, et al., J Immunother Emphasis Tumor Immunol 1996(6):414-418).

[378] CpG immunostimulatory oligonucleotides have also been reported to enhance the effect of adjuvants under vaccine conditions. In practice, CpG oligonucleotides act by activating the innate (non-adaptive) immune system through Toll-like receptors (TLRs), mainly TLR9. CpG-activated TLR9 activation enhances antigen-specific humoral and cellular responses to a wide range of antigens, including peptide or protein antigens, live or killed viruses, dendritic cell immunogenic pharmaceutical compositions, autologous cellular immunogenic compositions, and polysaccharide conjugates in both prophylactic and therapeutic immunogenic pharmaceutical formulations. compositions. Of note, it enhances dendritic cell maturation and differentiation, leading to increased TH1 cell activation and production of strong cytotoxic T lymphocytes (CTLs), even in the absence of CD4 T cell assistance. TH1 displacement induced by TLR9 stimulation persists even in the presence of adjuvants such as alum or Incomplete Freund's Adjuvant (IFA), which tend to promote TH2 displacement. CpG oligonucleotides are even more adjuvant when formulated or co-administered with other adjuvants or in formulations such as microparticles, nanoparticles, lipid emulsions or similar formulations, which are especially needed to induce a strong response when the antigen is relatively weak. They also accelerate the immune response and allow for reduced antigen doses with comparable antibody responses to a full dose of an immunogenic pharmaceutical formulation without CpG in some experiments (Arthur M. Krieg, Nature Reviews, Drug Discovery, 5, June 2006, 471-484). US Pat. No. 6,406,705 B1 describes the combined use of CpG oligonucleotides, nucleic acid free adjuvants, and antigen to induce an antigen-specific immune response. A commercially available CpG TLR9 antagonist is dSLIM (Double Stem-Loop Immunomodulator) from Mologen (Berlin, GERMANY), which is a component of the pharmaceutical composition described herein. Other TLR binding molecules can also be used, such as TLR 7, TLR 8 and/or TLR 9 binding RNA.

[379] Other examples of suitable adjuvants include, but are not limited to, chemically modified CpG (e.g., CpR, Idera), poly(I:C) (e.g., poly:CI2U), non-CpG bacterial DNA or RNA, ssRNA40 for TLR8 as well as immunoactive small molecule compounds and antibodies such as cyclophosphamide, sunitinib, bevacizumab, celebrex, NCX-4016, sildenafil, tadalafil, vardenafil, sorafinib, XL-999, CP-547632, pazopanib, ZD2171, AZD2171, ipilimumab, tremelimumab75 and SC581 , which may act therapeutically and/or as an adjuvant. The person skilled in the art can easily determine without undue experimentation the amount and concentration of adjuvants and additives suitable in the context of the present invention. Additional adjuvants include colony stimulating factors such as granulocyte macrophage colony stimulator (GM-CSF, Sargramostim).

[380] In certain embodiments, the implementation of the immunogenic composition of the present invention may contain more than one other adjuvant. In addition, the invention relates to a therapeutic composition containing any adjuvant substance, including any of the above substances or combinations thereof. Such a neoantigenic therapeutic (eg, humoral or cell-mediated immune response) is also envisioned. In certain embodiments, the immunogenic composition comprises neoantigenic therapeutic agents (e.g., peptides, polynucleotides, TCRs, CARs, cells containing TCRs or CARs, a polypeptide containing dendritic cells, a dendritic cell containing a polynucleotide, an antibody, etc.), and an adjuvant may be administered separately in any suitable sequence.

[381] The carrier may be present regardless of the adjuvant. The function of the carrier may, for example, be to increase the molecular weight of a particular mutant in order to increase its activity or immunogenicity, to provide stability, to increase biological activity, or to increase the serum half-life. In addition, the carrier may facilitate the presentation of the peptides to T cells. The carrier may be any suitable carrier known to those skilled in the art, such as a protein or an antigen-presenting cell. The carrier protein may be, but is not limited to, saucer hemocyanin, serum proteins such as transferrin, bovine serum albumin, human serum albumin, thyroglobulin or ovalbumin, immunoglobulins, or hormones such as insulin or palmitic acid. In certain embodiments, the carrier comprises a human fibrosis type III domain (Koide et al. Methods Enzymol, 2012; 503: 135-56). For immunization of humans, the carrier must be a physiologically acceptable carrier, acceptable to humans, and safe. However, tetanus toxin and/or diphtheria toxoid are suitable carriers In certain embodiments of the invention. Alternatively, the carrier may be dextrans, eg Sepharose.

[382] In certain embodiments, polypeptides can be synthesized as multiply linked peptides as an alternative to linking the polypeptide to a carrier to increase immunogenicity. Such molecules are also known as multiple antigenic peptides (MAPS).

[383] Neoantigens that induce an immune response can be used as a composition in combination with an acceptable carrier or excipient. Such compositions are suitable for in vitro or in vivo assay, or for administration to an individual in vivo or ex vivo for the treatment of an individual with a disease.

[384] Thus, in addition to the active ingredient, pharmaceutical compositions may contain a pharmaceutically acceptable excipient, carrier, buffer, stabilizer, or other substances well known to those skilled in the art. Such substances must be non-toxic and must not interfere with the effectiveness of the active ingredient. The exact nature of the carrier or other material will depend on the route of administration.

[385] Pharmaceutical formulations containing a protein of interest, such as the neoantigen described herein, can be prepared for storage by mixing the desired purity neoantigen with optional physiologically acceptable carriers, excipients, or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Oslo, A Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients or stabilizers are those which are non-toxic to recipients at the dosages and concentrations employed and include buffers such as phosphate, citrate and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, alkyl parabens such as methyl paraben or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol and m-cresol); low molecular weight (less than 10 residues) polypeptides; proteins such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates, including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium; metal complexes (eg Zn-protein complexes), and/or non-ionic surfactants such as TWEEN®, PLURONICS® or polyethylene glycol (PEG).

[386] Acceptable carriers are physiologically acceptable to the patient to whom they are administered, and retain the therapeutic properties of the compounds with/in which they are administered. Acceptable carriers and formulations thereof are generally described in, for example, Remington Pharmaceutical Sciences (18th Edition, A. Gennaro, Mack Publishing Co., Easton, PA, 1990). One exemplary carrier is saline. A pharmaceutically acceptable carrier is a pharmaceutically acceptable substance, composition, or carrier, such as a liquid or solid excipient, diluent, excipient, solvent, or encapsulating material, intended to carry or transport test compounds from the site of administration of one organ or body part to another organ or body part. or in an in vitro assay system. Acceptable carriers are compatible with the other ingredients of the formulation and do not harm the individual to whom they are administered. Also, an acceptable carrier should not alter the specific activity of the neoantigens.

[387] In one aspect, provided herein are pharmaceutically acceptable or physiologically acceptable compositions containing solvents (aqueous or non-aqueous), solutions, emulsions, dispersion media, coatings, isotonic and absorption-promoting or absorption-delaying agents compatible with pharmaceutical administration. Thus, pharmaceutical compositions or pharmaceutical formulations refer to a composition suitable for pharmaceutical use in an individual. Pharmaceutical compositions and compositions contain an amount of a neoantigen (or a polynucleotide encoding a neoantigen) and a pharmaceutically or physiologically acceptable carrier. Compositions can be formulated to be compatible with a particular route of administration (ie, systemic or local). Thus, the compositions include carriers, diluents or excipients suitable for administration by a variety of routes.

[388] In certain embodiments, the composition further comprises a suitable additive to improve the stability of the neoantigen in the composition and/or to control the rate of release of the composition. Acceptable additives do not alter the specific activity of neoantigens. Illustrative acceptable additives include, but are not limited to, sugar such as mannitol, sorbitol, glucose, xylitol, trehalose, sorbose, sucrose, galactose, dextran, dextrose, fructose, lactose, and mixtures thereof. Acceptable additives can be combined with acceptable carriers and/or excipients such as dextrose. Alternatively, exemplary suitable additives include, but are not limited to, a surfactant such as polysorbate 20 or polysorbate 80 to increase peptide stability and reduce gelation of the solution. The surfactant can be added to the composition in an amount of 0.01% to 5% solution. The addition of such acceptable additives increases the stability and shelf life of the composition.

[389] The pharmaceutical composition can be administered, for example, by injection. Compositions for injection include aqueous solutions (if water-soluble) or dispersions and sterile powders for the immediate preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include saline, bacteriostatic water, or phosphate buffered saline (PBS). The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (eg glycerol, propylene glycol and liquid polyethylene glycol, etc.) and suitable mixtures thereof. The liquid state can be maintained, for example, by using a coating such as lecithin, by maintaining the required particle size in the case of a dispersion, and by using surfactants. Antibacterial and antifungal agents include, for example, parabens, chlorobutanol, phenol, ascorbic acid, and thimerosal. Isotonicity agents such as sugars, polyalcohols such as mannitol, sorbitol and sodium chloride can be included in the compositions. The resulting solutions can be packaged for use as is or lyophilized, then the lyophilized preparation can be combined with a sterile solution prior to administration. For intravenous administration, injection or injection at the site of the lesion, the active ingredient is in the form of a parenterally acceptable aqueous solution that does not contain pyrogens and has suitable pH, isotonicity and stability. Those skilled in the art are able to prepare suitable solutions using, for example, isotonic vehicles such as sodium chloride injection, Ringer's solution injection, lactated Ringer's solution injection. If necessary, preservatives, stabilizers, buffers, antioxidants and/or other additives can be added. Sterile injectable solutions can be prepared by administering the active ingredient in the required amount in a suitable solvent with one or a combination of the ingredients listed above, followed by filtered sterilization. Typically, dispersions are prepared by incorporating the active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients listed above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying, which allows the preparation of a powder of the active ingredient plus any additional desired ingredient from its previously sterile-filtered solution.

[390] the Compositions can be traditionally administered intravenously, such as, for example, by injection of a standard dose. For injection, the active ingredient may be in the form of a parenterally acceptable aqueous solution which is substantially free of pyrogens and has suitable pH, isotonicity and stability. Suitable solutions can be prepared using, for example, isotonic vehicles such as sodium chloride injection, Ringer's solution injection, lactated Ringer's solution injection. If necessary, preservatives, stabilizers, buffers, antioxidants and/or other additives can be added. In addition, the compositions can be administered by aerosolization.

[391] In certain embodiments, the composition is lyophilized, for example, to increase shelf life. When the compositions are provided for use in medicaments or in any of the methods provided herein, it is contemplated that the composition may be substantially free of pyrogens such that the composition will not cause an inflammatory response or an unsafe allergic reaction when administered to a human patient. Testing compositions for pyrogens and obtaining substantially pyrogen-free compositions is well understood by those skilled in the art and can be prepared using commercially available kits.

[392] Acceptable carriers may contain a compound that stabilizes, increases or retards absorption, or increases or retards clearance. Such compounds include, for example, carbohydrates such as glucose, sucrose or dextrans; low molecular weight proteins; compositions that reduce the clearance or hydrolysis of peptides; or excipients or other stabilizers and/or buffers. Agents that delay absorption include, for example, aluminum monostearate and gelatin. Detergents can also be used to stabilize or increase or decrease the absorption of a pharmaceutical composition, including liposomal carriers. To protect against cleavage, the compound may be complexed with the composition to render it resistant to acidic and enzymatic hydrolysis, or the compound may be complexed in a suitable stable carrier such as a liposome.

[393] Compositions can be administered in a manner compatible with the dosage formulation and in a therapeutically effective amount. The amount to be administered depends on the individual being treated, the ability of the individual's immune system to utilize the active ingredient, and the degree of binding capacity desired. The exact amounts of active ingredient to be administered depend on the judgment of the practitioner and are specific to each individual. Suitable regimens for initial administration and secondary injections of antigen are also variable, but are typical for initial administration followed by repeated doses at intervals of one or more hours by subsequent injection or other administration. Alternatively, continuous intravenous infusions are assumed to be sufficient to maintain blood concentrations.

[394] Immunogenic pharmaceutical compositions based on peptides can be formulated using any of the well-known techniques, carriers and excipients, as is appropriate and understood in this field. The polypeptides may be a mixture of several polypeptides containing the same sequence, or a mixture of several copies of different polypeptides. Peptides can be modified, for example, by lipidation or attachment to a carrier protein. Lipidation may be the covalent attachment of a lipid group to a polypeptide. Lipidized peptides or lipidated polypeptides can stabilize the structures and can increase the effectiveness of the treatment.

[395] Lipidation can be divided into several different types, such as N-myristoylation, palmitoylation, addition of a GPI anchor, prenylation, and several additional types of modifications. N-myristoylation is the covalent addition of myristate, a saturated C ₁₄ acid, to a glycine residue. Palmitoylation is a thioether bond of long chain fatty acids (C ₁₆ ) to cysteine residues. The addition of a GPI anchor is the linkage of glycosyl-phosphatidylinositol (GPI) via an amide bond. Prenylation is a thioether bond of an isoprenoid lipid (eg, farnesyl (C-15), geranylgeranyl (C-20)) to cysteine residues. Additional types of modifications may include the addition of S-diacylglycerol to the sulfur atom of cysteines, the conjugation of O-octanoyl via serine or threonine residues, the conjugation of S-archaeol to cysteine residues, and the attachment of cholesterol.

[396] Fatty acids to obtain lipidized peptides may include C ₂ -C ₃₀ saturated, monounsaturated or polyunsaturated fatty acyl groups. Exemplary fatty acids may contain palmitoyl, myristoyl, stearoyl, and decanoyl groups. In some instances, a lipid fragment that has an adjuvant property is attached to a polypeptide of interest to elicit or enhance immunogenicity in the absence of an external adjuvant. A lipidated peptide or lipopeptide may be referred to as a self-adjuvant lipopeptide. Any of the fatty acids described above and elsewhere in the present description may cause or enhance the immunogenicity of the polypeptide of interest. A fatty acid that may cause or enhance immunogenicity may contain palmitoyl, myristoyl, stearoyl, lauroyl, octanoyl and decanoyl groups.

[397] Polypeptides, as naked peptides or lipidated peptides can be introduced into a liposome. In some cases, lipidated peptides can be introduced into a liposome. For example, the lipid portion of a lipidated peptide may spontaneously integrate into the lipid bilayer of a liposome. Thus, the lipopeptide can be presented on the "surface" of the liposome.

[398] Exemplary liposomes suitable for inclusion in formulations include, but are not limited to, multilamellar vesicles (MLV), oligolamellar vesicles (OLV), unilamellar vesicles (UV), small unilamellar vesicles (SUV), medium sized unilamellar vesicles (MUV ), large unilamellar vesicles (LUV), giant unilamellar vesicles (GUV), multivesicular vesicles (MVV), single or oligolamellar vesicles obtained by the reverse phase evaporation method (REV), multilamellar vesicles obtained by the reverse phase evaporation method (MLV-REV), stable plurilamellar vesicles (SPLV), frozen and thawed MLVs (FATMLV), harvestable vesicles (VET), French press-produced vesicles (FPV), fusion-produced vesicles (FUV), dehydration-rehydration vesicles (DRV), and vesicles ( BSV).

[399] Depending on the preparation method, liposomes can be single-layered or multilayered and can vary in size with diameters ranging from about 0.02 microns to greater than about 10 microns. Liposomes can adsorb many types of cells and then release the enclosed agent (eg, the peptide described herein). In some cases, liposomes fuse with the target cell, causing the contents of the liposome to then enter the target cell. The liposome can be endocytosed by cells that are phagocytes. Endocytosis may be accompanied by intralysosomal degradation of liposomal lipids and release of encapsulated agents.

[400] The liposomes provided herein may also contain carrier lipids Carrier lipids. In certain embodiments, the carrier lipids are phospholipids. Carrier lipids capable of forming liposomes include, but are not limited to, dipalmitoylphosphatidylcholine (DPPC), phosphatidylcholine (PC; lecithin), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylserine (PS). Other suitable phospholipids further include distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidiglycerol (DPPG), distearoylphosphatidylglycerol (DSPG), dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidic acid (DPPA); dimyristoylphosphatidic acid (DMPA), distearoylphosphatidic acid (DSPA), dipalmitoylphosphatidylserine (DPPS), dimyristoylphosphatidylserine (DMPS), distearoylphosphatidylserine (DSPS), dipalmitoylphosphatidylethanolamine (DPPE), dimyristoylphosphatidylethanolamine (DMPE), distearoylphosphatidylethanolamine (DSPE) and the like. or their combinations. In certain embodiments, the liposomes further comprise a sterol (eg, cholesterol) that modulates the formation of liposomes. The carrier lipids can be any known non-phosphate polar lipids.

[401] The pharmaceutical composition can be encapsulated in liposomes using well known technology. Biodegradable microspheres can also be used as carriers for the pharmaceutical compositions of the present invention.

[402] The pharmaceutical composition can be administered in liposomes or microspheres (or microparticles). Methods for preparing liposomes and microspheres for administration to a patient are well known to those skilled in the art. Essentially, the substance is dissolved in an aqueous solution, appropriate phospholipids and lipids are added, if necessary, along with surfactants, and the substance is dialyzed or sonicated, if necessary.

[403] Microspheres formed from polymers or proteins are well known to those skilled in the art and can be adapted to pass through the gastrointestinal tract directly into the bloodstream. Alternatively, the compound can be enclosed and the microspheres or microsphere composite implanted for sustained release over a period of time ranging from days to months.

[404] The polypeptide can also be attached to a carrier protein for delivery. The carrier protein may be an immunogenic element of the carrier and may be attached by any recombinant technique. Exemplary carrier proteins include mariculture saucer hemocyanin (mcKLH), pegylated mcKLH, Blue Carrier* proteins, bovine serum albumin (BSA), cationized BSA, ovalbumin, and bacterial proteins such as tetanus toxin (TT).

[405] the Polypeptide can also be obtained in the form of multiple antigenic peptides (MAP). Peptides can be attached at the N-terminus or C-terminus to small non-immunogenic nuclei. Peptides built on this core can provide highly localized peptide density. The nucleus may be a dendritic residue of the nucleus or a matrix consisting of bifunctional units. Suitable core molecules for constructing a MAP may include ammonia, ethylenediamine, aspartic acid, glutamic acid, and lysine. For example, a lysine core molecule can be attached via peptide bonds through each of its amino groups to two additional lysines.

[406] The polypeptide can be chemically synthesized or recombinantly expressed in a cellular system or in a cell-free system. The peptide can be synthesized, for example, by liquid phase synthesis, solid phase synthesis or peptide synthesis using microwave radiation. The polypeptide can be modified, for example, by acylation, alkylation, amidation, argylation, polyglutamylation, polyglycylation, butyrylation, gamma-carboxylation, glycosylation, malonylation, hydroxylation, iodination, addition of nucleotides (e.g., ADP-ribosylation), oxidation, phosphorylation, adenylation, propionylation , S-glutathionylation, S-nitrosylation, succinylation, sulfation, glycation, palmitoylation, myristoylation, isoprenylation or prenylation (e.g., farnesylation or geranylgeranylation), glipation, lipoylation, flavin fragment attachment (e.g., FMN or FAD), heme C attachment, phosphopantetheynylation , retinylidene formation of the Schiff base, formation of dichtamide, addition of ethanolamine phosphoglycerol, formation of hypusine, biotinylation, pegylation, ISG-ylation, sumoylation, ubiquitination, non-dyding, nubulation, citrullination , deamidation, elimination, carbamylation, or combinations thereof.

[407] After obtaining the polypeptide, the polypeptide can be subjected to one or more stages of purification steps to remove impurities. The purification step may be a chromatographic step using separation methods such as affinity based, size based, ion exchange based or the like. In certain cases, the polypeptide is not more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.9% or 100% pure or free of impurities. In certain instances, the polypeptide is at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.9% or 100% pure or free of impurities.

[408] The polypeptide may contain naturally occurring amino acids, non-natural amino acids, or a combination thereof. An amino acid residue may refer to a molecule containing both an amino group and a carboxyl group. Suitable amino acids include, without limitation, both the D- and L-isomers of natural amino acids, as well as non-natural amino acids obtained by organic synthesis or other metabolic pathways. As used herein, the term "amino acid" includes, without limitation, α-amino acids, natural amino acids, non-natural amino acids, and amino acid analogs.

[409] The term "α-amino acid" can refer to a molecule containing both an amino group and a carboxyl group associated with a carbon, which is designated as α-carbon.

[410] The term "β-amino acid" may refer to a molecule containing both an amino group and a carboxyl group in the β-configuration.

[411] "Natural amino acid" may refer to any of the twenty amino acids commonly found in naturally synthesized peptides known by the single letter abbreviations A, R, N, C, D, Q, E, G, H, I, L , K, M, F, P, S, T, W, Y, and V. A table summarizing the properties of natural amino acids can be found, for example, in US Patent Application Publication No. 20130123169, which is incorporated herein by reference. .

[412] The peptide provided herein may contain one or more hydrophobic, polar, or charged amino acids. "Hydrophobic amino acids" includes small hydrophobic amino acids and large hydrophobic amino acids. A "small hydrophobic amino acid" may be glycine, alanine, proline, and analogs thereof. "Large hydrophobic amino acids" may be valine, leucine, isoleucine, phenylalanine, methionine, tryptophan, and analogs thereof. "Polar amino acids" may be serine, threonine, asparagine, glutamine, cysteine, tyrosine, and analogs thereof. "Charged amino acids" may be lysine, arginine, histidine, aspartate, glutamate, and analogs thereof.

[413] The peptide provided herein may contain one or more amino acid analogs. An "amino acid analog" may be a molecule that is structurally similar to an amino acid and that can be replaced by an amino acid in the formation of a peptidomimetic macrocycle. Amino acid analogs include, without limitation, β-amino acids and amino acids where the amino group or carboxy group is replaced with a similar reactive group (eg, replacement of a primary amine with a secondary or tertiary amine, or replacement of a carboxy group with an ether).

[414] The peptide provided herein may contain one or more non-natural amino acids. A "non-natural amino acid" may be an amino acid that is not one of the 20 amino acids commonly found in naturally synthesized peptides and is known by the single letter abbreviations A, R, N, C, D, Q, E, G, H, I, L, K, M, F, P, S, T, W, Y, and V. Non-natural amino acids or amino acid analogs include the structures disclosed, for example, in US Patent Application Publication No. 20130123169, which is incorporated herein by reference.

[415] Amino acid analogs may include analogs of β-amino acids. Examples of β-amino acid analogs and analogs of alanine, valine, glycine, leucine, arginine, lysine, aspartic acids, glutamic acids, cysteine, methionine, phenylalanine, tyrosine, proline, serine, threonine and tryptophan may include the structures disclosed, for example, in the publication US patent application No. 20130123169, which is incorporated into the present description by reference.

[416] Amino acid analogs may be racemic. In some cases, the D-isomer of the amino acid analog is used. In some cases, the L-isomer of the amino acid analog is used. In some cases, the amino acid analog contains chiral centers that are in the R or S configuration. Sometimes the amino group(s) of the β-amino acid analog are replaced by a protecting group, such as tert-butyloxycarbonyl group (BOC), 9-fluorenylmethyloxycarbonyl (FMOC), tosyl, etc. .P. Sometimes the carboxylic acid functional group of the β-amino acid analog is protected, for example, in the form of its ester derivative. In some cases, a salt of an amino acid analog is used.

[417] A "non-essential" amino acid residue can be one that can be altered in the sequence of a wild-type polypeptide without abolishing or substantially altering its primary biological or biochemical activity (eg, receptor binding or activation). An "essential" amino acid residue may be one which, when altered in the sequence of a wild-type polypeptide, results in the abolition or substantial elimination of the primary biological or biochemical activity of the polypeptide.

[418]. A "conservative amino acid substitution" may be a "conservative amino acid substitution" in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families may include amino acids with basic side chains (e.g. K, R, H), acidic side chains (e.g. D, E), uncharged polar side chains (e.g. G, N, Q, S, T, Y, C ), non-polar side chains (e.g., A, V, L, I, P, F, M, W), beta-branched side chains (e.g., T, V, I), and aromatic side chains (e.g., Y, F, W, H). Thus, a non-essential amino acid residue in a polypeptide is theoretically calculated, for example, can be replaced by another amino acid residue from the same side chain family. Other examples of acceptable substitutions may be substitutions based on isosteric considerations (eg norleucine for methionine) or other properties (eg 2-thienylalanine for phenylalanine or 6-Cl-tryptophan for tryptophan).

[419] Immunogenic pharmaceutical compositions based on nucleic acids can also be administered to the individual. The immunogenic nucleic acid pharmaceutical composition can be formulated using any of the known methods, carriers and excipients as appropriate and understood in the art. The nucleic acid can be DNA, genomic DNA or cDNA, RNA, or a hybrid, where the nucleic acid can contain combinations of deoxyribo- and ribonucleotides and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine, hypoxanthine, isocytosine, and isoguanine. Nucleic acids can be produced by chemical synthesis or by recombinant methods. The immunogenic pharmaceutical composition may be a DNA-based immunogenic pharmaceutical composition, an RNA-based immunogenic pharmaceutical composition, a DNA/RNA hybrid immunogenic pharmaceutical composition, or a hybrid nucleic acid/peptide pharmaceutical composition. The peptide may be a peptide derived from a peptide in Table 1 or 2, a peptide that has a sequence that is at least 40%, 50%, 60%, 70%, 80%, 90%, 95% or more homologous sequence to the peptide in Table 1 or 2, or a peptide that has a sequence that is no more than 40%, 50%, 60%, 70%, 80%, 90%, 95% or less of the homologous sequence of the peptide in Table 1, or 2.

[420] Described herein, a nucleic acid may contain phosphodiester bonds, although in some cases, as described below (for example, when designing primers and probes, such as labeled probes), nucleic acid analogues are included that may have alternative backbones containing, for example, phosphoramide, phosphorothioate, O-methylphosphoramidite linkages and peptide nucleic acid backbones and linkages. Other nucleic acid analogs include compounds with bicyclic structures, including closed nucleic acids, positive backbones, and non-ribose backbones. Nucleic acids containing one or more carbocyclic sugars are also included in the definition of nucleic acids. Locked nucleic acids (LNAs) are also included in the definition of nucleic acid analogues. LNAs are a class of nucleic acid analogs in which the ribose ring is "closed" by a methylene bridge connecting the 2'-O atom to the 4'-C atom. These modifications of the ribose phosphate backbone can be made to improve the stability and half-life of such molecules in physiological environments. For example, PNA:DNA and DNA-DNA hybrids may exhibit higher stability and thus may be used in certain embodiments. Nucleic acids may be single-stranded or double-stranded, as indicated, or contain portions of a double-stranded or single-stranded sequence. Depending on the application, nucleic acids can be DNA (including, for example, genomic DNA, mitochondrial DNA, and cDNA), RNA (including, for example, mRNA and rRNA), or a hybrid, where the nucleic acid contains any combination of deoxyribo- and ribonucleotides and any combination bases including uracil, adenine, thymine, cytosine, guanine, inosine, xatanin hypoxatanin, isocytosine, isoguanine, etc.

[421] Nucleic acid immunogenic pharmaceutical compositions may be in the form of a vector. The vector may be a circular plasmid or a linear nucleic acid. A circular plasmid or a linear nucleic acid may direct the expression of a particular nucleotide sequence in the appropriate cell of an individual. The vector may contain a promoter operably linked to a nucleotide sequence encoding a polypeptide that may be operably linked to termination signals. The vector may contain sequences necessary for the correct translation of the nucleotide sequence. The vector containing the nucleotide sequence of interest may be chimeric, which means that at least one of its components may be heterologous with respect to at least one of its other components. Expression of a nucleotide sequence in an expression cassette may be under the control of a constitutive promoter or an inducible promoter that can initiate transcription only when the host cell is exposed to some particular intrinsic or extrinsic stimulus.

[422] The vector may be a plasmid. The plasmid may be suitable for transfection of cells with a nucleic acid encoding a polypeptide, and the transformed host cells may be cultured and maintained under conditions in which expression of the polypeptide occurs.

[423] the Plasmid may contain a nucleic acid sequence that encodes one or more of the various polypeptides described in the present description. One plasmid may contain a coding sequence for one polypeptide or a coding sequence for more than one polypeptide. In some cases, the plasmid may further contain a coding sequence that encodes an adjuvant such as an immunostimulatory molecule such as a cytokine.

[424] The plasmid may further contain an initiation codon, which may be upstream of the coding sequence, and a stop codon, which may be downstream of the coding sequence. The initiation and termination codon may be in reading frame with the coding sequence. The plasmid may also contain a promoter that is operably linked to the coding sequence and an enhancer upstream of the coding sequence. The enhancer can be human actin, human myosin, human hemoglobin, human creatine, or a viral enhancer such as CMV, FMDV, RSV, or EBV.

[425] The plasmid may also contain a mammalian origin of replication to maintain the extrachromosomal plasmid and obtain multiple copies of the plasmid in the cell. The plasmid may also contain a regulatory sequence which may be well suited for gene expression in the cell into which the plasmid is introduced. The coding sequence may contain a codon that can provide more efficient transcription of the coding sequence in the host cell.

[426] The nucleic acid immunogenic pharmaceutical compositions can also be a linear nucleic acid immunogenic pharmaceutical composition or a linear expression cassette that is capable of being efficiently delivered to an individual by electroporation and expressing one or more of the polypeptides described herein.

[427] Cell-based immunogenic pharmaceutical compositions can also be administered to an individual. For example, an antigen presenting cell (APC) immunogenic pharmaceutical composition may be formulated using any of the well known techniques, carriers, and excipients, as is conventional and understood in the art. APCs include monocytes, monocyte-derived cells, macrophages, and dendritic cells. In some instances, the APC immunogenic pharmaceutical composition may be a dendritic cell immunogenic pharmaceutical composition.

[428] The dendritic cell immunogenic pharmaceutical composition can be prepared by any of the methods well known in the art. In some instances, immunogenic pharmaceutical compositions based on dendritic cells can be prepared ex vivo or in vivo . The ex vivo method may include the use of ex vivo autologous primed DCs with the polypeptides described herein to activate or load DCs prior to administration to a patient. An in vivo method may include targeting specific DC receptors using antibodies linked to the polypeptides described herein. The DC-based immunogenic pharmaceutical composition may further contain DC activators such as TLR3, TLR-7-8 and CD40 agonists. The DC-based immunogenic pharmaceutical composition may further comprise adjuvants and a pharmaceutically acceptable carrier.

[429] An adjuvant can be used to enhance the immune response (humoral and/or cellular) elicited in a patient receiving an immunogenic pharmaceutical composition. In some cases, adjuvants can induce a Th1 type response. In other cases, adjuvants may induce a Th2 type response. The Th1 type response can be characterized by the production of cytokines such as IFN-γ, in contrast to the Th2 type response, which can be characterized by the production of cytokines such as IL-4, IL-5 and IL-10.

[430] In certain aspects, lipid-based adjuvants such as MPLA and MDP can be used with the immunogenic pharmaceutical compositions described herein. Monophosphoryl lipid A (MPLA), for example, is an adjuvant that causes increased presentation of liposomal antigen to specific T lymphocytes. In addition, muramyl dipeptide (MDP) can also be used as a suitable adjuvant in combination with the immunogenic pharmaceutical formulations described herein.

[431] The adjuvant may also contain stimulatory molecules such as cytokines. Non-limiting examples of cytokines include: CCL20, interferon-α (IFN-a), interferon-β (IFN-β), interferon-γ, platelet-derived growth factor (PDGF), TNFα, TNFp, GM-CSF, epidermal growth factor (EGF) , skin T-cell-attracting chemokine (CTACK), thymus-expressed epithelial chemokine (TECK), mucosal-associated epithelial chemokine (MEC), IL-12, IL-15, IL-28, MHC, CD80, CD86, IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-18, MCP-1, MIP-la, MIP-1-, IL-8, L-selectin, P -selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1, VLA-1, Mac-1, pl50.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA -3, M-CSF, G-CSF, IL-18 mutants, CD40, CD40L, vascular growth factor, fibroblast growth factor, IL-7, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Fit, Apo -1, p55, WSL-1, DR3, TRAMP, Apo-3, AIR, LARD, NGRF, DR4, DRS, KILLER, TRAIL-R2, TRICK2, DR6, ICE caspase, Fos, c-jun, Sp-1, Ap-1, Ap-2, p38, p65Rel, MyD88, IRAK, TRAF6, IkB, inactive NIK, SAP K, SAP-I, JNK , interferon response genes, NFkB, Bax, TRAIL, TRAILrec, TRAILrecDR5, TRAIL-R3, TRAIL-R4, RANK, RANK LIGAND, Ox40, Ox40 LIGAND, NKG2D, MICA, MICB, NKG2A, NKG2B, NKG2C, NKG2E, NKG2F, TAPI and TAP2.

[432] Additional adjuvants include: MCP-1, MIP-la, MIP-lp, IL-8, RANTES, L-selectin, P-selectin, E-selectin, CD34, GlyCAM-1, MadCAM-1, LFA-1 , VLA-1, Mac-1, pl50.95, PECAM, ICAM-1, ICAM-2, ICAM-3, CD2, LFA-3, M-CSF, G-CSF, IL-4, IL-18 mutants , CD40, CD40L, vascular growth factor, fibroblast growth factor, IL-7, IL-22, nerve growth factor, vascular endothelial growth factor, Fas, TNF receptor, Fit, Apo-1, p55, WSL-1, DR3, TRAMP , Apo-3, AIR, LARD, NGRF, DR4, DR5, KILLER, TRAIL-R2, TRICK2, DR6, caspase ICE, Fos, c-jun, Sp-1, Ap-1, Ap-2, p38, p65Rel, MyD88, IRAK, TRAF6, IkB, Inactive NIK, SAP K, SAP-1, JNK, interferon response genes, NFkB, Bax, TRAIL, TRAILrec, TRAILrecDRC5, TRAIL-R3, TRAIL-R4, RANK, RANK ligand, Ox40, ligand Ox40, NKG2D, MICA, MICB, NKG2A, NKG2B, NKG2C, NKG2E, NKG2F, TAP1, TAP2 and their functional fragments.

[433] In certain aspects, the adjuvant may be a Toll-like receptor modulator. Examples of Toll-like receptor modulators include TLR-9 agonists and, but are not limited to, small molecule Toll-like receptor modulators such as imiquimod. Other examples of adjuvants that are used in combination with the immunogenic pharmaceutical composition described herein may include, but are not limited to, saponin, CpG ODN, etc. In some instances, the adjuvant is selected from bacterial toxins, polyoxypropylene-polyoxyethylene block polymers, aluminum salts, liposomes, CpG polymers, oil-in-water emulsions, or combinations thereof. In some cases, the adjuvant is an oil-in-water emulsion. The oil-in-water emulsion may contain at least one oil and at least one surfactant, wherein the oil(s) and surfactant(s) are biodegradable (metabolizable) and biocompatible. Oil droplets in an emulsion can be less than 5 µm in diameter and can even be submicron in diameter, such small sizes being achieved with a microfluidic filter to ensure stable emulsions. Droplets smaller than 220 nm can be filter sterilized.

[434] In some cases, the immunogenic pharmaceutical composition may contain carriers and excipients (including, but not limited to, buffers, carbohydrates, mannitol, proteins, polypeptides, or amino acids such as glycine, antioxidants, bacteriostatic agents, chelating agents, suspending agents, thickeners and/or preservatives), water, oils, including oils, from petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc., saline solutions, aqueous solutions dextrose and glycerin, flavoring agents, colorants, detackifiers and other suitable additives, adjuvants or binders, other pharmaceutically acceptable excipients as necessary to approximate physiological conditions such as pH buffering agents, tonicity regulators, emulsifiers, wetting agents, etc. .d. Examples of excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, skimmed milk powder, glycerin, propylene, glycol, water, ethanol, etc. P. In other cases, the pharmaceutical preparation contains little to no preservatives. In other cases, the pharmaceutical preparation may contain at least one preservative. It is understood that while any suitable carrier known to those skilled in the art may be used to administer the pharmaceutical compositions described herein, the type of carrier will vary depending on the route of administration.

[435] The immunogenic pharmaceutical composition may contain preservatives such as thiomersal or 2-phenoxyethanol. In some instances, the immunogenic pharmaceutical composition is substantially free (eg, <10 μg/mL) of mercury, eg, free of thiomersal. α-tocopherol succinate can be used as an alternative to mercury compounds.

[436] To regulate tonicity, a physiological salt, such as sodium salt, can be incorporated into the immunogenic pharmaceutical composition. Other salts may include potassium chloride, potassium dihydrogen phosphate, disodium phosphate and/or magnesium chloride, or the like.

[437] The immunogenic pharmaceutical composition may have an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg, in the range of 240-360 mOsm/kg, or in the range of 290-310 mOsm/kg.

[438] The immunogenic pharmaceutical composition may contain one or more buffers, such as Tris buffer; borate buffer; succinate buffer; histidine buffer (especially with aluminum hydroxide adjuvant); or citrate buffer. Buffers, in some cases, are in the range of 5-20 mm.

[439] The pH value of the immunogenic pharmaceutical composition may be from about 5.0 to about 8.5, from about 6.0 to about 8.0, from about 6.5 to about 7.5, or from about 7.0 to about 7.8.

[440] The immunogenic pharmaceutical composition may be sterile. The immunogenic pharmaceutical composition may be non-pyrogenic, eg containing <1 EU (endotoxin unit, standard measure) per dose and may be <0.1 EU per dose. The composition may not contain gluten.

[441] The immunogenic pharmaceutical composition may contain a detergent, for example, a polyoxyethylene sorbitan ester surfactant (known as "Tweens") or an octoxynol (such as octoxynol-9 (Triton X-100) or t-octylphenoxypolyethoxyethanol). The detergent may be present only in trace amounts. The immunogenic pharmaceutical composition may contain less than 1 mg/ml each of octoxynol-10 and polysorbate 80. Other trace components may be antibiotics (eg, neomycin, kanamycin, polymyxin B).

[442] The immunogenic pharmaceutical composition can be formulated as a sterile solution or suspension in suitable carriers well known in the art. Pharmaceutical compositions may be sterilized by conventional well known sterilization techniques, or they may be sterilized. The resulting aqueous solutions can be packaged for use as is or in a lyophilized form, where the lyophilized preparation is combined with a sterile solution prior to administration.

[443] The immunogenic pharmaceutical composition can be formulated with one or more pharmaceutically acceptable salts. Pharmaceutically acceptable salts may include pharmaceutical salts of inorganic ions such as, for example, sodium, potassium, calcium, magnesium ions, and the like. Such salts may include salts with inorganic or organic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, mandelic acid. , malic acid, citric acid, tartaric acid or maleic acid. In addition, if the agent(s) contains a carboxy group or other acidic group, it can be converted into a pharmaceutically acceptable addition salt with inorganic or organic bases. Examples of suitable bases include sodium hydroxide, potassium hydroxide, ammonia, cyclohexylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, and the like.

[444] Pharmaceutical compositions containing, for example, an active agent such as a peptide, nucleic acid, antibody, or fragments thereof and/or APCs described herein, in combination with one or more adjuvants, can be formulated to contain certain molar ratios . For example, molar ratios of from about 99:1 to about 1:99 of the active agent, such as a peptide, nucleic acid, antibody, or fragments thereof, and/or the APCs described herein, can be used in combination with one or more adjuvants. In some cases, the range of molar ratios of the active agent, such as a peptide, nucleic acid, antibody or fragments thereof and/or the APC described herein in combination with one or more adjuvants, can be selected from about 80:20 to about 20:80; approximately 75:25 to approximately 25:75, approximately 70:30 to approximately 30:70, approximately 66:33 to approximately 33:66, approximately 60:40 to approximately 40:60; approximately 50:50 and approximately 90:10 until approximately 10:90. The molar ratio of the active agent, such as a peptide, nucleic acid, antibody or fragments thereof, and/or the APC described herein, in combination with one or more adjuvants may be about 1:9, and in some cases can be about 1:1. The active agent, such as a peptide, nucleic acid, antibody, or fragments thereof, and/or the APC described herein, in combination with one or more adjuvants, may be formulated together in a single dose, e.g., in a single vial, suppository, tablet, capsule, aerosol spray. ; or each agent, form and/or compound may be formulated in separate units, eg two vials, suppositories, tablets, two capsules, tablets and vial, aerosol spray, and the like.

[445] In some cases, the immunogenic pharmaceutical composition can be administered with an additional agent. The choice of additional agent may depend, at least in part, on the condition being treated. An additional agent may include, for example, any agents having a therapeutic effect on a pathogen infection (e.g., a viral infection), including, for example, drugs used to treat inflammatory conditions such as NSAIDs, e.g., ibuprofen, naproxen, acetaminophen, ketoprofen or aspirin. As another example, the formulations may additionally contain one or more supplements such as vitamin C, E, or other antioxidants.

[446] A pharmaceutical composition containing an active agent such as a peptide, nucleic acid, antibody or fragments thereof and/or the APC described herein in combination with one or more adjuvants can be formulated in a conventional manner using one or more physiologically acceptable carriers, containing excipients, diluents and/or excipients, for example, which facilitate the processing of the active agents into preparations that can be administered. The correct composition may depend at least in part on the chosen route of administration. The agent(s) described herein can be delivered to a patient using several routes or routes of administration, including oral, buccal, topical, rectal, intradermal, transmucosal, subcutaneous, intravenous, intramuscular, and inhalation.

[447] Active agents can be formulated for parenteral administration (eg, by injection, eg, bolus injection or continuous infusion) and can be presented as a unit dosage form in ampoules, pre-filled syringes, small volume infusions, or in multi-dose containers with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, for example solutions in aqueous polyethylene glycol.

[448] For injectable formulations, the carrier may be selected from those known in the art to be suitable, including aqueous solutions or oily suspensions, or emulsions with sesame oil, corn oil, cottonseed oil, or peanut oil, as well as elixirs, mannitol , dextrose or sterile aqueous solution and similar pharmaceutical carriers. The composition may also contain polymeric compositions that are biocompatible, biodegradable, such as a copolymer of lactic and glycolic acids. These agents can be formulated into drug loaded microspheres or nanospheres and further coated or derivatized to provide excellent sustained release characteristics. Carriers suitable for perocular or intraocular injection include, for example, suspensions of the therapeutic agent in water for injection, liposomes, and carriers suitable for lipophilic substances. Other carriers for perocular or intraocular injection are well known in the art.

[449] In some cases, the pharmaceutical composition is formulated in accordance with conventional methods in the form of a pharmaceutical composition adapted for intravenous administration to humans. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. If necessary, the composition may also contain a solubilizer and a local anesthetic such as lidocaine to relieve pain at the injection site. Typically, the ingredients are either supplied separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or concentrate without water in a sealed container such as an ampoule or sachet indicating the amount of active agent. Where the composition is to be administered by infusion, it can be dispersed in an infusion bottle containing sterile pharmaceutical water or saline. When the composition is administered by injection, an ampoule of sterile water for injection or saline may be provided so that the ingredients may be mixed prior to administration.

[450] When administered by injection, the active agent can be formulated in aqueous solutions, in particular in physiologically compatible buffers such as Hanks' solution, Ringer's solution, or physiological saline buffer. The solution may contain adjuvants such as suspending, stabilizing and/or dispersing agents. Alternatively, the active compound may be in powder form for reconstitution with a suitable vehicle, eg sterile, pyrogen-free water, prior to use. In another embodiment, the pharmaceutical composition does not contain an adjuvant or any other substance added to enhance the immune response stimulated by the peptide. In another embodiment, the pharmaceutical composition contains a substance that inhibits the immune response to the peptide.

[451] In addition to the formulations described previously, the active agents can also be formulated as a depot preparation. Such long acting formulations may be administered by implantation or transdermal delivery (eg, subcutaneous or intramuscular), intramuscular injection, or use of a transdermal patch. Thus, for example, the agents can be formulated with suitable polymeric or hydrophobic materials (eg as an emulsion in a suitable oil) or ion exchange resins, or as sparingly soluble derivatives, eg as a sparingly soluble salt.

[452] In cases where pharmaceutical compositions containing one or more agents have a local and regional effect when locally administered or injected at or near a specific site of infection. Direct topical application, for example, a viscous liquid, solution, suspension, dimethyl sulfoxide (DMSO) based solutions, liposomal formulations, gel, jelly, cream, lotion, ointment, suppository, foam, or aerosol spray, can be used for topical application to obtain, for example , local and/or regional effects. Pharmaceutically acceptable carriers for such a formulation include, for example, lower aliphatic alcohols, polyglycols (eg, glycerol or polyethylene glycol), fatty acid esters, oils, fats, silicones, and the like. Such formulations may also include preservatives (eg p-hydroxybenzoic acid esters) and/or antioxidants (eg ascorbic acid and tocopherol). See also Dermatological Formulations: Percutaneous absorption, Barry (Ed.), Marcel Dekker Incl, 1983. In another embodiment, topical/topical formulations containing a transporter, carrier, or ion channel inhibitor are used to treat viral infections of the epidermis or mucosa.

[453] Pharmaceutical compositions may contain a cosmetically or dermatologically acceptable carrier. Such carriers are compatible with skin, nails, mucous membranes, tissues and/or hair and may include any conventional cosmetic or dermatological carrier that meets these requirements. One of ordinary skill in the art can easily select such carriers. When formulating a skin ointment, the agent or combination of agents can be formulated in an oily hydrocarbon base, an anhydrous absorbent base, a water-in-oil absorbent base, a water-removable base, and/or an oil-in-water water-soluble base. Examples of such carriers and excipients include, but are not limited to, humectants (eg urea), glycols (eg propylene glycol), alcohols (eg ethanol), fatty acids (eg oleic acid), surfactants (eg isopropyl myristate). and sodium lauryl sulfate), pyrrolidones, glycerol monolaurate, sulfoxides, terpenes (e.g. menthol), amines, amides, alkanes, alkanols, water, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols.

[454] Ointments and creams can, for example, be formulated with an aqueous or oily base with the addition of suitable thickeners and/or gelling agents. Lotions can be formulated with an aqueous or oily base and generally also contain one or more emulsifiers, stabilizing agents, dispersing agents, suspending agents, thickeners or coloring agents. The design and use of transdermal patches for the delivery of pharmaceuticals is well known in the art. Such patches can be designed for continuous, pulsatile, or on-demand delivery of pharmaceuticals.

[455] Lubricants that can be used to prepare pharmaceutical compositions and dosage forms may include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oil (eg, peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil), zinc stearate, ethyl oleate, ethyl laureth, agar, or mixtures thereof. Additional lubricants include, for example, siloid silica gel, coagulated synthetic silica aerosol, or mixtures thereof. The lubricant may optionally be added in an amount of less than about 1 weight percent of the pharmaceutical composition.

[456] Pharmaceutical compositions may be in any form suitable for topical use, including aqueous, hydroalcoholic or oily solutions, lotion or serum dispersions, aqueous, anhydrous or oily gels, emulsions obtained by dispersion of an oily phase in an aqueous phase ( O/W or oil in water) or vice versa (W/O or water in oil), microemulsions or, alternatively, microcapsules, microparticles or lipid vesicle dispersions of the ionic and/or non-ionic type. These compositions can be obtained by conventional methods. The number of different constituent compositions is the amount generally used in this field. These compositions are in particular creams for protection, treatment or care, milks, lotions, gels or foams for the face, hands, body and/or mucous membranes or for cleansing the skin. The compositions may also consist of solid preparations that make up soaps or cleansing bars.

[457] Pharmaceutical compositions may contain adjuvants such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, fragrances, excipients, sunscreens, odor absorbers, and colorants. The amounts of these various adjuvants are those commonly used in the art and range from, for example, about 0.01% to about 20% of the total weight of the composition. Depending on their nature, such adjuvants can be introduced into the fatty phase, into the aqueous phase and/or into lipid vesicles.

[458] In cases involving topical/local application, pharmaceutical compositions may contain one or more absorption enhancers. For example, formulations may contain suitable solid or gel phase carriers or excipients that enhance absorption or facilitate delivery of the agents or combinations of agents of the invention across a permeation barrier, such as the skin. Many of these absorption enhancers are known in the local art and include, for example, water, alcohols (eg, terpenes such as methanol, ethanol, 2-propanol), sulfoxides (eg, dimethyl sulfoxide, decimethyl sulfoxide, tetradecyl methyl sulfoxide), pyrrolidones (eg. , 2-pyrrolidone, N-methyl-2-pyrrolidone, N-(2-hydroxyethyl)pyrrolidone), laurocaram, acetone, dimethylacetamide, dimethylformamide, tetrahydrofurfuryl alcohol, L-α-amino acids, anionic, cationic, amphoteric or non-ionic surfactants substances (eg isopropyl myristate and sodium lauryl sulfate), fatty acids, fatty alcohols (eg oleic acid), amines, amides, clofibric acid amines, hexamethylene lauramide, proteolytic enzymes, bisabolol, d-limonene, urea and N,N-diethyl-m -toluamide and the like. Additional examples include humectants (eg, urea), glycols (eg, propylene glycol and polyethylene glycol), glycerol monolaurate, alkanes, alkanols, ORGELASE, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and/or other polymers. In another embodiment, the pharmaceutical compositions contain one or more of these absorption enhancers.

[459] Topical/topical pharmaceutical compositions may contain one or more antimicrobial preservatives such as quaternary ammonium compounds, organic mercury compounds, p-hydroxybenzoates, aromatic alcohols, chlorobutanol, and the like.

[460] Pharmaceutical compositions can be formulated as aerosol solutions, suspensions, or dry powders. The aerosol can be administered through the respiratory system or nasal passages. For example, one skilled in the art will appreciate that the composition of the present invention may be suspended or dissolved in a suitable carrier, such as a pharmaceutically acceptable propellant, and administered directly to the lungs using a nasal spray or inhaler. For example, an aerosol formulation containing a transporter, carrier, or ion channel inhibitor may be dissolved, suspended, or emulsified in a propellant or mixture of solvent and propellant, for example, for administration as a nasal spray or inhaler. Aerosol formulations may contain any acceptable pressurized propellant, such as cosmetically or dermatologically, or a pharmaceutically acceptable propellant, as is commonly used in the art.

[461] Aerosol composition for nasal administration, as a rule, is an aqueous solution intended for introduction into the nasal passages in drops or sprays. Nasal solutions may be similar to nasal secretions in that they are generally isotonic and lightly buffered to maintain a pH of about 5.5 to about 6.5, although pH values outside this range may additionally be used. Antimicrobial agents or preservatives may also be included in the composition.

[462] The aerosol composition for inhalations and inhalers can be designed such that the agent or combination of agents is transferred to the respiratory tree of the individual when administered via the nasal or oral respiratory tract. Inhalation solutions can be administered, for example, by means of a nebulizer. Inhalations or insufflations containing finely dispersed or liquid drugs can be delivered to the respiratory system as a pharmaceutical aerosol of a solution or suspension of the agent or combination of agents in a propellant, for example, to aid in distribution. The propellants may be liquefied gases, including halocarbons such as fluorocarbons such as fluorinated chlorinated hydrocarbons, hydrochlorofluorocarbons and hydrochlorocarbons, as well as hydrocarbons and hydrocarbon ethers.

[463] Halocarbon propellants may include fluorocarbon propellants in which all hydrogen atoms are replaced by fluorine, chlorofluorocarbon propellants in which all hydrogen atoms are replaced by chlorine and at least one fluorine, hydrogen-containing fluorocarbon propellants, and hydrogen-containing chlorofluorocarbon propellants. Hydrocarbon propellants useful in the invention include, for example, propane, isobutane, n-butane, pentane, isopentane and neopentane. A mixture of hydrocarbons can also be used as a propellant. Ether based propellants include, for example, dimethyl ether as well as ethers. The aerosol composition of the invention may also contain more than one propellant. For example, an aerosol composition may contain more than one propellant from the same class, such as two or more fluorocarbons; or more than one, more than two, more than three propellants from different classes such as hydrofluorocarbon and hydrocarbon. The pharmaceutical compositions of the present invention can also be dispensed with a pressurized gas, for example an inert gas such as carbon dioxide, nitrous oxide or nitrogen.

[464] Aerosol formulations may also contain other components such as ethanol, isopropanol, propylene glycol, as well as surfactants or other components such as oils and detergents. These components may serve to stabilize the formulation and/or lubricate the valve components.

[465] An aerosol formulation can be pressurized and can be formulated as an aerosol using solutions, suspensions, emulsions, powders, and semi-solids. For example, an aerosol formulation solution may contain a solution of an agent of the invention, such as a transporter, carrier, or ion channel inhibitor (substantially) in pure propellant or as a mixture of propellant and solvent. The solvent can be used to dissolve the agent and/or slow down the evaporation of the propellant. Solvents may include, for example, water, ethanol and glycols. Any combination of suitable solvents may be used, optionally in combination with preservatives, antioxidants and/or other aerosol ingredients.

[466] The aerosol formulation may be a dispersion or suspension. The suspension aerosol formulation may contain a suspension of the agent or combination of agents of the present invention, for example a transporter, carrier or ion channel inhibitor, and a dispersing agent. Dispersants may include, for example, sorbitan trioleate, oleyl alcohol, oleic acid, lecithin, and corn oil. The suspension aerosol formulation may also contain lubricants, preservatives, an antioxidant, and/or other aerosol components.

[467] An aerosol formulation can similarly be formulated as an emulsion. The emulsion aerosol formulation may contain, for example, an alcohol such as ethanol, a surfactant, water, and a propellant, as well as an agent or combination of agents of the invention, such as a transporter, carrier, or ion channel. The surfactant used may be non-ionic, anionic or cationic. One example of an emulsion aerosol formulation contains, for example, ethanol, a surfactant, water, and a propellant. Another example of an emulsion aerosol formulation contains, for example, vegetable oil, glyceryl monostearate and propane.

[468] Pharmaceutical compounds can be formulated for administration as suppositories. A low melting wax such as a mixture of triglycerides, fatty acid glycerides, Witepsol S55 (trademark of Dynamite Nobel Chemical, Germany) or cocoa butter is first melted and the active ingredient is homogeneously dispersed, for example by stirring. The molten homogeneous mixture is then poured into molds of suitable size, left to cool and solidify.

[469] Pharmaceutical compositions can be formulated for vaginal administration. Pessaries, tampons, creams, gels, pastes, foams or sprays containing, in addition to the active ingredient, such carriers as are known in the art to be suitable.

[470] Pharmaceutical compositions can be degradably coupled to biocompatible polymers for use in sustained release formulations on, in, or attached to an insert for topical, intraocular, periocular, or systemic administration. Controlled release from a biocompatible polymer can also be used with a water soluble polymer to form a drop formulation. Controlled release from a biocompatible polymer, such as, for example, PLGA microspheres or nanospheres, can be used in a formulation suitable for intraocular implantation or injection for sustained release administration. Any suitable biodegradable and biocompatible polymer can be used.

IV. Combinations of CTL peptides and HTL peptides

[471] Immunogenic or vaccine compositions containing the neoantigenic polypeptides and polynucleotides described herein, or analogues thereof, that have immunostimulatory activity can be modified to obtain desired characteristics, such as improved serum half-life, or to increase immunogenicity.

[472] For example, the ability of neoantigenic peptides to induce CTL activity can be enhanced by linking the peptide to a sequence that contains at least one epitope that is capable of inducing a helper T cell response. In certain embodiments, the CTL epitope/HTL epitope conjugates are linked using a spacer molecule. A spacer typically consists of relatively small, neutral molecules, such as amino acids or amino acid mimetics, that are essentially uncharged under physiological conditions. The spacers are typically selected from, for example, Ala, Gly or other neutral non-polar amino acid spacers or neutral polar amino acids. It should be understood that an optionally present spacer need not contain the same residues and thus may be a hetero- or homo-oligomer. If present, a spacer will typically be at least one or two residues, more typically three to six residues. Alternatively, the CTL peptide can be coupled to the T helper peptide without a spacer.

[473] Although a CTL peptide epitope can be linked directly to a T-helper peptide epitope, CTL epitope/HTL epitope conjugates can be linked using a spacer molecule. A spacer typically consists of relatively small, neutral molecules, such as amino acids or amino acid mimetics, that are substantially uncharged under physiological conditions. The spacers are typically selected from, for example, Ala, Gly or other neutral non-polar amino acid spacers or neutral polar amino acids. It should be understood that an optionally present spacer need not contain the same residues and thus may be a hetero- or homo-oligomer. If present, a spacer will typically be at least one or two residues, more typically three to six residues. The CTL peptide epitope can be linked to the T-helper peptide epitope either directly or via a spacer to the N-terminus or C-terminus of the CTL peptide. The N-terminus of the immunogenic peptide or T-helper peptide may be acylated.

[474] HTL peptide epitopes can also be modified to change their biological properties. For example, peptides containing HTL epitopes may contain D-amino acids to enhance their resistance to proteases and thus prolong serum half-life. In addition, epitope peptides can be conjugated to other molecules such as lipids, proteins or sugars or any other synthetic compound to increase their biological activity. For example, a T helper peptide can be conjugated to one or more palmitic acid chains at the N- or C-terminus.

[475] In certain embodiments, the implementation of the T-helper peptide is a peptide that is recognized by T-helper cells present in the majority of the population. This can be done by selecting amino acid sequences that bind to many, most or all of the HLA class II molecules. These are known as "loosely HLA-restricted" or "promiscuous" T-helper sequences. Examples of amino acid sequences that are promiscuous include those from antigens such as tetanus toxin at positions 830-843 (QYIKANSKFIGITE), Plasmodium falciparum CS protein at positions 378-398 (DIEKKIAKMEKASSVFNVVNS), and Streptococcus 18 kDa protein at positions 116 (GAVDSILGGVATYGAA) . Other examples include peptides carrying the DR 1-4-7 supermotif or any of the DR3 motifs.

[476] Alternatively, synthetic peptides capable of stimulating T-helper lymphocytes can be prepared in a weakly HLA-restricted form using non-naturally occurring amino acid sequences (see, for example, PCT publication WO 95/07707). Such synthetic compounds, referred to as Pan-DR binding epitopes (eg, PADRE, Epimmune, Inc., San Diego, CA), are designed to bind to most HLA-DR (human HLA class II) molecules. For example, a pan-DR binding epitope peptide having the formula: aKXVWANTLKAAa where "X" is either cyclohexylalanine, phenylalanine, or tyrosine and a is D-alanine or L-alanine that binds to most of the HLA- DR, and stimulates the response of T-helper lymphocytes in most individuals, regardless of their HLA type. The pan-DR binding epitope alternative includes all "L"-natural amino acids and can be provided as nucleic acids that encode the epitope.

[477] In certain embodiments, it may be desirable to administer a neoantigen-based therapeutic (e.g., peptides, polynucleotides, TCRs, CARs, TCR or CAR containing cells, polypeptide containing dendritic cells, polynucleotide containing dendritic cells, antibody, etc. .) in pharmaceutical compositions (eg immunogenic compositions) at least one component that primes cytotoxic T-lymphocytes. Lipids have been identified as agents capable of priming CTL in vivo against viral antigens. For example, palmitic acid residues can be attached to the ε- and α-amino groups of the lysine residue and then linked, for example, to one or more linking residues such as Gly, Gly-Gly-, Ser, Ser-Ser or the like, with an immunogenic neoantigenic peptide. The lipidated peptide can then be injected either directly into a micelle or particle incorporated into a liposome, or emulsified in an adjuvant. In certain embodiments, a particularly effective immunogenic construct comprises palmitic acid attached to the ε- and α-amino groups of Lys, which is attached by linking, for example, Ser-Ser, to the amino terminus of the immunogenic peptide.

[478] As another example of lipid priming of CTL responses, E. coli lipoproteins such as tripalmitoyl-S-glycerylcysteineinterylserine (P3CSS) can be used to prime virus-specific CTLs when covalently attached to the appropriate peptide. (See, for example, Deres, et al., Nature 342: 561, 1989). The neoantigenic peptides described herein can be coupled to, for example, P3CSS and a lipopeptide administered to an individual to specifically prime the CTL response to the target antigen. Furthermore, since the induction of neutralizing antibodies can also be primed with P3CSS-conjugated epitopes, the two such compositions can be combined to more effectively elicit both humoral and cell-mediated responses to infection.

[479] As noted herein, additional amino acids can be added to the ends of a neoantigenic peptide to allow for ease of linking the peptides to each other, to link to a carrier support or larger peptide, to modify the physical or chemical properties of the peptide or oligopeptide, or the like. P. Amino acids such as tyrosine, cysteine, lysine, glutamic or aspartic acid or the like can be introduced at the C- or N-terminus of the peptide or oligopeptide. However, it should be noted that modification at the C-terminus of a T-cell epitope may, in some cases, change the binding characteristics of a peptide. In addition, peptide or oligopeptide sequences may differ from the natural sequence in that they are modified by terminal NH2 acylation, e.g., alkanoyl (C1-C20) or thioglycolyl acetylation, C-terminal amidation, e.g., ammonia, methylamine, etc. In some cases, these modifications may provide sites for binding to a substrate or another molecule.

[480] An embodiment of an immunogenic composition described herein comprises administering ex vivo a mixture of an epitope-bearing neoantigenic polypeptide or polynucleotides to PBMCs or DCs isolated therefrom from a patient's blood. You can use a pharmaceutical agent to facilitate the collection of dendritic cells (DC), including GM-CSF, IL-4, IL-6, IL-1β and TNFα. After loading the DCs with peptides or polynucleotides encoding the peptides and prior to re-infusion in patients, the DCs are washed to remove unbound peptides. In this embodiment, the vaccine or immunogenic composition contains peptide-loaded DCs that present peptide epitopes complexed with HLA molecules on their surfaces. The composition is then administered to the patient. In other embodiments, such loaded DCs are used to stimulate T cells suitable for use in T cell therapy.

V. Multi-epitope immunogenic compositions

[481] A number of different approaches are available that allow the simultaneous delivery of multiple epitopes. The nucleic acids encoding the neoantigenic peptides described herein are a particularly useful embodiment of the invention. In certain embodiments, the nucleic acid is RNA. In certain embodiments, minigenic constructs encoding a neoantigenic peptide containing one or more of the epitopes described herein are used to introduce nucleic acids encoding the neoantigenic peptides described herein.

[482] The use of multi-epitope minigenes is described in An L. and Whitton, J. L., J. Virol. 71:2292, 1997; Thomson, S. A. et al., J. Immunol. 157:822, 1996; Whitton, J. L. et al., J. Virol. 67:348, 1993; Hanke, R. et al., Vaccine 16: 426, 1998. For example, a multi-epitope DNA plasmid can be constructed that encodes neoantigenic peptides carrying a supermotif and/or motif, a universal helper T-cell epitope (or multiple tumor-associated HTL antigen epitopes), and signal sequence of the translocation of the endoplasmic reticulum.

[483] The immunogenicity of a multi-epitope minigene can be tested in transgenic mice to assess the magnitude of the immune response induced against the tested epitopes. In addition, the immunogenicity of DNA-encoded epitopes in vivo can be compared with the in vitro responses of specific CTL lines against target cells transfected with plasmid DNA. Thus, these experiments may show that the minigene serves both purposes: 1.) induces a cell-mediated and/or humoral response and 2.) induced immune cells recognize cells expressing encoded epitopes.

[484] For example, to obtain a DNA sequence encoding selected neoepitopes (minigene) for expression in human cells, the amino acid sequences of the epitopes can be reverse translated. A human codon preference table can be used to guide the selection of codons for each amino acid. These neoepitope-encoding DNA sequences can be directly attached such that upon translation a contiguous polypeptide sequence is formed. Additional elements can be introduced into the minigene construct to optimize expression and/or immunogenicity. Examples of amino acid sequences that can be reverse translated and introduced into the minigene sequence include: HLA class I epitopes, HLA class II epitopes, ubiquitinylation signal sequence, and/or endoplasmic reticulum targeting signal. In addition, the HLA presentation of CTL and HTL epitopes can be improved by introducing synthetic (eg, poly-alanine) or natural flanking sequences adjacent to the CTL or HTL epitopes; such larger peptides containing the epitope(s) are within the scope of the invention.

[485] The minigene sequence can be converted to DNA by assembling oligonucleotides that encode the plus and minus strands of the minigene. Overlapping oligonucleotides (30-100 bases long) can be synthesized, phosphorylated, purified and annealed under suitable conditions using well known methods. The ends of the oligonucleotides can be connected, for example, using T4 DNA ligase. Such a synthetic minigene encoding an epitope polypeptide can then be cloned into the desired expression vector.

[486] To ensure expression in target cells, standard regulatory sequences well known to those skilled in the art can be introduced into the vector. For example, a promoter with a forward cloning site to introduce a minigene; polyadenylation signal for efficient transcription termination; origin of E. coli replication site; and a selectable E. coli marker (eg, resistance to ampicillin or kanamycin). Many promoters can be used for this purpose, for example the human cytomegalovirus (hCMV) promoter. See, for example, US Pat. Nos. 5,580,859 and 5,589,466 for other suitable promoter sequences.

[487] Additional vector modifications can be used to optimize minigene expression and immunogenicity. In some cases, introns are necessary for efficient gene expression, and one or more synthetic or natural introns can be introduced into the transcribed region of the minigene. The introduction of stabilizing mRNA sequences and sequences for replication in mammalian cells can also be envisaged to increase minigene expression.

[488] Once an expression vector has been selected, the minigene can be cloned into the polylinker region downstream of the promoter. This plasmid is transformed into a suitable E. coli strain and DNA is prepared by standard methods. The orientation and DNA sequence of the minigene, as well as all other elements included in the vector, can be confirmed using restriction mapping and DNA sequence analysis. Bacterial cells containing the correct plasmid can be stored as a stock cell bank and a working cell bank.

[489] In addition, immunomodulatory sequences appear to play a role in the immunogenicity of DNA vaccines. If desired, these sequences can be introduced into the vector outside the minigene coding sequence to increase immunogenicity. In certain embodiments, the sequences are immunostimulatory. In another embodiment, the sequences are ISS or CpG.

[490] In certain embodiments, a bicistronic expression vector can be used that allows the production of minigene-encoded epitopes and a second protein (introduced to increase or decrease immunogenicity). Examples of proteins or polypeptides that can significantly enhance the immune response when co-expressed include cytokines (eg, IL-2, IL-12, GM-CSF), cytokine-inducing molecules (eg, LeIF), costimulatory molecules, or for HTL pan responses. -DR-binding proteins. Helper (HTL) epitopes can be coupled to intracellular targeting signals and expressed separately from expressed CTL epitopes; this allows the HTL epitopes to be directed to a cellular compartment different from that of the CTL epitopes. If desired, this may facilitate more efficient introduction of HTL epitopes via the HLA class II pathway, thereby improving HTL induction. In contrast to the induction of HTL or CTL, specific reduction of the immune response by co-expression of immunosuppressive molecules (eg, TGF-β) may be beneficial in certain diseases.

[491] Therapeutic amounts of plasmid DNA can be obtained, for example, by fermentation in E. coli followed by purification. Aliquots from the working cell bank are used to inoculate the growth medium and grown to saturation in shake flasks or a bioreactor according to well known methods. Plasmid DNA can be purified using standard bioseparation technologies such as solid phase anion exchange resins available from QIAGEN, Inc. (Valencia, California). If required, supercoiled DNA can be isolated from open circular and linear forms using gel electrophoresis or other methods.

[492] Purified plasmid DNA can be prepared for injection using various formulations. The simplest of these is the reconstitution of lyophilized DNA in sterile phosphate buffered saline (PBS). This approach, known as "naked DNA", is currently being used for intramuscular (IM) administration in clinical trials. To maximize the immunotherapeutic effect of minigene-based DNA vaccines, an alternative method of formulating purified plasmid DNA can be used. Various methods have been described and new methods may become available. Cationic lipids can also be used in the formulation (see, for example, WO 93/24640, Mannino & Gould-Fogerite, BioTechniques 6 (7): 682 (1988), US Pat. No. 5,279,833, WO 91/06309 and Felgner et al. ., Proc. Nat'l Acad. Sci. USA, 84: 7413 (1987) In addition, glycolipids, fusogenic liposomes, peptides, and compounds that together are protective, interactive, non-condensable compounds (PINCs) can also be complexed with purified plasmid DNA to influence variables such as stability, intramuscular distribution, or transport to certain organs or cell types.

[493] In another embodiment, the nucleic acid is introduced into cells using high-speed cell deformation. During high-speed deformation, the cells are compressed so that temporary disturbances occur in the cell membrane, which allows the nucleic acid to enter the cell. Alternatively, the protein can be obtained from expression vectors, for example in a bacterial expression vector, and the proteins can then be delivered to the cell.

[494] Target cell sensitization can be used as a functional analysis of the expression and presentation of HLA class I minigene-encoded CTG epitopes. For example, plasmid DNA is introduced into a mammalian cell line that is suitable as a target for standard CTL chromium release assays. The transfection method used depends on the final composition. Electroporation can be used for "naked" DNA, while cationic lipids allow direct transfection in vitro . A green fluorescent protein (GFP) expression plasmid can be co-transfected to allow enrichment of the transfected cells by fluorescence activated sorting (FACS). These cells are then labeled with 51 chromium ( ⁵¹ Cr) and used as target cells for epitope-specific CTL lines; cytolysis, ⁵¹ Cr release is detected, indicating the production and provision of HLA minigene-encoded CTG epitopes. Expression of HTL epitopes can be assessed in a similar manner using assays to assess HTL activity.

[495] In vivo immunogenicity is a second approach for functional testing of minigene DNA compositions. Transgenic mice expressing the appropriate human HLA proteins are immunized with the DNA product. The dose and route of administration depend on the formulation (eg, IM for DNA in PBS, intraperitoneal (IP) for lipid-complexed DNA). An exemplary protocol is as follows: twenty-one days after immunization, splenocytes are harvested and re-stimulated for 1 week in the presence of peptides encoding each test epitope. CTL effector cells are then assayed for cytolysis of peptide-loaded, ⁵¹ Cr-labeled target cells by standard methods. Lysis of target cells that have been sensitized with loaded HLA peptide epitopes corresponding to minigene-encoded epitopes demonstrates the function of a DNA vaccine to induce CTL in vivo . The immunogenicity of HTL epitopes is assessed in transgenic mice in a similar manner.

[496] Alternatively, nucleic acids can be administered using ballistic delivery, as described, for example, in US Pat. No. 5,204,253. This method introduces particles consisting entirely of DNA. In another alternative embodiment, DNA can be attached to particles such as gold particles.

VI. Cells for use in the invention

[497] In one aspect, the present invention also provides cells expressing a receptor that recognizes a neoantigen that activates an immunopositive cell (e.g., a T cell receptor (TCR) or a chimeric antigen receptor (CAR)) and methods of using such cells to treat a disease. which requires an enhanced immune response.

[498] Such cells include genetically modified immunoreactive cells (e.g., T cells, natural killer (NK) cells, cytotoxic T lymphocytes (CTL), T lymphocyte helper (HTL) cells) expressing the antigen recognition receptor (eg, TCR or CAR) that binds one of the neoantigenic peptides described herein, and uses, therefore, for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired. T cell activation is mediated by TCR or antigen-targeted CAR.

[499] The present invention relates to cells expressing a combination of an antigen recognition receptor that activates an immunoreactive cell (e.g., TCR, CAR) and a chimeric costimulatory receptor (CCR), and methods of using such cells to treat a disease that requires enhanced immune response. response. In certain embodiments, tumor antigen-specific T cells, NK cells, CTL cells, or other immunoresponsive cells are used as shuttles to selectively enrich one or more co-stimulatory ligands to treat or prevent neoplasia. Such cells are administered to a human subject in need thereof for the treatment or prevention of a particular cancer.

[500] In certain embodiments, human tumor antigen-specific lymphocytes that can be used in the methods of the invention include, without limitation, donor peripheral blood lymphocytes genetically modified to express chimeric antigen receptors (CARs) (Sadelain, M., et al. 2003 Nat Rev Cancer 3: 35-45), donor peripheral blood lymphocytes genetically modified to express a full-length tumor antigen-recognizing T-cell receptor complex containing a and p heterodimer (Morgan RA, et al., Science Science, 314: 126-129 ), cultures of lymphocytes derived from infiltrating tumor lymphocytes (TIL) in tumor biopsies (Panelli MC et al., 2000 J Immunol 164: 495-504, Panelli, MC, et al., 2000 J Immunol 164: 4382-4392), and selectively expanded in vitro antigen-specific peripheral blood leukocytes using artificial antigen-presenting cells (AAPC) or loaded dendritic cells (Dupont, J., et al., 2005 Cancer Res., 65: 5417-5427; Papanicolaou, GA, et al. 2003 Blood 102: 2498-2505). T cells can be autologous, allogeneic, or in vitro derived from engineered progenitor or stem cells.

[501] In certain embodiments, the immunotherapeutic agent is an engineered receptor. In certain embodiments, the engineered receptor is a chimeric antigen receptor (CAR), T cell receptor (TCR) or B cell receptor (BCR), adoptive T cell therapy (ACT), or a derivative thereof. In other aspects, the engineered receptor is a chimeric antigen receptor (CAR). In some aspects, the CAR is a first generation CAR. In other aspects, the CAR is a second generation CAR. In other aspects, the CAR is a third generation CAR.

[502] In certain aspects, a CAR comprises an extracellular region, a transmembrane region, and an intracellular region. In certain aspects, the intracellular region contains at least one T cell co-stimulatory domain. In certain aspects, the T cell costimulatory domain is selected from the group consisting of CD27, CD28, TNFRS9 (4-1BB), TNFRSF4 (OX40), TNFRSF8 (CD30), CD40LG (CD40L), ICOS, ITGB2 (LFA-1), CD2 , CD7, KLRC2 (NKG2C), TNFRS18 (GITR), TNFRSF14 (HVEM), or any combination thereof.

[503] In certain aspects, the engineered receptor binds to a target. In certain aspects, the binding is specific to a peptide specific to one or more individuals suffering from a disease or condition.

[504] In certain aspects, the immunotherapeutic agent is a cell, as described in detail in the present description. In certain aspects, the immunotherapeutic agent is a cell containing a receptor that specifically binds a peptide. In certain aspects, the immunotherapeutic agent is a cell used in combination with the peptides/nucleic acids of the present invention. In certain embodiments, the cell is a patient cell. In certain embodiments, the cell is a T cell. In certain embodiments, the cell is a tumor-infiltrating lymphocyte.

[505] In certain aspects, an individual with a condition or disease is treated depending on the individual's T-cell receptor repertoire. In certain embodiments, the antigen vaccine is selected based on the individual's T-cell receptor repertoire. In certain embodiments, the individual is treated with T cells expressing TCRs specific for an antigen or peptide. In certain embodiments, the individual is treated with a TCR specific antigen or peptide, eg, TCR specific to the individual. In certain embodiments, the individual is treated with an antigen or peptide specific for T-cells expressing TCRs, eg, individual-specific TCRs. In certain embodiments, the individual is treated with an antigen or peptide specific for the individual's TCR.

[506] In certain embodiments, an immunogenic antigenic composition or vaccine is selected based on TCRs identified in one or more individuals. In certain embodiments, identification of the T cell repertoire and testing in functional assays is used to determine the immunogenic composition or vaccine to be administered to one or more individuals with a condition or disease. In certain embodiments, the implementation of the immunogenic composition is an antigenic vaccine. In certain embodiments, the implementation of the antigenic vaccine contains specific antigenic peptides for the individual. In certain embodiments, the antigenic peptides to be incorporated into the antigen vaccine are selected based on the quantification of the individual's specific TCRs that bind to the antigens. In certain embodiments, antigenic peptides are selected based on the binding affinity of the peptide to the TCR. In certain embodiments, the selection is based on a combination of both amount and binding affinity. For example, a TCR that binds antigen strongly in a functional assay, but which is highly represented in the TCR repertoire, may be a good candidate for an antigen vaccine because predominantly T-cells expressing TCR will proliferate.

[507] In certain embodiments, antigens are selected for administration to one or more individuals based on binding to the TCR. In certain embodiments, T cells can be propagated, such as T cells from an individual with a disease or condition. Propagated T cells that express TCRs specific for the immunogenic antigenic peptide can be reintroduced into the individual. In certain embodiments, suitable cells, such as PBMCs, are transduced or transfected with polynucleotides to express TCRs specific for an immunogenic antigenic peptide and administered to an individual. T cells expressing TCRs specific for the immunogenic antigenic peptide can be expanded and reintroduced into the individual. In certain embodiments, T cells that express TCRs specific for an immunogenic antigenic peptide that result in cytolytic activity when incubated with autologous diseased tissue can be expanded and administered to a patient. In certain embodiments, T cells used in functional assays resulting in binding to an immunogenic antigenic peptide can be expanded and administered to a patient. In certain embodiments, TCRs that have been determined to bind to individual-specific immunogenic antigenic peptides can be expressed in T cells and administered to the individual.

Costimulatory ligands

[508] In certain embodiments, cells of the invention are provided with at least one co-stimulatory ligand that is not an antigen-specific signal essential for full activation of an immune cell. Costimulatory ligands include, but are not limited to, tumor necrosis factor (TNF) ligands, cytokines (such as IL-2, IL-12, IL-15, or IL21), and the immunoglobulin (Ig) ligand superfamily.

[509] Tumor necrosis factor (TNF) is a cytokine involved in systemic inflammation and stimulating the acute phase response. Its main role is to regulate immune cells. Tumor necrosis factor (TNF) ligands share a number of common features. Most ligands are synthesized as type II transmembrane proteins containing a short cytoplasmic segment and a relatively long extracellular region. TNF ligands include, but are not limited to, nerve growth factor (NGF), CD4OL (CD4OL)/CD154, CD137L/4-1BBL, tumor necrosis factor alpha (TNFα), CD134L/OX4OL/CD252, CD27L/CD70, Fas ligand (FasL) , CD3OL/CD153, tumor necrosis factor β (TNF β)/lymphotoxin-alpha (LTa), lymphotoxin-beta (eq(3), CD257/B cell activating factor (BAFF)/Blys/THANK/Ta11-1 apoptosis-induced ligand TNF (TRAIL), LIGHT (TNFSF14) The immunoglobulin (Ig) superfamily is a large group of cell surface proteins and soluble proteins that are involved in cell recognition, binding or adhesion These proteins share structural features with immunoglobulins - they contain the immunoglobulin domain (fold) The immunoglobulin ligand superfamily includes, but is not limited to, CD80 and CD86, both ligands for CD28.

[510] Compositions containing genetically modified immunoreactive cells of the invention can be provided systemically or directly to an individual for the treatment of neoplasia. In certain embodiments, the cells of the invention are directly injected into an organ of interest (eg, an organ affected by a tumor). Alternatively, compositions containing genetically modified immunoreactive cells are provided directly to the organ of interest, eg, by administration to the circulatory system (eg, tumor vasculature). Proliferation and differentiation promoting agents can be provided before, during, or after cell administration to increase the production of T cells, NK cells, or CTL cells in vitro or in vivo .

[511] The modified cells can be administered in any physiologically acceptable vehicle, usually intravascularly, although they can also be injected into bone or other convenient site where the cells can find a suitable site for regeneration and differentiation (eg, thymus). Genetically modified immunoreactive cells according to the invention may contain a population of purified cells. Those skilled in the art can readily determine the percentage of genetically modified immunoreactive cells in a population using various known methods such as fluorescence activated cell sorting (FACS). Dosages can be easily adjusted by those skilled in the art (eg, a decrease in purity may require an increase in dosage). The cells may be administered by injection, catheter, or the like. Factors may also be included, if desired, including, but not limited to, interleukins such as IL-2, IL-3, IL-6, and IL-11, as well as other interleukins, colony stimulating factors such as G-, M-, and GM-CSF, interferons such as interferon-γ and erythropoietin.

[512] The compositions of the invention include pharmaceutical compositions containing genetically modified immunoreactive cells or their precursors and a pharmaceutically acceptable carrier. Administration may be autologous or heterologous. For example, immunoreactive cells or progenitors can be obtained from one individual and administered to the same individual or another compatible individual. The peripheral blood-derived immunoreactive cells of the invention or their progeny (e.g., in vivo , ex vivo , or in vitro ) can be administered by localized injection, including catheter insertion, systemic injection, localized injection, intravenous injection, or parenteral administration. When a therapeutic composition of the present invention (eg, a pharmaceutical composition containing a genetically modified immunoreactive cell) is administered, it is typically formulated as a unit injectable dose (solution, suspension, emulsion).

VII. Methods of use and pharmaceutical compositions

[513] Neoantigen-based therapeutics (e.g., peptides, polynucleotides, TCRs, CARs, TCR or CAR-containing cells, polypeptide-containing dendritic cells, polynucleotide-containing dendritic cells, antibody, etc.) described herein , are useful in a number of applications, including, but not limited to, methods of therapeutic treatment, such as the treatment of cancer. In certain embodiments, the methods of therapeutic treatment include immunotherapy. In certain embodiments, the neoantigen peptide is useful for activating, stimulating, increasing and/or enhancing an immune response, redirecting an existing immune response to a new target, increasing tumor immunogenicity, inhibiting tumor growth, reducing tumor volume, increasing tumor cell apoptosis, and/or reducing tumorigenicity. tumors. The methods of administration may be in vitro , ex vivo or in vivo .

[514] In certain aspects, the present invention relates to methods for activating an immune response in an individual using a therapeutic agent based on the neoantigen described in the present description. In certain embodiments, the invention provides methods for stimulating an immune response in an individual using a neoantigen therapeutic agent as described herein. In certain embodiments, the invention relates to methods for enhancing an immune response in an individual using the neoantigenic peptide described herein. In certain embodiments, the invention relates to methods for enhancing an immune response using a neoantigenic peptide. In certain embodiments, activating, stimulating, increasing, and/or enhancing an immune response includes increasing cellular immunity. In certain embodiments, the implementation of the activation, stimulation, increase and/or enhancement of the immune response includes an increase in the activity of T cells or humoral immunity. In certain embodiments, the implementation of the activation, stimulation, increase and/or enhancement of the immune response includes an increase in the activity of CTL or HTL. In certain embodiments, the implementation of the activation, stimulation, increase and/or enhancement of the immune response includes increasing the activity of NK cells. In certain embodiments, activating, stimulating, increasing, and/or enhancing an immune response includes increasing T cell activity and increasing NK cell activity. In certain embodiments, activating, stimulating, increasing, and/or enhancing an immune response includes increasing CTL activity and increasing NK cell activity. In certain embodiments, activating, stimulating, increasing, and/or enhancing an immune response includes inhibiting or decreasing Treg suppressive activity. In certain embodiments, the implementation of the immune response is the result of antigenic stimulation. In certain embodiments, the antigen challenge is a tumor cell. In certain embodiments, the antigen challenge is a cancer.

[515] In certain embodiments, the invention relates to methods of activating, stimulating, enhancing, and/or enhancing an immune response using a neoantigen-based therapeutic agent described herein. In certain embodiments, the method comprises administering to an individual in need thereof a therapeutically effective amount of a neoantigen therapeutic agent that delivers the neoantigenic polypeptide or polynucleotide to the tumor cell. In certain embodiments, the method comprises administering to an individual in need thereof a therapeutically effective amount of a neoantigen therapeutic agent that binds to a tumor associated antigen and is internalized by the tumor cell. In certain embodiments, the method comprises administering to an individual in need thereof a therapeutically effective amount of a neoantigenic polypeptide that is internalized by the tumor cell and the neoantigenic peptide is processed by the cell. In certain embodiments, the method comprises administering to an individual in need thereof a therapeutically effective amount of a neoantigenic polypeptide that is internalized by the tumor cell and the antigenic peptide is presented on the surface of the tumor cell. In certain embodiments, the method includes administering to an individual in need thereof a therapeutically effective amount of a neoantigenic polypeptide that is internalized by the tumor cell, processed by the cell, and the antigenic peptide is presented on the surface of the tumor cell.

[516] In certain embodiments, the method includes administering to an individual in need thereof a therapeutically effective amount of a neoantigenic polypeptide or polynucleotide described herein that delivers an exogenous polypeptide comprising at least one antigenic peptide to a tumor cell where the antigenic peptide is presented on a surface. tumor cell. In certain embodiments, the antigenic peptide is presented on the surface of the tumor cell in association with an MHC class I molecule. In certain embodiments, the antigenic peptide is presented on the surface of the tumor cell in association with an MHC class II molecule.

[517] In certain embodiments, the method includes contacting a tumor cell with a neoantigenic polypeptide or polynucleotide described herein that delivers an exogenous polypeptide comprising at least one antigenic peptide to the tumor cell, where the antigenic peptide is presented on the surface of the tumor cell. . In certain embodiments, the antigenic peptide is presented on the surface of the tumor cell in association with an MHC class I molecule. In certain embodiments, the antigenic peptide is presented on the surface of the tumor cell in association with an MHC class II molecule.

[518] In certain embodiments, the method includes administering to an individual in need thereof a therapeutically effective amount of a neoantigenic polypeptide or polynucleotide described herein that delivers an exogenous polypeptide comprising at least one antigenic peptide to a tumor cell where the antigenic peptide is presented on a surface. tumor cell, and an immune response against the tumor cell is induced. In certain embodiments, the immune response against the tumor cell is increased. In certain embodiments, the neoantigen polypeptide or polynucleotide delivers an exogenous polypeptide containing at least one antigenic peptide to a tumor cell, where the antigenic peptide is presented on the surface of the tumor cell, and inhibit tumor growth.

[519] In certain embodiments, the method includes administering to an individual in need thereof a therapeutically effective amount of a neoantigenic polypeptide or polynucleotide described herein that delivers an exogenous polypeptide comprising at least one antigenic peptide to a tumor cell where the antigenic peptide is presented on a surface. tumor cell, and cytotoxic activity of T cells directed against the tumor cell is induced. In certain embodiments, the cytotoxic activity of T cells against the tumor cell is enhanced. In certain embodiments, the cytotoxic activity of T cells against the tumor cell is increased.

[520] In certain embodiments, a method for enhancing an immune response in an individual comprises administering to the individual a therapeutically effective amount of a neoantigen-based therapeutic agent described herein, wherein the agent is an antibody that specifically binds to a neoantigen described herein. In certain embodiments, a method for enhancing an immune response in an individual comprises administering to the individual a therapeutically effective amount of an antibody.

[521] The present invention relates to methods for redirecting an existing immune response to a tumor. In certain embodiments, a method of redirecting an existing immune response to a tumor comprises administering to an individual a therapeutically effective amount of a neoantigen therapeutic agent as described herein. In certain embodiments, an existing immune response is directed against the virus. In certain embodiments, the virus is selected from the group consisting of: measles virus, varicella-zoster virus (VZV; varicella-zoster virus), influenza virus, mumps virus, poliovirus, rubella virus, rotavirus, hepatitis A virus (HAV), hepatitis virus B (HBV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In certain embodiments, the virus is a varicella-zoster virus. In certain embodiments, the virus is a cytomegalovirus. In certain embodiments, the virus is a measles virus. In certain embodiments, the present immune response has been acquired following natural infection with the virus. In certain embodiments, the implementation of the existing immune response was acquired after vaccination against the virus. In certain embodiments, the present immune response is a cell-mediated response. In certain embodiments, the existing immune response includes cytotoxic T cells (CTL) or HTL.

[522] In certain embodiments, a method of redirecting an existing immune response to a tumor in an individual comprises administering a fusion protein comprising (i) an antibody that specifically binds to a neoantigen, and (ii) at least one neoantigenic peptide as described herein, wherein (a) the fusion protein is internalized by the tumor cell after binding to a tumor associated antigen; (b) the neoantigenic peptide is processed and presented on the tumor cell surface associated with a MHC class I molecule; and (c) the class I neoantigenic peptide/MHC complex is recognized by cytotoxic T cells. In certain embodiments, the cytotoxic T cells are memory T cells. In certain embodiments, memory T cells are the result of vaccination with a neoantigenic peptide.

[523] The present invention relates to methods for increasing the immunogenicity of a tumor. In certain embodiments, a method for increasing the immunogenicity of a tumor comprises contacting the tumor or tumor cells with an effective amount of a neoantigen therapeutic agent as described herein. In certain embodiments, a method for increasing the immunogenicity of a tumor comprises administering to a subject a therapeutically effective amount of a neoantigen therapeutic agent as described herein.

[524] The present invention also relates to methods for inhibiting tumor growth using a therapeutic agent based on the neoantigen described in the present description. In certain embodiments, a method for inhibiting tumor growth comprises contacting a mixture of cells with a neoantigen therapeutic agent in vitro . For example, an immortalized cell line or a malignant cell line mixed with immune cells (eg, T cells) is cultured in a medium to which a neoantigenic peptide is added. In certain embodiments, tumor cells are isolated from a patient sample, such as a tissue biopsy, pleural effusion, or blood sample, mixed with immune cells (eg, T cells), and cultured in a medium to which a neoantigen-based therapeutic is added. In certain embodiments, the neoantigen therapeutic increases, stimulates, and/or enhances the activity of immune cells. In certain embodiments, the neoantigen therapeutic inhibits tumor cell growth. In certain embodiments, the neoantigen therapeutic agent activates the cytolysis of tumor cells.

[525] In certain embodiments, the individual is a human. In certain embodiments, the individual has a tumor, or the individual has had a tumor that has been at least partially removed.

[526] In certain embodiments, a method for inhibiting tumor growth includes redirecting an existing immune response to a new target, comprising administering to an individual a therapeutically effective amount of a neoantigen-based therapeutic agent, wherein the existing immune response is directed against an antigenic peptide delivered to a tumor cell by the neoantigenic peptide.

[527] In certain embodiments, the implementation of the tumor contains malignant stem cells. In certain embodiments, the incidence of malignant stem cells in a tumor is reduced by administration of a neoantigenic therapeutic agent. In certain embodiments, a method is provided for reducing the incidence of malignant stem cells in a tumor in an individual, comprising administering to the individual a therapeutically effective amount of a neoantigen-based therapeutic agent.

[528] In addition, in certain aspects, the invention relates to a method of reducing the oncogenicity of a tumor in an individual, comprising administering to the individual a therapeutically effective amount of a neoantigen-based therapeutic agent described in the present description. In certain embodiments, the implementation of the tumor contains malignant stem cells. In certain embodiments, the oncogenicity of a tumor is reduced by reducing the incidence of malignant stem cells in the tumor. In certain embodiments, the methods include the use of a neoantigen therapeutic agent as described herein. In certain embodiments, the incidence of malignant stem cells in a tumor is reduced by administration of a neoantigen therapeutic agent as described herein.

[529] In certain embodiments, the tumor is a solid tumor. In certain embodiments, the tumor is a tumor selected from the group consisting of: colorectal tumor, pancreatic tumor, lung tumor, ovarian tumor, liver tumor, breast tumor, kidney tumor, prostate tumor, neuroendocrine tumor, gastrointestinal tumor , melanoma tumors, cervical tumors, bladder tumors, glioblastomas, and head and neck tumors. In certain embodiments, the tumor is a colorectal tumor. In certain embodiments, the tumor is an ovarian tumor. In certain embodiments, the tumor is a breast tumor. In certain embodiments, the tumor is a lung tumor. In certain embodiments, the tumor is a pancreatic tumor. In certain embodiments, the tumor is a melanoma tumor. In certain embodiments, the tumor is a solid tumor.

[530] The present invention further relates to methods for treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of a neoantigen therapeutic agent described herein.

[531] In certain embodiments, a method of treating cancer comprises redirecting an existing immune response to a novel target, wherein the method comprises administering to the individual a therapeutically effective amount of a neoantigen-based therapeutic agent, wherein the existing immune response is directed against an antigenic peptide delivered to the cancer cell by the neoantigenic peptide.

[532] The present invention provides methods for treating cancer comprising administering to a subject a therapeutically effective amount of a neoantigen therapeutic agent described herein (eg, a subject in need of treatment). In certain embodiments, the individual is a human. In certain embodiments, the implementation of the individual suffers from a malignant tumor. In certain embodiments, the implementation of the individual suffered from a tumor at least partially resected.

[533] In certain embodiments, the cancer is a cancer selected from the group consisting of colorectal cancer, pancreatic cancer, lung cancer, ovarian cancer, liver cancer, breast cancer, kidney cancer, prostate cancer, gastrointestinal cancer, melanoma, cervical cancer, neuroendocrine cancer, bladder cancer, glioblastoma, and head and neck cancer. In certain embodiments, the cancer is pancreatic cancer. In certain embodiments, the cancer is ovarian cancer. In certain embodiments, the cancer is colorectal cancer. In certain embodiments, the cancer is breast cancer. In certain embodiments, the cancer is prostate cancer. In certain embodiments, the cancer is lung cancer. In certain embodiments, the cancer is a melanoma. In certain embodiments, the cancer is a solid cancer. In certain embodiments, the implementation of a malignant tumor contains a solid tumor.

[534] In certain embodiments, the cancer is a hematologic cancer. In a specific embodiment, the cancer is selected from the group consisting of: acute myelogenous leukemia (AML), Hodgkin's lymphoma, multiple myeloma, T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia, chronic myelogenous leukemia (CML), non-Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and cutaneous T-cell lymphoma (CTCL).

[535] In certain embodiments, the neoantigen therapeutic is administered as a combination treatment. Combination treatment with two or more therapeutic agents uses agents that work through different mechanisms of action, although this is not necessary. Combination treatment using an agent with different mechanisms of action may result in additive or synergistic effects. Combination treatment may allow a lower dose of each agent than is used in monotherapy, thus reducing toxic side effects and/or increasing the therapeutic index of the agent(s). Combination treatment may reduce the likelihood that resistant malignant cells will develop. In certain embodiments, the combination treatment includes a therapeutic agent that acts on (eg, enhances or activates) an immune response and a therapeutic agent that acts (eg, inhibits or kills) tumor/malignant cells.

[536] Malignant tumors include, but are not limited to, B-cell malignancy, e.g., multiple myeloma, Waldenström macroglobulinemia, heavy chain diseases such as, e.g., alpha heavy chain disease, gamma heavy chain disease, and mu- heavy chains, benign monoclonal gammopathy and immunocytic amyloidosis, melanomas, breast cancer, lung cancer, bronchial cancer, colorectal cancer, prostate cancer (eg, metastatic, hormone-resistant prostate cancer), pancreatic cancer, gastric cancer, ovarian cancer, cancer bladder cancer, brain or central nervous system cancer, peripheral nervous system cancer, esophageal cancer, cervical cancer, uterine or endometrial cancer, oral or pharyngeal cancer, liver cancer, kidney cancer, testicular cancer, bile duct cancer, cancer small intestine or appendix, salivary gland cancer, thyroid cancer, adrenal cancer, osteos arcoma, chondrosarcoma, malignant tumor of hematological tissues, etc. Other non-limiting examples of cancer types applicable to the methods of the present invention include human sarcomas and carcinomas, e.g., fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, tumor Ewing, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, liver cancer, choriocarcinoma, seminoma, fetal carcinoma, Wilms tumor, cervical cancer, bone cancer, brain tumor, testicular cancer, lung carcinoma, small cell carcinoma lung cancer, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma; leukemias, for example, acute lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia); chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia) and polycythemia vera, lymphoma (Hodgkin's disease and non-Hodgkin's lymphoma), multiple myeloma, Waldenström's macroglobulinemia and heavy chain disease. In certain embodiments, the cancer whose phenotype is determined by the method of the invention is an epithelial cancer, such as, but not limited to, bladder cancer, breast cancer, cervical cancer, colon cancer, gynecological cancer, kidney cancer, throat cancer, lung cancer, oral cancer, head and neck cancer, ovarian cancer, pancreatic cancer, prostate cancer, or skin cancer. In other embodiments, the cancer is breast cancer, prostate cancer, lung cancer, or colon cancer. In other embodiments, the epithelial cancer is non-small cell lung cancer, non-papillary renal cell carcinoma, cervical carcinoma, ovarian carcinoma (eg, serous ovarian carcinoma), or breast carcinoma. Epithelial cancers can be characterized in a number of other ways, including, but not limited to, serous, endometrioid, mucoid, clear cell, Brenner, or undifferentiated. In certain embodiments, the present invention is used in the treatment, diagnosis, and/or prognosis of lymphoma or subtypes thereof, including, but not limited to, mantle cell lymphoma. Lymphoproliferative disorders are also considered proliferative diseases.

[537] In certain embodiments, the combination of an agent described herein and at least one additional therapeutic agent results in additive or synergistic results. In certain embodiments, the combination treatment results in an increase in the therapeutic index of the agent. In certain embodiments, the combination treatment results in an increase in the therapeutic index of the additional therapeutic agent(s). In certain embodiments, the combination treatment results in a reduction in toxicity and/or side effects of the agent. In certain embodiments, the combination treatment results in a reduction in toxicity and/or side effects of the additional therapeutic agent(s).

[538] In certain embodiments, in addition to administering a neoantigen therapeutic agent described herein, the method or treatment further comprises administering at least one additional therapeutic agent. The additional therapeutic agent may be administered before, simultaneously with, and/or after administration of the agent. In certain embodiments, at least one additional therapeutic agent includes 1, 2, 3 or more additional therapeutic agents.

[539] Therapeutic agents that can be administered in combination with a neoantigen therapeutic agent described herein include chemotherapeutic agents. Thus, in certain embodiments, the method or treatment comprises administering an agent described herein in combination with a chemotherapeutic agent or in combination with a mixture of chemotherapeutic agents. Treatment with the agent can be carried out before, simultaneously with or after chemotherapy. Combined administration may include co-administration in the same pharmaceutical formulation or using separate formulations, or sequential administration in any order, but generally over such a period of time that all active agents can exhibit their biological activities simultaneously. The preparation and dosing regimens of each of the chemotherapeutic agents may be used according to the manufacturer's instructions or as empirically determined by the practitioner. The drug and dosing schedules for each chemotherapy are also described in The Chemotherapy Source Book, 4th Edition, 2008, M. C. Perry, Editor, Lippincott, Williams & Wilkins, Philadelphia, PA.

[540] Suitable classes of chemotherapeutic agents include, for example, antitubulin agents, auristatins, DNA minor groove binding agents, inhibitors of DNA replication, alkylating agents (e.g., platinum complexes such as cisplatin, mono(platinum), bis(platinum), and trinuclear complexes platinum and carboplatin), anthracyclines, antibiotics, antifolates, antimetabolites, chemosensitiser, duocarmycin, etoposide, fluorinated pyrimidines, ionophores, lexitropsins, nitrosoureas, platinols, purine antimetabolites, puromycins, radiation sensitizer, steroids, taxanes, topoisomerase inhibitors, vinca alkaloids; or the like. In certain embodiments, the second therapeutic agent is an alkylating agent, an antimetabolite, an antimitotic agent, a topoisomerase inhibitor, or an angiogenesis inhibitor.

[541] Chemotherapeutic agents useful in the present invention include, but are not limited to, alkylating agents such as thiotepa and cyclophosphamide (CYTOXAN); alkylsulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carbokwon, meturedopa and uredopa; ethyleneimines and methylamelainin, including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylolmelamine; nitrogen mustards such as chlorambucil, chlornaphasine, holofosfamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembihin, fenestein, prednimustine, trofosfamide, uramustine; nitrosoureas such as carmustine, chlorzotocin, fotemustine, lomustine, nimustine, ranimustine; antibiotics such as aclacinomycins, actinomycin, autramycin, azaserin, bleomycins, cactinomycin, calichimicin, carabicin, kanomycin, carsinophilin, chromomycins, dactinomycin, daunorubicin, detoubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, pyromycin, quelamycin, rhodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimetricsate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprin, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytosine arabinoside, dideoxyuridine, doxyfluridine, enocytabine, floxuridine, 5-FU; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenal agents such as aminoglutethimide, mitotane, trilostane; folic acid supplements such as floric acid; aceglatone; glycoside aldophosphamide aminolevulinic acid; amsacrine; bestrabucil; bisantren, edatraksat; defofamine; demecolcin; diaziquon; elfornitine; elliptin acetate; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainin; mitaguazone; mitoxantrone; mopidanmol; nitracrine; pentostatin; phenamet; pyrarubicin; losoxantrone; podophyllic acid; 2-ethylhydrazide; procarbazine; PSK; razoxane; sisofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; urethane; vindesine; dacarbazine; mannomostine; mitobronitol; mitolactol; pipobroman; hacytosine; arabinoside (Ara-C); taxoids such as paclitaxel (TAXOL) and docetaxel (TAXOTHER); chlorambucil; gemcitabine ; 6-thioguanine; mercaptopurine; platinum analogues such as cisplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitomycin C; mitoxantrone; vincristine; vinorelbine; navelbin; novantrone; teniposide; daunomycin; aminopterin; ibandronate; CPT11, topoisomerase inhibitor RFS 2000, difluoromethylornithine (DMFO), retinoic acid, esperamycins, capecitabine (XELODA), and pharmaceutically acceptable salts, acids, or derivatives of any of the compounds listed above. tumors such as antiestrogen including, for example, tamoxifen, raloxifene, aromatase-inhibiting 4(5)-imidazoles, 4-hydroxy tamoxifen, trioxifene, keoxy fen, LY117018, onapristone and toremifene (FARESTON), and antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide and goserelin, and pharmaceutically acceptable salts, acids or derivatives of any of the above compounds. In certain embodiments, the additional therapeutic agent is cisplatin. In certain embodiments, the additional therapeutic agent is carboplatin.

[542] In certain embodiments, the chemotherapeutic agent is a topoisomerase inhibitor. Topoisomerase inhibitors are chemotherapeutic agents that interfere with the action of the topoisomerase enzyme (eg, topoisomerase I or II). Topoisomerase inhibitors include, but are not limited to, doxorubicin HCl, daunorubicin citrate, mitoxantrone HCl, actinomycin D, etoposide, topotecan HCl, teniposide (VM-26) and irinotecan, as well as pharmaceutically acceptable salts, acids or derivatives of any of the above compounds. In certain embodiments, the additional therapeutic agent is irinotecan.

[543] In certain embodiments, the chemotherapeutic agent is an antimetabolite. An antimetabolite is a chemical compound with a structure that is similar to a metabolite required for normal biochemical reactions, but different enough to interfere with one or more of the normal functions of cells, such as cell division. Antimetabolites include, but are not limited to, gemcitabine, fluorouracil, capecitabine, sodium methotrexate, ralitrexed, pemetrexed, tegafur, cytosine arabinoside, thioguanine, 5-azacytidine, 6-mercaptopurine, azathioprine, 6-thioguanine, pentostatin, fludarabine phosphate, and cladribine, as well as the pharmaceutical acceptable salts, acids or derivatives of any of the above compounds. In certain embodiments, the additional therapeutic agent is gemcitabine.

[544] In certain embodiments, the chemotherapeutic agent is an antimitotic agent, including, but not limited to, agents that bind tubulin. In certain embodiments, the agent is a taxane. In certain embodiments, the agent is paclitaxel or docetaxel, or a pharmaceutically acceptable salt, acid, or derivative of paclitaxel or docetaxel. In certain embodiments, the agent is paclitaxel (TAXOL), docetaxel (TAXOTHER), albumin-bound paclitaxel (ABRAXAN), DHA-paclitaxel, or PG-paclitaxel. In certain alternative embodiments, the antimitotic agent comprises a vinca alkaloid such as vincristine, vinblastine, vinorelbine, or vindesine, or pharmaceutically acceptable salts, acids, or derivatives thereof. In certain embodiments, the antimitotic agent is an Eg5 kinesin inhibitor or a mitotic kinase inhibitor such as Aurora A or Plk1. In certain embodiments, the additional therapeutic agent is paclitaxel. In certain embodiments, the additional therapeutic agent is albumin-bound paclitaxel.

[545] In certain embodiments, the implementation of additional therapeutic agent includes an agent, such as a small molecular weight compound. For example, treatment may include the combined administration of an agent of the present invention with a small molecule compound that acts as an inhibitor against tumor-associated antigens, including, but not limited to, EGFR, HER2 (ErbB2) and/or VEGF. In certain embodiments, the agent of the present invention is administered in combination with a protein kinase inhibitor selected from the group consisting of: gefitinib (IRESSA), erlotinib (TARCEVA), sunitinib (SUTENT), lapatanib, vandetanib (ZACTIMA), AEE788, CI-1033, cediranib (RESENTIN), sorafenib (NEXAVAR), and pazopanib (GW786034B). In certain embodiments, the additional therapeutic agent contains an mTOR inhibitor. In another embodiment, the additional therapeutic agent is chemotherapy or other inhibitors that decrease the number of Treg cells. In certain embodiments, the therapeutic agent is a cyclophosphamide or an anti-CTLA4 antibody. In another embodiment, the additional therapeutic agent reduces the presence of myeloid suppressor cells. In an additional embodiment, the additional therapeutic agent is carbotaxol. In another embodiment, the additional therapeutic agent shifts cells toward a T helper 1 response. In an additional embodiment, the additional therapeutic agent is ibrutinib.

[546] In certain embodiments, the implementation of additional therapeutic agent contains a biological molecule, such as an antibody. For example, treatment may include the combined administration of an agent of the present invention with antibodies to tumor-associated antigens, including, but not limited to, antibodies that bind EGFR, HER2/ErbB2 and/or VEGF. In certain embodiments, the additional therapeutic agent is an antibody specific for malignant stem cell markers. In certain embodiments, the additional therapeutic agent is an antibody that is an inhibitor of angiogenesis (eg, an antibody to VEGF or the VEGF receptor). In certain embodiments, the additional therapeutic agent is bevacizumab (AVASTIN), ramucirumab, trastuzumab (HERCEPTIN), pertuzumab (OMNITARG), panitumumab (VECTIBIX), nimotuzumab, zalutumumab, or cetuximab (ERBITUX).

[547] The agents and compositions provided herein may be used alone or in combination with conventional treatment regimens such as surgery, radiation, chemotherapy, and/or bone marrow transplantation (autologous, syngeneic, allogeneic, or unrelated). A set of tumor antigens may be useful, for example, in a large proportion of patients with malignant tumors.

[548] In certain embodiments, at least one or more chemotherapeutic agents can be administered in addition to a composition containing an immunogenic vaccine. In certain embodiments, one or more chemotherapeutic agents may belong to different classes of chemotherapeutic agents.

[549] Examples of chemotherapeutic agents include, but are not limited to, alkylating agents such as nitrogen mustards (eg, mechlorethamine (nitrogen mustard), chlorambucil, cyclophosphamide (Cytoxan®), ifosfamide, and melphalan); nitrosoureas (eg, N-nitro-N-methylurea, streptozocin, carmustine (BCNU), lomustine, and semustine); alkylsulfonates (eg busulfan); tetrazines (eg dacarbazine (DTIC), mitozolomide and temozolomide (Temodar®)); aziridines (eg, thiotepa, mitomycin, and diaziquone); platinum-based drugs (eg cisplatin, carboplatin and oxaliplatin); non-classical alkylating agents such as procarbazine and altretamine (hexamethylmelamine); antimetabolites such as 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), capecitabine (Xeloda®), cladribine, chlorofarabine, cytarabine (Ara-C®), defitabine, floxuridine, fludarabine, nelarabine, gemcitabine ( Gemzar®), hydroxyurea, methotrexate, pemetrexed (Alimta®), pentostatin, thioguanine, vidase; anti-microtubule agents such as vinca alkaloids (eg vincristine, vinblastine, vinorelbine, vindesine and vinflunine); taxanes (eg paclitaxel (Taxol®), docetaxel (Taxotere®)); podophyllotoxin (eg, etoposide and teniposide); epothilones (eg, ixabepilone (Ixempra®)); estramustine (Emcyt®); anticancer antibiotics such as anthracyclines (eg daunorubicin, doxorubicin (Adriamycin®, epirubicin, idarubicin); actinomycin D and bleomycin; topoisomerase I inhibitors such as topotecan and irinotecan (CPT-11); topoisomerase II inhibitors such as etoposide (VP -16), teniposide, mitoxantrone, novobiocin, merbarone, and aclarubicin; corticosteroids such as prednisone, methylprednisolone (Solumedrol®) and dexamethasone (Decadron®); L-asparaginase; bortezomib (Velcade®); immunotherapy agents such as rituximab (Rituxan ®), alemtuzumab (Campath®), thalidomide, lenalidomide (Revlimid®), BCG, interleukin-2, interferon-alpha, and cancer vaccines such as Provenge®; hormone therapies such as fulvestrant (Faslodex®), tamoxifen , toremifene (Fareston®), anastrozole (Arimidex®), exemestane (Aromasin®), letrozole ((Femara®), megestrol acetate (Megace®), estrogens, bicalutamide (Casodex®), flutamide (Eulexin®), nilutamide (Nilandron® ), leupro lead (Lupron®) and goserelin (Zoladex®); differentiation agents such as retinoids, tretinoin (ATRA or Atralin®), bexarotene (Targretin®) and arsenic trioxide (Arsenox®) and targeted therapeutics such as imatinib (Gleevec®), gefitinib (Iressa®) and sunitinib (Sutent® ). In certain embodiments, the chemotherapy is a "cocktail" therapy. Examples of "cocktail" therapy include, but are not limited to, CHOP/R-CHOP (rituxan, cyclophosphamide, hydroxydoxorubicin, vincristine, and prednisone), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, hydroxydoxorubicin), Hyper-CVAD (cyclophosphamide, vincristine, hydroxydoxorubicin, dexamethasone), FOLFOX (fluorouracil (5-FU), leucovorin, oxaliplatin), ICE (ifosfamide, carboplatin, etoposide), DHAP (high dose cytarabine [ara-C], dexamethasone, cisplatin), ESHAP (etoposide, methylprednisolone , cytarabine [ara-C], cisplatin) and CMF (cyclophosphamide, methotrexate, fluorouracil).

[550] In certain embodiments, the additional therapeutic agent comprises a second immunotherapeutic agent. In certain embodiments, the additional immunotherapeutic agent includes, but is not limited to, a colony stimulating factor, an interleukin, an antibody that blocks immunosuppressive functions (e.g., anti-CTLA-4 antibody, anti-CD28 antibody, anti-CD3 antibody, anti-PD-1 antibody, anti- PD-L1, anti-TIGIT antibody), antibody that enhances immune cell functions (eg, anti-GITR antibody, anti-OX-40 antibody, anti-CD40 antibody, or anti-4-1BB antibody), Toll-like receptor (eg, TLR4, TLR7 , TLR9), a soluble ligand (e.g., GITRL, GITRL-Fc, OX-40L, OX-40L-Fc, CD40L, CD40L-Fc, 4-1BB ligand, or 4-1BB ligand-Fc), or a member of the B7 family (e.g., CD80, CD86). In certain embodiments, the additional immunotherapeutic agent targets CTLA-4, CD28, CD3, PD-1, PD-L1, TIGIT, GITR, OX-40, CD-40, or 4-1BB.

[551] In certain embodiments, the additional therapeutic agent is an immune checkpoint inhibitor. In certain embodiments, the immune checkpoint inhibitor is an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody, an anti-CD28 antibody, an anti-TIGIT antibody, an anti-LAG3 antibody, an anti-TIM3 antibody, an anti-GITR antibody, an anti- 4-1BB or anti-OX-40 antibody. In certain embodiments, the additional therapeutic agent is an anti-TIGIT antibody. In certain embodiments, the additional therapeutic agent is an anti-PD-1 antibody selected from the group consisting of: nivolumab (OPDIVO), pemobrolizumab (KEYTRUDA), pidilzumab, MEDI0680, REGN2810, BGB-A317, and PDR001. In certain embodiments, the additional therapeutic agent is an anti-PD-L1 antibody selected from the group consisting of: BMS935559 (MDX-1105), atexolizumab (MPDL3280A), durvalumab (MEDI4736), and avelumab (MSB0010718C). In certain embodiments, the additional therapeutic agent is an anti-CTLA-4 antibody selected from the group consisting of: ipilimumab (EPBOI) and tremelimumab. In certain embodiments, the additional therapeutic agent is an anti-LAG-3 antibody selected from the group consisting of: BMS-986016 and LAG525. In certain embodiments, the additional therapeutic agent is an anti-OX-40 antibody selected from the group consisting of: MEDI6469, MEDI0562, and MOXR0916. In certain embodiments, the additional therapeutic agent is an anti-4-1BB antibody selected from the group consisting of: PF-05082566.

[552] In certain embodiments, the neoantigen therapeutic can be administered in combination with a biological molecule selected from the group consisting of: adrenomedullin (AM), angiopoietin (Ang), BMP, BDNF, EGF, erythropoietin (EPO), FGF, GDNF, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), stem cell factor (SCF), GDF9, HGF, HDGF, IGF, migration stimulating factor, myostatin (GDF-8), NGF, neurotrophins, PDGF, thrombopoietin, TGFα, TGFβ, TNFα, VEGF, PlGF, IFN-gamma, IL-1, IL-2, IL-3, IL-4, IL-5, IL -6, IL-7, IL-12, IL-15 and IL-18.

[553] In certain embodiments, treatment with a neoantigen therapeutic agent described herein may be accompanied by surgical removal of tumors, removal of malignant cells, or any other surgical therapy deemed necessary by the attending physician.

[554] In certain embodiments, the implementation of the treatment includes the introduction of a therapeutic agent based neoantigen described in the present description, in combination with radiation therapy. Treatment with the agent can be carried out before, simultaneously or sequentially with radiation therapy. A physician skilled in the art can determine dosing regimens for such radiation therapy.

[555] Combination administration may include co-administration in the same pharmaceutical formulation or using separate formulations, or sequential administration in any order, but generally over such a period of time that all active agents can exhibit their biological activities simultaneously.

[556] It should be understood that the combination of a neoantigen-based therapeutic agent described herein and at least one additional therapeutic agent can be administered in any order or simultaneously. In certain embodiments, the agent is administered to patients who have previously received treatment with a second therapeutic agent. In certain other embodiments, the neoantigen therapeutic and the second therapeutic are administered substantially simultaneously or together. For example, an individual may receive an agent during a course of treatment with a second therapeutic agent (eg, chemotherapy). In certain embodiments, the neoantigen therapeutic is administered during 1 year of treatment with the second therapeutic. It will further be appreciated that two (or more) agents or treatments may be administered to an individual within hours or minutes (ie, substantially simultaneously).

[557] For the treatment of a disease, an appropriate dose of a neoantigen therapeutic agent described herein depends on the type of disease being treated, the severity and course of the disease, the response of the disease, whether the agent is administered for therapeutic or prophylactic purposes, previous therapy, clinical history patient, etc., all at the discretion of the attending physician. The neoantigen therapeutic may be administered once or over a series of treatment cycles ranging from several days to several months, or until treatment is given or a reduction in the disease state (eg, reduction in tumor size) is obtained. Optimal dosing regimens are calculated based on measurements of drug accumulation in the patient's body, and they vary depending on the relative potency of the individual agent. The administering physician can determine the optimal doses, dosing methods and frequency of repetitions.

[558] In certain embodiments, the neoantigen therapeutic may be administered at an initial higher "loading" dose followed by one or more lower doses. In certain embodiments, the frequency of administration can also be varied. In certain embodiments, the dosing regimen may include administering an initial dose followed by additional doses (or "maintenance" doses) once a week, once every two weeks, once every three weeks, or once every month. For example, the dosing regimen may include administering an initial loading dose followed by a weekly maintenance dose, eg, half the initial dose. Or, the dosing regimen may include administration of an initial loading dose followed by maintenance doses, for example, half of the initial dose a week later. Or, the dosing regimen may include the administration of three initial doses over 3 weeks, followed by the administration of maintenance doses, for example, in the same amount a week later.

[559] As is known to those skilled in the art, administration of any therapeutic agent may result in side effects and/or toxicity. In some instances, side effects and/or toxicities are so severe as to preclude administration of a particular agent at a therapeutically effective dose. In some cases, therapy must be discontinued and other means may be tried. However, many drugs in the same therapeutic class have similar side effects and/or toxicities, which means that the patient either has to stop therapy or, if possible, suffer from unpleasant side effects associated with the therapeutic agent.

[560] In certain embodiments, the dosing regimen may be limited to a specific number of administrations or "cycles". In certain embodiments, the agent is administered for 3, 4, 5, 6, 7, 8 or more cycles. For example, an agent is administered every 2 weeks for 6 cycles, an agent is administered every 3 weeks for 6 cycles, an agent is administered every 2 weeks for 4 cycles, an agent is administered every 3 weeks for 4 cycles, and so on. Dosing regimens can be defined and then modified by those skilled in the art.

[561] The present invention relates to methods of administering to an individual a therapeutic agent based on the neoantigen described in the present description, including the use of an intermittent dosing strategy for administering one or more agents that can reduce side effects and / or toxicities associated with the administration of the agent, a chemotherapeutic agent etc. In certain embodiments, a method of treating cancer in a human subject comprises administering to the subject a therapeutically effective dose of a neoantigen-based therapeutic agent in combination with a therapeutically effective dose of a chemotherapeutic agent, wherein one or both are administered according to an intermittent dosing strategy. In certain embodiments, a method of treating cancer in a human subject comprises administering to the subject a therapeutically effective dose of a neoantigen-based therapeutic agent in combination with a therapeutically effective dose of a second immunotherapeutic agent, wherein one or both are administered according to an intermittent dosing strategy. In certain embodiments, an intermittent dosing strategy comprises administering an initial dose of a neoantigen-based therapeutic agent to an individual and administering subsequent doses of the agent approximately once every 2 weeks. In certain embodiments, the intermittent dosing strategy comprises administering an initial dose of a neoantigen-based therapeutic agent to an individual, and administering subsequent doses of the agent about once every 3 weeks. In certain embodiments, the intermittent dosing strategy comprises administering an initial dose of a neoantigen-based therapeutic agent to an individual and administering subsequent doses of the agent approximately once every 4 weeks. In certain embodiments, the agent is administered using an intermittent dosing strategy and the additional therapeutic agent is administered weekly.

[562] The present invention relates to compositions containing a therapeutic agent based on the neoantigen described in the present description. The present invention also relates to pharmaceutical compositions comprising the neoantigen therapeutic described herein and a pharmaceutically acceptable carrier. In certain embodiments, pharmaceutical compositions find use in immunotherapy. In certain embodiments, the compositions find use in inhibiting tumor growth. In certain embodiments, pharmaceutical compositions find use in inhibiting tumor growth in an individual (eg, a human patient). In certain embodiments, the compositions find use in the treatment of cancer. In certain embodiments, the pharmaceutical compositions find use in the treatment of cancer in an individual (eg, a human patient).

[563] Formulations are prepared for storage and use by combining the neoantigen therapeutic of the present invention with a pharmaceutically acceptable carrier (eg, carrier or excipient). Those skilled in the art generally consider pharmaceutically acceptable carriers, excipients and/or stabilizers to be the inactive ingredients of a formulation or pharmaceutical composition. Illustrative compositions are given in WO 2015/095811.

[564] Suitable pharmaceutically acceptable carriers include, but are not limited to, non-toxic buffers such as phosphate, citrate and other organic acids; salts such as sodium chloride; antioxidants including ascorbic acid and methionine; preservatives such as octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, alkyl parabens such as methyl paraben or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol and m-cresol; low molecular weight polypeptides (eg, less than about 10 amino acid residues); proteins such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; carbohydrates such as monosaccharides, disaccharides, glucose, mannose or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium; metal complexes such as Zn-protein complexes; and non-ionic surfactants such as TWEEN or polyethylene glycol (PEG). (Remington: The Science and Practice of Pharmacy, 22st Edition, 2012, Pharmaceutical Press, London). In certain embodiments, the carrier is 5% dextrose in water.

[565] The pharmaceutical compositions described herein can be administered in any number of ways for local or systemic treatment. Administration may be topical via epidermal or transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders; pulmonary by inhalation or insufflation of powders or aerosols, including by nebulizer, intratracheal and intranasal; oral or parenteral, including intravenous, intraarterial, intratumoral, subcutaneous, intraperitoneal, intramuscular (eg, injection or infusion), or intracranial (eg, intrathecal or intraventricular).

[566] The therapeutic composition may be in unit dosage form. Such formulations include tablets, pills, capsules, powders, granules, solutions or suspensions in water or non-aqueous vehicles, or suppositories.

[567] The neoantigenic peptides described herein can also be microencapsulated. Such microcapsules are prepared, for example, by coacervation methods or by interfacial polymerization, for example, microcapsules of hydroxymethylcellulose or gelatin and microcapsules of poly(methyl methacrylate), respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in microemulsions as described in Remington: The Science and Practice of Pharmacy, 22st Edition, 2012, Pharmaceutical Press, London.

[568] In certain embodiments, the implementation of the pharmaceutical compositions contain a therapeutic agent based neoantigen described in the present description, in combination with liposomes. Methods for preparing liposomes are known to those skilled in the art. For example, some liposomes can be prepared by reverse phase evaporation with a lipid composition containing phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes can be forced through filters of a certain pore size to obtain liposomes with the desired diameter.

[569] In certain embodiments, sustained release preparations containing the neoantigenic peptides described herein can be obtained. Suitable examples of sustained release formulations include semi-permeable matrices of solid hydrophobic polymers containing the agent, where the matrices are in the form of shaped articles (eg, films or microcapsules). Examples of sustained release matrices include polyesters, hydrogels such as poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol), polylactides, copolymers of L-glutamic acid and 7-ethyl-L-glutamate, non-degradable ethylene-vinyl acetate copolymers, degradable lactic acid-glycolic acid such as LUPRON DEPOT™ (injectable microspheres consisting of a copolymer of lactic acid-glycolic acid and leuprolide acetate), sucrose acetate isobutyrate and poly-D-(-)-3-hydroxybutyric acid.

[570] the Present invention relates to methods of treatment, including immunogenic vaccine. Methods for treating a disease (such as a cancer or a viral infection) are provided. The method may include administering to the subject an effective amount of a composition containing an immunogenic antigen. In certain embodiments, the antigen is a viral antigen. In certain embodiments, the antigen is a tumor antigen.

[571] Non-limiting examples of vaccines that can be obtained include a peptide-based vaccine, a nucleic acid-based vaccine, an antibody-based vaccine, a T-cell-based vaccine, and an antigen-presenting cell-based vaccine.

[572] Vaccine compositions can be formulated using one or more physiologically acceptable carriers, including excipients and adjuvants that facilitate the processing of active agents into formulations that can be used for pharmaceutical purposes. The correct composition can be selected depending on the route of administration. Any of the known methods, carriers and excipients can be used as appropriate and understood in this field.

[573] In some cases, the vaccine composition is formulated as a peptide-based vaccine, a nucleic acid-based vaccine, an antibody-based vaccine, or a cell-based vaccine. For example, the vaccine composition may contain naked cDNA in cationic lipid formulations; lipopeptides (e.g., Vitiello A. et al., J. Clin. Invest. 95:341, 1995), naked cDNA, or peptides encapsulated, for example, in poly(DL-lactide-coglycolide) ("PLG") microspheres (see eg Eldridge, et al., Molec Immunol 28:287-294, 1991: Alonso et al, Vaccine 12:299-306, 1994; Jones et al, Vaccine 13:675-681, 1995); peptide composition contained in immunostimulatory complexes (ISCOMS) (eg, Takahashi et al, Nature 344:873-875, 1990; Hu et al, Clin Exp Immunol. 113:235-243, 1998); or multiple antigenic peptide (MAP) systems (see, for example, Tam, J. P., Proc. Natl Acad. Sci. U.S.A. 85:5409-5413, 1988; Tarn, J.P., J. Immunol. Methods 196:17-32, 1996 ). In some cases, the vaccine is formulated as a peptide-based vaccine or a nucleic acid-based vaccine in which the nucleic acid encodes polypeptides. In some cases, the vaccine is formulated as an antibody-based vaccine. In some cases, the vaccine is formulated as a cell-based vaccine.

[574] The amino acid sequence of the identified disease-specific immunogenic neoantigenic peptide can be used to develop a pharmaceutically acceptable composition. The antigen source can be, but is not limited to, natural or synthetic proteins, including glycoproteins, peptides, and superantigens; antibody/antigen complexes; lipoproteins; RNA or its translation product; and DNA or a polypeptide encoded by the DNA. The antigen source may also contain untransformed, transformed, transfected or transduced cells or cell lines. Cells can be transformed, transfected or transduced using any of a number of expression or retroviral vectors known to those skilled in the art that can be used to express recombinant antigens. Expression can also be obtained in any suitable host cell that has been transformed, transfected or transduced with an expression or retroviral vector containing a DNA molecule encoding the recombinant antigen(s). Any number of transfection, transformation and transduction protocols known to those skilled in the art can be used. Recombinant vaccinia vectors and cells infected with the vaccinia vector can be used as an antigen source.

[575] The composition may contain a synthetic disease-specific immunogenic neoantigenic peptide. The composition may contain two or more disease-specific immunogenic neoantigenic peptides. The composition may contain a disease-specific immunogenic peptide precursor (such as protein, peptide, DNA and RNA). The disease-specific immunogenic peptide precursor can be formed or formed in the identified disease-specific immunogenic neoantigenic peptide. In certain embodiments, the therapeutic composition comprises an immunogenic peptide precursor. The disease-specific immunogenic peptide precursor may be a prodrug. In certain embodiments, a composition comprising a disease-specific immunogenic neoantigenic peptide may further comprise an adjuvant. For example, the neoantigenic peptide can be used as a vaccine. In certain embodiments, the implementation of the immunogenic vaccine may contain a pharmaceutically acceptable immunogenic neoantigenic peptide. In certain embodiments, the implementation of the immunogenic vaccine may contain a pharmaceutically acceptable precursor of the immunogenic neoantigenic peptide (such as protein, peptide, DNA and RNA). In certain embodiments, the method of treatment comprises administering to the subject an effective amount of an antibody specifically recognizing an immunogenic neoantigenic peptide. In certain embodiments, the method of treatment comprises administering to the subject an effective amount of a soluble TCR or TCR analog that specifically recognizes an immunogenic neoantigenic peptide.

[576] The methods described herein are particularly useful in personalized medicine, where immunogenic neoantigenic peptides are used to develop therapeutic agents (such as vaccines or therapeutic antibodies) for the same individual. Thus, a method of treating a disease in an individual may include identifying an immunogenic neoantigenic peptide in the individual by the methods described herein; and synthesis of the peptide (or its precursor); and administering the peptide or antibody specifically recognizing the peptide to the subject. In certain embodiments, the expression profile of an immunogenic neoantigen can serve as the main basis for obtaining personalized vaccines for a particular patient. In certain embodiments, the expression profile of an immunogenic neoantigen can serve as the main basis for obtaining vaccines for a group of patients with a particular disease. Thus, specific diseases, such as specific types of tumors, can be selectively treated in a group of patients.

[577] In certain embodiments, the peptides described herein are structurally normal (“shared”) antigens that can be recognized by autologous disease-targeting T cells in a large subset of patients. In certain embodiments, the antigen expression profile of a group of diseased individuals whose disease expresses structurally normal ("shared") neoantigens is determined.

[578] There are a number of ways to obtain immunogenic neoantigens. Proteins or peptides can be produced by any method known to those skilled in the art, including expression of proteins, polypeptides, or peptides by standard molecular biology techniques, isolation of proteins or peptides from natural sources, in vitro translation, or chemical synthesis of proteins or peptides. In general, such disease-specific neoantigens can be generated in vitro or in vivo . Immunogenic neoantigens can be produced in vitro as peptides or polypeptides, which can then be formulated into a personalized vaccine or immunogenic composition and administered to an individual. In vitro production of immunogenic neoantigens may involve peptide synthesis or expression of a peptide/polypeptide from a DNA or RNA molecule in any of a number of bacterial, eukaryotic, or viral recombinant expression systems, followed by purification of the expressed peptide/polypeptide. Alternatively, immunogenic neoantigens can be produced in vivo by introducing molecules (eg, DNA, RNA, and viral expression systems) that encode an immunogenic neoantigen into an individual, after which the encoded immunogenic neoantigens are expressed. In certain embodiments, a polynucleotide encoding an immunogenic neoantigenic peptide can be used to generate the neoantigenic peptide in vitro .

[579] In certain embodiments, the implementation of the polynucleotide contains a sequence with at least 60%, 65%, 70%l, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity to the polynucleotide encoding the immunogenic neoantigen.

[580] A polynucleotide can be, for example, DNA, cDNA, PNA, CNA, RNA, single-stranded and/or double-stranded, native or stabilized forms of polynucleotides, or combinations thereof. A nucleic acid encoding an immunogenic neoantigenic peptide may or may not contain introns, provided that it encodes a peptide. In certain embodiments, in vitro translation is used to produce the peptide.

[581] Expression vectors containing neoantigen coding sequences as well as host cells containing expression vectors are also contemplated. Expression vectors suitable for use in the present invention may contain at least one expression control element operably linked to a nucleic acid sequence. Expression control elements are introduced into the vector to control and regulate the expression of the nucleic acid sequence. Examples of expression control elements are well known in the art and include, for example, the lac system, lambda phage operator and promoter regions, yeast promoters, and promoters derived from polyoma virus, adenovirus, retrovirus, or SV40. Additional functional elements include, but are not limited to, leader sequences, termination codons, polyadenylation signals, and any other sequences necessary or preferred for proper transcription and subsequent translation of the nucleic acid sequence in the host system. One skilled in the art will appreciate that the correct combination of expression control elements will depend on the host system chosen. Further it will be understood that the expression vector must contain additional elements necessary for the transfer and subsequent replication of the expression vector containing the nucleic acid sequence in the host system. Examples of such elements include, but are not limited to, origins of replication and selectable markers.

[582] Neoantigenic peptides can be provided in the form of RNA or cDNA molecules encoding the desired neoantigenic peptides. One or more neoantigenic peptides of the invention may be encoded by a single expression vector. Typically, the DNA is introduced into an expression vector, such as a plasmid, in the correct orientation and in the correct reading frame for expression, if necessary, the DNA can be linked to suitable regulatory control nucleotide sequences for transcription and translation recognized by the desired host (e.g., bacteria), although such controls are typically available on the expression vector. The vector is then introduced into host bacteria for cloning by standard methods. Suitable expression vectors for eukaryotic hosts, especially mammals or humans, include, for example, vectors containing expression control sequences from SV40, bovine papillomavirus, adenovirus, and cytomegalovirus. Suitable expression vectors for bacterial hosts include known bacterial plasmids such as plasmids from E. coli including pCR 1, pBR322, pMB9 and their derivatives, broader host range plasmids such as M13, and single-stranded DNA filamentous phages.

[583] In embodiments, a DNA sequence encoding a polypeptide of interest can be constructed by chemical synthesis using an oligonucleotide synthesizer. Such oligonucleotides can be designed based on the amino acid sequence of the desired polypeptide and codons chosen that are preferred in the host cell in which the recombinant polypeptide of interest is being produced. Standard methods can be used to synthesize an isolated polynucleotide sequence encoding an isolated polypeptide of interest.

[584] Suitable host cells for polypeptide expression include prokaryotic, yeast, insect, or higher eukaryotic cells under the control of suitable promoters. Prokaryotes include Gram-negative or Gram-positive organisms such as E. coli or bacilli . Higher eukaryotic cells include developed cell lines derived from mammals. Cell-free translation systems can be used. Suitable cloning and expression vectors for use with bacterial, fungal, yeast and mammalian host cells are well known in the art. Various mammalian or insect cell culture systems can be used to express the recombinant protein. Exemplary mammalian host cell lines include, but are not limited to, COS-7, L cells, C127, 3T3, Chinese hamster ovary (CHO), 293, HeLa, and BHK cell lines. Mammalian expression vectors may contain non-transcribed elements such as an origin of replication, an appropriate promoter and enhancer associated with the gene to be expressed, and other 5' or 3' flanking non-transcribed sequences, and 5' or 3' non-translated sequences. such as essential ribosome binding sites, polyadenylation sites, splicing donor and acceptor sites, and transcription termination sequences.

[585] Proteins produced by the transformed host can be purified by any suitable method. Such standard methods include chromatography (eg, ion exchange, affinity and size distribution column chromatography, etc.), centrifugation, differential solubility, or any other standard protein purification method. Affinity tags such as hexahistidine, maltose binding domain, flu coat influenza coat sequence, glutathione S-transferase, and the like. can be attached to a protein for ease of purification by passing through a suitable affinity column. Isolated proteins can also be physically characterized using methods such as proteolysis, nuclear magnetic resonance, and X-ray diffraction crystallography.

[586] The vaccine may contain a structure that binds to the polypeptide sequence described in the present description. The structure may be an antibody. An antibody based vaccine can be formulated using any of the well known methods, carriers and excipients as is generally accepted and understood in the art. In certain embodiments, the peptides described herein can be used to produce neoantigen-specific therapeutics, such as antibody-based therapeutics. For example, neoantigens can be used to induce and/or identify antibodies specifically recognizing neoantigens. These antibodies can be used as therapeutic agents. The antibody may be a natural antibody, a chimeric antibody, a humanized antibody, or may be an antibody fragment. An antibody may recognize one or more of the polypeptides described herein. An antibody can recognize a polypeptide that contains a sequence that is no more than 40%, 50%, 60%, 70%, 80%, 90%, 95% or less homologous to the sequence of the polypeptide described herein. The antibody can recognize a polypeptide that contains a sequence that is at least 40%, 50%, 60%, 70%, 80%, 90%, 95% or more homologous to the sequence of the polypeptide described in the present description. An antibody can recognize a polypeptide with a sequence length of at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or more of the sequence length of the polypeptide described herein. An antibody can recognize a polypeptide with a sequence length that is no more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or less of the sequence length of the polypeptide described herein.

[587] The present invention also contemplates the use of nucleic acid molecules as carriers for delivering neoantigenic peptides/polypeptides to an individual in need in vivo in the form of, for example, DNA/RNA vaccines.

[588] In certain embodiments, the vaccine is a nucleic acid vaccine. In certain embodiments, neoantigens can be administered to an individual using a plasmid. Plasmids can be introduced into animal tissues in a number of different ways, for example, by injection or aerosol instillation of naked DNA onto mucosal surfaces such as those of the nose and lungs. In certain embodiments, physical delivery can be used, such as using a "gene gun". The precise choice of expression vectors may depend on the peptides/polypeptides to be expressed and is within the skill of the art.

[589] In certain embodiments, the nucleic acid encodes an immunogenic peptide or a peptide precursor. In certain embodiments, the nucleic acid vaccine contains sequences flanking a sequence encoding an immunogenic peptide or peptide precursor. In certain embodiments, the nucleic acid vaccine contains more than one immunogenic epitope. In certain embodiments, the nucleic acid vaccine is a DNA vaccine. In certain embodiments, the nucleic acid vaccine is an RNA vaccine. In certain embodiments, the RNA-based vaccine contains mRNA. In certain embodiments, the RNA-based vaccine contains naked mRNA. In certain embodiments, the RNA-based vaccine contains a modified mRNA (eg, an mRNA protected from degradation using a protoamine, an mRNA containing a modified 5'-CAP structure, or an mRNA containing modified nucleotides). In certain embodiments, the RNA-based vaccine comprises a single-stranded mRNA.

[590] The polynucleotide may be substantially pure or contained in a suitable vector or delivery system. Suitable vectors and delivery systems include viral ones, such as systems based on adenovirus, vaccinia virus, retroviruses, herpes virus, adeno-associated virus, or hybrids containing elements of more than one virus. Non-viral delivery systems include cationic lipids and cationic polymers (eg, cationic liposomes).

[591] One or more neoantigenic peptides can be encoded and expressed in vivo using virus-based systems. Viral vectors can be used as recombinant vectors in the present invention, where a portion of the viral genome is removed to introduce new genes without compromising the infectivity of the virus. The viral vector of the present invention is a non-pathogenic virus. In certain embodiments, the viral vector has a tropism for a particular cell type in a mammal. In another embodiment, the viral vector of the present invention is capable of infecting professional antigen presenting cells such as dendritic cells and macrophages. In yet another embodiment of the present invention, the viral vector is capable of infecting any cell in a mammal. The viral vector can also infect tumor cells. Viral vectors useful in the present invention include, but are not limited to, a poxvirus such as ospavaccine virus, avian pox virus, chicken pox virus, and highly attenuated vaccinia virus (Ankara or MVA), retrovirus, adenovirus, baculovirus, and the like.

[592] The vaccine can be delivered in a variety of ways. Delivery routes may include oral (including buccal and sublingual), rectal, nasal, topical, transdermal patch, pulmonary, vaginal, suppository, or parenteral (including intramuscular, intraarterial, intrathecal, intradermal, intraperitoneal, subcutaneous and intravenous) administration or in a form suitable for administration by aerosolization, inhalation or insufflation. General information on drug delivery systems can be found in Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems (Lippencott Williams & Wilkins, Baltimore Md. (1999). The vaccine described herein may be administered into muscle or may be administered via intradermal or subcutaneous injection, or transdermally, such as by iontophoresis Epidermal administration of the vaccine may be used.

[593] In some cases, the vaccine can also be formulated for administration through the nasal passages. Formulations suitable for nasal administration, where the carrier is a liquid, may contain a coarse powder with a particle size, for example, in the range of from about 10 to about 500 micrometers, which is administered in the manner in which tobacco is taken, i. by rapid inhalation through the nasal passage from a container of powder held close to the nose. The formulation may be a nasal spray, nasal drops, or may be administered by aerosol administration via a nebulizer. The composition may contain aqueous or oily solutions of the vaccine.

[594] The vaccine may be a liquid preparation such as a suspension, syrup, or elixir. The vaccine may also be a preparation for parenteral, subcutaneous, intradermal, intramuscular or intravenous administration (eg, injection), such as a sterile suspension or emulsion.

[595] The vaccine may contain a substance for a single immunization, or may contain a substance for multiple immunizations (ie, a set of "multiple doses"). In multi-dose packages, it is preferable to introduce a preservative. As an alternative to (or in addition to) the inclusion of a preservative in multi-dose compositions, the compositions may be contained in a container with an aseptic disposal adapter.

[596] The vaccine can be administered in a dose volume of approximately 0.5 ml, although half the dose (ie, approximately 0.25 ml) may be administered to children. In some cases, the vaccine may be administered at a higher dose, such as approximately 1 ml.

[597] The vaccine can be administered in a treatment regimen with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more course doses. In some cases, the vaccine is administered according to the treatment regimen with 1, 2, 3 or 4 course doses. In some cases, the vaccine is administered according to the treatment regimen with 1 course dose. In some cases, the vaccine is administered according to a treatment regimen with 2 course doses.

[598] The first dose and the second dose can be administered separately at intervals of approximately 0 days, 1 day, 2 days, 5 days, 7 days, 14 days, 21 days, 30 days, 2 months, 4 months, 6 months, 9 months , 1 year, 1.5 years, 2 years, 3 years, 4 years or more.

[599] the Vaccine described in the present description, you can enter every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more years. In some instances, the vaccine described herein is administered every 2, 3, 4, 5, 6, 7 or more years. In some instances, the vaccine described herein is administered every 4, 5, 6, 7 or more years. In some cases, the vaccine described in the present description is administered once.

[600] Dosage examples are not limiting and are used only to illustrate specific dosing regimens for administering the vaccine described here. An effective amount for use in humans can be determined in animal models. For example, a human dosage may be formulated to achieve circulating, hepatic, local, and/or gastrointestinal concentrations found to be effective in animals. Based on animal and other types of data, those skilled in the art can determine effective amounts of a vaccine composition suitable for humans.

[601] An effective amount with reference to an agent or combination of agents generally means dosing regimens, routes of administration, formulations, etc. that have been recommended or approved by any of the various regulatory or advisory bodies in the medical or pharmaceutical field (e.g., the FDA , AMA) or manufacturer or supplier.

[602] In certain aspects, the vaccine and kit described in the present description can be stored from 2°C to 8°C. In some cases, the vaccine is not stored frozen. In some cases, the vaccine is stored at temperatures such as -20°C or -80°C. In some cases, the vaccine is stored without access to light.

VIII. Sets

[603] A therapeutic agent based on the neoantigen described in the present description can be provided in the form of a kit along with instructions for administration. Typically, the kit contains the desired neoantigen therapeutic in a container, unit dosage form, and instructions for administration. Additional therapeutic agents such as cytokines, lymphokines, checkpoint inhibitors, antibodies may also be included in the kit. Other kit components that are also desirable to include are, for example, a sterile syringe, reinjection doses, and other desired excipients.

[604] Also provided herein are kits and articles of manufacture for use with one or more of the methods described herein. Kits may contain one or more neoantigenic polypeptides. The kits may also contain nucleic acids that encode one or more polypeptides described herein, antibodies that recognize one or more polypeptides described herein, or APC-based cells activated with one or more polypeptides described herein. Kits may additionally contain adjuvants, reagents, and buffers necessary for formulating and delivering vaccines.

[605] Kits may also contain a carrier, package, or container that is divided into compartments to receive one or more containers, such as vials, test tubes, and the like, where each of the container(s) contains one of the individual elements, such as polypeptides and adjuvants for use in the method described in the present description. Suitable containers include, for example, bottles, vials, syringes, and test tubes. Containers can be made from various materials such as glass or plastic.

[606] Industrial products provided in the present description contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs, bottles, vials, bags, containers, bottles, and any packaging material suitable for the formulation selected and the intended route of administration and treatment. The kit typically contains labels listing the contents and/or instructions for use and package inserts with instructions for use. A set of instructions is usually also included.

[607] the Invention is described in more detail through specific examples. The following examples are provided for illustrative purposes and are not intended to limit the invention in any way. Those skilled in the art will readily recognize various non-critical parameters that can be changed or modified in order to obtain alternative embodiments of the invention. All patents, patent applications and cited publications listed in the present specification are incorporated herein by reference in their entirety.

EXAMPLES

Example 1 Identification of Mutant Sequences with Immunogenic Potential

[608] Applicants have discovered mutations that are often found in patients with malignant tumors. See tables 1 and 2.

[609] The neoantigenic peptides described herein can be derived from the mutations shown in Tables 1 and 2. For example, the neoantigenic peptide can be derived by a substitution mutation, such as a KRAS G12V mutation. The neoantigenic peptide may be a peptide containing 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90 or 100 amino acid residues of a protein, e.g. KRAS, including substitution (G12V). The substitutions can be located anywhere along the entire length of the neoantigenic peptide. For example, it can be located in the N-terminal third of the neoantigenic peptide, in the central third of the neoantigenic peptide, or in the C-terminal third of the neoantigenic peptide. In another example, the substituted residue is located 2-5 residues from the N-terminus or 2-5 residues from the C-terminus. Neoantigenic peptides can similarly be derived from tumor-specific mutations, where the neoantigenic peptide contains one or more or all of the introduced residues.

[610] Neoantigenic peptides can also be derived from frameshift mutations, fusion polypeptides, in-frame deletions, and splicing variants. The tumor-specific polypeptides resulting from these mutations can be characterized by the presence of a transition point between the germline-encoded polypeptide sequence and the tumor-specific mutant polypeptide encoded by the tumor-specific mutation. The neoantigenic peptide may be approximately 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50 , 60, 70, 80, 90, or 100 amino acid residues that span the transition between the native germline-encoded sequence and the tumor-specific polypeptide sequence. The transition point can be located anywhere along the entire length of the neoantigenic peptide. For example, it may be located in the N-terminal third of the neoantigenic peptide, in the central third of the neoantigenic peptide, or in the C-terminal third of the neoantigenic peptide. In another example, the transition point is located 2-5 residues from the N-terminus or 2-5 residues from the C-terminus. The frameshift neoantigenic peptide and splicing variants can also be a peptide composed of tumor-specific mutant residues.

[611] For each mutation event shown in Tables 1 and 2, the full length amino acid sequence of the mutant protein was obtained. Any constituents of 9 monomeric units or 10 monomeric units not found in the germline protein sequence were discarded as a neo-peptide and evaluated for binding ability on the six common HLA alleles (HLA-A01:01, HLA-A02:01. HLA- A03:01, HLA-A11:01, HLA-A24:02, HLA-B07:02 and HLA-B08:01) using available algorithms. Any peptide gaining more than 1000 nM was isolated. The isolated peptides are shown in Tables 1 and 2 followed by the high-scoring HLA allele in parentheses.

Table 1

Gene Illustrative protein change Sequence context with mutation Peptides (example(s) of the HLA allele) Illustrative diseases TABLE 1A POINT MUTATION 1 ABL1 E255K VADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYG K VYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVC GQYGKVYEG (A02.01) GQYGKVYEGV (A02.01) KLGGGQYGK (A03.01) KLGGGQYGKV (A02.01) KVYEGVWKK (A02.01, A03.01)
KVYEGVWKKY (A03.01)
QYGKVYEGV(A24.02)
QYGKVYEGVW (A24.02) Chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), gastrointestinal stromal tumors (GIST) ABL1 E255V VADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQYG V VYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVC GQYGVVYEG (A02.01)
GQYGVVYEGV (A02.01)
KLGGGQYGV(A02.01)
KLGGGQYGVV (A02.01)
QYGVVYEGV(A24.02)
QYGVVYEGVW (A24.02)
VVYEGVWKK (A02.01, A03.01)
VVYEGVWKKY (A03.01) Chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), gastrointestinal stromal tumors (GIST) ABL1 M351T LLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSA T EYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKF ATQISSATEY (A01.01)
ISSATEYLEK (A03.01)
SSATEYLEK (A03.01)
TQISSATEYL (A02.01)
YMATQISSAT (A02.01) Chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), gastrointestinal stromal tumors (GIST) ABL1 T315I SLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYII I EFMTYGNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLA FYIIIEFMTY (A24.02)
IIEFMTYGNL (A02.01)
IIIEFMTYG (A02.01)
IIIEFMTYGN (A02.01)
YIIIEFMTYG (A02.01) Chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), gastrointestinal stromal tumors (GIST) ABL1 Y253H STVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERTDITMKHKLGGGQ H GEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLG GQHGEVYEGV(A02.01)
KLGGGQHGEV (A02.01) Chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), gastrointestinal stromal tumors (GIST) ALK G1269A SSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKI A DFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLL KIADFGMAR (A03.01)
RVAKIADFGM (A02.01, B07.02) NSCLC ALK L1196M QVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFIL M ELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFI FILMELMAGG (A02.01)
ILMELMAGG (A02.01)
ILMELMAGGD (A02.01)
LMELMAGGDL (A02.01)
LPRFILMEL (B07.02, B08.01)
LPRFILMELM (B07.02)
LQSLPRFILM (A02.01, B08.01)
SLPRFILMEL (A02.01, A24.02, B07.02, B08.01) NSCLC BRAF V600E MIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLAT E KSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELM LATEKSRWS (A02.01, B08.01)
LATEKSRWSG (A02.01, B08.01) CRC, GBM, KIRP, LUAD, SKCM, THCA BTK C481S MIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANG S LLNYLREMRHRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVND EYMANGSLL (A24.02)
MANGSLLNY (A01.01, A03.01, A11.01)
MANGSLLNYL (A02.01, B07.02, B08.01)
SLLNYLREM (A02.01, B07.02, B08.01)
YMANGSLLN (A02.01)
YMANGSLLNY (A01.01, A03.01, A11.01) CLL EEF1B2 S43G MGFGDLKSPAGLQVLNDYLADKSYIEGYVPSQADVAVFEAVS G PPPADLCHALRWYNHIKSYEKASLPGVKKALGKYGPADVEDTTGSGAT GPPPADLCHAL (B07.02) BLCA, KIRP, PRAD, SKCM EGFR S492R SLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKLFGTSGQKTKII R NRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCNLL IIRNRGENSCK (A03.01) CRC EGFR T790M IPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLI M QLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA CLTSTVQLIM (A01.01, A02.01)
IMQLMPFGC (A02.01)
IMQLMPFGCL (A02.01, A24.02, B08.01)
LIMQLMPFG (A02.01)
LIMQLMPFGC (A02.01)
LTSTVQLIM (A01.01)
MQLMPFGCL (A02.01, B07.02, B08.01)
MQLMPFGCLL (A02.01, A24.02, B08.01)
QLIMQLMPF (A02.01, A24.02, B08.01)
QLIMQLMPFG (A02.01)
STVQLIMQL (A02.01)
VQLIMQLMPF (A02.01, A24.02, B08.01) NSCLC, PRAD ERBB3 V104M ERCEVVMGNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLR M VRGTQVYDGKFAIFVMLNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDK CRC, stomach cancer ESR1 D538G HLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLY G LLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEA GLLLEMLDA (A02.01)
LYGLLLEML (A24.02)
NVVPLYGLL (A02.01)
PLYGLLLEM (A02.01)
PLYGLLEML (A02.01, A24.02)
VPLYGLLLEM (B07.02)
VVPLYGLLL (A02.01, A24.02) Mammary cancer ESR1 S463P NQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFL P STLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSH FLPSTLKSL (A02.01, A24.02, B08.01)
GVYTFLPST (A02.01)
GVYTFLPSTL (A02.01, A24.02)
TFLPSTLKSL (A24.02)
VYTFLPSTL (A24.02)
YTFLPSTLK (A03.01) Mammary cancer ESR1 Y537C IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPL C DLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE NVVPLCDLL (A02.01)
NVVPLCDLLL (A02.01)
PLCDLLLEM (A02.01)
PLCDLLLEML (A02.01)
VPLCDLLLEM (B07.02)
VVPLCDLLL (A02.01, A24.02) Mammary cancer ESR1 Y537N IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPL N DLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE NVVPLNDLL (A02.01)
NVVPLNDLLL (A02.01)
PLNDLLLEM (A02.01)
PLNDLLLEML (A02.01)
VPLNDLLLEM (B07.02) Mammary cancer ESR1 Y537S IHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPL S DLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGE NVVPLSDLL (A02.01)
NVVPLSDLLL (A02.01)
PLSDLLLEM (A02.01)
PLSDLLLEML (A02.01)
VPLSDLLLEM (B07.02)
VVPLSDLLL (A02.01, A24.02) Mammary cancer FGFR3 S249C HRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLER C PHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVG VLERCHRPI (A02.01, B08.01)
YTLDVLERC (A02.01) BLCA, HNSC, KIRP, LUSC FRG1B L52S AVKLSDSRIALKSGYGKYLGINSDELVGHSDAIGPREQWEPVFQNGKMAL S ASNSCFIRCNEAGDIEAKSKTAGEEEMIKIRSCAEKETKKKDDIPEEDKG FQNGKMALS (A02.01) GBM, KIRP, PRAD, SKCM HER2 V777 l
(resistance) GSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAG L GSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM VMAGLGSPYV (A02.01, A03.01) BRCA IDH1 R132H RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIG H HAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM KPIIIGHHA (B07.02) BLCA, GBM, PRAD IDH1 R132C RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIG C HAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM KPIIIIGCHA (B07.02) BLCA, GBM, PRAD IDH1 R132G RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIG G HAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM KPIIIGGHA (B07.02) BLCA, BRCA, CRC, GBM, HNSC, LUAD, PAAD, PRAD, UCEC IDH1 R132S RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIG S HAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM KPIIIGSHA (B07.02) BLCA, BRCA, GBM, HNSC, LIHC, LUAD, LUSC, PAAD, SKCM, UCEC KIT T670I VAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGACTIGGPTLVI I EYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE IIEYCCYGDL (A02.01)
TIGGPTLVII (A02.01)
VIIEYCCYG (A02.01) gastrointestinal stromal tumors (GIST) KIT V654A VEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNI A NLLGACTIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYK HMNIANLLGA (A02.01)
IANLLGACTI (A02.01)
MNIANLLGA (A02.01)
YLGNHMNIA (A02.01, B08.01)
YLGNHMNIAN (A02.01) gastrointestinal stromal tumors (GIST) MEK C121S ISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE S NSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSI VLHESNSPY(A03.01)
VLHESNSPYI (A02.01) Melanoma MEK P124 l LGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNS L YIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVI LQVLHECNSL (A02.01, B08.01)
LYIVGFYGAF (A24.02)
NSLYIVGFY (A01.01)
QVLHECNSL (A02.01, B08.01)
SLYIVGFYG (A02.01)
SLYIVGFYGA (A02.01)
VLHECNSLY (A03.01)
VLHECNSLYI (A02.01, A03.01) Melanoma MYC E39D MPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQS D LQPPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGG FYQQQQQSDL (A24.02)
QQQSDLQPPA (A02.01)
QQSDLQPPA(A02.01)
YQQQQQSDL (A02.01, B08.01) lymphoid malignant tumor; Burkitt's lymphoma MYC P57S FTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELL S TPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLG FELLSTPPL (A02.01, B08.01)
LLSTPPLSPS (A02.01) lymphoid malignant tumor MYC T58I TNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFELLP I PPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGG FELLPIPPL (A02.01)
IWKKFELLPI (A24.02)
LLPIPPLSPS (A02.01, B07.02)
LPIPPLSPS (B07.02) Neuroblastoma PDGFRa T674I VAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYII I EYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSYVILS IIEYCFYGDL (A02.01)
IIIEYCFYG (A02.01)
IYIIIEYCF (A24.02)
IYIIIEYCFY (A24.02)
YIIIEYCFYG (A02.01) Chronic eosinophilic leukemia PIK3CA E542K IEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLS K ITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPP KITEQEKDFL (A02.01) BLCA, BRCA, CESC, CRC, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, PRAD, UCEC PIK3CA E545K HANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLSEIT K QEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKP STRDPLSEITK (A03.01)
DPLSEITK (A03.01) BLCA, BRCA, CESC, CRC, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, PRAD, SKCM, UCEC PIK3CA H1047R LFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDA R HGGWTTKMDWIFHTIKQHALN BRCA, CESC, CRC, GBM, HNSC, LIHC, LUAD, LUSC, PRAD, UCEC POLE P286R QRGGVITDEEETSKKIADQLDNIVDMREYDVPYHIRLSIDIETTKLPLKF R DAETDQIMMISYMIDGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCVFN LPLKFRDAET (B07.02) Colorectal adenocarcinoma; adenocarcinoma of the uterus/endometrium; Colorectal adenocarcinoma, MSI+; uterine/endometrial adenocarcinoma, MSI+; endometroid carcinoma; endometrial serous carcinoma Endometrial carcinosarcoma is a malignant mesodermal mixed tumor; glioma; astrocytoma; GBM PTEN R130Q KFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKG Q TGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY QTGVMICAYL (A02.01) BRCA, CESC, CRC, GBM, KIRC, LUSC, UCEC RAC1 P29S MQAIKCVVVGDGAVGKTCLLISYTTNAF S GEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTVGET AFSGEYIPTV (A02.01, A24.02) Melanoma TP53 G245S IRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMG S MNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEP SMNRRPILT (A02.01, B08.01)
YMCNSSCMGS (A02.01) BLCA, BRCA, CRC, GBM, HNSC, LUSC, PAAD, PRAD TP53 R175H TYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVR H CPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEV BLCA, BRCA, CRC, GBM, HNSC, LUAD, PAAD, PRAD, UCEC TP53 R248Q EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMN Q RPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE GMNQRPILT (A02.01) BLCA, BRCA, CRC, GBM, HNSC, KIRC, LIHC, LUSC, PAAD, PRAD, UCEC TP53 R248W EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMN W RPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE GMNWRPILT (A02.01) BLCA, BRCA, CRC, GBM, HNSC, LIHC, LUSC, PAAD, SKCM, UCEC TP53 R273C PEVGSDCTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEV C VCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPL LLGRNSFEVC (A02.01) BLCA, BRCA, CRC, GBM, HNSC, LUSC, PAAD, UCEC TABLE 1B MSI-BASED READING FRAME SHIFT 1 ACVR2A D96fs; +1 GVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDDINCYDRTDCVEKK RQP* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome ACVR2A D96fs; -one GVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWLDDINCYDRTDCVEKK TALKYIFVAVRAICVMKSFLIFRRWKSHSPLQIQLHLSHPITTSCSIPWCHLC* ALKYIFVAV (A02.01, B08.01)
ALKYIFVAVR (A03.01)
AVRAICVMK (A03.01)
AVRAICVMKS (A03.01)
CVEKKTALK (A03.01)
CVEKKTALKY (A01.01)
CVMKSFLIF (A24.02, B08.01)
CVMKSFLIFR (A03.01)
FLIFRRWKS (A02.01, B08.01)
FRRWKSHSPL(B08.01)
FVAVRAICV (A02.01, B08.01)
FVAVRAICVM (B08.01)
IQLHLSHPI(A02.01)
KSFLIFRRWK (A03.01)
KTALKYIFV (A02.01)
KYIFVAVRAI (A24.02)
RWKSHSPLQI (A24.02)
TALKYIFVAV (A02.01, B08.01)
VAVRAICVMK (A03.01)
VMKSFLIFR (A03.01)
VMKSFLIFRR (A03.01)
YIFVAVRAI (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome C15ORF40 L132fs; +1 TAEAVNVAIAAPPSEGEANAELCRYLSKVLELRKSDVVLDKVGLALFFFF FETKSCSVAQAGVQWRSLGSLQPPPPGFKLFSCLSFLSSWDYRRMPPCLANFCIFNRDGVSPCWSGWS* ALFFFFFET (A02.01)
ALFFFFFETK (A03.01)
AQAGVQWRSL (A02.01)
CLANFCIFNR (A03.01)
CLSFLSSWDY (A01.01, A03.01)
FFETKSCSV(B08.01)
FFFETKSCSV (A02.01)
FKLFSCLSFL (A02.01)
FLSSWDYRRM (A02.01)
GFKLFSCLSF (A24.02)
KLFSCLSFL (A02.01, A03.01)
KLFSCLSFLS (A02.01, A03.01)
LALFFFFFET (A02.01)
LFFFFFETK (A03.01)
LSFLSSWDY (A01.01)
LSFLSSWDYR (A03.01)
RMPPCLANF (A24.02)
RRMPPCLANF (A24.02)
SLQPPPPGFK (A03.01)
VQWRSLGSL (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome CNOT1 L1544fs; +1 LSVIIFFFVYIWHWALPLILNNHHICLMSSIILDCNSVRQSIMSVCFFFF SVIFSTRCLTDSRYPNICWFK* FFSVIFST (A02.01)
MSVCFFFFSV (A02.01)
SVCFFFFSV (A02.01, B08.01)
SVCFFFFSVI (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome CNOT1 L1544fs; -one LSVIIFFFVYIWHWALPLILNNHHICLMSSIILDCNSVRQSIMSVCFFFF CYILNTMFDR* FFCYILNTMF (A24.02)
MSVCFFFFCY (A01.01)
SVCFFFFCYI (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome EIF2B3 A151fs; -one VLVLSCDLITDVALHEVVDLFRAYDASLAMLMRKGQDSIEPVPGQKGKKK QWSSVTSLEWTAQERGCSSWLMKQTWMKSWSLRDPSYRSILEYVSTRVLWMPTSTV* KQWSSVTSL (A02.01)
VLWMPTSTV (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome EPHB2 K1020fs; -one SIQVMRAQMNQIQSVEGQPLARRPRATGRTKRCQPRDVTKKTCNSNDGKK REWEKRKQILGGGGKYKEYFLKRILIRKAMTVLAGDKKGLGRFMRCVQSETKAVSLQLPLGR* ILIRKAMTV (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome ESRP1 N512fs; +1 LDFLGEFATDIRTHGVHMVLNHQGRPSGDAFIQMKSADRAFMAAQKCHKK KHEGQIC* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome ESRP1 N512fs; -one LDFLGEFATDIRTHGVHMVLNHQGRPSGDAFIQMKSADRAFMAAQKCHKK T* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome FAM111B A273fs; -one GALCKDGRFRSDIGEFEWKLKEGHKKIYGKQSMVDEVSGKVLEMDISKKK HYNRKISIKKLNRMKVPLMKLITRV* RMKVPLMK (A03.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome GBP3 T585fs; -one RERAQLLEEQEKTLTSKLQEQARVLKERCQGESTQLQNEIQKLQKTLKKK PRDICRIS* TLKKKPRDI (B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome JAK1 P861fs; +1 VNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFEALLK TSN* LIEGFEALLK (A03.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome JAK1 K860fs; -one CRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEEQNPDIVSEK NQQLKWTPHILKSAS* QQLKWTPHI (A02.01)
QLKWTPHILK (A03.01)
IVSEKNQQLK (A03.01)
QLKWTPHILK (A03.01)
QQLKWTPHI (A24.02)
NQQLKWTPHIL (B08.01)
NQQLKWTPHI (B08.01)
QLKWTPHIL(B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome LMAN1 E305fs; +1 DDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQELDKKK RGIPEGPPRPPRAACGGNI* GPPRPPRAAC (B07.02)
PPRPPRAAC (B07.02)B MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome LMAN1 E305fs; -one DDHDVLSFLTFQLTEPGKEPPTPDKEISEKEKEKYQEEFEHFQQELDKKK RNSRRATPTSKGSLRRKYLRV* SLRRKYLRV (B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome MSH3 N385fs; +1 TKSTLIGEDVNPLIKLDDAVNVDEIMTDTSTSYLLCISENKENVRDKKKG QHFYWHCGSAACHRRGCV* SAACHRRGCV (B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome MSH3 K383fs; -one LYTKSTLIGEDVNPLIKLDDAVNVDEIMTDTSTSYLLCISENKENVRDKK RATFLLALWECSLPQARLCLIVSRTLLLVQS* ALWECSLPQA (A02.01)
CLIVSRTLL (B08.01)
CLIVSRTLLL (A02.01, B08.01)
FLLALWECS (A02.01)
FLLALWECSL (A02.01, B08.01)
IVSRTLLLV (A02.01)
LIVSRTLLL (A02.01, B08.01)
LIVSRTLLLV (A02.01)
LLALWECSL (A02.01, B08.01)
LPQARLCLI (B08.01, B07.02)
LPQARLCLIV (B08.01)
NVRDKKRATF (B08.01)
SLPQARLCLI (A02.01, B08.01) MSI+CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome NDUFC2 A70fs; +1 LPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQLLYITAFFF CWILSCKT* FFCWILSCK (A03.01)
FFFCWILSCK (A03.01)
ITAFFFCWI (A02.01)
LYITAFFFW(A24.02)
YITAFFFFCWI(A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome NDUFC2 F69fs; -one SLPPPKLTDPRLLYIGFLGYCSGLIDNLIRRRPIATAGLHRQLLYITAFF LLDIIL* ITAFFLLDI (A02.01)
LLYITAFFL (A02.01, B08.01)
LLYITAFFLL (A02.01, A24.02)
LYITAFFLL (A24.02)
LYITAFFLLD (A24.02)
YITAFFLLDI (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome RBM27 Q817; +1 NQSGGAGEDCQIFSTPGHPMIYSSSNLKTPSKLCSGSKSHDVQEVLKKK TGSNEVTTRYEEKKTGSVRKANRMPKDVNIQVRKKQKHETRRKSKYNEDFERAWREDLTIKR* GSNEVTTRY (A01.01)
MPKDVNIQV (B07.02) V V
TGSNEVTTRY (A01.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome RPL22 K16fs; +1 MAPVKKLVVKGGKKK EASSEVHS* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome RPL22 K15fs; -one MAPVKKLVVKGGKK RSKF* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SEC31A I462fs; +1 MPSHQGAEQQQQQHHVFISQVVTEKEFLSRSDQLQQAVQSQGFINYCQKK N* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SEC31A I462fs; -one MPSHQGAEQQQQQHHVFISQVVTEKEFLSRSDQLQQAVQSQGFINYCQKK LMLLRLNLRKMCGPF* KKLMLLRLNL (A02.01)
KLMLLRLNL (A02.01, A03.01, B07.02, B08.01)
KLMLLRLNLR (A03.01)
LLRLNLRKM (B08.01)
LMLLRLNL (B08.01)
LMLLRLNLRK (A03.01)
LNLRKMCGPF (B08.01)
MLLRLNLRK (A03.01)
MLLRLNLRKM (A02.01, A03.01, B08.01)
NLRKMCGPF(B08.01)
NYCQKKLMLL (A24.02)
YCQKKLMMLL (B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SEC63 K530fs; +1 AEVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKKK ETFKKKTYTCAITTVKATETKAGKWSRWE* FKKKTYTCAI (B08.01)
ITTVKATETK (A03.01)
KSKKKETFK (A03.01)
KSKKKETFKK(A03.01)
KTYTCAITTV (A02.01, A24.02)
TFKKKTYTC(B08.01)
TYTCAITTV (A24.02)
TYTCAITTVK (A03.01)
YTCAITTVK (A03.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SEC63 K529fs; -one MAEVFEKEQSICAAEEQPAEDGQGETNKNRTKGGWQQKSKGPKKTAKSKK RNL* TAKSKKRNL (B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SLC35F5 C248fs; -one NIMEIRQLPSSHALEAKLSRMSYPVKEQESILKTVGKLTATQVAKISFFF ALCGFWQICHIKKHFQTHKLL* FALCGFWQI (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SMAP1 K172fs; +1 YEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKKK GREKERKGARKAGKTTYS* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome SMAP1 K171fs; -one KYEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKK RKRKREKRSQKSRQNHLQLKSCRRKISNWSLKKVPALKKLRSPLWIF* LKKLRSP (B08.01)
SLKKVPAL (B08.01)
RKISNWSLKK (A03.01)
VPALKKLRSP (B07.02) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome TFAM E148fs; +1 IYQDAYRAEWQVYKEEISRFKEQLTPSQIMSLEKEIMDKHLKRKAMTKKK RVNTAWKTKKTSFSL* KRVNTAWKTK (A03.01)
MTKKKRVNTA (B08.01)
RVNTAWKTK (A03.01)
RVNTAWKTKK (A03.01)
TKKKRVNTA (B08.01)
WKTKKTSFSL (B08.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome TFAM E148fs; -one IYQDAYRAEWQVYKEEISRFKEQLTPSQIMSLEKEIMDKHLKRKAMTKKK S* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome TGFBR2 P129fs; +1 KPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKK AW* MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome TGFBR2 K128fs: -1 EKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKK SLVRLSSCVPVALMSAMTTSSSQKNITPAILTCC* ALMSAMTTS (A02.01)
AMTTSSSQK (A03.01, A11.01)
AMTTSSSQKN (A03.01)
CIMKEKKSL (B08.01)
CIMKEKKSLV (B08.01)
IMKEKKSL (B08.01)
IMKEKKSLV (B08.01)
KSLVRLSSCV (A02.01)
LVRLSSCVPV (A02.01)
RLSSCVPVA (A02.01, A03.01)
RLSSCVPVAL (A02.01)
SAMTTSSSQK (A03.01, A11.01)
SLVRLSSCV (A02.01)
VPVALMSAM (B07.02)
VRLSSCVPVA (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome THAP5 K99fs; -one VPSKYQFLCSDHFTPDSLDIRWGIRYLKQTAVPTIFSLPEDNQGKDPSKK NPRRKTWKMRKKYAQKPSQKNHLY* KMRKKYAQK(A03.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome TTK R854fs; -one GTTEEMKYVLGQLVGLNSPNSILKAAKTLYEHYSGGESHNSSSSKTFEKK GEKNDLQLFVMSDTTYKIYWTVILLNPCGNLHLKTTSL* FVMSDTYK (A03.01)
FVMSDTYKI (A02.01)
KTFEKKGEK (A03.01)
LFVMSDTTYK (A03.01)
MSDTTYKIY (A01.01)
VMSDTTYKI (A02.01)
VMSDTTYKIY (A01.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome XPOT F126fs; -one QQLIRETLISWLQAQMLNPQPEKTFIRNKAAQVFALLFVTEYLTKWPKFF LTFSQ* YLTKWPKFFL (A02.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome TABLE 1C READING FRAME SHIFT 1 APC V1352fs
F1354fs
Q1378fs
S1398fs AKFQQCHSTLEPNPADCRVLVYLQNQPGTKLLNFLQERNLPPKVVLRHPKVHLNTMFRRPHSCLADVLLSVHLIVLRVVRLPAPFRVNHAVEW* FLQERNLPP (A02.01)
FRRPHSCLA (B08.01)
LIVLRVVRL (B08.01)
LLSVHLIVL (A02.01, B08.01) CRC, LUAD, UCEC, STAD APC S1421fs
R1435fs
T1438fs
P1442fs
P1443fs
V1452fs
P1453fs
K1462fs
E1464fs APVIFQIALDKPCHQAEVKHLHHLLKQLKPSEKYLKIKHLLLKRERVDLSKLQ* EVKHLHHLL (B08.01)
HLHHLLKQLK (A03.01)
HLLLKRERV (B08.01)
KIKHLLLKR (A03.01)
KPSEKYLKI (B07.02)
KYLKIKHLL (A24.02)
KYLKIKHLLL (A24.02)
LLKQLKPSEK (A03.01)
LLKRERVDL (B08.01)
LLLKRERVDL (B08.01)
QLKPSEKYLK (A03.01)
YLKIKHLLL (A02.01, B08.01)
YLKIKHLLLK (A03.01) CRC, LUAD, UCEC, STAD APC T1487fs
H1490fs
L1488fs MLQFRGSRFQMLILYYILPRKVLQMDFLVHPA* ILPRKVLQM (B08.01)
KVLQMDFLV (A02.01, A24.02)
LPRKVLQMDF (B07.02, B08.01)
LQMDFLVHPA(A02.01)
QMDFLVHPA(A02.01)
YILPRKVLQM (A02.01, B08.01) CRC, LUAD, UCEC, STAD ARID1A Q1306fs
S1316fs
Y1324fs
T1348fs
G1351fs
G1378fs
P1467fs * APSPASRLQC (B07.02)
HPLAPMPSKT (B07.02)
ILPLPQLLL (A02.01)
LLLSADQQA (A02.01)
LPTQTRGCI (B07.02)
LPTQTRGCIL (B07.02)
RISCLPTQTR (A03.01)
SLAETVSLH (A03.01)
TPRSSSSSS (B07.02)
TPRSSSSSSS (B07.02) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS ARID1A S674fs
P725fs
R727fs
I736fs AHQGFPAAKESRVIQLSLLSLLIPPLTCLASEALPRPLLALPPVLLSLAQDHSRLLQCQATRCHLGHPVASRTASCILP* ALPPVLLSL (A02.01)
ALPPVLLSLA (A02.01)
ALPRPLLAL (A02.01)
ASRTASCIL (B07.02)
EALPRPLLAL (B08.01)
HLGHPVASR (A03.01)
HPVASRTAS (B07.02)
HPVASRTASC (B07.02)
IIQLSLLSLL (A02.01)
IQLSLLSLL (A02.01)
IQLSLSLLI (A02.01, A24.02)
LLALPPVLL (A02.01)
LLIPPLTCL (A02.01)
LLIPPLTTCLA (A02.01)
LLSLLIPPL (A02.01)
LLSLLIPPLT (A02.01)
LPRPLLALPP (B07.02)
QLSLSLLI (A02.01)
RLLQCQATR (A03.01)
RPLLALPPV (B07.02)
RPLLALPPVL (B07.02)
SLAQDHRL (A02.01)
SLAQDHRLL (A02.01)
SLLIPPLTCL (A02.01)
SLLSLLIPP (A02.01)
SLLSLLIPPL (A02.01, B08.01) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS ARID1A G414fs
Q473fs
H477fs
S499fs
P504fs
Q548fs
P549fs PILAATGTSVRTAARTWVPRAAIRVPDPAAVPDDHAGPGAECHGRPLLYTADSSLWTTRPQRVWSTGPDSILQPAKSSPSAAAATLLPATTVPDPSCPTFVSAAATVSTTTAPVLSASILPAAIPASTSAVPGSIPLPAVDDTAAPPEPAPLLTATGSVSLPAAATSAASTLDALPAGCVSSAPVSAVPANCLFPAALPSTAGAISRFIWVSGILSPLNDLQ* AAATSAASTL(B07.02)
AAIPASTSAV (B07.02)
AIPASTSAV (A02.01)
ALPAGCVSSA (A02.01)
APLLTATGSV(B07.02)
APVLSASIL (B07.02)
ATLLPATTV (A02.01)
ATVSTTTAPV (A02.01)
AVPANCLFPA (A02.01)
CLFPAALPST (A02.01)
CPTFVSAAA (B07.02)
FPAALPSTA (B07.02)
FPAALPSTAG (B07.02)
GAECHGRPL(B07.02)
GAISRFIWV (A02.01)
ILPAAIPAST (A02.01)
IWVSGILSPL (A24.02)
LLTATGSVSL (A02.01)
LLYTADSSL (A02.01)
LPAAATSAA (B07.02)
LPAAATSAAS (B07.02)
LPAAIPAST (B07.02)
LPAGCVSSA (B07.02)
LPAGCVSSAP (B07.02)
LYTADSSLW (A24.02)
QPAKSSPSA (B07.02)
QPAKSPSAA (B07.02)
RFIWVSGIL (A24.02)
RPQRVWSTG (B07.02)
RVWSTGPDSI (A02.01)
SAVPGSIPL (B07.02)
SILPAAIPA (A02.01)
SLPAAATSA (A02.01)
SLPAAATSAA (A02.01)
SLWTTRPQR (A03.01)
SLWTTRPQRV (A02.01)
SPSAAAATL (B07.02)
SPSAAAATLL (B07.02)
TLDALPAGCV (A02.01)
TVSTTTAPV (A02.01)
VLSASILPA (A02.01)
VLSASILPAA (A02.01)
VPANCLFPA (B07.02)
VPANCLFPAA (B07.02)
VPDPSCPTF (B07.02)
VPGSIPLPA(B07.02)
VPGSIPLPAV (B07.02)
WVSGILSPL (A02.01)
YTADSSLWTT (A02.01) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS ARID1A T433fs
A441fs
Y447fs
P483fs
P484fs
P504fs
S519fs
H544fs
P549fs
P554fs
Q563fs PCRAGRRVPWAASLIHSRFLMDNAPAGMVNRARLHITTSKVLTLSSSSHPTPSNHRPRPLMPNLRISSSHSLNHHSSSPLSLHTPSSHPSLHISSPRLHTPPSSRRHSSTPRASPPTHSHRLSLLTSSSNLSSQHPRRSPSRLRILSPSLSSPSKLPIPSSASLHRRSYLKIHLGLRHPQPPQ* APAGMVNRA (B07.02)
ASLHRRSYL (B08.01)
ASLHRRSYLK (A03.01)
FLLMDNKAPA (A02.01)
HPRRPSRL (B07.02, B08.01)
HPSLHISSP(B07.02)
HRRSYLKIHL (B08.01)
HSRFLMNDNK (A03.01)
KLPIPSSASL (A02.01)
KVLTLSSSSH (A03.01)
LIHSRFLLM (B08.01)
LLMDNKAPA (A02.01)
LMDNKAPAGM (A02.01)
LPIPSSASL (B07.02)
MPNLRISSS (B07.02, B08.01)
MPNLRISSSH (B07.02)
NLRISSSHSL (B07.02, B08.01)
PPTHSHRLSL (B07.02)
RAGRRVPWAAA (B08.01)
RARLHITTSK (A03.01)
RISSSHSLNH (A03.01)
RLHTPPSSR (A03.01)
RLHTPPSSRR (A03.01)
RLRILSPSL (A02.01, B07.02, B08.01)
RPLMPNLRI (B07.02)
RPRPLMPNL (B07.02)
SASLHRRSYL (B07.02, B08.01)
SLHISSPRL (A02.01)
SLHRRSYLK (A03.01)
SLHRRSYLKI (B08.01)
SLIHSFLL (A02.01)
SLIHSRFLLM (A02.01, B08.01)
SLLTSSSNL (A02.01)
SLNHHSSSPL (A02.01, B07.02, B08.01)
SLSSPSKLPI (A02.01)
SPLSLHTPS (B07.02)
SPLSLHTPSS(B07.02)
SPPTHSHRL(B07.02)
SPRLHTPPS (B07.02)
SPRLHTPPSS (B07.02)
SPSLSSPSKL (B07.02)
SYLKIHLGL (A24.02)
TPSNHRPRPL (B07.02, B08.01)
TPSSHPSLHI (B07.02) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS ARID1A A2137fs
P2139fs
L1970fs
V1994fs RTNPTVRMRPHCVPFWTGRILLPSAASVCPIPFEACHLCQAMTLRCPNTQGCCSSWAS* CVPFWTGRIL (B07.02)
HCVPFWTGRIL (B07.02)
ILLPSAASV (A02.01)
ILLPSAASVC (A02.01)
LLPSAASVCPI (A02.01)
LPSAASVCPI (B07.02)
MRPHCVPF (B08.01)
RILLPSAASV (A02.01)
RMRPHCVPF (A24.02, B07.02, B08.01)
RMRPHCVPFW (A24.02)
RTNPTVRMR (A03.01)
SVCPIPFEA (A02.01)
TVRMRPHCV (B08.01)
TVRMRPHCVPF (B08.01)
VPFWTGRIL(B07.02)
VPFWTGRILL (B07.02)
VRMRPHCVPF (B08.01) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS ARID1A N756fs
S764fs
T783fs
Q799fs
A817fs TNQALPKIEVICRGTPRCPSTVPPSPAQPYLRVSLPEDRYTQAWAPTSRTPWGAMVPRGVSMAHKVATPGSQTIMPCPMPTTPVQAWLEA* AMVPRGVSM (B07.02, B08.01)
AMVPRGVSMA (A02.01)
AWAPTSRTPW(A24.02)
CPMPTTPVQA (B07.02)
CPSTVPPSPA (B07.02)
GAMVPRGVSM (B07.02, B08.01)
MPCPMPTTPV (B07.02)
MPTTPVQAW(B07.02)
MPTTPVQAWL (B07.02)
SLPEDRYTQA (A02.01)
SPAQPYLRV (B07.02)
SPAQPYLRVS (B07.02)
TIMPCPMPT (A02.01)
TPVQAWLEA (B07.02)
TSRTPWGAM (B07.02)
VPPSPAQPYL (B07.02)
VPRGVSMAH (B07.02) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS β2M N62fs
E67fs
L74fs
F82fs
T91fs
E94fs RMERELKKWSIQTCLSARTGLSISCTTLNSPPLKKMSMPAV* CLSARTGLSI (B08.01)
CTTLNSPPLK (A03.01)
GLSISCTTL (A02.01)
SPPLKKMSM (B07.02, B08.01)
TLNSPPLKK (A03.01)
TTLNSPPLK (A03.01)
TTLNSPPLKK (A03.01) CRC, STAD, SKCM, HNSC β2M L13fs
S14fs LCSRYSLFLAWRLSSVLQRFRFTHVIQQRMESQIS* LQRFRFTHV(B08.01)
LQRFRFTHVI(B08.01)
RLSSVLQRF (A24.02)
RLSSVLQRFR (A03.01)
VLQRFRFTHV (A02.01, B08.01) CRC, STAD, SKCM, HNSC CDH1 A691fs
P708fs
L711fs RSACVTVKGPLASVGRHSLSKQDCKFLPFWGFLEEFLLC* ASVGRHSLSK (A03.01)
KFLPFWGFL (A24.02)
LASVGRHSL(B07.02)
LPFWGFLEEF (B07.02)
PFWGFLEEF (A24.02)
SVGRHSLSK (A03.01) ILC Luma Breast cancer CDH1 H121fs
P126fs
H128fs
N144fs
V157fs
P159fs
N166fs
N181fs
F189fs
P201fs
F205fs IQWGTTTAPRPIRPPFLESKQNCSHFPTPLLASEDRRETGLFPSAAQKMKKAHFLKTWFRSNPTKTKKARFSTASLAKELTHPLLVSLLLKEKQDG* APRPIRPPF (B07.02)
APRPIRPPFL (B07.02)
AQKMKKAHFL (B08.01)
FLPSAAQKM (A02.01)
GLFLPSAAQK (A03.01)
HPLLVSLLL (B07.02)
KAHFLKTWFR (A03.01)
KARFSTASL (B07.02)
KMKKAHFLK (A03.01)
KTWFRSNPTK (A03.01)
LAKELTHPL (B07.02, B08.01)
LAKELTHPLL (B08.01)
NPTKTKKARF (B07.02)
QKMKKAHFL(B08.01)
RFSTASLAK (A03.01)
RPIRPPFLES (B07.02)
RSNPTKTKK (A03.01)
SLAKELTHPL (A02.01, B08.01)
TKKARFSTA (B08.01) ILC Luma Breast cancer CDH1 V114fs
P127fs
V132fs
P160fs PTDPFLGLRLGLHLQKVFHQSHAEYSGAPPPPPAPSGLRFWNPSRIAHISQLLSWPQKTEERLGYSSHQLPRK* GLRFWNPSR (A03.01)
ISQLLSWPQK (A03.01)
RIAHISQLL (A02.01)
RLGYSSHQL (A02.01)
SQLLSWPQK (A03.01)
SRIAHISQL (B08.01)
WPQKTEERL (B07.02)
YSSHQLPRK (A03.01) ILC Luma Breast cancer CDH1 L731fs
R749fs
E757fs
G759fs FCCSCCFFGGERWSKSPYCPQRMTPGTTFITMMKKEAEKRTRTLT* CPQRMTPGTT (B07.02)
EAEKRTRTL (B08.01)
GTTFITMMK (A03.01)
GTTFITMMKK (A03.01)
ITMMKKEAEK (A03.01)
RMTPGTTFI (A02.01)
SPYCPQRMT (B07.02)
TMMKKEAEK (A03.01)
TPGTTFITM (B07.02)
TPGTTFITM (B07.02)
TTFITMMKK (A03.01) ILC Luma Breast cancer CDH1 S19fs
E24fs
S36fs WRRNCKAPVSLRKSVQTPARSSPARPDRTRRLPSLGVPGQPWALGAAASRRCCCCCRSPLGSARSRSPATLALTPRATRSRCPGATWREAASWAE* CPGATWREA (B07.02)
CPGATWREAA (B07.02)
RSRCPGATWR (A03.01)
TPRATRSRC (B07.02) ILC Luma Breast cancer GATA3 P394fs
P387fs
S398fs
H400fs
M401fs
S408fs
P409fs
S408fs
P409fs
T419fs
H424fs
P425fs
S427fs
F431fs
S430fs
H434fs
H435fs
S438fs
M443fs
G444fs
*445fs PGRPLQTHVLPEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHRHGLEPCSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLKAESKIMFATLQRSSLWCLCSNH* HVLPEPHLAL (B07.02)
RPLQTHVLPE (B07.02)
VLWTTPPLQH (A03.01) Mammary cancer GATA3 P426fs
H434fs
P433fs
T441fs PRPRRCTRHPACPLDHTTPPAWSPPWVRALLDAHRAPSESPCSPFRLAFLQEQYHEA* APSESPCSPF (B07.02)
CPLDHTTPPA (B07.02)
FLQEQYHEA (A02.01, B08.01)
RLAFLQEQYH (A03.01)
SPCSPFRLAF (B07.02)
SPPWVRALL (B07.02)
YPACPLDHTTT (B07.02) Mammary cancer MLL2 P519fs
E524fs
P647fs
S654fs
L656fs
R755fs
L761fs
Q773fs TRRCHCCPHLRSHPCPHHLRNHPRPHHLRHHACHHHLRNCPHPHFLRHCTCPGRWRNRPSLRRLRSLLCLPHLNHHLFLHWRSRPCLHRKSHPHLLHLRRLYPHHLKHRPCPHHLKNLLCPRHLRNCPLPRHLKHLACLHHLRSHPCPLHLKSHPCLHHRRHLVCSHHLKSLLCPLHLRSLPFPHHLRHHACPHHLRTRLCPHHLKNHLCPPHLRYRAYPPCLWCHACLHRLRNLPCPHRLRSLPRPLHLRLHASPHHLRTPPHPHHLRTHLLPHHRRTRSCPCRWRSHPCCHYLRSRNSAPGPRGRTCHPGLRSRTCPPGLRSHTYLRRLRSHTCPPSLRSHAYALCLRSHTCPPRLRDHICPLSLRNCTCPPRLRSRTCLLCLRSHACPPNLRNHTCPPSLRSHACPPGLRNRICPLSLRSHPCPLGLKSPLRSQANALHLRSCPCSLPLGNHPYLPCLESQPCLSLGNHLCPLCPRSCRCPHLGSHPCRLS* ALHLRSPC(B08.01)
CLHHRRHLV (B08.01)
CLHHRRHLVC (B08.01)
CLHRKSHL (B08.01)
CLRSHACPP(B08.01)
CLRSHTCPP(B08.01)
CLWCHACLH (A03.01)
CPHHLKNHL(B07.02)
CPHHLKNLL (B07.02)
CPHHLRTRL (B07.02, B08.01)
CPLHLRSLPF (B07.02, B08.01)
CPLPRHLKHL (B07.02, B08.01)
CPLSLRSHPC(B07.02)
CPRHLRNCPL (B07.02, B08.01)
FPHHLRHHA (B07.02, B08.01)
FPHHLRHHAC (B07.02, B08.01)
GLRSRTCPP(B08.01)
HACLHRLRNL (B08.01)
HLACLHHLR (A03.01)
HLCPPHLRY (A03.01)
HLCPPHLRYR (A03.01)
HLKHLACLH (A03.01)
HLKHRPCPH (B08.01)
HLKNHLCPP(B08.01)
HLKSHPCLH(A03.01)
HLKSLLCPL (A02.01, B08.01)
HLLHLRRLY (A03.01)
HLRNCPLPR (A03.01)
HLRNCPLPRH (A03.01)
HLRRLYPHHL (B08.01)
HLRSHPCPL (B07.02, B08.01)
HLRSHPCPLH (A03.01)
HLRSLPFPH (A03.01)
HLRTRLCPH (A03.01, B08.01)
HLVCSHHLK (A03.01)
HPCLHHRRHL (B07.02, B08.01)
HPGLRSRTC (B07.02)
HPHLLHLRRL (B07.02, B08.01)
HRKSHPHLL(B08.01)
HRRTRSCPC(B08.01)
KSHPHLLHLR (A03.01)
KSLLCPLHLR (A03.01)
LLCPLHLRSL (A02.01, B08.01)
LLHLRRLYPH (B08.01)
LPRHLKHLA (B07.02)
LPRHLKHLAC (B07.02, B08.01)
LRRLRSHTC(B08.01)
LRRLYPHHL (B08.01)
LVCSHHLKSL(B08.01)
NLRNHTCPPS (B08.01)
PLHLRSLPF (B08.01)
RLCPHHLKNH (A03.01)
RLYPHHLKH (A03.01)
RLYPHHLKHR (A03.01)
RPCPHHLKNL (B07.02)
RSHPCPLHLK (A03.01)
RSLPFPHLR (A03.01)
RTRLCPHHL (B07.02)
RTRLCPHHLK (A03.01)
SLLCPLHLR (A03.01)
SLRSHACPP(B08.01)
SPLRSQANA (B07.02)
YLRRLRSHT(B08.01)
YPHHLKHRPC (B07.02, B08.01) STAD, BLCA, CRC, HNSC, BRCA PTEN I122fs
I135fs
A148fs
L152fs
D162fs
I168fs SWKGTNWCNDMCIFITSGQIFKGTRGPRFLWGSKDQRQKGSNYSQSEALCVLL* FITSGQIFK (A03.01)
IFITSGQIF (A24.02)
SQSEALCVL(A02.01)
SQSEALCVLL (A02.01) UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM PTEN L265fs
K266fs KRTKCFTFG* UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM PTEN A39fs
E40fs
V45fs
R47fs
N48fs PIFIQTLLLWDFLQKDLKAYTGTILMM* AYTGTILMM (A24.02)
DLKAYTGTIL (B08.01) UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM PTEN T319fs
T321fs
K327fs
A328fs
A333fs QKMILTKQIKTKPTDTFLQILR* ILTKQIKTK (A03.01)
KMILTKQIK (A03.01)
KPTDTFLQI (B07.02)
KPTDTFLQIL (B07.02)
MILTKQIKTK (A03.01) UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM PTEN N63fs
E73fs
A86fs
N94fs GFWIQSIKTITRYTIFVLKDIMTPPNLIAELHNILLKTITHHS* ITRYTIFVLK (A03.01)
LIAELHNIL (A02.01)
LIAELHNILL (A02.01)
MTPPNLIAEL (A02.01)
NLIAELHNI (A02.01)
NLIAELHNIL (A02.01)
RYTIFVLKDI (A24.02)
TITRYTIFVL (A02.01)
TPPNLIAEL (B07.02) UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM PTEN T202fs
G209fs
C211fs
I224fs
G230fs
P231fs
R233fs
D236fs NYSNVQWRNLQSSVCGLPAKGEDIFLQFRTHTTGRQVHVL* FLQFRTHTT (A02.01, B08.01)
LPAKGEDIFL (B07.02)
LQFRTHTTGR (A03.01)
NLQSSVCGL (A02.01)
SSVCGLPAK (A03.01)
VQWRNLQSSV (A02.01) UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM PTEN G251fs
E256fs
K260fs
Q261fs
L265fs
M270fs
H272fs
T286fs
E288fs YQSRVLPQTEQDAKKGQNVSLLGKYILHTRTRGNLRKSRKWKSM* GQNVSLLGK (A03.01)
HTRTRGNLRK (A03.01)
ILHTTRGNL (B08.01)
KGQNVSLLGK(A03.01)
LLGKYILHT (A02.01)
LRKSRKWKSM (B08.01)
SLLGKYILH (A03.01)
SLLGKYILHT (A02.01) UCEC, PRAD, SKCM, STAD, BRCA, LUSC, KIRC, LIHC, KIRP, GBM TP53 A70fs
P72fs
A76fs
A79fs
P89fs
W91fs
S96fs
V97fs
V97fs
G108fs
G117fs
S121fs
V122fs
C124fs
K139fs
V143fs SSQNARGCSPRGPCTSSSYTGGPCTSPLLAPVIFCPFPENLPGQLRFPSGLLAFWDSQVCDLHVLPCPQQDVLPTGQDLPCAAVG* CTSPLLAPV (A02.01)
FPENLPGQL(B07.02)
GLLAFWDSQV (A02.01)
IFCPFPENL(A24.02)
LLAFWDSQV (A02.01)
LLAPVIFCP (A02.01)
LLAPVIFCPF (A02.01, A24.02)
LPCPQQDVL (B07.02)
RFPSGLLAF (A24.02)
RFPSGLLAFW (A24.02)
SPLLAPVIF (B07.02)
SPRGPCTSS (B07.02)
SPRGPCTSSS (B07.02)
SQVCDLHVL (A02.01)
VIFCPFPENL(A02.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 V173fs
H178fs
D186fs
H193fs
L194fs
E198fs
V203fs
E204fs
L206fs
D207fs
N210fs
T211fs
F212fs
V225fs
S241fs GAAPTMSAAQIAMVWPLLSILSEWKEICVWSIWMTETLFDIVWWCPMSRLRLALTVPPSTTTTCVTVPAWAA* AMVWPLLSI (A02.01)
AMVWPLLSIL (A02.01)
AQIAMVWPL (A02.01, A24.02)
AQIAMVWPLL (A02.01)
CPMSRLRLA (B07.02, B08.01)
CPMSRLRLAL (B07.02, B08.01)
IAMVWPLLSI (A02.01, A24.02, B08.01)
ILSEWKEICV (A02.01)
IVWWCPMSR (A03.01)
IVWWCPMSRL (A02.01)
IWMTETLFDI (A24.02)
LLSILSEWK (A03.01)
MSAAQIAMV (A02.01)
MSRLRLALT (B08.01)
MSRLRLALTV (B08.01)
MVWPLLSIL (A02.01)
RLALTVPPST (A02.01)
TLFDIVWWC (A02.01)
TLFDIVWWCP (A02.01)
TMSAAQIAMV (A02.01)
VWSIWMTETL (A24.02)
WMTETLFDI (A02.01, A24.02)
WMTETLFDIV (A01.01, A02.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 R248fs
P250fs
S260fs
N263fs
G266fs
N268fs
V272fs
V274fs
P278fs
D281fs
R282fs
T284fs
E285fs
L289fs
K292fs
P301fs
S303fs
T312fs
S314fs
K319fs
K320fs
P322fs
Y327fs
F328fs
L330fs
R333fs
R335fs
R337fs
E339fs TGGPSSPSSHWKTPVVIYWDGTALRCVFVPVLGETGAQRKRISARKGSLTTSCPQGALSEHCPTTPAPLPSQRRNHWMENISPFRSVGVSASRCSES* ALRCVFVPV (A02.01, B08.01)
ALRCVFVPVL (A02.01, B08.01)
ALSEHCPTT (A02.01)
AQRKRISARK (A03.01)
GAQRKRISA (B08.01)
HWMENISPF (A24.02)
LPSQRRNHW(B07.02)
LPSQRRNHWM (B07.02, B08.01)
NISPFRSVGV (A02.01)
RISARKGSL (B07.02, B08.01)
SPFRSVGVSA (B07.02)
SPSSHWKTPV (B07.02, B08.01)
TALRCVFVPV (A02.01)
VIYWDGTAL (A02.01)
VIYWDGTALR (A03.01)
VLGETGAQRK (A03.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 S149fs
P151fs
P152fs
V157fs
Q165fs
S166fs
H168fs
V173fs FHTPARHPRPRHGHLQAVTAHDGGCEALPPP* HPRPRHGHL (B07.02, B08.01)
HPRPRHGHLQ (B07.02)
RPRHGHLQA (B07.02)
RPRHGHLQAV (B07.02, B08.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 P47fs
D48fs
D49fs
Q52fs
F54fs
E56fs
P58fs
P60fs
E62fs
M66fs
P72fs
V73fs
P75fs
A78fs
P82fs
P85fs
S96fs
P98fs
T102fs
Y103fs
G108fs
F109fs
R110fs
G117fs CCPRTILNNGSLKTQVQMKLPECQRLLPPWPLHQQLLHRRPLHQPPPGPCHLLSLPRKPTRAATVSVWASCILGQPSL* GSLKTQVQMK (A03.01)
PPGPCHLSLSL (B07.02)
RTILNNGSLK (A03.01)
SLKTQVQMK (A03.01)
SLKTQVQMKL (B08.01)
TILNNGSLK (A03.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 L26fs
P27fs
P34fs
P36fs
A39fs
Q38fs VRKHFQTYGNYFLKTTFCPPCRPKQWMI* CPPCRPKQWM (B07.02)
TTFCPPCRPK (A03.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 C124fs
L130fs
N131fs
C135fs
K139fs
A138fs
T140fs
V143fs
Q144fs
V147fs
T150fs
P151fs
P152fs
G154fs
R156fs
R158fs
A161fs LARTPLPSTRCFANWPRPALCSCGLIPHPRPAPASAPWPSTSSHST* CFANWPRPAL (A24.02)
FANWPRPAL (B07.02, B08.01)
GLIPHPRPA (A02.01)
HPRPAPASA (B07.02, B08.01)
HPRPAPASAP (B07.02)
IPHPRPAPA (B07.02, B08.01)
IPHPRPAPAS (B07.02)
RPALCSCGL (B07.02)
RPALCSCGLI (B07.02)
TPLPSTRCF (B07.02)
WPRPALCSC(B07.02)
WPRPALCSCG (B07.02) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC VHL L178fs
D179fs
L184fs
T202fs
R205fs
D213fs
G212fs ELQETGHRQVALRRSGRPPKCAERPGAADTGAHCTSTDGRLKISVETYTVSSQLLMVLMSLDLDTGLVPSLVSKCLILRVK* ALRRSGRPPK (A03.01)
GLVPSLVSK (A03.01)
KISVETYTV (A02.01)
LLMVLMSLDL (A02.01, B08.01)
LMSLDLDTGL (A02.01)
LMVLMSLDL (A02.01)
LVSKCLILRV (A02.01)
QLLMVLMSL (A02.01, B08.01)
RPGAADTGA (B07.02)
RPGAADTGAH (B07.02)
SLDLDTGLV (A02.01)
SLVSKCLIL (A02.01, B08.01)
SQLLMVLMSL (A02.01)
TVSSQLLMV (A02.01)
TYTVSSQLL (A24.02)
TYTVSSQLLM (A24.02)
VLMSLDLDT (A02.01)
VPSLVSKCL (B07.02)
VSKCLILRVK (A03.01)
YTVSSQLLM (A01.01)
YTVSSQLLMV (A02.01) KIRC, KIRP VHL L158fs
K159fs
R161fs
Q164fs KSDASRLSGA* KIRC, KIRP VHL P146fs
I147fs
F148fs
L158fs RTAYFCQYHTASVYSERAMPPGCPEPSQA* FCQYHTASV (B08.01) KIRC, KIRP VHL S68fs
S72fs
I75fs
S80fs
P86fs
P97fs
I109fs
H115fs
L116fs
G123fs
T124fs
N131fs
L135fs
V137fs
G144fs
D143fs
I147fs TRASPPRSSSAIAVRASCCPYGSTSTASRSPTQRCRLARAAASTATEVTFGSSEMQGHTMGFWLTKLNYLCHLSMLTDSLFLPISHCQCIL* CPYGSTSTA (B07.02)
CPYGSTSTAS (B07.02)
LARAAASTAT (B07.02)
MLTDSLFLP (A02.01)
PPRSSSAIAV (B07.02)
RAAASTATEV (B07.02)
SPPRSSSAI (B07.02)
SPPRSSSAIA (B07.02)
SPTQRCLA(B07.02)
TQRCRLARA(B08.01)
TQRCRLARAA (B08.01) KIRC, KIRP VHL K171fs
P172fs
N174fs
L178fs
D179fs
L188fs SSLRITGDWTSSGRSTKIWKTTQMCRKTWSG* KIWKTTQMCR (A03.01)
WTSSGRSTK(A03.01) KIRC, KIRP VHL V62fs
V66fs
Q73fs
V84fs
F91fs
T100fs
P103fs
S111fs
L116fs
H115fs
D126fs RRRRGGVGRRGVRPGRVRPGGTGRRGGDGGRAAAARAALGELARALPGHLLQSQSARRAARMAQLRRRAAALPNAAAWHGPPHPQLPRSPLALQRCRDTRWASG* ALGELARAL (A02.01)
AQLRRRAAA (B08.01)
AQLRRRAAAL (B08.01)
ARRAARMAQL(B08.01)
HPQLPRSPL (B07.02, B08.01)
HPQLPRSPLA(B07.02)
LARALPGHL (B07.02)
LARALPGHLL (B07.02)
MAQLRRRAA (B07.02, B08.01)
MAQLRRRAAA (B07.02, B08.01)
QLRRRAAAL (B07.02, B08.01)
RAAALPNAAA (B07.02)
RMAQLRRRAA (B07.02, B08.01)
SQSARRAARM(B08.01) KIRC, KIRP TABLE 1D CRYPTIC EXON 1 AR-v7 cryptic terminal exon SCKVFFKRAAEGKQKYLCASRNDCTIDKFRRKNCPSCRLRKCYEAGMTLG EKFRVGNCKHLKMTRP* GMTLGEKFRV (A02:01)
RVGNCKHLK (A03.01) Prostate cancer, castration-resistant prostate cancer TABLE 1E OUTSIDE FRAME FUSION STRUCTURES ^1.3 AC011997.1:LRRC69 AC011997.1:LRRC69 *out of frame MAGAPPPASLPPCSLISDCCASNQRDSVGVGPSEP: G : NNIKICNESASRK* GPSEPGNNI (B07.02)
KICNESASRK (A03.01) LUSC, Breast Cancer, Head and Neck Cancer, LUAD EEF1DP3 EEF1DP3:FRY *out of frame HGWRPFLPVRARSRWNRRLDVTVANGR: S : WKYGWSLLRVPQVNGIQVLNVSLKSSSNVISYE* GIQVLNVSLK (A03.01)
IQVLNVSLK (A03.01)
KSSSNVISY (A01.01, A03.01)
KYGWSLRV (A24.02)
RSWKYGWSL (A02.01)
SLKSSSNVI (B08.01)
SWKYGWSLL (A24.02)
TVANGRSWK (A03.01)
VPQVNGIQV (B07.02)
VPQVNGIQVL (B07.02)
VTVANGRSWK (A03.01)
WSLLRVPQV(B08.01) Mammary cancer MAD1L1:MAFK MAD1L1:MAFK RLKEVFQTKIQEFRKACYTLTGYQIDITTENQYRLTSLYAEHPGDCLIFK:: LRVPGSSVLVTVPGL* HPGDCLIFKL(B07.02)
KLRVPGSV(B07.02)
KLRVPGSSVL (B07.02)
RVPGSSVLV (A02.01)
SVLVTVPGL (A02.01)
VPGSSVLVTV (B07.02) CLL PPP1R1B:STARD3 PPP1R1B:STARD3 AEVLKVIRQSAGQKTTCGQGLEGPWERPPPLDESERDGGSEDQVEDPALS: A : LLLRPRPPRPEVGAHQDEQAAQGADPRLGAQPACRGLPGLLTVPQPEPLLAPPSAA* ALLLRPRPPR (A03.01)
ALSALLLRPR (A03.01) Mammary cancer Table 1F IN FRAME DELETIONS AND FUNCTIONS ^1,2 BCR:ABL BCR:ABL ERAEWRENIREQQKKCFRSFSLTSVELQMLTNSCVKLQTVHSIPLTINKE:: EALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASG LTINKEEAL (A02.01, B08.01) CML, AML BCR:ABL BCR:ABL ELQMLTNSCVKLQTVHSIPLTINKEDDESPGLYGFLNVIVHSATGFKQSS: K : ALQRPVASDFEPQGLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGD IVHSATGFK (A03.01)
ATGFKQSSK (A03.01) CML, AML C11orf95:RELA C11orf95:RELA ISNSWDAHLGLGACGEAEGLGVQGAEEEEEEEEEEEEEGAGVPACPPKGP: E : LFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTD ELFPLIFPA (A02.01, B08.01)
KGPELFPLI (A02.01, A24.02)
KGPELFPLIF (A24.02) supratentorial ependymoma CBFB:MYH11 (variant "type a") LQRLDGMGCLEFDEERAQQEDALAQQAFEEARRRTREFEDRDRSHREEME:: VHELEKSKRALETQMEEMKTQLEELEDELQATEDAKLRLEVNMQALKGQF AML CD74:ROS1 (exon6:exon32) KGSFPENLRHLKNTMETIDWKVFESWMHHWLLFEMSRHSLEQKPTDAPPK:: AGVPNKPGIPKLLEGSKNSIQWEKAEDNGCRITYYILEIRKSTSNNLQNQ KPTDAPPKAGV (B07.02) NSCLC resistant to crizotinib EGFR EGFRvIII (internal deletion) MRPSGTAGAALLALLAALCPASRALEEKK: G :NYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKD ALEEKKGNYV (A02.01) GBM EGFR:SEPT14 EGFR:SEPT14 LPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQ:: LQDKFEHLKMIQQEEIRKLEEEKKQLEGEIIDFYKMKAASEALQTQLSTD IQLQDKFEHL (A02.01, B08.01)
QLQDKFEHL (A02.01, B08.01)
QLQDKFEHLK (A03.01)
YLVIQLQDKF (A02.01, A24.02) GBM, glioma, head and neck cancer EML4:ALK EML4:ALK SWENSDDSRNKLSKIPSTPKLIPKVTKTADKHKDVIINQAKMSTREKNSQ: V : YRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDL QVYRRKHQEL (B08.01)
STREKNSQV (B08.01)
VYRRKHQEL (A24.02, B08.01) NSCLC FGFR3:TACC3 FGFR3:TACC3 EGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTD:: VKATQEENRELRSRCEELHGKNLELGKIMDRFEEVVYQAMEEVQKQKELS VLTVTSTDV (A02.01)
VLTVTSTDVK (A03.01) Bladder cancer, LUSC NAB:STAT6 NAB:STAT6 ("option 1" Chmielecki et al.) RDNTLLLRRVELFSSRQVARESTYLSSLKGSRLHPEELGGPPLKKLKQE:: ATSKSQI MSLWGLVSKMPEKVQRLYVDFPQHLRHLLGDWLESQPWEFLVGSDAFCC IMSLWGLVS (A02.01)
IMSLWGLVSK (A03.01)
KLKQEATSK (A03.01)
QIMSLWGLV (A02.01)
SQIMSLWGL (A02.01, A24.02, B08.01)
SQIMSLWGLV (A02.01)
TSKSQIMSL(B08.01) solitary fibrous tumor NDRG1:ERG NDRG1:ERG MSREMQDVDLAEVKPLVEKGETITGLLQEFDVQ:: EALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDW LLQEFDVQEA (A02.01)
LQEFDVQEAL (A02.01) prostate cancer PML:RARA PML:RARA (exon3:exon3) VLDMHGFLRQALCRLRQEEPQSLQAAVRTDGFDEFKVRLQDLSSCITQGK: A : IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKG Acute promyelocytic leukemia PML:RARA PML:RARA (exon6:exon3) RSSPEQPRPSTSKAVSPPHLDGPPSPRSPVIGSEVFLPNSNHVASGAGEA: A : IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKG acute promyelocytic leukemia RUNX1 RUNX1(ex5)-RUNX1T1(ex2) VARFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKITVDGPREPR: N : RTEKHSTMPDSPVDVKTQSRLTPPTMPPPPTTQGAPRTSSFTPTTLTNGT GPREPRNRT (B07.02)
RNRTEKHSTM (B08.01) AML TMPRSS2:ERG TMPRSS2:ERG MALNS::EALSVVSEDQSLFECAYGTPHLAKTEMTASSSSDYGQTSKMSPRVPQQDW ALNSEALSV (A02.01)
ALNSEALSVV (A02.01)
MALNSEALSV (A02.01, B08.01) prostate cancer

¹ Underlined AAs represent non-native AAs

² AAs in bold are native AAs of the amino acid sequence encoded by the second of the two fused genes.

³ Bold and underlined AAs are non-native AAs of the amino acid sequence encoded by the second of the two fused genes due to a frameshift.

table 2

Gene Illustrative protein change Sequence context with mutation Peptides (example(s) of HLA allele) Illustrative diseases Table 2A POINT MUTATIONS1 AKT1 E17K MSDVAIVKEGWLHKRG K YIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTER KYIKTWRPRY (A24.02)
WLHKRGKYI (A02.01, B07.02, B08.01)
WLHKRGKYIK (A03.01) BRCA, CESC, HNSC, LUSC, PRAD, SKCM, THCA ANAPC1 T537A TMLVLEGSGNLVLYTGVVRVGKVFIPGLPAPSLTMSNTMPRPSTPLDGVS A PKPLSKLLGSLDEVVLLSPVPELRDSSKLHDSLYNEDCTFQQLGTYIHSI APKPLSKLL (B07.02)
GVSAPKPLSK (A03.01)
VSAPKPLSK (A03.01) GBM, LUSC, PAAD, PRAD, SKCM FGFR3 S249C HRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLER C PHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVG CPHRPILQA (B07.02) BLCA, HNSC, KIRP, LUSC FRG1B I10T MREPIYMHSTMVFLPWELHTKKGPSPPEQFMAVKLSDSR T ALKSGYGKYLGINSDELVGHSDAIGPREQWEPVFQNGKMALLASNSCFIR KLSDSRTAL (A02.01, B07.02, B08.01)
KLSDSRTALK (A03.01)
LSDSRTALK (A01.01, A03.01)
RTALKSGYGK (A03.01)
TALKSGYGK (A03.01) KIRP, PRAD, SKCM FRG1B L52S AVKLSDSRIALKSGYGKYLGINSDELVGHSDAIGPREQWEPVFQNGKMAL S ASNSCFIRCNEAGDIEAKSKTAGEEEMIKIRSCAEKETKKKDDIPEEDKG ALSASNSCF (A02.01, A24.02, B07.02)
ALSASNSCFI (A02.01)
FQNGKMALSA (A02.01, B08.01) GBM, KIRP, PRAD, SKCM HER2 L755S
(resistance) AMPNQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKV S RENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGC KVSRENTSPK (A03.01) BRCA IDH1 R132G RVEEFKLKQMWKSPNGTIRNILGGTVFREAIICKNIPRLVSGWVKPIIIG G HAYGDQYRATDFVVPGPGKVEITYTPSDGTQKVTYLVHNFEEGGGVAMGM KPIIIGGHAY (B07.02) BLCA, BRCA, CRC, GBM, HNSC, LUAD, PAAD, PRAD, UCEC KRAS G12C MTEYKLVVVGA C GVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQE KLVVVGACGV (A02.01)
LVVVGACGV (A02.01)
VVGACGVGK (A03.01, A11.01)
VVVGACGVGK (A03.01) BRCA, CESC, CRC, HNSC, LUAD, PAAD, UCEC KRAS G12D MTEYKLVVVGA D GVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQE VVGADGVGK (A11.01)
VVVGADGVGK (A11.01)
KLVVVGADGV (A02.01)
LVVVGADGV (A02.01) BLCA, BRCA, CESC, CRC, GBM, HNSC, KIRP, LIHC, LUAD, PAAD, SKCM, UCEC KRAS G12V MTEYKLVVVGA V GVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQE KLVVVGAVGV (A02.01)
LVVVGAVGV (A02.01)
VVGAVGVGK (A03.01, A11.01)
VVVGAVGVGK (A03.01, A11.01) BRCA, CESC, CRC, LUAD, PAAD, THCA, UCEC KRAS Q61H AGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG H EEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPM ILDTAGHEEY (A01.01) CRC, LUSC, PAAD, SKCM, UCEC KRAS Q61 l AGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG L EEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPM ILDTAGLEEY (A01.01)
LLDILDTAGL (A02.01) CRC, GBM, HNSC, LUAD, SKCM, UCEC NRAS Q61K AGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG K EEYSAMRDQYMRTGEGFLCVFAINNSKSFADINLYREQIKRVKDSDDVPM ILDTAGKEEY (A01.01) BLCA, CRC, LIHC, LUAD, LUSC, SKCM, THCA, UCEC NRAS Q61R AGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG R EEYSAMRDQYMRTGEGFLCVFAINNSKSFADINLYREQIKRVKDSDDVPM ILDTAGREEY (A01.01) BLCA, CRC, LUSC, PAAD, PRAD, SKCM, THCA, UCEC PIK3CA E542K IEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLKAISTRDPLS K ITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPP AISTRDPLSK (A03.01) BLCA, BRCA, CESC, CRC, GBM, HNSC, KIRC, KIRP, LIHC, LUAD, LUSC, PRAD, UCEC PTEN R130Q KFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKG Q TGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY QTGVMICAY (A01.01) BRCA, CESC, CRC, GBM, KIRC, LUSC, UCEC RAC1 P29S MQAIKCVVVGDGAVGKTCLLISYTTNAF S GEYIPTVFDNYSANVMVDGKPVNLGLWDTAGQEDYDRLRPLSYPQTVGET FSGEYIPTV (A02.01)
TTNAFSGEY (A01.01)
YTTNAFSGEY (A01.01) Melanoma SF3B1 K700E AVCKSKKSWQARHTGIKIVQQIAILMGCAILPHLRSLVEIIEHGLVDEQQ E VRTISALAIAALAEAATPYGIESFDSVLKPLWKGIRQHRGKGLAAFLKAI GLVDEQQEV (A02.01) AML associated with MDS; Chronic lymphocytic leukemia-small cell lymphoma; myelodysplastic syndrome; AML; breast carcinomas of the luminal type NS; chronic myeloid leukemia; ductal carcinoma of the pancreas; chronic myelomonocytic leukemia; chronic lymphocytic leukemia-small cell lymphoma; myelofibrosis; myelodysplastic syndrome; PRAD; essential thrombocythemia; medullomyoblastoma SPOP F133 l YLSLYLLLVSCPKSEVRAKFKFSILNAKGEETKAMESQRAYRFVQGKDWG L KKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQDSVNISGQNTMNMVKVPE FVQGKDWGL (A02.01, B08.01) PRAD SPOP F133V YLSLYLLLVSCPKSEVRAKFKFSILNAKGEETKAMESQRAYRFVQGKDWG V KKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQDSVNISGQNTMNMVKVPE FVQGKDWGV (A02.01) PRAD TP53 G245S IRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMG S MNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEP CMGSMNRRPI (A02.01, B08.01)
GSMNRRPIL (B08.01)
MGSMNRRPI(B08.01)
MGSMNRRPIL (B08.01)
SMNRRPILTI (A02.01, A24.02, B08.01) BLCA, BRCA, CRC, GBM, HNSC, LUSC, PAAD, PRAD TP53 R248Q EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMN Q RPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE CMGGMNQRPI (A02.01, B08.01)
GMNQRPILTI (A02.01, B08.01)
NQRPILTI (A02.01, B08.01) BLCA, BRCA, CRC, GBM, HNSC, KIRC, LIHC, LUSC, PAAD, PRAD, UCEC TP53 R248W EGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMN W RPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHE CMGGMNWRPI (A02.01, A24.02, B08.01)
GMNWRPILTI (A02.01, B08.01)
MNWRPILTI (A02.01, A24.02, B08.01)
MNWRPILTI (A02.01, A24.02) BLCA, BRCA, CRC, GBM, HNSC, LIHC, LUSC, PAAD, SKCM, UCEC TP53 R273C PEVGSDCTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEV C VCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPL NSFEVCVCA (A02.01) BLCA, BRCA, CRC, GBM, HNSC, LUSC, PAAD, UCEC TP53 R273H PEVGSDCTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEV H VCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPL NSFEVHVCA (A02.01) BRCA, CRC, GBM, HNSC, LIHC, LUSC, PAAD, UCEC TP53 Y220C TEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVP C EPPEVGSDCTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSF VVPCEPPEV (A02.01)
VVVPCEPPEV (A02.01) BLCA, BRCA, GBM, HNSC, LIHC, LUAD, LUSC, PAAD, SKCM, UCEC Table 2B MSI-ASSOCIATED READING FRAME SHIFTS 1 MSH6 F1088fs; +1 YNFDKNYKDWQSAVECIAVLDVLLCLANYSRGGDGPMCRPVILLPEDTPP LLRA ILLPEDTPPL (A02.01)B
LLPEDTPPL (A02.01) B B MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer, Lynch syndrome Table 2C READING FRAME SHIFT 1 APC F1354fs AKFQQCHSTLEPNPADCRVLVYLQNQPGTKLLNFLQERNLPPKVVLRHPKVHLNTMFRRPHSCLADVLLSVHLIVLRVVRLPAPFRVNHAVEW* APFRVNHAV (B07.02)
CLADVLLSV (A02.01)
FLQERNLPPK (A03.01)
HLIVLRVVRL (A02.01, B08.01)
HPKVHLNTTM (B07.02, B08.01)
HPKVHLNTMF (B07.02, B08.01)
KVHLNTMFR (A03.01)
KVHLNTMFRR (A03.01)
LPAPFRVNHA (B07.02)
MFRRPHSCL (B07.02, B08.01)
MFRRPHSCLA (B08.01)
NTMFRRPHSC (B08.01)
RPHSCLADV (B07.02)
RPHSCLADVL (B07.02)
RVVRLPAPFR (A03.01)
SVHLIVLRV (A02.01)
TMFRRPHSC (B08.01)
TMFRRPHSCL (A02.01, B08.01)
VLLSVHLIV (A02.01)
VLLSVHLIVL (A02.01)
VLRVVRLPA (B08.01)
VVRLPAPFR (A03.01) CRC, LUAD, UCEC, STAD ARID1A Y1324fs * AMPILPLPQL (A02.01)
APLLAAPSPA(B07.02)
APRTNFHSS (B07.02)
APRTNFHSSL (B07.02, B08.01)
CPQPSSPSLPA (B07.02)
GQWMAHMAL(A02.01)
GQWMAHMALL (A02.01)
HMALLPSGTK (A03.01)
HTALGRGSL(B07.02)
IPMAISSPP (B07.02)
IPMAISSPPK (B07.02)
KLPSLPLSK (A03.01)
KLPSLPLSKM (A02.01)
KMYTTSMAM (A02.01, A03.01)
LLAAPPSPASR (A03.01)
LLLSADQQAA (A02.01)
LLSADQQAA (A02.01)
LPASNKLPS (B07.02)
LPASNKLPSL (B07.02, B08.01)
LPLPQLLSA (B07.02)
LPSLPLSKM (B07.02)
LSKMYTTSM (B08.01)
MALLPSGTK (A03.01)
MPILPLPQL (B07.02)
MPILPLPQLL (B07.02)
MYTTSMAMPI (A24.02)
PMAISSPPK (A03.01)
QWMAHMALL (A24.02)
SKMYTTSMAM (B07.02)
SMAMPILPL (A02.01, B07.02, B08.01)
SNKLPSLPL (B08.01)
SPASRLQCI (B07.02, B08.01)
SPPKAPLLAA (B07.02)
SPSLPASNKL (B07.02)
YTTSMAMPI (A02.01)
YTTSMAMPIL (A02.01) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS ARID1A G1848fs RSYRRMIHLWWTAQISLGVCRSLTVACCTGGLVGGTPLSISRPTSRARQSCCCLPGLTHPAHQPLGSM* CLPGLTHPA (A02.01)
GLTHPAHQPL (A02.01)
HPAHQPLGSM (B07.02)
LTHPAHQPL(B07.02)
RPTSRARQSC (B07.02)
RQSCCLPGL (A02.01)
TSRARQSCCL(B08.01) STAD, UCEC, BLCA, BRCA, LUSC, CESC, KIRC, UCS β2M L13fs QHSGRDVSLRGLSCARATLSFWPGGYPAYSKDSGLLTSSSSREWKVKFPELLCVWVSSIRH* ELLCVWVSSI (A02.01)
EWKVKFPEL (B08.01)
KFPELLCVW(A24.02)
LLCVWVSSI (A02.01)
LLTSSSSREWK (A03.01)
LTSSSREWK (A03.01)
YPAYSKDSGL (B07.02) CRC, STAD, SKCM, HNSC GATA3 L328fs
N334fs AQAKAVCSQESRDVLCELSDHHNHTLEEECQWGPCLQCLWALLQASQY* CLQCLWALL (A02.01)
CQWGPCLQCL (A02.01)
QWGPCLQCL (A24.02)
QWGPCLQCLW (A24.02) Mammary cancer GATA3 H400fs
S408fs
S408fs
S430fs
H434fs
H435fs PGRPLQTHVLPEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHRHGLEPCSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLKAESKIMFATLQRSSLWCLCSNH* AIQPVLWTT (A02.01)
ALQPLQPHA (A02.01)
DLHFCRSSIM (B08.01)
EPHLALQPL (B07.02, B08.01)
ESKIMFATL (B08.01)
FATLQRSSL (B07.02, B08.01)
FLKAESKIM (B08.01)
FLKAESKIMF (B08.01)
GPPARVPAV (B07.02)
IMKPKRDGYM (B08.01)
KIMFATLQR (A03.01)
KPKRDGYMF (B07.02)
KPKRDGYMFL(B07.02)
LHFCRSSIM (B08.01)
LQHGHRHGL(B08.01)
MFATLQRSSL (B07.02, B08.01)
MFLKAESKI (A24.02)
MLTGPPARV (A02.01)
QPVLWTTPPL (B07.02)
SMLTGPPARV (A02.01)
TLQRSSLWCL (A02.01)
VLPEPHLAL (A02.01)
VPAVPFDLHF (B07.02)
YMFLKAESK (A03.01)
YMFLKAESKI (A02.01, A03.01, A24.02, B08.01) Mammary cancer MLL2 P647fs
L656fs APGPRGRTC(B07.02)
CLRSHTCPPR (A03.01)
CLWCHACLHR (A03.01)
CPHLGSHPC(B07.02)
CPLGLKSPL(B07.02)
CPRSCRCPH (B07.02)
CPRSCRCPHL (B07.02, B08.01)
CSLPLGNHPY(A01.01)
GLRNRICPL (A02.01, B07.02, B08.01)
GLRSHTYLR (A03.01)
GLRSHTYLRR (A03.01)
GPRGRTCHPG (B07.02)
HLGSHPCRL(B08.01)
HLRLHASPH (A03.01)
HLRSCPCSL (B07.02, B08.01)
HLRTHLLPH (A03.01)
HLRTHLLPHH (A03.01)
HLRYRAYPP (B08.01)
HLRYRAYPPC (B08.01)
HPHHLRTHL(B07.02)
HPHHLRTHLL (B07.02, B08.01)
HTYLRRLRSH (A03.01)
LPCPHRLRSL (B07.02, B08.01)
LPHHRRTRSC (B07.02, B08.01)
LPLGNHPYL (B07.02)
LPRPLHLRL (B07.02, B08.01)
NLRNHTCPP(B08.01)
PPRLRSRTCL (B07.02, B08.01)
RLHASPHL (A02.01)
RLHASPHLR (A03.01)
RLRDHICPL (A02.01, B07.02, B08.01)
RLRNLPCPPH (A03.01)
RLRNLPCPHR (A03.01)
RLRSHTCPP(B08.01)
RLRSLPRPL (B07.02, B08.01)
RLRSLPRPLH (A03.01)
RLRSRTCLL (B07.02, B08.01)
RNRICPLSL (B07.02, B08.01)
RPLHLRLHA (B07.02)
RPLHLRLHAS (B07.02)
RSHACPPGLR (A03.01)
RSHACPPNLR (A03.01)
RSHAYALCLR (A03.01)
RSHPCCHYLR (A03.01)
RSHPCPLGLK (A03.01)
RSHTCPPSLR (A03.01)
RSLPRPLHLR (A03.01)
RSRTCLLCL (B07.02)
RSRTCLLCLR (A03.01)
RSRTCPPGL(B07.02)
RSRTCPPGLR (A03.01)
RTHLLPHHRR (A03.01)
RTRSCPCRWR (A03.01)
RYRAYPPCL (A24.02)
RYRAYPPCLW (A24.02)
SLGNHLCPL (A02.01, B07.02, B08.01)
SLPLGNHPYL (A02.01)
SLPRPLHLRL (A02.01)
SLRNCTCPPR (A03.01)
SLRSHAYAL (A02.01, B07.02, B08.01)
SLRSHPCPL (A02.01, B07.02, B08.01)
SPHHLRTPP(B07.02)
SPHHLRTPPH (B07.02)
SPLRSQANAL (B07.02, B08.01)
YLRRLRSHTTC (B08.01)
YLRSRNSAP(B08.01)
YLRSRNSAPG (B08.01) STAD, BLCA, CRC, HNSC, BRCA MLL2 P2354fs GPRSHPLPRLWHLLLQVTQTSFALAPTLTHMLSPH* ALAPTLTHM (A02.01)
ALAPTLTHML (A02.01)
LLQVTQTSFA (A02.01)
LQVTQTSFAL (A02.01)
RLWHLLLQV (A02.01)
RLWHLLLQVT (A02.01) STAD, BLCA, CRC, HNSC, BRCA RNF43 G659fs PLGLVPWTRWCPQGKPRFPAMSTTTATGTTTTKSGSSGMAGSLAQKPESPSPGLLFLGHSPSQSHLLLISKSPDPTQQPLRGGSLTHSAPGPSLSQPLAQLTPPASAPVPAVCSTCKNPASLPDTHRGKGGGVPPSPPLALGPRMQLCTQLARFFPITPPVWHILGPQRHTP* CTQLARFFPI (A24.02)
FFPITPPVW(A24.02)
FPITPPVWHI (B07.02)
GPRMQLCTQL (B07.02, B08.01)
ITPPVWHIL (A24.02)
LALGPRMQL (B07.02)
MQLCTQLARF (A24.02)
RFFPITPPV (A02.01, A24.02)
RFFPITPPVW (A24.02)
RMQLCTQLA (A02.01)
RMQLCTQLAR (A03.01)
SPPLALGPRM (B07.02)
TQLARFFPI (A02.01, A24.02, B08.01) STAD SMAP1 E169fs KYEKKKYYDKNAIAITNISSSDAPLQPLVSSPSLQAAVDKNKLEKEKEKK RKRKREKRSQKSRQNHLQLKSCRRKISNWSLKKVPALKKLRSPLWIF KSRQNHLQL(B07.02)
ALKKLRSP (B08.01, B07.02)
HLQLKSCRRK (A03.01)
KISNWSLKK (A03.01, A11.01)
KISNWSLKKV (A03.01)
KLRSPWIF (A24.02)
KSRQNHLQLK (A03.01)
NWSLKKVPAL (B08.01)
SLKKVPALK (A03.01, A11.01)
SLKKVPALKK (A03.01)
SQKSRQNHL(B08.01)
WSLKKVPAL(B08.01)
WSLKKVPALK (A03.01) MSI+ CRC, MSI+ uterine/endometrial cancer, MSI+ gastric cancer TP53 P58fs
P72fs
G108fs
R110fs CCPRTILNNGSLKTQVQMKLPECQRLLPPWPLHQQLLHRRPLHQPPPGPCHLLSLPRKPTRAATVSVWASCILGQPSL* KLPECQRLL (A02.01)
KPTRAATVSV (B07.02)
LPPWPLHQQL (B07.02)
LPRKPTRAA (B07.02, B08.01)
LPRKPTRAAT (B07.02)
QQLLHRRP (B08.01)
RLLPPWPLH (A03.01) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC TP53 P152fs LARTPLPSTRCFANWPRPALCSCGLIPHPRPAPASAPWPSTSSHST* APASAPWPST (B07.02)
APWPSTSSH(B07.02)
RPAPASAPW(B07.02)
WPSTSSHST(B07.02) BRCA, CRC, LUAD, PRAD, HNSC, LUSC, PAAD, STAD, BLCA, OV, LIHC, SKCM, UCEC, LAML, UCS, KICH, GBM, ACC UBR5 K2120fs SQGLYSSSASSGKCLMEVTVDRNCLEVLPTKMSYAANLKNVMNMQNRQKK KGKNSPCCQKKLRVQNQGHLLMILLHN* RVQNQGHLL (B07.02) V V VHL L116fs
G123fs TRASPPRSSSAIAVRASCCPYGSTSTASRSPTQRCRLARAAASTATEVTFGSSEMQGHTMGFWLTKLNYLCHLSMLTDSLFLPISHCQCIL* FLPISHCQCI (A02.01)
FWLTKLNYL (A24.02, B08.01)
HLSMLTDSL (A02.01)
HTMGFWLTK (A03.01)
HTMGFWLTKL (A02.01)
KLNYLCHLSM (A02.01)
LPISHCQCI (B07.02, B08.01)
LPISHCQCIL (B07.02, B08.01)
LTDSLFLPI (A01.01, A02.01)
LTKLNYLCHL(B08.01)
MLTDSLFLPI (A01.01, A02.01, B08.01)
MQGHTMGFWL (A02.01)
NYLCHLSML (A24.02)
SMLTDSLFL (A02.01)
TMGFWLTKL (A02.01)
YLCHLSMLT (A02.01) KIRC, KIRP TABLE2D BOX ¹ HER2 G776insYVMA LGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMA YVMA GVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW ILDEAYVMAY (A01.01)
VMAYVMAGV (A02.01)
YVMAYVMAG (A02.01, B07.02, B08.01)
YVMAYVMAGV (A02.01, B07.02, B08.01) Lungs' cancer

¹ Underlined AAs represent non-native AAs

² AAs in bold are native AAs of the amino acid sequence encoded by the second of the two fused genes.

³ Bold and underlined AAs are non-native AAs of the amino acid sequence encoded by the second of the two fused genes due to a frameshift.

[612] In the tables above, for one or more exemplary fusions, the sequence that precedes the first ":" belongs to the sequence of the exon of the polypeptide encoded by the first gene, the sequence that comes after the second ":" belongs to the sequence of the exon of the polypeptide encoded by the second gene, and the amino acid between the ":" characters is encoded by a codon that is split between the sequence of the exon of the polypeptide encoded by the first gene and the sequence of the exon of the polypeptide encoded by the second gene.

However, in certain embodiments, such as NAB:STAT6, the NAB exon is linked to the 5' UTR of STAT6 and the first amino acid that appears after the junction is the normal STAT6 start codon (there is no reading frame in this region (because it is usually not broadcast).

AR-V7 in the tables above can also be considered, in certain embodiments, an AR gene splicing variant that encodes a protein that does not contain a ligand-binding domain found in a full length AR.

Example 2 HLA Class I and Class II Binding Assays

[613] The following example of peptide binding to HLA molecules demonstrates the quantification of the binding affinity of class I and class II HLA peptides. Binding assays can be performed using motif-bearing or non-motif-bearing peptides.

[614] As sources of HLA class I molecules, CIR transfectants or 721.22 Epstein-Barr virus (EBV) transformed homozygous cell lines, fibroblasts, are used. Cell lysates are prepared and HLA molecules are purified according to the disclosed protocols (Sidney et al., Current Protocols in Immunology 18.3.1 (1998), Sidney, et al., J. Immunol., 154:247 (1995), Sette, et al., Mol. Immunol., 31: 813 (1994)). HLA molecules are isolated from lysates using affinity chromatography. The lysates are passed through a column of Sepharose CL-4B beads bound to the appropriate antibody. The anti-HLA antibody column is then washed with 10 mM Tris-HCl, pH 8.0, in 1% NP-40, PBS and PBS containing 0.4% n-octylglucoside, and the HLA molecules are eluted with 50 mM diethylamine in 0.15 M NaCl containing 0.4% n-octylglucoside, pH 11.5. To the eluate is added 1/25 volume of 2.0 M Tris, pH 6.8 to lower the pH to ~8.0. The eluates are then concentrated by centrifugation in Centriprep 30 concentrators (Amicon, Beverly, MA). Protein content was assessed by BCA protein assay (Pierce Chemical Co., Rockford, IL) and confirmed by SDS-PAGE.

[615] A detailed description of the protocol used to measure the binding affinity of peptides to MHC class I and class II has been published (Sette et al., Mol. Immunol., 31: 813, 1994; Sidney et al., Current Protocols in Immunology, Margulies, Ed., John Wiley & Sons, New York, Section 18.3, 1998). Briefly, purified MHC molecules (5 to 500 nM) are incubated with various unlabeled peptide inhibitors and 1-10 nM ¹²⁵ I radiolabeled peptide probes for 48 hours in PBS containing 0.05% Nonidet P-40 (NP40 ) (or 20% w/v diginonin for H-2 IA assays) in the presence of a mixture of protease inhibitors. All assays are run at pH 7.0, except for DRB1*0301, which is run at pH 4.5, and DRB1*1601 (DR2w21β1) and DRB4*0101 (DRw53), which is run at pH 5.0.

[616] After incubation, the MHC-peptide complexes are separated from the free peptide by gel filtration on 7.8 mm×15 cm TSK200 columns (TosoHaas 16215, Montgomeryville, PA). Because the large size of the radiolabeled peptide used for the DRB1*1501 (DR2w2β1) assay makes it difficult to separate bound from unbound peaks under these conditions, all DRB1*1501 (DR2w2β1) assays were performed using a TSK2000 7.8 mm x 30 cm column. , eluted at a rate of 0.6 ml/min. The eluate from the TSK columns was passed through a Beckman 170 radioisotope detector and the radioactivity was plotted and combined using a Hewlett-Packard 3396A integrator and the fraction of bound peptide was determined.

[617] Radioactively labeled peptides are iodinated by the chloramine-T method. Typically, in preliminary experiments, each MHC preparation is titrated in the presence of fixed amounts of radiolabeled peptides to determine the concentration of HLA molecules required to bind 10-20% of the total radioactivity. All subsequent inhibition and direct binding assays are performed using these HLA concentrations.

[618] Because under these conditions [label]<[HLA] and IC50≥[HLA], the measured IC ₅₀ values are a reasonably accurate approximation of the true K _D values. Peptide inhibitors are typically tested at concentrations from 120 μg/ml to 1.2 ng/ml and tested in two to four completely independent experiments. To allow comparison of data from different experiments, relative binding is calculated for each peptide by dividing the IC ₅₀ of the positive control for inhibition by the IC ₅₀ for each test peptide (generally unlabeled versions of the radiolabeled probe peptide). For database and comparisons between experiments, relative binding values are compared. These values can subsequently be converted back to IC ₅₀ nM values by dividing the IC ₅₀ nM of positive inhibition controls by the relative binding of the peptide of interest. This data compilation method proved to be the most accurate and consistent for comparing peptides that were tested on different days, or with different lots of purified MHC.

[619] Because the antibody used to purify HLA-DR (LB3.1) is an α chain, β1 molecules are not separated from β3 (and/or β4 and β5) molecules. The specificity of the β1 binding assay is evident in the cases of DRB1*0101 (DR1), DRB1*0802 (DR8w2) and DRB1*0803 (DR8w3) where β3 is not expressed. This has also been demonstrated for DRB1*0301 (DR3) and DRB3*0101 (DR52a), DRB1*0401 (DR4w4), DRB1*0404 (DR4w14), DRB1*0405 (DR4w15), DRB1*1101 (DR5), DRB1*1201 (DR5w12), DRB1*1302 (DR6w19) and DRB1*0701 (DR7). The problem of β-chain specificity for DRB1*1501 (DR2w2β1), DRB5*0101 (DR2w2β2), DRB1*1601 (DR2w21β1), DRB5*0201 (DR51Dw21) and DRB4*0101 (DRw53) is analyzed using fibroblasts. The development and validation of assays for the specificity of the DRβ molecule have been described previously (see, for example, Southwood et al., J. Immunol., 160: 3363-3373, 1998).

[620] A detailed description of the protocol used to measure the binding stability of peptides to MHC class I has been published (Harndahl et al., J. Immunol Methods, 374: 5-12, 2011). Briefly, synthetic genes encoding biotinylated MHC-I heavy and light chains are expressed in E. coli and purified from inclusion bodies by standard methods. The light chain (β2m) is radiolabeled with iodine ( ¹²⁵ I) and combined with the purified MHC-I heavy chain and the peptide of interest at 18°C to initiate the formation of the pMHC-I complex. These reactions are carried out on streptavidin-coated microplates to bind biotinylated MHC-I heavy chains to the surface and allow the measurement of radiolabeled light chains to monitor complex formation. Dissociation is initiated by adding higher concentrations of loose light chain and incubation at 37°C. Stability is defined as the length of time in hours it takes for half of the complexes to dissociate, as measured by a scintillation counter.

[621] Live cell/flow cytometric assays can also be performed, for example, assay using a TAP-deficient T2 hybridoma cell line (American Type Culture Collection (ATCC accession number CRL-1992), Manassas, Va.). TAP deficiency in this cell line results in an inefficient MHCI loading in the ER and an excess of empty MHCIs. Salter and Cresswell, EMBO J. 5: 943-49 (1986); Salter, Immunogenetics 21: 235-46 (1985). Empty MHCIs are very unstable and short lived. When T2 cells are cultured at lower temperatures, empty MHCIs appear permanently on the cell surface where they can be stabilized by exogenous addition of MHCI binding peptides. For this binding assay, peptide-receptor MHCIs were induced by culturing aliquots of 10 ⁷ T2 cells overnight at 26° C. in serum-free AIM-V medium alone or in medium containing increasing concentrations (from 0.1 to 100 μM) of the peptide. Cells were then washed twice with PBS and then incubated with fluorescently labeled HLA-A0201 specific monoclonal antibody BB7.2 to quantify cell surface expression. Samples were obtained on a FACS Calibur device (Becton Dickinson) and the mean fluorescence intensity (MFI) was determined using the accompanying Cellquest software.

Example 3 HLA Class I Binding Affinity

[622] HLA binding assays were used to evaluate the interaction affinity of a given epitope for a selected HLA molecule or stability. Each of these measurements was, for example, an indication of the ability of an epitope to elicit a CD8+ T cell response.

[623] A subset of the peptides from Table 1 (n=562) was synthesized and their affinity for their given HLA class I molecule was measured as described. Values are shown in Table 3. Measurements were plotted against the theoretically calculated affinity in Figure 1. These data show a strong correlation between prediction and measurement (dashed line fits best, R2=0.45), demonstrating the value of the predictions. However, outliers demonstrate the importance of these measurements. Thick vertical and horizontal lines are shown at 500 nM for theoretically calculated affinity and observed affinity, respectively. 500 nM is generally accepted in the art as the maximum affinity for an epitope that is "weakly binding" to HLA class I. Thus, in the lower right quadrant (predicted over 500 nM, measured less than 500 nM) are epitopes that are considered very weak binders, but were observed to bind in an acceptable range. The epitopes in this quadrant (n=75) represent 30.5% of the epitopes that are not considered predictive binding (combination of lower right and upper right quadrants, n=246).

Table 3: Binding affinity and stability of HLA class I

Mutation allele Peptide Theoretical calculated affinity (IC ₅₀ ; (nM)) Observed affinity (IC ₅₀ ; (nM)) Stability (T _1/2 (h)) ABL1, M351T A02.01 TQISSATEYL 2921.0 2644.0 0 ABL1, T315I A02.01 YIIIEFMTYG 3502.0 186.0 0 ABL1, T315I A02.01 IIIEFMTYG 1991.0 779.0 0 ABL1, T315I A02.01 IIIEFMTYGN 16793.0 1551.0 0 ABL1, T315I A02.01 IIEFMTYGNL 2134.0 9702.0 0 ABL1, Y253H A02.01 KLGGGQHGEV 1705.0 387.0 0.4 AKT1, E17K B08.01 WLHKRGKYI 47.0 417.0 1.3 AKT1, E17K A02.01 WLHKRGKYI 4972.0 1250.0 1.2 AKT1, E17K B07.02 WLHKRGKYI 7185.0 2648.0 0 ALK, G1269A A02.01 RVAKIADFGM 5258.0 125.0 0.5 ALK, G1269A B07.02 RVAKIADFGM 7260.0 9723.0 0.2 ALK, L1196M A02.01 SLPRFILMEL 94.0 26.0 0.5 ALK, L1196M A02.01 ILMELMAGG 192.0 223.0 0.5 ALK, L1196M A02.01 LMELMAGGDL 5617.0 311.0 8.9 ALK, L1196M A02.01 LQSLPRFILM 2519.0 413.0 0 ALK, L1196M B07.02 SLPRFILMEL 17.0 583.0 0.4 ALK, L1196M B08.01 LQSLPRFILM 1288.0 1547.0 0 ALK, L1196M A02.01 FILMELMAGG 189.0 1580.0 0 ALK, L1196M B08.01 SLPRFILMEL 686.0 1762.0 0 ALK, L1196M A24.02 SLPRFILMEL 5143.0 2774.0 0.2 ALK, L1196M A02.01 ILMELMAGGD 5761.0 3451.0 0 APC, AVEW A02.01 VLLSVHLIV 36.0 72.0 eleven APC, AVEW A02.01 CLADVLLSV 5.0 219.0 24 APC, VHPA A02.01 KVLQMDFLV 25.0 11.0 6.4 APC, VHPA A02.01 LQMDFLVHPA 26.0 68.0 1.5 β2M,...MPAV A03.01 TTLNSPPLKK 62.5 14.3 not measured β2M,...MPAV A03.01 TTLNSPPLK 165.4 9.8 not measured β2M,...MPAV A03.01 TLNSPPLKK 27.5 5.4 not measured β2M,...MPAV A03.01 CTTLNSPPLK 225.3 63.6 not measured β2M,...MPAV B08.01 CLSARTGLSI 1106.6 149.6 not measured β2M,...MPAV A02.01 GLSISCTTL 669.0 114.5 not measured β2M,...SIRH A03.01 LTSSSREWK 413.9 117.8 not measured β2M,...SIRH A03.01 LLTSSSSREWK 206.1 1769.8 not measured β2M,...SIRH B07.02 YPAYSKDSGL 41.1 79.5 not measured β2M,...SIRH B08.01 EWKVKFPEL 488.7 538.4 not measured β2M,...SIRH A24.02 KFPELLCVW 83.7 13.7 not measured β2M,...SQIS B08.01 LQRFRFTHV 55.5 37.3 not measured β2M,...SQIS A24.02 RLSSVLQRF 288.9 28.2 not measured β2M,...SQIS A02.01 VLQRFRFTHV 163.4 106.7 not measured β2M,...SQIS B08.01 VLQRFRFTHV 264.1 480.1 not measured β2M,...SQIS A03.01 RLSSVLQRFR 168.1 12.5 not measured BCR:ABL (e13a2, aka b2a2) B08.01 LTINKEEAL 4972.0 895.0 0 BCR:ABL (e13a2, aka b2a2) A02.01 LTINKEEAL 12671.0 4413.0 0 BRAF, V600E A02.01 LATEKSRWSG 39130.0 23337.0 0 BRAF, V600E B08.01 LATEKSRWS 24674.0 36995.0 0 BRAF, V600E B08.01 LATEKSRWSG 13368.0 46582.0 0 BRAF, V600E A02.01 LATEKSRWS 39109.0 60997.0 0 BTK, C481S A02.01 SLLNYLREM 48.0 87.0 3 BTK, C481S A02.01 MANGSLLNYL 2979.0 1082.0 0 BTK, C481S B07.02 SLLNYLREM 6544.0 1110.0 0 BTK, C481S B08.01 SLLNYLREM 1091.0 1230.0 0 BTK, C481S A02.01 YMANGSLLN 7856.0 4444.0 0 BTK, C481S B07.02 MANGSLLNYL 8921.0 17715.0 0 BTK, C481S B08.01 MANGSLLNYL 7639.0 19853.0 0 BTK, C481S A03.01 MANGSLLNY 1030.3 35.6 not measured BTK, C481S A01.01 MANGSLLNY 285.7 439.0 not measured BTK, C481S A24.02 EYMANGSLL 213.2 5.0 not measured BTK, C481S A01.01 YMANGSLNY 95.7 13.2 not measured BTK, C481S A03.01 YMANGSLNY 109.4 95.9 not measured C11orf95:RELA A02.01 ELFPLIFPA 13.0 13.0 5.1 C11orf95:RELA A24.02 KGPELFPLI 909.0 14.0 1.7 C11orf95:RELA A02.01 KGPELFPLI 6840.0 101.0 0.3 C11orf95:RELA B08.01 ELFPLIFPA 7316.0 449.0 0 C15ORF40(+1) A02.01 KLFSCLSFL 6.0 6.0 14.3 C15ORF40(+1) A03.01 KLFSCLSFL 1488.0 308.0 0.8 C15ORF40(+1) A03.01 SLQPPPPGFK 26.3 19.0 not measured C15ORF40(+1) A03.01 LFFFFETK 658.4 413.3 not measured C15ORF40(+1) A02.01 ALFFFFFET 28.9 470.7 not measured C15ORF40(+1) A03.01 ALFFFFFETK 31.5 216.4 not measured C15ORF40(+1) A02.01 FFFETKSCSV 754.5 61.2 not measured C15ORF40(+1) B08.01 FFETKSCSV 807.6 7.6 not measured C15ORF40(+1) A01.01 LSFLSSWDY 211.1 52.9 not measured C15ORF40(+1) A02.01 FLSSWDYRRM 62.2 323.5 not measured C15ORF40(+1) A03.01 LSFLSSWDYR 508.7 100.9 not measured C15ORF40(+1) A02.01 FKLFSCLSFL 9.9 662.9 not measured C15ORF40(+1) A02.01 VQWRSLGSL 986.0 4733.2 not measured C15ORF40(+1) A02.01 KLFSCLSFLS 65.1 0.6 not measured C15ORF40(+1) A03.01 KLFSCLSFLS 805.1 104.0 not measured C15ORF40(+1) A02.01 AQAGVQWRSL 630.2 670.0 not measured C15ORF40(+1) A24.02 RRMPPCLANF 253.0 141.1 not measured C15ORF40(+1) A03.01 CLSFLSSWDY 890.5 2705.8 not measured C15ORF40(+1) A24.02 GFKLFSCLSF 387.4 643.0 not measured C15ORF40(+1) A24.02 RMPPCLANF 34.4 8.7 not measured C15ORF40(+1) A03.01 CLANFCIFNR 575.4 221.8 not measured C15ORF40(+1) A01.01 CLSFLSSWDY 538.7 987.3 not measured CNOT1(+1) A02.01 SVCFFFFSV 27.0 175.0 9.4 CNOT1(+1) B08.01 SVCFFFFSV 4940.0 10599.0 0 CNOT1(+1) A02.01 MSVCFFFFSV 131.0 1706.4 not measured CNOT1(+1) A02.01 FFFSVIFST 608.9 4556.0 not measured CNOT1(-1) A01.01 MSVCFFFFCY 310.4 4369.3 not measured CNOT1(-1) A02.01 SVCFFFFCYI 237.2 519.8 not measured CNOT1(-1) A24.02 FFCYILNTMF 583.4 73.4 not measured EGFR, T790M A02.01 MQLMPFGCLL 21.0 20.0 0.4 EGFR, T790M A02.01 MQLMPFGCL 842.0 166.0 0.4 EGFR, T790M A02.01 LIMQLMPFGC 1984.0 177.0 0.4 EGFR, T790M A02.01 QLIMQLMPF 2511.0 227.0 0.3 EGFR, T790M B08.01 QLIMQLMPF 891.0 388.0 0 EGFR, T790M B08.01 IMQLMPFGCL 1302.0 548.0 0 EGFR, T790M A02.01 CLTSTVQLIM 3465.0 716.0 0 EGFR, T790M A02.01 IMQLMPFGCL 143.0 837.0 0.5 EGFR, T790M A02.01 IMQLMPFGC 1123.0 1607.0 0.4 EGFR, T790M B07.02 MQLMPFGCL 10169.0 2270.0 0 EGFR, T790M A24.02 QLIMQLMPF 3209.0 2389.0 0.4 EGFR, T790M A02.01 LIMQLMPFG 4961.0 3513.0 0 EGFR, T790M A24.02 VQLIMQLMPF 1455.0 4559.0 0 EGFR, T790M A02.01 VQLIMQLMPF 4464.0 5492.0 0 EGFR, T790M A02.01 QLIMQLMPFG 5751.0 5926.0 0 EGFR, T790M B08.01 MQLMPFGCL 1105.0 7045.0 0 EGFR, T790M A02.01 STVQLIMQL 2151.0 8537.0 0 EGFR, T790M A01.01 CLTSTVQLIM 2998.0 11036.0 0 EGFR, T790M B08.01 MQLMPFGCLL 970.0 14056.0 0 EGFR, T790M B08.01 VQLIMQLMPF 3370.0 17898.0 0 EGFR, T790M A24.02 IMQLMPFGCL 4394.0 18102.0 0 EGFR, T790M A24.02 MQLMPFGCLL 4168.0 23572.0 0 EGFR, T790M A01.01 LTSTVQLIM 1000.7 2891.1 not measured EGFR:SEPT14 B08.01 QLQDKFEHL 917.0 989.0 0 EGFR:SEPT14 A02.01 QLQDKFEHL 422.0 1155.0 0.6 EGFR:SEPT14 A02.01 YLVIQLQDKF 9963.0 2057.0 0 EGFR:SEPT14 A24.02 YLVIQLQDKF 9508.0 2152.0 2.6 EGFR:SEPT14 A02.01 IQLQDKFEHL 820.0 4265.0 0.2 EGFR:SEPT14 B08.01 IQLQDKFEHL 4278.0 10247.0 0 EGFRvIII (internal deletion) A02.01 ALEEKKGNYV 2445.0 141.0 0 EIF2B3(-1) A02.01 KQWSSVTSL 54.4 26.5 not measured EML4:ALK B08.01 QVYRRKHQEL 194.0 160.0 0 EPHB2(-1) A02.01 ILIRKAMTV 38.2 19.5 not measured ESR1, D538G A24.02 PLYGLLLEML 1519.0 444.0 6.3 ESR1, D538G A02.01 GLLLEMLDA 705.0 558.0 0.4 ESR1, D538G A02.01 PLYGLLLEM 349.0 640.0 0.7 ESR1, D538G A24.02 VVPLYGLLL 2965.0 658.0 0.8 ESR1, D538G A02.01 PLYGLLLEML 542.0 797.0 0 ESR1, D538G A02.01 VVPLYGLLL 4432.0 1039.0 0.6 ESR1, D538G A02.01 NVVPLYGLL 4835.0 10471.0 0 ESR1, D538G B07.02 VPLYGLLLEM 145.1 27.9 not measured ESR1, D538G A24.02 LYGLLLEML 218.3 0.8 not measured ESR1, S463P A02.01 FLPSTLKSL 71.0 21.0 2.1 ESR1, S463P A02.01 GVYTFLPST 307.0 779.0 1.3 ESR1, S463P A24.02 FLPSTLKSL 10723.0 995.0 one ESR1, S463P A02.01 GVYTFLPSTL 248.0 1197.0 0.4 ESR1, S463P B08.01 FLPSTLKSL 2314.0 1968.0 0 ESR1, S463P A24.02 GVYTFLPSTL 954.0 7696.0 0 ESR1, Y537C A02.01 PLCDLLLEM 1067.0 602.0 0.8 ESR1, Y537C A02.01 VVPLCDLLL 5533.0 1200.0 0 ESR1, Y537C A02.01 NVVPLCDLLL 1964.0 1373.0 0 ESR1, Y537C A02.01 PLCDLLLEML 1320.0 2008.0 0.9 ESR1, Y537C A02.01 NVVPLCDLL 3473.0 3027.0 0 ESR1, Y537C A24.02 VVPLCDLLL 7992.0 3888.0 0.4 ESR1, Y537N A02.01 PLNDLLLEM 1062.0 151.0 4.2 ESR1, Y537N A02.01 NVVPLNDLL 4725.0 2900.0 0 ESR1, Y537N A02.01 NVVPLNDLLL 2606.0 4190.0 0 ESR1, Y537N A02.01 PLNDLLLEML 1741.0 11957.0 0 ESR1, Y537S A02.01 PLSDLLLEM 713.0 404.0 2.7 ESR1, Y537S A02.01 NVVPLSDLLL 2510.0 741.0 0 ESR1, Y537S A02.01 NVVPLSDLL 4259.0 916.0 0 ESR1, Y537S A02.01 VVPLSDLLL 8320.0 2551.0 0 ESR1, Y537S A02.01 PLSDLLLEML 1138.0 6469.0 0 ESR1, Y537S A24.02 VVPLSDLLL 8463.0 8252.0 0.5 FAM111B(-1) A03.01 RMKVPLMK 58.9 33.0 not measured FGFR3, S249C A02.01 YTLDVLERC 3309.0 1764.0 6.6 FGFR3, S249C B08.01 VLERCPHRPI 3629.0 7223.0 0 FGFR3, S249C A02.01 VLERCPHRPI 4505.0 15321.0 0 FGFR3:TACC3 A02.01 VLTVTSTDV 1255.0 295.0 1.1 FRG1B, I10T B07.02 KLSDSRTAL 225.0 9.0 6.8 FRG1B, I10T A02.01 KLSDSRTAL 275.0 111.0 2.8 FRG1B, I10T B08.01 KLSDSRTAL 3276.0 122.0 0 FRG1B, L52S A02.01 ALSASNSCFI 327.0 226.0 0.8 FRG1B, L52S B08.01 FQNGKMALSA 7796.0 425.0 0 FRG1B, L52S B07.02 ALSASNSCF 13989.0 684.0 0 FRG1B, L52S A02.01 ALSASNSCF 7913.0 728.0 0.3 FRG1B, L52S A02.01 FQNGKMALS 2305.0 3276.0 0 FRG1B, L52S A02.01 FQNGKMALSA 1205.0 6158.0 0 FRG1B, L52S A24.02 ALSASNSCF 9672.0 16338.0 0.2 GATA3...CSNH B08.01 FLKAESKIM 263.4 21.9 not measured GATA3...CSNH B08.01 LQHGHRHGL 693.0 550.4 not measured GATA3...CSNH B07.02 EPHLALQPL 106.6 17.0 not measured GATA3...CSNH B07.02 RPLQTHVLPE 968.0 2534.4 not measured GATA3...CSNH B08.01 FATLQRSSL 138.0 26.6 not measured GATA3...CSNH B07.02 MFATLQRSSL 1285.0 266.9 not measured GATA3...CSNH A24.02 MFLKAESKI 1065.7 332.1 not measured GATA3...CSNH B07.02 FATLQRSSL 261.9 14.0 not measured GATA3...CSNH A02.01 MLTGPPARV 145.4 10.6 not measured GATA3...CSNH B08.01 EPHLALQPL 1128.3 12.4 not measured GATA3...CSNH B07.02 GPPARVPAV 297.6 221.2 not measured GATA3...CSNH B08.01 MFATLQRSSL 220.5 53.4 not measured GATA3...CSNH A02.01 ALQPLQPHA 644.4 603.9 not measured GATA3...CSNH A03.01 VLWTTPPLQH 962.3 16.0 not measured GATA3...CSNH A02.01 VLPEPHLAL 140.7 16.0 not measured GATA3...CSNH B07.02 HVLPEPHLAL 1057.2 1332.6 not measured GATA3...CSNH A03.01 YMFLKAESK 53.1 79.8 not measured GATA3...CSNH B07.02 VPAVPFDLHF 1996.2 2114.2 not measured GATA3...CSNH A02.01 AIQPVLWTT 229.3 8.1 not measured GATA3...CSNH A02.01 TLQRSSLWCL 319.2 117.7 not measured GATA3...CSNH A03.01 KIMFATLQR 62.5 2.5 not measured GATA3...CSNH B07.02 QPVLWTTPPL 54.4 109.3 not measured GATA3...CSNH B08.01 ESKIMFATL 253.7 17.7 not measured GATA3...CSNH B08.01 IMKPKRDGYM 342.1 33.2 not measured GATA3...CSNH B07.02 KPKRDGYMF 109.7 28.2 not measured GATA3...CSNH B08.01 FLKAESKIMF 1539.9 82.3 not measured GATA3...CSNH B07.02 KPKRDGYMFL 32.5 98.1 not measured GATA3...CSNH B08.01 LHFCRSSIM 2141.2 118.7 not measured GATA3CSNH A02.01 SMLTGPPARV 57.0 15.0 21.7 GATA3CSNH B08.01 YMFLKAESKI 606.0 32.0 0.4 GATA3CSNH A02.01 YMFLKAESKI 163.0 166.0 0.6 GATA3CSNH A03.01 YMFLKAESKI 1338.0 21111.0 0 GATA3 YHEA A02.01 FLQEQYHEA 7.0 11.0 9.5 GATA3 YHEA B08.01 FLQEQYHEA 1222.0 2285.0 0 GBP3(-1) B08.01 TLKKKPRDI 286.3 3.3 not measured HER2, G776insYVMA A02.01 VMAYVMAGV 6.0 2.0 16.5 HER2, G776insYVMA A02.01 YVMAYVMAGV 5.0 57.0 20.9 HER2, G776insYVMA B07.02 YVMAYVMAG 6910.0 170.0 0 HER2, G776insYVMA B08.01 YVMAYVMAGV 721.0 353.0 0 HER2, G776insYVMA A02.01 YVMAYVMAG 841.0 11535.0 2.5 HER2, G776insYVMA B08.01 YVMAYVMAG 836.0 19413.0 1.2 HER2, G776insYVMA B07.02 YVMAYVMAGV 11445.0 52630.0 0 HER2, L755S A03.01 KVSRENTSPK 66.0 7.0 13.5 HER2, V777L A02.01 VMAGLGSPYV 20.0 102.0 2.9 HER2, V777L A03.01 VMAGLGSPYV 3951.0 11222.0 0 JAK1(-1) A02.01 SLMPAHWSI 4.0 48.0 5 JAK1(-1) A02.01 LSLMPAHWSI 21.0 164.0 0.4 JAK1(-1) B08.01 SLMPAHWSI 282.0 177.0 0 JAK1(-1) A02.01 FQMQPLSLM 33.0 553.0 0.3 JAK1(-1) A24.02 SLMPAHWSI 194.0 633.0 0.4 JAK1(-1) B08.01 LSLMPAHWSI 1914.0 860.0 0 JAK1(-1) B07.02 SLMPAHWSI 3907.0 1040.0 0 JAK1(-1) B08.01 FQMQPLSLM 2261.0 6714.0 0 JAK1(-1) B07.02 FQMQPLSLM 3458.0 10207.0 0 JAK1(-1) A24.02 LSLMPAHWSI 2125.0 12398.0 0 JAK1(-1) A24.02 FQMQPLSLM 4021.0 14612.0 0 KIT, T670I A02.01 VIIEYCCYG 4225.0 191.0 0.5 KIT, T670I A02.01 IIEYCCYGDL 3918.0 7310.0 0 KIT, T670I A02.01 TIGGPTLVII 5425.0 10685.0 0 KIT, V654A A02.01 YLGNHMNIA 92.0 117.0 0.6 KIT, V654A A02.01 MNIANLLGA 4522.0 128.0 0.3 KIT, V654A A02.01 HMNIANLLGA 294.0 430.0 0 KIT, V654A B08.01 YLGNHMNIA 2480.0 872.0 0 KIT, V654A A02.01 YLGNHMNIAN 7103.0 1342.0 0 KIT, V654A A02.01 IANLLGACTI 11214.0 6417.0 0 KRAS, G12C A02.01 KLVVVGACGV 204.0 150.0 one KRAS, G12C A02.01 LVVVGACGV 658.0 1213.0 0.6 KRAS, G12C A03.01 VVVGACGVGK 300.7 1.6 not measured KRAS, G12C A03.01 VVGACGVGK 182.0 4.1 not measured KRAS, G12D A02.01 KLVVVGADGV 361.0 184.0 0.9 KRAS, G12D A02.01 LVVVGADGV 2120.0 1192.0 0 KRAS, G12V A02.01 KLVVVGAVGV 163.0 96.0 0.9 KRAS, G12V A02.01 LVVVGAVGV 453.0 975.0 0.6 KRAS, G12V A03.01 VVGAVGVGK 168.9 1.9 not measured KRAS, Q61H A01.01 ILDTAGHEEY 131.8 64.2 not measured KRAS, Q61L A01.01 ILDTAGLEEY 65.9 8.6 not measured KRAS, Q61L A02.01 LLDILDTAGL 113.4 715.7 not measured LMAN1(+1) B07.02 GPPRPPRAAC 69.3 48.6 not measured LMAN1(+1) B07.02 PPRPPRAAC 263.7 32.8 not measured LMAN1(-1) B08.01 SLRRKYLRV 28.0 0.4 not measured MEK, C121S A02.01 VLHESNSPYI 189.0 131.0 1.9 MEK, P124L A02.01 VLHECNSLYI 67.0 10.0 5.1 MEK, P124L A02.01 SLYIVGFYGA 104.0 390.0 0.4 MEK, P124L A02.01 SLYIVGFYG 2987.0 1063.0 0 MEK, P124L A02.01 LQVLHECNSL 5803.0 4723.0 0 MEK, P124L A02.01 QVLHECNSL 8695.0 7774.0 0.5 MEK, P124L A03.01 VLHECNSLYI 4733.0 10500.0 0 MEK, P124L B08.01 QVLHECNSL 6854.0 14532.0 0 MEK, P124L B08.01 LQVLHECNSL 2782.0 19316.0 0 MLL2,...LSPH A02.01 LLQVTQTSFA 1935.0 676.9 not measured MLL2,...LSPH A02.01 RLWHLLLQV 8.3 1.3 not measured MLL2,...LSPH A02.01 LQVTQTSFAL 1147.4 718.3 not measured MLL2,...LSPH A02.01 RLWHLLLQVT 140.8 50.9 not measured MLL2,...LSPH A02.01 ALAPTLTHM 98.4 59.0 not measured MLL2,...LSPH A02.01 ALAPTLTHML 66.4 39.0 not measured MLL2, CRLS B08.01 SLGNHLCPL 136.0 6.0 0.5 MLL2, CRLS A02.01 SLGNHLCPL 28.0 18.0 3.5 MLL2, CRLS B07.02 SLGNHLCPL 3967.0 2590.0 0 MSH3(-1) A02.01 LLALWECSL 46.0 15.0 four MSH3(-1) A02.01 FLLALWECSL 17.0 114.0 10.8 MSH3(-1) B08.01 LLALWECSL 1454.0 154.0 0 MSH3(-1) B08.01 FLLALWECSL 671.0 13100.0 0 MSH3(-1) A02.01 LIVSRTLLL 755.0 173.5 not measured MSH3(-1) A02.01 LIVSRTLLLV 146.6 10920.6 not measured MSH3(-1) B08.01 LIVSRTLLL 270.7 881.7 not measured MSH3(-1) A02.01 IVSRTLLLV 166.2 12.7 not measured MSH3(-1) B08.01 SLPQARLCLI 632.3 4313.9 not measured MSH3(-1) B08.01 CLIVSRTLLL 835.7 1100.4 not measured MSH3(-1) B08.01 LPQARLCLI 136.5 15.0 not measured MSH3(-1) A02.01 SLPQARLCLI 782.4 112.9 not measured MSH3(-1) A02.01 CLIVSRTLLL 560.5 2005.1 not measured MSH3(-1) A02.01 FLLALWECS 686.6 93.2 not measured MSH3(-1) A02.01 FLLALWECSL 16.6 0.9 not measured MSH3(-1) A02.01 LLALWECSL 46.1 12.5 not measured MSH3(-1) B07.02 LPQARLCLI 134.6 72.6 not measured MSH3(-1) B08.01 CLIVSRTLL 915.0 126.7 not measured MSH3(-1) A02.01 ALWECSLPQA 24.6 9.0 not measured MSH3(-1) B08.01 LPQARLCLIV 591.4 152.1 not measured MSH6(+1) A02.01 LLPEDTPPL 8.9 2.8 not measured MSH6(+1) A02.01 ILLPEDTPPL 16.3 6.7 not measured MYC, E39D A02.01 QQSDLQPPA 4930.0 70.0 0 MYC, E39D A02.01 QQQSDLQPPA 11835.0 646.0 0 MYC, E39D A02.01 YQQQQQSDL 8842.0 799.0 0.4 MYC, E39D B08.01 YQQQQQSDL 5259.0 18868.0 0 MYC, P57S A02.01 FELLSTPPL 2509.0 225.0 0 MYC, P57S A02.01 LLSTPPLSPS 5226.0 1770.0 0 MYC, P57S B08.01 FELLSTPPL 4208.0 3179.0 0 MYC, T58I A02.01 LLPIPPLSPS 2071.0 449.0 0 MYC, T58I A02.01 FELLPIPPL 2472.0 553.0 0 NAB:STAT6 ("option 1" Chmielecki et al.) A02.01 SQIMSLWGL 14.0 62.0 one NAB:STAT6 ("option 1" Chmielecki et al.) A02.01 IMSLWGLVS 3630.0 7321.0 0 NAB:STAT6 ("option 1" Chmielecki et al.) A24.02 SQIMSLWGL 1604.0 8516.0 0 NAB:STAT6 ("option 1" Chmielecki et al.) B08.01 SQIMSLWGL 4587.0 15997.0 0 NDRG1:ERG A02.01 LLQEFDVQEA 200.0 45.0 2.5 NDRG1:ERG A02.01 LQEFDVQEAL 2229.0 50280.0 0 NDUFC2(-KCDT14)(+1) A02.01 ITAFFFCWI 437.7 7490.4 not measured NDUFC2(-KCDT14)(+1) A24.02 LYITAFFFW 46.6 45.3 not measured NDUFC2(-KCDT14)(+1) A03.01 FFFCWILSCK 325.9 597.1 not measured NDUFC2(-KCDT14)(+1) A03.01 FFCWILSCK 985.7 184.9 not measured NDUFC2(-KCDT14)(-1) A02.01 LLYITAFFL 24.0 713.0 17 NDUFC2(-KCDT14)(-1) B08.01 LLYITAFFL 3588.0 9592.0 0 NDUFC2(-KCDT14)(-1) A02.01 ITAFFLLDI 699.0 78.7 not measured NDUFC2(-KCDT14)(-1) A02.01 YITAFFLLDI 157.0 64.5 not measured NDUFC2(-KCDT14)(-1) A24.02 LYITAFFLL 15.6 0.1 not measured NDUFC2(-KCDT14)(-1) A02.01 LLYITAFFLL 43.7 323.2 not measured NDUFC2(-KCDT14)(-1) A24.02 LLYITAFFLL 59.7 60.1 not measured NDUFC2(-KCDT14)(-1) A24.02 LYITAFFLLD 414.3 0.4 not measured NRAS, Q61K A01.01 ILDTAGKEEY 272.6 14.3 not measured NRAS, Q61R A01.01 ILDTAGREEY 255.8 7.0 not measured PDGFRa, T674I A02.01 IIIEYCFYG 693.0 16.0 1.2 PDGFRa, T674I A02.01 YIIIEYCFYG 1529.0 113.0 0 PDGFRa, T674I A02.01 IIEYCFYGDL 3049.0 1090.0 0 PIK3CA, E542K A02.01 KITEQEKDFL 12548.0 1397.0 0 PIK3CA, E542K A03.01 AISTRDPLSK 41.3 57.5 not measured PTEN, R130Q A02.01 QTGVMICAYL 3786.0 9760.0 0 RAC1, P29S A02.01 FSGEYIPTV 21.0 3.0 6.8 RAC1, P29S A02.01 AFSGEYIPTV 1008.0 781.0 0 RAC1, P29S A01.01 TTNAFSGEY 23.0 4.4 not measured RAC1, P29S A01.01 YTTNAFSGEY 20.0 10.5 not measured RBM27(+1) B07.02 MPKDVNIQV 291.6 12.5 not measured RBM27(+1) A01.01 TGSNEVTTRY 343.9 15545.2 not measured RBM27(+1) A01.01 GSNEVTTRY 151.6 605.5 not measured RNF43, RHTP A02.01 TQLARFFPI 17.0 19.0 0 RNF43, RHTP A24.02 TQLARFFPI 268.0 52.0 0 RNF43, RHTP B08.01 TQLARFFPI 41.0 9150.0 0 SEC31A(-1) A02.01 KLMLLRLNL 58.0 17.0 16.9 SEC31A(-1) B08.01 KLMLLRLNL 421.0 29.0 0 SEC31A(-1) B07.02 KLMLLRLNL 2969.0 133.0 1.5 SEC31A(-1) A03.01 KLMLLRLNL 4664.0 210.0 0 SEC31A(-1) B08.01 LLRLNLRKM 185.1 68.2 not measured SEC31A(-1) A03.01 MLLRLNLRKM 171.4 116.9 not measured SEC31A(-1) A03.01 KLMLLRLNLR 95.4 48.4 not measured SEC31A(-1) A03.01 MLLRLNLRK 14.6 1.3 not measured SEC31A(-1) A03.01 LMLLRLNLRK 23.9 6.0 not measured SEC31A(-1) A02.01 MLLRLNLRKM 508.5 2507.4 not measured SEC31A(-1) B08.01 MLLRLNLRKM 565.9 95.3 not measured SEC31A(-1) A02.01 KLMLLRLNL 57.6 2.6 not measured SEC31A(-1) B08.01 LMLLRLNL 116.0 9.3 not measured SEC31A(-1) B08.01 KLMLLRLNL 420.6 58.4 not measured SEC31A(-1) A02.01 KKLMLLRLNL 275.4 288.9 not measured SEC31A(-1) B08.01 NLRKMCGPF 163.5 35.9 not measured SEC31A(-1) B08.01 YCQKKLML 203.1 222.1 not measured SEC31A(-1) B08.01 LNLRKMCGPF 782.2 438.7 not measured SEC63(+1) A03.01 YTCAITTVK 279.0 122.4 not measured SEC63(+1) A03.01 TYTCAITTVK 556.4 2362.2 not measured SEC63(+1) A03.01 ITTVKATETK 795.8 1245.3 not measured SEC63(+1) A03.01 KSKKKETFKK 744.0 39.6 not measured SEC63(+1) B08.01 TFKKKTYTC 648.2 77.9 not measured SEC63(+1) A03.01 KSKKKETFK 411.0 74.3 not measured SEC63(+1) B08.01 FKKKTYTCAI 562.8 384.9 not measured SEC63(-1) B08.01 TAKSKKRNL 213.8 30.6 not measured SF3B1, K700E A02.01 GLVDEQQEV 50.0 44.0 7.4 SLC35F5(-1) A02.01 FALCGFWQI 10.5 0.4 not measured SMAP1(-1) A03.01 KSRQNHLQLK 88.1 4.7 not measured SMAP1(-1) B07.02 KSRQNHLQL 329.5 78.0 not measured SMAP1(-1) A24.02 KLRSPWIF 504.5 828.2 not measured SMAP1(-1) A03.01 KISNWSLKK 11.5 8.8 not measured SMAP1(-1) A11.01 KISNWSLKK 15.3 9.8 not measured SMAP1(-1) A11.01 SLKKVPALK 117.6 129.1 not measured SMAP1(-1) B08.01 SLKKVPAL 66.8 7.9 not measured SMAP1(-1) A03.01 WSLKKVPALK 148.9 94.9 not measured SMAP1(-1) A03.01 KISNWSLKKV 168.3 114.6 not measured SMAP1(-1) A03.01 RKISNWSLKK 20.8 130.6 not measured SMAP1(-1) A03.01 SLKKVPALK 29.6 4.4 not measured SMAP1(-1) B08.01 SQKSRQNHL 305.0 44.6 not measured SMAP1(-1) B07.02 ALKKLRSPPL 355.5 223.2 not measured SMAP1(-1) B08.01 ALKKLRSPPL 58.9 0.5 not measured SMAP1(-1) B08.01 WSLKKVPAL 110.7 12.5 not measured SMAP1(-1) A03.01 HLQLKSCRRK 216.7 96.9 not measured SMAP1(-1) B08.01 LKKLRSPPL 139.6 0.6 not measured SMAP1(-1) A03.01 SLKKVPALKK 43.1 9.6 not measured SPOP, F133L A02.01 FVQGKDWGL 121.0 34.0 2.1 SPOP, F133L B08.01 FVQGKDWGL 1401.0 207.0 0 TFAM(+1) A03.01 RVNTAWKTK 136.4 8.6 not measured TFAM(+1) A03.01 RVNTAWKTKK 70.6 2.3 not measured TFAM(+1) B08.01 TKKKRVNTA 312.4 159.4 not measured TFAM(+1) A03.01 KRVNTAWKTK 304.1 331.6 not measured TFAM(+1) B08.01 WKTKKTSFSL 930.6 112.2 not measured TFAM(+1) B08.01 MTKKKRVNTA 534.2 186.9 not measured TGFBR2(-1) A02.01 RLSSCVPVA 83.0 4.0 18.7 TGFBR2(-1) A03.01 RLSSCVPVA 4264.0 439.0 0 TGFBR2(-1) A03.01 AMTTSSSQK 48.5 8.3 not measured TGFBR2(-1) A03.01 AMTTSSSQKN 887.2 2336.5 not measured TGFBR2(-1) B08.01 IMKEKKSL 69.8 14.1 not measured TGFBR2(-1) A02.01 KSLVRLSSCV 903.1 279.8 not measured TGFBR2(-1) A02.01 SLVRLSSCV 177.3 29.9 not measured TGFBR2(-1) A11.01 SAMTTSSSQK 36.4 15.8 not measured TGFBR2(-1) B08.01 IMKEKKSLV 80.8 16.8 not measured TGFBR2(-1) A11.01 AMTTSSSQK 89.9 161.6 not measured TGFBR2(-1) A03.01 SAMTTSSSQK 96.7 15.7 not measured TGFBR2(-1) A02.01 RLSSCVPVAL 84.5 54.2 not measured TGFBR2(-1) A02.01 VRLSSCVPVA 640.6 1206.8 not measured TGFBR2(-1) A02.01 RLSSCVPVA 82.7 49.5 not measured TGFBR2(-1) B08.01 CIMKEKKSL 218.5 7.5 not measured TGFBR2(-1) A02.01 ALMSAMTTS 320.4 139.1 not measured TGFBR2(-1) A02.01 LVRLSSCVPV 132.7 1237.6 not measured THAP5(-1) A03.01 KMRKKYAQK 23.7 5.7 not measured TMPRSS2:ERG A02.01 ALNSEALSV 66.0 14.0 9.1 TMPRSS2:ERG A02.01 ALNSEALSVV 84.0 15.0 2.9 TMPRSS2:ERG A02.01 MALNSEALSV 198.0 129.0 0.7 TMPRSS2:ERG B08.01 MALNSEALSV 8512.0 13457.0 0 TP53, AAVG A02.01 GLLAFWDSQV 57.0 10.0 14.2 TP53, AAVG A02.01 LLAFWDSQV 13.0 68.0 12.8 TP53, AWAA A02.01 WMTETLFDI 7.0 14.0 four TP53, AWAA A02.01 WMTETLFDIV 15.0 40.0 0.4 TP53, AWAA A24.02 WMTETLFDI 4936.0 713.0 0 TP53, AWAA A01.01 WMTETLFDIV 4046.0 14394.0 0 TP53, CSES B07.02 LPSQRRNHWM 89.0 10.0 6.5 TP53, CSES B08.01 LPSQRRNHWM 325.0 47.0 0.7 TP53, CSES A02.01 ALSEHCPTT 208.0 79.0 27.3 TP53, G245S B08.01 CMGSMNRRPI 1204.0 80.0 0 TP53, G245S A02.01 YMCNSCMGS 2485.0 81.0 0.8 TP53, G245S B08.01 SMNRRPILTI 260.0 337.0 0 TP53, G245S A02.01 SMNRRPILTI 1644.0 1198.0 0.3 TP53, G245S B08.01 SMNRRPILT 2536.0 1282.0 0 TP53, G245S A02.01 CMGSMNRRPI 7822.0 1989.0 0 TP53, G245S A02.01 SMNRRPILT 7251.0 3839.0 0 TP53, G245S A24.02 SMNRRPILTI 10308.0 16292.0 0 TP53, G245S B08.01 GSMNRRPIL 636.7 15.5 not measured TP53, G245S B08.01 MGSMNRRPIL 89.1 6.3 not measured TP53, G245S B08.01 MGSMNRRPI 324.2 29.1 not measured TP53, QPSL B07.02 LPRKPTRAAT 47.0 3.0 3.7 TP53, QPSL B07.02 LPRKPTRAA 8.0 8.0 5.5 TP53, QPSL B07.02 KPTRAATVSV 12.0 8.0 3 TP53, QPSL B08.01 LPRKPTRAA 873.0 1158.0 0 TP53, R248Q B08.01 NQRPILTI 3433.0 20.0 0 TP53, R248Q A02.01 GMNQRPILTI 1787.0 709.0 0.4 TP53, R248Q A02.01 GMNQRPILT 8115.0 3029.0 0 TP53, R248Q A02.01 CMGGMNQRPI 3025.0 3673.0 0 TP53, R248Q A02.01 NQRPILTI 10855.0 9606.0 0 TP53, R248Q B08.01 CMGGMNQRPI 6364.0 18766.0 0 TP53, R248Q B08.01 GMNQRPILTI 3266.0 29251.0 0 TP53, R248W B08.01 MNWRPILTI 6447.0 1.0 0 TP53, R248W A02.01 GMNWRPILTI 189.0 282.0 0.5 TP53, R248W A02.01 CMGGMNWRPI 354.0 346.0 0.4 TP53, R248W A02.01 MNWRPILTI 5834.0 516.0 3.8 TP53, R248W A02.01 MNWRPILTI 8158.0 1026.0 0.4 TP53, R248W B08.01 GMNWRPILTI 3990.0 1045.0 0 TP53, R248W A02.01 GMNWRPILT 3416.0 1130.0 0 TP53, R248W B08.01 CMGGMNWRPI 3218.0 2248.0 0 TP53, R248W A24.02 CMGGMNWRPI 9521.0 4453.0 0 TP53, R248W A24.02 MNWRPILTI 3634.0 6977.0 0.2 TP53, R248W A24.02 MNWRPILTI 1517.0 44901.0 0 TP53, R273C A02.01 LLGRNSFEVC 1272.0 2081.0 0 TP53, R273C A02.01 NSFEVCVCA 4239.0 2200.0 0 TP53, R273H A02.01 NSFEVHVCA 6768.0 503.0 0 TP53, SHST B07.02 HPRPAPASA 13.0 11.0 4.9 TP53, SHST B08.01 HPRPAPASA 1718.0 25.0 0 TP53, Y220C A02.01 VVPCEPPEV 1268.0 187.0 0.9 TTK(-1) A02.01 VMSDTTYKI 15.8 19.6 not measured TTK(-1) A03.01 LFVMSDTYK 57.9 749.4 not measured TTK(-1) A02.01 FVMSDTYKI 16.0 62.4 not measured TTK(-1) A03.01 FVMSDTYK 63.1 66.9 not measured TTK(-1) A03.01 KTFEKKGEK 81.3 32.2 not measured TTK(-1) A01.01 VMSDTTYKIY 245.1 375.8 not measured TTK(-1) A01.01 MSDTTYKIY 18.9 10.2 not measured UBR5(-1) B07.02 RVQNQGHLL 429.1 826.5 not measured VHL, QCL A02.01 MLTDSLFLPI 8.0 16.0 one VHL, QCL A02.01 SMLTDSLFL 14.0 31.0 9.8 VHL, QCL B08.01 MLTDSLFLPI 2581.0 110.0 0 VHL, QCL A01.01 MLTDSLFLPI 429.0 7673.0 0 XPOT(-1) A02.01 YLTKWPKFFL 10.7 42.9 not measured

Example 3 HLA Class I Binding Stability

[624] The subset of peptides used for affinity measurements was also used for stability measurements using the assay described (n=275). These data are shown in Table 3. The data is plotted according to the 4 groups in Figure 2, with the median and interquartile intervals overlapping. Less than 50 nM was considered by field as a strong binder, 50-150 nM was considered an intermediate binder, 150-500 nM was considered a weak binder, and more than 500 nM was considered a very weak binder. The relationship between observed stability and observed affinity was evident due to the decrease in the mean stability over these stability intervals between groups. However, there is significant overlap between groups, and generally all groups show epitopes with observed stability over many hours, including very weak binders.

Example 4 Immunogenicity Assays

[625] Immunogenicity assays are used to test the ability of each test peptide to proliferate T cells. Mature professional APCs are obtained for these assays as follows. Monocytes are enriched from PBMCs of healthy human donors using a bead-based kit (Miltenyi). Enriched cells are seeded in GM-CSF and IL-4 to induce immature DCs. After 5 days, immature DCs are incubated at 37°C with each peptide for 1 hour before adding a mixture of mature cytokines (GM-CSF, IL-1, IL-4, IL-6, TNFα, PGE1β). Cells are incubated at 37°C until mature DC.

[626] After DC maturation, PBMCs (either as such or enriched for T cells) are added to mature dendritic cells with proliferating cytokines. Cultures are monitored for peptide-specific T cells using a combination of functional assays and/or tetramer staining. Parallel immunogenicity assays with the modified and parental peptides allowed comparison of the relative efficiency with which the peptides promoted the expansion of peptide-specific T cells.

[627] Tetramer staining. MHC tetramers are purchased or manufactured in an experimental laboratory and used to measure the expression of peptide-specific T cells in immunogenicity assays. For evaluation, the tetramer is added to 1×10 ⁵ cells in PBS containing 1% FCS and 0.1% sodium azide (FACS buffer) according to the manufacturer's instructions. Cells are incubated in the dark for 20 minutes at room temperature. Then, antibodies specific for T cell markers such as CD8 are added to the final concentration suggested by the manufacturer and the cells are incubated in the dark at 4°C for 20 minutes. Cells are washed with cold FACS buffer and resuspended in buffer containing 1% formaldehyde. Cells are registered on a FACS Calibur (Becton Dickinson) and analyzed using Cellquest software (Becton Dickinson). For the analysis of tetramer-positive cells, the lymphocyte discrimination window is taken from the forward and side scatter diagram. Data is provided as the percentage of cells that were CD8 ⁺ /tetramer ⁺ .

[628] Intracellular staining for cytokines . In the absence of well-established staining of tetramers to identify populations of antigen-specific T cells, antigen specificity can be assessed using an assessment of cytokine production using well known flow cytometry assays. Briefly, T cells are stimulated with a peptide of interest and compared to a control. Following stimulation, cytokine production by CD4 ⁺ T cells (eg, IFNγ and TNFα) is assessed by intracellular staining. These cytokines, especially IFNγ, were used to identify stimulated cells.

[629] ELISPOT . Peptide-specific T cells were functionally enumerated using an ELISPOT assay (BD Biosciences) that measured the release of IFN-gamma by T cells on a per cell basis. Target cells (T2 or HLA-A0201 transfected with C1R) were loaded with 10 μM peptide for 1 hour at 37°C and washed three times. 1×0 ⁵ peptide-loaded targets were co-cultured in wells of an ELISPOT plate with varying concentrations of T cells (from 5×10 ² to 2×10 ³ ) taken from immunogenic cultures. The plates were developed according to the manufacturer's protocol and analyzed on an ELISPOT reader (Cellular Technology Ltd.) with accompanying software. Spots corresponding to the number of T cells producing IFN-gamma are given as the absolute number of spots per seeded T cells. T cells expanded to the modified peptides are tested not only for their ability to recognize targets loaded with the modified peptide, but also for their ability to recognize targets loaded with the original peptide.

[630] CD107 staining. CD107a and b are expressed on the surface of CD8 ⁺ T cells after activation by a cognate peptide. T cell lytic granules have a lipid bilayer that contains lysosomal membrane glycoproteins ("LAMP"), which include CD107a and b molecules. When cytotoxic T cells are activated through the T cell receptor, the membranes of these lytic granules are mobilized and fuse with the plasma membrane of the T cell. The contents of the granule are released, resulting in the death of the target cell. Because the granule membrane fuses with the plasma membrane, C107a and b are exposed to the cell surface and thus are markers of degranulation. Since degranulation, as measured by CD107 a and b staining, is based on a single cell, the assay is used to functionally enumerate peptide-specific T cells. For analysis, the peptide was added to C1R cells transfected with HLA-A0201 to a final concentration of 20 μM, the cells were incubated for 1 hour at 37°C and washed three times. 1×10 ⁵ peptide-loaded C1R cells were aliquoted in tubes and antibodies specific for CD107a and b were added to the final concentration suggested by the manufacturer (Becton Dickinson). Antibodies are added prior to the addition of T cells to "capture" the CD107 molecules, as they temporarily appear on the surface during analysis. Then add 1×10 ⁵ T cells from the immunogenic culture and incubate the samples for 4 hours at 37°C. T cells are further stained for additional cell surface molecules such as CD8 and recorded on a FACS Calibur device (Becton Dickinson). Data are analyzed using the accompanying Cellquest software and results are reported as percentages of CD8 ⁺ CD107 a and b ⁺ cells.

[631] Cytotoxicity assays . Cytotoxic activity is measured using a chromium release assay. T2 target cells are labeled for 1 hour at 37° C. with Na ⁵¹ Cr and washed. Then add 5×10 ³ T2 target cells to various amounts of T cells from the immunogenic culture. The release of chromium is measured in the supernatant collected 4 hours after incubation at 37°C. The percentage of specific lysis is calculated as follows:

Experimental release - spontaneous release / total release - spontaneous release × 100

[632] Immunogenicity assays were performed to assess whether each peptide could elicit a T-cell response by antigen-specific propagation. While current methods are imperfect and thus negative results do not imply that the peptide is unable to induce a response, a positive result demonstrates that the peptide can induce a T cell response. Several peptides from Table 3 were tested for their ability to induce CD8 ⁺ T cell responses with multimeric readouts as described. Each positive result was measured with a second multimer preparation to eliminate any preparation-related bias. Several examples of positive multimeric staining are shown in Figures 3-6, with multimer negative cells (left) and antigen specific (double multimer positive) cells (right).

[633] HLA-A02:01 ⁺ T cells were co-cultured with monocytic dendritic cells loaded with TMPRSS2::ERG fusion neoepitope (ALNSEALSV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for TMPRSS2::ERG fused neoepitope using multimers (original: BV421 and PE; confirmation: APC and BUV396) (figure 3).

[634] HLA-A02:01 ⁺ T cells were co-cultured with monocytic dendritic cells loaded with GATA3 frameshift neoepitope (SMLTGPPARV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the GATA3 frameshift neoepitope using multimers (initial: APC and BUV396; confirmation: PE and BV421) (Figure 4).

[635] HLA-A02: ⁰¹⁺ T cells were co-cultured with monocytic dendritic cells loaded with frameshifted β2M neoepitope (LLCVWVSSI; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity for the frameshifted β2M neoepitope using multimers (initial: PE and APC; confirmation: PE and BV421) (figure 5).

[636] HLA-A02:01 ⁺ T cells were co-cultured with monocytic dendritic cells loaded with KRAS G12C neoepitope (KLVVVGACGV; HLA-A02:01) for 10 days. CD8 ⁺ T cells were analyzed for antigenic specificity to the neoepitope KRAS G12C with a frameshift using multimers (initial: BUV396 and BV421; confirmation: APC and BUV396) (figure 6).

[637] Although antigen-specific CD8 ⁺ T cell responses are readily assessed using the well-established HLA class I multimeric technology, a separate assay for evaluation is necessary for CD4 ⁺ T cell responses, due to the fact that HLA class II multimeric technology is not generally accepted. To assess CD4 ⁺ T cell responses, T cells were restimulated with the peptide of interest and compared to controls. In the case of an entirely new sequence (eg, resulting from a frameshift or fusion), the control was not a peptide. In the case of a point mutation, the control was a WT peptide. After stimulation, cytokine production by CD4 ⁺ T cells (eg, IFNγ and TNFα) was assessed by intracellular staining. These cytokines, especially IFNγ, were used to identify stimulated cells. Antigen-specific CD4 ⁺ T cell responses showed increased production of cytokines relative to control. Examples of antigen-specific CD4 ⁺ T cell responses generated against neopeptides are shown in Figures 7-9.

[638] T cells were co-cultured with monocytic dendritic cells loaded with frameshifted β2M neopeptides for 20 days (restimulation with fresh monocytic dendritic cells on day 20). CD4 ⁺ T cells were analyzed for antigen specificity by intracellular staining for cytokines after re-stimulation with monocytic dendritic cells loaded with frameshifted β2M peptide for 24 hours compared to controls without peptide (Figure 7).

[639] Naive T cells were co-cultured with monocytic dendritic cells loaded with neopeptide BTK C481S for 20 days (re-stimulation with fresh monocytic dendritic cells on day 20). CD4 ⁺ T cells were analyzed for antigen specificity by intracellular staining for cytokines after re-stimulation with monocytic dendritic cells loaded with neopeptide BTK C481S for 24 hours, compared with the control wild-type BTK peptide (figure 8).

[640] Naive T cells were co-cultured with monocytic dendritic cells loaded with GATA3 frameshift neopeptides for 20 days (re-stimulation with fresh monocytic dendritic cells on day 20). CD4 ⁺ T cells were analyzed for antigen specificity by intracellular staining for cytokines after re-stimulation with monocytic dendritic cells loaded with GATA3 frameshift peptide for 24 hours compared to control without peptide (Figure 9).

Example 5: Selection of CTL and HTL Epitopes for Introduction into a Tumor-Specific Vaccine

[641] This example illustrates the procedure for selecting peptide epitopes for vaccine compositions of the invention. The peptides in the composition may be in the form of nucleic acid sequences, single or one or more sequences (ie minigene) encoding the peptide(s), or may be single-epitope and/or multi-epitope peptides.

[642] Epitopes are selected that, when administered, mimic immune responses that have been observed to correlate with tumor clearance. For example, a vaccine may contain 1-2 epitopes that come from at least one antigenic region of the tumor. Epitopes from one region can be used in combination with epitopes from one or more additional tumor antigenic regions.

[643] Epitopes can be selected, for example, which have an IC ₅₀ binding affinity of 500 nM or less for a class I or class II HLA molecule, an IC _{50 of} 1000 nM or less.

[644] When preparing polyepitope compositions, such as a minigene, it is generally desirable to obtain as small a peptide as possible that encompasses the epitopes of interest. The principles used are similar, if not the same, to those used in selecting a peptide containing nested epitopes. However, in addition, after determining the nucleic acid sequence to be provided as a minigene, the peptide sequence encoded by it is analyzed to determine if any "junction epitopes" have been formed. A binding epitope is a potential HLA binding epitope, eg, as predicted based on motif analysis. Epitope binding should generally be avoided because the recipient may bind to the HLA molecule and mount an immune response to that epitope, which is not present in the native protein sequence.

[645] Peptide epitopes for introduction into vaccine compositions, for example, are selected from those listed in the tables. The vaccine composition of the selected peptides, when administered, is safe, effective, and elicits an immune response similar in magnitude to that which inhibits tumor growth.

Example 6 Peptide Composition for Prophylactic or Therapeutic Uses

[646] The immunogenic or vaccine compositions of the invention are used to inhibit tumor growth. For example, a polyepitope composition (or nucleic acid containing polyepitomes) containing multiple CTL and HTL epitopes is administered to humans suffering from tumors. The dose of the peptide for immunization is about 1 to about 50,000 micrograms, typically 100-5000 micrograms, for a 70 kg patient. Initial administration may be followed by booster doses at week 4 followed by assessment of the magnitude of the patient's immune response using methods that determine the presence of epitope-specific CTL populations in a PBMC sample. Additional booster doses are administered as needed. The composition has been found to be safe and effective in inhibiting tumor growth.

[647] Alternatively, the polyepitope composition can be administered as a nucleic acid, such as RNA, according to methods known in the art and described herein.

[648] Neoantigenic binding agents, such as TCR or CAR, can be administered according to methods known in the art and described herein. Binding agents can be administered as polynucleotides, eg DNA or RNA encoding binding agents as part of a cell therapy. Alternatively, binding agents may be prepared as antibodies or fragments thereof capable of recognizing a specific peptide:MHC complex associated with cytotoxic agents or T cell binding agents capable of redirecting the patient's T cells to tumor cells expressing the epitopes shown in the tables.

[649] Neoantigenic peptides, polynucleotides, binding agents, or cells expressing such molecules can be delivered to the same patient by many methods known in the art, and can be further combined with other anti-cancer therapies (e.g., chemotherapy, surgery, radiation , checkpoint inhibitors, etc.).

Example 7: Introduction of the composition using dendritic cells

[650] Vaccines containing the epitopes of the invention can be administered using dendritic cells. In this example, peptide-loaded or nucleic acid-loaded dendritic cells can be administered to a patient to stimulate an in vivo CTL response. In this method, dendritic cells are isolated, expanded and loaded with a vaccine containing a peptide or DNA or RNA encoding the CTL and HTL epitopes of the invention. The dendritic cells are infused back into the patient to induce CTL and HTL responses in vivo . The induced CTL and HTL then destroy (CTL) or facilitate destruction (HTL) of specific tumor target cells that carry the proteins from which the epitopes in the vaccine are derived.

[651] Alternatively, ex vivo CTL or HTL responses to a particular tumor-associated antigen can be induced by incubation in a patient's tissue culture or genetically compatible CTL or HTL progenitor cells in conjunction with a source of antigen-presenting cells, such as dendritic cells, and appropriate immunogenic peptides or nucleic acids. . After an appropriate incubation time (typically approximately 7-28 days) during which progenitor cells have been activated and expanded into effector cells, the cells are infused back into the patient where they destroy (CTL) or facilitate destruction (HTL) of their specific cells- targets, i.e. tumor cells.

Example 8: Identification of neoepitopes

[652] Cancer cells containing individual genetic changes that change the amino acid sequence can generate potential new T-cell epitopes, such as those presented in the tables. Determining which patient tumors contain tumor-specific neoepitopes, as identified in the tables, may include identifying DNA mutations. As one approach, whole genome or whole exome sequencing of tumors can be performed using conventional methods and compared with matched germline samples from patients. As an additional approach, sequencing of tumor RNA and corresponding suitable normal samples can also be performed. As an additional approach, it is also possible to perform specific assays based on targeted sequencing, or next generation sequencing methods or conventional Sanger sequencing. In addition, highly specific polymerase chain reaction assays can be developed.

Example 9: Specificity of recognition of neoantigenic peptide by CD8 ⁺ or CD4 ⁺ cells

[653] In various embodiments, the present invention includes disclosure of information about the difference between mutant sequences and wild-type sequences using vaccine-induced CD8 ⁺ cells. To determine whether vaccine-induced T cells can recognize a naturally processed antigen, a tumor cell line can be transduced with a multi-minigene construct encoding mutant (MUT) or wild-type (WT) sequences of the peptides introduced into the vaccine. Each minigene can be composed of 21 a.a. encoding MUT or WT sequences. Vaccine-induced cells specific for a protein containing a particular mutation can be incubated with MUT or WT expressing malignant cells, supernatants can be collected after 24 hours of incubation, and IFN-γ produced by cells can be measured in supernatants by ELISA.

[654] Recognition by neoantigen-specific cells of mutant and wild type peptides can also be determined in a standard 4 hour ⁵¹ Cr release assay.

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SEQUENCE LIST

<110> NEON THERAPEUTICS, INC.

<120> NEOANTIGENS AND THEIR USE

<130> 50401-705.601

<140> PCT/US2017/025462

<141> 2017-03-31

<150> 62/316.571

<151> 2016-04-01

<150> 62/316.567

<151> 2016-04-01

<150> 62/316.552

<151> 2016-03-31

<150> 62/316.547

<151> 2016-03-31

<150> 62/316.533

<151> 2016-03-31

<150> 62/316.530

<151> 2016-03-31

<160> 1834

<170>PatentIn version 3.5

<210> 1

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1

Val Ala Asp Gly Leu Ile Thr Thr Leu His Tyr Pro Ala Pro Lys Arg

1 5 10 15

Asn Lys Pro Thr Val Tyr Gly Val Ser Pro Asn Tyr Asp Lys Trp Glu

20 25 30

Met Glu Arg Thr Asp Ile Thr Met Lys His Lys Leu Gly Gly Gly Gln

35 40 45

Tyr Gly Lys Val Tyr Glu Gly Val Trp Lys Lys Tyr Ser Leu Thr Val

50 55 60

Ala Val Lys Thr Leu Lys Glu Asp Thr Met Glu Val Glu Glu Phe Leu

65 70 75 80

Lys Glu Ala Ala Val Met Lys Glu Ile Lys His Pro Asn Leu Val Gln

85 90 95

Leu Leu Gly Val Cys

100

<210> 2

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 2

Val Ala Asp Gly Leu Ile Thr Thr Leu His Tyr Pro Ala Pro Lys Arg

1 5 10 15

Asn Lys Pro Thr Val Tyr Gly Val Ser Pro Asn Tyr Asp Lys Trp Glu

20 25 30

Met Glu Arg Thr Asp Ile Thr Met Lys His Lys Leu Gly Gly Gly Gln

35 40 45

Tyr Gly Val Val Tyr Glu Gly Val Trp Lys Lys Tyr Ser Leu Thr Val

50 55 60

Ala Val Lys Thr Leu Lys Glu Asp Thr Met Glu Val Glu Glu Phe Leu

65 70 75 80

Lys Glu Ala Ala Val Met Lys Glu Ile Lys His Pro Asn Leu Val Gln

85 90 95

Leu Leu Gly Val Cys

100

<210> 3

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 3

Leu Leu Gly Val Cys Thr Arg Glu Pro Pro Phe Tyr Ile Ile Thr Glu

1 5 10 15

Phe Met Thr Tyr Gly Asn Leu Leu Asp Tyr Leu Arg Glu Cys Asn Arg

20 25 30

Gln Glu Val Asn Ala Val Val Leu Leu Tyr Met Ala Thr Gln Ile Ser

35 40 45

Ser Ala Thr Glu Tyr Leu Glu Lys Lys Asn Phe Ile His Arg Asp Leu

50 55 60

Ala Ala Arg Asn Cys Leu Val Gly Glu Asn His Leu Val Lys Val Ala

65 70 75 80

Asp Phe Gly Leu Ser Arg Leu Met Thr Gly Asp Thr Tyr Thr Ala His

85 90 95

Ala Gly Ala Lys Phe

100

<210> 4

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 4

Ser Leu Thr Val Ala Val Lys Thr Leu Lys Glu Asp Thr Met Glu Val

1 5 10 15

Glu Glu Phe Leu Lys Glu Ala Ala Val Met Lys Glu Ile Lys His Pro

20 25 30

Asn Leu Val Gln Leu Leu Gly Val Cys Thr Arg Glu Pro Pro Phe Tyr

35 40 45

Ile Ile Ile Glu Phe Met Thr Tyr Gly Asn Leu Leu Asp Tyr Leu Arg

50 55 60

Glu Cys Asn Arg Gln Glu Val Asn Ala Val Val Leu Leu Tyr Met Ala

65 70 75 80

Thr Gln Ile Ser Ser Ala Met Glu Tyr Leu Glu Lys Lys Asn Phe Ile

85 90 95

His Arg Asp Leu Ala

100

<210> 5

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 5

Ser Thr Val Ala Asp Gly Leu Ile Thr Thr Leu His Tyr Pro Ala Pro

1 5 10 15

Lys Arg Asn Lys Pro Thr Val Tyr Gly Val Ser Pro Asn Tyr Asp Lys

20 25 30

Trp Glu Met Glu Arg Thr Asp Ile Thr Met Lys His Lys Leu Gly Gly

35 40 45

Gly Gln His Gly Glu Val Tyr Glu Gly Val Trp Lys Lys Tyr Ser Leu

50 55 60

Thr Val Ala Val Lys Thr Leu Lys Glu Asp Thr Met Glu Val Glu Glu

65 70 75 80

Phe Leu Lys Glu Ala Ala Val Met Lys Glu Ile Lys His Pro Asn Leu

85 90 95

Val Gln Leu Leu Gly

100

<210> 6

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 6

Ser Ser Leu Ala Met Leu Asp Leu Leu His Val Ala Arg Asp Ile Ala

1 5 10 15

Cys Gly Cys Gln Tyr Leu Glu Glu Asn His Phe Ile His Arg Asp Ile

20 25 30

Ala Ala Arg Asn Cys Leu Leu Thr Cys Pro Gly Pro Gly Arg Val Ala

35 40 45

Lys Ile Ala Asp Phe Gly Met Ala Arg Asp Ile Tyr Arg Ala Ser Tyr

50 55 60

Tyr Arg Lys Gly Gly Cys Ala Met Leu Pro Val Lys Trp Met Pro Pro

65 70 75 80

Glu Ala Phe Met Glu Gly Ile Phe Thr Ser Lys Thr Asp Thr Trp Ser

85 90 95

Phe Gly Val Leu Leu

100

<210> 7

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 7

Gln Val Ala Val Lys Thr Leu Pro Glu Val Cys Ser Glu Gln Asp Glu

1 5 10 15

Leu Asp Phe Leu Met Glu Ala Leu Ile Ile Ser Lys Phe Asn His Gln

20 25 30

Asn Ile Val Arg Cys Ile Gly Val Ser Leu Gln Ser Leu Pro Arg Phe

35 40 45

Ile Leu Met Glu Leu Met Ala Gly Gly Asp Leu Lys Ser Phe Leu Arg

50 55 60

Glu Thr Arg Pro Arg Pro Ser Gln Pro Ser Ser Leu Ala Met Leu Asp

65 70 75 80

Leu Leu His Val Ala Arg Asp Ile Ala Cys Gly Cys Gln Tyr Leu Glu

85 90 95

Glu Asn His Phe Ile

100

<210> 8

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 8

Met Ile Lys Leu Ile Asp Ile Ala Arg Gln Thr Ala Gln Gly Met Asp

1 5 10 15

Tyr Leu His Ala Lys Ser Ile Ile His Arg Asp Leu Lys Ser Asn Asn

20 25 30

Ile Phe Leu His Glu Asp Leu Thr Val Lys Ile Gly Asp Phe Gly Leu

35 40 45

Ala Thr Glu Lys Ser Arg Trp Ser Gly Ser His Gln Phe Glu Gln Leu

50 55 60

Ser Gly Ser Ile Leu Trp Met Ala Pro Glu Val Ile Arg Met Gln Asp

65 70 75 80

Lys Asn Pro Tyr Ser Phe Gln Ser Asp Val Tyr Ala Phe Gly Ile Val

85 90 95

Leu Tyr Glu Leu Met

100

<210> 9

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 9

Met Ile Lys Glu Gly Ser Met Ser Glu Asp Glu Phe Ile Glu Glu Ala

1 5 10 15

Lys Val Met Met Asn Leu Ser His Glu Lys Leu Val Gln Leu Tyr Gly

20 25 30

Val Cys Thr Lys Gln Arg Pro Ile Phe Ile Ile Thr Glu Tyr Met Ala

35 40 45

Asn Gly Ser Leu Leu Asn Tyr Leu Arg Glu Met Arg His Arg Phe Gln

50 55 60

Thr Gln Gln Leu Leu Glu Met Cys Lys Asp Val Cys Glu Ala Met Glu

65 70 75 80

Tyr Leu Glu Ser Lys Gln Phe Leu His Arg Asp Leu Ala Ala Arg Asn

85 90 95

Cys Leu Val Asn Asp

100

<210> 10

<211> 93

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 10

Met Gly Phe Gly Asp Leu Lys Ser Pro Ala Gly Leu Gln Val Leu Asn

1 5 10 15

Asp Tyr Leu Ala Asp Lys Ser Tyr Ile Glu Gly Tyr Val Pro Ser Gln

20 25 30

Ala Asp Val Ala Val Phe Glu Ala Val Ser Gly Pro Pro Pro Ala Asp

35 40 45

Leu Cys His Ala Leu Arg Trp Tyr Asn His Ile Lys Ser Tyr Glu Lys

50 55 60

Glu Lys Ala Ser Leu Pro Gly Val Lys Lys Ala Leu Gly Lys Tyr Gly

65 70 75 80

Pro Ala Asp Val Glu Asp Thr Thr Gly Ser Gly Ala Thr

85 90

<210> 11

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 11

Ser Leu Asn Ile Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser

1 5 10 15

Asp Gly Asp Val Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn

20 25 30

Thr Ile Asn Trp Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys

35 40 45

Ile Ile Arg Asn Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val

50 55 60

Cys His Ala Leu Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg

65 70 75 80

Asp Cys Val Ser Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp

85 90 95

Lys Cys Asn Leu Leu

100

<210> 12

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 12

Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser Pro Lys Ala

1 5 10 15

Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser Val Asp Asn

20 25 30

Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser Thr Val Gln

35 40 45

Leu Ile Met Gln Leu Met Pro Phe Gly Cys Leu Leu Asp Tyr Val Arg

50 55 60

Glu His Lys Asp Asn Ile Gly Ser Gln Tyr Leu Leu Asn Trp Cys Val

65 70 75 80

Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg Leu Val His

85 90 95

Arg Asp Leu Ala Ala

100

<210> 13

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 13

Glu Arg Cys Glu Val Val Met Gly Asn Leu Glu Ile Val Leu Thr Gly

1 5 10 15

His Asn Ala Asp Leu Ser Phe Leu Gln Trp Ile Arg Glu Val Thr Gly

20 25 30

Tyr Val Leu Val Ala Met Asn Glu Phe Ser Thr Leu Pro Leu Pro Asn

35 40 45

Leu Arg Met Val Arg Gly Thr Gln Val Tyr Asp Gly Lys Phe Ala Ile

50 55 60

Phe Val Met Leu Asn Tyr Asn Thr Asn Ser Ser His Ala Leu Arg Gln

65 70 75 80

Leu Arg Leu Thr Gln Leu Thr Glu Ile Leu Ser Gly Gly Val Tyr Ile

85 90 95

Glu Lys Asn Asp Lys

100

<210> 14

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 14

His Leu Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg

1 5 10 15

Leu Ala Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn

20 25 30

Lys Gly Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro

35 40 45

Leu Tyr Gly Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu His Ala

50 55 60

Pro Thr Ser Arg Gly Gly Ala Ser Val Glu Glu Thr Asp Gln Ser His

65 70 75 80

Leu Ala Thr Ala Gly Ser Thr Ser Ser His Ser Leu Gln Lys Tyr Tyr

85 90 95

Ile Thr Gly Glu Ala

100

<210> 15

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 15

Asn Gln Gly Lys Cys Val Glu Gly Met Val Glu Ile Phe Asp Met Leu

1 5 10 15

Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu Glu

20 25 30

Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr Thr

35 40 45

Phe Leu Pro Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile His

50 55 60

Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala Lys

65 70 75 80

Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu Leu

85 90 95

Leu Ile Leu Ser His

100

<210> 16

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 16

Ile His Leu Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln

1 5 10 15

Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser

20 25 30

Asn Lys Gly Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val

35 40 45

Pro Leu Cys Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu His

50 55 60

Ala Pro Thr Ser Arg Gly Gly Ala Ser Val Glu Glu Thr Asp Gln Ser

65 70 75 80

His Leu Ala Thr Ala Gly Ser Thr Ser Ser His Ser Leu Gln Lys Tyr

85 90 95

Tyr Ile Thr Gly Glu

100

<210> 17

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 17

Ile His Leu Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln

1 5 10 15

Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser

20 25 30

Asn Lys Gly Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val

35 40 45

Pro Leu Asn Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu His

50 55 60

Ala Pro Thr Ser Arg Gly Gly Ala Ser Val Glu Glu Thr Asp Gln Ser

65 70 75 80

His Leu Ala Thr Ala Gly Ser Thr Ser Ser His Ser Leu Gln Lys Tyr

85 90 95

Tyr Ile Thr Gly Glu

100

<210> 18

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 18

Ile His Leu Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln

1 5 10 15

Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser

20 25 30

Asn Lys Gly Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val

35 40 45

Pro Leu Ser Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu His

50 55 60

Ala Pro Thr Ser Arg Gly Gly Ala Ser Val Glu Glu Thr Asp Gln Ser

65 70 75 80

His Leu Ala Thr Ala Gly Ser Thr Ser Ser His Ser Leu Gln Lys Tyr

85 90 95

Tyr Ile Thr Gly Glu

100

<210> 19

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 19

His Arg Ile Gly Gly Ile Lys Leu Arg His Gln Gln Trp Ser Leu Val

1 5 10 15

Met Glu Ser Val Val Pro Ser Asp Arg Gly Asn Tyr Thr Cys Val Val

20 25 30

Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr Tyr Thr Leu Asp Val Leu

35 40 45

Glu Arg Cys Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala Asn

50 55 60

Gln Thr Ala Val Leu Gly Ser Asp Val Glu Phe His Cys Lys Val Tyr

65 70 75 80

Ser Asp Ala Gln Pro His Ile Gln Trp Leu Lys His Val Glu Val Asn

85 90 95

Gly Ser Lys Val Gly

100

<210> 20

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 20

Ala Val Lys Leu Ser Asp Ser Arg Ile Ala Leu Lys Ser Gly Tyr Gly

1 5 10 15

Lys Tyr Leu Gly Ile Asn Ser Asp Glu Leu Val Gly His Ser Asp Ala

20 25 30

Ile Gly Pro Arg Glu Gln Trp Glu Pro Val Phe Gln Asn Gly Lys Met

35 40 45

Ala Leu Ser Ala Ser Asn Ser Cys Phe Ile Arg Cys Asn Glu Ala Gly

50 55 60

Asp Ile Glu Ala Lys Ser Lys Thr Ala Gly Glu Glu Glu Met Ile Lys

65 70 75 80

Ile Arg Ser Cys Ala Glu Lys Glu Thr Lys Lys Lys Asp Asp Ile Pro

85 90 95

Glu Glu Asp Lys Gly

100

<210> 21

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 21

Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly Ile Trp Ile Pro Asp

1 5 10 15

Gly Glu Asn Val Lys Ile Pro Val Ala Ile Lys Val Leu Arg Glu Asn

20 25 30

Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met

35 40 45

Ala Gly Leu Gly Ser Pro Tyr Val Ser Arg Leu Leu Gly Ile Cys Leu

50 55 60

Thr Ser Thr Val Gln Leu Val Thr Gln Leu Met Pro Tyr Gly Cys Leu

65 70 75 80

Leu Asp His Val Arg Glu Asn Arg Gly Arg Leu Gly Ser Gln Asp Leu

85 90 95

Leu Asn Trp Cys Met

100

<210> 22

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 22

Arg Val Glu Glu Phe Lys Leu Lys Gln Met Trp Lys Ser Pro Asn Gly

1 5 10 15

Thr Ile Arg Asn Ile Leu Gly Gly Thr Val Phe Arg Glu Ala Ile Ile

20 25 30

Cys Lys Asn Ile Pro Arg Leu Val Ser Gly Trp Val Lys Pro Ile Ile

35 40 45

Ile Gly His His Ala Tyr Gly Asp Gln Tyr Arg Ala Thr Asp Phe Val

50 55 60

Val Pro Gly Pro Gly Lys Val Glu Ile Thr Tyr Thr Pro Ser Asp Gly

65 70 75 80

Thr Gln Lys Val Thr Tyr Leu Val His Asn Phe Glu Glu Gly Gly Gly

85 90 95

Val Ala Met Gly Met

100

<210> 23

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 23

Arg Val Glu Glu Phe Lys Leu Lys Gln Met Trp Lys Ser Pro Asn Gly

1 5 10 15

Thr Ile Arg Asn Ile Leu Gly Gly Thr Val Phe Arg Glu Ala Ile Ile

20 25 30

Cys Lys Asn Ile Pro Arg Leu Val Ser Gly Trp Val Lys Pro Ile Ile

35 40 45

Ile Gly Cys His Ala Tyr Gly Asp Gln Tyr Arg Ala Thr Asp Phe Val

50 55 60

Val Pro Gly Pro Gly Lys Val Glu Ile Thr Tyr Thr Pro Ser Asp Gly

65 70 75 80

Thr Gln Lys Val Thr Tyr Leu Val His Asn Phe Glu Glu Gly Gly Gly

85 90 95

Val Ala Met Gly Met

100

<210> 24

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 24

Arg Val Glu Glu Phe Lys Leu Lys Gln Met Trp Lys Ser Pro Asn Gly

1 5 10 15

Thr Ile Arg Asn Ile Leu Gly Gly Thr Val Phe Arg Glu Ala Ile Ile

20 25 30

Cys Lys Asn Ile Pro Arg Leu Val Ser Gly Trp Val Lys Pro Ile Ile

35 40 45

Ile Gly Gly His Ala Tyr Gly Asp Gln Tyr Arg Ala Thr Asp Phe Val

50 55 60

Val Pro Gly Pro Gly Lys Val Glu Ile Thr Tyr Thr Pro Ser Asp Gly

65 70 75 80

Thr Gln Lys Val Thr Tyr Leu Val His Asn Phe Glu Glu Gly Gly Gly

85 90 95

Val Ala Met Gly Met

100

<210> 25

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 25

Arg Val Glu Glu Phe Lys Leu Lys Gln Met Trp Lys Ser Pro Asn Gly

1 5 10 15

Thr Ile Arg Asn Ile Leu Gly Gly Thr Val Phe Arg Glu Ala Ile Ile

20 25 30

Cys Lys Asn Ile Pro Arg Leu Val Ser Gly Trp Val Lys Pro Ile Ile

35 40 45

Ile Gly Ser His Ala Tyr Gly Asp Gln Tyr Arg Ala Thr Asp Phe Val

50 55 60

Val Pro Gly Pro Gly Lys Val Glu Ile Thr Tyr Thr Pro Ser Asp Gly

65 70 75 80

Thr Gln Lys Val Thr Tyr Leu Val His Asn Phe Glu Glu Gly Gly Gly

85 90 95

Val Ala Met Gly Met

100

<210> 26

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 26

Val Glu Ala Thr Ala Tyr Gly Leu Ile Lys Ser Asp Ala Ala Met Thr

1 5 10 15

Val Ala Val Lys Met Leu Lys Pro Ser Ala His Leu Thr Glu Arg Glu

20 25 30

Ala Leu Met Ser Glu Leu Lys Val Leu Ser Tyr Leu Gly Asn His Met

35 40 45

Asn Ile Ala Asn Leu Leu Gly Ala Cys Thr Ile Gly Gly Pro Thr Leu

50 55 60

Val Ile Thr Glu Tyr Cys Cys Tyr Gly Asp Leu Leu Asn Phe Leu Arg

65 70 75 80

Arg Lys Arg Asp Ser Phe Ile Cys Ser Lys Gln Glu Asp His Ala Glu

85 90 95

Ala Ala Leu Tyr Lys

100

<210> 27

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 27

Ile Ser Glu Leu Gly Ala Gly Asn Gly Gly Val Val Phe Lys Val Ser

1 5 10 15

His Lys Pro Ser Gly Leu Val Met Ala Arg Lys Leu Ile His Leu Glu

20 25 30

Ile Lys Pro Ala Ile Arg Asn Gln Ile Ile Arg Glu Leu Gln Val Leu

35 40 45

His Glu Ser Asn Ser Pro Tyr Ile Val Gly Phe Tyr Gly Ala Phe Tyr

50 55 60

Ser Asp Gly Glu Ile Ser Ile Cys Met Glu His Met Asp Gly Gly Ser

65 70 75 80

Leu Asp Gln Val Leu Lys Lys Ala Gly Arg Ile Pro Glu Gln Ile Leu

85 90 95

Gly Lys Val Ser Ile

100

<210> 28

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 28

Leu Gly Ala Gly Asn Gly Gly Val Val Phe Lys Val Ser His Lys Pro

1 5 10 15

Ser Gly Leu Val Met Ala Arg Lys Leu Ile His Leu Glu Ile Lys Pro

20 25 30

Ala Ile Arg Asn Gln Ile Ile Arg Glu Leu Gln Val Leu His Glu Cys

35 40 45

Asn Ser Leu Tyr Ile Val Gly Phe Tyr Gly Ala Phe Tyr Ser Asp Gly

50 55 60

Glu Ile Ser Ile Cys Met Glu His Met Asp Gly Gly Ser Leu Asp Gln

65 70 75 80

Val Leu Lys Lys Ala Gly Arg Ile Pro Glu Gln Ile Leu Gly Lys Val

85 90 95

Ser Ile Ala Val Ile

100

<210> 29

<211> 89

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 29

Met Pro Leu Asn Val Ser Phe Thr Asn Arg Asn Tyr Asp Leu Asp Tyr

1 5 10 15

Asp Ser Val Gln Pro Tyr Phe Tyr Cys Asp Glu Glu Glu Asn Phe Tyr

20 25 30

Gln Gln Gln Gln Gln Ser Asp Leu Gln Pro Pro Ala Pro Ser Glu Asp

35 40 45

Ile Trp Lys Lys Phe Glu Leu Leu Pro Thr Pro Pro Leu Ser Pro Ser

50 55 60

Arg Arg Ser Gly Leu Cys Ser Pro Ser Tyr Val Ala Val Thr Pro Phe

65 70 75 80

Ser Leu Arg Gly Asp Asn Asp Gly Gly

85

<210> 30

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 30

Phe Thr Asn Arg Asn Tyr Asp Leu Asp Tyr Asp Ser Val Gln Pro Tyr

1 5 10 15

Phe Tyr Cys Asp Glu Glu Glu Asn Phe Tyr Gln Gln Gln Gln Gln Ser

20 25 30

Glu Leu Gln Pro Pro Ala Pro Ser Glu Asp Ile Trp Lys Lys Phe Glu

35 40 45

Leu Leu Ser Thr Pro Pro Leu Ser Pro Ser Arg Arg Ser Gly Leu Cys

50 55 60

Ser Pro Ser Tyr Val Ala Val Thr Pro Phe Ser Leu Arg Gly Asp Asn

65 70 75 80

Asp Gly Gly Gly Gly Ser Phe Ser Thr Ala Asp Gln Leu Glu Met Val

85 90 95

Thr Glu Leu Leu Gly

100

<210> 31

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 31

Thr Asn Arg Asn Tyr Asp Leu Asp Tyr Asp Ser Val Gln Pro Tyr Phe

1 5 10 15

Tyr Cys Asp Glu Glu Glu Asn Phe Tyr Gln Gln Gln Gln Gln Ser Glu

20 25 30

Leu Gln Pro Pro Ala Pro Ser Glu Asp Ile Trp Lys Lys Phe Glu Leu

35 40 45

Leu Pro Ile Pro Pro Leu Ser Pro Ser Arg Arg Ser Gly Leu Cys Ser

50 55 60

Pro Ser Tyr Val Ala Val Thr Pro Phe Ser Leu Arg Gly Asp Asn Asp

65 70 75 80

Gly Gly Gly Gly Ser Phe Ser Thr Ala Asp Gln Leu Glu Met Val Thr

85 90 95

Glu Leu Leu Gly Gly

100

<210> 32

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 32

Val Ala Val Lys Met Leu Lys Pro Thr Ala Arg Ser Ser Glu Lys Gln

1 5 10 15

Ala Leu Met Ser Glu Leu Lys Ile Met Thr His Leu Gly Pro His Leu

20 25 30

Asn Ile Val Asn Leu Leu Gly Ala Cys Thr Lys Ser Gly Pro Ile Tyr

35 40 45

Ile Ile Ile Glu Tyr Cys Phe Tyr Gly Asp Leu Val Asn Tyr Leu His

50 55 60

Lys Asn Arg Asp Ser Phe Leu Ser His His Pro Glu Lys Pro Lys Lys

65 70 75 80

Glu Leu Asp Ile Phe Gly Leu Asn Pro Ala Asp Glu Ser Thr Arg Ser

85 90 95

Tyr Val Ile Leu Ser

100

<210> 33

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 33

Ile Glu Glu His Ala Asn Trp Ser Val Ser Arg Glu Ala Gly Phe Ser

1 5 10 15

Tyr Ser His Ala Gly Leu Ser Asn Arg Leu Ala Arg Asp Asn Glu Leu

20 25 30

Arg Glu Asn Asp Lys Glu Gln Leu Lys Ala Ile Ser Thr Arg Asp Pro

35 40 45

Leu Ser Lys Ile Thr Glu Gln Glu Lys Asp Phe Leu Trp Ser His Arg

50 55 60

His Tyr Cys Val Thr Ile Pro Glu Ile Leu Pro Lys Leu Leu Leu Ser

65 70 75 80

Val Lys Trp Asn Ser Arg Asp Glu Val Ala Gln Met Tyr Cys Leu Val

85 90 95

Lys Asp Trp Pro

100

<210> 34

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 34

His Ala Asn Trp Ser Val Ser Arg Glu Ala Gly Phe Ser Tyr Ser His

1 5 10 15

Ala Gly Leu Ser Asn Arg Leu Ala Arg Asp Asn Glu Leu Arg Glu Asn

20 25 30

Asp Lys Glu Gln Leu Lys Ala Ile Ser Thr Arg Asp Pro Leu Ser Glu

35 40 45

Ile Thr Lys Gln Glu Lys Asp Phe Leu Trp Ser His Arg His Tyr Cys

50 55 60

Val Thr Ile Pro Glu Ile Leu Pro Lys Leu Leu Leu Ser Val Lys Trp

65 70 75 80

Asn Ser Arg Asp Glu Val Ala Gln Met Tyr Cys Leu Val Lys Asp Trp

85 90 95

Pro Pro Ile Lys Pro

100

<210> 35

<211> 72

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 35

Leu Phe Ile Asn Leu Phe Ser Met Met Leu Gly Ser Gly Met Pro Glu

1 5 10 15

Leu Gln Ser Phe Asp Asp Ile Ala Tyr Ile Arg Lys Thr Leu Ala Leu

20 25 30

Asp Lys Thr Glu Gln Glu Ala Leu Glu Tyr Phe Met Lys Gln Met Asn

35 40 45

Asp Ala Arg His Gly Gly Trp Thr Thr Lys Met Asp Trp Ile Phe His

50 55 60

Thr Ile Lys Gln His Ala Leu Asn

65 70

<210> 36

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 36

Gln Arg Gly Gly Val Ile Thr Asp Glu Glu Glu Thr Ser Lys Lys Ile

1 5 10 15

Ala Asp Gln Leu Asp Asn Ile Val Asp Met Arg Glu Tyr Asp Val Pro

20 25 30

Tyr His Ile Arg Leu Ser Ile Asp Ile Glu Thr Thr Lys Leu Pro Leu

35 40 45

Lys Phe Arg Asp Ala Glu Thr Asp Gln Ile Met Met Ile Ser Tyr Met

50 55 60

Ile Asp Gly Gln Gly Tyr Leu Ile Thr Asn Arg Glu Ile Val Ser Glu

65 70 75 80

Asp Ile Glu Asp Phe Glu Phe Thr Pro Lys Pro Glu Tyr Glu Gly Pro

85 90 95

Phe Cys Val Phe Asn

100

<210> 37

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 37

Lys Phe Asn Cys Arg Val Ala Gln Tyr Pro Phe Glu Asp His Asn Pro

1 5 10 15

Pro Gln Leu Glu Leu Ile Lys Pro Phe Cys Glu Asp Leu Asp Gln Trp

20 25 30

Leu Ser Glu Asp Asp Asn His Val Ala Ala Ile His Cys Lys Ala Gly

35 40 45

Lys Gly Gln Thr Gly Val Met Ile Cys Ala Tyr Leu Leu His Arg Gly

50 55 60

Lys Phe Leu Lys Ala Gln Glu Ala Leu Asp Phe Tyr Gly Glu Val Arg

65 70 75 80

Thr Arg Asp Lys Lys Gly Val Thr Ile Pro Ser Gln Arg Arg Tyr Val

85 90 95

Tyr Tyr Tyr Ser Tyr

100

<210> 38

<211> 79

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 38

Met Gln Ala Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys

1 5 10 15

Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Ala Phe Ser Gly Glu Tyr

20 25 30

Ile Pro Thr Val Phe Asp Asn Tyr Ser Ala Asn Val Met Val Asp Gly

35 40 45

Lys Pro Val Asn Leu Gly Leu Trp Asp Thr Ala Gly Gln Glu Asp Tyr

50 55 60

Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Val Gly Glu Thr

65 70 75

<210> 39

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 39

Ile Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn

1 5 10 15

Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly

20 25 30

Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys

35 40 45

Met Gly Ser Met Asn Arg Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu

50 55 60

Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val

65 70 75 80

Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg

85 90 95

Lys Lys Gly Glu Pro

100

<210> 40

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 40

Thr Tyr Ser Pro Ala Leu Asn Lys Met Phe Cys Gln Leu Ala Lys Thr

1 5 10 15

Cys Pro Val Gln Leu Trp Val Asp Ser Thr Pro Pro Pro Gly Thr Arg

20 25 30

Val Arg Ala Met Ala Ile Tyr Lys Gln Ser Gln His Met Thr Glu Val

35 40 45

Val Arg His Cys Pro His Glu Arg Cys Ser Asp Ser Asp Gly Leu

50 55 60

Ala Pro Pro Gln His Leu Ile Arg Val Glu Gly Asn Leu Arg Val Glu

65 70 75 80

Tyr Leu Asp Asp Arg Asn Thr Phe Arg His Ser Val Val Val Pro Tyr

85 90 95

Glu Pro Pro Glu Val

100

<210> 41

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 41

Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe Arg

1 5 10 15

His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp Cys

20 25 30

Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly

35 40 45

Met Asn Gln Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser

50 55 60

Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala Cys

65 70 75 80

Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys Gly

85 90 95

Glu Pro His His Glu

100

<210> 42

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 42

Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe Arg

1 5 10 15

His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val Gly Ser Asp Cys

20 25 30

Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly

35 40 45

Met Asn Trp Arg Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser

50 55 60

Gly Asn Leu Leu Gly Arg Asn Ser Phe Glu Val Arg Val Cys Ala Cys

65 70 75 80

Pro Gly Arg Asp Arg Arg Thr Glu Glu Glu Asn Leu Arg Lys Lys Gly

85 90 95

Glu Pro His His Glu

100

<210> 43

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 43

Pro Glu Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys

1 5 10 15

Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile

20 25 30

Ile Thr Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe

35 40 45

Glu Val Cys Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu

50 55 60

Glu Asn Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly

65 70 75 80

Ser Thr Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro

85 90 95

Lys Lys Lys Pro Leu

100

<210> 44

<211> 93

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 44

Ala Lys Phe Gln Gln Cys His Ser Thr Leu Glu Pro Asn Pro Ala Asp

1 5 10 15

Cys Arg Val Leu Val Tyr Leu Gln Asn Gln Pro Gly Thr Lys Leu Leu

20 25 30

Asn Phe Leu Gln Glu Arg Asn Leu Pro Pro Lys Val Val Leu Arg His

35 40 45

Pro Lys Val His Leu Asn Thr Met Phe Arg Arg Pro His Ser Cys Leu

50 55 60

Ala Asp Val Leu Leu Ser Val His Leu Ile Val Leu Arg Val Val Arg

65 70 75 80

Leu Pro Ala Pro Phe Arg Val Asn His Ala Val Glu Trp

85 90

<210> 45

<211> 53

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 45

Ala Pro Val Ile Phe Gln Ile Ala Leu Asp Lys Pro Cys His Gln Ala

1 5 10 15

Glu Val Lys His Leu His His Leu Leu Lys Gln Leu Lys Pro Ser Glu

20 25 30

Lys Tyr Leu Lys Ile Lys His Leu Leu Leu Lys Arg Glu Arg Val Asp

35 40 45

Leu Ser Lys Leu Gln

fifty

<210> 46

<211> 33

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 46

Met Leu Gln Phe Arg Gly Ser Arg Phe Phe Gln Met Leu Ile Leu Tyr

1 5 10 15

Tyr Ile Leu Pro Arg Lys Val Leu Gln Met Asp Phe Leu Val His Pro

20 25 30

Ala

<210> 47

<211> 179

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 47

Ala Leu Gly Pro His Ser Arg Ile Ser Cys Leu Pro Thr Gln Thr Arg

1 5 10 15

Gly Cys Ile Leu Leu Ala Ala Thr Pro Arg Ser Ser Ser Ser Ser Ser Ser

20 25 30

Ser Asn Asp Met Ile Pro Met Ala Ile Ser Ser Pro Pro Lys Ala Pro

35 40 45

Leu Leu Ala Ala Pro Ser Pro Ala Ser Arg Leu Gln Cys Ile Asn Ser

50 55 60

Asn Ser Arg Ile Thr Ser Gly Gln Trp Met Ala His Met Ala Leu Leu

65 70 75 80

Pro Ser Gly Thr Lys Gly Arg Cys Thr Ala Cys His Thr Ala Leu Gly

85 90 95

Arg Gly Ser Leu Ser Ser Ser Ser Cys Pro Gln Pro Ser Pro Ser Leu

100 105 110

Pro Ala Ser Asn Lys Leu Pro Ser Leu Pro Leu Ser Lys Met Tyr Thr

115 120 125

Thr Ser Met Ala Met Pro Ile Leu Pro Leu Pro Gln Leu Leu Leu Ser

130 135 140

Ala Asp Gln Gln Ala Ala Pro Arg Thr Asn Phe His Ser Ser Leu Ala

145 150 155 160

Glu Thr Val Ser Leu His Pro Leu Ala Pro Met Pro Ser Lys Thr Cys

165 170 175

His His Lys

<210> 48

<211> 79

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 48

Ala His Gln Gly Phe Pro Ala Ala Lys Glu Ser Arg Val Ile Gln Leu

1 5 10 15

Ser Leu Leu Ser Leu Leu Ile Pro Pro Leu Thr Cys Leu Ala Ser Glu

20 25 30

Ala Leu Pro Arg Pro Leu Leu Ala Leu Pro Pro Val Leu Leu Ser Leu

35 40 45

Ala Gln Asp His Ser Arg Leu Leu Gln Cys Gln Ala Thr Arg Cys His

50 55 60

Leu Gly His Pro Val Ala Ser Arg Thr Ala Ser Cys Ile Leu Pro

65 70 75

<210> 49

<211> 222

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 49

Pro Ile Leu Ala Ala Thr Gly Thr Ser Val Arg Thr Ala Ala Arg Thr

1 5 10 15

Trp Val Pro Arg Ala Ala Ile Arg Val Pro Asp Pro Ala Ala Val Pro

20 25 30

Asp Asp His Ala Gly Pro Gly Ala Glu Cys His Gly Arg Pro Leu Leu

35 40 45

Tyr Thr Ala Asp Ser Ser Leu Trp Thr Thr Arg Pro Gln Arg Val Trp

50 55 60

Ser Thr Gly Pro Asp Ser Ile Leu Gln Pro Ala Lys Ser Ser Pro Ser

65 70 75 80

Ala Ala Ala Ala Thr Leu Leu Pro Ala Thr Thr Val Pro Asp Pro Ser

85 90 95

Cys Pro Thr Phe Val Ser Ala Ala Ala Thr Val Ser Thr Thr Thr Ala

100 105 110

Pro Val Leu Ser Ala Ser Ile Leu Pro Ala Ala Ile Pro Ala Ser Thr

115 120 125

Ser Ala Val Pro Gly Ser Ile Pro Leu Pro Ala Val Asp Asp Thr Ala

130 135 140

Ala Pro Pro Glu Pro Ala Pro Leu Leu Thr Ala Thr Gly Ser Val Ser

145 150 155 160

Leu Pro Ala Ala Ala Thr Ser Ala Ala Ser Thr Leu Asp Ala Leu Pro

165 170 175

Ala Gly Cys Val Ser Ser Ala Pro Val Ser Ala Val Pro Ala Asn Cys

180 185 190

Leu Phe Pro Ala Ala Leu Pro Ser Thr Ala Gly Ala Ile Ser Arg Phe

195 200 205

Ile Trp Val Ser Gly Ile Leu Ser Pro Leu Asn Asp Leu Gln

210 215 220

<210> 50

<211> 185

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 50

Pro Cys Arg Ala Gly Arg Arg Val Pro Trp Ala Ala Ser Leu Ile His

1 5 10 15

Ser Arg Phe Leu Leu Met Asp Asn Lys Ala Pro Ala Gly Met Val Asn

20 25 30

Arg Ala Arg Leu His Ile Thr Thr Ser Lys Val Leu Thr Leu Ser Ser

35 40 45

Ser Ser His Pro Thr Pro Ser Asn His Arg Pro Arg Pro Leu Met Pro

50 55 60

Asn Leu Arg Ile Ser Ser Ser His Ser Leu Asn His His Ser Ser Ser

65 70 75 80

Pro Leu Ser Leu His Thr Pro Ser Ser His Pro Ser Leu His Ile Ser

85 90 95

Ser Pro Arg Leu His Thr Pro Pro Ser Ser Arg Arg His Ser Ser Thr

100 105 110

Pro Arg Ala Ser Pro Pro Thr His Ser His Arg Leu Ser Leu Leu Thr

115 120 125

Ser Ser Ser Asn Leu Ser Ser Gln His Pro Arg Arg Ser Pro Ser Arg

130 135 140

Leu Arg Ile Leu Ser Pro Ser Leu Ser Ser Pro Ser Lys Leu Pro Ile

145 150 155 160

Pro Ser Ser Ala Ser Leu His Arg Arg Ser Tyr Leu Lys Ile His Leu

165 170 175

Gly Leu Arg His Pro Gln Pro Pro Gln

180 185

<210> 51

<211> 58

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 51

Arg Thr Asn Pro Thr Val Arg Met Arg Pro His Cys Val Pro Phe Trp

1 5 10 15

Thr Gly Arg Ile Leu Leu Pro Ser Ala Ala Ser Val Cys Pro Ile Pro

20 25 30

Phe Glu Ala Cys His Leu Cys Gln Ala Met Thr Leu Arg Cys Pro Asn

35 40 45

Thr Gln Gly Cys Cys Ser Ser Trp Ala Ser

50 55

<210> 52

<211> 90

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 52

Thr Asn Gln Ala Leu Pro Lys Ile Glu Val Ile Cys Arg Gly Thr Pro

1 5 10 15

Arg Cys Pro Ser Thr Val Pro Pro Ser Pro Ala Gln Pro Tyr Leu Arg

20 25 30

Val Ser Leu Pro Glu Asp Arg Tyr Thr Gln Ala Trp Ala Pro Thr Ser

35 40 45

Arg Thr Pro Trp Gly Ala Met Val Pro Arg Gly Val Ser Met Ala His

50 55 60

Lys Val Ala Thr Pro Gly Ser Gln Thr Ile Met Pro Cys Pro Met Pro

65 70 75 80

Thr Thr Pro Val Gln Ala Trp Leu Glu Ala

85 90

<210> 53

<211> 41

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 53

Arg Met Glu Arg Glu Leu Lys Lys Trp Ser Ile Gln Thr Cys Leu Ser

1 5 10 15

Ala Arg Thr Gly Leu Ser Ile Ser Cys Thr Thr Leu Asn Ser Pro Pro

20 25 30

Leu Lys Lys Met Ser Met Pro Ala Val

35 40

<210> 54

<211> 35

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 54

Leu Cys Ser Arg Tyr Ser Leu Phe Leu Ala Trp Arg Leu Ser Ser Val

1 5 10 15

Leu Gln Arg Phe Arg Phe Thr His Val Ile Gln Gln Arg Met Glu Ser

20 25 30

Gln Ile Ser

35

<210> 55

<211> 39

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 55

Arg Ser Ala Cys Val Thr Val Lys Gly Pro Leu Ala Ser Val Gly Arg

1 5 10 15

His Ser Leu Ser Lys Gln Asp Cys Lys Phe Leu Pro Phe Trp Gly Phe

20 25 30

Leu Glu Glu Phe Leu Leu Cys

35

<210> 56

<211> 97

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 56

Ile Gln Trp Gly Thr Thr Thr Ala Pro Arg Pro Ile Arg Pro Pro Phe

1 5 10 15

Leu Glu Ser Lys Gln Asn Cys Ser His Phe Pro Thr Pro Leu Leu Ala

20 25 30

Ser Glu Asp Arg Arg Glu Thr Gly Leu Phe Leu Pro Ser Ala Ala Gln

35 40 45

Lys Met Lys Lys Ala His Phe Leu Lys Thr Trp Phe Arg Ser Asn Pro

50 55 60

Thr Lys Thr Lys Lys Ala Arg Phe Ser Thr Ala Ser Leu Ala Lys Glu

65 70 75 80

Leu Thr His Pro Leu Leu Val Ser Leu Leu Leu Lys Glu Lys Gln Asp

85 90 95

gly

<210> 57

<211> 73

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 57

Pro Thr Asp Pro Phe Leu Gly Leu Arg Leu Gly Leu His Leu Gln Lys

1 5 10 15

Val Phe His Gln Ser His Ala Glu Tyr Ser Gly Ala Pro Pro Pro Pro

20 25 30

Pro Ala Pro Ser Gly Leu Arg Phe Trp Asn Pro Ser Arg Ile Ala His

35 40 45

Ile Ser Gln Leu Leu Ser Trp Pro Gln Lys Thr Glu Glu Arg Leu Gly

50 55 60

Tyr Ser Ser His Gln Leu Pro Arg Lys

65 70

<210> 58

<211> 45

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 58

Phe Cys Cys Ser Cys Cys Phe Phe Gly Gly Glu Arg Trp Ser Lys Ser

1 5 10 15

Pro Tyr Cys Pro Gln Arg Met Thr Pro Gly Thr Thr Phe Ile Thr Met

20 25 30

Met Lys Lys Glu Ala Glu Lys Arg Thr Arg Thr Leu Thr

35 40 45

<210> 59

<211> 95

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 59

Trp Arg Arg Asn Cys Lys Ala Pro Val Ser Leu Arg Lys Ser Val Gln

1 5 10 15

Thr Pro Ala Arg Ser Ser Pro Ala Arg Pro Asp Arg Thr Arg Arg Leu

20 25 30

Pro Ser Leu Gly Val Pro Gly Gln Pro Trp Ala Leu Gly Ala Ala Ala

35 40 45

Ser Arg Arg Cys Cys Cys Cys Cys Arg Ser Pro Leu Gly Ser Ala Arg

50 55 60

Ser Arg Ser Pro Ala Thr Leu Ala Leu Thr Pro Arg Ala Thr Arg Ser

65 70 75 80

Arg Cys Pro Gly Ala Thr Trp Arg Glu Ala Ala Ser Trp Ala Glu

85 90 95

<210> 60

<211> 113

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 60

Pro Gly Arg Pro Leu Gln Thr His Val Leu Pro Glu Pro His Leu Ala

1 5 10 15

Leu Gln Pro Leu Gln Pro His Ala Asp His Ala His Ala Asp Ala Pro

20 25 30

Ala Ile Gln Pro Val Leu Trp Thr Thr Pro Pro Leu Gln His Gly His

35 40 45

Arg His Gly Leu Glu Pro Cys Ser Met Leu Thr Gly Pro Pro Ala Arg

50 55 60

Val Pro Ala Val Pro Phe Asp Leu His Phe Cys Arg Ser Ser Ile Met

65 70 75 80

Lys Pro Lys Arg Asp Gly Tyr Met Phe Leu Lys Ala Glu Ser Lys Ile

85 90 95

Met Phe Ala Thr Leu Gln Arg Ser Ser Leu Trp Cys Leu Cys Ser Asn

100 105 110

His

<210> 61

<211> 57

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 61

Pro Arg Pro Arg Arg Cys Thr Arg His Pro Ala Cys Pro Leu Asp His

1 5 10 15

Thr Thr Pro Pro Ala Trp Ser Pro Pro Trp Val Arg Ala Leu Leu Asp

20 25 30

Ala His Arg Ala Pro Ser Glu Ser Pro Cys Ser Pro Phe Arg Leu Ala

35 40 45

Phe Leu Gln Glu Gln Tyr His Glu Ala

50 55

<210> 62

<211> 494

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 62

Thr Arg Arg Cys His Cys Cys Pro His Leu Arg Ser His Pro Cys Pro

1 5 10 15

His His Leu Arg Asn His Pro Arg Pro His His Leu Arg His His Ala

20 25 30

Cys His His His Leu Arg Asn Cys Pro His Pro His Phe Leu Arg His

35 40 45

Cys Thr Cys Pro Gly Arg Trp Arg Asn Arg Pro Ser Leu Arg Arg Leu

50 55 60

Arg Ser Leu Leu Cys Leu Pro His Leu Asn His His Leu Phe Leu His

65 70 75 80

Trp Arg Ser Arg Pro Cys Leu His Arg Lys Ser His Pro His Leu Leu

85 90 95

His Leu Arg Arg Leu Tyr Pro His His Leu Lys His Arg Pro Cys Pro

100 105 110

His His Leu Lys Asn Leu Leu Cys Pro Arg His Leu Arg Asn Cys Pro

115 120 125

Leu Pro Arg His Leu Lys His Leu Ala Cys Leu His His Leu Arg Ser

130 135 140

His Pro Cys Pro Leu His Leu Lys Ser His Pro Cys Leu His His Arg

145 150 155 160

Arg His Leu Val Cys Ser His His Leu Lys Ser Leu Leu Cys Pro Leu

165 170 175

His Leu Arg Ser Leu Pro Phe Pro His His Leu Arg His His Ala Cys

180 185 190

Pro His His Leu Arg Thr Arg Leu Cys Pro His His Leu Lys Asn His

195 200 205

Leu Cys Pro Pro His Leu Arg Tyr Arg Ala Tyr Pro Pro Cys Leu Trp

210 215 220

Cys His Ala Cys Leu His Arg Leu Arg Asn Leu Pro Cys Pro His Arg

225 230 235 240

Leu Arg Ser Leu Pro Arg Pro Leu His Leu Arg Leu His Ala Ser Pro

245 250 255

His His Leu Arg Thr Pro Pro His Pro His His Leu Arg Thr His Leu

260 265 270

Leu Pro His His Arg Arg Thr Arg Ser Cys Pro Cys Arg Trp Arg Ser

275 280 285

His Pro Cys Cys His Tyr Leu Arg Ser Arg Asn Ser Ala Pro Gly Pro

290 295 300

Arg Gly Arg Thr Cys His Pro Gly Leu Arg Ser Arg Thr Cys Pro Pro

305 310 315 320

Gly Leu Arg Ser His Thr Tyr Leu Arg Arg Leu Arg Ser His Thr Cys

325 330 335

Pro Pro Ser Leu Arg Ser His Ala Tyr Ala Leu Cys Leu Arg Ser His

340 345 350

Thr Cys Pro Pro Arg Leu Arg Asp His Ile Cys Pro Leu Ser Leu Arg

355 360 365

Asn Cys Thr Cys Pro Pro Arg Leu Arg Ser Arg Thr Cys Leu Leu Cys

370 375 380

Leu Arg Ser His Ala Cys Pro Asn Leu Arg Asn His Thr Cys Pro

385 390 395 400

Pro Ser Leu Arg Ser His Ala Cys Pro Pro Gly Leu Arg Asn Arg Ile

405 410 415

Cys Pro Leu Ser Leu Arg Ser His Pro Cys Pro Leu Gly Leu Lys Ser

420 425 430

Pro Leu Arg Ser Gln Ala Asn Ala Leu His Leu Arg Ser Cys Pro Cys

435 440 445

Ser Leu Pro Leu Gly Asn His Pro Tyr Leu Pro Cys Leu Glu Ser Gln

450 455 460

Pro Cys Leu Ser Leu Gly Asn His Leu Cys Pro Leu Cys Pro Arg Ser

465 470 475 480

Cys Arg Cys Pro His Leu Gly Ser His Pro Cys Arg Leu Ser

485 490

<210> 63

<211> 53

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 63

Ser Trp Lys Gly Thr Asn Trp Cys Asn Asp Met Cys Ile Phe Ile Thr

1 5 10 15

Ser Gly Gln Ile Phe Lys Gly Thr Arg Gly Pro Arg Phe Leu Trp Gly

20 25 30

Ser Lys Asp Gln Arg Gln Lys Gly Ser Asn Tyr Ser Gln Ser Glu Ala

35 40 45

Leu Cys Val Leu Leu

fifty

<210> 64

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 64

Lys Arg Thr Lys Cys Phe Thr Phe Gly

fifteen

<210> 65

<211> 27

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 65

Pro Ile Phe Ile Gln Thr Leu Leu Leu Trp Asp Phe Leu Gln Lys Asp

1 5 10 15

Leu Lys Ala Tyr Thr Gly Thr Ile Leu Met Met

20 25

<210> 66

<211> 22

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 66

Gln Lys Met Ile Leu Thr Lys Gln Ile Lys Thr Lys Pro Thr Asp Thr

1 5 10 15

Phe Leu Gln Ile Leu Arg

twenty

<210> 67

<211> 43

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 67

Gly Phe Trp Ile Gln Ser Ile Lys Thr Ile Thr Arg Tyr Thr Ile Phe

1 5 10 15

Val Leu Lys Asp Ile Met Thr Pro Asn Leu Ile Ala Glu Leu His

20 25 30

Asn Ile Leu Leu Lys Thr Ile Thr His His Ser

35 40

<210> 68

<211> 40

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 68

Asn Tyr Ser Asn Val Gln Trp Arg Asn Leu Gln Ser Ser Val Cys Gly

1 5 10 15

Leu Pro Ala Lys Gly Glu Asp Ile Phe Leu Gln Phe Arg Thr His Thr

20 25 30

Thr Gly Arg Gln Val His Val Leu

35 40

<210> 69

<211> 44

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 69

Tyr Gln Ser Arg Val Leu Pro Gln Thr Glu Gln Asp Ala Lys Lys Gly

1 5 10 15

Gln Asn Val Ser Leu Leu Gly Lys Tyr Ile Leu His Thr Arg Thr Arg

20 25 30

Gly Asn Leu Arg Lys Ser Arg Lys Trp Lys Ser Met

35 40

<210> 70

<211> 85

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 70

Ser Ser Gln Asn Ala Arg Gly Cys Ser Pro Arg Gly Pro Cys Thr Ser

1 5 10 15

Ser Ser Tyr Thr Gly Gly Pro Cys Thr Ser Pro Leu Leu Ala Pro Val

20 25 30

Ile Phe Cys Pro Phe Pro Glu Asn Leu Pro Gly Gln Leu Arg Phe Pro

35 40 45

Ser Gly Leu Leu Ala Phe Trp Asp Ser Gln Val Cys Asp Leu His Val

50 55 60

Leu Pro Cys Pro Gln Gln Asp Val Leu Pro Thr Gly Gln Asp Leu Pro

65 70 75 80

Cys Ala Ala Val Gly

85

<210> 71

<211> 72

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 71

Gly Ala Ala Pro Thr Met Ser Ala Ala Gln Ile Ala Met Val Trp Pro

1 5 10 15

Leu Leu Ser Ile Leu Ser Glu Trp Lys Glu Ile Cys Val Trp Ser Ile

20 25 30

Trp Met Thr Glu Thr Leu Phe Asp Ile Val Trp Trp Cys Pro Met Ser

35 40 45

Arg Leu Arg Leu Ala Leu Thr Val Pro Ser Thr Thr Thr Thr Cys

50 55 60

Val Thr Val Pro Ala Trp Ala Ala

65 70

<210> 72

<211> 97

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 72

Thr Gly Gly Pro Ser Ser Pro Ser Ser His Trp Lys Thr Pro Val Val

1 5 10 15

Ile Tyr Trp Asp Gly Thr Ala Leu Arg Cys Val Phe Val Pro Val Leu

20 25 30

Gly Glu Thr Gly Ala Gln Arg Lys Arg Ile Ser Ala Arg Lys Gly Ser

35 40 45

Leu Thr Thr Ser Cys Pro Gln Gly Ala Leu Ser Glu His Cys Pro Thr

50 55 60

Thr Pro Ala Pro Leu Pro Ser Gln Arg Arg Asn His Trp Met Glu Asn

65 70 75 80

Ile Ser Pro Phe Arg Ser Val Gly Val Ser Ala Ser Arg Cys Ser Glu

85 90 95

Ser

<210> 73

<211> 31

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 73

Phe His Thr Pro Ala Arg His Pro Arg Pro Arg His Gly His Leu Gln

1 5 10 15

Ala Val Thr Ala His Asp Gly Gly Cys Glu Ala Leu Pro Pro Pro

20 25 30

<210> 74

<211> 78

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 74

Cys Cys Pro Arg Thr Ile Leu Asn Asn Gly Ser Leu Lys Thr Gln Val

1 5 10 15

Gln Met Lys Leu Pro Glu Cys Gln Arg Leu Leu Pro Pro Trp Pro Leu

20 25 30

His Gln Gln Leu Leu His Arg Arg Pro Leu His Gln Pro Pro Pro Gly

35 40 45

Pro Cys His Leu Leu Ser Leu Pro Arg Lys Pro Thr Arg Ala Ala Thr

50 55 60

Val Ser Val Trp Ala Ser Cys Ile Leu Gly Gln Pro Ser Leu

65 70 75

<210> 75

<211> 28

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 75

Val Arg Lys His Phe Gln Thr Tyr Gly Asn Tyr Phe Leu Lys Thr Thr

1 5 10 15

Phe Cys Pro Pro Cys Arg Pro Lys Gln Trp Met Ile

20 25

<210> 76

<211> 46

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 76

Leu Ala Arg Thr Pro Leu Pro Ser Thr Arg Cys Phe Ala Asn Trp Pro

1 5 10 15

Arg Pro Ala Leu Cys Ser Cys Gly Leu Ile Pro His Pro Arg Pro Ala

20 25 30

Pro Ala Ser Ala Pro Trp Pro Ser Thr Ser Ser His Ser Thr

35 40 45

<210> 77

<211> 81

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 77

Glu Leu Gln Glu Thr Gly His Arg Gln Val Ala Leu Arg Arg Ser Gly

1 5 10 15

Arg Pro Pro Lys Cys Ala Glu Arg Pro Gly Ala Ala Asp Thr Gly Ala

20 25 30

His Cys Thr Ser Thr Asp Gly Arg Leu Lys Ile Ser Val Glu Thr Tyr

35 40 45

Thr Val Ser Ser Gln Leu Leu Met Val Leu Met Ser Leu Asp Leu Asp

50 55 60

Thr Gly Leu Val Pro Ser Leu Val Ser Lys Cys Leu Ile Leu Arg Val

65 70 75 80

Lys

<210> 78

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 78

Lys Ser Asp Ala Ser Arg Leu Ser Gly Ala

1 5 10

<210> 79

<211> 29

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 79

Arg Thr Ala Tyr Phe Cys Gln Tyr His Thr Ala Ser Val Tyr Ser Glu

1 5 10 15

Arg Ala Met Pro Pro Gly Cys Pro Glu Pro Ser Gln Ala

20 25

<210> 80

<211> 91

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 80

Thr Arg Ala Ser Pro Pro Arg Ser Ser Ser Ala Ile Ala Val Arg Ala

1 5 10 15

Ser Cys Cys Pro Tyr Gly Ser Thr Ser Thr Ala Ser Arg Ser Pro Thr

20 25 30

Gln Arg Cys Arg Leu Ala Arg Ala Ala Ala Ser Thr Ala Thr Glu Val

35 40 45

Thr Phe Gly Ser Ser Glu Met Gln Gly His Thr Met Gly Phe Trp Leu

50 55 60

Thr Lys Leu Asn Tyr Leu Cys His Leu Ser Met Leu Thr Asp Ser Leu

65 70 75 80

Phe Leu Pro Ile Ser His Cys Gln Cys Ile Leu

85 90

<210> 81

<211> 31

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 81

Ser Ser Leu Arg Ile Thr Gly Asp Trp Thr Ser Ser Gly Arg Ser Thr

1 5 10 15

Lys Ile Trp Lys Thr Thr Gln Met Cys Arg Lys Thr Trp Ser Gly

20 25 30

<210> 82

<211> 104

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 82

Arg Arg Arg Arg Gly Gly Val Gly Arg Arg Gly Val Arg Pro Gly Arg

1 5 10 15

Val Arg Pro Gly Gly Thr Gly Arg Arg Gly Gly Asp Gly Gly Arg Ala

20 25 30

Ala Ala Ala Arg Ala Ala Leu Gly Glu Leu Ala Arg Ala Leu Pro Gly

35 40 45

His Leu Leu Gln Ser Gln Ser Ala Arg Arg Ala Ala Arg Met Ala Gln

50 55 60

Leu Arg Arg Arg Ala Ala Ala Leu Pro Asn Ala Ala Ala Trp His Gly

65 70 75 80

Pro Pro His Pro Gln Leu Pro Arg Ser Pro Leu Ala Leu Gln Arg Cys

85 90 95

Arg Asp Thr Arg Trp Ala Ser Gly

100

<210> 83

<211> 53

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 83

Gly Val Glu Pro Cys Tyr Gly Asp Lys Asp Lys Arg Arg His Cys Phe

1 5 10 15

Ala Thr Trp Lys Asn Ile Ser Gly Ser Ile Glu Ile Val Lys Gln Gly

20 25 30

Cys Trp Leu Asp Asp Ile Asn Cys Tyr Asp Arg Thr Asp Cys Val Glu

35 40 45

Lys Lys Arg Gln Pro

fifty

<210> 84

<211> 103

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 84

Gly Val Glu Pro Cys Tyr Gly Asp Lys Asp Lys Arg Arg His Cys Phe

1 5 10 15

Ala Thr Trp Lys Asn Ile Ser Gly Ser Ile Glu Ile Val Lys Gln Gly

20 25 30

Cys Trp Leu Asp Asp Ile Asn Cys Tyr Asp Arg Thr Asp Cys Val Glu

35 40 45

Lys Lys Thr Ala Leu Lys Tyr Ile Phe Val Ala Val Arg Ala Ile Cys

50 55 60

Val Met Lys Ser Phe Leu Ile Phe Arg Arg Trp Lys Ser His Ser Pro

65 70 75 80

Leu Gln Ile Gln Leu His Leu Ser His Pro Ile Thr Thr Ser Cys Ser

85 90 95

Ile Pro Trp Cys His Leu Cys

100

<210> 85

<211> 118

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 85

Thr Ala Glu Ala Val Asn Val Ala Ile Ala Ala Pro Pro Ser Glu Gly

1 5 10 15

Glu Ala Asn Ala Glu Leu Cys Arg Tyr Leu Ser Lys Val Leu Glu Leu

20 25 30

Arg Lys Ser Asp Val Val Leu Asp Lys Val Gly Leu Ala Leu Phe Phe

35 40 45

Phe Phe Phe Glu Thr Lys Ser Cys Ser Val Ala Gln Ala Gly Val Gln

50 55 60

Trp Arg Ser Leu Gly Ser Leu Gln Pro Pro Pro Pro Gly Phe Lys Leu

65 70 75 80

Phe Ser Cys Leu Ser Phe Leu Ser Ser Trp Asp Tyr Arg Arg Met Pro

85 90 95

Pro Cys Leu Ala Asn Phe Cys Ile Phe Asn Arg Asp Gly Val Ser Pro

100 105 110

Cys Trp Ser Gly Trp Ser

115

<210> 86

<211> 71

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 86

Leu Ser Val Ile Ile Phe Phe Phe Val Tyr Ile Trp His Trp Ala Leu

1 5 10 15

Pro Leu Ile Leu Asn Asn His His Ile Cys Leu Met Ser Ser Ile Ile

20 25 30

Leu Asp Cys Asn Ser Val Arg Gln Ser Ile Met Ser Val Cys Phe Phe

35 40 45

Phe Phe Ser Val Ile Phe Ser Thr Arg Cys Leu Thr Asp Ser Arg Tyr

50 55 60

Pro Asn Ile Cys Trp Phe Lys

65 70

<210> 87

<211> 60

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 87

Leu Ser Val Ile Ile Phe Phe Phe Val Tyr Ile Trp His Trp Ala Leu

1 5 10 15

Pro Leu Ile Leu Asn Asn His His Ile Cys Leu Met Ser Ser Ile Ile

20 25 30

Leu Asp Cys Asn Ser Val Arg Gln Ser Ile Met Ser Val Cys Phe Phe

35 40 45

Phe Phe Cys Tyr Ile Leu Asn Thr Met Phe Asp Arg

50 55 60

<210> 88

<211> 106

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 88

Val Leu Val Leu Ser Cys Asp Leu Ile Thr Asp Val Ala Leu His Glu

1 5 10 15

Val Val Asp Leu Phe Arg Ala Tyr Asp Ala Ser Leu Ala Met Leu Met

20 25 30

Arg Lys Gly Gln Asp Ser Ile Glu Pro Val Pro Gly Gln Lys Gly Lys

35 40 45

Lys Lys Gln Trp Ser Ser Val Thr Ser Leu Glu Trp Thr Ala Gln Glu

50 55 60

Arg Gly Cys Ser Ser Trp Leu Met Lys Gln Thr Trp Met Lys Ser Trp

65 70 75 80

Ser Leu Arg Asp Pro Ser Tyr Arg Ser Ile Leu Glu Tyr Val Ser Thr

85 90 95

Arg Val Leu Trp Met Pro Thr Ser Thr Val

100 105

<210> 89

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 89

Ser Ile Gln Val Met Arg Ala Gln Met Asn Gln Ile Gln Ser Val Glu

1 5 10 15

Gly Gln Pro Leu Ala Arg Arg Pro Arg Ala Thr Gly Arg Thr Lys Arg

20 25 30

Cys Gln Pro Arg Asp Val Thr Lys Lys Thr Cys Asn Ser Asn Asp Gly

35 40 45

Lys Lys Arg Glu Trp Glu Lys Arg Lys Gln Ile Leu Gly Gly Gly Gly

50 55 60

Lys Tyr Lys Glu Tyr Phe Leu Lys Arg Ile Leu Ile Arg Lys Ala Met

65 70 75 80

Thr Val Leu Ala Gly Asp Lys Lys Gly Leu Gly Arg Phe Met Arg Cys

85 90 95

Val Gln Ser Glu Thr Lys Ala Val Ser Leu Gln Leu Pro Leu Gly Arg

100 105 110

<210> 90

<211> 57

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 90

Leu Asp Phe Leu Gly Glu Phe Ala Thr Asp Ile Arg Thr His Gly Val

1 5 10 15

His Met Val Leu Asn His Gln Gly Arg Pro Ser Gly Asp Ala Phe Ile

20 25 30

Gln Met Lys Ser Ala Asp Arg Ala Phe Met Ala Ala Gln Lys Cys His

35 40 45

Lys Lys Lys His Glu Gly Gln Ile Cys

50 55

<210> 91

<211> 51

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 91

Leu Asp Phe Leu Gly Glu Phe Ala Thr Asp Ile Arg Thr His Gly Val

1 5 10 15

His Met Val Leu Asn His Gln Gly Arg Pro Ser Gly Asp Ala Phe Ile

20 25 30

Gln Met Lys Ser Ala Asp Arg Ala Phe Met Ala Ala Gln Lys Cys His

35 40 45

Lys Lys Thr

fifty

<210> 92

<211> 75

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 92

Gly Ala Leu Cys Lys Asp Gly Arg Phe Arg Ser Asp Ile Gly Glu Phe

1 5 10 15

Glu Trp Lys Leu Lys Glu Gly His Lys Lys Ile Tyr Gly Lys Gln Ser

20 25 30

Met Val Asp Glu Val Ser Gly Lys Val Leu Glu Met Asp Ile Ser Lys

35 40 45

Lys Lys His Tyr Asn Arg Lys Ile Ser Ile Lys Lys Leu Asn Arg Met

50 55 60

Lys Val Pro Leu Met Lys Leu Ile Thr Arg Val

65 70 75

<210> 93

<211> 58

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 93

Arg Glu Arg Ala Gln Leu Leu Glu Glu Gln Glu Lys Thr Leu Thr Ser

1 5 10 15

Lys Leu Gln Glu Gln Ala Arg Val Leu Lys Glu Arg Cys Gln Gly Glu

20 25 30

Ser Thr Gln Leu Gln Asn Glu Ile Gln Lys Leu Gln Lys Thr Leu Lys

35 40 45

Lys Lys Pro Arg Asp Ile Cys Arg Ile Ser

50 55

<210> 94

<211> 53

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 94

Val Asn Thr Leu Lys Glu Gly Lys Arg Leu Pro Cys Pro Pro Asn Cys

1 5 10 15

Pro Asp Glu Val Tyr Gln Leu Met Arg Lys Cys Trp Glu Phe Gln Pro

20 25 30

Ser Asn Arg Thr Ser Phe Gln Asn Leu Ile Glu Gly Phe Glu Ala Leu

35 40 45

Leu Lys Thr Ser Asn

fifty

<210> 95

<211> 65

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 95

Cys Arg Pro Val Thr Pro Ser Cys Lys Glu Leu Ala Asp Leu Met Thr

1 5 10 15

Arg Cys Met Asn Tyr Asp Pro Asn Gln Arg Pro Phe Phe Arg Ala Ile

20 25 30

Met Arg Asp Ile Asn Lys Leu Glu Glu Gln Asn Pro Asp Ile Val Ser

35 40 45

Glu Lys Asn Gln Gln Leu Lys Trp Thr Pro His Ile Leu Lys Ser Ala

50 55 60

Ser

65

<210> 96

<211> 69

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 96

Asp Asp His Asp Val Leu Ser Phe Leu Thr Phe Gln Leu Thr Glu Pro

1 5 10 15

Gly Lys Glu Pro Pro Thr Pro Asp Lys Glu Ile Ser Glu Lys Glu Lys

20 25 30

Glu Lys Tyr Gln Glu Glu Phe Glu His Phe Gln Gln Glu Leu Asp Lys

35 40 45

Lys Lys Arg Gly Ile Pro Glu Gly Pro Pro Arg Pro Pro Arg Ala Ala

50 55 60

Cys Gly Gly Asn Ile

65

<210> 97

<211> 71

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 97

Asp Asp His Asp Val Leu Ser Phe Leu Thr Phe Gln Leu Thr Glu Pro

1 5 10 15

Gly Lys Glu Pro Pro Thr Pro Asp Lys Glu Ile Ser Glu Lys Glu Lys

20 25 30

Glu Lys Tyr Gln Glu Glu Phe Glu His Phe Gln Gln Glu Leu Asp Lys

35 40 45

Lys Lys Arg Asn Ser Arg Arg Ala Thr Pro Thr Ser Lys Gly Ser Leu

50 55 60

Arg Arg Lys Tyr Leu Arg Val

65 70

<210> 98

<211> 68

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 98

Thr Lys Ser Thr Leu Ile Gly Glu Asp Val Asn Pro Leu Ile Lys Leu

1 5 10 15

Asp Asp Ala Val Asn Val Asp Glu Ile Met Thr Asp Thr Ser Thr Ser

20 25 30

Tyr Leu Leu Cys Ile Ser Glu Asn Lys Glu Asn Val Arg Asp Lys Lys

35 40 45

Lys Gly Gln His Phe Tyr Trp His Cys Gly Ser Ala Ala Cys His Arg

50 55 60

Arg Gly Cys Val

65

<210> 99

<211> 81

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 99

Leu Tyr Thr Lys Ser Thr Leu Ile Gly Glu Asp Val Asn Pro Leu Ile

1 5 10 15

Lys Leu Asp Asp Ala Val Asn Val Asp Glu Ile Met Thr Asp Thr Ser

20 25 30

Thr Ser Tyr Leu Leu Cys Ile Ser Glu Asn Lys Glu Asn Val Arg Asp

35 40 45

Lys Lys Arg Ala Thr Phe Leu Leu Ala Leu Trp Glu Cys Ser Leu Pro

50 55 60

Gln Ala Arg Leu Cys Leu Ile Val Ser Arg Thr Leu Leu Leu Val Gln

65 70 75 80

Ser

<210> 100

<211> 58

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 100

Leu Pro Pro Pro Lys Leu Thr Asp Pro Arg Leu Leu Tyr Ile Gly Phe

1 5 10 15

Leu Gly Tyr Cys Ser Gly Leu Ile Asp Asn Leu Ile Arg Arg Arg Pro

20 25 30

Ile Ala Thr Ala Gly Leu His Arg Gln Leu Leu Tyr Ile Thr Ala Phe

35 40 45

Phe Phe Cys Trp Ile Leu Ser Cys Lys Thr

50 55

<210> 101

<211> 56

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 101

Ser Leu Pro Pro Pro Lys Leu Thr Asp Pro Arg Leu Leu Tyr Ile Gly

1 5 10 15

Phe Leu Gly Tyr Cys Ser Gly Leu Ile Asp Asn Leu Ile Arg Arg Arg

20 25 30

Pro Ile Ala Thr Ala Gly Leu His Arg Gln Leu Leu Tyr Ile Thr Ala

35 40 45

Phe Phe Leu Leu Asp Ile Ile Leu

50 55

<210> 102

<211> 112

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 102

Asn Gln Ser Gly Gly Ala Gly Glu Asp Cys Gln Ile Phe Ser Thr Pro

1 5 10 15

Gly His Pro Lys Met Ile Tyr Ser Ser Ser Asn Leu Lys Thr Pro Ser

20 25 30

Lys Leu Cys Ser Gly Ser Lys Ser His Asp Val Gln Glu Val Leu Lys

35 40 45

Lys Lys Thr Gly Ser Asn Glu Val Thr Thr Arg Tyr Glu Glu Glu Lys Lys

50 55 60

Thr Gly Ser Val Arg Lys Ala Asn Arg Met Pro Lys Asp Val Asn Ile

65 70 75 80

Gln Val Arg Lys Lys Gln Lys His Glu Thr Arg Arg Lys Ser Lys Tyr

85 90 95

Asn Glu Asp Phe Glu Arg Ala Trp Arg Glu Asp Leu Thr Ile Lys Arg

100 105 110

<210> 103

<211> 23

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 103

Met Ala Pro Val Lys Lys Leu Val Val Lys Gly Gly Lys Lys Lys Glu

1 5 10 15

Ala Ser Ser Glu Val His Ser

twenty

<210> 104

<211> 18

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 104

Met Ala Pro Val Lys Lys Leu Val Val Lys Gly Gly Lys Lys Arg Ser

1 5 10 15

Lys Phe

<210> 105

<211> 51

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 105

Met Pro Ser His Gln Gly Ala Glu Gln Gln Gln Gln Gln His His Val

1 5 10 15

Phe Ile Ser Gln Val Val Thr Glu Lys Glu Phe Leu Ser Arg Ser Asp

20 25 30

Gln Leu Gln Gln Ala Val Gln Ser Gln Gly Phe Ile Asn Tyr Cys Gln

35 40 45

Lys Lys Asn

fifty

<210> 106

<211> 65

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 106

Met Pro Ser His Gln Gly Ala Glu Gln Gln Gln Gln Gln His His Val

1 5 10 15

Phe Ile Ser Gln Val Val Thr Glu Lys Glu Phe Leu Ser Arg Ser Asp

20 25 30

Gln Leu Gln Gln Ala Val Gln Ser Gln Gly Phe Ile Asn Tyr Cys Gln

35 40 45

Lys Lys Leu Met Leu Leu Arg Leu Asn Leu Arg Lys Met Cys Gly Pro

50 55 60

Phe

65

<210> 107

<211> 79

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 107

Ala Glu Val Phe Glu Lys Glu Gln Ser Ile Cys Ala Ala Glu Glu Gln

1 5 10 15

Pro Ala Glu Asp Gly Gln Gly Glu Thr Asn Lys Asn Arg Thr Lys Gly

20 25 30

Gly Trp Gln Gln Lys Ser Lys Gly Pro Lys Lys Thr Ala Lys Ser Lys

35 40 45

Lys Lys Glu Thr Phe Lys Lys Lys Thr Tyr Thr Cys Ala Ile Thr Thr

50 55 60

Val Lys Ala Thr Glu Thr Lys Ala Gly Lys Trp Ser Arg Trp Glu

65 70 75

<210> 108

<211> 53

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 108

Met Ala Glu Val Phe Glu Lys Glu Gln Ser Ile Cys Ala Ala Glu Glu

1 5 10 15

Gln Pro Ala Glu Asp Gly Gln Gly Glu Thr Asn Lys Asn Arg Thr Lys

20 25 30

Gly Gly Trp Gln Gln Lys Ser Lys Gly Pro Lys Lys Thr Ala Lys Ser

35 40 45

Lys Lys Arg Asn Leu

fifty

<210> 109

<211> 71

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 109

Asn Ile Met Glu Ile Arg Gln Leu Pro Ser Ser His Ala Leu Glu Ala

1 5 10 15

Lys Leu Ser Arg Met Ser Tyr Pro Val Lys Glu Gln Glu Ser Ile Leu

20 25 30

Lys Thr Val Gly Lys Leu Thr Ala Thr Gln Val Ala Lys Ile Ser Phe

35 40 45

Phe Phe Ala Leu Cys Gly Phe Trp Gln Ile Cys His Ile Lys Lys His

50 55 60

Phe Gln Thr His Lys Leu Leu

65 70

<210> 110

<211> 68

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 110

Tyr Glu Lys Lys Lys Tyr Tyr Asp Lys Asn Ala Ile Ala Ile Thr Asn

1 5 10 15

Ile Ser Ser Ser Asp Ala Pro Leu Gln Pro Leu Val Ser Ser Pro Ser

20 25 30

Leu Gln Ala Ala Val Asp Lys Asn Lys Leu Glu Lys Glu Lys Glu Lys

35 40 45

Lys Lys Gly Arg Glu Lys Glu Arg Lys Gly Ala Arg Lys Ala Gly Lys

50 55 60

Thr Thr Tyr Ser

65

<210> 111

<211> 97

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 111

Lys Tyr Glu Lys Lys Lys Tyr Tyr Asp Lys Asn Ala Ile Ala Ile Thr

1 5 10 15

Asn Ile Ser Ser Ser Asp Ala Pro Leu Gln Pro Leu Val Ser Ser Pro

20 25 30

Ser Leu Gln Ala Ala Val Asp Lys Asn Lys Leu Glu Lys Glu Lys Glu

35 40 45

Lys Lys Arg Lys Arg Lys Arg Glu Lys Arg Ser Gln Lys Ser Arg Gln

50 55 60

Asn His Leu Gln Leu Lys Ser Cys Arg Arg Lys Ile Ser Asn Trp Ser

65 70 75 80

Leu Lys Lys Val Pro Ala Leu Lys Lys Leu Arg Ser Pro Leu Trp Ile

85 90 95

Phe

<210> 112

<211> 65

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 112

Ile Tyr Gln Asp Ala Tyr Arg Ala Glu Trp Gln Val Tyr Lys Glu Glu

1 5 10 15

Ile Ser Arg Phe Lys Glu Gln Leu Thr Pro Ser Gln Ile Met Ser Leu

20 25 30

Glu Lys Glu Ile Met Asp Lys His Leu Lys Arg Lys Ala Met Thr Lys

35 40 45

Lys Lys Arg Val Asn Thr Ala Trp Lys Thr Lys Lys Thr Ser Phe Ser

50 55 60

Leu

65

<210> 113

<211> 51

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 113

Ile Tyr Gln Asp Ala Tyr Arg Ala Glu Trp Gln Val Tyr Lys Glu Glu

1 5 10 15

Ile Ser Arg Phe Lys Glu Gln Leu Thr Pro Ser Gln Ile Met Ser Leu

20 25 30

Glu Lys Glu Ile Met Asp Lys His Leu Lys Arg Lys Ala Met Thr Lys

35 40 45

Lys Lys Ser

fifty

<210> 114

<211> 52

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 114

Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn

1 5 10 15

Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp

20 25 30

Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys

35 40 45

Lys Lys Ala Trp

fifty

<210> 115

<211> 84

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 115

Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu

1 5 10 15

Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His

20 25 30

Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu

35 40 45

Lys Lys Ser Leu Val Arg Leu Ser Ser Cys Val Pro Val Ala Leu Met

50 55 60

Ser Ala Met Thr Thr Ser Ser Ser Gln Lys Asn Ile Thr Pro Ala Ile

65 70 75 80

Leu Thr Cys Cys

<210> 116

<211> 74

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 116

Val Pro Ser Lys Tyr Gln Phe Leu Cys Ser Asp His Phe Thr Pro Asp

1 5 10 15

Ser Leu Asp Ile Arg Trp Gly Ile Arg Tyr Leu Lys Gln Thr Ala Val

20 25 30

Pro Thr Ile Phe Ser Leu Pro Glu Asp Asn Gln Gly Lys Asp Pro Ser

35 40 45

Lys Lys Asn Pro Arg Arg Lys Thr Trp Lys Met Arg Lys Lys Tyr Ala

50 55 60

Gln Lys Pro Ser Gln Lys Asn His Leu Tyr

65 70

<210> 117

<211> 88

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 117

Gly Thr Thr Glu Glu Met Lys Tyr Val Leu Gly Gln Leu Val Gly Leu

1 5 10 15

Asn Ser Pro Asn Ser Ile Leu Lys Ala Ala Lys Thr Leu Tyr Glu His

20 25 30

Tyr Ser Gly Gly Glu Ser His Asn Ser Ser Ser Ser Ser Lys Thr Phe Glu

35 40 45

Lys Lys Gly Glu Lys Asn Asp Leu Gln Leu Phe Val Met Ser Asp Thr

50 55 60

Thr Tyr Lys Ile Tyr Trp Thr Val Ile Leu Leu Asn Pro Cys Gly Asn

65 70 75 80

Leu His Leu Lys Thr Thr Ser Leu

85

<210> 118

<211> 55

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 118

Gln Gln Leu Ile Arg Glu Thr Leu Ile Ser Trp Leu Gln Ala Gln Met

1 5 10 15

Leu Asn Pro Gln Pro Glu Lys Thr Phe Ile Arg Asn Lys Ala Ala Gln

20 25 30

Val Phe Ala Leu Leu Phe Val Thr Glu Tyr Leu Thr Lys Trp Pro Lys

35 40 45

Phe Phe Leu Thr Phe Ser Gln

50 55

<210> 119

<211> 100

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 119

Glu Arg Ala Glu Trp Arg Glu Asn Ile Arg Glu Gln Gln Lys Lys Cys

1 5 10 15

Phe Arg Ser Phe Ser Leu Thr Ser Val Glu Leu Gln Met Leu Thr Asn

20 25 30

Ser Cys Val Lys Leu Gln Thr Val His Ser Ile Pro Leu Thr Ile Asn

35 40 45

Lys Glu Glu Ala Leu Gln Arg Pro Val Ala Ser Asp Phe Glu Pro Gln

50 55 60

Gly Leu Ser Glu Ala Ala Arg Trp Asn Ser Lys Glu Asn Leu Leu Ala

65 70 75 80

Gly Pro Ser Glu Asn Asp Pro Asn Leu Phe Val Ala Leu Tyr Asp Phe

85 90 95

Val Ala Ser Gly

100

<210> 120

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 120

Glu Leu Gln Met Leu Thr Asn Ser Cys Val Lys Leu Gln Thr Val His

1 5 10 15

Ser Ile Pro Leu Thr Ile Asn Lys Glu Asp Asp Glu Ser Pro Gly Leu

20 25 30

Tyr Gly Phe Leu Asn Val Ile Val His Ser Ala Thr Gly Phe Lys Gln

35 40 45

Ser Ser Lys Ala Leu Gln Arg Pro Val Ala Ser Asp Phe Glu Pro Gln

50 55 60

Gly Leu Ser Glu Ala Ala Arg Trp Asn Ser Lys Glu Asn Leu Leu Ala

65 70 75 80

Gly Pro Ser Glu Asn Asp Pro Asn Leu Phe Val Ala Leu Tyr Asp Phe

85 90 95

Val Ala Ser Gly Asp

100

<210> 121

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 121

Ile Ser Asn Ser Trp Asp Ala His Leu Gly Leu Gly Ala Cys Gly Glu

1 5 10 15

Ala Glu Gly Leu Gly Val Gln Gly Ala Glu Glu Glu Glu Glu Glu Glu

20 25 30

Glu Glu Glu Glu Glu Glu Gly Ala Gly Val Pro Ala Cys Pro Pro Lys

35 40 45

Gly Pro Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala

50 55 60

Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met

65 70 75 80

Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly

85 90 95

Glu Arg Ser Thr Asp

100

<210> 122

<211> 100

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 122

Leu Gln Arg Leu Asp Gly Met Gly Cys Leu Glu Phe Asp Glu Glu Arg

1 5 10 15

Ala Gln Gln Glu Asp Ala Leu Ala Gln Gln Ala Phe Glu Glu Glu Ala Arg

20 25 30

Arg Arg Thr Arg Glu Phe Glu Asp Arg Asp Arg Ser His Arg Glu Glu

35 40 45

Met Glu Val His Glu Leu Glu Lys Ser Lys Arg Ala Leu Glu Thr Gln

50 55 60

Met Glu Glu Met Lys Thr Gln Leu Glu Glu Leu Glu Asp Glu Leu Gln

65 70 75 80

Ala Thr Glu Asp Ala Lys Leu Arg Leu Glu Val Asn Met Gln Ala Leu

85 90 95

Lys Gly Gln Phe

100

<210> 123

<211> 100

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 123

Lys Gly Ser Phe Pro Glu Asn Leu Arg His Leu Lys Asn Thr Met Glu

1 5 10 15

Thr Ile Asp Trp Lys Val Phe Glu Ser Trp Met His His Trp Leu Leu

20 25 30

Phe Glu Met Ser Arg His Ser Leu Glu Gln Lys Pro Thr Asp Ala Pro

35 40 45

Pro Lys Ala Gly Val Pro Asn Lys Pro Gly Ile Pro Lys Leu Leu Glu

50 55 60

Gly Ser Lys Asn Ser Ile Gln Trp Glu Lys Ala Glu Asp Asn Gly Cys

65 70 75 80

Arg Ile Thr Tyr Tyr Ile Leu Glu Ile Arg Lys Ser Thr Ser Asn Asn

85 90 95

Leu Gln Asn Gln

100

<210> 124

<211> 100

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 124

Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr Met Ile Met Val

1 5 10 15

Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys Phe Arg Glu Leu

20 25 30

Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln Arg Tyr Leu Val

35 40 45

Ile Gln Leu Gln Asp Lys Phe Glu His Leu Lys Met Ile Gln Gln Glu

50 55 60

Glu Ile Arg Lys Leu Glu Glu Glu Lys Lys Gln Leu Glu Gly Glu Ile

65 70 75 80

Ile Asp Phe Tyr Lys Met Lys Ala Ala Ser Glu Ala Leu Gln Thr Gln

85 90 95

Leu Ser Thr Asp

100

<210> 125

<211> 80

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 125

Met Arg Pro Ser Gly Thr Ala Gly Ala Ala Leu Leu Ala Leu Leu Ala

1 5 10 15

Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Gly Asn Tyr

20 25 30

Val Val Thr Asp His Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser

35 40 45

Tyr Glu Met Glu Glu Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly

50 55 60

Pro Cys Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp

65 70 75 80

<210> 126

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 126

Ser Trp Glu Asn Ser Asp Asp Ser Arg Asn Lys Leu Ser Lys Ile Pro

1 5 10 15

Ser Thr Pro Lys Leu Ile Pro Lys Val Thr Lys Thr Ala Asp Lys His

20 25 30

Lys Asp Val Ile Ile Asn Gln Ala Lys Met Ser Thr Arg Glu Lys Asn

35 40 45

Ser Gln Val Tyr Arg Arg Lys His Gln Glu Leu Gln Ala Met Gln Met

50 55 60

Glu Leu Gln Ser Pro Glu Tyr Lys Leu Ser Lys Leu Arg Thr Ser Thr

65 70 75 80

Ile Met Thr Asp Tyr Asn Pro Asn Tyr Cys Phe Ala Gly Lys Thr Ser

85 90 95

Ser Ile Ser Asp Leu

100

<210> 127

<211> 100

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 127

Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr His Asp Leu Tyr

1 5 10 15

Met Ile Met Arg Glu Cys Trp His Ala Ala Pro Ser Gln Arg Pro Thr

20 25 30

Phe Lys Gln Leu Val Glu Asp Leu Asp Arg Val Leu Thr Val Thr Ser

35 40 45

Thr Asp Val Lys Ala Thr Gln Glu Glu Asn Arg Glu Leu Arg Ser Arg

50 55 60

Cys Glu Glu Leu His Gly Lys Asn Leu Glu Leu Gly Lys Ile Met Asp

65 70 75 80

Arg Phe Glu Glu Val Val Tyr Gln Ala Met Glu Glu Val Gln Lys Gln

85 90 95

Lys Glu Leu Ser

100

<210> 128

<211> 107

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 128

Arg Asp Asn Thr Leu Leu Leu Arg Arg Val Glu Leu Phe Ser Leu Ser

1 5 10 15

Arg Gln Val Ala Arg Glu Ser Thr Tyr Leu Ser Ser Leu Lys Gly Ser

20 25 30

Arg Leu His Pro Glu Glu Leu Gly Gly Pro Pro Leu Lys Lys Leu Lys

35 40 45

Gln Glu Ala Thr Ser Lys Ser Gln Ile Met Ser Leu Trp Gly Leu Val

50 55 60

Ser Lys Met Pro Pro Glu Lys Val Gln Arg Leu Tyr Val Asp Phe Pro

65 70 75 80

Gln His Leu Arg His Leu Leu Gly Asp Trp Leu Glu Ser Gln Pro Trp

85 90 95

Glu Phe Leu Val Gly Ser Asp Ala Phe Cys Cys

100 105

<210> 129

<211> 83

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 129

Met Ser Arg Glu Met Gln Asp Val Asp Leu Ala Glu Val Lys Pro Leu

1 5 10 15

Val Glu Lys Gly Glu Thr Ile Thr Gly Leu Leu Gln Glu Phe Asp Val

20 25 30

Gln Glu Ala Leu Ser Val Val Ser Glu Asp Gln Ser Leu Phe Glu Cys

35 40 45

Ala Tyr Gly Thr Pro His Leu Ala Lys Thr Glu Met Thr Ala Ser Ser

50 55 60

Ser Ser Asp Tyr Gly Gln Thr Ser Lys Met Ser Pro Arg Val Pro Gln

65 70 75 80

Gln Asp Trp

<210> 130

<211> 55

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 130

Met Ala Leu Asn Ser Glu Ala Leu Ser Val Val Ser Glu Asp Gln Ser

1 5 10 15

Leu Phe Glu Cys Ala Tyr Gly Thr Pro His Leu Ala Lys Thr Glu Met

20 25 30

Thr Ala Ser Ser Ser Ser Asp Tyr Gly Gln Thr Ser Lys Met Ser Pro

35 40 45

Arg Val Pro Gln Gln Asp Trp

50 55

<210> 131

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 131

Val Leu Asp Met His Gly Phe Leu Arg Gln Ala Leu Cys Arg Leu Arg

1 5 10 15

Gln Glu Glu Pro Gln Ser Leu Gln Ala Ala Val Arg Thr Asp Gly Phe

20 25 30

Asp Glu Phe Lys Val Arg Leu Gln Asp Leu Ser Ser Cys Ile Thr Gln

35 40 45

Gly Lys Ala Ile Glu Thr Gln Ser Ser Ser Ser Glu Glu Glu Ile Val Pro

50 55 60

Ser Pro Pro Ser Pro Pro Pro Leu Pro Arg Ile Tyr Lys Pro Cys Phe

65 70 75 80

Val Cys Gln Asp Lys Ser Ser Gly Tyr His Tyr Gly Val Ser Ala Cys

85 90 95

Glu Gly Cys Lys Gly

100

<210> 132

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 132

Arg Ser Ser Pro Glu Gln Pro Arg Pro Ser Thr Ser Lys Ala Val Ser

1 5 10 15

Pro Pro His Leu Asp Gly Pro Pro Ser Pro Arg Ser Pro Val Ile Gly

20 25 30

Ser Glu Val Phe Leu Pro Asn Ser Asn His Val Ala Ser Gly Ala Gly

35 40 45

Glu Ala Ala Ile Glu Thr Gln Ser Ser Ser Ser Glu Glu Glu Ile Val Pro

50 55 60

Ser Pro Pro Ser Pro Pro Pro Leu Pro Arg Ile Tyr Lys Pro Cys Phe

65 70 75 80

Val Cys Gln Asp Lys Ser Ser Gly Tyr His Tyr Gly Val Ser Ala Cys

85 90 95

Glu Gly Cys Lys Gly

100

<210> 133

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 133

Val Ala Arg Phe Asn Asp Leu Arg Phe Val Gly Arg Ser Gly Arg Gly

1 5 10 15

Lys Ser Phe Thr Leu Thr Ile Thr Val Phe Thr Asn Pro Pro Gln Val

20 25 30

Ala Thr Tyr His Arg Ala Ile Lys Ile Thr Val Asp Gly Pro Arg Glu

35 40 45

Pro Arg Asn Arg Thr Glu Lys His Ser Thr Met Pro Asp Ser Pro Val

50 55 60

Asp Val Lys Thr Gln Ser Arg Leu Thr Pro Pro Thr Met Pro Pro Pro

65 70 75 80

Pro Thr Thr Gln Gly Ala Pro Arg Thr Ser Ser Phe Thr Pro Thr Thr

85 90 95

Leu Thr Asn Gly Thr

100

<210> 134

<211> 66

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 134

Ser Cys Lys Val Phe Phe Lys Arg Ala Ala Glu Gly Lys Gln Lys Tyr

1 5 10 15

Leu Cys Ala Ser Arg Asn Asp Cys Thr Ile Asp Lys Phe Arg Arg Lys

20 25 30

Asn Cys Pro Ser Cys Arg Leu Arg Lys Cys Tyr Glu Ala Gly Met Thr

35 40 45

Leu Gly Glu Lys Phe Arg Val Gly Asn Cys Lys His Leu Lys Met Thr

50 55 60

ArgPro

65

<210> 135

<211> 49

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 135

Met Ala Gly Ala Pro Pro Pro Ala Ser Leu Pro Pro Cys Ser Leu Ile

1 5 10 15

Ser Asp Cys Cys Ala Ser Asn Gln Arg Asp Ser Val Gly Val Gly Pro

20 25 30

Ser Glu Pro Gly Asn Asn Ile Lys Ile Cys Asn Glu Ser Ala Ser Arg

35 40 45

Lys

<210> 136

<211> 60

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 136

His Gly Trp Arg Pro Phe Leu Pro Val Arg Ala Arg Ser Arg Trp Asn

1 5 10 15

Arg Arg Leu Asp Val Thr Val Ala Asn Gly Arg Ser Trp Lys Tyr Gly

20 25 30

Trp Ser Leu Leu Arg Val Pro Gln Val Asn Gly Ile Gln Val Leu Asn

35 40 45

Val Ser Leu Lys Ser Ser Ser Asn Val Ile Ser Tyr

50 55 60

<210> 137

<211> 65

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 137

Arg Leu Lys Glu Val Phe Gln Thr Lys Ile Gln Glu Phe Arg Lys Ala

1 5 10 15

Cys Tyr Thr Leu Thr Gly Tyr Gln Ile Asp Ile Thr Thr Glu Asn Gln

20 25 30

Tyr Arg Leu Thr Ser Leu Tyr Ala Glu His Pro Gly Asp Cys Leu Ile

35 40 45

Phe Lys Leu Arg Val Pro Gly Ser Ser Val Leu Val Thr Val Pro Gly

50 55 60

Leu

65

<210> 138

<211> 107

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 138

Ala Glu Val Leu Lys Val Ile Arg Gln Ser Ala Gly Gln Lys Thr Thr

1 5 10 15

Cys Gly Gln Gly Leu Glu Gly Pro Trp Glu Arg Pro Pro Pro Leu Asp

20 25 30

Glu Ser Glu Arg Asp Gly Gly Ser Glu Asp Gln Val Glu Asp Pro Ala

35 40 45

Leu Ser Ala Leu Leu Leu Arg Pro Arg Pro Pro Arg Pro Glu Val Gly

50 55 60

Ala His Gln Asp Glu Gln Ala Ala Gln Gly Ala Asp Pro Arg Leu Gly

65 70 75 80

Ala Gln Pro Ala Cys Arg Gly Leu Pro Gly Leu Leu Thr Val Pro Gln

85 90 95

Pro Glu Pro Leu Leu Ala Pro Pro Ser Ala Ala

100 105

<210> 139

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 139

Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly Ile Trp Ile Pro Asp

1 5 10 15

Gly Glu Asn Val Lys Ile Pro Val Ala Ile Lys Val Leu Arg Glu Asn

20 25 30

Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met

35 40 45

Ala Gly Leu Gly Ser Pro Tyr Val Ser Arg Leu Leu Gly Ile Cys Leu

50 55 60

Thr Ser Thr Val Gln Leu Val Thr Gln Leu Met Pro Tyr Gly Cys Leu

65 70 75 80

Leu Asp His Val Arg Glu Asn Arg Gly Arg Leu Gly Ser Gln Asp Leu

85 90 95

Leu Asn Trp Cys Met

100

<210> 140

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 140

Ala Leu Asn Ser Glu Ala Leu Ser Val

fifteen

<210> 141

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 141

Ser Met Leu Thr Gly Pro Pro Ala Arg Val

1 5 10

<210> 142

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 142

Leu Leu Cys Val Trp Val Ser Ser Ile

fifteen

<210> 143

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 143

Lys Leu Val Val Val Gly Ala Cys Gly Val

1 5 10

<210> 144

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 144

Asp Phe Gly Leu Ala Thr Glu Lys Ser Arg

1 5 10

<210> 145

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 145

Phe Gly Leu Ala Thr Glu Lys Ser Arg Trp

1 5 10

<210> 146

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 146

Glu Ala Val Ser Gly Pro Pro Pro Ala

fifteen

<210> 147

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 147

Phe Glu Ala Val Ser Gly Pro Pro Pro

fifteen

<210> 148

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 148

Phe Glu Ala Val Ser Gly Pro Pro Pro Ala

1 5 10

<210> 149

<211> 102

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 149

Met Ser Leu Asn Ile Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile

1 5 10 15

Ser Asp Gly Asp Val Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala

20 25 30

Asn Thr Ile Asn Trp Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr

35 40 45

Lys Ile Ile Arg Asn Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln

50 55 60

Val Cys His Ala Leu Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro

65 70 75 80

Arg Asp Cys Val Ser Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val

85 90 95

Asp Lys Cys Asn Leu Leu

100

<210> 150

<211> 23

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 150

Glu Phe Ser Thr Leu Pro Leu Pro Asn Leu Arg Met Val Arg Gly Thr

1 5 10 15

Gln Val Tyr Asp Gly Lys Phe

twenty

<210> 151

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 151

Arg Met Val Arg Gly Thr Gln Val Tyr

fifteen

<210> 152

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 152

Leu Pro Leu Pro Asn Leu Arg Met Val

fifteen

<210> 153

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 153

Leu Arg Met Val Arg Gly Thr Gln Val

fifteen

<210> 154

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 154

Thr Leu Pro Leu Pro Asn Leu Arg Met Val

1 5 10

<210> 155

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 155

Asn Leu Arg Met Val Arg Gly Thr Gln Val

1 5 10

<210> 156

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 156

Leu Arg Met Val Arg Gly Thr Gln Val Tyr

1 5 10

<210> 157

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 157

Asp Val Leu Glu Arg Cys Pro His Arg

fifteen

<210> 158

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 158

Leu Glu Arg Cys Pro His Arg Pro Ile

fifteen

<210> 159

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 159

Cys Pro His Arg Pro Ile Leu Gln Ala

fifteen

<210> 160

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 160

Leu Glu Arg Cys Pro His Arg Pro Ile Leu

1 5 10

<210> 161

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 161

Ser Ala Ser Asn Ser Cys Phe Ile Arg

fifteen

<210> 162

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 162

Leu Ser Ala Ser Asn Ser Cys Phe Ile

fifteen

<210> 163

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 163

Ala Leu Ser Ala Ser Asn Ser Cys Phe

fifteen

<210> 164

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 164

Phe Gln Asn Gly Lys Met Ala Leu Ser Ala

1 5 10

<210> 165

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 165

Pro Ile Ile Ile Gly His His Ala Tyr

fifteen

<210> 166

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 166

Gly His His Ala Tyr Gly Asp Gln Tyr

fifteen

<210> 167

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 167

Lys Pro Ile Ile Ile Gly His His Ala Tyr

1 5 10

<210> 168

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 168

Ile Gly His His Ala Tyr Gly Asp Gln Tyr

1 5 10

<210> 169

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 169

Pro Ile Ile Ile Gly Cys His Ala Tyr

fifteen

<210> 170

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 170

Gly Cys His Ala Tyr Gly Asp Gln Tyr

fifteen

<210> 171

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 171

Lys Pro Ile Ile Ile Gly Cys His Ala Tyr

1 5 10

<210> 172

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 172

Ile Gly Cys His Ala Tyr Gly Asp Gln Tyr

1 5 10

<210> 173

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 173

Pro Ile Ile Ile Gly Gly His Ala Tyr

fifteen

<210> 174

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 174

Gly Gly His Ala Tyr Gly Asp Gln Tyr

fifteen

<210> 175

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 175

Lys Pro Ile Ile Ile Gly Gly His Ala Tyr

1 5 10

<210> 176

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 176

Ile Gly Gly His Ala Tyr Gly Asp Gln Tyr

1 5 10

<210> 177

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 177

Ile Ser Thr Arg Asp Pro Leu Ser Lys

fifteen

<210> 178

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 178

Ser Thr Arg Asp Pro Leu Ser Lys Ile

fifteen

<210> 179

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 179

Leu Ser Lys Ile Thr Glu Gln Glu Lys

fifteen

<210> 180

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 180

Ala Ile Ser Thr Arg Asp Pro Leu Ser Lys

1 5 10

<210> 181

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 181

Ser Lys Ile Thr Glu Gln Glu Lys Asp Phe

1 5 10

<210> 182

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 182

Ser Glu Ile Thr Lys Gln Glu Lys Asp Phe

1 5 10

<210> 183

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 183

Lys Gln Glu Lys Asp Phe Leu Trp Ser His

1 5 10

<210> 184

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 184

Phe Met Lys Gln Met Asn Asp Ala Arg

fifteen

<210> 185

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 185

Lys Gln Met Asn Asp Ala Arg His Gly

fifteen

<210> 186

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 186

Arg His Gly Gly Trp Thr Thr Lys Met

fifteen

<210> 187

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 187

Tyr Phe Met Lys Gln Met Asn Asp Ala Arg

1 5 10

<210> 188

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 188

Phe Met Lys Gln Met Asn Asp Ala Arg His

1 5 10

<210> 189

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 189

Lys Gln Met Asn Asp Ala Arg His Gly Gly

1 5 10

<210> 190

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 190

Gln Met Asn Asp Ala Arg His Gly Gly Trp

1 5 10

<210> 191

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 191

Ala Arg His Gly Gly Trp Thr Thr Lys Met

1 5 10

<210> 192

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 192

Thr Thr Lys Leu Pro Leu Lys Phe Arg

fifteen

<210> 193

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 193

Arg Asp Ala Glu Thr Asp Gln Ile Met

fifteen

<210> 194

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 194

Lys Phe Arg Asp Ala Glu Thr Asp Gln Ile

1 5 10

<210> 195

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 195

Glu Thr Thr Lys Leu Pro Leu Lys Phe Arg

1 5 10

<210> 196

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 196

Arg Asp Ala Glu Thr Asp Gln Ile Met Met

1 5 10

<210> 197

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 197

Gln Thr Gly Val Met Ile Cys Ala Tyr

fifteen

<210> 198

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 198

Gly Lys Gly Gln Thr Gly Val Met Ile

fifteen

<210> 199

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 199

Gly Gln Thr Gly Val Met Ile Cys Ala Tyr

1 5 10

<210> 200

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 200

Lys Ala Gly Lys Gly Gln Thr Gly Val Met

1 5 10

<210> 201

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 201

Thr Thr Asn Ala Phe Ser Gly Glu Tyr

fifteen

<210> 202

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 202

Phe Ser Gly Glu Tyr Ile Pro Thr Val

fifteen

<210> 203

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 203

Ser Gly Glu Tyr Ile Pro Thr Val Phe

fifteen

<210> 204

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 204

Tyr Thr Thr Asn Ala Phe Ser Gly Glu Tyr

1 5 10

<210> 205

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 205

Thr Thr Asn Ala Phe Ser Gly Glu Tyr Ile

1 5 10

<210> 206

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 206

Phe Ser Gly Glu Tyr Ile Pro Thr Val Phe

1 5 10

<210> 207

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 207

Ser Ser Cys Met Gly Ser Met Asn Arg

fifteen

<210> 208

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 208

Gly Ser Met Asn Arg Arg Pro Ile Leu

fifteen

<210> 209

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 209

Met Gly Ser Met Asn Arg Arg Pro Ile

fifteen

<210> 210

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 210

Cys Asn Ser Ser Cys Met Gly Ser Met

fifteen

<210> 211

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 211

Ser Met Asn Arg Arg Pro Ile Leu Thr Ile

1 5 10

<210> 212

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 212

Ser Ser Cys Met Gly Ser Met Asn Arg Arg

1 5 10

<210> 213

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 213

Asn Ser Ser Cys Met Gly Ser Met Asn Arg

1 5 10

<210> 214

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 214

Met Gly Ser Met Asn Arg Arg Pro Ile Leu

1 5 10

<210> 215

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 215

Met Cys Asn Ser Ser Cys Met Gly Ser Met

1 5 10

<210> 216

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 216

Cys Met Gly Ser Met Asn Arg Arg Pro Ile

1 5 10

<210> 217

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 217

Thr Glu Val Val Arg His Cys Pro His

fifteen

<210> 218

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 218

Val Val Arg His Cys Pro His His Glu Arg

1 5 10

<210> 219

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 219

Ser Gln His Met Thr Glu Val Val Arg His

1 5 10

<210> 220

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 220

Met Asn Gln Arg Pro Ile Leu Thr Ile

fifteen

<210> 221

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 221

Asn Gln Arg Pro Ile Leu Thr Ile Ile

fifteen

<210> 222

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 222

Cys Met Gly Gly Met Asn Gln Arg Pro Ile

1 5 10

<210> 223

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 223

Gly Met Asn Gln Arg Pro Ile Leu Thr Ile

1 5 10

<210> 224

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 224

Ser Ser Cys Met Gly Gly Met Asn Gln Arg

1 5 10

<210> 225

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 225

Asn Gln Arg Pro Ile Leu Thr Ile Ile Thr

1 5 10

<210> 226

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 226

Asn Trp Arg Pro Ile Leu Thr Ile Ile

fifteen

<210> 227

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 227

Ser Ser Cys Met Gly Gly Met Asn Trp

fifteen

<210> 228

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 228

Met Gly Gly Met Asn Trp Arg Pro Ile

fifteen

<210> 229

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 229

Met Asn Trp Arg Pro Ile Leu Thr Ile

fifteen

<210> 230

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 230

Cys Met Gly Gly Met Asn Trp Arg Pro Ile

1 5 10

<210> 231

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 231

Gly Met Asn Trp Arg Pro Ile Leu Thr Ile

1 5 10

<210> 232

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 232

Ser Ser Cys Met Gly Gly Met Asn Trp Arg

1 5 10

<210> 233

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 233

Met Asn Trp Arg Pro Ile Leu Thr Ile Ile

1 5 10

<210> 234

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 234

Asn Ser Ser Cys Met Gly Gly Met Asn Trp

1 5 10

<210> 235

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 235

Asn Ser Phe Glu Val Cys Val Cys Ala

fifteen

<210> 236

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 236

Glu Val Cys Val Cys Ala Cys Pro Gly Arg

1 5 10

<210> 237

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 237

Phe Glu Val Cys Val Cys Ala Cys Pro Gly

1 5 10

<210> 238

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 238

Lys Leu Asn Arg Met Lys Val Pro Leu

fifteen

<210> 239

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 239

Pro Leu Met Lys Leu Ile Thr Arg Val

fifteen

<210> 240

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 240

Arg Met Lys Val Pro Leu Met Lys Leu

fifteen

<210> 241

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 241

Ile Ser Lys Lys Lys His Tyr Asn Arg

fifteen

<210> 242

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 242

Ser Lys Lys Lys His Tyr Asn Arg Lys

fifteen

<210> 243

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 243

Lys His Tyr Asn Arg Lys Ile Ser Ile

fifteen

<210> 244

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 244

His Tyr Asn Arg Lys Ile Ser Ile Lys

fifteen

<210> 245

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 245

Tyr Asn Arg Lys Ile Ser Ile Lys Lys

fifteen

<210> 246

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 246

Lys Ile Ser Ile Lys Lys Leu Asn Arg

fifteen

<210> 247

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 247

Ser Ile Lys Lys Leu Asn Arg Met Lys

fifteen

<210> 248

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 248

Leu Asn Arg Met Lys Val Pro Leu Met

fifteen

<210> 249

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 249

Ile Ser Ile Lys Lys Leu Asn Arg Met

fifteen

<210> 250

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 250

Met Lys Val Pro Leu Met Lys Leu Ile

fifteen

<210> 251

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 251

Lys Leu Asn Arg Met Lys Val Pro Leu Met

1 5 10

<210> 252

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 252

Arg Met Lys Val Pro Leu Met Lys Leu Ile

1 5 10

<210> 253

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 253

Ile Ser Ile Lys Lys Leu Asn Arg Met Lys

1 5 10

<210> 254

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 254

Ile Ser Lys Lys Lys His Tyr Asn Arg Lys

1 5 10

<210> 255

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 255

Lys His Tyr Asn Arg Lys Ile Ser Ile Lys

1 5 10

<210> 256

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 256

His Tyr Asn Arg Lys Ile Ser Ile Lys Lys

1 5 10

<210> 257

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 257

Lys Ile Ser Ile Lys Lys Leu Asn Arg Met

1 5 10

<210> 258

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 258

Ser Ile Lys Lys Leu Asn Arg Met Lys Val

1 5 10

<210> 259

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 259

Leu Asn Arg Met Lys Val Pro Leu Met Lys

1 5 10

<210> 260

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 260

Lys Val Pro Leu Met Lys Leu Ile Thr Arg

1 5 10

<210> 261

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 261

Asp Ile Ser Lys Lys Lys His Tyr Asn Arg

1 5 10

<210> 262

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 262

Lys Lys His Tyr Asn Arg Lys Ile Ser Ile

1 5 10

<210> 263

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 263

Lys Lys Leu Asn Arg Met Lys Val Pro Leu

1 5 10

<210> 264

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 264

Val Pro Leu Met Lys Leu Ile Thr Arg Val

1 5 10

<210> 265

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 265

Val Val Lys Gly Gly Lys Lys Arg Ser Lys

1 5 10

<210> 266

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 266

Val Lys Gly Gly Lys Lys Arg Ser Lys

fifteen

<210> 267

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 267

Ala Leu Lys Lys Leu Arg Ser Pro Leu

fifteen

<210> 268

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 268

Lys Ile Ser Asn Trp Ser Leu Lys Lys

fifteen

<210> 269

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 269

Ser Leu Lys Lys Val Pro Ala Leu Lys

fifteen

<210> 270

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 270

Lys Leu Arg Ser Pro Leu Trp Ile Phe

fifteen

<210> 271

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 271

Lys Lys Arg Lys Arg Lys Arg Glu Lys

fifteen

<210> 272

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 272

Arg Lys Arg Glu Lys Arg Ser Gln Lys

fifteen

<210> 273

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 273

Arg Ser Gln Lys Ser Arg Gln Asn His

fifteen

<210> 274

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 274

Ser Gln Lys Ser Arg Gln Asn His Leu

fifteen

<210> 275

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 275

Lys Ser Arg Gln Asn His Leu Gln Leu

fifteen

<210> 276

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 276

Arg Arg Lys Ile Ser Asn Trp Ser Leu

fifteen

<210> 277

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 277

Arg Lys Ile Ser Asn Trp Ser Leu Lys

fifteen

<210> 278

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 278

Lys Val Pro Ala Leu Lys Lys Leu Arg

fifteen

<210> 279

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 279

His Leu Gln Leu Lys Ser Cys Arg Arg

fifteen

<210> 280

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 280

Trp Ser Leu Lys Lys Val Pro Ala Leu

fifteen

<210> 281

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 281

Arg Gln Asn His Leu Gln Leu Lys Ser

fifteen

<210> 282

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 282

Lys Lys Val Pro Ala Leu Lys Lys Leu

fifteen

<210> 283

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 283

Leu Lys Lys Leu Arg Ser Pro Leu Trp

fifteen

<210> 284

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 284

Lys Lys Leu Arg Ser Pro Leu Trp Ile

fifteen

<210> 285

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 285

Lys Ile Ser Asn Trp Ser Leu Lys Lys Val

1 5 10

<210> 286

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 286

Lys Ser Arg Gln Asn His Leu Gln Leu Lys

1 5 10

<210> 287

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 287

Ser Leu Lys Lys Val Pro Ala Leu Lys Lys

1 5 10

<210> 288

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 288

Trp Ser Leu Lys Lys Val Pro Ala Leu Lys

1 5 10

<210> 289

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 289

Lys Arg Lys Arg Glu Lys Arg Ser Gln Lys

1 5 10

<210> 290

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 290

Arg Ser Gln Lys Ser Arg Gln Asn His Leu

1 5 10

<210> 291

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 291

His Leu Gln Leu Lys Ser Cys Arg Arg Lys

1 5 10

<210> 292

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 292

Arg Arg Lys Ile Ser Asn Trp Ser Leu Lys

1 5 10

<210> 293

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 293

Cys Arg Arg Lys Ile Ser Asn Trp Ser Leu

1 5 10

<210> 294

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 294

Asn Trp Ser Leu Lys Lys Val Pro Ala Leu

1 5 10

<210> 295

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 295

Gln Lys Ser Arg Gln Asn His Leu Gln Leu

1 5 10

<210> 296

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 296

Arg Gln Asn His Leu Gln Leu Lys Ser Cys

1 5 10

<210> 297

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 297

Leu Gln Leu Lys Ser Cys Arg Arg Lys Ile

1 5 10

<210> 298

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 298

Ala Leu Lys Lys Leu Arg Ser Pro Leu Trp

1 5 10

<210> 299

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 299

Ala Asp Val Leu Leu Ser Val His Leu

fifteen

<210> 300

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 300

Ala Asp Val Leu Leu Ser Val His Leu Ile

1 5 10

<210> 301

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 301

Ala Pro Phe Arg Val Asn His Ala Val

fifteen

<210> 302

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 302

Ala Arg His Lys Ala Val Glu Phe Leu

fifteen

<210> 303

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 303

Cys Leu Ala Asp Val Leu Leu Ser Val

fifteen

<210> 304

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 304

Cys Leu Ala Asp Val Leu Leu Ser Val His

1 5 10

<210> 305

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 305

Asp Val Leu Leu Ser Val His Leu Ile

fifteen

<210> 306

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 306

Asp Val Leu Leu Ser Val His Leu Ile Val

1 5 10

<210> 307

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 307

Phe Leu Gln Glu Arg Asn Leu Pro Pro Lys

1 5 10

<210> 308

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 308

Phe Arg Val Asn His Ala Val Glu Trp

fifteen

<210> 309

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 309

His Leu Ile Val Leu Arg Val Val Arg

fifteen

<210> 310

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 310

His Leu Ile Val Leu Arg Val Val Arg Leu

1 5 10

<210> 311

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 311

His Leu Asn Thr Met Phe Arg Arg Pro His

1 5 10

<210> 312

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 312

His Pro Lys Val His Leu Asn Thr Met

fifteen

<210> 313

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 313

His Pro Lys Val His Leu Asn Thr Met Phe

1 5 10

<210> 314

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 314

Lys Ala Val Glu Phe Leu Gln Glu Arg

fifteen

<210> 315

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 315

Lys Val His Leu Asn Thr Met Phe Arg

fifteen

<210> 316

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 316

Lys Val His Leu Asn Thr Met Phe Arg Arg

1 5 10

<210> 317

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 317

Lys Val Val Leu Arg His Pro Lys Val

fifteen

<210> 318

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 318

Leu Leu Ser Val His Leu Ile Val Leu

fifteen

<210> 319

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 319

Leu Leu Ser Val His Leu Ile Val Leu Arg

1 5 10

<210> 320

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 320

Leu Pro Ala Pro Phe Arg Val Asn His

fifteen

<210> 321

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 321

Leu Pro Ala Pro Phe Arg Val Asn His Ala

1 5 10

<210> 322

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 322

Leu Gln Glu Arg Asn Leu Pro Pro Lys Val

1 5 10

<210> 323

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 323

Leu Arg Val Val Arg Leu Pro Ala Pro Phe

1 5 10

<210> 324

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 324

Leu Ser Val His Leu Ile Val Leu Arg

fifteen

<210> 325

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 325

Leu Ser Val His Leu Ile Val Leu Arg Val

1 5 10

<210> 326

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 326

Met Phe Arg Arg Pro His Ser Cys Leu

fifteen

<210> 327

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 327

Met Phe Arg Arg Pro His Ser Cys Leu Ala

1 5 10

<210> 328

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 328

Asn Leu Pro Pro Lys Val Val Leu Arg

fifteen

<210> 329

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 329

Asn Thr Met Phe Arg Arg Pro His Ser Cys

1 5 10

<210> 330

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 330

Gln Glu Arg Asn Leu Pro Pro Lys Val

fifteen

<210> 331

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 331

Arg His Pro Lys Val His Leu Asn Thr Met

1 5 10

<210> 332

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 332

Arg Asn Leu Pro Pro Lys Val Val Leu

fifteen

<210> 333

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 333

Arg Asn Leu Pro Pro Lys Val Val Leu Arg

1 5 10

<210> 334

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 334

Arg Pro His Ser Cys Leu Ala Asp Val

fifteen

<210> 335

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 335

Arg Pro His Ser Cys Leu Ala Asp Val Leu

1 5 10

<210> 336

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 336

Arg Val Val Arg Leu Pro Ala Pro Phe

fifteen

<210> 337

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 337

Arg Val Val Arg Leu Pro Ala Pro Phe Arg

1 5 10

<210> 338

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 338

Ser Ala Arg His Lys Ala Val Glu Phe Leu

1 5 10

<210> 339

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 339

Ser Val His Leu Ile Val Leu Arg Val

fifteen

<210> 340

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 340

Ser Val His Leu Ile Val Leu Arg Val Val

1 5 10

<210> 341

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 341

Thr Met Phe Arg Arg Pro His Ser Cys

fifteen

<210> 342

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 342

Thr Met Phe Arg Arg Pro His Ser Cys Leu

1 5 10

<210> 343

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 343

Val Glu Phe Leu Gln Glu Arg Asn Leu

fifteen

<210> 344

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 344

Val Leu Leu Ser Val His Leu Ile Val

fifteen

<210> 345

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 345

Val Leu Leu Ser Val His Leu Ile Val Leu

1 5 10

<210> 346

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 346

Val Leu Arg His Pro Lys Val His Leu

fifteen

<210> 347

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 347

Val Leu Arg Val Val Arg Leu Pro Ala

fifteen

<210> 348

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 348

Val Val Arg Leu Pro Ala Pro Phe Arg

fifteen

<210> 349

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 349

Val Val Arg Leu Pro Ala Pro Phe Arg Val

1 5 10

<210> 350

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 350

Ala Ala Trp Arg Ser Cys Ile Ala Leu

fifteen

<210> 351

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 351

Ala Ala Trp Arg Ser Cys Ile Ala Leu Trp

1 5 10

<210> 352

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 352

Ala Glu Thr Val Ser Leu His Pro Leu

fifteen

<210> 353

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 353

Ala Glu Thr Val Ser Leu His Pro Leu Ala

1 5 10

<210> 354

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 354

Ala His Met Ala Leu Leu Pro Ser Gly

fifteen

<210> 355

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 355

Ala Leu Trp Cys Ala Ser Ser Val Thr

fifteen

<210> 356

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 356

Ala Met Pro Ile Leu Pro Leu Pro Gln Leu

1 5 10

<210> 357

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 357

Ala Pro Leu Leu Ala Ala Pro Ser Pro Ala

1 5 10

<210> 358

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 358

Ala Pro Arg Thr Asn Phe His Ser Ser

fifteen

<210> 359

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 359

Ala Pro Arg Thr Asn Phe His Ser Ser Leu

1 5 10

<210> 360

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 360

Ala Ser Asn Lys Leu Pro Ser Leu Pro Leu

1 5 10

<210> 361

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 361

Ala Trp Arg Ser Cys Ile Ala Leu Trp

fifteen

<210> 362

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 362

Cys Ala Gly Arg Trp Leu Trp Tyr Cys Trp

1 5 10

<210> 363

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 363

Cys Ile Ala Leu Trp Cys Ala Ser Ser Val

1 5 10

<210> 364

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 364

Cys Pro Gln Pro Ser Pro Ser Leu Pro Ala

1 5 10

<210> 365

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 365

Cys Arg Arg Ala Val Ser Ala Thr Ser Trp

1 5 10

<210> 366

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 366

Cys Thr Ala Cys His Thr Ala Leu Gly Arg

1 5 10

<210> 367

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 367

Asp Gln Gln Ala Ala Pro Arg Thr Asn Phe

1 5 10

<210> 368

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 368

Glu Thr Val Ser Leu His Pro Leu Ala

fifteen

<210> 369

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 369

Phe His Ser Ser Leu Ala Glu Thr Val

fifteen

<210> 370

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 370

Gly Met Tyr Ser Pro Ser Arg Tyr Pro Arg

1 5 10

<210> 371

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 371

Gly Gln Trp Met Ala His Met Ala Leu

fifteen

<210> 372

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 372

Gly Gln Trp Met Ala His Met Ala Leu Leu

1 5 10

<210> 373

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 373

Gly Arg Cys Thr Ala Cys His Thr Ala Leu

1 5 10

<210> 374

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 374

Gly Thr Ala Trp Gln Leu Val Pro Leu

fifteen

<210> 375

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 375

His Met Ala Leu Leu Pro Ser Gly Thr

fifteen

<210> 376

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 376

His Met Ala Leu Leu Pro Ser Gly Thr Lys

1 5 10

<210> 377

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 377

His Pro Leu Ala Pro Met Pro Ser Lys

fifteen

<210> 378

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 378

His Ser Ser Leu Ala Glu Thr Val Ser Leu

1 5 10

<210> 379

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 379

His Thr Ala Leu Gly Arg Gly Ser Leu

fifteen

<210> 380

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 380

Ile Ala Leu Trp Cys Ala Ser Ser Val

fifteen

<210> 381

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 381

Ile Leu Ala Thr Pro Ser Ala Ala

fifteen

<210> 382

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 382

Ile Leu Ala Thr Pro Ser Ala Ala Trp

1 5 10

<210> 383

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 383

Ile Pro Met Ala Ile Ser Ser Pro Pro

fifteen

<210> 384

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 384

Ile Pro Met Ala Ile Ser Ser Pro Pro Lys

1 5 10

<210> 385

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 385

Ile Ser Ser Pro Pro Lys Ala Pro Leu

fifteen

<210> 386

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 386

Ile Ser Ser Pro Pro Lys Ala Pro Leu Leu

1 5 10

<210> 387

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 387

Ile Thr Ser Gly Gln Trp Met Ala His Met

1 5 10

<210> 388

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 388

Lys Gly Arg Cys Thr Ala Cys His Thr

fifteen

<210> 389

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 389

Lys Gly Arg Cys Thr Ala Cys His Thr Ala

1 5 10

<210> 390

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 390

Lys Leu Pro Ser Leu Pro Leu Ser Lys

fifteen

<210> 391

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 391

Lys Leu Pro Ser Leu Pro Leu Ser Lys Met

1 5 10

<210> 392

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 392

Lys Met Tyr Thr Thr Ser Met Ala Met

fifteen

<210> 393

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 393

Lys Met Tyr Thr Thr Ser Met Ala Met Pro

1 5 10

<210> 394

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 394

Leu Ala Ala Pro Ser Pro Ala Ser Arg

fifteen

<210> 395

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 395

Leu Ala Ala Pro Ser Pro Ala Ser Arg Leu

1 5 10

<210> 396

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 396

Leu Ala Glu Thr Val Ser Leu His Pro Leu

1 5 10

<210> 397

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 397

Leu Ala Thr Pro Ser Ala Ala Trp

fifteen

<210> 398

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 398

Leu Ala Thr Pro Pro Ser Ala Ala Trp Arg

1 5 10

<210> 399

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 399

Leu Leu Ala Ala Pro Ser Pro Ala Ser Arg

1 5 10

<210> 400

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 400

Leu Leu Leu Ser Ala Asp Gln Gln Ala Ala

1 5 10

<210> 401

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 401

Leu Leu Ser Ala Asp Gln Gln Ala Ala

fifteen

<210> 402

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 402

Leu Pro Ala Ser Asn Lys Leu Pro Ser

fifteen

<210> 403

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 403

Leu Pro Ala Ser Asn Lys Leu Pro Ser Leu

1 5 10

<210> 404

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 404

Leu Pro Leu Pro Gln Leu Leu Leu Ser

fifteen

<210> 405

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 405

Leu Pro Leu Pro Gln Leu Leu Leu Ser Ala

1 5 10

<210> 406

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 406

Leu Pro Ser Leu Pro Leu Ser Lys Met

fifteen

<210> 407

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 407

Leu Pro Ser Leu Pro Leu Ser Lys Met Tyr

1 5 10

<210> 408

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 408

Leu Gln Cys Ile Asn Ser Asn Ser Arg Ile

1 5 10

<210> 409

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 409

Leu Gln Cys Arg Arg Ala Val Ser Ala

fifteen

<210> 410

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 410

Leu Gln Cys Arg Arg Ala Val Ser Ala Thr

1 5 10

<210> 411

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 411

Leu Ser Ala Asp Gln Gln Ala Ala Pro Arg

1 5 10

<210> 412

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 412

Leu Ser Lys Met Tyr Thr Thr Ser Met

fifteen

<210> 413

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 413

Leu Ser Lys Met Tyr Thr Thr Ser Met Ala

1 5 10

<210> 414

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 414

Leu Trp Cys Ala Ser Ser Val Thr Glu Arg

1 5 10

<210> 415

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 415

Leu Trp Tyr Cys Trp Pro Thr Trp Leu

fifteen

<210> 416

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 416

Leu Trp Tyr Cys Trp Pro Thr Trp Leu Arg

1 5 10

<210> 417

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 417

Met Ala His Met Ala Leu Leu Pro Ser

fifteen

<210> 418

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 418

Met Ala Leu Leu Pro Ser Gly Thr Lys

fifteen

<210> 419

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 419

Met Pro Ile Leu Pro Leu Pro Gln Leu

fifteen

<210> 420

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 420

Met Pro Ile Leu Pro Leu Pro Gln Leu Leu

1 5 10

<210> 421

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 421

Met Tyr Ser Pro Ser Arg Tyr Pro Arg

fifteen

<210> 422

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 422

Met Tyr Thr Thr Ser Met Ala Met Pro Ile

1 5 10

<210> 423

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 423

Pro Met Ala Ile Ser Ser Pro Pro Lys

fifteen

<210> 424

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 424

Gln Leu Val Pro Leu Gln Cys Arg Arg

fifteen

<210> 425

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 425

Gln Gln Ala Ala Pro Arg Thr Asn Phe

fifteen

<210> 426

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 426

Gln Gln Ala Ala Pro Arg Thr Asn Phe His

1 5 10

<210> 427

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 427

Gln Trp Met Ala His Met Ala Leu Leu

fifteen

<210> 428

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 428

Arg Ala Val Ser Ala Thr Ser Trp Ala

fifteen

<210> 429

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 429

Arg Ala Val Ser Ala Thr Ser Trp Ala Ser

1 5 10

<210> 430

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 430

Arg Cys Ala Gly Arg Trp Leu Trp Tyr

fifteen

<210> 431

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 431

Arg Cys Thr Ala Cys His Thr Ala Leu

fifteen

<210> 432

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 432

Arg Gly Thr Ala Trp Gln Leu Val Pro Leu

1 5 10

<210> 433

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 433

Arg Leu Gln Cys Ile Asn Ser Asn Ser Arg

1 5 10

<210> 434

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 434

Arg Arg Ala Val Ser Ala Thr Ser Trp

fifteen

<210> 435

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 435

Arg Thr Asn Phe His Ser Ser Leu Ala

fifteen

<210> 436

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 436

Arg Thr Asn Phe His Ser Ser Leu Ala Glu

1 5 10

<210> 437

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 437

Arg Thr Arg Cys Ala Gly Arg Trp Leu

fifteen

<210> 438

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 438

Arg Thr Arg Cys Ala Gly Arg Trp Leu Trp

1 5 10

<210> 439

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 439

Arg Trp Leu Trp Tyr Cys Trp Pro Thr

fifteen

<210> 440

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 440

Arg Trp Leu Trp Tyr Cys Trp Pro Thr Trp

1 5 10

<210> 441

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 441

Ser Ala Ala Trp Arg Ser Cys Ile Ala

fifteen

<210> 442

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 442

Ser Ala Ala Trp Arg Ser Cys Ile Ala Leu

1 5 10

<210> 443

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 443

Ser Gly Gln Trp Met Ala His Met Ala Leu

1 5 10

<210> 444

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 444

Ser Lys Met Tyr Thr Thr Ser Met Ala

fifteen

<210> 445

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 445

Ser Lys Met Tyr Thr Thr Ser Met Ala Met

1 5 10

<210> 446

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 446

Ser Met Ala Met Pro Ile Leu Pro Leu

fifteen

<210> 447

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 447

Ser Asn Lys Leu Pro Ser Leu Pro Leu

fifteen

<210> 448

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 448

Ser Pro Ala Ser Arg Leu Gln Cys Ile

fifteen

<210> 449

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 449

Ser Pro Pro Lys Ala Pro Leu Leu Ala Ala

1 5 10

<210> 450

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 450

Ser Pro Ser Leu Pro Ala Ser Asn Lys Leu

1 5 10

<210> 451

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 451

Ser Arg Ile Thr Ser Gly Gln Trp Met

fifteen

<210> 452

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 452

Ser Ser Cys Pro Gln Pro Ser Pro Ser Leu

1 5 10

<210> 453

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 453

Ser Ser Leu Ala Glu Thr Val Ser Leu

fifteen

<210> 454

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 454

Ser Ser Asn Asp Met Ile Pro Met Ala Ile

1 5 10

<210> 455

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 455

Ser Ser Ser Asn Asp Met Ile Pro Met

fifteen

<210> 456

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 456

Ser Ser Ser Ser Asn Asp Met Ile Pro Met

1 5 10

<210> 457

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 457

Ser Ser Ser Ser Ser Ser Asn Asp Met

fifteen

<210> 458

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 458

Ser Ser Ser Ser Ser Ser Ser Asn Asp Met

1 5 10

<210> 459

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 459

Thr Ala Cys His Thr Ala Leu Gly Arg

fifteen

<210> 460

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 460

Thr Glu Arg Thr Arg Cys Ala Gly Arg Trp

1 5 10

<210> 461

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 461

Thr Ser Met Ala Met Pro Ile Leu Pro Leu

1 5 10

<210> 462

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 462

Thr Thr Ser Met Ala Met Pro Ile Leu

fifteen

<210> 463

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 463

Thr Val Ser Leu His Pro Leu Ala Pro Met

1 5 10

<210> 464

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 464

Thr Trp Leu Arg Gly Thr Ala Trp Gln Leu

1 5 10

<210> 465

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 465

Val Pro Leu Gln Cys Arg Arg Ala Val

fifteen

<210> 466

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 466

Val Ser Leu His Pro Leu Ala Pro Met

fifteen

<210> 467

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 467

Val Thr Glu Arg Thr Arg Cys Ala Gly Arg

1 5 10

<210> 468

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 468

Trp Leu Arg Gly Thr Ala Trp Gln Leu

fifteen

<210> 469

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 469

Trp Leu Arg Gly Thr Ala Trp Gln Leu Val

1 5 10

<210> 470

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 470

Trp Leu Trp Tyr Cys Trp Pro Thr Trp

fifteen

<210> 471

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 471

Trp Leu Trp Tyr Cys Trp Pro Thr Trp Leu

1 5 10

<210> 472

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 472

Trp Met Ala His Met Ala Leu Leu Pro Ser

1 5 10

<210> 473

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 473

Trp Pro Thr Trp Leu Arg Gly Thr Ala

fifteen

<210> 474

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 474

Trp Pro Thr Trp Leu Arg Gly Thr Ala Trp

1 5 10

<210> 475

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 475

Trp Tyr Cys Trp Pro Thr Trp Leu Arg

fifteen

<210> 476

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 476

Tyr Pro Arg Ser Ser Ser Ser Ser Ser

fifteen

<210> 477

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 477

Tyr Pro Arg Ser Ser Ser Ser Ser Ser Ser Ser

1 5 10

<210> 478

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 478

Tyr Thr Thr Ser Met Ala Met Pro Ile

fifteen

<210> 479

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 479

Tyr Thr Thr Ser Met Ala Met Pro Ile Leu

1 5 10

<210> 480

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 480

Ala Leu Ala Val Leu Ala Leu Leu Ser Phe

1 5 10

<210> 481

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 481

Ala Leu Leu Ser Phe Trp Pro Gly Gly Tyr

1 5 10

<210> 482

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 482

Asp Ser Gly Leu Leu Thr Ser Ser Ser Arg

1 5 10

<210> 483

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 483

Glu Leu Leu Cys Val Trp Val Ser Ser Ile

1 5 10

<210> 484

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 484

Glu Trp Lys Val Lys Phe Pro Glu Leu

fifteen

<210> 485

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 485

Phe Pro Glu Leu Leu Cys Val Trp Val

fifteen

<210> 486

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 486

Phe Trp Pro Gly Gly Tyr Pro Ala Tyr

fifteen

<210> 487

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 487

Gly Leu Leu Thr Ser Ser Ser Arg Glu Trp

1 5 10

<210> 488

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 488

Lys Phe Pro Glu Leu Leu Cys Val Trp

fifteen

<210> 489

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 489

Lys Phe Pro Glu Leu Leu Cys Val Trp Val

1 5 10

<210> 490

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 490

Lys Val Lys Phe Pro Glu Leu Leu Cys

fifteen

<210> 491

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 491

Lys Val Lys Phe Pro Glu Leu Leu Cys Val

1 5 10

<210> 492

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 492

Leu Ala Val Leu Ala Leu Leu Ser Phe

fifteen

<210> 493

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 493

Leu Ala Val Leu Ala Leu Leu Ser Phe Trp

1 5 10

<210> 494

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 494

Leu Leu Cys Val Trp Val Ser Ser Ile Arg

1 5 10

<210> 495

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 495

Leu Leu Ser Phe Trp Pro Gly Gly Tyr

fifteen

<210> 496

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 496

Leu Leu Thr Ser Ser Ser Arg Glu Trp

fifteen

<210> 497

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 497

Leu Leu Thr Ser Ser Ser Arg Glu Trp Lys

1 5 10

<210> 498

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 498

Leu Ser Phe Trp Pro Gly Gly Tyr Pro Ala

1 5 10

<210> 499

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 499

Leu Thr Ser Ser Ser Arg Glu Trp Lys

fifteen

<210> 500

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 500

Leu Thr Ser Ser Ser Arg Glu Trp Lys Val

1 5 10

<210> 501

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 501

Arg Glu Trp Lys Val Lys Phe Pro Glu

fifteen

<210> 502

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 502

Arg Glu Trp Lys Val Lys Phe Pro Glu Leu

1 5 10

<210> 503

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 503

Ser Phe Trp Pro Gly Gly Tyr Pro Ala

fifteen

<210> 504

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 504

Ser Phe Trp Pro Gly Gly Tyr Pro Ala Tyr

1 5 10

<210> 505

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 505

Ser Ser Arg Glu Trp Lys Val Lys Phe

fifteen

<210> 506

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 506

Ser Ser Ser Arg Glu Trp Lys Val Lys

fifteen

<210> 507

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 507

Ser Ser Ser Arg Glu Trp Lys Val Lys Phe

1 5 10

<210> 508

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 508

Thr Ser Ser Ser Arg Glu Trp Lys Val

fifteen

<210> 509

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 509

Thr Ser Ser Ser Arg Glu Trp Lys Val Lys

1 5 10

<210> 510

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 510

Val Lys Phe Pro Glu Leu Leu Cys Val

fifteen

<210> 511

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 511

Val Lys Phe Pro Glu Leu Leu Cys Val Trp

1 5 10

<210> 512

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 512

Trp Lys Val Lys Phe Pro Glu Leu Leu

fifteen

<210> 513

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 513

Tyr Pro Ala Tyr Ser Lys Asp Ser Gly Leu

1 5 10

<210> 514

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 514

Ala Ala Leu Ser Arg His Asn Val Leu

fifteen

<210> 515

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 515

Ala Asp Ala Pro Ala Ile Gln Pro Val

fifteen

<210> 516

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 516

Ala Asp Ala Pro Ala Ile Gln Pro Val Leu

1 5 10

<210> 517

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 517

Ala Glu Ser Lys Ile Met Phe Ala Thr

fifteen

<210> 518

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 518

Ala Glu Ser Lys Ile Met Phe Ala Thr Leu

1 5 10

<210> 519

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 519

Ala Ile Gln Pro Val Leu Trp Thr Thr

fifteen

<210> 520

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 520

Ala Leu Gln Pro Leu Gln Pro His Ala

fifteen

<210> 521

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 521

Ala Pro Ala Ile Gln Pro Val Leu Trp

fifteen

<210> 522

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 522

Ala Arg Val Pro Ala Val Pro Phe Asp Leu

1 5 10

<210> 523

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 523

Ala Thr Leu Gln Arg Ser Ser Leu Trp

fifteen

<210> 524

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 524

Ala Val Pro Phe Asp Leu His Phe Cys Arg

1 5 10

<210> 525

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 525

Cys Ser Met Leu Thr Gly Pro Pro Ala

fifteen

<210> 526

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 526

Cys Ser Met Leu Thr Gly Pro Pro Ala Arg

1 5 10

<210> 527

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 527

Asp Leu His Phe Cys Arg Ser Ser Ile

fifteen

<210> 528

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 528

Asp Leu His Phe Cys Arg Ser Ser Ile Met

1 5 10

<210> 529

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 529

Glu Pro His Leu Ala Leu Gln Pro Leu

fifteen

<210> 530

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 530

Glu Ser Lys Ile Met Phe Ala Thr Leu

fifteen

<210> 531

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 531

Phe Ala Thr Leu Gln Arg Ser Ser Leu

fifteen

<210> 532

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 532

Phe Ala Thr Leu Gln Arg Ser Ser Leu Trp

1 5 10

<210> 533

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 533

Phe Cys Arg Ser Ser Ile Met Lys Pro Lys

1 5 10

<210> 534

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 534

Phe Asp Leu His Phe Cys Arg Ser Ser Ile

1 5 10

<210> 535

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 535

Phe Leu Lys Ala Glu Ser Lys Ile Met

fifteen

<210> 536

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 536

Phe Leu Lys Ala Glu Ser Lys Ile Met Phe

1 5 10

<210> 537

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 537

Gly Pro Pro Ala Arg Val Pro Ala Val

fifteen

<210> 538

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 538

Gly Tyr Met Phe Leu Lys Ala Glu Ser Lys

1 5 10

<210> 539

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 539

His Ala Asp Ala Pro Ala Ile Gln Pro Val

1 5 10

<210> 540

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 540

His Ala His Ala Asp Ala Pro Ala Ile

fifteen

<210> 541

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 541

His Phe Cys Arg Ser Ser Ile Met Lys

fifteen

<210> 542

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 542

His Leu Ala Leu Gln Pro Leu Gln Pro His

1 5 10

<210> 543

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 543

His Met Ser Ser Leu Ser His Ile Ser Ala

1 5 10

<210> 544

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 544

His Pro Leu Gln His Gly His Arg His

fifteen

<210> 545

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 545

His Pro Pro Ser Ser Leu Ser Phe Trp

fifteen

<210> 546

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 546

His Arg His Gly Leu Glu Pro Cys Ser Met

1 5 10

<210> 547

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 547

Ile Met Phe Ala Thr Leu Gln Arg Ser

fifteen

<210> 548

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 548

Ile Met Phe Ala Thr Leu Gln Arg Ser Ser

1 5 10

<210> 549

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 549

Ile Met Lys Pro Lys Arg Asp Gly Tyr

fifteen

<210> 550

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 550

Ile Met Lys Pro Lys Arg Asp Gly Tyr Met

1 5 10

<210> 551

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 551

Lys Ala Glu Ser Lys Ile Met Phe Ala

fifteen

<210> 552

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 552

Lys Ile Met Phe Ala Thr Leu Gln Arg

fifteen

<210> 553

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 553

Lys Pro Lys Arg Asp Gly Tyr Met Phe

fifteen

<210> 554

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 554

Lys Pro Lys Arg Asp Gly Tyr Met Phe Leu

1 5 10

<210> 555

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 555

Leu Ala Leu Gln Pro Leu Gln Pro His

fifteen

<210> 556

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 556

Leu His Phe Cys Arg Ser Ser Ile Met

fifteen

<210> 557

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 557

Leu His Phe Cys Arg Ser Ser Ile Met Lys

1 5 10

<210> 558

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 558

Leu Lys Ala Glu Ser Lys Ile Met Phe

fifteen

<210> 559

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 559

Leu Gln His Gly His Arg His Gly Leu

fifteen

<210> 560

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 560

Leu Gln Pro His Ala Asp His Ala His

fifteen

<210> 561

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 561

Leu Gln Arg Ser Ser Leu Trp Cys Leu

fifteen

<210> 562

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 562

Leu Gln Arg Ser Ser Leu Trp Cys Leu Cys

1 5 10

<210> 563

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 563

Leu Ser Phe Gly Pro His His Pro Leu

fifteen

<210> 564

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 564

Leu Ser Phe Gly Pro His Pro Pro Leu

fifteen

<210> 565

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 565

Leu Ser Phe Trp Thr Thr Pro Pro Leu

fifteen

<210> 566

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 566

Leu Ser His Ile Ser Ala Leu Gln Pro Leu

1 5 10

<210> 567

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 567

Met Phe Ala Thr Leu Gln Arg Ser Ser Leu

1 5 10

<210> 568

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 568

Met Phe Leu Lys Ala Glu Ser Lys Ile

fifteen

<210> 569

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 569

Met Phe Leu Lys Ala Glu Ser Lys Ile Met

1 5 10

<210> 570

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 570

Met His Pro Pro Ser Ser Leu Ser Phe Trp

1 5 10

<210> 571

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 571

Met Lys Pro Lys Arg Asp Gly Tyr Met Phe

1 5 10

<210> 572

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 572

Met Leu Thr Gly Pro Pro Ala Arg Val

fifteen

<210> 573

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 573

Met Ser Ser Leu Ser His Ile Ser Ala

fifteen

<210> 574

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 574

Met Ser Ser Leu Ser His Ile Ser Ala Leu

1 5 10

<210> 575

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 575

Asn Pro Ala Ala Leu Ser Arg His Asn Val

1 5 10

<210> 576

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 576

Pro Ala Arg Val Pro Ala Val Pro Phe

fifteen

<210> 577

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 577

Pro Ala Val Pro Phe Asp Leu His Phe

fifteen

<210> 578

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 578

Pro Glu Pro His Leu Ala Leu Gln Pro Leu

1 5 10

<210> 579

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 579

Pro Pro Ala Arg Val Pro Ala Val Pro Phe

1 5 10

<210> 580

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 580

Gln Pro Val Leu Trp Thr Thr Pro Pro Leu

1 5 10

<210> 581

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 581

Arg His Gly Leu Glu Pro Cys Ser Met

fifteen

<210> 582

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 582

Arg His Asn Val Leu Pro Glu Pro His Leu

1 5 10

<210> 583

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 583

Arg Ser Ser Ile Met Lys Pro Lys Arg

fifteen

<210> 584

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 584

Ser Ala Leu Gln Pro Leu Gln Pro His

fifteen

<210> 585

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 585

Ser His Ile Ser Ala Leu Gln Pro Leu

fifteen

<210> 586

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 586

Ser Ile Met Lys Pro Lys Arg Asp Gly Tyr

1 5 10

<210> 587

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 587

Ser Leu Ser Phe Gly Pro His His Pro Leu

1 5 10

<210> 588

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 588

Ser Leu Ser Phe Gly Pro His Pro Pro Leu

1 5 10

<210> 589

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 589

Ser Leu Ser Phe Trp Thr Thr Pro Pro Leu

1 5 10

<210> 590

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 590

Ser Met Leu Thr Gly Pro Pro Ala Arg

fifteen

<210> 591

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 591

Ser Ser Leu Ser His Ile Ser Ala Leu

fifteen

<210> 592

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 592

Thr Leu Gln Arg Ser Ser Leu Trp Cys Leu

1 5 10

<210> 593

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 593

Thr Thr Pro Pro Leu Gln His Gly His Arg

1 5 10

<210> 594

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 594

Val Leu Pro Glu Pro His Leu Ala Leu

fifteen

<210> 595

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 595

Val Pro Ala Val Pro Phe Asp Leu His Phe

1 5 10

<210> 596

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 596

Val Pro Phe Asp Leu His Phe Cys Arg

fifteen

<210> 597

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 597

Tyr Met Phe Leu Lys Ala Glu Ser Lys

fifteen

<210> 598

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 598

Tyr Met Phe Leu Lys Ala Glu Ser Lys Ile

1 5 10

<210> 599

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 599

Ala Pro Gly Pro Arg Gly Arg Thr Cys

fifteen

<210> 600

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 600

Cys His Tyr Leu Arg Ser Arg Asn Ser Ala

1 5 10

<210> 601

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 601

Cys Leu Arg Ser His Thr Cys Pro Pro Arg

1 5 10

<210> 602

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 602

Cys Leu Trp Cys His Ala Cys Leu His Arg

1 5 10

<210> 603

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 603

Cys Pro His Leu Gly Ser His Pro Cys

fifteen

<210> 604

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 604

Cys Pro His Arg Leu Arg Ser Leu Pro Arg

1 5 10

<210> 605

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 605

Cys Pro Leu Gly Leu Lys Ser Pro Leu

fifteen

<210> 606

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 606

Cys Pro Pro Gly Leu Arg Asn Arg Ile

fifteen

<210> 607

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 607

Cys Pro Pro Gly Leu Arg Ser His Thr Tyr

1 5 10

<210> 608

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 608

Cys Pro Pro Arg Leu Arg Asp His Ile

fifteen

<210> 609

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 609

Cys Pro Pro Ser Leu Arg Ser His Ala Tyr

1 5 10

<210> 610

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 610

Cys Pro Arg Ser Cys Arg Cys Pro His

fifteen

<210> 611

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 611

Cys Pro Arg Ser Cys Arg Cys Pro His Leu

1 5 10

<210> 612

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 612

Cys Ser Leu Pro Leu Gly Asn His Pro Tyr

1 5 10

<210> 613

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 613

Cys Thr Cys Pro Pro Arg Leu Arg Ser Arg

1 5 10

<210> 614

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 614

Asp His Ile Cys Pro Leu Ser Leu Arg

fifteen

<210> 615

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 615

Glu Glu Ser Pro Met Ser Pro His Leu

fifteen

<210> 616

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 616

Glu Ser Pro Met Ser Pro His Leu Arg

fifteen

<210> 617

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 617

Glu Ser Pro Met Ser Pro His Leu Arg Tyr

1 5 10

<210> 618

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 618

Glu Val Ser Arg Leu Ser Pro Cys Leu

fifteen

<210> 619

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 619

Gly Leu Lys Ser Pro Leu Arg Ser Gln Ala

1 5 10

<210> 620

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 620

Gly Leu Arg Asn Arg Ile Cys Pro Leu

fifteen

<210> 621

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 621

Gly Leu Arg Asn Arg Ile Cys Pro Leu Ser

1 5 10

<210> 622

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 622

Gly Leu Arg Ser His Thr Tyr Leu Arg

fifteen

<210> 623

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 623

Gly Leu Arg Ser His Thr Tyr Leu Arg Arg

1 5 10

<210> 624

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 624

Gly Leu Arg Ser Arg Thr Cys Pro Pro Gly

1 5 10

<210> 625

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 625

His Ala Cys Pro Pro Gly Leu Arg Asn Arg

1 5 10

<210> 626

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 626

His Ala Tyr Ala Leu Cys Leu Arg Ser His

1 5 10

<210> 627

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 627

His His Leu Arg Thr His Leu Leu Pro His

1 5 10

<210> 628

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 628

His Leu Gly Ser His Pro Cys Arg Leu

fifteen

<210> 629

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 629

His Leu Leu Pro His His Arg Arg Thr Arg

1 5 10

<210> 630

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 630

His Leu Arg Leu His Ala Ser Pro His

fifteen

<210> 631

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 631

His Leu Arg Leu His Ala Ser Pro His His

1 5 10

<210> 632

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 632

His Leu Arg Ser Cys Pro Cys Ser Leu

fifteen

<210> 633

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 633

His Leu Arg Thr His Leu Leu Pro His

fifteen

<210> 634

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 634

His Leu Arg Thr His Leu Leu Pro His His

1 5 10

<210> 635

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 635

His Leu Arg Thr Pro Pro His Pro His

fifteen

<210> 636

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 636

His Leu Arg Thr Pro Pro His Pro His His

1 5 10

<210> 637

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 637

His Leu Arg Tyr Arg Ala Tyr Pro Pro

fifteen

<210> 638

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 638

His Leu Arg Tyr Arg Ala Tyr Pro Pro Cys

1 5 10

<210> 639

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 639

His Pro Cys Cys His Tyr Leu Arg Ser Arg

1 5 10

<210> 640

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 640

His Pro His His Leu Arg Thr His Leu

fifteen

<210> 641

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 641

His Pro His His Leu Arg Thr His Leu Leu

1 5 10

<210> 642

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 642

His Arg Leu Arg Ser Leu Pro Arg Pro Leu

1 5 10

<210> 643

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 643

His Thr Tyr Leu Arg Arg Leu Arg Ser

fifteen

<210> 644

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 644

His Thr Tyr Leu Arg Arg Leu Arg Ser His

1 5 10

<210> 645

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 645

His Tyr Leu Arg Ser Arg Asn Ser Ala

fifteen

<210> 646

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 646

Lys Ser Pro Leu Arg Ser Gln Ala Asn Ala

1 5 10

<210> 647

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 647

Leu Glu Ser Gln Pro Cys Leu Ser Leu

fifteen

<210> 648

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 648

Leu His Leu Arg Leu His Ala Ser Pro His

1 5 10

<210> 649

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 649

Leu His Leu Arg Ser Cys Pro Cys Ser Leu

1 5 10

<210> 650

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 650

Leu Leu Pro His His Arg Arg Thr Arg

fifteen

<210> 651

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 651

Leu Pro Cys Pro His Arg Leu Arg Ser Leu

1 5 10

<210> 652

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 652

Leu Pro His His Arg Arg Thr Arg Ser

fifteen

<210> 653

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 653

Leu Pro His His Arg Arg Thr Arg Ser Cys

1 5 10

<210> 654

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 654

Leu Pro Leu Gly Asn His Pro Tyr Leu

fifteen

<210> 655

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 655

Leu Pro Arg Pro Leu His Leu Arg Leu

fifteen

<210> 656

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 656

Leu Arg Leu His Ala Ser Pro His His Leu

1 5 10

<210> 657

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 657

Leu Arg Asn Cys Thr Cys Pro Pro Arg Leu

1 5 10

<210> 658

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 658

Leu Arg Asn His Thr Cys Pro Pro Ser Leu

1 5 10

<210> 659

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 659

Leu Arg Asn Arg Ile Cys Pro Leu Ser Leu

1 5 10

<210> 660

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 660

Leu Arg Ser Cys Pro Cys Ser Leu Pro Leu

1 5 10

<210> 661

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 661

Leu Arg Ser His Ala Cys Pro Pro Gly Leu

1 5 10

<210> 662

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 662

Leu Arg Ser His Ala Cys Pro Pro Asn Leu

1 5 10

<210> 663

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 663

Leu Arg Ser His Ala Tyr Ala Leu Cys Leu

1 5 10

<210> 664

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 664

Leu Arg Ser His Thr Cys Pro Pro Arg Leu

1 5 10

<210> 665

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 665

Leu Arg Ser His Thr Cys Pro Pro Ser Leu

1 5 10

<210> 666

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 666

Leu Arg Ser His Thr Tyr Leu Arg Arg Leu

1 5 10

<210> 667

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 667

Leu Arg Ser Leu Pro Arg Pro Leu His Leu

1 5 10

<210> 668

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 668

Leu Arg Ser Gln Ala Asn Ala Leu His Leu

1 5 10

<210> 669

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 669

Leu Arg Thr Pro Pro His Pro His His Leu

1 5 10

<210> 670

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 670

Leu Arg Tyr Arg Ala Tyr Pro Pro Cys Leu

1 5 10

<210> 671

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 671

Leu Ser Leu Gly Asn His Leu Cys Pro Leu

1 5 10

<210> 672

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 672

Leu Ser Leu Arg Ser His Pro Cys Pro Leu

1 5 10

<210> 673

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 673

Leu Trp Cys His Ala Cys Leu His Arg Leu

1 5 10

<210> 674

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 674

Met Ser Pro His Leu Arg Tyr Arg Ala

fifteen

<210> 675

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 675

Met Ser Pro His Leu Arg Tyr Arg Ala Tyr

1 5 10

<210> 676

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 676

Asn Leu Pro Cys Pro His Arg Leu Arg

fifteen

<210> 677

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 677

Asn Leu Arg Asn His Thr Cys Pro Pro

fifteen

<210> 678

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 678

Pro Met Ser Pro His Leu Arg Tyr Arg

fifteen

<210> 679

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 679

Pro Pro Arg Leu Arg Ser Arg Thr Cys Leu

1 5 10

<210> 680

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 680

Pro Pro Ser Leu Arg Ser His Ala Tyr

fifteen

<210> 681

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 681

Arg Ala Tyr Pro Pro Cys Leu Trp Cys His

1 5 10

<210> 682

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 682

Arg Asp His Ile Cys Pro Leu Ser Leu

fifteen

<210> 683

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 683

Arg Gly Arg Thr Cys His Pro Gly Leu

fifteen

<210> 684

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 684

Arg Gly Arg Thr Cys His Pro Gly Leu Arg

1 5 10

<210> 685

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 685

Arg Leu His Ala Ser Pro His His Leu

fifteen

<210> 686

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 686

Arg Leu His Ala Ser Pro His His Leu Arg

1 5 10

<210> 687

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 687

Arg Leu Arg Asp His Ile Cys Pro Leu

fifteen

<210> 688

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 688

Arg Leu Arg Asp His Ile Cys Pro Leu Ser

1 5 10

<210> 689

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 689

Arg Leu Arg Asn Leu Pro Cys Pro His

fifteen

<210> 690

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 690

Arg Leu Arg Asn Leu Pro Cys Pro His Arg

1 5 10

<210> 691

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 691

Arg Leu Arg Ser His Thr Cys Pro Pro

fifteen

<210> 692

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 692

Arg Leu Arg Ser His Thr Cys Pro Pro Ser

1 5 10

<210> 693

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 693

Arg Leu Arg Ser Leu Pro Arg Pro Leu

fifteen

<210> 694

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 694

Arg Leu Arg Ser Leu Pro Arg Pro Leu His

1 5 10

<210> 695

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 695

Arg Leu Arg Ser Arg Thr Cys Leu Leu

fifteen

<210> 696

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 696

Arg Leu Arg Ser Arg Thr Cys Leu Leu Cys

1 5 10

<210> 697

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 697

Arg Leu Ser Pro Cys Leu Trp Cys His Ala

1 5 10

<210> 698

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 698

Arg Asn His Thr Cys Pro Pro Ser Leu

fifteen

<210> 699

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 699

Arg Asn His Thr Cys Pro Pro Ser Leu Arg

1 5 10

<210> 700

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 700

Arg Asn Leu Pro Cys Pro His Arg Leu Arg

1 5 10

<210> 701

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 701

Arg Asn Arg Ile Cys Pro Leu Ser Leu

fifteen

<210> 702

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 702

Arg Asn Arg Ile Cys Pro Leu Ser Leu Arg

1 5 10

<210> 703

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 703

Arg Pro Leu His Leu Arg Leu His Ala

fifteen

<210> 704

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 704

Arg Pro Leu His Leu Arg Leu His Ala Ser

1 5 10

<210> 705

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 705

Arg Ser Cys Pro Cys Arg Trp Arg Ser His

1 5 10

<210> 706

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 706

Arg Ser Cys Pro Cys Ser Leu Pro Leu

fifteen

<210> 707

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 707

Arg Ser His Ala Cys Pro Pro Gly Leu

fifteen

<210> 708

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 708

Arg Ser His Ala Cys Pro Pro Gly Leu Arg

1 5 10

<210> 709

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 709

Arg Ser His Ala Cys Pro Pro Asn Leu

fifteen

<210> 710

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 710

Arg Ser His Ala Cys Pro Pro Asn Leu Arg

1 5 10

<210> 711

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 711

Arg Ser His Ala Tyr Ala Leu Cys Leu

fifteen

<210> 712

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 712

Arg Ser His Ala Tyr Ala Leu Cys Leu Arg

1 5 10

<210> 713

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 713

Arg Ser His Pro Cys Cys His Tyr Leu

fifteen

<210> 714

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 714

Arg Ser His Pro Cys Cys His Tyr Leu Arg

1 5 10

<210> 715

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 715

Arg Ser His Pro Cys Pro Leu Gly Leu

fifteen

<210> 716

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 716

Arg Ser His Pro Cys Pro Leu Gly Leu Lys

1 5 10

<210> 717

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 717

Arg Ser His Thr Cys Pro Pro Arg Leu

fifteen

<210> 718

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 718

Arg Ser His Thr Cys Pro Pro Arg Leu Arg

1 5 10

<210> 719

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 719

Arg Ser His Thr Cys Pro Pro Ser Leu

fifteen

<210> 720

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 720

Arg Ser His Thr Cys Pro Pro Ser Leu Arg

1 5 10

<210> 721

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 721

Arg Ser His Thr Tyr Leu Arg Arg Leu

fifteen

<210> 722

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 722

Arg Ser His Thr Tyr Leu Arg Arg Leu Arg

1 5 10

<210> 723

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 723

Arg Ser Leu Pro Arg Pro Leu His Leu

fifteen

<210> 724

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 724

Arg Ser Leu Pro Arg Pro Leu His Leu Arg

1 5 10

<210> 725

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 725

Arg Ser Gln Ala Asn Ala Leu His Leu

fifteen

<210> 726

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 726

Arg Ser Gln Ala Asn Ala Leu His Leu Arg

1 5 10

<210> 727

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 727

Arg Ser Arg Asn Ser Ala Pro Gly Pro

fifteen

<210> 728

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 728

Arg Ser Arg Asn Ser Ala Pro Gly Pro Arg

1 5 10

<210> 729

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 729

Arg Ser Arg Thr Cys Leu Leu Cys Leu

fifteen

<210> 730

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 730

Arg Ser Arg Thr Cys Leu Leu Cys Leu Arg

1 5 10

<210> 731

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 731

Arg Ser Arg Thr Cys Pro Pro Gly Leu

fifteen

<210> 732

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 732

Arg Ser Arg Thr Cys Pro Pro Gly Leu Arg

1 5 10

<210> 733

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 733

Arg Thr Cys His Pro Gly Leu Arg Ser Arg

1 5 10

<210> 734

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 734

Arg Thr His Leu Leu Pro His His Arg

fifteen

<210> 735

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 735

Arg Thr His Leu Leu Pro His His Arg Arg

1 5 10

<210> 736

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 736

Arg Thr Pro Pro His Pro His His Leu

fifteen

<210> 737

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 737

Arg Thr Pro Pro His Pro His His Leu Arg

1 5 10

<210> 738

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 738

Arg Thr Arg Ser Cys Pro Cys Arg Trp

fifteen

<210> 739

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 739

Arg Thr Arg Ser Cys Pro Cys Arg Trp Arg

1 5 10

<210> 740

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 740

Arg Trp Arg Ser His Pro Cys Cys His

fifteen

<210> 741

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 741

Arg Trp Arg Ser His Pro Cys Cys His Tyr

1 5 10

<210> 742

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 742

Arg Tyr Arg Ala Tyr Pro Pro Cys Leu

fifteen

<210> 743

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 743

Arg Tyr Arg Ala Tyr Pro Pro Cys Leu Trp

1 5 10

<210> 744

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 744

Ser His Ala Tyr Ala Leu Cys Leu Arg

fifteen

<210> 745

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 745

Ser Leu Gly Asn His Leu Cys Pro Leu

fifteen

<210> 746

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 746

Ser Leu Pro Leu Gly Asn His Pro Tyr

fifteen

<210> 747

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 747

Ser Leu Pro Leu Gly Asn His Pro Tyr Leu

1 5 10

<210> 748

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 748

Ser Leu Pro Arg Pro Leu His Leu Arg

fifteen

<210> 749

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 749

Ser Leu Pro Arg Pro Leu His Leu Arg Leu

1 5 10

<210> 750

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 750

Ser Leu Arg Asn Cys Thr Cys Pro Pro Arg

1 5 10

<210> 751

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 751

Ser Leu Arg Ser His Ala Cys Pro Pro Gly

1 5 10

<210> 752

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 752

Ser Leu Arg Ser His Ala Tyr Ala Leu

fifteen

<210> 753

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 753

Ser Leu Arg Ser His Ala Tyr Ala Leu Cys

1 5 10

<210> 754

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 754

Ser Leu Arg Ser His Pro Cys Pro Leu

fifteen

<210> 755

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 755

Ser Leu Arg Ser His Pro Cys Pro Leu Gly

1 5 10

<210> 756

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 756

Ser Pro His His Leu Arg Thr Pro Pro

fifteen

<210> 757

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 757

Ser Pro His His Leu Arg Thr Pro Pro His

1 5 10

<210> 758

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 758

Ser Pro His Leu Arg Tyr Arg Ala Tyr

fifteen

<210> 759

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 759

Ser Pro Leu Arg Ser Gln Ala Asn Ala Leu

1 5 10

<210> 760

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 760

Ser Pro Met Ser Pro His Leu Arg Tyr

fifteen

<210> 761

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 761

Ser Pro Met Ser Pro His Leu Arg Tyr Arg

1 5 10

<210> 762

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 762

Ser Gln Ala Asn Ala Leu His Leu Arg

fifteen

<210> 763

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 763

Ser Gln Ala Asn Ala Leu His Leu Arg Ser

1 5 10

<210> 764

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 764

Val Ser Arg Leu Ser Pro Cys Leu Trp

fifteen

<210> 765

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 765

Trp Arg Ser His Pro Cys Cys His Tyr

fifteen

<210> 766

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 766

Trp Arg Ser His Pro Cys Cys His Tyr Leu

1 5 10

<210> 767

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 767

Tyr Leu Pro Cys Leu Glu Ser Gln Pro Cys

1 5 10

<210> 768

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 768

Tyr Leu Arg Arg Leu Arg Ser His Thr Cys

1 5 10

<210> 769

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 769

Tyr Leu Arg Ser Arg Asn Ser Ala Pro

fifteen

<210> 770

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 770

Tyr Leu Arg Ser Arg Asn Ser Ala Pro Gly

1 5 10

<210> 771

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 771

Lys Met Leu Lys Arg Thr Lys Cys Phe

fifteen

<210> 772

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 772

Met Leu Lys Arg Thr Lys Cys Phe Thr

fifteen

<210> 773

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 773

Leu Lys Arg Thr Lys Cys Phe Thr Phe

fifteen

<210> 774

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 774

Met Leu Lys Arg Thr Lys Cys Phe Thr Phe

1 5 10

<210> 775

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 775

Lys Gln Asn Lys Met Leu Lys Arg Thr Lys

1 5 10

<210> 776

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 776

Lys Met Leu Lys Arg Thr Lys Cys Phe Thr

1 5 10

<210> 777

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 777

Asn Lys Met Leu Lys Arg Thr Lys Cys Phe

1 5 10

<210> 778

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 778

Ala Pro Ala Ser Ala Pro Trp Pro Ser Thr

1 5 10

<210> 779

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 779

Ala Pro Pro Trp Pro Leu His Gln Gln Leu

1 5 10

<210> 780

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 780

Ala Pro Trp Pro Ser Thr Ser Ser His

fifteen

<210> 781

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 781

Ala Ser Cys Ile Leu Gly Gln Pro Ser Leu

1 5 10

<210> 782

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 782

Ala Thr Val Ser Val Trp Ala Ser Cys Ile

1 5 10

<210> 783

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 783

Cys Gln Arg Leu Leu Pro Pro Trp Pro Leu

1 5 10

<210> 784

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 784

His Gln Pro Pro Pro Gly Pro Cys His Leu

1 5 10

<210> 785

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 785

His Gln Gln Leu Leu His Arg Arg Pro Leu

1 5 10

<210> 786

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 786

Ile Glu Gln Trp Phe Thr Glu Asp Gln Val

1 5 10

<210> 787

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 787

Lys Leu Pro Glu Cys Gln Arg Leu Leu

fifteen

<210> 788

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 788

Lys Pro Thr Arg Ala Ala Thr Val Ser Val

1 5 10

<210> 789

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 789

Lys Thr Tyr Gln Gly Ser Tyr Gly Phe Val

1 5 10

<210> 790

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 790

Lys Thr Tyr Gln Gly Ser Tyr Val Ser

fifteen

<210> 791

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 791

Lys Thr Tyr Gln Gly Ser Tyr Val Ser Val

1 5 10

<210> 792

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 792

Leu Leu Ser Leu Pro Arg Lys Pro Thr Arg

1 5 10

<210> 793

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 793

Leu Pro Pro Trp Pro Leu His Gln Gln Leu

1 5 10

<210> 794

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 794

Leu Pro Arg Lys Pro Thr Arg Ala Ala

fifteen

<210> 795

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 795

Leu Pro Arg Lys Pro Thr Arg Ala Ala Thr

1 5 10

<210> 796

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 796

Leu Ser Leu Pro Arg Lys Pro Thr Arg

fifteen

<210> 797

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 797

Met Lys Leu Pro Glu Cys Gln Arg Leu

fifteen

<210> 798

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 798

Met Lys Leu Pro Glu Cys Gln Arg Leu Leu

1 5 10

<210> 799

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 799

Met Pro Glu Ala Ala Pro Pro Trp Pro Leu

1 5 10

<210> 800

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 800

Pro Glu Ala Ala Pro Pro Trp Pro Leu

fifteen

<210> 801

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 801

Pro Thr Arg Ala Ala Thr Val Ser Val

fifteen

<210> 802

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 802

Gln Met Lys Leu Pro Glu Cys Gln Arg

fifteen

<210> 803

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 803

Gln Gln Leu Leu His Arg Arg Pro Leu

fifteen

<210> 804

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 804

Gln Gln Leu Leu His Arg Arg Pro Leu His

1 5 10

<210> 805

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 805

Gln Arg Leu Leu Pro Pro Trp Pro Leu

fifteen

<210> 806

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 806

Gln Trp Phe Thr Glu Asp Gln Val Gln Met

1 5 10

<210> 807

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 807

Arg Ala Ala Thr Val Ser Val Trp Ala

fifteen

<210> 808

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 808

Arg Leu Leu Pro Pro Trp Pro Leu His

fifteen

<210> 809

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 809

Arg Met Pro Glu Ala Ala Pro Pro Trp

fifteen

<210> 810

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 810

Arg Pro Ala Pro Ala Ser Ala Pro Trp

fifteen

<210> 811

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 811

Ser Leu Pro Arg Lys Pro Thr Arg Ala

fifteen

<210> 812

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 812

Ser Leu Pro Arg Lys Pro Thr Arg Ala Ala

1 5 10

<210> 813

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 813

Ser Gln Lys Thr Tyr Gln Gly Ser Tyr Val

1 5 10

<210> 814

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 814

Ser Thr Pro Arg Pro Ala Pro Ala Ser Ala

1 5 10

<210> 815

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 815

Ser Tyr Gly Phe Val Trp Ala Ser Cys

fifteen

<210> 816

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 816

Ser Tyr Gly Phe Val Trp Ala Ser Cys Ile

1 5 10

<210> 817

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 817

Ser Tyr Val Ser Val Trp Ala Ser Cys

fifteen

<210> 818

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 818

Ser Tyr Val Ser Val Trp Ala Ser Cys Ile

1 5 10

<210> 819

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 819

Thr Glu Asp Gln Val Gln Met Lys Leu

fifteen

<210> 820

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 820

Thr Pro Arg Pro Ala Pro Ala Ser Ala

fifteen

<210> 821

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 821

Thr Pro Arg Pro Ala Pro Ala Ser Ala Pro

1 5 10

<210> 822

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 822

Thr Arg Ala Ala Thr Val Ser Val Trp

fifteen

<210> 823

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 823

Thr Val Ser Val Trp Ala Ser Cys Ile

fifteen

<210> 824

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 824

Thr Val Ser Val Trp Ala Ser Cys Ile Leu

1 5 10

<210> 825

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 825

Thr Tyr Gln Gly Ser Tyr Gly Phe Val

fifteen

<210> 826

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 826

Thr Tyr Gln Gly Ser Tyr Gly Phe Val Trp

1 5 10

<210> 827

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 827

Thr Tyr Gln Gly Ser Tyr Val Ser Val

fifteen

<210> 828

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 828

Thr Tyr Gln Gly Ser Tyr Val Ser Val Trp

1 5 10

<210> 829

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 829

Val Ser Val Trp Ala Ser Cys Ile Leu

fifteen

<210> 830

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 830

Trp Pro Leu His Gln Gln Leu Leu His

fifteen

<210> 831

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 831

Trp Pro Ser Thr Ser Ser His Ser Thr

fifteen

<210> 832

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 832

Tyr Gly Phe Val Trp Ala Ser Cys Ile

fifteen

<210> 833

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 833

Tyr Gly Phe Val Trp Ala Ser Cys Ile Leu

1 5 10

<210> 834

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 834

Tyr Gln Gly Ser Tyr Gly Phe Val Trp

fifteen

<210> 835

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 835

Tyr Gln Gly Ser Tyr Gly Phe Val Trp Ala

1 5 10

<210> 836

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 836

Tyr Gln Gly Ser Tyr Val Ser Val Trp

fifteen

<210> 837

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 837

Tyr Gln Gly Ser Tyr Val Ser Val Trp Ala

1 5 10

<210> 838

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 838

Tyr Val Ser Val Trp Ala Ser Cys Ile

fifteen

<210> 839

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 839

Tyr Val Ser Val Trp Ala Ser Cys Ile Leu

1 5 10

<210> 840

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 840

Cys His Leu Ser Met Leu Thr Asp Ser Leu

1 5 10

<210> 841

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 841

Glu Met Glyn Gly His Thr Met Gly Phe

fifteen

<210> 842

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 842

Phe Leu Pro Ile Ser His Cys Gln Cys

fifteen

<210> 843

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 843

Phe Leu Pro Ile Ser His Cys Gln Cys Ile

1 5 10

<210> 844

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 844

Phe Arg Asp Ala Gly His Thr Met Gly Phe

1 5 10

<210> 845

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 845

Phe Trp Leu Thr Lys Leu Asn Tyr Leu

fifteen

<210> 846

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 846

Gly Phe Trp Leu Thr Lys Leu Asn Tyr

fifteen

<210> 847

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 847

Gly Phe Trp Leu Thr Lys Leu Asn Tyr Leu

1 5 10

<210> 848

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 848

Gly Ser Ser Glu Met Glyn Gly His Thr Met

1 5 10

<210> 849

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 849

His Leu Ser Met Leu Thr Asp Ser Leu

fifteen

<210> 850

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 850

His Leu Ser Met Leu Thr Asp Ser Leu Phe

1 5 10

<210> 851

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 851

His Ser Tyr Arg Gly His Leu Gly Ser Ser

1 5 10

<210> 852

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 852

His Thr Met Gly Phe Trp Leu Thr Lys

fifteen

<210> 853

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 853

His Thr Met Gly Phe Trp Leu Thr Lys Leu

1 5 10

<210> 854

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 854

Lys Glu Arg Cys Leu Gln Leu Ser Gly Ala

1 5 10

<210> 855

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 855

Lys Leu Asn Tyr Leu Cys His Leu Ser Met

1 5 10

<210> 856

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 856

Leu Phe Arg Asp Ala Gly His Thr Met

fifteen

<210> 857

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 857

Leu Asn Tyr Leu Cys His Leu Ser Met

fifteen

<210> 858

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 858

Leu Asn Tyr Leu Cys His Leu Ser Met Leu

1 5 10

<210> 859

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 859

Leu Pro Ile Ser His Cys Gln Cys Ile

fifteen

<210> 860

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 860

Leu Pro Ile Ser His Cys Gln Cys Ile Leu

1 5 10

<210> 861

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 861

Leu Ser Met Leu Thr Asp Ser Leu Phe

fifteen

<210> 862

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 862

Leu Ser Met Leu Thr Asp Ser Leu Phe Leu

1 5 10

<210> 863

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 863

Leu Thr Asp Ser Leu Phe Leu Pro Ile

fifteen

<210> 864

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 864

Leu Thr Lys Leu Asn Tyr Leu Cys His Leu

1 5 10

<210> 865

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 865

Met Gly Phe Trp Leu Thr Lys Leu Asn Tyr

1 5 10

<210> 866

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 866

Met Leu Thr Asp Ser Leu Phe Leu Pro Ile

1 5 10

<210> 867

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 867

Met Gln Gly His Thr Met Gly Phe Trp

fifteen

<210> 868

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 868

Met Gln Gly His Thr Met Gly Phe Trp Leu

1 5 10

<210> 869

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 869

Asn Tyr Leu Cys His Leu Ser Met Leu

fifteen

<210> 870

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 870

Arg Asp Ala Gly His Thr Met Gly Phe

fifteen

<210> 871

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 871

Arg Asp Ala Gly His Thr Met Gly Phe Trp

1 5 10

<210> 872

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 872

Arg Gly His Leu Gly Ser Ser Glu Met

fifteen

<210> 873

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 873

Arg Ile His Ser Tyr Arg Gly His Leu Gly

1 5 10

<210> 874

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 874

Ser Glu Met Gln Gly His Thr Met Gly

fifteen

<210> 875

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 875

Ser Glu Met Gln Gly His Thr Met Gly Phe

1 5 10

<210> 876

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 876

Ser Leu Phe Leu Pro Ile Ser His Cys

fifteen

<210> 877

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 877

Ser Met Leu Thr Asp Ser Leu Phe Leu

fifteen

<210> 878

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 878

Ser Ser Glu Met Gln Gly His Thr Met

fifteen

<210> 879

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 879

Thr Lys Leu Asn Tyr Leu Cys His Leu

fifteen

<210> 880

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 880

Thr Leu Lys Glu Arg Cys Leu Gln Leu

fifteen

<210> 881

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 881

Thr Met Gly Phe Trp Leu Thr Lys Leu

fifteen

<210> 882

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 882

Trp Leu Phe Arg Asp Ala Gly His Thr

fifteen

<210> 883

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 883

Trp Leu Phe Arg Asp Ala Gly His Thr Met

1 5 10

<210> 884

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 884

Tyr Leu Cys His Leu Ser Met Leu Thr

fifteen

<210> 885

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 885

Tyr Arg Gly His Leu Gly Ser Ser Glu Met

1 5 10

<210> 886

<211> 14

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 886

Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu

1 5 10

<210> 887

<211> 21

<212> Protein

<213> Plasmodium falciparum

<400> 887

Asp Ile Glu Lys Lys Ile Ala Lys Met Glu Lys Ala Ser Ser Val Phe

1 5 10 15

Asn Val Val Asn Ser

twenty

<210> 888

<211> 16

<212> Protein

<213> Streptococcus sp.

<400> 888

Gly Ala Val Asp Ser Ile Leu Gly Val Ala Thr Tyr Gly Ala Ala

1 5 10 15

<210> 889

<211> 13

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<220>

<221> MOD_RES

<222> (1)..(1)

<223> D-alanine or L-alanine

<220>

<221> MOD_RES

<222> (3)..(3)

<223> Cyclohexylalanine, phenylalanine, or tyrosine

<220>

<221> MOD_RES

<222> (13)..(13)

<223> D-alanine or L-alanine

<400> 889

Ala Lys Xaa Val Trp Ala Asn Thr Leu Lys Ala Ala Ala

1 5 10

<210> 890

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 890

Val Ala Val Lys Met Leu Lys Pro Ser Ala His Leu Thr Glu Arg Glu

1 5 10 15

Ala Leu Met Ser Glu Leu Lys Val Leu Ser Tyr Leu Gly Asn His Met

20 25 30

Asn Ile Val Asn Leu Leu Gly Ala Cys Thr Ile Gly Gly Pro Thr Leu

35 40 45

Val Ile Ile Glu Tyr Cys Cys Tyr Gly Asp Leu Leu Asn Phe Leu Arg

50 55 60

Arg Lys Arg Asp Ser Phe Ile Cys Ser Lys Gln Glu Asp His Ala Glu

65 70 75 80

Ala Ala Leu Tyr Lys Asn Leu Leu His Ser Lys Glu Ser Ser Cys Ser

85 90 95

Asp Ser Thr Asn Glu

100

<210> 891

<211> 61

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 891

His Gly Trp Arg Pro Phe Leu Pro Val Arg Ala Arg Ser Arg Trp Asn

1 5 10 15

Arg Arg Leu Asp Val Thr Val Ala Asn Gly Arg Ser Trp Lys Tyr Gly

20 25 30

Trp Ser Leu Leu Arg Val Pro Gln Val Asn Gly Ile Gln Val Leu Asn

35 40 45

Val Ser Leu Lys Ser Ser Ser Asn Val Ile Ser Tyr Glu

50 55 60

<210> 892

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 892

Gly Gln Tyr Gly Lys Val Tyr Glu Gly

fifteen

<210> 893

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 893

Gly Glyn Tyr Gly Lys Val Tyr Glu Gly Val

1 5 10

<210> 894

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 894

Lys Leu Gly Gly Gly Glyn Tyr Gly Lys

fifteen

<210> 895

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 895

Lys Leu Gly Gly Gly Gln Tyr Gly Lys Val

1 5 10

<210> 896

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 896

Lys Val Tyr Glu Gly Val Trp Lys Lys

fifteen

<210> 897

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 897

Lys Val Tyr Glu Gly Val Trp Lys Lys Tyr

1 5 10

<210> 898

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 898

Gln Tyr Gly Lys Val Tyr Glu Gly Val

fifteen

<210> 899

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 899

Gln Tyr Gly Lys Val Tyr Glu Gly Val Trp

1 5 10

<210> 900

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 900

Gly Gln Tyr Gly Val Val Tyr Glu Gly

fifteen

<210> 901

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 901

Gly Gln Tyr Gly Val Val Tyr Glu Gly Val

1 5 10

<210> 902

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 902

Lys Leu Gly Gly Gly Glyn Tyr Gly Val

fifteen

<210> 903

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 903

Lys Leu Gly Gly Gly Glyn Tyr Gly Val Val

1 5 10

<210> 904

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 904

Gln Tyr Gly Val Val Tyr Glu Gly Val

fifteen

<210> 905

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 905

Gln Tyr Gly Val Val Tyr Glu Gly Val Trp

1 5 10

<210> 906

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 906

Val Val Tyr Glu Gly Val Trp Lys Lys

fifteen

<210> 907

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 907

Val Val Tyr Glu Gly Val Trp Lys Lys Tyr

1 5 10

<210> 908

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 908

Ala Thr Gln Ile Ser Ser Ala Thr Glu Tyr

1 5 10

<210> 909

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 909

Ile Ser Ser Ala Thr Glu Tyr Leu Glu Lys

1 5 10

<210> 910

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 910

Ser Ser Ala Thr Glu Tyr Leu Glu Lys

fifteen

<210> 911

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 911

Thr Gln Ile Ser Ser Ala Thr Glu Tyr Leu

1 5 10

<210> 912

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 912

Tyr Met Ala Thr Gln Ile Ser Ser Ala Thr

1 5 10

<210> 913

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 913

Phe Tyr Ile Ile Ile Glu Phe Met Thr Tyr

1 5 10

<210> 914

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 914

Ile Ile Glu Phe Met Thr Tyr Gly Asn Leu

1 5 10

<210> 915

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 915

Ile Ile Ile Glu Phe Met Thr Tyr Gly

fifteen

<210> 916

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 916

Ile Ile Ile Glu Phe Met Thr Tyr Gly Asn

1 5 10

<210> 917

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 917

Tyr Ile Ile Ile Glu Phe Met Thr Tyr Gly

1 5 10

<210> 918

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 918

Gly Gln His Gly Glu Val Tyr Glu Gly Val

1 5 10

<210> 919

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 919

Lys Leu Gly Gly Gly Gln His Gly Glu Val

1 5 10

<210> 920

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 920

Lys Ile Ala Asp Phe Gly Met Ala Arg

fifteen

<210> 921

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 921

Arg Val Ala Lys Ile Ala Asp Phe Gly Met

1 5 10

<210> 922

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 922

Phe Ile Leu Met Glu Leu Met Ala Gly Gly

1 5 10

<210> 923

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 923

Ile Leu Met Glu Leu Met Ala Gly Gly

fifteen

<210> 924

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 924

Ile Leu Met Glu Leu Met Ala Gly Gly Asp

1 5 10

<210> 925

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 925

Leu Met Glu Leu Met Ala Gly Gly Asp Leu

1 5 10

<210> 926

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 926

Leu Pro Arg Phe Ile Leu Met Glu Leu

fifteen

<210> 927

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 927

Leu Pro Arg Phe Ile Leu Met Glu Leu Met

1 5 10

<210> 928

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 928

Leu Gln Ser Leu Pro Arg Phe Ile Leu Met

1 5 10

<210> 929

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 929

Ser Leu Pro Arg Phe Ile Leu Met Glu Leu

1 5 10

<210> 930

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 930

Leu Ala Thr Glu Lys Ser Arg Trp Ser

fifteen

<210> 931

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 931

Leu Ala Thr Glu Lys Ser Arg Trp Ser Gly

1 5 10

<210> 932

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 932

Glu Tyr Met Ala Asn Gly Ser Leu Leu

fifteen

<210> 933

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 933

Met Ala Asn Gly Ser Leu Leu Asn Tyr

fifteen

<210> 934

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 934

Met Ala Asn Gly Ser Leu Leu Asn Tyr Leu

1 5 10

<210> 935

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 935

Ser Leu Leu Asn Tyr Leu Arg Glu Met

fifteen

<210> 936

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 936

Tyr Met Ala Asn Gly Ser Leu Leu Asn

fifteen

<210> 937

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 937

Tyr Met Ala Asn Gly Ser Leu Leu Asn Tyr

1 5 10

<210> 938

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 938

Gly Pro Pro Pro Ala Asp Leu Cys His Ala Leu

1 5 10

<210> 939

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 939

Ile Ile Arg Asn Arg Gly Glu Asn Ser Cys Lys

1 5 10

<210> 940

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 940

Cys Leu Thr Ser Thr Val Gln Leu Ile Met

1 5 10

<210> 941

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 941

Ile Met Gln Leu Met Pro Phe Gly Cys

fifteen

<210> 942

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 942

Ile Met Gln Leu Met Pro Phe Gly Cys Leu

1 5 10

<210> 943

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 943

Leu Ile Met Gln Leu Met Pro Phe Gly

fifteen

<210> 944

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 944

Leu Ile Met Gln Leu Met Pro Phe Gly Cys

1 5 10

<210> 945

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 945

Leu Thr Ser Thr Val Gln Leu Ile Met

fifteen

<210> 946

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 946

Met Gln Leu Met Pro Phe Gly Cys Leu

fifteen

<210> 947

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 947

Met Gln Leu Met Pro Phe Gly Cys Leu Leu

1 5 10

<210> 948

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 948

Gln Leu Ile Met Gln Leu Met Pro Phe

fifteen

<210> 949

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 949

Gln Leu Ile Met Gln Leu Met Pro Phe Gly

1 5 10

<210> 950

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 950

Ser Thr Val Gln Leu Ile Met Gln Leu

fifteen

<210> 951

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 951

Val Gln Leu Ile Met Gln Leu Met Pro Phe

1 5 10

<210> 952

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 952

Gly Leu Leu Leu Glu Met Leu Asp Ala

fifteen

<210> 953

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 953

Leu Tyr Gly Leu Leu Leu Glu Met Leu

fifteen

<210> 954

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 954

Asn Val Val Pro Leu Tyr Gly Leu Leu

fifteen

<210> 955

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 955

Pro Leu Tyr Gly Leu Leu Leu Glu Met

fifteen

<210> 956

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 956

Pro Leu Tyr Gly Leu Leu Leu Glu Met Leu

1 5 10

<210> 957

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 957

Val Pro Leu Tyr Gly Leu Leu Leu Glu Met

1 5 10

<210> 958

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 958

Val Val Pro Leu Tyr Gly Leu Leu Leu

fifteen

<210> 959

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 959

Phe Leu Pro Ser Thr Leu Lys Ser Leu

fifteen

<210> 960

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 960

Gly Val Tyr Thr Phe Leu Pro Ser Thr

fifteen

<210> 961

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 961

Gly Val Tyr Thr Phe Leu Pro Ser Thr Leu

1 5 10

<210> 962

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 962

Thr Phe Leu Pro Ser Thr Leu Lys Ser Leu

1 5 10

<210> 963

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 963

Val Tyr Thr Phe Leu Pro Ser Thr Leu

fifteen

<210> 964

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 964

Tyr Thr Phe Leu Pro Ser Thr Leu Lys

fifteen

<210> 965

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 965

Asn Val Val Pro Leu Cys Asp Leu Leu

fifteen

<210> 966

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 966

Asn Val Val Pro Leu Cys Asp Leu Leu Leu

1 5 10

<210> 967

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 967

Pro Leu Cys Asp Leu Leu Leu Glu Met

fifteen

<210> 968

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 968

Pro Leu Cys Asp Leu Leu Leu Glu Met Leu

1 5 10

<210> 969

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 969

Val Pro Leu Cys Asp Leu Leu Leu Glu Met

1 5 10

<210> 970

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 970

Val Val Pro Leu Cys Asp Leu Leu Leu

fifteen

<210> 971

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 971

Asn Val Val Pro Leu Asn Asp Leu Leu

fifteen

<210> 972

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 972

Asn Val Val Pro Leu Asn Asp Leu Leu Leu

1 5 10

<210> 973

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 973

Pro Leu Asn Asp Leu Leu Leu Glu Met

fifteen

<210> 974

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 974

Pro Leu Asn Asp Leu Leu Leu Glu Met Leu

1 5 10

<210> 975

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 975

Val Pro Leu Asn Asp Leu Leu Leu Glu Met

1 5 10

<210> 976

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 976

Asn Val Val Pro Leu Ser Asp Leu Leu

fifteen

<210> 977

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 977

Asn Val Val Pro Leu Ser Asp Leu Leu Leu

1 5 10

<210> 978

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 978

Pro Leu Ser Asp Leu Leu Leu Glu Met

fifteen

<210> 979

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 979

Pro Leu Ser Asp Leu Leu Leu Glu Met Leu

1 5 10

<210> 980

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 980

Val Pro Leu Ser Asp Leu Leu Leu Glu Met

1 5 10

<210> 981

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 981

Val Val Pro Leu Ser Asp Leu Leu Leu

fifteen

<210> 982

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 982

Val Leu Glu Arg Cys Pro His Arg Pro Ile

1 5 10

<210> 983

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 983

Tyr Thr Leu Asp Val Leu Glu Arg Cys

fifteen

<210> 984

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 984

Phe Gln Asn Gly Lys Met Ala Leu Ser

fifteen

<210> 985

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 985

Val Met Ala Gly Leu Gly Ser Pro Tyr Val

1 5 10

<210> 986

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 986

Lys Pro Ile Ile Ile Gly His His Ala

fifteen

<210> 987

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 987

Lys Pro Ile Ile Ile Gly Cys His Ala

fifteen

<210> 988

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 988

Lys Pro Ile Ile Ile Gly Gly His Ala

fifteen

<210> 989

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 989

Lys Pro Ile Ile Ile Gly Ser His Ala

fifteen

<210> 990

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 990

Ile Ile Glu Tyr Cys Cys Tyr Gly Asp Leu

1 5 10

<210> 991

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 991

Thr Ile Gly Gly Pro Thr Leu Val Ile Ile

1 5 10

<210> 992

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 992

Val Ile Ile Glu Tyr Cys Cys Tyr Gly

fifteen

<210> 993

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 993

His Met Asn Ile Ala Asn Leu Leu Gly Ala

1 5 10

<210> 994

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 994

Ile Ala Asn Leu Leu Gly Ala Cys Thr Ile

1 5 10

<210> 995

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 995

Met Asn Ile Ala Asn Leu Leu Gly Ala

fifteen

<210> 996

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 996

Tyr Leu Gly Asn His Met Asn Ile Ala

fifteen

<210> 997

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 997

Tyr Leu Gly Asn His Met Asn Ile Ala Asn

1 5 10

<210> 998

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 998

Val Leu His Glu Ser Asn Ser Pro Tyr

fifteen

<210> 999

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 999

Val Leu His Glu Ser Asn Ser Pro Tyr Ile

1 5 10

<210> 1000

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1000

Leu Gln Val Leu His Glu Cys Asn Ser Leu

1 5 10

<210> 1001

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1001

Leu Tyr Ile Val Gly Phe Tyr Gly Ala Phe

1 5 10

<210> 1002

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1002

Asn Ser Leu Tyr Ile Val Gly Phe Tyr

fifteen

<210> 1003

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1003

Gln Val Leu His Glu Cys Asn Ser Leu

fifteen

<210> 1004

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1004

Ser Leu Tyr Ile Val Gly Phe Tyr Gly

fifteen

<210> 1005

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1005

Ser Leu Tyr Ile Val Gly Phe Tyr Gly Ala

1 5 10

<210> 1006

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1006

Val Leu His Glu Cys Asn Ser Leu Tyr

fifteen

<210> 1007

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1007

Val Leu His Glu Cys Asn Ser Leu Tyr Ile

1 5 10

<210> 1008

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1008

Phe Tyr Gln Gln Gln Gln Gln Ser Asp Leu

1 5 10

<210> 1009

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1009

Gln Gln Gln Ser Asp Leu Gln Pro Pro Ala

1 5 10

<210> 1010

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1010

Gln Gln Ser Asp Leu Gln Pro Pro Ala

fifteen

<210> 1011

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1011

Tyr Gln Gln Gln Gln Gln Ser Asp Leu

fifteen

<210> 1012

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1012

Phe Glu Leu Leu Ser Thr Pro Pro Leu

fifteen

<210> 1013

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1013

Leu Leu Ser Thr Pro Pro Leu Ser Pro Ser

1 5 10

<210> 1014

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1014

Phe Glu Leu Leu Pro Ile Pro Pro Leu

fifteen

<210> 1015

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1015

Ile Trp Lys Lys Phe Glu Leu Leu Pro Ile

1 5 10

<210> 1016

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1016

Leu Leu Pro Ile Pro Pro Leu Ser Pro Ser

1 5 10

<210> 1017

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1017

Leu Pro Ile Pro Pro Leu Ser Pro Ser

fifteen

<210> 1018

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1018

Ile Ile Glu Tyr Cys Phe Tyr Gly Asp Leu

1 5 10

<210> 1019

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1019

Ile Ile Ile Glu Tyr Cys Phe Tyr Gly

fifteen

<210> 1020

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1020

Ile Tyr Ile Ile Ile Glu Tyr Cys Phe

fifteen

<210> 1021

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1021

Ile Tyr Ile Ile Ile Glu Tyr Cys Phe Tyr

1 5 10

<210> 1022

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1022

Tyr Ile Ile Ile Glu Tyr Cys Phe Tyr Gly

1 5 10

<210> 1023

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1023

Lys Ile Thr Glu Gln Glu Lys Asp Phe Leu

1 5 10

<210> 1024

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1024

Ser Thr Arg Asp Pro Leu Ser Glu Ile Thr Lys

1 5 10

<210> 1025

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1025

Asp Pro Leu Ser Glu Ile Thr Lys

fifteen

<210> 1026

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1026

Leu Pro Leu Lys Phe Arg Asp Ala Glu Thr

1 5 10

<210> 1027

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1027

Gln Thr Gly Val Met Ile Cys Ala Tyr Leu

1 5 10

<210> 1028

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1028

Ala Phe Ser Gly Glu Tyr Ile Pro Thr Val

1 5 10

<210> 1029

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1029

Ser Met Asn Arg Arg Pro Ile Leu Thr

fifteen

<210> 1030

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1030

Tyr Met Cys Asn Ser Ser Cys Met Gly Ser

1 5 10

<210> 1031

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1031

Gly Met Asn Gln Arg Pro Ile Leu Thr

fifteen

<210> 1032

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1032

Gly Met Asn Trp Arg Pro Ile Leu Thr

fifteen

<210> 1033

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1033

Leu Leu Gly Arg Asn Ser Phe Glu Val Cys

1 5 10

<210> 1034

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1034

Ala Leu Lys Tyr Ile Phe Val Ala Val

fifteen

<210> 1035

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1035

Ala Leu Lys Tyr Ile Phe Val Ala Val Arg

1 5 10

<210> 1036

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1036

Ala Val Arg Ala Ile Cys Val Met Lys

fifteen

<210> 1037

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1037

Ala Val Arg Ala Ile Cys Val Met Lys Ser

1 5 10

<210> 1038

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1038

Cys Val Glu Lys Lys Thr Ala Leu Lys

fifteen

<210> 1039

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1039

Cys Val Glu Lys Lys Thr Ala Leu Lys Tyr

1 5 10

<210> 1040

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1040

Cys Val Met Lys Ser Phe Leu Ile Phe

fifteen

<210> 1041

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1041

Cys Val Met Lys Ser Phe Leu Ile Phe Arg

1 5 10

<210> 1042

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1042

Phe Leu Ile Phe Arg Arg Trp Lys Ser

fifteen

<210> 1043

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1043

Phe Arg Arg Trp Lys Ser His Ser Pro Leu

1 5 10

<210> 1044

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1044

Phe Val Ala Val Arg Ala Ile Cys Val

fifteen

<210> 1045

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1045

Phe Val Ala Val Arg Ala Ile Cys Val Met

1 5 10

<210> 1046

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1046

Ile Gln Leu His Leu Ser His Pro Ile

fifteen

<210> 1047

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1047

Lys Ser Phe Leu Ile Phe Arg Arg Trp Lys

1 5 10

<210> 1048

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1048

Lys Thr Ala Leu Lys Tyr Ile Phe Val

fifteen

<210> 1049

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1049

Lys Tyr Ile Phe Val Ala Val Arg Ala Ile

1 5 10

<210> 1050

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1050

Arg Trp Lys Ser His Ser Pro Leu Gln Ile

1 5 10

<210> 1051

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1051

Thr Ala Leu Lys Tyr Ile Phe Val Ala Val

1 5 10

<210> 1052

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1052

Val Ala Val Arg Ala Ile Cys Val Met Lys

1 5 10

<210> 1053

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1053

Val Met Lys Ser Phe Leu Ile Phe Arg

fifteen

<210> 1054

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1054

Val Met Lys Ser Phe Leu Ile Phe Arg Arg

1 5 10

<210> 1055

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1055

Tyr Ile Phe Val Ala Val Arg Ala Ile

fifteen

<210> 1056

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1056

Ala Leu Phe Phe Phe Phe Phe Glu Thr

fifteen

<210> 1057

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1057

Ala Leu Phe Phe Phe Phe Phe Glu Thr Lys

1 5 10

<210> 1058

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1058

Ala Gln Ala Gly Val Gln Trp Arg Ser Leu

1 5 10

<210> 1059

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1059

Cys Leu Ala Asn Phe Cys Ile Phe Asn Arg

1 5 10

<210> 1060

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1060

Cys Leu Ser Phe Leu Ser Ser Trp Asp Tyr

1 5 10

<210> 1061

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1061

Phe Phe Glu Thr Lys Ser Cys Ser Val

fifteen

<210> 1062

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1062

Phe Phe Phe Glu Thr Lys Ser Cys Ser Val

1 5 10

<210> 1063

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1063

Phe Lys Leu Phe Ser Cys Leu Ser Phe Leu

1 5 10

<210> 1064

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1064

Phe Leu Ser Ser Trp Asp Tyr Arg Arg Met

1 5 10

<210> 1065

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1065

Gly Phe Lys Leu Phe Ser Cys Leu Ser Phe

1 5 10

<210> 1066

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1066

Lys Leu Phe Ser Cys Leu Ser Phe Leu

fifteen

<210> 1067

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1067

Lys Leu Phe Ser Cys Leu Ser Phe Leu Ser

1 5 10

<210> 1068

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1068

Leu Ala Leu Phe Phe Phe Phe Phe Glu Thr

1 5 10

<210> 1069

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1069

Leu Phe Phe Phe Phe Phe Glu Thr Lys

fifteen

<210> 1070

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1070

Leu Ser Phe Leu Ser Ser Trp Asp Tyr

fifteen

<210> 1071

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1071

Leu Ser Phe Leu Ser Ser Trp Asp Tyr Arg

1 5 10

<210> 1072

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1072

Arg Met Pro Pro Cys Leu Ala Asn Phe

fifteen

<210> 1073

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1073

Arg Arg Met Pro Cys Leu Ala Asn Phe

1 5 10

<210> 1074

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1074

Ser Leu Gln Pro Pro Pro Pro Gly Phe Lys

1 5 10

<210> 1075

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1075

Val Gln Trp Arg Ser Leu Gly Ser Leu

fifteen

<210> 1076

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1076

Phe Phe Phe Ser Val Ile Phe Ser Thr

fifteen

<210> 1077

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1077

Met Ser Val Cys Phe Phe Phe Phe Ser Val

1 5 10

<210> 1078

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1078

Ser Val Cys Phe Phe Phe Phe Ser Val

fifteen

<210> 1079

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1079

Ser Val Cys Phe Phe Phe Phe Ser Val Ile

1 5 10

<210> 1080

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1080

Phe Phe Cys Tyr Ile Leu Asn Thr Met Phe

1 5 10

<210> 1081

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1081

Met Ser Val Cys Phe Phe Phe Phe Cys Tyr

1 5 10

<210> 1082

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1082

Ser Val Cys Phe Phe Phe Phe Cys Tyr Ile

1 5 10

<210> 1083

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1083

Lys Gln Trp Ser Ser Val Thr Ser Leu

fifteen

<210> 1084

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1084

Val Leu Trp Met Pro Thr Ser Thr Val

fifteen

<210> 1085

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1085

Ile Leu Ile Arg Lys Ala Met Thr Val

fifteen

<210> 1086

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1086

Arg Met Lys Val Pro Leu Met Lys

fifteen

<210> 1087

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1087

Thr Leu Lys Lys Lys Pro Arg Asp Ile

fifteen

<210> 1088

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1088

Leu Ile Glu Gly Phe Glu Ala Leu Leu Lys

1 5 10

<210> 1089

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1089

Gln Gln Leu Lys Trp Thr Pro His Ile

fifteen

<210> 1090

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1090

Gln Leu Lys Trp Thr Pro His Ile Leu Lys

1 5 10

<210> 1091

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1091

Ile Val Ser Glu Lys Asn Gln Gln Leu Lys

1 5 10

<210> 1092

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1092

Asn Gln Gln Leu Lys Trp Thr Pro His Ile Leu

1 5 10

<210> 1093

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1093

Asn Gln Gln Leu Lys Trp Thr Pro His Ile

1 5 10

<210> 1094

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1094

Gln Leu Lys Trp Thr Pro His Ile Leu

fifteen

<210> 1095

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1095

Gly Pro Pro Arg Pro Pro Arg Ala Ala Cys

1 5 10

<210> 1096

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1096

Pro Pro Arg Pro Pro Arg Ala Ala Cys

fifteen

<210> 1097

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1097

Ser Leu Arg Arg Lys Tyr Leu Arg Val

fifteen

<210> 1098

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1098

Ser Ala Ala Cys His Arg Arg Gly Cys Val

1 5 10

<210> 1099

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1099

Ala Leu Trp Glu Cys Ser Leu Pro Gln Ala

1 5 10

<210> 1100

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1100

Cys Leu Ile Val Ser Arg Thr Leu Leu

fifteen

<210> 1101

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1101

Cys Leu Ile Val Ser Arg Thr Leu Leu Leu

1 5 10

<210> 1102

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1102

Phe Leu Leu Ala Leu Trp Glu Cys Ser

fifteen

<210> 1103

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1103

Phe Leu Leu Ala Leu Trp Glu Cys Ser Leu

1 5 10

<210> 1104

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1104

Ile Val Ser Arg Thr Leu Leu Leu Val

fifteen

<210> 1105

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1105

Leu Ile Val Ser Arg Thr Leu Leu Leu

fifteen

<210> 1106

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1106

Leu Ile Val Ser Arg Thr Leu Leu Leu Val

1 5 10

<210> 1107

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1107

Leu Leu Ala Leu Trp Glu Cys Ser Leu

fifteen

<210> 1108

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1108

Leu Pro Gln Ala Arg Leu Cys Leu Ile

fifteen

<210> 1109

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1109

Leu Pro Gln Ala Arg Leu Cys Leu Ile Val

1 5 10

<210> 1110

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1110

Asn Val Arg Asp Lys Lys Arg Ala Thr Phe

1 5 10

<210> 1111

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1111

Ser Leu Pro Gln Ala Arg Leu Cys Leu Ile

1 5 10

<210> 1112

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1112

Phe Phe Cys Trp Ile Leu Ser Cys Lys

fifteen

<210> 1113

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1113

Phe Phe Phe Cys Trp Ile Leu Ser Cys Lys

1 5 10

<210> 1114

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1114

Ile Thr Ala Phe Phe Phe Cys Trp Ile

fifteen

<210> 1115

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1115

Leu Tyr Ile Thr Ala Phe Phe Phe Cys Trp

1 5 10

<210> 1116

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1116

Tyr Ile Thr Ala Phe Phe Phe Cys Trp Ile

1 5 10

<210> 1117

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1117

Ile Thr Ala Phe Phe Leu Leu Asp Ile

fifteen

<210> 1118

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1118

Leu Leu Tyr Ile Thr Ala Phe Phe Leu

fifteen

<210> 1119

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1119

Leu Leu Tyr Ile Thr Ala Phe Phe Leu Leu

1 5 10

<210> 1120

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1120

Leu Tyr Ile Thr Ala Phe Phe Leu Leu

fifteen

<210> 1121

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1121

Leu Tyr Ile Thr Ala Phe Phe Leu Leu Asp

1 5 10

<210> 1122

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1122

Tyr Ile Thr Ala Phe Phe Leu Leu Asp Ile

1 5 10

<210> 1123

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1123

Gly Ser Asn Glu Val Thr Thr Arg Tyr

fifteen

<210> 1124

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1124

Met Pro Lys Asp Val Asn Ile Gln Val

fifteen

<210> 1125

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1125

Thr Gly Ser Asn Glu Val Thr Thr Arg Tyr

1 5 10

<210> 1126

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1126

Lys Lys Leu Met Leu Leu Arg Leu Asn Leu

1 5 10

<210> 1127

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1127

Lys Leu Met Leu Leu Arg Leu Asn Leu

fifteen

<210> 1128

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1128

Lys Leu Met Leu Leu Arg Leu Asn Leu Arg

1 5 10

<210> 1129

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1129

Leu Leu Arg Leu Asn Leu Arg Lys Met

fifteen

<210> 1130

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1130

Leu Met Leu Leu Arg Leu Asn Leu

fifteen

<210> 1131

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1131

Leu Met Leu Leu Arg Leu Asn Leu Arg Lys

1 5 10

<210> 1132

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1132

Leu Asn Leu Arg Lys Met Cys Gly Pro Phe

1 5 10

<210> 1133

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1133

Met Leu Leu Arg Leu Asn Leu Arg Lys

fifteen

<210> 1134

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1134

Met Leu Leu Arg Leu Asn Leu Arg Lys Met

1 5 10

<210> 1135

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1135

Asn Leu Arg Lys Met Cys Gly Pro Phe

fifteen

<210> 1136

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1136

Asn Tyr Cys Gln Lys Lys Leu Met Leu Leu

1 5 10

<210> 1137

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1137

Tyr Cys Gln Lys Lys Leu Met Leu Leu

fifteen

<210> 1138

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1138

Phe Lys Lys Lys Thr Tyr Thr Cys Ala Ile

1 5 10

<210> 1139

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1139

Ile Thr Thr Val Lys Ala Thr Glu Thr Lys

1 5 10

<210> 1140

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1140

Lys Ser Lys Lys Lys Glu Thr Phe Lys

fifteen

<210> 1141

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1141

Lys Ser Lys Lys Lys Glu Thr Phe Lys Lys

1 5 10

<210> 1142

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1142

Lys Thr Tyr Thr Cys Ala Ile Thr Thr Val

1 5 10

<210> 1143

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1143

Thr Phe Lys Lys Lys Thr Tyr Thr Cys

fifteen

<210> 1144

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1144

Thr Tyr Thr Cys Ala Ile Thr Thr Val

fifteen

<210> 1145

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1145

Thr Tyr Thr Cys Ala Ile Thr Thr Val Lys

1 5 10

<210> 1146

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1146

Tyr Thr Cys Ala Ile Thr Thr Val Lys

fifteen

<210> 1147

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1147

Thr Ala Lys Ser Lys Lys Arg Asn Leu

fifteen

<210> 1148

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1148

Phe Ala Leu Cys Gly Phe Trp Gln Ile

fifteen

<210> 1149

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1149

Leu Lys Lys Leu Arg Ser Pro Leu

fifteen

<210> 1150

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1150

Ser Leu Lys Lys Val Pro Ala Leu

fifteen

<210> 1151

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1151

Arg Lys Ile Ser Asn Trp Ser Leu Lys Lys

1 5 10

<210> 1152

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1152

Val Pro Ala Leu Lys Lys Leu Arg Ser Pro Leu

1 5 10

<210> 1153

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1153

Lys Arg Val Asn Thr Ala Trp Lys Thr Lys

1 5 10

<210> 1154

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1154

Met Thr Lys Lys Lys Arg Val Asn Thr Ala

1 5 10

<210> 1155

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1155

Arg Val Asn Thr Ala Trp Lys Thr Lys

fifteen

<210> 1156

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1156

Arg Val Asn Thr Ala Trp Lys Thr Lys Lys

1 5 10

<210> 1157

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1157

Thr Lys Lys Lys Arg Val Asn Thr Ala

fifteen

<210> 1158

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1158

Trp Lys Thr Lys Lys Thr Ser Phe Ser Leu

1 5 10

<210> 1159

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1159

Ala Leu Met Ser Ala Met Thr Thr Ser

fifteen

<210> 1160

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1160

Ala Met Thr Thr Ser Ser Ser Gln Lys

fifteen

<210> 1161

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1161

Ala Met Thr Thr Ser Ser Ser Gln Lys Asn

1 5 10

<210> 1162

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1162

Cys Ile Met Lys Glu Lys Lys Ser Leu

fifteen

<210> 1163

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1163

Cys Ile Met Lys Glu Lys Lys Ser Leu Val

1 5 10

<210> 1164

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1164

Ile Met Lys Glu Lys Lys Ser Leu

fifteen

<210> 1165

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1165

Ile Met Lys Glu Lys Lys Ser Leu Val

fifteen

<210> 1166

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1166

Lys Ser Leu Val Arg Leu Ser Ser Cys Val

1 5 10

<210> 1167

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1167

Leu Val Arg Leu Ser Ser Cys Val Pro Val

1 5 10

<210> 1168

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1168

Arg Leu Ser Ser Cys Val Pro Val Ala

fifteen

<210> 1169

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1169

Arg Leu Ser Ser Cys Val Pro Val Ala Leu

1 5 10

<210> 1170

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1170

Ser Ala Met Thr Thr Ser Ser Ser Ser Gln Lys

1 5 10

<210> 1171

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1171

Ser Leu Val Arg Leu Ser Ser Cys Val

fifteen

<210> 1172

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1172

Val Pro Val Ala Leu Met Ser Ala Met

fifteen

<210> 1173

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1173

Val Arg Leu Ser Ser Cys Val Pro Val Ala

1 5 10

<210> 1174

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1174

Lys Met Arg Lys Lys Tyr Ala Gln Lys

fifteen

<210> 1175

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1175

Phe Val Met Ser Asp Thr Thr Tyr Lys

fifteen

<210> 1176

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1176

Phe Val Met Ser Asp Thr Thr Tyr Lys Ile

1 5 10

<210> 1177

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1177

Lys Thr Phe Glu Lys Lys Gly Glu Lys

fifteen

<210> 1178

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1178

Leu Phe Val Met Ser Asp Thr Thr Tyr Lys

1 5 10

<210> 1179

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1179

Met Ser Asp Thr Thr Tyr Lys Ile Tyr

fifteen

<210> 1180

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1180

Val Met Ser Asp Thr Thr Tyr Lys Ile

fifteen

<210> 1181

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1181

Val Met Ser Asp Thr Thr Tyr Lys Ile Tyr

1 5 10

<210> 1182

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1182

Tyr Leu Thr Lys Trp Pro Lys Phe Phe Leu

1 5 10

<210> 1183

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1183

Phe Leu Gln Glu Arg Asn Leu Pro Pro

fifteen

<210> 1184

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1184

Phe Arg Arg Pro His Ser Cys Leu Ala

fifteen

<210> 1185

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1185

Leu Ile Val Leu Arg Val Val Arg Leu

fifteen

<210> 1186

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1186

Glu Val Lys His Leu His His Leu Leu

fifteen

<210> 1187

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1187

His Leu His His Leu Leu Lys Gln Leu Lys

1 5 10

<210> 1188

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1188

His Leu Leu Leu Lys Arg Glu Arg Val

fifteen

<210> 1189

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1189

Lys Ile Lys His Leu Leu Leu Lys Arg

fifteen

<210> 1190

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1190

Lys Pro Ser Glu Lys Tyr Leu Lys Ile

fifteen

<210> 1191

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1191

Lys Tyr Leu Lys Ile Lys His Leu Leu

fifteen

<210> 1192

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1192

Lys Tyr Leu Lys Ile Lys His Leu Leu Leu

1 5 10

<210> 1193

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1193

Leu Leu Lys Gln Leu Lys Pro Ser Glu Lys

1 5 10

<210> 1194

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1194

Leu Leu Lys Arg Glu Arg Val Asp Leu

fifteen

<210> 1195

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1195

Leu Leu Leu Lys Arg Glu Arg Val Asp Leu

1 5 10

<210> 1196

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1196

Gln Leu Lys Pro Ser Glu Lys Tyr Leu Lys

1 5 10

<210> 1197

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1197

Tyr Leu Lys Ile Lys His Leu Leu Leu

fifteen

<210> 1198

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1198

Tyr Leu Lys Ile Lys His Leu Leu Leu Lys

1 5 10

<210> 1199

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1199

Ile Leu Pro Arg Lys Val Leu Gln Met

fifteen

<210> 1200

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1200

Lys Val Leu Gln Met Asp Phe Leu Val

fifteen

<210> 1201

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1201

Leu Pro Arg Lys Val Leu Gln Met Asp Phe

1 5 10

<210> 1202

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1202

Leu Gln Met Asp Phe Leu Val His Pro Ala

1 5 10

<210> 1203

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1203

Gln Met Asp Phe Leu Val His Pro Ala

fifteen

<210> 1204

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1204

Tyr Ile Leu Pro Arg Lys Val Leu Gln Met

1 5 10

<210> 1205

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1205

Ala Pro Ser Pro Ala Ser Arg Leu Gln Cys

1 5 10

<210> 1206

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1206

His Pro Leu Ala Pro Met Pro Ser Lys Thr

1 5 10

<210> 1207

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1207

Ile Leu Pro Leu Pro Gln Leu Leu Leu

fifteen

<210> 1208

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1208

Leu Leu Leu Ser Ala Asp Gln Gln Ala

fifteen

<210> 1209

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1209

Leu Pro Thr Gln Thr Arg Gly Cys Ile

fifteen

<210> 1210

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1210

Leu Pro Thr Gln Thr Arg Gly Cys Ile Leu

1 5 10

<210> 1211

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1211

Arg Ile Ser Cys Leu Pro Thr Gln Thr Arg

1 5 10

<210> 1212

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1212

Ser Leu Ala Glu Thr Val Ser Leu His

fifteen

<210> 1213

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1213

Thr Pro Arg Ser Ser Ser Ser Ser Ser

fifteen

<210> 1214

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1214

Thr Pro Arg Ser Ser Ser Ser Ser Ser Ser Ser

1 5 10

<210> 1215

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1215

Ala Leu Pro Pro Val Leu Leu Ser Leu

fifteen

<210> 1216

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1216

Ala Leu Pro Pro Val Leu Leu Ser Leu Ala

1 5 10

<210> 1217

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1217

Ala Leu Pro Arg Pro Leu Leu Ala Leu

fifteen

<210> 1218

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1218

Ala Ser Arg Thr Ala Ser Cys Ile Leu

fifteen

<210> 1219

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1219

Glu Ala Leu Pro Arg Pro Leu Leu Ala Leu

1 5 10

<210> 1220

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1220

His Leu Gly His Pro Val Ala Ser Arg

fifteen

<210> 1221

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1221

His Pro Val Ala Ser Arg Thr Ala Ser

fifteen

<210> 1222

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1222

His Pro Val Ala Ser Arg Thr Ala Ser Cys

1 5 10

<210> 1223

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1223

Ile Ile Gln Leu Ser Leu Leu Ser Leu Leu

1 5 10

<210> 1224

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1224

Ile Gln Leu Ser Leu Leu Ser Leu Leu

fifteen

<210> 1225

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1225

Ile Gln Leu Ser Leu Leu Ser Leu Leu Ile

1 5 10

<210> 1226

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1226

Leu Leu Ala Leu Pro Pro Val Leu Leu

fifteen

<210> 1227

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1227

Leu Leu Ile Pro Pro Leu Thr Cys Leu

fifteen

<210> 1228

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1228

Leu Leu Ile Pro Pro Leu Thr Cys Leu Ala

1 5 10

<210> 1229

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1229

Leu Leu Ser Leu Leu Ile Pro Pro Leu

fifteen

<210> 1230

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1230

Leu Leu Ser Leu Leu Ile Pro Pro Leu Thr

1 5 10

<210> 1231

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1231

Leu Pro Arg Pro Leu Leu Ala Leu Pro Pro

1 5 10

<210> 1232

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1232

Gln Leu Ser Leu Leu Ser Leu Leu Ile

fifteen

<210> 1233

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1233

Arg Leu Leu Gln Cys Gln Ala Thr Arg

fifteen

<210> 1234

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1234

Arg Pro Leu Leu Ala Leu Pro Pro Val

fifteen

<210> 1235

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1235

Arg Pro Leu Leu Ala Leu Pro Pro Val Leu

1 5 10

<210> 1236

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1236

Ser Leu Ala Gln Asp His Ser Arg Leu

fifteen

<210> 1237

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1237

Ser Leu Ala Gln Asp His Ser Arg Leu Leu

1 5 10

<210> 1238

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1238

Ser Leu Leu Ile Pro Pro Leu Thr Cys Leu

1 5 10

<210> 1239

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1239

Ser Leu Leu Ser Leu Leu Ile Pro

fifteen

<210> 1240

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1240

Ser Leu Leu Ser Leu Leu Ile Pro Pro Leu

1 5 10

<210> 1241

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1241

Ala Ala Ala Thr Ser Ala Ala Ser Thr Leu

1 5 10

<210> 1242

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1242

Ala Ala Ile Pro Ala Ser Thr Ser Ala Val

1 5 10

<210> 1243

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1243

Ala Ile Pro Ala Ser Thr Ser Ala Val

fifteen

<210> 1244

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1244

Ala Leu Pro Ala Gly Cys Val Ser Ser Ala

1 5 10

<210> 1245

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1245

Ala Pro Leu Leu Thr Ala Thr Gly Ser Val

1 5 10

<210> 1246

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1246

Ala Pro Val Leu Ser Ala Ser Ile Leu

fifteen

<210> 1247

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1247

Ala Thr Leu Leu Pro Ala Thr Thr Val

fifteen

<210> 1248

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1248

Ala Thr Val Ser Thr Thr Thr Ala Pro Val

1 5 10

<210> 1249

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1249

Ala Val Pro Ala Asn Cys Leu Phe Pro Ala

1 5 10

<210> 1250

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1250

Cys Leu Phe Pro Ala Ala Leu Pro Ser Thr

1 5 10

<210> 1251

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1251

Cys Pro Thr Phe Val Ser Ala Ala Ala

fifteen

<210> 1252

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1252

Phe Pro Ala Ala Leu Pro Ser Thr Ala

fifteen

<210> 1253

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1253

Phe Pro Ala Ala Leu Pro Ser Thr Ala Gly

1 5 10

<210> 1254

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1254

Gly Ala Glu Cys His Gly Arg Pro Leu

fifteen

<210> 1255

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1255

Gly Ala Ile Ser Arg Phe Ile Trp Val

fifteen

<210> 1256

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1256

Ile Leu Pro Ala Ala Ile Pro Ala Ser Thr

1 5 10

<210> 1257

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1257

Ile Trp Val Ser Gly Ile Leu Ser Pro Leu

1 5 10

<210> 1258

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1258

Leu Leu Thr Ala Thr Gly Ser Val Ser Leu

1 5 10

<210> 1259

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1259

Leu Leu Tyr Thr Ala Asp Ser Ser Leu

fifteen

<210> 1260

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1260

Leu Pro Ala Ala Ala Thr Ser Ala Ala

fifteen

<210> 1261

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1261

Leu Pro Ala Ala Ala Thr Ser Ala Ala Ser

1 5 10

<210> 1262

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1262

Leu Pro Ala Ala Ile Pro Ala Ser Thr

fifteen

<210> 1263

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1263

Leu Pro Ala Gly Cys Val Ser Ser Ala

fifteen

<210> 1264

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1264

Leu Pro Ala Gly Cys Val Ser Ser Ala Pro

1 5 10

<210> 1265

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1265

Leu Tyr Thr Ala Asp Ser Ser Leu Trp

fifteen

<210> 1266

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1266

Gln Pro Ala Lys Ser Ser Pro Ser Ala

fifteen

<210> 1267

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1267

Gln Pro Ala Lys Ser Ser Pro Ser Ala Ala

1 5 10

<210> 1268

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1268

Arg Phe Ile Trp Val Ser Gly Ile Leu

fifteen

<210> 1269

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1269

Arg Pro Gln Arg Val Trp Ser Thr Gly

fifteen

<210> 1270

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1270

Arg Val Trp Ser Thr Gly Pro Asp Ser Ile

1 5 10

<210> 1271

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1271

Ser Ala Val Pro Gly Ser Ile Pro Leu

fifteen

<210> 1272

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1272

Ser Ile Leu Pro Ala Ala Ile Pro Ala

fifteen

<210> 1273

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1273

Ser Leu Pro Ala Ala Ala Thr Ser Ala

fifteen

<210> 1274

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1274

Ser Leu Pro Ala Ala Ala Thr Ser Ala Ala

1 5 10

<210> 1275

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1275

Ser Leu Trp Thr Thr Arg Pro Gln Arg

fifteen

<210> 1276

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1276

Ser Leu Trp Thr Thr Arg Pro Gln Arg Val

1 5 10

<210> 1277

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1277

Ser Pro Ser Ala Ala Ala Ala Thr Leu

fifteen

<210> 1278

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1278

Ser Pro Ser Ala Ala Ala Ala Thr Leu Leu

1 5 10

<210> 1279

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1279

Thr Leu Asp Ala Leu Pro Ala Gly Cys Val

1 5 10

<210> 1280

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1280

Thr Val Ser Thr Thr Thr Ala Pro Val

fifteen

<210> 1281

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1281

Val Leu Ser Ala Ser Ile Leu Pro Ala

fifteen

<210> 1282

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1282

Val Leu Ser Ala Ser Ile Leu Pro Ala Ala

1 5 10

<210> 1283

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1283

Val Pro Ala Asn Cys Leu Phe Pro Ala

fifteen

<210> 1284

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1284

Val Pro Ala Asn Cys Leu Phe Pro Ala Ala

1 5 10

<210> 1285

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1285

Val Pro Asp Pro Ser Cys Pro Thr Phe

fifteen

<210> 1286

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1286

Val Pro Gly Ser Ile Pro Leu Pro Ala

fifteen

<210> 1287

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1287

Val Pro Gly Ser Ile Pro Leu Pro Ala Val

1 5 10

<210> 1288

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1288

Trp Val Ser Gly Ile Leu Ser Pro Leu

fifteen

<210> 1289

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1289

Tyr Thr Ala Asp Ser Ser Leu Trp Thr Thr

1 5 10

<210> 1290

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1290

Ala Pro Ala Gly Met Val Asn Arg Ala

fifteen

<210> 1291

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1291

Ala Ser Leu His Arg Arg Ser Tyr Leu

fifteen

<210> 1292

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1292

Ala Ser Leu His Arg Arg Ser Tyr Leu Lys

1 5 10

<210> 1293

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1293

Phe Leu Leu Met Asp Asn Lys Ala Pro Ala

1 5 10

<210> 1294

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1294

His Pro Arg Arg Ser Pro Ser Arg Leu

fifteen

<210> 1295

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1295

His Pro Ser Leu His Ile Ser Ser Pro

fifteen

<210> 1296

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1296

His Arg Arg Ser Tyr Leu Lys Ile His Leu

1 5 10

<210> 1297

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1297

His Ser Arg Phe Leu Leu Met Asp Asn Lys

1 5 10

<210> 1298

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1298

Lys Leu Pro Ile Pro Ser Ser Ala Ser Leu

1 5 10

<210> 1299

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1299

Lys Val Leu Thr Leu Ser Ser Ser Ser His

1 5 10

<210> 1300

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1300

Leu Ile His Ser Arg Phe Leu Leu Met

fifteen

<210> 1301

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1301

Leu Leu Met Asp Asn Lys Ala Pro Ala

fifteen

<210> 1302

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1302

Leu Met Asp Asn Lys Ala Pro Ala Gly Met

1 5 10

<210> 1303

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1303

Leu Pro Ile Pro Ser Ser Ala Ser Leu

fifteen

<210> 1304

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1304

Met Pro Asn Leu Arg Ile Ser Ser Ser

fifteen

<210> 1305

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1305

Met Pro Asn Leu Arg Ile Ser Ser Ser His

1 5 10

<210> 1306

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1306

Asn Leu Arg Ile Ser Ser Ser His Ser Leu

1 5 10

<210> 1307

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1307

Pro Pro Thr His Ser His Arg Leu Ser Leu

1 5 10

<210> 1308

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1308

Arg Ala Gly Arg Arg Val Pro Trp Ala Ala

1 5 10

<210> 1309

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1309

Arg Ala Arg Leu His Ile Thr Thr Ser Lys

1 5 10

<210> 1310

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1310

Arg Ile Ser Ser Ser His Ser Leu Asn His

1 5 10

<210> 1311

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1311

Arg Leu His Thr Pro Pro Ser Ser Arg

fifteen

<210> 1312

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1312

Arg Leu His Thr Pro Pro Ser Ser Arg Arg

1 5 10

<210> 1313

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1313

Arg Leu Arg Ile Leu Ser Pro Ser Leu

fifteen

<210> 1314

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1314

Arg Pro Leu Met Pro Asn Leu Arg Ile

fifteen

<210> 1315

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1315

Arg Pro Arg Pro Leu Met Pro Asn Leu

fifteen

<210> 1316

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1316

Ser Ala Ser Leu His Arg Arg Ser Tyr Leu

1 5 10

<210> 1317

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1317

Ser Leu His Ile Ser Ser Pro Arg Leu

fifteen

<210> 1318

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1318

Ser Leu His Arg Arg Ser Tyr Leu Lys

fifteen

<210> 1319

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1319

Ser Leu His Arg Arg Ser Tyr Leu Lys Ile

1 5 10

<210> 1320

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1320

Ser Leu Ile His Ser Arg Phe Leu Leu

fifteen

<210> 1321

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1321

Ser Leu Ile His Ser Arg Phe Leu Leu Met

1 5 10

<210> 1322

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1322

Ser Leu Leu Thr Ser Ser Ser Asn Leu

fifteen

<210> 1323

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1323

Ser Leu Asn His His Ser Ser Ser Pro Leu

1 5 10

<210> 1324

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1324

Ser Leu Ser Ser Pro Ser Lys Leu Pro Ile

1 5 10

<210> 1325

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1325

Ser Pro Leu Ser Leu His Thr Pro Ser

fifteen

<210> 1326

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1326

Ser Pro Leu Ser Leu His Thr Pro Ser Ser

1 5 10

<210> 1327

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1327

Ser Pro Pro Thr His Ser His Arg Leu

fifteen

<210> 1328

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1328

Ser Pro Arg Leu His Thr Pro Pro Ser

fifteen

<210> 1329

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1329

Ser Pro Arg Leu His Thr Pro Pro Ser Ser

1 5 10

<210> 1330

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1330

Ser Pro Ser Leu Ser Ser Pro Ser Lys Leu

1 5 10

<210> 1331

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1331

Ser Tyr Leu Lys Ile His Leu Gly Leu

fifteen

<210> 1332

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1332

Thr Pro Ser Asn His Arg Pro Arg Pro Leu

1 5 10

<210> 1333

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1333

Thr Pro Ser Ser His Pro Ser Leu His Ile

1 5 10

<210> 1334

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1334

Cys Val Pro Phe Trp Thr Gly Arg Ile Leu

1 5 10

<210> 1335

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1335

His Cys Val Pro Phe Trp Thr Gly Arg Ile Leu

1 5 10

<210> 1336

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1336

Ile Leu Leu Pro Ser Ala Ala Ser Val

fifteen

<210> 1337

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1337

Ile Leu Leu Pro Ser Ala Ala Ser Val Cys

1 5 10

<210> 1338

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1338

Leu Leu Pro Ser Ala Ala Ser Val Cys Pro Ile

1 5 10

<210> 1339

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1339

Leu Pro Ser Ala Ala Ser Val Cys Pro Ile

1 5 10

<210> 1340

<211> 8

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1340

Met Arg Pro His Cys Val Pro Phe

fifteen

<210> 1341

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1341

Arg Ile Leu Leu Pro Ser Ala Ala Ser Val

1 5 10

<210> 1342

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1342

Arg Met Arg Pro His Cys Val Pro Phe

fifteen

<210> 1343

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1343

Arg Met Arg Pro His Cys Val Pro Phe Trp

1 5 10

<210> 1344

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1344

Arg Thr Asn Pro Thr Val Arg Met Arg

fifteen

<210> 1345

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1345

Ser Val Cys Pro Ile Pro Phe Glu Ala

fifteen

<210> 1346

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1346

Thr Val Arg Met Arg Pro His Cys Val

fifteen

<210> 1347

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1347

Thr Val Arg Met Arg Pro His Cys Val Pro Phe

1 5 10

<210> 1348

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1348

Val Pro Phe Trp Thr Gly Arg Ile Leu

fifteen

<210> 1349

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1349

Val Pro Phe Trp Thr Gly Arg Ile Leu Leu

1 5 10

<210> 1350

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1350

Val Arg Met Arg Pro His Cys Val Pro Phe

1 5 10

<210> 1351

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1351

Ala Met Val Pro Arg Gly Val Ser Met

fifteen

<210> 1352

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1352

Ala Met Val Pro Arg Gly Val Ser Met Ala

1 5 10

<210> 1353

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1353

Ala Trp Ala Pro Thr Ser Arg Thr Pro Trp

1 5 10

<210> 1354

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1354

Cys Pro Met Pro Thr Thr Pro Val Gln Ala

1 5 10

<210> 1355

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1355

Cys Pro Ser Thr Val Pro Ser Pro Ala

1 5 10

<210> 1356

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1356

Gly Ala Met Val Pro Arg Gly Val Ser Met

1 5 10

<210> 1357

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1357

Met Pro Cys Pro Met Pro Thr Thr Pro Val

1 5 10

<210> 1358

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1358

Met Pro Thr Thr Pro Val Gln Ala Trp

fifteen

<210> 1359

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1359

Met Pro Thr Thr Pro Val Gln Ala Trp Leu

1 5 10

<210> 1360

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1360

Ser Leu Pro Glu Asp Arg Tyr Thr Gln Ala

1 5 10

<210> 1361

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1361

Ser Pro Ala Gln Pro Tyr Leu Arg Val

fifteen

<210> 1362

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1362

Ser Pro Ala Gln Pro Tyr Leu Arg Val Ser

1 5 10

<210> 1363

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1363

Thr Ile Met Pro Cys Pro Met Pro Thr

fifteen

<210> 1364

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1364

Thr Pro Val Gln Ala Trp Leu Glu Ala

fifteen

<210> 1365

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1365

Thr Ser Arg Thr Pro Trp Gly Ala Met

fifteen

<210> 1366

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1366

Val Pro Pro Ser Pro Ala Gln Pro Tyr Leu

1 5 10

<210> 1367

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1367

Val Pro Arg Gly Val Ser Met Ala His

fifteen

<210> 1368

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1368

Cys Leu Ser Ala Arg Thr Gly Leu Ser Ile

1 5 10

<210> 1369

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1369

Cys Thr Thr Leu Asn Ser Pro Pro Leu Lys

1 5 10

<210> 1370

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1370

Gly Leu Ser Ile Ser Cys Thr Thr Leu

fifteen

<210> 1371

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1371

Ser Pro Pro Leu Lys Lys Met Ser Met

fifteen

<210> 1372

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1372

Thr Leu Asn Ser Pro Pro Leu Lys Lys

fifteen

<210> 1373

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1373

Thr Thr Leu Asn Ser Pro Pro Leu Lys

fifteen

<210> 1374

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1374

Thr Thr Leu Asn Ser Pro Pro Leu Lys Lys

1 5 10

<210> 1375

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1375

Leu Gln Arg Phe Arg Phe Thr His Val

fifteen

<210> 1376

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1376

Leu Gln Arg Phe Arg Phe Thr His Val Ile

1 5 10

<210> 1377

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1377

Arg Leu Ser Ser Val Leu Gln Arg Phe

fifteen

<210> 1378

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1378

Arg Leu Ser Ser Val Leu Gln Arg Phe Arg

1 5 10

<210> 1379

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1379

Val Leu Gln Arg Phe Arg Phe Thr His Val

1 5 10

<210> 1380

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1380

Ala Ser Val Gly Arg His Ser Leu Ser Lys

1 5 10

<210> 1381

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1381

Lys Phe Leu Pro Phe Trp Gly Phe Leu

fifteen

<210> 1382

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1382

Leu Ala Ser Val Gly Arg His Ser Leu

fifteen

<210> 1383

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1383

Leu Pro Phe Trp Gly Phe Leu Glu Glu Phe

1 5 10

<210> 1384

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1384

Pro Phe Trp Gly Phe Leu Glu Glu Phe

fifteen

<210> 1385

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1385

Ser Val Gly Arg His Ser Leu Ser Lys

fifteen

<210> 1386

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1386

Ala Pro Arg Pro Ile Arg Pro Pro Phe

fifteen

<210> 1387

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1387

Ala Pro Arg Pro Ile Arg Pro Pro Phe Leu

1 5 10

<210> 1388

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1388

Ala Gln Lys Met Lys Lys Ala His Phe Leu

1 5 10

<210> 1389

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1389

Phe Leu Pro Ser Ala Ala Gln Lys Met

fifteen

<210> 1390

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1390

Gly Leu Phe Leu Pro Ser Ala Ala Gln Lys

1 5 10

<210> 1391

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1391

His Pro Leu Leu Val Ser Leu Leu Leu

fifteen

<210> 1392

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1392

Lys Ala His Phe Leu Lys Thr Trp Phe Arg

1 5 10

<210> 1393

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1393

Lys Ala Arg Phe Ser Thr Ala Ser Leu

fifteen

<210> 1394

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1394

Lys Met Lys Lys Ala His Phe Leu Lys

fifteen

<210> 1395

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1395

Lys Thr Trp Phe Arg Ser Asn Pro Thr Lys

1 5 10

<210> 1396

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1396

Leu Ala Lys Glu Leu Thr His Pro Leu

fifteen

<210> 1397

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1397

Leu Ala Lys Glu Leu Thr His Pro Leu Leu

1 5 10

<210> 1398

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1398

Asn Pro Thr Lys Thr Lys Lys Ala Arg Phe

1 5 10

<210> 1399

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1399

Gln Lys Met Lys Lys Ala His Phe Leu

fifteen

<210> 1400

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1400

Arg Phe Ser Thr Ala Ser Leu Ala Lys

fifteen

<210> 1401

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1401

Arg Pro Ile Arg Pro Pro Phe Leu Glu Ser

1 5 10

<210> 1402

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1402

Arg Ser Asn Pro Thr Lys Thr Lys Lys

fifteen

<210> 1403

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1403

Ser Leu Ala Lys Glu Leu Thr His Pro Leu

1 5 10

<210> 1404

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1404

Thr Lys Lys Ala Arg Phe Ser Thr Ala

fifteen

<210> 1405

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1405

Gly Leu Arg Phe Trp Asn Pro Ser Arg

fifteen

<210> 1406

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1406

Ile Ser Gln Leu Leu Ser Trp Pro Gln Lys

1 5 10

<210> 1407

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1407

Arg Ile Ala His Ile Ser Gln Leu Leu

fifteen

<210> 1408

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1408

Arg Leu Gly Tyr Ser Ser His Gln Leu

fifteen

<210> 1409

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1409

Ser Gln Leu Leu Ser Trp Pro Gln Lys

fifteen

<210> 1410

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1410

Ser Arg Ile Ala His Ile Ser Gln Leu

fifteen

<210> 1411

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1411

Trp Pro Gln Lys Thr Glu Glu Arg Leu

fifteen

<210> 1412

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1412

Tyr Ser Ser His Gln Leu Pro Arg Lys

fifteen

<210> 1413

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1413

Cys Pro Gln Arg Met Thr Pro Gly Thr Thr

1 5 10

<210> 1414

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1414

Glu Ala Glu Lys Arg Thr Arg Thr Leu

fifteen

<210> 1415

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1415

Gly Thr Thr Phe Ile Thr Met Met Lys

fifteen

<210> 1416

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1416

Gly Thr Thr Phe Ile Thr Met Met Lys Lys

1 5 10

<210> 1417

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1417

Ile Thr Met Met Lys Lys Glu Ala Glu Lys

1 5 10

<210> 1418

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1418

Arg Met Thr Pro Gly Thr Thr Phe Ile

fifteen

<210> 1419

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1419

Ser Pro Tyr Cys Pro Gln Arg Met Thr

fifteen

<210> 1420

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1420

Thr Met Met Lys Lys Glu Ala Glu Lys

fifteen

<210> 1421

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1421

Thr Pro Gly Thr Thr Phe Ile Thr Met

fifteen

<210> 1422

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1422

Thr Pro Gly Thr Thr Phe Ile Thr Met Met

1 5 10

<210> 1423

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1423

Thr Thr Phe Ile Thr Met Met Lys Lys

fifteen

<210> 1424

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1424

Cys Pro Gly Ala Thr Trp Arg Glu Ala

fifteen

<210> 1425

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1425

Cys Pro Gly Ala Thr Trp Arg Glu Ala Ala

1 5 10

<210> 1426

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1426

Arg Ser Arg Cys Pro Gly Ala Thr Trp Arg

1 5 10

<210> 1427

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1427

Thr Pro Arg Ala Thr Arg Ser Arg Cys

fifteen

<210> 1428

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1428

His Val Leu Pro Glu Pro His Leu Ala Leu

1 5 10

<210> 1429

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1429

Arg Pro Leu Gln Thr His Val Leu Pro Glu

1 5 10

<210> 1430

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1430

Val Leu Trp Thr Thr Pro Pro Leu Gln His

1 5 10

<210> 1431

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1431

Ala Pro Ser Glu Ser Pro Cys Ser Pro Phe

1 5 10

<210> 1432

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1432

Cys Pro Leu Asp His Thr Thr Pro Pro Ala

1 5 10

<210> 1433

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1433

Phe Leu Gln Glu Gln Tyr His Glu Ala

fifteen

<210> 1434

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1434

Arg Leu Ala Phe Leu Gln Glu Gln Tyr His

1 5 10

<210> 1435

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1435

Ser Pro Cys Ser Pro Phe Arg Leu Ala Phe

1 5 10

<210> 1436

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1436

Ser Pro Pro Trp Val Arg Ala Leu Leu

fifteen

<210> 1437

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1437

Tyr Pro Ala Cys Pro Leu Asp His Thr Thr

1 5 10

<210> 1438

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1438

Ala Leu His Leu Arg Ser Cys Pro Cys

fifteen

<210> 1439

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1439

Cys Leu His His Arg Arg His Leu Val

fifteen

<210> 1440

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1440

Cys Leu His His Arg Arg His Leu Val Cys

1 5 10

<210> 1441

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1441

Cys Leu His Arg Lys Ser His Pro His Leu

1 5 10

<210> 1442

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1442

Cys Leu Arg Ser His Ala Cys Pro Pro

fifteen

<210> 1443

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1443

Cys Leu Arg Ser His Thr Cys Pro Pro

fifteen

<210> 1444

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1444

Cys Leu Trp Cys His Ala Cys Leu His

fifteen

<210> 1445

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1445

Cys Pro His His Leu Lys Asn His Leu

fifteen

<210> 1446

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1446

Cys Pro His His Leu Lys Asn Leu Leu

fifteen

<210> 1447

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1447

Cys Pro His His Leu Arg Thr Arg Leu

fifteen

<210> 1448

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1448

Cys Pro Leu His Leu Arg Ser Leu Pro Phe

1 5 10

<210> 1449

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1449

Cys Pro Leu Pro Arg His Leu Lys His Leu

1 5 10

<210> 1450

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1450

Cys Pro Leu Ser Leu Arg Ser His Pro Cys

1 5 10

<210> 1451

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1451

Cys Pro Arg His Leu Arg Asn Cys Pro Leu

1 5 10

<210> 1452

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1452

Phe Pro His His Leu Arg His His Ala

fifteen

<210> 1453

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1453

Phe Pro His His Leu Arg His His Ala Cys

1 5 10

<210> 1454

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1454

Gly Leu Arg Ser Arg Thr Cys Pro Pro

fifteen

<210> 1455

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1455

His Ala Cys Leu His Arg Leu Arg Asn Leu

1 5 10

<210> 1456

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1456

His Leu Ala Cys Leu His His Leu Arg

fifteen

<210> 1457

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1457

His Leu Cys Pro Pro His Leu Arg Tyr

fifteen

<210> 1458

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1458

His Leu Cys Pro Pro His Leu Arg Tyr Arg

1 5 10

<210> 1459

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1459

His Leu Lys His Leu Ala Cys Leu His

fifteen

<210> 1460

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1460

His Leu Lys His Arg Pro Cys Pro His

fifteen

<210> 1461

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1461

His Leu Lys Asn His Leu Cys Pro Pro

fifteen

<210> 1462

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1462

His Leu Lys Ser His Pro Cys Leu His

fifteen

<210> 1463

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1463

His Leu Lys Ser Leu Leu Cys Pro Leu

fifteen

<210> 1464

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1464

His Leu Leu His Leu Arg Arg Leu Tyr

fifteen

<210> 1465

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1465

His Leu Arg Asn Cys Pro Leu Pro Arg

fifteen

<210> 1466

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1466

His Leu Arg Asn Cys Pro Leu Pro Arg His

1 5 10

<210> 1467

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1467

His Leu Arg Arg Leu Tyr Pro His His Leu

1 5 10

<210> 1468

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1468

His Leu Arg Ser His Pro Cys Pro Leu

fifteen

<210> 1469

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1469

His Leu Arg Ser His Pro Cys Pro Leu His

1 5 10

<210> 1470

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1470

His Leu Arg Ser Leu Pro Phe Pro His

fifteen

<210> 1471

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1471

His Leu Arg Thr Arg Leu Cys Pro His

fifteen

<210> 1472

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1472

His Leu Val Cys Ser His His Leu Lys

fifteen

<210> 1473

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1473

His Pro Cys Leu His His Arg Arg His Leu

1 5 10

<210> 1474

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1474

His Pro Gly Leu Arg Ser Arg Thr Cys

fifteen

<210> 1475

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1475

His Pro His Leu Leu His Leu Arg Arg Leu

1 5 10

<210> 1476

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1476

His Arg Lys Ser His Pro His Leu Leu

fifteen

<210> 1477

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1477

His Arg Arg Thr Arg Ser Cys Pro Cys

fifteen

<210> 1478

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1478

Lys Ser His Pro His Leu Leu His Leu Arg

1 5 10

<210> 1479

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1479

Lys Ser Leu Leu Cys Pro Leu His Leu Arg

1 5 10

<210> 1480

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1480

Leu Leu Cys Pro Leu His Leu Arg Ser Leu

1 5 10

<210> 1481

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1481

Leu Leu His Leu Arg Arg Leu Tyr Pro His

1 5 10

<210> 1482

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1482

Leu Pro Arg His Leu Lys His Leu Ala

fifteen

<210> 1483

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1483

Leu Pro Arg His Leu Lys His Leu Ala Cys

1 5 10

<210> 1484

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1484

Leu Arg Arg Leu Arg Ser His Thr Cys

fifteen

<210> 1485

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1485

Leu Arg Arg Leu Tyr Pro His His Leu

fifteen

<210> 1486

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1486

Leu Val Cys Ser His His Leu Lys Ser Leu

1 5 10

<210> 1487

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1487

Asn Leu Arg Asn His Thr Cys Pro Pro Ser

1 5 10

<210> 1488

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1488

Pro Leu His Leu Arg Ser Leu Pro Phe

fifteen

<210> 1489

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1489

Arg Leu Cys Pro His His Leu Lys Asn His

1 5 10

<210> 1490

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1490

Arg Leu Tyr Pro His His Leu Lys His

fifteen

<210> 1491

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1491

Arg Leu Tyr Pro His His Leu Lys His Arg

1 5 10

<210> 1492

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1492

Arg Pro Cys Pro His His Leu Lys Asn Leu

1 5 10

<210> 1493

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1493

Arg Ser His Pro Cys Pro Leu His Leu Lys

1 5 10

<210> 1494

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1494

Arg Ser Leu Pro Phe Pro His His Leu Arg

1 5 10

<210> 1495

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1495

Arg Thr Arg Leu Cys Pro His His Leu

fifteen

<210> 1496

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1496

Arg Thr Arg Leu Cys Pro His His Leu Lys

1 5 10

<210> 1497

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1497

Ser Leu Leu Cys Pro Leu His Leu Arg

fifteen

<210> 1498

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1498

Ser Leu Arg Ser His Ala Cys Pro Pro

fifteen

<210> 1499

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1499

Ser Pro Leu Arg Ser Gln Ala Asn Ala

fifteen

<210> 1500

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1500

Tyr Leu Arg Arg Leu Arg Ser His Thr

fifteen

<210> 1501

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1501

Tyr Pro His His Leu Lys His Arg Pro Cys

1 5 10

<210> 1502

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1502

Phe Ile Thr Ser Gly Gln Ile Phe Lys

fifteen

<210> 1503

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1503

Ile Phe Ile Thr Ser Gly Gln Ile Phe

fifteen

<210> 1504

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1504

Ser Gln Ser Glu Ala Leu Cys Val Leu

fifteen

<210> 1505

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1505

Ser Gln Ser Glu Ala Leu Cys Val Leu Leu

1 5 10

<210> 1506

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1506

Ala Tyr Thr Gly Thr Ile Leu Met Met

fifteen

<210> 1507

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1507

Asp Leu Lys Ala Tyr Thr Gly Thr Ile Leu

1 5 10

<210> 1508

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1508

Ile Leu Thr Lys Gln Ile Lys Thr Lys

fifteen

<210> 1509

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1509

Lys Met Ile Leu Thr Lys Gln Ile Lys

fifteen

<210> 1510

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1510

Lys Pro Thr Asp Thr Phe Leu Gln Ile

fifteen

<210> 1511

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1511

Lys Pro Thr Asp Thr Phe Leu Gln Ile Leu

1 5 10

<210> 1512

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1512

Met Ile Leu Thr Lys Gln Ile Lys Thr Lys

1 5 10

<210> 1513

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1513

Ile Thr Arg Tyr Thr Ile Phe Val Leu Lys

1 5 10

<210> 1514

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1514

Leu Ile Ala Glu Leu His Asn Ile Leu

fifteen

<210> 1515

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1515

Leu Ile Ala Glu Leu His Asn Ile Leu Leu

1 5 10

<210> 1516

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1516

Met Thr Pro Pro Asn Leu Ile Ala Glu Leu

1 5 10

<210> 1517

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1517

Asn Leu Ile Ala Glu Leu His Asn Ile

fifteen

<210> 1518

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1518

Asn Leu Ile Ala Glu Leu His Asn Ile Leu

1 5 10

<210> 1519

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1519

Arg Tyr Thr Ile Phe Val Leu Lys Asp Ile

1 5 10

<210> 1520

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1520

Thr Ile Thr Arg Tyr Thr Ile Phe Val Leu

1 5 10

<210> 1521

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1521

Thr Pro Pro Asn Leu Ile Ala Glu Leu

fifteen

<210> 1522

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1522

Phe Leu Gln Phe Arg Thr His Thr Thr

fifteen

<210> 1523

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1523

Leu Pro Ala Lys Gly Glu Asp Ile Phe Leu

1 5 10

<210> 1524

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1524

Leu Gln Phe Arg Thr His Thr Thr Gly Arg

1 5 10

<210> 1525

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1525

Asn Leu Gln Ser Ser Val Cys Gly Leu

fifteen

<210> 1526

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1526

Ser Ser Val Cys Gly Leu Pro Ala Lys

fifteen

<210> 1527

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1527

Val Gln Trp Arg Asn Leu Gln Ser Ser Val

1 5 10

<210> 1528

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1528

Gly Gln Asn Val Ser Leu Leu Gly Lys

fifteen

<210> 1529

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1529

His Thr Arg Thr Arg Gly Asn Leu Arg Lys

1 5 10

<210> 1530

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1530

Ile Leu His Thr Arg Thr Arg Gly Asn Leu

1 5 10

<210> 1531

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1531

Lys Gly Gln Asn Val Ser Leu Leu Gly Lys

1 5 10

<210> 1532

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1532

Leu Leu Gly Lys Tyr Ile Leu His Thr

fifteen

<210> 1533

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1533

Leu Arg Lys Ser Arg Lys Trp Lys Ser Met

1 5 10

<210> 1534

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1534

Ser Leu Leu Gly Lys Tyr Ile Leu His

fifteen

<210> 1535

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1535

Ser Leu Leu Gly Lys Tyr Ile Leu His Thr

1 5 10

<210> 1536

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1536

Cys Thr Ser Pro Leu Leu Ala Pro Val

fifteen

<210> 1537

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1537

Phe Pro Glu Asn Leu Pro Gly Gln Leu

fifteen

<210> 1538

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1538

Gly Leu Leu Ala Phe Trp Asp Ser Gln Val

1 5 10

<210> 1539

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1539

Ile Phe Cys Pro Phe Pro Glu Asn Leu

fifteen

<210> 1540

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1540

Leu Leu Ala Phe Trp Asp Ser Gln Val

fifteen

<210> 1541

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1541

Leu Leu Ala Pro Val Ile Phe Cys Pro

fifteen

<210> 1542

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1542

Leu Leu Ala Pro Val Ile Phe Cys Pro Phe

1 5 10

<210> 1543

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1543

Leu Pro Cys Pro Gln Gln Asp Val Leu

fifteen

<210> 1544

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1544

Arg Phe Pro Ser Gly Leu Leu Ala Phe

fifteen

<210> 1545

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1545

Arg Phe Pro Ser Gly Leu Leu Ala Phe Trp

1 5 10

<210> 1546

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1546

Ser Pro Leu Leu Ala Pro Val Ile Phe

fifteen

<210> 1547

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1547

Ser Pro Arg Gly Pro Cys Thr Ser Ser

fifteen

<210> 1548

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1548

Ser Pro Arg Gly Pro Cys Thr Ser Ser Ser

1 5 10

<210> 1549

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1549

Ser Gln Val Cys Asp Leu His Val Leu

fifteen

<210> 1550

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1550

Val Ile Phe Cys Pro Phe Pro Glu Asn Leu

1 5 10

<210> 1551

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1551

Ala Met Val Trp Pro Leu Leu Ser Ile

fifteen

<210> 1552

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1552

Ala Met Val Trp Pro Leu Leu Ser Ile Leu

1 5 10

<210> 1553

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1553

Ala Gln Ile Ala Met Val Trp Pro Leu

fifteen

<210> 1554

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1554

Ala Gln Ile Ala Met Val Trp Pro Leu Leu

1 5 10

<210> 1555

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1555

Cys Pro Met Ser Arg Leu Arg Leu Ala

fifteen

<210> 1556

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1556

Cys Pro Met Ser Arg Leu Arg Leu Ala Leu

1 5 10

<210> 1557

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1557

Ile Ala Met Val Trp Pro Leu Leu Ser Ile

1 5 10

<210> 1558

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1558

Ile Leu Ser Glu Trp Lys Glu Ile Cys Val

1 5 10

<210> 1559

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1559

Ile Val Trp Trp Cys Pro Met Ser Arg

fifteen

<210> 1560

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1560

Ile Val Trp Trp Cys Pro Met Ser Arg Leu

1 5 10

<210> 1561

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1561

Ile Trp Met Thr Glu Thr Leu Phe Asp Ile

1 5 10

<210> 1562

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1562

Leu Leu Ser Ile Leu Ser Glu Trp Lys

fifteen

<210> 1563

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1563

Met Ser Ala Ala Gln Ile Ala Met Val

fifteen

<210> 1564

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1564

Met Ser Arg Leu Arg Leu Ala Leu Thr

fifteen

<210> 1565

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1565

Met Ser Arg Leu Arg Leu Ala Leu Thr Val

1 5 10

<210> 1566

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1566

Met Val Trp Pro Leu Leu Ser Ile Leu

fifteen

<210> 1567

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1567

Arg Leu Ala Leu Thr Val Pro Pro Ser Thr

1 5 10

<210> 1568

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1568

Thr Leu Phe Asp Ile Val Trp Trp Cys

fifteen

<210> 1569

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1569

Thr Leu Phe Asp Ile Val Trp Trp Cys Pro

1 5 10

<210> 1570

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1570

Thr Met Ser Ala Ala Gln Ile Ala Met Val

1 5 10

<210> 1571

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1571

Val Trp Ser Ile Trp Met Thr Glu Thr Leu

1 5 10

<210> 1572

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1572

Trp Met Thr Glu Thr Leu Phe Asp Ile

fifteen

<210> 1573

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1573

Trp Met Thr Glu Thr Leu Phe Asp Ile Val

1 5 10

<210> 1574

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1574

Ala Leu Arg Cys Val Phe Val Pro Val

fifteen

<210> 1575

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1575

Ala Leu Arg Cys Val Phe Val Pro Val Leu

1 5 10

<210> 1576

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1576

Ala Leu Ser Glu His Cys Pro Thr Thr

fifteen

<210> 1577

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1577

Ala Gln Arg Lys Arg Ile Ser Ala Arg Lys

1 5 10

<210> 1578

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1578

Gly Ala Gln Arg Lys Arg Ile Ser Ala

fifteen

<210> 1579

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1579

His Trp Met Glu Asn Ile Ser Pro Phe

fifteen

<210> 1580

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1580

Leu Pro Ser Gln Arg Arg Asn His Trp

fifteen

<210> 1581

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1581

Leu Pro Ser Gln Arg Arg Asn His Trp Met

1 5 10

<210> 1582

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1582

Asn Ile Ser Pro Phe Arg Ser Val Gly Val

1 5 10

<210> 1583

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1583

Arg Ile Ser Ala Arg Lys Gly Ser Leu

fifteen

<210> 1584

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1584

Ser Pro Phe Arg Ser Val Gly Val Ser Ala

1 5 10

<210> 1585

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1585

Ser Pro Ser Ser His Trp Lys Thr Pro Val

1 5 10

<210> 1586

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1586

Thr Ala Leu Arg Cys Val Phe Val Pro Val

1 5 10

<210> 1587

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1587

Val Ile Tyr Trp Asp Gly Thr Ala Leu

fifteen

<210> 1588

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1588

Val Ile Tyr Trp Asp Gly Thr Ala Leu Arg

1 5 10

<210> 1589

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1589

Val Leu Gly Glu Thr Gly Ala Gln Arg Lys

1 5 10

<210> 1590

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1590

His Pro Arg Pro Arg His Gly His Leu

fifteen

<210> 1591

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1591

His Pro Arg Pro Arg His Gly His Leu Gln

1 5 10

<210> 1592

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1592

Arg Pro Arg His Gly His Leu Gln Ala

fifteen

<210> 1593

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1593

Arg Pro Arg His Gly His Leu Gln Ala Val

1 5 10

<210> 1594

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1594

Gly Ser Leu Lys Thr Gln Val Gln Met Lys

1 5 10

<210> 1595

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1595

Pro Pro Gly Pro Cys His Leu Leu Ser Leu

1 5 10

<210> 1596

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1596

Arg Thr Ile Leu Asn Asn Gly Ser Leu Lys

1 5 10

<210> 1597

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1597

Ser Leu Lys Thr Gln Val Gln Met Lys

fifteen

<210> 1598

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1598

Ser Leu Lys Thr Gln Val Gln Met Lys Leu

1 5 10

<210> 1599

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1599

Thr Ile Leu Asn Asn Gly Ser Leu Lys

fifteen

<210> 1600

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1600

Cys Pro Pro Cys Arg Pro Lys Gln Trp Met

1 5 10

<210> 1601

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1601

Thr Thr Phe Cys Pro Pro Cys Arg Pro Lys

1 5 10

<210> 1602

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1602

Cys Phe Ala Asn Trp Pro Arg Pro Ala Leu

1 5 10

<210> 1603

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1603

Phe Ala Asn Trp Pro Arg Pro Ala Leu

fifteen

<210> 1604

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1604

Gly Leu Ile Pro His Pro Arg Pro Ala

fifteen

<210> 1605

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1605

His Pro Arg Pro Ala Pro Ala Ser Ala

fifteen

<210> 1606

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1606

His Pro Arg Pro Ala Pro Ala Ser Ala Pro

1 5 10

<210> 1607

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1607

Ile Pro His Pro Arg Pro Ala Pro Ala

fifteen

<210> 1608

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1608

Ile Pro His Pro Arg Pro Ala Pro Ala Ser

1 5 10

<210> 1609

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1609

Arg Pro Ala Leu Cys Ser Cys Gly Leu

fifteen

<210> 1610

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1610

Arg Pro Ala Leu Cys Ser Cys Gly Leu Ile

1 5 10

<210> 1611

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1611

Thr Pro Leu Pro Ser Thr Arg Cys Phe

fifteen

<210> 1612

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1612

Trp Pro Arg Pro Ala Leu Cys Ser Cys

fifteen

<210> 1613

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1613

Trp Pro Arg Pro Ala Leu Cys Ser Cys Gly

1 5 10

<210> 1614

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1614

Ala Leu Arg Arg Ser Gly Arg Pro Pro Lys

1 5 10

<210> 1615

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1615

Gly Leu Val Pro Ser Leu Val Ser Lys

fifteen

<210> 1616

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1616

Lys Ile Ser Val Glu Thr Tyr Thr Val

fifteen

<210> 1617

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1617

Leu Leu Met Val Leu Met Ser Leu Asp Leu

1 5 10

<210> 1618

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1618

Leu Met Ser Leu Asp Leu Asp Thr Gly Leu

1 5 10

<210> 1619

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1619

Leu Met Val Leu Met Ser Leu Asp Leu

fifteen

<210> 1620

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1620

Leu Val Ser Lys Cys Leu Ile Leu Arg Val

1 5 10

<210> 1621

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1621

Gln Leu Leu Met Val Leu Met Ser Leu

fifteen

<210> 1622

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1622

Arg Pro Gly Ala Ala Asp Thr Gly Ala

fifteen

<210> 1623

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1623

Arg Pro Gly Ala Ala Asp Thr Gly Ala His

1 5 10

<210> 1624

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1624

Ser Leu Asp Leu Asp Thr Gly Leu Val

fifteen

<210> 1625

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1625

Ser Leu Val Ser Lys Cys Leu Ile Leu

fifteen

<210> 1626

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1626

Ser Gln Leu Leu Met Val Leu Met Ser Leu

1 5 10

<210> 1627

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1627

Thr Val Ser Ser Gln Leu Leu Met Val

fifteen

<210> 1628

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1628

Thr Tyr Thr Val Ser Ser Gln Leu Leu

fifteen

<210> 1629

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1629

Thr Tyr Thr Val Ser Ser Gln Leu Leu Met

1 5 10

<210> 1630

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1630

Val Leu Met Ser Leu Asp Leu Asp Thr

fifteen

<210> 1631

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1631

Val Pro Ser Leu Val Ser Lys Cys Leu

fifteen

<210> 1632

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1632

Val Ser Lys Cys Leu Ile Leu Arg Val Lys

1 5 10

<210> 1633

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1633

Tyr Thr Val Ser Ser Gln Leu Leu Met

fifteen

<210> 1634

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1634

Tyr Thr Val Ser Ser Gln Leu Leu Met Val

1 5 10

<210> 1635

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1635

Phe Cys Gln Tyr His Thr Ala Ser Val

fifteen

<210> 1636

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1636

Cys Pro Tyr Gly Ser Thr Ser Thr Ala

fifteen

<210> 1637

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1637

Cys Pro Tyr Gly Ser Thr Ser Thr Ala Ser

1 5 10

<210> 1638

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1638

Leu Ala Arg Ala Ala Ala Ser Thr Ala Thr

1 5 10

<210> 1639

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1639

Met Leu Thr Asp Ser Leu Phe Leu Pro

fifteen

<210> 1640

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1640

Pro Pro Arg Ser Ser Ser Ala Ile Ala Val

1 5 10

<210> 1641

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1641

Arg Ala Ala Ala Ser Thr Ala Thr Glu Val

1 5 10

<210> 1642

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1642

Ser Pro Pro Arg Ser Ser Ser Ala Ile

fifteen

<210> 1643

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1643

Ser Pro Pro Arg Ser Ser Ser Ala Ile Ala

1 5 10

<210> 1644

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1644

Ser Pro Thr Gln Arg Cys Arg Leu Ala

fifteen

<210> 1645

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1645

Thr Gln Arg Cys Arg Leu Ala Arg Ala

fifteen

<210> 1646

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1646

Thr Gln Arg Cys Arg Leu Ala Arg Ala Ala

1 5 10

<210> 1647

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1647

Lys Ile Trp Lys Thr Thr Gln Met Cys Arg

1 5 10

<210> 1648

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1648

Trp Thr Ser Ser Gly Arg Ser Thr Lys

fifteen

<210> 1649

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1649

Ala Leu Gly Glu Leu Ala Arg Ala Leu

fifteen

<210> 1650

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1650

Ala Gln Leu Arg Arg Arg Ala Ala Ala

fifteen

<210> 1651

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1651

Ala Gln Leu Arg Arg Arg Ala Ala Ala Leu

1 5 10

<210> 1652

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1652

Ala Arg Arg Ala Ala Arg Met Ala Gln Leu

1 5 10

<210> 1653

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1653

His Pro Gln Leu Pro Arg Ser Pro Leu

fifteen

<210> 1654

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1654

His Pro Gln Leu Pro Arg Ser Pro Leu Ala

1 5 10

<210> 1655

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1655

Leu Ala Arg Ala Leu Pro Gly His Leu

fifteen

<210> 1656

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1656

Leu Ala Arg Ala Leu Pro Gly His Leu Leu

1 5 10

<210> 1657

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1657

Met Ala Gln Leu Arg Arg Arg Ala Ala

fifteen

<210> 1658

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1658

Met Ala Gln Leu Arg Arg Arg Ala Ala Ala

1 5 10

<210> 1659

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1659

Gln Leu Arg Arg Arg Ala Ala Ala Leu

fifteen

<210> 1660

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1660

Arg Ala Ala Ala Leu Pro Asn Ala Ala Ala

1 5 10

<210> 1661

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1661

Arg Met Ala Gln Leu Arg Arg Arg Ala Ala

1 5 10

<210> 1662

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1662

Ser Gln Ser Ala Arg Arg Ala Ala Arg Met

1 5 10

<210> 1663

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1663

Gly Met Thr Leu Gly Glu Lys Phe Arg Val

1 5 10

<210> 1664

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1664

Arg Val Gly Asn Cys Lys His Leu Lys

fifteen

<210> 1665

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1665

Gly Pro Ser Glu Pro Gly Asn Asn Ile

fifteen

<210> 1666

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1666

Lys Ile Cys Asn Glu Ser Ala Ser Arg Lys

1 5 10

<210> 1667

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1667

Gly Ile Gln Val Leu Asn Val Ser Leu Lys

1 5 10

<210> 1668

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1668

Ile Gln Val Leu Asn Val Ser Leu Lys

fifteen

<210> 1669

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1669

Lys Ser Ser Ser Asn Val Ile Ser Tyr

fifteen

<210> 1670

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1670

Lys Tyr Gly Trp Ser Leu Leu Arg Val

fifteen

<210> 1671

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1671

Arg Ser Trp Lys Tyr Gly Trp Ser Leu

fifteen

<210> 1672

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1672

Ser Leu Lys Ser Ser Ser Asn Val Ile

fifteen

<210> 1673

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1673

Ser Trp Lys Tyr Gly Trp Ser Leu Leu

fifteen

<210> 1674

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1674

Thr Val Ala Asn Gly Arg Ser Trp Lys

fifteen

<210> 1675

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1675

Val Pro Gln Val Asn Gly Ile Gln Val

fifteen

<210> 1676

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1676

Val Pro Gln Val Asn Gly Ile Gln Val Leu

1 5 10

<210> 1677

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1677

Val Thr Val Ala Asn Gly Arg Ser Trp Lys

1 5 10

<210> 1678

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1678

Trp Ser Leu Leu Arg Val Pro Gln Val

fifteen

<210> 1679

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1679

His Pro Gly Asp Cys Leu Ile Phe Lys Leu

1 5 10

<210> 1680

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1680

Lys Leu Arg Val Pro Gly Ser Ser Val

fifteen

<210> 1681

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1681

Lys Leu Arg Val Pro Gly Ser Ser Val Leu

1 5 10

<210> 1682

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1682

Arg Val Pro Gly Ser Ser Val Leu Val

fifteen

<210> 1683

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1683

Ser Val Leu Val Thr Val Pro Gly Leu

fifteen

<210> 1684

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1684

Val Pro Gly Ser Ser Val Leu Val Thr Val

1 5 10

<210> 1685

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1685

Ala Leu Leu Leu Arg Pro Arg Pro Pro Arg

1 5 10

<210> 1686

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1686

Ala Leu Ser Ala Leu Leu Leu Arg Pro Arg

1 5 10

<210> 1687

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1687

Leu Thr Ile Asn Lys Glu Glu Ala Leu

fifteen

<210> 1688

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1688

Ile Val His Ser Ala Thr Gly Phe Lys

fifteen

<210> 1689

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1689

Ala Thr Gly Phe Lys Gln Ser Ser Lys

fifteen

<210> 1690

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1690

Glu Leu Phe Pro Leu Ile Phe Pro Ala

fifteen

<210> 1691

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1691

Lys Gly Pro Glu Leu Phe Pro Leu Ile

fifteen

<210> 1692

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1692

Lys Gly Pro Glu Leu Phe Pro Leu Ile Phe

1 5 10

<210> 1693

<211> 11

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1693

Lys Pro Thr Asp Ala Pro Pro Lys Ala Gly Val

1 5 10

<210> 1694

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1694

Ala Leu Glu Glu Lys Lys Gly Asn Tyr Val

1 5 10

<210> 1695

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1695

Ile Gln Leu Gln Asp Lys Phe Glu His Leu

1 5 10

<210> 1696

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1696

Gln Leu Gln Asp Lys Phe Glu His Leu

fifteen

<210> 1697

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1697

Gln Leu Gln Asp Lys Phe Glu His Leu Lys

1 5 10

<210> 1698

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1698

Tyr Leu Val Ile Gln Leu Gln Asp Lys Phe

1 5 10

<210> 1699

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1699

Gln Val Tyr Arg Arg Lys His Gln Glu Leu

1 5 10

<210> 1700

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1700

Ser Thr Arg Glu Lys Asn Ser Gln Val

fifteen

<210> 1701

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1701

Val Tyr Arg Arg Lys His Gln Glu Leu

fifteen

<210> 1702

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1702

Val Leu Thr Val Thr Ser Thr Asp Val

fifteen

<210> 1703

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1703

Val Leu Thr Val Thr Ser Thr Asp Val Lys

1 5 10

<210> 1704

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1704

Ile Met Ser Leu Trp Gly Leu Val Ser

fifteen

<210> 1705

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1705

Ile Met Ser Leu Trp Gly Leu Val Ser Lys

1 5 10

<210> 1706

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1706

Lys Leu Lys Gln Glu Ala Thr Ser Lys

fifteen

<210> 1707

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1707

Gln Ile Met Ser Leu Trp Gly Leu Val

fifteen

<210> 1708

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1708

Ser Gln Ile Met Ser Leu Trp Gly Leu

fifteen

<210> 1709

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1709

Ser Gln Ile Met Ser Leu Trp Gly Leu Val

1 5 10

<210> 1710

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1710

Thr Ser Lys Ser Gln Ile Met Ser Leu

fifteen

<210> 1711

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1711

Leu Leu Gln Glu Phe Asp Val Gln Glu Ala

1 5 10

<210> 1712

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1712

Leu Gln Glu Phe Asp Val Gln Glu Ala Leu

1 5 10

<210> 1713

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1713

Gly Pro Arg Glu Pro Arg Asn Arg Thr

fifteen

<210> 1714

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1714

Arg Asn Arg Thr Glu Lys His Ser Thr Met

1 5 10

<210> 1715

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1715

Ala Leu Asn Ser Glu Ala Leu Ser Val Val

1 5 10

<210> 1716

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1716

Met Ala Leu Asn Ser Glu Ala Leu Ser Val

1 5 10

<210> 1717

<211> 67

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1717

Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly

1 5 10 15

Lys Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp

20 25 30

Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg

35 40 45

Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys

50 55 60

Thr Glu Arg

65

<210> 1718

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1718

Thr Met Leu Val Leu Glu Gly Ser Gly Asn Leu Val Leu Tyr Thr Gly

1 5 10 15

Val Val Arg Val Gly Lys Val Phe Ile Pro Gly Leu Pro Ala Pro Ser

20 25 30

Leu Thr Met Ser Asn Thr Met Pro Arg Pro Ser Thr Pro Leu Asp Gly

35 40 45

Val Ser Ala Pro Lys Pro Leu Ser Lys Leu Leu Gly Ser Leu Asp Glu

50 55 60

Val Val Leu Leu Ser Pro Val Pro Glu Leu Arg Asp Ser Ser Lys Leu

65 70 75 80

His Asp Ser Leu Tyr Asn Glu Asp Cys Thr Phe Gln Gln Leu Gly Thr

85 90 95

Tyr Ile His Ser Ile

100

<210> 1719

<211> 90

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1719

Met Arg Glu Pro Ile Tyr Met His Ser Thr Met Val Phe Leu Pro Trp

1 5 10 15

Glu Leu His Thr Lys Lys Gly Pro Ser Pro Pro Glu Gln Phe Met Ala

20 25 30

Val Lys Leu Ser Asp Ser Arg Thr Ala Leu Lys Ser Gly Tyr Gly Lys

35 40 45

Tyr Leu Gly Ile Asn Ser Asp Glu Leu Val Gly His Ser Asp Ala Ile

50 55 60

Gly Pro Arg Glu Gln Trp Glu Pro Val Phe Gln Asn Gly Lys Met Ala

65 70 75 80

Leu Leu Ala Ser Asn Ser Cys Phe Ile Arg

85 90

<210> 1720

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1720

Ala Met Pro Asn Gln Ala Gln Met Arg Ile Leu Lys Glu Thr Glu Leu

1 5 10 15

Arg Lys Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys

20 25 30

Gly Ile Trp Ile Pro Asp Gly Glu Asn Val Lys Ile Pro Val Ala Ile

35 40 45

Lys Val Ser Arg Glu Asn Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu

50 55 60

Asp Glu Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val Ser Arg

65 70 75 80

Leu Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr Gln Leu

85 90 95

Met Pro Tyr Gly Cys

100

<210> 1721

<211> 62

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1721

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Cys Gly Val Gly Lys

1 5 10 15

Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr

20 25 30

Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly

35 40 45

Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu

50 55 60

<210> 1722

<211> 62

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1722

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Asp Gly Val Gly Lys

1 5 10 15

Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr

20 25 30

Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly

35 40 45

Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu

50 55 60

<210> 1723

<211> 62

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1723

Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Val Gly Val Gly Lys

1 5 10 15

Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His Phe Val Asp Glu Tyr

20 25 30

Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Val Ile Asp Gly

35 40 45

Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr Ala Gly Gln Glu

50 55 60

<210> 1724

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1724

Ala Gly Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn

1 5 10 15

His Phe Val Asp Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys

20 25 30

Gln Val Val Ile Asp Gly Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr

35 40 45

Ala Gly His Glu Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg Thr

50 55 60

Gly Glu Gly Phe Leu Cys Val Phe Ala Ile Asn Asn Thr Lys Ser Phe

65 70 75 80

Glu Asp Ile His His Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp Ser

85 90 95

Glu Asp Val Pro Met

100

<210> 1725

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1725

Ala Gly Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn

1 5 10 15

His Phe Val Asp Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys

20 25 30

Gln Val Val Ile Asp Gly Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr

35 40 45

Ala Gly Leu Glu Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg Thr

50 55 60

Gly Glu Gly Phe Leu Cys Val Phe Ala Ile Asn Asn Thr Lys Ser Phe

65 70 75 80

Glu Asp Ile His His Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp Ser

85 90 95

Glu Asp Val Pro Met

100

<210> 1726

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1726

Ala Gly Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn

1 5 10 15

His Phe Val Asp Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys

20 25 30

Gln Val Val Ile Asp Gly Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr

35 40 45

Ala Gly Lys Glu Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg Thr

50 55 60

Gly Glu Gly Phe Leu Cys Val Phe Ala Ile Asn Asn Ser Lys Ser Phe

65 70 75 80

Ala Asp Ile Asn Leu Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp Ser

85 90 95

Asp Asp Val Pro Met

100

<210> 1727

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1727

Ala Gly Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn

1 5 10 15

His Phe Val Asp Glu Tyr Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys

20 25 30

Gln Val Val Ile Asp Gly Glu Thr Cys Leu Leu Asp Ile Leu Asp Thr

35 40 45

Ala Gly Arg Glu Glu Tyr Ser Ala Met Arg Asp Gln Tyr Met Arg Thr

50 55 60

Gly Glu Gly Phe Leu Cys Val Phe Ala Ile Asn Asn Ser Lys Ser Phe

65 70 75 80

Ala Asp Ile Asn Leu Tyr Arg Glu Gln Ile Lys Arg Val Lys Asp Ser

85 90 95

Asp Asp Val Pro Met

100

<210> 1728

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1728

Ala Val Cys Lys Ser Lys Lys Ser Trp Gln Ala Arg His Thr Gly Ile

1 5 10 15

Lys Ile Val Gln Gln Ile Ala Ile Leu Met Gly Cys Ala Ile Leu Pro

20 25 30

His Leu Arg Ser Leu Val Glu Ile Ile Glu His Gly Leu Val Asp Glu

35 40 45

Gln Gln Glu Val Arg Thr Ile Ser Ala Leu Ala Ile Ala Ala Leu Ala

50 55 60

Glu Ala Ala Thr Pro Tyr Gly Ile Glu Ser Phe Asp Ser Val Leu Lys

65 70 75 80

Pro Leu Trp Lys Gly Ile Arg Gln His Arg Gly Lys Gly Leu Ala Ala

85 90 95

Phe Leu Lys Ala Ile

100

<210> 1729

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1729

Tyr Leu Ser Leu Tyr Leu Leu Leu Val Ser Cys Pro Lys Ser Glu Val

1 5 10 15

Arg Ala Lys Phe Lys Phe Ser Ile Leu Asn Ala Lys Gly Glu Glu Thr

20 25 30

Lys Ala Met Glu Ser Gln Arg Ala Tyr Arg Phe Val Gln Gly Lys Asp

35 40 45

Trp Gly Leu Lys Lys Phe Ile Arg Arg Asp Phe Leu Leu Asp Glu Ala

50 55 60

Asn Gly Leu Leu Pro Asp Asp Lys Leu Thr Leu Phe Cys Glu Val Ser

65 70 75 80

Val Val Gln Asp Ser Val Asn Ile Ser Gly Gln Asn Thr Met Asn Met

85 90 95

Val Lys Val Pro Glu

100

<210> 1730

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1730

Tyr Leu Ser Leu Tyr Leu Leu Leu Val Ser Cys Pro Lys Ser Glu Val

1 5 10 15

Arg Ala Lys Phe Lys Phe Ser Ile Leu Asn Ala Lys Gly Glu Glu Thr

20 25 30

Lys Ala Met Glu Ser Gln Arg Ala Tyr Arg Phe Val Gln Gly Lys Asp

35 40 45

Trp Gly Val Lys Lys Phe Ile Arg Arg Asp Phe Leu Leu Asp Glu Ala

50 55 60

Asn Gly Leu Leu Pro Asp Asp Lys Leu Thr Leu Phe Cys Glu Val Ser

65 70 75 80

Val Val Gln Asp Ser Val Asn Ile Ser Gly Gln Asn Thr Met Asn Met

85 90 95

Val Lys Val Pro Glu

100

<210> 1731

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1731

Pro Glu Val Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys

1 5 10 15

Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile

20 25 30

Ile Thr Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe

35 40 45

Glu Val His Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu Glu

50 55 60

Glu Asn Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro Pro Gly

65 70 75 80

Ser Thr Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser Pro Gln Pro

85 90 95

Lys Lys Lys Pro Leu

100

<210> 1732

<211> 101

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1732

Thr Glu Val Val Arg Arg Cys Pro His His Glu Arg Cys Ser Asp Ser

1 5 10 15

Asp Gly Leu Ala Pro Pro Gln His Leu Ile Arg Val Glu Gly Asn Leu

20 25 30

Arg Val Glu Tyr Leu Asp Asp Arg Asn Thr Phe Arg His Ser Val Val

35 40 45

Val Pro Cys Glu Pro Pro Glu Val Gly Ser Asp Cys Thr Thr Ile His

50 55 60

Tyr Asn Tyr Met Cys Asn Ser Ser Cys Met Gly Gly Met Asn Arg Arg

65 70 75 80

Pro Ile Leu Thr Ile Ile Thr Leu Glu Asp Ser Ser Gly Asn Leu Leu

85 90 95

Gly Arg Asn Ser Phe

100

<210> 1733

<211> 54

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1733

Tyr Asn Phe Asp Lys Asn Tyr Lys Asp Trp Gln Ser Ala Val Glu Cys

1 5 10 15

Ile Ala Val Leu Asp Val Leu Leu Cys Leu Ala Asn Tyr Ser Arg Gly

20 25 30

Gly Asp Gly Pro Met Cys Arg Pro Val Ile Leu Leu Pro Glu Asp Thr

35 40 45

Pro Pro Leu Leu Arg Ala

fifty

<210> 1734

<211> 67

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1734

Arg Ser Tyr Arg Arg Met Ile His Leu Trp Trp Thr Ala Gln Ile Ser

1 5 10 15

Leu Gly Val Cys Arg Ser Leu Thr Val Ala Cys Cys Thr Gly Gly Leu

20 25 30

Val Gly Gly Thr Pro Leu Ser Ile Ser Arg Pro Thr Ser Arg Ala Arg

35 40 45

Gln Ser Cys Cys Leu Pro Gly Leu Thr His Pro Ala His Gln Pro Leu

50 55 60

Gly Ser Met

65

<210> 1735

<211> 60

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1735

Gln His Ser Gly Arg Asp Val Ser Leu Arg Gly Leu Ser Cys Ala Arg

1 5 10 15

Ala Thr Leu Ser Phe Trp Pro Gly Gly Tyr Pro Ala Tyr Ser Lys Asp

20 25 30

Ser Gly Leu Leu Thr Ser Ser Ser Arg Glu Trp Lys Val Lys Phe Pro

35 40 45

Glu Leu Leu Cys Val Trp Val Ser Ser Ile Arg His

50 55 60

<210> 1736

<211> 48

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1736

Ala Gln Ala Lys Ala Val Cys Ser Gln Glu Ser Arg Asp Val Leu Cys

1 5 10 15

Glu Leu Ser Asp His His Asn His Thr Leu Glu Glu Glu Glu Cys Gln Trp

20 25 30

Gly Pro Cys Leu Gln Cys Leu Trp Ala Leu Leu Gln Ala Ser Gln Tyr

35 40 45

<210> 1737

<211> 35

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1737

Gly Pro Arg Ser His Pro Leu Pro Arg Leu Trp His Leu Leu Leu Gln

1 5 10 15

Val Thr Gln Thr Ser Phe Ala Leu Ala Pro Thr Leu Thr His Met Leu

20 25 30

Ser Pro His

35

<210> 1738

<211> 172

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1738

Pro Leu Gly Leu Val Pro Trp Thr Arg Trp Cys Pro Gln Gly Lys Pro

1 5 10 15

Arg Phe Pro Ala Met Ser Thr Thr Thr Ala Thr Gly Thr Thr Thr Thr

20 25 30

Lys Ser Gly Ser Ser Gly Met Ala Gly Ser Leu Ala Gln Lys Pro Glu

35 40 45

Ser Pro Ser Pro Gly Leu Leu Phe Leu Gly His Ser Pro Ser Gln Ser

50 55 60

His Leu Leu Leu Ile Ser Lys Ser Pro Asp Pro Thr Gln Gln Pro Leu

65 70 75 80

Arg Gly Gly Ser Leu Thr His Ser Ala Pro Gly Pro Ser Leu Ser Gln

85 90 95

Pro Leu Ala Gln Leu Thr Pro Pro Ala Ser Ala Pro Val Pro Ala Val

100 105 110

Cys Ser Thr Cys Lys Asn Pro Ala Ser Leu Pro Asp Thr His Arg Gly

115 120 125

Lys Gly Gly Gly Val Pro Pro Ser Pro Pro Leu Ala Leu Gly Pro Arg

130 135 140

Met Gln Leu Cys Thr Gln Leu Ala Arg Phe Phe Pro Ile Thr Pro Pro

145 150 155 160

Val Trp His Ile Leu Gly Pro Gln Arg His Thr Pro

165 170

<210> 1739

<211> 77

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1739

Ser Gln Gly Leu Tyr Ser Ser Ser Ala Ser Ser Gly Lys Cys Leu Met

1 5 10 15

Glu Val Thr Val Asp Arg Asn Cys Leu Glu Val Leu Pro Thr Lys Met

20 25 30

Ser Tyr Ala Ala Asn Leu Lys Asn Val Met Asn Met Gln Asn Arg Gln

35 40 45

Lys Lys Lys Gly Lys Asn Ser Pro Cys Cys Gln Lys Lys Leu Arg Val

50 55 60

Gln Asn Gln Gly His Leu Leu Met Ile Leu Leu His Asn

65 70 75

<210> 1740

<211> 104

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

polypeptide

<400> 1740

Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly Ile Trp Ile Pro

1 5 10 15

Asp Gly Glu Asn Val Lys Ile Pro Val Ala Ile Lys Val Leu Arg Glu

20 25 30

Asn Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val

35 40 45

Met Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val Ser Arg Leu

50 55 60

Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr Gln Leu Met

65 70 75 80

Pro Tyr Gly Cys Leu Leu Asp His Val Arg Glu Asn Arg Gly Arg Leu

85 90 95

Gly Ser Gln Asp Leu Leu Asn Trp

100

<210> 1741

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1741

Lys Tyr Ile Lys Thr Trp Arg Pro Arg Tyr

1 5 10

<210> 1742

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1742

Trp Leu His Lys Arg Gly Lys Tyr Ile

fifteen

<210> 1743

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1743

Trp Leu His Lys Arg Gly Lys Tyr Ile Lys

1 5 10

<210> 1744

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1744

Ala Pro Lys Pro Leu Ser Lys Leu Leu

fifteen

<210> 1745

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1745

Gly Val Ser Ala Pro Lys Pro Leu Ser Lys

1 5 10

<210> 1746

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1746

Val Ser Ala Pro Lys Pro Leu Ser Lys

fifteen

<210> 1747

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1747

Lys Leu Ser Asp Ser Arg Thr Ala Leu

fifteen

<210> 1748

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1748

Lys Leu Ser Asp Ser Arg Thr Ala Leu Lys

1 5 10

<210> 1749

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1749

Leu Ser Asp Ser Arg Thr Ala Leu Lys

fifteen

<210> 1750

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1750

Arg Thr Ala Leu Lys Ser Gly Tyr Gly Lys

1 5 10

<210> 1751

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1751

Thr Ala Leu Lys Ser Gly Tyr Gly Lys

fifteen

<210> 1752

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1752

Ala Leu Ser Ala Ser Asn Ser Cys Phe Ile

1 5 10

<210> 1753

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1753

Lys Val Ser Arg Glu Asn Thr Ser Pro Lys

1 5 10

<210> 1754

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1754

Leu Val Val Val Gly Ala Cys Gly Val

fifteen

<210> 1755

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1755

Val Val Gly Ala Cys Gly Val Gly Lys

fifteen

<210> 1756

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1756

Val Val Val Gly Ala Cys Gly Val Gly Lys

1 5 10

<210> 1757

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1757

Val Val Gly Ala Asp Gly Val Gly Lys

fifteen

<210> 1758

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1758

Val Val Val Gly Ala Asp Gly Val Gly Lys

1 5 10

<210> 1759

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1759

Lys Leu Val Val Val Gly Ala Asp Gly Val

1 5 10

<210> 1760

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1760

Leu Val Val Val Gly Ala Asp Gly Val

fifteen

<210> 1761

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1761

Lys Leu Val Val Val Gly Ala Val Gly Val

1 5 10

<210> 1762

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1762

Leu Val Val Val Gly Ala Val Gly Val

fifteen

<210> 1763

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1763

Val Val Gly Ala Val Gly Val Gly Lys

fifteen

<210> 1764

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1764

Val Val Val Gly Ala Val Gly Val Gly Lys

1 5 10

<210> 1765

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1765

Ile Leu Asp Thr Ala Gly His Glu Glu Tyr

1 5 10

<210> 1766

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1766

Ile Leu Asp Thr Ala Gly Leu Glu Glu Tyr

1 5 10

<210> 1767

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1767

Leu Leu Asp Ile Leu Asp Thr Ala Gly Leu

1 5 10

<210> 1768

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1768

Ile Leu Asp Thr Ala Gly Lys Glu Glu Tyr

1 5 10

<210> 1769

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1769

Ile Leu Asp Thr Ala Gly Arg Glu Glu Tyr

1 5 10

<210> 1770

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1770

Gly Leu Val Asp Glu Gln Gln Glu Val

fifteen

<210> 1771

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1771

Phe Val Gln Gly Lys Asp Trp Gly Leu

fifteen

<210> 1772

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1772

Phe Val Gln Gly Lys Asp Trp Gly Val

fifteen

<210> 1773

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1773

Asn Ser Phe Glu Val His Val Cys Ala

fifteen

<210> 1774

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1774

Val Val Pro Cys Glu Pro Pro Glu Val

fifteen

<210> 1775

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1775

Val Val Val Pro Cys Glu Pro Pro Glu Val

1 5 10

<210> 1776

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1776

Ile Leu Leu Pro Glu Asp Thr Pro Pro Leu

1 5 10

<210> 1777

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1777

Leu Leu Pro Glu Asp Thr Pro Pro Leu

fifteen

<210> 1778

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1778

Cys Leu Pro Gly Leu Thr His Pro Ala

fifteen

<210> 1779

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1779

Gly Leu Thr His Pro Ala His Gln Pro Leu

1 5 10

<210> 1780

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1780

His Pro Ala His Gln Pro Leu Gly Ser Met

1 5 10

<210> 1781

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1781

Leu Thr His Pro Ala His Gln Pro Leu

fifteen

<210> 1782

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1782

Arg Pro Thr Ser Arg Ala Arg Gln Ser Cys

1 5 10

<210> 1783

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1783

Arg Gln Ser Cys Cys Leu Pro Gly Leu

fifteen

<210> 1784

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1784

Thr Ser Arg Ala Arg Gln Ser Cys Cys Leu

1 5 10

<210> 1785

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1785

Cys Leu Gln Cys Leu Trp Ala Leu Leu

fifteen

<210> 1786

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1786

Cys Gln Trp Gly Pro Cys Leu Gln Cys Leu

1 5 10

<210> 1787

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1787

Gln Trp Gly Pro Cys Leu Gln Cys Leu

fifteen

<210> 1788

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1788

Gln Trp Gly Pro Cys Leu Gln Cys Leu Trp

1 5 10

<210> 1789

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1789

Gly Pro Arg Gly Arg Thr Cys His Pro Gly

1 5 10

<210> 1790

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1790

Ala Leu Ala Pro Thr Leu Thr His Met

fifteen

<210> 1791

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1791

Ala Leu Ala Pro Thr Leu Thr His Met Leu

1 5 10

<210> 1792

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1792

Leu Leu Gln Val Thr Gln Thr Ser Phe Ala

1 5 10

<210> 1793

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1793

Leu Gln Val Thr Gln Thr Ser Phe Ala Leu

1 5 10

<210> 1794

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1794

Arg Leu Trp His Leu Leu Leu Gln Val

fifteen

<210> 1795

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1795

Arg Leu Trp His Leu Leu Leu Gln Val Thr

1 5 10

<210> 1796

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1796

Cys Thr Gln Leu Ala Arg Phe Phe Pro Ile

1 5 10

<210> 1797

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1797

Phe Phe Pro Ile Thr Pro Pro Val Trp

fifteen

<210> 1798

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1798

Phe Pro Ile Thr Pro Pro Val Trp His Ile

1 5 10

<210> 1799

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1799

Gly Pro Arg Met Gln Leu Cys Thr Gln Leu

1 5 10

<210> 1800

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1800

Ile Thr Pro Pro Val Trp His Ile Leu

fifteen

<210> 1801

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1801

Leu Ala Leu Gly Pro Arg Met Gln Leu

fifteen

<210> 1802

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1802

Met Gln Leu Cys Thr Gln Leu Ala Arg Phe

1 5 10

<210> 1803

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1803

Arg Phe Phe Pro Ile Thr Pro Pro Val

fifteen

<210> 1804

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1804

Arg Phe Phe Pro Ile Thr Pro Pro Val Trp

1 5 10

<210> 1805

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1805

Arg Met Gln Leu Cys Thr Gln Leu Ala

fifteen

<210> 1806

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1806

Arg Met Gln Leu Cys Thr Gln Leu Ala Arg

1 5 10

<210> 1807

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1807

Ser Pro Pro Leu Ala Leu Gly Pro Arg Met

1 5 10

<210> 1808

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1808

Thr Gln Leu Ala Arg Phe Phe Pro Ile

fifteen

<210> 1809

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1809

Arg Val Gln Asn Gln Gly His Leu Leu

fifteen

<210> 1810

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1810

Ile Leu Asp Glu Ala Tyr Val Met Ala Tyr

1 5 10

<210> 1811

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1811

Val Met Ala Tyr Val Met Ala Gly Val

fifteen

<210> 1812

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1812

Tyr Val Met Ala Tyr Val Met Ala Gly

fifteen

<210> 1813

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1813

Tyr Val Met Ala Tyr Val Met Ala Gly Val

1 5 10

<210> 1814

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1814

Ala Val Glu Trp

one

<210> 1815

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1815

Val His Pro Ala

one

<210> 1816

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1816

Met Pro Ala Val

one

<210> 1817

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1817

Ser Ile Arg His

one

<210> 1818

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1818

Ser Gln Ile Ser

one

<210> 1819

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1819

Cys Ser Asn His

one

<210> 1820

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1820

Tyr His Glu Ala

one

<210> 1821

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1821

Tyr Val Met Ala

one

<210> 1822

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1822

Leu Ser Pro His

one

<210> 1823

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1823

Cys Arg Leu Ser

one

<210> 1824

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1824

Arg His Thr Pro

one

<210> 1825

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1825

Ala Ala Val Gly

one

<210> 1826

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1826

Ala Trp Ala Ala

one

<210> 1827

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1827

Cys Ser Glu Ser

one

<210> 1828

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1828

Gln Pro Ser Leu

one

<210> 1829

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1829

Ser His Ser Thr

one

<210> 1830

<211> 4

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1830

Gln Cys Ile Leu

one

<210> 1831

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1831

Ser Leu Met Pro Ala His Trp Ser Ile

fifteen

<210> 1832

<211> 10

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1832

Leu Ser Leu Met Pro Ala His Trp Ser Ile

1 5 10

<210> 1833

<211> 9

<212> Protein

<213> Artificial sequence

<220>

<223> Artificial sequence description: synthetic

peptide

<400> 1833

Phe Gln Met Gln Pro Leu Ser Leu Met

fifteen

<210> 1834

<211> 6

<212> Protein

<213> Artificial sequence

<220>

<223> Synthetic sequence description: synthetic

label 6xHis

<400> 1834

His His His His His His His

fifteen

<---

Claims (33)

1. Pharmaceutical composition for use in the treatment of breast cancer in a subject, containing: (i) an effective amount of a recombinant or synthetic neoantigenic peptide or an effective amount of a polynucleotide expression vector encoding a recombinant neoantigenic peptide; and (ii) a pharmaceutically acceptable excipient; wherein the neoantigenic peptide comprises a tumor-specific neoepitope comprising one or more contiguous mutant amino acids encoded by a sequence obtained by a frameshift mutation in the GATA3 gene, wherein the tumor-specific neoepitope is encoded by the GATA3 gene of the subject's cancer cells or is expressed by the subject's cancer cells, and wherein the tumor-specific neoepitope is not expressed by the subject's non-cancerous cells or not encoded by the GATA3 genome of non-cancerous cells, where neoantigenic peptide has a length of 8 to 100 amino acids; and where: (a) the subject expresses a major histocompatibility complex (MHC) encoded by the HLA B07:02 allele and the tumor-specific neoepitope is EPHLALQPL or MFATLQRSSL; (b) the subject expresses MHC encoded by the HLA B08:01 allele and the tumor specific neoepitope is EPHLALQPL, FLKAESKIMF, IMKPKRDGYM, LHFCRSSIM, MFATLQRSSL, or YMFLKAESKI; (c) the subject expresses MHC encoded by the HLA A24:02 allele and the tumor-specific neoepitope is MFLKAESKI; (d) the subject expresses MHC encoded by the HLA A02:01 allele and the tumor-specific neoepitope is VLPEPHLAL; and/or (e) the subject expresses MHC encoded by the HLA A03:01 allele and the tumor-specific neoepitope is VLWTTPPLQH. 2. The pharmaceutical composition of claim 1, wherein the tumor-specific neoepitope binds to a class I MHC molecule with a binding affinity of 500 nM or less. 3. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence VLWTTPPLQH (SEQ ID NO: 1430) and the subject expresses an MHC molecule encoded by the A03:01 HLA allele. 4. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence EPHLALQPL (SEQ ID NO: 529) and the subject expresses an MHC molecule encoded by the B07:02 or B08:01 HLA allele. 5. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence FLKAESKIMF (SEQ ID NO: 536) and the subject expresses an MHC molecule encoded by the B08:01 HLA allele. 6. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence IMKPKRDGYM (SEQ ID NO: 550) and the subject expresses an MHC molecule encoded by the B08:01 HLA allele. 7. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence LHFCRSSIM (SEQ ID NO: 556) and the subject expresses an MHC molecule encoded by the B08:01 HLA allele. 8. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence MFATLQRSSL (SEQ ID NO: 567) and the subject expresses an MHC molecule encoded by the B07:02 or B08:01 HLA allele. 9. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence MFLKAESKI (SEQ ID NO: 568) and the subject expresses an MHC molecule encoded by the A24:02 HLA allele. 10. The pharmaceutical composition according to claim 1, wherein the tumor-specific neoepitope has the sequence VLPEPHLAL (SEQ ID NO: 594) and the subject expresses an MHC molecule encoded by the A02.01 HLA allele. 11. The pharmaceutical composition of claim 1 wherein the breast cancer is selected from the group consisting of metastatic breast cancer, invasive breast carcinoma, NS luminal type breast carcinoma, HER-2 positive breast cancer, and MSI+ breast cancer. 12. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition further comprises an adjuvant. 13. A pharmaceutical composition according to claim 1 for use in the treatment of breast cancer in a subject in combination with an immune checkpoint inhibitor. 14. A pharmaceutical composition according to claim 1 for use in the treatment of breast cancer in a subject in combination with letrozole. 15. A pharmaceutical composition according to claim 1 for use in the treatment of breast cancer in a subject in combination with a fulvestrant. 16. The pharmaceutical composition according to claim 1, wherein the polynucleotide encoding the recombinant neoantigenic peptide is DNA. 17. The pharmaceutical composition according to claim 1, wherein the polynucleotide encoding the recombinant neoantigenic peptide is messenger RNA (mRNA). 18. The pharmaceutical composition according to claim 1, wherein the polynucleotide expression vector encoding the recombinant neoantigenic peptide is an RNA expression vector. 19. The pharmaceutical composition according to claim 1, wherein the recombinant or synthetic neoantigenic peptide contains more than 10 amino acid residues. 20. The pharmaceutical composition of claim 19, wherein each of the amino acids of the recombinant or synthetic neoantigenic peptide is a mutant amino acid encoded by the reading frame. 21. The pharmaceutical composition of claim 20, wherein the recombinant or synthetic neoantigenic peptide is endogenously processed. 22. The pharmaceutical composition of claim 20, wherein the sequence of the recombinant or synthetic neoantigenic peptide contains one or more changes to improve the biochemical property of the polypeptide. 23. The pharmaceutical composition of claim 22, wherein the recombinant or synthetic neoantigenic peptide contains one or more changes to increase the likelihood of efficient proteasome processing of the peptide.

Images