                         SEQUENCE LISTING

<110>  SANOFI
 
<120>  THERAPEUTIC RNA AND ANTI-PD1 ANTIBODIES FOR ADVANCED STAGE SOLID 
       TUMOR CANCERS

<130>  01183-0031-00PCT

<150>  US 62/794,896
<151>  2019-01-21

<150>  US 62/926,379
<151>  2019-10-25

<150>  EP 19306471.4
<151>  2019-11-14

<160>  41    

<170>  PatentIn version 3.5

<210>  1

<400>  1
000

<210>  2

<400>  2
000

<210>  3
<211>  145
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: 5 UTR (DNA)

<400>  3
ggaataaact agtctcaaca caacatatac aaaacaaacg aatctcaagc aatcaagcat       60

tctacttcta ttgcagcaat ttaaatcatt tcttttaaag caaaagcaat tttctgaaaa      120

ttttcaccat ttacgaacga tagcc                                            145


<210>  4
<211>  145
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: 5 UTR (RNA)

<400>  4
ggaauaaacu agucucaaca caacauauac aaaacaaacg aaucucaagc aaucaagcau       60

ucuacuucua uugcagcaau uuaaaucauu ucuuuuaaag caaaagcaau uuucugaaaa      120

uuuucaccau uuacgaacga uagcc                                            145


<210>  5
<211>  52
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Alternative Mod 5 UTR (DNA)

<400>  5
agacgaacta gtattcttct ggtccccaca gactcagaga gaacccgcca cc               52


<210>  6
<211>  52
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Alternative Mod 5 UTR (RNA)

<400>  6
agacgaacua guauucuucu gguccccaca gacucagaga gaacccgcca cc               52


<210>  7
<211>  317
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: 3 UTR (DNA)

<400>  7
ctcgagctgg tactgcatgc acgcaatgct agctgcccct ttcccgtcct gggtaccccg       60

agtctccccc gacctcgggt cccaggtatg ctcccacctc cacctgcccc actcaccacc      120

tctgctagtt ccagacacct cccaagcacg cagcaatgca gctcaaaacg cttagcctag      180

ccacaccccc acgggaaaca gcagtgatta acctttagca ataaacgaaa gtttaactaa      240

gctatactaa ccccagggtt ggtcaatttc gtgccagcca caccgagacc tggtccagag      300

tcgctagccg cgtcgct                                                     317


<210>  8
<211>  317
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: 3 UTR (RNA)

<400>  8
cucgagcugg uacugcaugc acgcaaugcu agcugccccu uucccguccu ggguaccccg       60

agucuccccc gaccucgggu cccagguaug cucccaccuc caccugcccc acucaccacc      120

ucugcuaguu ccagacaccu cccaagcacg cagcaaugca gcucaaaacg cuuagccuag      180

ccacaccccc acgggaaaca gcagugauua accuuuagca auaaacgaaa guuuaacuaa      240

gcuauacuaa ccccaggguu ggucaauuuc gugccagcca caccgagacc ugguccagag      300

ucgcuagccg cgucgcu                                                     317


<210>  9

<400>  9
000

<210>  10

<400>  10
000

<210>  11

<400>  11
000

<210>  12

<400>  12
000

<210>  13

<400>  13
000

<210>  14
<211>  539
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(539)
<223>  Human IL-12sc (amino acid)

<400>  14

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu 
1               5                   10                  15      


Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val 
            20                  25                  30          


Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu 
        35                  40                  45              


Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln 
    50                  55                  60                  


Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys 
65                  70                  75                  80  


Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val 
                85                  90                  95      


Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp 
            100                 105                 110         


Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe 
        115                 120                 125             


Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp 
    130                 135                 140                 


Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser 
                165                 170                 175     


Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu 
            180                 185                 190         


Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile 
        195                 200                 205             


Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr 
    210                 215                 220                 


Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn 
225                 230                 235                 240 


Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp 
                245                 250                 255     


Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr 
            260                 265                 270         


Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg 
        275                 280                 285             


Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala 
    290                 295                 300                 


Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser 
305                 310                 315                 320 


Glu Trp Ala Ser Val Pro Cys Ser Gly Ser Ser Gly Gly Gly Gly Ser 
                325                 330                 335     


Pro Gly Gly Gly Ser Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro 
            340                 345                 350         


Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val 
        355                 360                 365             


Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys 
    370                 375                 380                 


Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser 
385                 390                 395                 400 


Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys 
                405                 410                 415     


Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala 
            420                 425                 430         


Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr 
        435                 440                 445             


Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys 
    450                 455                 460                 


Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu 
465                 470                 475                 480 


Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr 
                485                 490                 495     


Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys 
            500                 505                 510         


Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr 
        515                 520                 525             


Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
    530                 535                 


<210>  15
<211>  1623
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(1623)
<223>  Human non-optimized IL-12sc (CDS DNA)

<400>  15
atgtgtcacc agcagttggt catctcttgg ttttccctgg tttttctggc atctcccctc       60

gtggccatat gggaactgaa gaaagatgtt tatgtcgtag aattggattg gtatccggat      120

gcccctggag aaatggtggt cctcacctgt gacacccctg aagaagatgg tatcacctgg      180

accttggacc agagcagtga ggtcttaggc tctggcaaaa ccctgaccat ccaagtcaaa      240

gagtttggag atgctggcca gtacacctgt cacaaaggag gcgaggttct aagccattcg      300

ctcctgctgc ttcacaaaaa ggaagatgga atttggtcca ctgatatttt aaaggaccag      360

aaagaaccca aaaataagac ctttctaaga tgcgaggcca agaattattc tggacgtttc      420

acctgctggt ggctgacgac aatcagtact gatttgacat tcagtgtcaa aagcagcaga      480

gggtcttctg acccccaagg ggtgacgtgc ggagctgcta cactctctgc agagagagtc      540

agaggggaca acaaggagta tgagtactca gtggagtgcc aggaggacag tgcctgccca      600

gctgctgagg agagtctgcc cattgaggtc atggtggatg ccgttcacaa gctcaagtat      660

gaaaactaca ccagcagctt cttcatcagg gacatcatca aacctgaccc acccaagaac      720

ttgcagctga agccattaaa gaattctcgg caggtggagg tcagctggga gtaccctgac      780

acctggagta ctccacattc ctacttctcc ctgacattct gcgttcaggt ccagggcaag      840

agcaagagag aaaagaaaga tagagtcttc acggacaaga cctcagccac ggtcatctgc      900

cgcaaaaatg ccagcattag cgtgcgggcc caggaccgct actatagctc atcttggagc      960

gaatgggcat ctgtgccctg cagtggctct agcggagggg gaggctctcc tggcggggga     1020

tctagcagaa acctccccgt ggccactcca gacccaggaa tgttcccatg ccttcaccac     1080

tcccaaaacc tgctgagggc cgtcagcaac atgctccaga aggccagaca aactctagaa     1140

ttttaccctt gcacttctga ggaaattgat catgaagata tcacaaaaga taaaaccagc     1200

acagtggagg cctgtttacc attggaatta accaagaatg agagttgcct aaattccaga     1260

gagacctctt tcataactaa tgggagttgc ctggcctcca gaaagacctc ttttatgatg     1320

gccctgtgcc ttagtagtat ttatgaagac ttgaagatgt accaggtgga gttcaagacc     1380

atgaatgcaa agcttctgat ggatcctaag aggcagatct ttctagatca aaacatgctg     1440

gcagttattg atgagctgat gcaggccctg aatttcaaca gtgagactgt gccacaaaaa     1500

tcctcccttg aagaaccgga tttttataaa actaaaatca agctctgcat acttcttcat     1560

gctttcagaa ttcgggcagt gactattgat agagtgatga gctatctgaa tgcttcctga     1620

tga                                                                   1623


<210>  16
<211>  1623
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(1623)
<223>  Human optimized IL-12sc (CDS DNA)

<400>  16
atgtgtcacc agcagctggt gatctcatgg ttctccctgg tatttctggc atctcctctt       60

gtcgcaatct gggaactgaa gaaagacgtg tatgtcgttg agctcgactg gtatccggat      120

gcgcctggcg agatggtggt gctgacctgt gacaccccag aggaggatgg gatcacttgg      180

acccttgatc aatcctccga agtgctcggg tctggcaaga ctctgaccat acaagtgaaa      240

gagtttggcg atgccgggca gtacacttgc cataagggcg gagaagttct gtcccactca      300

ctgctgctgc tgcacaagaa agaggacgga atttggagta ccgatatcct gaaagatcag      360

aaagagccca agaacaaaac cttcttgcgg tgcgaagcca agaactactc agggagattt      420

acttgttggt ggctgacgac gatcagcacc gatctgactt tctccgtgaa atcaagtagg      480

ggatcatctg accctcaagg agtcacatgt ggagcggcta ctctgagcgc tgaacgcgta      540

agaggggaca ataaggagta cgagtatagc gttgagtgcc aagaggatag cgcatgcccc      600

gccgccgaag aatcattgcc cattgaagtg atggtggatg ctgtacacaa gctgaagtat      660

gagaactaca caagctcctt cttcatccgt gacatcatca aaccagatcc tcctaagaac      720

ctccagctta aacctctgaa gaactctaga caggtggaag tgtcttggga gtatcccgac      780

acctggtcta caccacattc ctacttcagt ctcacattct gcgttcaggt acagggcaag      840

tccaaaaggg agaagaagga tcgggtcttt acagataaaa caagtgccac cgttatatgc      900

cggaagaatg cctctatttc tgtgcgtgcg caggacagat actatagcag ctcttggagt      960

gaatgggcca gtgtcccatg ttcagggtca tccggtggtg gcggcagccc cggaggcggt     1020

agctccagaa atctccctgt ggctacacct gatccaggca tgtttccctg tttgcaccat     1080

agccaaaacc tcctgagagc agtcagcaac atgctccaga aagctagaca aacactggaa     1140

ttctacccat gcacctccga ggaaatagat cacgaggata tcactaagga caaaacaagc     1200

actgtcgaag catgccttcc cttggaactg acaaagaacg agagttgcct taattcaaga     1260

gaaacatctt tcattacaaa cggtagctgc ttggcaagca gaaaaacatc ttttatgatg     1320

gccctttgtc tgagcagtat ttatgaggat ctcaaaatgt accaggtgga gtttaagacc     1380

atgaatgcca agctgctgat ggacccaaag agacagattt tcctcgatca gaatatgctg     1440

gctgtgattg atgaactgat gcaggccttg aatttcaaca gcgaaaccgt tccccagaaa     1500

agcagtcttg aagaacctga cttttataag accaagatca aactgtgtat tctcctgcat     1560

gcctttagaa tcagagcagt cactatagat agagtgatgt cctacctgaa tgcttcctga     1620

tga                                                                   1623


<210>  17
<211>  1623
<212>  RNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(1623)
<223>  Human non-optimized IL-12sc (RNA encoding CDS)

<400>  17
augugucacc agcaguuggu caucucuugg uuuucccugg uuuuucuggc aucuccccuc       60

guggccauau gggaacugaa gaaagauguu uaugucguag aauuggauug guauccggau      120

gccccuggag aaaugguggu ccucaccugu gacaccccug aagaagaugg uaucaccugg      180

accuuggacc agagcaguga ggucuuaggc ucuggcaaaa cccugaccau ccaagucaaa      240

gaguuuggag augcuggcca guacaccugu cacaaaggag gcgagguucu aagccauucg      300

cuccugcugc uucacaaaaa ggaagaugga auuuggucca cugauauuuu aaaggaccag      360

aaagaaccca aaaauaagac cuuucuaaga ugcgaggcca agaauuauuc uggacguuuc      420

accugcuggu ggcugacgac aaucaguacu gauuugacau ucagugucaa aagcagcaga      480

gggucuucug acccccaagg ggugacgugc ggagcugcua cacucucugc agagagaguc      540

agaggggaca acaaggagua ugaguacuca guggagugcc aggaggacag ugccugccca      600

gcugcugagg agagucugcc cauugagguc augguggaug ccguucacaa gcucaaguau      660

gaaaacuaca ccagcagcuu cuucaucagg gacaucauca aaccugaccc acccaagaac      720

uugcagcuga agccauuaaa gaauucucgg cagguggagg ucagcuggga guacccugac      780

accuggagua cuccacauuc cuacuucucc cugacauucu gcguucaggu ccagggcaag      840

agcaagagag aaaagaaaga uagagucuuc acggacaaga ccucagccac ggucaucugc      900

cgcaaaaaug ccagcauuag cgugcgggcc caggaccgcu acuauagcuc aucuuggagc      960

gaaugggcau cugugcccug caguggcucu agcggagggg gaggcucucc uggcggggga     1020

ucuagcagaa accuccccgu ggccacucca gacccaggaa uguucccaug ccuucaccac     1080

ucccaaaacc ugcugagggc cgucagcaac augcuccaga aggccagaca aacucuagaa     1140

uuuuacccuu gcacuucuga ggaaauugau caugaagaua ucacaaaaga uaaaaccagc     1200

acaguggagg ccuguuuacc auuggaauua accaagaaug agaguugccu aaauuccaga     1260

gagaccucuu ucauaacuaa ugggaguugc cuggccucca gaaagaccuc uuuuaugaug     1320

gcccugugcc uuaguaguau uuaugaagac uugaagaugu accaggugga guucaagacc     1380

augaaugcaa agcuucugau ggauccuaag aggcagaucu uucuagauca aaacaugcug     1440

gcaguuauug augagcugau gcaggcccug aauuucaaca gugagacugu gccacaaaaa     1500

uccucccuug aagaaccgga uuuuuauaaa acuaaaauca agcucugcau acuucuucau     1560

gcuuucagaa uucgggcagu gacuauugau agagugauga gcuaucugaa ugcuuccuga     1620

uga                                                                   1623


<210>  18
<211>  1623
<212>  RNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(1623)
<223>  Human optimized IL-12sc (RNA encoding CDS)

<400>  18
augugucacc agcagcuggu gaucucaugg uucucccugg uauuucuggc aucuccucuu       60

gucgcaaucu gggaacugaa gaaagacgug uaugucguug agcucgacug guauccggau      120

gcgccuggcg agaugguggu gcugaccugu gacaccccag aggaggaugg gaucacuugg      180

acccuugauc aauccuccga agugcucggg ucuggcaaga cucugaccau acaagugaaa      240

gaguuuggcg augccgggca guacacuugc cauaagggcg gagaaguucu gucccacuca      300

cugcugcugc ugcacaagaa agaggacgga auuuggagua ccgauauccu gaaagaucag      360

aaagagccca agaacaaaac cuucuugcgg ugcgaagcca agaacuacuc agggagauuu      420

acuuguuggu ggcugacgac gaucagcacc gaucugacuu ucuccgugaa aucaaguagg      480

ggaucaucug acccucaagg agucacaugu ggagcggcua cucugagcgc ugaacgcgua      540

agaggggaca auaaggagua cgaguauagc guugagugcc aagaggauag cgcaugcccc      600

gccgccgaag aaucauugcc cauugaagug augguggaug cuguacacaa gcugaaguau      660

gagaacuaca caagcuccuu cuucauccgu gacaucauca aaccagaucc uccuaagaac      720

cuccagcuua aaccucugaa gaacucuaga cagguggaag ugucuuggga guaucccgac      780

accuggucua caccacauuc cuacuucagu cucacauucu gcguucaggu acagggcaag      840

uccaaaaggg agaagaagga ucgggucuuu acagauaaaa caagugccac cguuauaugc      900

cggaagaaug ccucuauuuc ugugcgugcg caggacagau acuauagcag cucuuggagu      960

gaaugggcca gugucccaug uucaggguca uccgguggug gcggcagccc cggaggcggu     1020

agcuccagaa aucucccugu ggcuacaccu gauccaggca uguuucccug uuugcaccau     1080

agccaaaacc uccugagagc agucagcaac augcuccaga aagcuagaca aacacuggaa     1140

uucuacccau gcaccuccga ggaaauagau cacgaggaua ucacuaagga caaaacaagc     1200

acugucgaag caugccuucc cuuggaacug acaaagaacg agaguugccu uaauucaaga     1260

gaaacaucuu ucauuacaaa cgguagcugc uuggcaagca gaaaaacauc uuuuaugaug     1320

gcccuuuguc ugagcaguau uuaugaggau cucaaaaugu accaggugga guuuaagacc     1380

augaaugcca agcugcugau ggacccaaag agacagauuu uccucgauca gaauaugcug     1440

gcugugauug augaacugau gcaggccuug aauuucaaca gcgaaaccgu uccccagaaa     1500

agcagucuug aagaaccuga cuuuuauaag accaagauca aacuguguau ucuccugcau     1560

gccuuuagaa ucagagcagu cacuauagau agagugaugu ccuaccugaa ugcuuccuga     1620

uga                                                                   1623


<210>  19
<211>  188
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(188)
<223>  Human IFN-alpha-2b (amino acid)

<400>  19

Met Ala Leu Thr Phe Ala Leu Leu Val Ala Leu Leu Val Leu Ser Cys 
1               5                   10                  15      


Lys Ser Ser Cys Ser Val Gly Cys Asp Leu Pro Gln Thr His Ser Leu 
            20                  25                  30          


Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser 
        35                  40                  45              


Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu 
    50                  55                  60                  


Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His 
65                  70                  75                  80  


Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser 
                85                  90                  95      


Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr 
            100                 105                 110         


Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val 
        115                 120                 125             


Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys 
    130                 135                 140                 


Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro 
145                 150                 155                 160 


Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu 
                165                 170                 175     


Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu 
            180                 185             


<210>  20
<211>  570
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(570)
<223>  Human non-optimized IFN-alpha-2b (CDS DNA)

<400>  20
atggccttga cctttgcttt actggtggcc ctcctggtgc tcagctgcaa gtcaagctgc       60

tctgtgggct gtgatctgcc tcaaacccac agcctgggta gcaggaggac cttgatgctc      120

ctggcacaga tgaggagaat ctctcttttc tcctgcttga aggacagaca tgactttgga      180

tttccccagg aggagtttgg caaccagttc caaaaggctg aaaccatccc tgtcctccat      240

gagatgatcc agcagatctt caaccttttc agcacaaagg actcatctgc tgcttgggat      300

gagaccctcc tagacaaatt ctacactgaa ctctaccagc agctgaatga cctggaagcc      360

tgtgtgatac agggggtggg ggtgacagag actcccctga tgaaggagga ctccattctg      420

gctgtgagga aatacttcca aagaatcact ctctatctga aagagaagaa atacagccct      480

tgtgcctggg aggttgtcag agcagaaatc atgagatctt tttctttgtc aacaaacttg      540

caagaaagtt taagaagtaa ggaatgatga                                       570


<210>  21
<211>  570
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(570)
<223>  Human optimized IFN-alpha-2b (CDS DNA)

<400>  21
atggccctga cttttgccct tctcgtggct ttgttggtgc tgagttgcaa atcttcctgt       60

agtgtcggat gtgatctgcc tcaaacccac agtctgggat ctaggagaac actgatgctg      120

ttggcacaga tgaggagaat tagcctcttt tcctgcctga aggatagaca tgacttcggc      180

tttccccaag aggagtttgg caatcagttc cagaaagcgg aaacgattcc cgttctgcac      240

gagatgatcc agcagatctt caacctcttt tcaaccaaag acagctcagc agcctgggat      300

gagacactgc tggacaaatt ctacacagaa ctgtatcagc agcttaacga tctggaggca      360

tgcgtgatcc aaggggttgg tgtgactgaa actccgctta tgaaggagga ctccattctg      420

gctgtacgga agtacttcca gagaataacc ctctatctga aggagaagaa gtactcacca      480

tgtgcttggg aagtcgtgag agccgaaatc atgagatcct tcagccttag caccaatctc      540

caggaatctc tgagaagcaa agagtgatga                                       570


<210>  22
<211>  570
<212>  RNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(570)
<223>  Human non-optimized IFN-alpha-2b (RNA encoding CDS)

<400>  22
auggccuuga ccuuugcuuu acugguggcc cuccuggugc ucagcugcaa gucaagcugc       60

ucugugggcu gugaucugcc ucaaacccac agccugggua gcaggaggac cuugaugcuc      120

cuggcacaga ugaggagaau cucucuuuuc uccugcuuga aggacagaca ugacuuugga      180

uuuccccagg aggaguuugg caaccaguuc caaaaggcug aaaccauccc uguccuccau      240

gagaugaucc agcagaucuu caaccuuuuc agcacaaagg acucaucugc ugcuugggau      300

gagacccucc uagacaaauu cuacacugaa cucuaccagc agcugaauga ccuggaagcc      360

ugugugauac aggggguggg ggugacagag acuccccuga ugaaggagga cuccauucug      420

gcugugagga aauacuucca aagaaucacu cucuaucuga aagagaagaa auacagcccu      480

ugugccuggg agguugucag agcagaaauc augagaucuu uuucuuuguc aacaaacuug      540

caagaaaguu uaagaaguaa ggaaugauga                                       570


<210>  23
<211>  570
<212>  RNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(570)
<223>  Human optimized IFN-alpha-2b (RNA encoding CDS)

<400>  23
auggcccuga cuuuugcccu ucucguggcu uuguuggugc ugaguugcaa aucuuccugu       60

agugucggau gugaucugcc ucaaacccac agucugggau cuaggagaac acugaugcug      120

uuggcacaga ugaggagaau uagccucuuu uccugccuga aggauagaca ugacuucggc      180

uuuccccaag aggaguuugg caaucaguuc cagaaagcgg aaacgauucc cguucugcac      240

gagaugaucc agcagaucuu caaccucuuu ucaaccaaag acagcucagc agccugggau      300

gagacacugc uggacaaauu cuacacagaa cuguaucagc agcuuaacga ucuggaggca      360

ugcgugaucc aagggguugg ugugacugaa acuccgcuua ugaaggagga cuccauucug      420

gcuguacgga aguacuucca gagaauaacc cucuaucuga aggagaagaa guacucacca      480

ugugcuuggg aagucgugag agccgaaauc augagauccu ucagccuuag caccaaucuc      540

caggaaucuc ugagaagcaa agagugauga                                       570


<210>  24
<211>  241
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(241)
<223>  Human IL-15 sushi (amino acid)

<400>  24

Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr 
            20                  25                  30          


Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser 
        35                  40                  45              


Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys 
    50                  55                  60                  


Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala 
65                  70                  75                  80  


Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp 
                85                  90                  95      


Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Gly Gly Gly Ser Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly Ser Leu Gln Asn 
        115                 120                 125             


Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln 
    130                 135                 140                 


Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro 
145                 150                 155                 160 


Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val 
                165                 170                 175     


Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn 
            180                 185                 190         


Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr 
        195                 200                 205             


Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys 
    210                 215                 220                 


Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn Thr 
225                 230                 235                 240 


Ser 
    


<210>  25
<211>  729
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(729)
<223>  Human IL-15 sushi (CDS DNA)

<400>  25
atggccccgc ggcgggcgcg cggctgccgg accctcggtc tcccggcgct gctactgctg       60

ctgctgctcc ggccgccggc gacgcggggc atcacgtgcc ctccccccat gtccgtggaa      120

cacgcagaca tctgggtcaa gagctacagc ttgtactcca gggagcggta catttgtaac      180

tctggtttca agcgtaaagc cggcacgtcc agcctgacgg agtgcgtgtt gaacaaggcc      240

acgaatgtcg cccactggac aacccccagt ctcaaatgca ttagagaccc tgccctggtt      300

caccaaaggc cagcgccacc cgggggagga tctggcggcg gtgggtctgg cgggggatct      360

ggcggaggag gaagcttaca gaactgggtg aatgtaataa gtgatttgaa aaaaattgaa      420

gatcttattc aatctatgca tattgatgct actttatata cggaaagtga tgttcacccc      480

agttgcaaag taacagcaat gaagtgcttt ctcttggagt tacaagttat ttcacttgag      540

tccggagatg caagtattca tgatacagta gaaaatctga tcatcctagc aaacaacagt      600

ttgtcttcta atgggaatgt aacagaatct ggatgcaaag aatgtgagga actggaggaa      660

aaaaatatta aagaattttt gcagagtttt gtacatattg tccaaatgtt catcaacact      720

tcttgatga                                                              729


<210>  26
<211>  729
<212>  RNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(729)
<223>  Human IL-15 sushi (RNA encoding CDS)

<400>  26
auggccccgc ggcgggcgcg cggcugccgg acccucgguc ucccggcgcu gcuacugcug       60

cugcugcucc ggccgccggc gacgcggggc aucacgugcc cuccccccau guccguggaa      120

cacgcagaca ucugggucaa gagcuacagc uuguacucca gggagcggua cauuuguaac      180

ucugguuuca agcguaaagc cggcacgucc agccugacgg agugcguguu gaacaaggcc      240

acgaaugucg cccacuggac aacccccagu cucaaaugca uuagagaccc ugcccugguu      300

caccaaaggc cagcgccacc cgggggagga ucuggcggcg gugggucugg cgggggaucu      360

ggcggaggag gaagcuuaca gaacugggug aauguaauaa gugauuugaa aaaaauugaa      420

gaucuuauuc aaucuaugca uauugaugcu acuuuauaua cggaaaguga uguucacccc      480

aguugcaaag uaacagcaau gaagugcuuu cucuuggagu uacaaguuau uucacuugag      540

uccggagaug caaguauuca ugauacagua gaaaaucuga ucauccuagc aaacaacagu      600

uugucuucua augggaaugu aacagaaucu ggaugcaaag aaugugagga acuggaggaa      660

aaaaauauua aagaauuuuu gcagaguuuu guacauauug uccaaauguu caucaacacu      720

ucuugauga                                                              729


<210>  27
<211>  144
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(144)
<223>  Human GM-CSF (amino acid)

<400>  27

Met Trp Leu Gln Ser Leu Leu Leu Leu Gly Thr Val Ala Cys Ser Ile 
1               5                   10                  15      


Ser Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His 
            20                  25                  30          


Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp 
        35                  40                  45              


Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe 
    50                  55                  60                  


Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys 
65                  70                  75                  80  


Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met 
                85                  90                  95      


Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser 
            100                 105                 110         


Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys 
        115                 120                 125             


Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu 
    130                 135                 140                 


<210>  28
<211>  438
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(438)
<223>  Human GM-CSF (CDS DNA)

<400>  28
atgtggctcc agagcctgct gctcttgggc actgtggcct gctccatctc tgcacccgcc       60

cgctcgccca gccccagcac gcagccctgg gagcatgtga atgccatcca ggaggcccgg      120

cgtctgctga acctgagtag agacactgct gctgagatga atgaaacagt agaagtcatc      180

tcagaaatgt ttgacctcca ggagccgacc tgcctacaga cccgcctgga gctgtacaag      240

cagggcctgc ggggcagcct caccaagctc aagggcccct tgaccatgat ggccagccac      300

tacaagcagc actgccctcc aaccccggaa acttcctgtg caacccagat tatcaccttt      360

gaaagtttca aagagaacct gaaggacttt ctgcttgtca tcccctttga ctgctgggag      420

ccagtccagg agtgatga                                                    438


<210>  29
<211>  438
<212>  RNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(438)
<223>  Human GM-CSF (RNA encoding CDS)

<400>  29
auguggcucc agagccugcu gcucuugggc acuguggccu gcuccaucuc ugcacccgcc       60

cgcucgccca gccccagcac gcagcccugg gagcauguga augccaucca ggaggcccgg      120

cgucugcuga accugaguag agacacugcu gcugagauga augaaacagu agaagucauc      180

ucagaaaugu uugaccucca ggagccgacc ugccuacaga cccgccugga gcuguacaag      240

cagggccugc ggggcagccu caccaagcuc aagggccccu ugaccaugau ggccagccac      300

uacaagcagc acugcccucc aaccccggaa acuuccugug caacccagau uaucaccuuu      360

gaaaguuuca aagagaaccu gaaggacuuu cugcuuguca uccccuuuga cugcugggag      420

ccaguccagg agugauga                                                    438


<210>  30
<211>  110
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Exemplary Poly-A

<400>  30
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa gcauaugacu aaaaaaaaaa aaaaaaaaaa       60

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa                 110


<210>  31
<211>  444
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Anti-PD1 Mab heavy chain

<400>  31

Glu Val Gln Leu Leu Glu Ser Gly Gly Val Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Phe 
            20                  25                  30          


Gly Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Gly Ile Ser Gly Gly Gly Arg Asp Thr Tyr Phe Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Lys Gly Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Val Lys Trp Gly Asn Ile Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        115                 120                 125             


Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 


Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 


Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                165                 170                 175     


Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            180                 185                 190         


Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn 
        195                 200                 205             


Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro 
    210                 215                 220                 


Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe 
225                 230                 235                 240 


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
                245                 250                 255     


Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe 
            260                 265                 270         


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
        275                 280                 285             


Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
    290                 295                 300                 


Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
305                 310                 315                 320 


Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala 
                325                 330                 335     


Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln 
            340                 345                 350         


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
        355                 360                 365             


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
    370                 375                 380                 


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
385                 390                 395                 400 


Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu 
                405                 410                 415     


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
            420                 425                 430         


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 


<210>  32
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Anti-PD1 Mab light chain

<400>  32

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Ser Ile Thr Ile Thr Cys Arg Ala Ser Leu Ser Ile Asn Thr Phe 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu His Gly Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Thr Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ser Asn Thr Pro Phe 
                85                  90                  95      


Thr Phe Gly Pro Gly Thr Val Val Asp Phe Arg Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  33
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: HCDR1

<400>  33

Gly Phe Thr Phe Ser Asn Phe Gly 
1               5               


<210>  34
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: HCDR2

<400>  34

Ile Ser Gly Gly Gly Arg Asp Thr 
1               5               


<210>  35
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: HCDR3

<400>  35

Val Lys Trp Gly Asn Ile Tyr Phe Asp Tyr 
1               5                   10  


<210>  36
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: LCDR1

<400>  36

Leu Ser Ile Asn Thr Phe 
1               5       


<210>  37
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: LCDR2

<400>  37

Ala Ala Ser 
1           


<210>  38
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: LCDR3

<400>  38

Gln Gln Ser Ser Asn Thr Pro Phe Thr 
1               5                   


<210>  39
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Anti-PD1 Mab VH

<400>  39

Glu Val Gln Leu Leu Glu Ser Gly Gly Val Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Phe 
            20                  25                  30          


Gly Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Gly Ile Ser Gly Gly Gly Arg Asp Thr Tyr Phe Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Lys Gly Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Val Lys Trp Gly Asn Ile Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  40
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Anti-PD1 Mab VL

<400>  40

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Ser Ile Thr Ile Thr Cys Arg Ala Ser Leu Ser Ile Asn Thr Phe 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu His Gly Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Thr Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Ser Asn Thr Pro Phe 
                85                  90                  95      


Thr Phe Gly Pro Gly Thr Val Val Asp Phe Arg 
            100                 105         


<210>  41
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: sgRNA

<400>  41
ggcgtatgta tcagtctcag                                                   20


