                         б

<110>  ҩƷ޹˾
 
<120>  ͬʱB7/CD28IL6/IL6R/GP130źͨ·ںϵ

<130>  LZ141689CN01

<160>  11    

<170>  PatentIn version 3.3

<210>  1
<211>  125
<212>  PRT
<213>  ˹

<220>
<223>  CTLA4

<400>  1

Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly 
1               5                   10                  15      


Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu 
            20                  25                  30          


Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val 
        35                  40                  45              


Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp 
    50                  55                  60                  


Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile 
65                  70                  75                  80  


Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu 
                85                  90                  95      


Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln 
            100                 105                 110         


Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp 
        115                 120                 125 


<210>  2
<211>  450
<212>  PRT
<213>  ˹

<220>
<223>  IL6¡

<400>  2

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


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


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


Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile 
    50                  55                  60                  


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


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


Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln 
            100                 105                 110         


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


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


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


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


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


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  3
<211>  217
<212>  PRT
<213>  ˹

<220>
<223>  IL6¡

<400>  3

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


Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu 
            20                  25                  30          


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


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


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


Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn 
                85                  90                  95      


Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr 
            100                 105                 110         


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


Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 
    130                 135                 140                 


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


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


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


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


Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215         


<210>  4
<211>  25
<212>  PRT
<213>  ˹

<220>
<223>  ź

<400>  4

Met Gly Val Leu Leu Thr Gln Arg Thr Leu Leu Ser Leu Val Leu Ala 
1               5                   10                  15      


Leu Leu Phe Pro Ser Met Ala Ser Met 
            20                  25  


<210>  5
<211>  25
<212>  PRT
<213>  ˹

<220>
<223>  

<400>  5

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            20                  25  


<210>  6
<211>  600
<212>  PRT
<213>  ˹

<220>
<223>  CTLA4--IL6¡

<400>  6

Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg Gly 
1               5                   10                  15      


Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr Glu 
            20                  25                  30          


Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu Val 
        35                  40                  45              


Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp Asp 
    50                  55                  60                  


Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr Ile 
65                  70                  75                  80  


Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val Glu 
                85                  90                  95      


Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Thr Gln 
            100                 105                 110         


Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
    130                 135                 140                 


Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly 
145                 150                 155                 160 


Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 
                165                 170                 175     


Phe Ser Leu Ser Asn Tyr Tyr Val Thr Trp Val Arg Gln Ala Pro Gly 
            180                 185                 190         


Lys Gly Leu Glu Trp Val Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala 
        195                 200                 205             


Tyr Ala Thr Ser Ala Ile Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
    210                 215                 220                 


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
225                 230                 235                 240 


Ala Val Tyr Tyr Cys Ala Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys 
                245                 250                 255     


Phe Asn Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
            260                 265                 270         


Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
        275                 280                 285             


Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro 
    290                 295                 300                 


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
305                 310                 315                 320 


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
                325                 330                 335     


Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
            340                 345                 350         


Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val 
        355                 360                 365             


Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    370                 375                 380                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
385                 390                 395                 400 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                405                 410                 415     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            420                 425                 430         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        435                 440                 445             


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    450                 455                 460                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
465                 470                 475                 480 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                485                 490                 495     


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


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        515                 520                 525             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    530                 535                 540                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
545                 550                 555                 560 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                565                 570                 575     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            580                 585                 590         


Ser Leu Ser Leu Ser Pro Gly Lys 
        595                 600 


<210>  7
<211>  1875
<212>  DNA
<213>  ˹

<220>
<223>  ź-CTLA4--IL6¡

<400>  7
atgggggtcc tgctgactca gagaacactg ctgtccctgg tcctggcact gctgtttcct     60

tcaatggctt caatggctat gcacgtcgct cagccagcag tggtcctggc atccagcaga    120

ggcatcgcca gtttcgtgtg cgagtacgct tcacccggaa aggcaacaga agtcagagtg    180

actgtcctgc gacaggcaga cagccaggtg accgaggtct gcgccgctac atatatgatg    240

ggcaacgaac tgacatttct ggacgattct atctgtactg gcacctctag tggaaaccaa    300

gtgaatctga ctatccaggg cctgcgcgct atggataccg gactgtacat ttgcaaggtg    360

gagctgatgt atccccctcc atactatctg gggattggta atggcaccca aatatacgtg    420

attgacccag agccctgtcc tgactctgat ggaggtggag gatccggagg tggaggaagc    480

gggggtggcg gatctggagg aggagggtct ggcggcggag gaagtgaagt gcagctggtg    540

gagtccggag gaggcctggt gcaacctgga ggctccctga ggctgtcctg tgctgccagc    600

ggcttctccc tgtccaacta ctacgtgacc tgggtgaggc aggctcctgg caagggactg    660

gagtgggtgg gcatcatcta cggctccgac gagaccgcct acgctacctc cgccatcggc    720

aggttcacca tctcccggga caactccaag aacaccctgt acctgcagat gaactccctg    780

agggccgagg acaccgccgt gtactactgc gctagggacg actccagcga ttgggacgcc    840

aagttcaacc tgtggggcca gggcacactg gtgaccgtgt ccagcgcttc aacaaaagga    900

ccttccgtgt ttccactggc accctctagt aagagtactt caggaggaac cgcagcactg    960

ggatgtctgg tgaaggacta cttcccagag cccgtcaccg tgtcttggaa cagtggagca   1020

ctgacctccg gggtccatac atttcctgcc gtgctgcagt catccggtct gtatagcctg   1080

agctctgtgg tcacagtccc aagttcatcc ctgggcaccc agacatacat ctgcaacgtg   1140

aatcacaaac cttccaatac taaggtcgac aagaaagtgg aaccaaaaag ctgtgataag   1200

actcatacct gcccaccttg tcctgcacca gagctgctgg gaggtccaag cgtgttcctg   1260

tttccaccca agcccaaaga cacactgatg atttctcgca cacccgaagt cacttgtgtg   1320

gtcgtggacg tgtcccacga ggatcctgaa gtcaagttca actggtacgt ggatggcgtc   1380

gaggtgcata atgctaagac caaacccaga gaggaacagt acaacagcac ctatcgcgtc   1440

gtgtctgtcc tgacagtgct gcaccaggat tggctgaacg gaaaggagta caagtgcaaa   1500

gtgagcaaca aggccctgcc cgctcctatc gagaagacca tttctaaggc taaaggccag   1560

cctagagaac cacaggtgta tacactgcct ccaagtcgcg acgagctgac aaaaaaccag   1620

gtctccctga cttgtctggt gaagggattc taccctagcg atatcgcagt ggagtgggaa   1680

tctaatgggc agccagaaaa caattataag accacacccc ctgtgctgga ctcagatggt   1740

tccttctttc tgtacagtaa actgaccgtg gacaagtcca ggtggcagca ggggaacgtc   1800

ttttcctgca gcgtgatgca tgaggccctg cacaatcatt acacacagaa atctctgagt   1860

ctgtcaccag gaaag                                                    1875


<210>  8
<211>  726
<212>  DNA
<213>  ˹

<220>
<223>  ź-IL6¡

<400>  8
atgggggtcc tgctgactca gagaacactg ctgtccctgg tcctggcact gctgtttcct     60

tcaatggctt caatggccat ccagatgaca cagtcccctt cctccctgag cgctagcgtc    120

ggagacaggg tgaccatcac ctgtcaggcc agccagtcca tcaacaacga gctgtcctgg    180

tatcagcaga agcccggcaa ggcccccaag ctgctgatct acagggcctc cacactggct    240

tccggagtgc cttccaggtt ttccggctcc ggcagcggaa ccgacttcac actgaccatc    300

tccagcctgc agcccgacga cttcgccacc tactactgtc agcagggcta ctccctgagg    360

aacatcgaca acgccttcgg cggcggcacc aaggtggaga tcaagaggac tgtggccgct    420

ccaagcgtct tcatttttcc accctctgac gaacagctga agtcagggac agcttccgtg    480

gtctgtctgc tgaacaattt ttaccccagg gaggccaaag tgcagtggaa ggtcgataac    540

gctctgcaga gcggaaattc tcaggagagt gtgacagaac aggactcaaa agattccact    600

tatagcctgt ctagtaccct gacactgtcc aaggcagact acgaaaagca taaagtgtat    660

gcctgtgagg tcacacatca gggtctgtca agccccgtca ctaagtcctt caatcgtggc    720

gaatgc                                                               726


<210>  9
<211>  22
<212>  DNA
<213>  ˹

<220>
<223>  

<400>  9
cccaagcttg ccaccatggg gg                                              22


<210>  10
<211>  24
<212>  DNA
<213>  ˹

<220>
<223>  

<400>  10
ccggaattct cactttcctg gtga                                            24


<210>  11
<211>  30
<212>  DNA
<213>  ˹

<220>
<223>  

<400>  11
ccggaattct cagcattcgc cacgattgaa                                      30


