                         SEQUENCE LISTING

<110>  KAHR Medical Ltd.
       SHANI, Noam
       GOZLAN, Yosi
       DRANITZKI ELHALEL, Michal
       BREMER, Edwin
       KAMINSKY, Ido
 
<120>  A PD1-CD70 FUSION PROTEIN AND METHODS OF USE THEREOF

<130>  72309

<150>  US 62/442,456
<151>  2017-01-05

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  306
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of the chimera protein (PD1- G  CD70)

<400>  1

Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr 
1               5                   10                  15      


Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe 
            20                  25                  30          


Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr 
        35                  40                  45              


Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu 
    50                  55                  60                  


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


Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn 
                85                  90                  95      


Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala 
            100                 105                 110         


Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg 
        115                 120                 125             


Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly 
    130                 135                 140                 


Gln Phe Gln Thr Leu Val Gly Gln Arg Phe Ala Gln Ala Gln Gln Gln 
145                 150                 155                 160 


Leu Pro Leu Glu Ser Leu Gly Trp Asp Val Ala Glu Leu Gln Leu Asn 
                165                 170                 175     


His Thr Gly Pro Gln Gln Asp Pro Arg Leu Tyr Trp Gln Gly Gly Pro 
            180                 185                 190         


Ala Leu Gly Arg Ser Phe Leu His Gly Pro Glu Leu Asp Lys Gly Gln 
        195                 200                 205             


Leu Arg Ile His Arg Asp Gly Ile Tyr Met Val His Ile Gln Val Thr 
    210                 215                 220                 


Leu Ala Ile Cys Ser Ser Thr Thr Ala Ser Arg His His Pro Thr Thr 
225                 230                 235                 240 


Leu Ala Val Gly Ile Cys Ser Pro Ala Ser Arg Ser Ile Ser Leu Leu 
                245                 250                 255     


Arg Leu Ser Phe His Gln Gly Cys Thr Ile Ala Ser Gln Arg Leu Thr 
            260                 265                 270         


Pro Leu Ala Arg Gly Asp Thr Leu Cys Thr Asn Leu Thr Gly Thr Leu 
        275                 280                 285             


Leu Pro Ser Arg Asn Thr Asp Glu Thr Phe Phe Gly Val Gln Trp Val 
    290                 295                 300                 


Arg Pro 
305     


<210>  2
<211>  150
<212>  PRT
<213>  homo sapiens

<400>  2

Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr 
1               5                   10                  15      


Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe 
            20                  25                  30          


Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr 
        35                  40                  45              


Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu 
    50                  55                  60                  


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


Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn 
                85                  90                  95      


Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala 
            100                 105                 110         


Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg 
        115                 120                 125             


Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly 
    130                 135                 140                 


Gln Phe Gln Thr Leu Val 
145                 150 


<210>  3
<211>  155
<212>  PRT
<213>  homo sapiens

<400>  3

Gln Arg Phe Ala Gln Ala Gln Gln Gln Leu Pro Leu Glu Ser Leu Gly 
1               5                   10                  15      


Trp Asp Val Ala Glu Leu Gln Leu Asn His Thr Gly Pro Gln Gln Asp 
            20                  25                  30          


Pro Arg Leu Tyr Trp Gln Gly Gly Pro Ala Leu Gly Arg Ser Phe Leu 
        35                  40                  45              


His Gly Pro Glu Leu Asp Lys Gly Gln Leu Arg Ile His Arg Asp Gly 
    50                  55                  60                  


Ile Tyr Met Val His Ile Gln Val Thr Leu Ala Ile Cys Ser Ser Thr 
65                  70                  75                  80  


Thr Ala Ser Arg His His Pro Thr Thr Leu Ala Val Gly Ile Cys Ser 
                85                  90                  95      


Pro Ala Ser Arg Ser Ile Ser Leu Leu Arg Leu Ser Phe His Gln Gly 
            100                 105                 110         


Cys Thr Ile Ala Ser Gln Arg Leu Thr Pro Leu Ala Arg Gly Asp Thr 
        115                 120                 125             


Leu Cys Thr Asn Leu Thr Gly Thr Leu Leu Pro Ser Arg Asn Thr Asp 
    130                 135                 140                 


Glu Thr Phe Phe Gly Val Gln Trp Val Arg Pro 
145                 150                 155 


<210>  4
<211>  305
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of the chimera protein (PD1- CD70, no 
       linker)

<400>  4

Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr 
1               5                   10                  15      


Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe 
            20                  25                  30          


Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr 
        35                  40                  45              


Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu 
    50                  55                  60                  


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


Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn 
                85                  90                  95      


Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala 
            100                 105                 110         


Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg 
        115                 120                 125             


Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly 
    130                 135                 140                 


Gln Phe Gln Thr Leu Val Gln Arg Phe Ala Gln Ala Gln Gln Gln Leu 
145                 150                 155                 160 


Pro Leu Glu Ser Leu Gly Trp Asp Val Ala Glu Leu Gln Leu Asn His 
                165                 170                 175     


Thr Gly Pro Gln Gln Asp Pro Arg Leu Tyr Trp Gln Gly Gly Pro Ala 
            180                 185                 190         


Leu Gly Arg Ser Phe Leu His Gly Pro Glu Leu Asp Lys Gly Gln Leu 
        195                 200                 205             


Arg Ile His Arg Asp Gly Ile Tyr Met Val His Ile Gln Val Thr Leu 
    210                 215                 220                 


Ala Ile Cys Ser Ser Thr Thr Ala Ser Arg His His Pro Thr Thr Leu 
225                 230                 235                 240 


Ala Val Gly Ile Cys Ser Pro Ala Ser Arg Ser Ile Ser Leu Leu Arg 
                245                 250                 255     


Leu Ser Phe His Gln Gly Cys Thr Ile Ala Ser Gln Arg Leu Thr Pro 
            260                 265                 270         


Leu Ala Arg Gly Asp Thr Leu Cys Thr Asn Leu Thr Gly Thr Leu Leu 
        275                 280                 285             


Pro Ser Arg Asn Thr Asp Glu Thr Phe Phe Gly Val Gln Trp Val Arg 
    290                 295                 300                 


Pro 
305 


<210>  5
<211>  312
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino-acid sequence of His-tagged PD1-CD70

<400>  5

His His His His His His Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg 
1               5                   10                  15      


Pro Trp Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu 
            20                  25                  30          


Gly Asp Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser 
        35                  40                  45              


Phe Val Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys 
    50                  55                  60                  


Leu Ala Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg 
65                  70                  75                  80  


Phe Arg Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val 
                85                  90                  95      


Val Arg Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile 
            100                 105                 110         


Ser Leu Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu 
        115                 120                 125             


Arg Val Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro 
    130                 135                 140                 


Ser Pro Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Gly Gln Arg Phe 
145                 150                 155                 160 


Ala Gln Ala Gln Gln Gln Leu Pro Leu Glu Ser Leu Gly Trp Asp Val 
                165                 170                 175     


Ala Glu Leu Gln Leu Asn His Thr Gly Pro Gln Gln Asp Pro Arg Leu 
            180                 185                 190         


Tyr Trp Gln Gly Gly Pro Ala Leu Gly Arg Ser Phe Leu His Gly Pro 
        195                 200                 205             


Glu Leu Asp Lys Gly Gln Leu Arg Ile His Arg Asp Gly Ile Tyr Met 
    210                 215                 220                 


Val His Ile Gln Val Thr Leu Ala Ile Cys Ser Ser Thr Thr Ala Ser 
225                 230                 235                 240 


Arg His His Pro Thr Thr Leu Ala Val Gly Ile Cys Ser Pro Ala Ser 
                245                 250                 255     


Arg Ser Ile Ser Leu Leu Arg Leu Ser Phe His Gln Gly Cys Thr Ile 
            260                 265                 270         


Ala Ser Gln Arg Leu Thr Pro Leu Ala Arg Gly Asp Thr Leu Cys Thr 
        275                 280                 285             


Asn Leu Thr Gly Thr Leu Leu Pro Ser Arg Asn Thr Asp Glu Thr Phe 
    290                 295                 300                 


Phe Gly Val Gln Trp Val Arg Pro 
305                 310         


<210>  6
<211>  554
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of SIRP alpha-41BBL

<400>  6

His His His His His Glu Glu Glu Leu Gln Val Ile Gln Pro Asp Lys 
1               5                   10                  15      


Ser Val Leu Val Ala Ala Gly Glu Thr Ala Thr Leu Arg Cys Thr Ala 
            20                  25                  30          


Thr Ser Leu Ile Pro Val Gly Pro Ile Gln Trp Phe Arg Gly Ala Gly 
        35                  40                  45              


Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg 
    50                  55                  60                  


Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn Asn Met Asp Phe Ser 
65                  70                  75                  80  


Ile Arg Ile Gly Asn Ile Thr Pro Ala Asp Ala Gly Thr Tyr Tyr Cys 
                85                  90                  95      


Val Lys Phe Arg Lys Gly Ser Pro Asp Asp Val Glu Phe Lys Ser Gly 
            100                 105                 110         


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


Ser Gly Pro Ala Ala Arg Ala Thr Pro Gln His Thr Val Ser Phe Thr 
    130                 135                 140                 


Cys Glu Ser His Gly Phe Ser Pro Arg Asp Ile Thr Leu Lys Trp Phe 
145                 150                 155                 160 


Lys Asn Gly Asn Glu Leu Ser Asp Phe Gln Thr Asn Val Asp Pro Val 
                165                 170                 175     


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


Thr Arg Glu Asp Val His Ser Gln Val Ile Cys Glu Val Ala His Val 
        195                 200                 205             


Thr Leu Gln Gly Asp Pro Leu Arg Gly Thr Ala Asn Leu Ser Glu Thr 
    210                 215                 220                 


Ile Arg Val Pro Pro Thr Leu Glu Val Thr Gln Gln Pro Val Arg Ala 
225                 230                 235                 240 


Glu Asn Gln Val Asn Val Thr Cys Gln Val Arg Lys Phe Tyr Pro Gln 
                245                 250                 255     


Arg Leu Gln Leu Thr Trp Leu Glu Asn Gly Asn Val Ser Arg Thr Glu 
            260                 265                 270         


Thr Ala Ser Thr Val Thr Glu Asn Lys Asp Gly Thr Tyr Asn Trp Met 
        275                 280                 285             


Ser Trp Leu Leu Val Asn Val Ser Ala His Arg Asp Asp Val Lys Leu 
    290                 295                 300                 


Thr Cys Gln Val Glu His Asp Gly Gln Pro Ala Val Ser Lys Ser His 
305                 310                 315                 320 


Asp Leu Lys Val Ser Ala His Pro Lys Glu Gln Gly Ser Asn Thr Ala 
                325                 330                 335     


Ala Glu Asn Thr Gly Ser Asn Glu Arg Asn Ile Tyr Gly Ala Cys Pro 
            340                 345                 350         


Trp Ala Val Ser Gly Ala Arg Ala Ser Pro Gly Ser Ala Ala Ser Pro 
        355                 360                 365             


Arg Leu Arg Glu Gly Pro Glu Leu Ser Pro Asp Asp Pro Ala Gly Leu 
    370                 375                 380                 


Leu Asp Leu Arg Gln Gly Met Phe Ala Gln Leu Val Ala Gln Asn Val 
385                 390                 395                 400 


Leu Leu Ile Asp Gly Pro Leu Ser Trp Tyr Ser Asp Pro Gly Leu Ala 
                405                 410                 415     


Gly Val Ser Leu Thr Gly Gly Leu Ser Tyr Lys Glu Asp Thr Lys Glu 
            420                 425                 430         


Leu Val Val Ala Lys Ala Gly Val Tyr Tyr Val Phe Phe Gln Leu Glu 
        435                 440                 445             


Leu Arg Arg Val Val Ala Gly Glu Gly Ser Gly Ser Val Ser Leu Ala 
    450                 455                 460                 


Leu His Leu Gln Pro Leu Arg Ser Ala Ala Gly Ala Ala Ala Leu Ala 
465                 470                 475                 480 


Leu Thr Val Asp Leu Pro Pro Ala Ser Ser Glu Ala Arg Asn Ser Ala 
                485                 490                 495     


Phe Gly Phe Gln Gly Arg Leu Leu His Leu Ser Ala Gly Gln Arg Leu 
            500                 505                 510         


Gly Val His Leu His Thr Glu Ala Arg Ala Arg His Ala Trp Gln Leu 
        515                 520                 525             


Thr Gln Gly Ala Thr Val Leu Gly Leu Phe Arg Val Thr Pro Glu Ile 
    530                 535                 540                 


Pro Ala Gly Leu Pro Ser Pro Arg Ser Glu 
545                 550                 


<210>  7
<211>  936
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of PD1-CD70 (with his tag)

<400>  7
caccatcatc accaccatcc tggctggttt ctggacagcc ccgacagacc ttggaaccct       60

cctacattca gccccgctct gctggtggtt accgagggcg ataatgccac cttcacctgt      120

agcttcagca acaccagcga gagcttcgtg ctgaactggt acagaatgag ccccagcaac      180

cagaccgaca agctggccgc ctttcctgag gatagatctc agcccggcca ggactgccgg      240

ttcagagtta cacagctgcc caacggccgg gacttccaca tgtctgtcgt ccgggccaga      300

agaaacgaca gcggcacata tctgtgcggc gccatttctc tggcccctaa ggctcagatc      360

aaagagagcc tgagagccga gctgagagtg acagaaagac gggccgaagt gcccacagct      420

cacccttcac cttctccaag acctgccggc cagtttcaga cactcgtggg acagagattc      480

gcccaggctc agcagcaact gcctctggaa tctctcggct gggatgttgc cgaactgcag      540

ctgaatcaca caggccctca gcaggacccc agactgtatt ggcaaggcgg acctgctctg      600

ggcagatcct ttctgcatgg ccccgagctg gataagggcc agctgagaat ccaccgcgac      660

ggcatctaca tggtgcacat ccaagtgacc ctggccatct gcagcagcac cacagcctct      720

agacatcacc ctaccacact ggccgtgggc atctgttctc cagccagcag atctatcagc      780

ctgctgcggc tgagcttcca ccagggatgt acaatcgcca gccagagact gacccctctg      840

gctagaggcg ataccctgtg caccaatctg accggcacac tgctgcccag ccggaacacc      900

gatgagacat tctttggcgt gcagtgggtc cgacct                                936


<210>  8
<211>  918
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of PD1-CD70

<400>  8
cctggctggt ttctggacag ccccgacaga ccttggaacc ctcctacatt cagccccgct       60

ctgctggtgg ttaccgaggg cgataatgcc accttcacct gtagcttcag caacaccagc      120

gagagcttcg tgctgaactg gtacagaatg agccccagca accagaccga caagctggcc      180

gcctttcctg aggatagatc tcagcccggc caggactgcc ggttcagagt tacacagctg      240

cccaacggcc gggacttcca catgtctgtc gtccgggcca gaagaaacga cagcggcaca      300

tatctgtgcg gcgccatttc tctggcccct aaggctcaga tcaaagagag cctgagagcc      360

gagctgagag tgacagaaag acgggccgaa gtgcccacag ctcacccttc accttctcca      420

agacctgccg gccagtttca gacactcgtg ggacagagat tcgcccaggc tcagcagcaa      480

ctgcctctgg aatctctcgg ctgggatgtt gccgaactgc agctgaatca cacaggccct      540

cagcaggacc ccagactgta ttggcaaggc ggacctgctc tgggcagatc ctttctgcat      600

ggccccgagc tggataaggg ccagctgaga atccaccgcg acggcatcta catggtgcac      660

atccaagtga ccctggccat ctgcagcagc accacagcct ctagacatca ccctaccaca      720

ctggccgtgg gcatctgttc tccagccagc agatctatca gcctgctgcg gctgagcttc      780

caccagggat gtacaatcgc cagccagaga ctgacccctc tggctagagg cgataccctg      840

tgcaccaatc tgaccggcac actgctgccc agccggaaca ccgatgagac attctttggc      900

gtgcagtggg tccgacct                                                    918


<210>  9
<211>  288
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of full length PD1

<400>  9

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln 
1               5                   10                  15      


Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp 
            20                  25                  30          


Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp 
        35                  40                  45              


Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val 
    50                  55                  60                  


Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala 
65                  70                  75                  80  


Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg 
                85                  90                  95      


Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg 
            100                 105                 110         


Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu 
        115                 120                 125             


Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val 
    130                 135                 140                 


Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro 
145                 150                 155                 160 


Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly 
                165                 170                 175     


Leu Leu Gly Ser Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys 
            180                 185                 190         


Ser Arg Ala Ala Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro 
        195                 200                 205             


Leu Lys Glu Asp Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly 
    210                 215                 220                 


Glu Leu Asp Phe Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro 
225                 230                 235                 240 


Cys Val Pro Glu Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly 
                245                 250                 255     


Met Gly Thr Ser Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg 
            260                 265                 270         


Ser Ala Gln Pro Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu 
        275                 280                 285             


<210>  10
<211>  867
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence of full length PD1

<400>  10
atgcagatcc cacaggcgcc ctggccagtc gtctgggcgg tgctacaact gggctggcgg       60

ccaggatggt tcttagactc cccagacagg ccctggaacc cccccacctt ctccccagcc      120

ctgctcgtgg tgaccgaagg ggacaacgcc accttcacct gcagcttctc caacacatcg      180

gagagcttcg tgctaaactg gtaccgcatg agccccagca accagacgga caagctggcc      240

gccttccccg aggaccgcag ccagcccggc caggactgcc gcttccgtgt cacacaactg      300

cccaacgggc gtgacttcca catgagcgtg gtcagggccc ggcgcaatga cagcggcacc      360

tacctctgtg gggccatctc cctggccccc aaggcgcaga tcaaagagag cctgcgggca      420

gagctcaggg tgacagagag aagggcagaa gtgcccacag cccaccccag cccctcaccc      480

aggccagccg gccagttcca aaccctggtg gttggtgtcg tgggcggcct gctgggcagc      540

ctggtgctgc tagtctgggt cctggccgtc atctgctccc gggccgcacg agggacaata      600

ggagccaggc gcaccggcca gcccctgaag gaggacccct cagccgtgcc tgtgttctct      660

gtggactatg gggagctgga tttccagtgg cgagagaaga ccccggagcc ccccgtgccc      720

tgtgtccctg agcagacgga gtatgccacc attgtctttc ctagcggaat gggcacctca      780

tcccccgccc gcaggggctc agctgacggc cctcggagtg cccagccact gaggcctgag      840

gatggacact gctcttggcc cctctga                                          867


<210>  11
<211>  450
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleic-acid sequence encoding the extracellular domain of the 
       human PD1 protein

<400>  11
ccaggatggt tcttagactc cccagacagg ccctggaacc cccccacctt ctccccagcc       60

ctgctcgtgg tgaccgaagg ggacaacgcc accttcacct gcagcttctc caacacatcg      120

gagagcttcg tgctaaactg gtaccgcatg agccccagca accagacgga caagctggcc      180

gccttccccg aggaccgcag ccagcccggc caggactgcc gcttccgtgt cacacaactg      240

cccaacgggc gtgacttcca catgagcgtg gtcagggccc ggcgcaatga cagcggcacc      300

tacctctgtg gggccatctc cctggccccc aaggcgcaga tcaaagagag cctgcgggca      360

gagctcaggg tgacagagag aagggcagaa gtgcccacag cccaccccag cccctcaccc      420

aggccagccg gccagttcca aaccctggtg                                       450


<210>  12
<211>  193
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence of full length CD70

<400>  12

Met Pro Glu Glu Gly Ser Gly Cys Ser Val Arg Arg Arg Pro Tyr Gly 
1               5                   10                  15      


Cys Val Leu Arg Ala Ala Leu Val Pro Leu Val Ala Gly Leu Val Ile 
            20                  25                  30          


Cys Leu Val Val Cys Ile Gln Arg Phe Ala Gln Ala Gln Gln Gln Leu 
        35                  40                  45              


Pro Leu Glu Ser Leu Gly Trp Asp Val Ala Glu Leu Gln Leu Asn His 
    50                  55                  60                  


Thr Gly Pro Gln Gln Asp Pro Arg Leu Tyr Trp Gln Gly Gly Pro Ala 
65                  70                  75                  80  


Leu Gly Arg Ser Phe Leu His Gly Pro Glu Leu Asp Lys Gly Gln Leu 
                85                  90                  95      


Arg Ile His Arg Asp Gly Ile Tyr Met Val His Ile Gln Val Thr Leu 
            100                 105                 110         


Ala Ile Cys Ser Ser Thr Thr Ala Ser Arg His His Pro Thr Thr Leu 
        115                 120                 125             


Ala Val Gly Ile Cys Ser Pro Ala Ser Arg Ser Ile Ser Leu Leu Arg 
    130                 135                 140                 


Leu Ser Phe His Gln Gly Cys Thr Ile Ala Ser Gln Arg Leu Thr Pro 
145                 150                 155                 160 


Leu Ala Arg Gly Asp Thr Leu Cys Thr Asn Leu Thr Gly Thr Leu Leu 
                165                 170                 175     


Pro Ser Arg Asn Thr Asp Glu Thr Phe Phe Gly Val Gln Trp Val Arg 
            180                 185                 190         


Pro 
    


<210>  13
<211>  582
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleic-acid sequence of full length CD70

<400>  13
atgccggagg agggttcggg ctgctcggtg cggcgcaggc cctatgggtg cgtcctgcgg       60

gctgctttgg tcccattggt cgcgggcttg gtgatctgcc tcgtggtgtg catccagcgc      120

ttcgcacagg ctcagcagca gctgccgctc gagtcacttg ggtgggacgt agctgagctg      180

cagctgaatc acacaggacc tcagcaggac cccaggctat actggcaggg gggcccagca      240

ctgggccgct ccttcctgca tggaccagag ctggacaagg ggcagctacg tatccatcgt      300

gatggcatct acatggtaca catccaggtg acgctggcca tctgctcctc cacgacggcc      360

tccaggcacc accccaccac cctggccgtg ggaatctgct ctcccgcctc ccgtagcatc      420

agcctgctgc gtctcagctt ccaccaaggt tgtaccattg cctcccagcg cctgacgccc      480

ctggcccgag gggacacact ctgcaccaac ctcactggga cacttttgcc ttcccgaaac      540

actgatgaga ccttctttgg agtgcagtgg gtgcgcccct ga                         582


<210>  14
<211>  465
<212>  DNA
<213>  Artificial sequence

<220>
<223>   Nucleic-acid sequence encoding the extracellular domain of the 
       human CD70

<400>  14
cagcgcttcg cacaggctca gcagcagctg ccgctcgagt cacttgggtg ggacgtagct       60

gagctgcagc tgaatcacac aggacctcag caggacccca ggctatactg gcaggggggc      120

ccagcactgg gccgctcctt cctgcatgga ccagagctgg acaaggggca gctacgtatc      180

catcgtgatg gcatctacat ggtacacatc caggtgacgc tggccatctg ctcctccacg      240

acggcctcca ggcaccaccc caccaccctg gccgtgggaa tctgctctcc cgcctcccgt      300

agcatcagcc tgctgcgtct cagcttccac caaggttgta ccattgcctc ccagcgcctg      360

acgcccctgg cccgagggga cacactctgc accaacctca ctgggacact tttgccttcc      420

cgaaacactg atgagacctt ctttggagtg cagtgggtgc gcccc                      465


<210>  15
<211>  167
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence  PD1

<400>  15

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln 
1               5                   10                  15      


Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp 
            20                  25                  30          


Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp 
        35                  40                  45              


Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val 
    50                  55                  60                  


Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala 
65                  70                  75                  80  


Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg 
                85                  90                  95      


Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg 
            100                 105                 110         


Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu 
        115                 120                 125             


Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val 
    130                 135                 140                 


Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro 
145                 150                 155                 160 


Arg Pro Ala Gly Gln Phe Gln 
                165         


<210>  16
<211>  122
<212>  PRT
<213>  Artificial sequence

<220>
<223>   Amino-acid sequence  PD1

<400>  16

Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr Phe Ser Pro Ala Leu 
1               5                   10                  15      


Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe Thr Cys Ser Phe Ser 
            20                  25                  30          


Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr Arg Met Ser Pro Ser 
        35                  40                  45              


Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu Asp Arg Ser Gln Pro 
    50                  55                  60                  


Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu Pro Asn Gly Arg Asp 
65                  70                  75                  80  


Phe His Met Ser Val Val Arg Ala Arg Arg Asn Asp Ser Gly Thr Tyr 
                85                  90                  95      


Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala Gln Ile Lys Glu Ser 
            100                 105                 110         


Leu Arg Ala Glu Leu Arg Val Thr Glu Arg 
        115                 120         


<210>  17
<211>  1020
<212>  DNA
<213>  Artificial sequence

<220>
<223>  cloning Nucleic acid sequence of PD1-CD70 in the vector

<400>  17
gaattcccgc cgccaccatg ggctggtcct gcatcattct gtttctggtg gccacagcca       60

ccggcgtgca ctctcaccat catcaccacc atcctggctg gtttctggac agccccgaca      120

gaccttggaa ccctcctaca ttcagccccg ctctgctggt ggttaccgag ggcgataatg      180

ccaccttcac ctgtagcttc agcaacacca gcgagagctt cgtgctgaac tggtacagaa      240

tgagccccag caaccagacc gacaagctgg ccgcctttcc tgaggataga tctcagcccg      300

gccaggactg ccggttcaga gttacacagc tgcccaacgg ccgggacttc cacatgtctg      360

tcgtccgggc cagaagaaac gacagcggca catatctgtg cggcgccatt tctctggccc      420

ctaaggctca gatcaaagag agcctgagag ccgagctgag agtgacagaa agacgggccg      480

aagtgcccac agctcaccct tcaccttctc caagacctgc cggccagttt cagacactcg      540

tgggacagag attcgcccag gctcagcagc aactgcctct ggaatctctc ggctgggatg      600

ttgccgaact gcagctgaat cacacaggcc ctcagcagga ccccagactg tattggcaag      660

gcggacctgc tctgggcaga tcctttctgc atggccccga gctggataag ggccagctga      720

gaatccaccg cgacggcatc tacatggtgc acatccaagt gaccctggcc atctgcagca      780

gcaccacagc ctctagacat caccctacca cactggccgt gggcatctgt tctccagcca      840

gcagatctat cagcctgctg cggctgagct tccaccaggg atgtacaatc gccagccaga      900

gactgacccc tctggctaga ggcgataccc tgtgcaccaa tctgaccggc acactgctgc      960

ccagccggaa caccgatgag acattctttg gcgtgcagtg ggtccgacct tgataagctt     1020


