                             

<110>  ϺƼɷ޹˾
 
<120>  һְ˳1PD-L1ĵɱ弰

<130>  

<160>  45    

<170>  PatentIn version 3.5

<210>  1
<211>  120
<212>  PRT
<213>  VHH-F2

<400>  1

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


Ser Leu Arg Leu Ala Cys Ala Val Ser Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly 
        35                  40                  45              


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


Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Leu 
65                  70                  75                  80  


Phe Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Ser Ala Met Tyr Tyr 
                85                  90                  95      


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Phe Gly Gln 
            100                 105                 110         


Gly Thr Gln Val Thr Val Ser Ser 
        115                 120 


<210>  2
<211>  360
<212>  DNA
<213>  VHH-F2

<400>  2
caggtgcagc tgcaggagtc tggaggaggc tcggtgcaga ctggagggtc tctgagactc       60

gcctgtgcag tctctagaga cagtgacgac ggtgccagct gtatggggtg gttccgccag      120

gctccaggga aggggcgcga gggggtcgca atcattttta atgctggtga acgtaccgac      180

tatggcgact ccgtgaaggg ccgattcacc atctcccaag acaacgccaa gaacacgctg      240

tttctacaaa tgaacagcct gaaacctgag gacagtgcca tgtactattg tgcgacagtt      300

tggtgtggtt cttgggtcgc gcgttctttc ggccagggga cccaggtcac cgtctcctca      360


<210>  3
<211>  353
<212>  PRT
<213>  chF2-C region

<400>  3

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


Ser Leu Arg Leu Ala Cys Ala Val Ser Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly 
        35                  40                  45              


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


Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Leu 
65                  70                  75                  80  


Phe Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Ser Ala Met Tyr Tyr 
                85                  90                  95      


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Phe Gly Gln 
            100                 105                 110         


Gly Thr Gln Val Thr Val Ser Ser Ala Ser Glu Pro Lys Ser Ser Asp 
        115                 120                 125             


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
    130                 135                 140                 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                165                 170                 175     


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
            180                 185                 190         


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
        195                 200                 205             


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
    210                 215                 220                 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
225                 230                 235                 240 


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                245                 250                 255     


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
            260                 265                 270         


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
        275                 280                 285             


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
    290                 295                 300                 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
305                 310                 315                 320 


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                325                 330                 335     


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
            340                 345                 350         


Gly 
    


<210>  4
<211>  1059
<212>  DNA
<213>  chF2-C region

<400>  4
caggtgcagc tgcaggagtc tggaggaggc tcggtgcaga ctggagggtc tctgagactc       60

gcctgtgcag tctctagaga cagtgacgac ggtgccagct gtatggggtg gttccgccag      120

gctccaggga aggggcgcga gggggtcgca atcattttta atgctggtga acgtaccgac      180

tatggcgact ccgtgaaggg ccgattcacc atctcccaag acaacgccaa gaacacgctg      240

tttctacaaa tgaacagcct gaaacctgag gacagtgcca tgtactattg tgcgacagtt      300

tggtgtggtt cttgggtcgc gcgttctttc ggccagggga cccaggtcac cgtctcctca      360

gctagcgagc ccaaatctag cgacaaaact cacacatgcc caccgtgccc agcacctgaa      420

ctcctggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatc      480

tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc      540

aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag      600

gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg      660

ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag      720

aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgcctcca      780

tctcgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat      840

cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc      900

acgcctcccg tgctggactc cgacggctcc ttcttcctct atagcaagct caccgtggac      960

aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac     1020

aaccactaca cgcagaagag cctctccctg tccccgggt                            1059


<210>  5
<211>  128
<212>  PRT
<213>  KN035

<400>  5

Gln 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 Lys Met Ser Ser Arg Arg 
            20                  25                  30          


Cys Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Arg Val 
        35                  40                  45              


Ala Lys Leu Leu Thr Thr Ser Gly Ser Thr Tyr Leu Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Asp Ser Phe Glu Asp Pro Thr Cys Thr Leu Val Thr Ser Ser 
            100                 105                 110         


Gly Ala Phe Gln Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125             


<210>  6
<211>  384
<212>  DNA
<213>  KN035

<400>  6
caggtgcagc tggtggagtc tggaggaggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctggcaa gatgtcctcc agacggtgca tggcctggtt ccgacaggct      120

cctggcaagg agcgagagcg ggtggccaag ctgctgacca cctccggctc cacctacctg      180

gccgactccg tgaagggacg gttcaccatc tccagggaca actccaagaa caccgtgtac      240

ctgcagatga actccctgcg agctgaggac accgccgtgt actactgcgc tgcagactcc      300

ttcgaggacc ccacctgcac cctggtgacc tcctctggag ccttccagta ctggggacag      360

ggcaccctgg tgaccgtgtc ctcc                                             384


<210>  7
<211>  120
<212>  PRT
<213>  hzF2

<400>  7

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  8
<211>  360
<212>  DNA
<213>  hzF2

<400>  8
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  9
<211>  353
<212>  PRT
<213>  hzF2-C region

<400>  9

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


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


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
    130                 135                 140                 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                165                 170                 175     


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
            180                 185                 190         


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
        195                 200                 205             


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
    210                 215                 220                 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
225                 230                 235                 240 


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                245                 250                 255     


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
            260                 265                 270         


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
        275                 280                 285             


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
    290                 295                 300                 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
305                 310                 315                 320 


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                325                 330                 335     


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
            340                 345                 350         


Gly 
    


<210>  10
<211>  1059
<212>  DNA
<213>  hzF2-C region

<400>  10
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360

gctagcgagc ccaaatctag cgacaaaact cacacatgcc caccgtgccc agcacctgaa      420

ctcctggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatc      480

tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc      540

aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag      600

gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg      660

ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag      720

aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgcctcca      780

tctcgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat      840

cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc      900

acgcctcccg tgctggactc cgacggctcc ttcttcctct atagcaagct caccgtggac      960

aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac     1020

aaccactaca cgcagaagag cctctccctg tccccgggt                            1059


<210>  11
<211>  120
<212>  PRT
<213>  hzF2-m1

<400>  11

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Ser Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  12
<211>  120
<212>  PRT
<213>  hzF2-m2

<400>  12

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 Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  13
<211>  120
<212>  PRT
<213>  hzF2-m3

<400>  13

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 Arg Asp Ser Ser Ser Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  14
<211>  120
<212>  PRT
<213>  hzF2-m4

<400>  14

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 Arg Asp Ser Asn Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  15
<211>  120
<212>  PRT
<213>  hzF2-m5

<400>  15

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 Arg Asp Ser Asp Asp Ala Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  16
<211>  120
<212>  PRT
<213>  hzF2-m6

<400>  16

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 Arg Asp Ser Asp Glu Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  17
<211>  120
<212>  PRT
<213>  hzF2-m7

<400>  17

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 Arg Asp Ser Asp Asp Ser Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  18
<211>  120
<212>  PRT
<213>  hzF2-m8

<400>  18

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  19
<211>  120
<212>  PRT
<213>  hzF2-m9

<400>  19

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 Arg Asp Ser Asp Glu Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  20
<211>  120
<212>  PRT
<213>  hzF2-m10

<400>  20

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Tyr Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  21
<211>  120
<212>  PRT
<213>  hzF2-m11

<400>  21

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Tyr Cys Gly Ser Tyr Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  22
<211>  120
<212>  PRT
<213>  hzF2-m12

<400>  22

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 Arg Asp Ser Asp Glu Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Trp Cys Gly Ser Trp Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  23
<211>  120
<212>  PRT
<213>  hzF2-m13

<400>  23

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 Arg Asp Ser Asp Asp Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Phe Cys Gly Ser Phe Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  24
<211>  120
<212>  PRT
<213>  hzF2-m14

<400>  24

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 Arg Asp Ser Asp Glu Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Tyr Cys Gly Ser Tyr Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  25
<211>  120
<212>  PRT
<213>  hzF2-m15

<400>  25

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 Arg Asp Ser Asp Glu Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Phe Cys Gly Ser Tyr Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  26
<211>  120
<212>  PRT
<213>  hzF2-m16

<400>  26

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 Arg Asp Ser Asp Glu Gly Ala 
            20                  25                  30          


Ser Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly 
        35                  40                  45              


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


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


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


Cys Ala Thr Val Phe Cys Gly Ser Phe Val Ala Arg Ser Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  27
<211>  360
<212>  DNA
<213>  hzF2-m1

<400>  27
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcca gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtccggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  28
<211>  360
<212>  DNA
<213>  hzF2-m2

<400>  28
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctggaga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  29
<211>  360
<212>  DNA
<213>  hzF2-m3

<400>  29
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccagcagc ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  30
<211>  360
<212>  DNA
<213>  hzF2-m4

<400>  30
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccaacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  31
<211>  360
<212>  DNA
<213>  hzF2-m5

<400>  31
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac gctgcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  32
<211>  360
<212>  DNA
<213>  hzF2-m6

<400>  32
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgag ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  33
<211>  360
<212>  DNA
<213>  hzF2-m7

<400>  33
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac tctgcctcct gcatgggctg gttcaggcag      120

gctcctggca agggcctgga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  34
<211>  360
<212>  DNA
<213>  hzF2-m8

<400>  34
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgtgggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  35
<211>  360
<212>  DNA
<213>  hzF2-m9

<400>  35
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgag ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  36
<211>  360
<212>  DNA
<213>  hzF2-m10

<400>  36
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tactgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  37
<211>  360
<212>  DNA
<213>  hzF2-m11

<400>  37
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tactgtggct cctacgtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  38
<211>  360
<212>  DNA
<213>  hzF2-m12

<400>  38
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgag ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgtgggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tggtgtggct cctgggtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  39
<211>  360
<212>  DNA
<213>  hzF2-m13

<400>  39
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgac ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgctggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

ttctgtggct ccttcgtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  40
<211>  360
<212>  DNA
<213>  hzF2-m14

<400>  40
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgag ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgtgggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

tactgtggct cctacgtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  41
<211>  360
<212>  DNA
<213>  hzF2-m15

<400>  41
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgag ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgtgggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

ttctgtggct cctacgtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  42
<211>  360
<212>  DNA
<213>  hzF2-m16

<400>  42
gaggtgcagc tggtggagtc tggaggtggc ctggtgcagc ctggaggctc cctgaggctg       60

tcctgcgctg cctctcggga ctccgacgag ggagcctcct gcatgggctg gttcaggcag      120

gctcctggca aggagagaga gggagtggcc atcatcttca acgtgggcga gcggaccgac      180

tacggcgact ccgtgaaggg acggttcacc atctccaggg acaacgccaa gaacaccctg      240

tacctgcaga tgaactccct gagagccgag gacacagccg tgtactactg cgctaccgtg      300

ttctgtggct ccttcgtggc tcggtcctgg ggacagggca ccctggtgac cgtgtcctcc      360


<210>  43
<211>  11
<212>  PRT
<213>  VHH-F2 CDR1

<400>  43

Arg Asp Ser Asp Asp Gly Ala Ser Cys Met Gly 
1               5                   10      


<210>  44
<211>  17
<212>  PRT
<213>  VHH-F2 CDR2

<400>  44

Ile Ile Phe Asn Ala Gly Glu Arg Thr Asp Tyr Gly Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  45
<211>  10
<212>  PRT
<213>  VHH-F2 CDR3

<400>  45

Val Trp Cys Gly Ser Trp Val Ala Arg Ser 
1               5                   10  


