                         SEQUENCE LISTING

<110>  MacroGenics, Inc.
       Wigginton, Jon Marc
       Lechleider, Robert Joseph
       Alderson, Ralph
 
<120>  Bi-Specific Monovalent Diabodies That Are Capable Of Binding 
       CD123 And CD3 And Uses Thereof

<130>  1301.0152P

<160>  24    

<170>  PatentIn version 3.5

<210>  1
<211>  110
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VLCD3 Domain of DART-A

<400>  1

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


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


Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Thr Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Thr Gly Ala 
65                  70                  75                  80  


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110 


<210>  2
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of VLCD3 Domain of DART-A

<400>  2

Arg Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn 
1               5                   10                  


<210>  3
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of VLCD3 Domain of DART-A

<400>  3

Gly Thr Asn Lys Arg Ala Pro 
1               5           


<210>  4
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of VLCD3 Domain of DART-A

<400>  4

Ala Leu Trp Tyr Ser Asn Leu Trp Val 
1               5                   


<210>  5
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker 1

<400>  5

Gly Gly Gly Ser Gly Gly Gly Gly 
1               5               


<210>  6
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VHCD123 Domain of DART-A

<400>  6

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


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


Gly Asp Ile Ile Pro Ser Asn Gly Ala Thr Phe Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Ser His Leu Leu Arg Ala Ser Trp Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  7
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of VHCD123 Domain of DART-A

<400>  7

Asp Tyr Tyr Met Lys 
1               5   


<210>  8
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of VHCD123 Domain of DART-A

<400>  8

Asp Ile Ile Pro Ser Asn Gly Ala Thr Phe Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  9
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of VHCD123 Domain of DART-A

<400>  9

Ser His Leu Leu Arg Ala Ser 
1               5           


<210>  10
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VLCD123 Domain of DART-A

<400>  10

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


Glu Arg Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


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


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Asp Tyr Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
            100                 105                 110         


Lys 
    


<210>  11
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of VLCD123 Domain of DART-A

<400>  11

Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  12
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of VLCD123 Domain of DART-A

<400>  12

Trp Ala Ser Thr Arg Glu Leu Ser 
1               5               


<210>  13
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of VLCD123 Domain of DART-A

<400>  13

Gln Asn Asp Tyr Ser Tyr Pro Tyr Thr 
1               5                   


<210>  14
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VHCD3 Domain of DART-A

<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 Gly Phe Thr Phe Ser Thr Tyr 
            20                  25                  30          


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


Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe 
            100                 105                 110         


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


<210>  15
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of VHCD3 Domain of DART-A

<400>  15

Thr Ala Met Met 
1               


<210>  16
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of VHCD3 Domain of DART-A

<400>  16

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
1               5                   10                  15      


Val Lys Asp 
            


<210>  17
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of VHCD3 Domain of DART-A

<400>  17

His Gly Asn Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr 
1               5                   10                  


<210>  18
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker 2

<400>  18

Gly Gly Cys Gly Gly Gly 
1               5       


<210>  19
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  E-Coil Heterodimer-Promoting Domain

<400>  19

Glu Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys Glu Val 
1               5                   10                  15      


Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys 
            20                  25              


<210>  20
<211>  28
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  K-Coil Heterodimer-Promoting Domain

<400>  20

Lys Val Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu Lys Val 
1               5                   10                  15      


Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys Glu 
            20                  25              


<210>  21
<211>  272
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  First Polypeptide Chain of Sequence-Optimized CD123 x CD3 
       Bi-specific Diabody (DART-A)

<400>  21

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


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


Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 
        35                  40                  45              


Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Trp Thr Pro Ala Arg Phe 
    50                  55                  60                  


Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Thr Gly Ala 
65                  70                  75                  80  


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


Leu Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly 
            100                 105                 110         


Gly Ser Gly Gly Gly Gly Glu Val Gln Leu Val Gln Ser Gly Ala Glu 
        115                 120                 125             


Leu Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly 
    130                 135                 140                 


Tyr Thr Phe Thr Asp Tyr Tyr Met Lys Trp Val Arg Gln Ala Pro Gly 
145                 150                 155                 160 


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


Phe Tyr Asn Gln Lys Phe Lys Gly Arg Val Thr Ile Thr Val Asp Lys 
            180                 185                 190         


Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 
        195                 200                 205             


Thr Ala Val Tyr Tyr Cys Ala Arg Ser His Leu Leu Arg Ala Ser Trp 
    210                 215                 220                 


Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly 
225                 230                 235                 240 


Cys Gly Gly Gly Glu Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu 
                245                 250                 255     


Glu Lys Glu Val Ala Ala Leu Glu Lys Glu Val Ala Ala Leu Glu Lys 
            260                 265                 270         


<210>  22
<211>  816
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucelotide Encoding First Polypeptide Chain of 
       Sequence-Optimized CD123 x CD3 Bi-specific Diabody (DART-A)

<400>  22
caggctgtgg tgactcagga gccttcactg accgtgtccc caggcggaac tgtgaccctg       60

acatgcagat ccagcacagg cgcagtgacc acatctaact acgccaattg ggtgcagcag      120

aagccaggac aggcaccaag gggcctgatc gggggtacaa acaaaagggc tccctggacc      180

cctgcacggt tttctggaag tctgctgggc ggaaaggccg ctctgactat taccggggca      240

caggccgagg acgaagccga ttactattgt gctctgtggt atagcaatct gtgggtgttc      300

gggggtggca caaaactgac tgtgctggga gggggtggat ccggcggcgg aggcgaggtg      360

cagctggtgc agtccggggc tgagctgaag aaacccggag cttccgtgaa ggtgtcttgc      420

aaagccagtg gctacacctt cacagactac tatatgaagt gggtcaggca ggctccagga      480

cagggactgg aatggatcgg cgatatcatt ccttccaacg gggccacttt ctacaatcag      540

aagtttaaag gcagggtgac tattaccgtg gacaaatcaa caagcactgc ttatatggag      600

ctgagctccc tgcgctctga agatacagcc gtgtactatt gtgctcggtc acacctgctg      660

agagccagct ggtttgctta ttggggacag ggcaccctgg tgacagtgtc ttccggagga      720

tgtggcggtg gagaagtggc cgcactggag aaagaggttg ctgctttgga gaaggaggtc      780

gctgcacttg aaaaggaggt cgcagccctg gagaaa                                816


<210>  23
<211>  280
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Second Polypeptide Chain of Sequence-Optimized CD123 x CD3 
       Bi-specific Diabody (DART-A)

<400>  23

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


Glu Arg Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


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


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Asp Tyr Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
            100                 105                 110         


Lys Gly Gly Gly Ser Gly Gly Gly Gly Glu Val Gln Leu Val Glu Ser 
        115                 120                 125             


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


Ala Ser Gly Phe Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln 
145                 150                 155                 160 


Ala Pro Gly Lys Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr 
                165                 170                 175     


Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr 
            180                 185                 190         


Ile Ser Arg Asp Asp Ser Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser 
        195                 200                 205             


Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn 
    210                 215                 220                 


Phe Gly Asn Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Leu Val Thr Val Ser Ser Gly Gly Cys Gly Gly Gly Lys Val Ala Ala 
                245                 250                 255     


Leu Lys Glu Lys Val Ala Ala Leu Lys Glu Lys Val Ala Ala Leu Lys 
            260                 265                 270         


Glu Lys Val Ala Ala Leu Lys Glu 
        275                 280 


<210>  24
<211>  840
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Polynucelotide Encoding Second Polypeptide Chain of 
       Sequence-Optimized CD123 x CD3 Bi-specific Diabody (DART-A)

<400>  24
gacttcgtga tgacacagtc tcctgatagt ctggccgtga gtctggggga gcgggtgact       60

atgtcttgca agagctccca gtcactgctg aacagcggaa atcagaaaaa ctatctgacc      120

tggtaccagc agaagccagg ccagccccct aaactgctga tctattgggc ttccaccagg      180

gaatctggcg tgcccgacag attcagcggc agcggcagcg gcacagattt taccctgaca      240

atttctagtc tgcaggccga ggacgtggct gtgtactatt gtcagaatga ttacagctat      300

ccctacactt tcggccaggg gaccaagctg gaaattaaag gaggcggatc cggcggcgga      360

ggcgaggtgc agctggtgga gtctggggga ggcttggtcc agcctggagg gtccctgaga      420

ctctcctgtg cagcctctgg attcaccttc agcacatacg ctatgaattg ggtccgccag      480

gctccaggga aggggctgga gtgggttgga aggatcaggt ccaagtacaa caattatgca      540

acctactatg ccgactctgt gaaggataga ttcaccatct caagagatga ttcaaagaac      600

tcactgtatc tgcaaatgaa cagcctgaaa accgaggaca cggccgtgta ttactgtgtg      660

agacacggta acttcggcaa ttcttacgtg tcttggtttg cttattgggg acaggggaca      720

ctggtgactg tgtcttccgg aggatgtggc ggtggaaaag tggccgcact gaaggagaaa      780

gttgctgctt tgaaagagaa ggtcgccgca cttaaggaaa aggtcgcagc cctgaaagag      840


