                         SEQUENCE LISTING

<110>  Pieris AG
 
<120>  Methods and Compositions for anti-VEGF and anti-cMet therapy

<130>  PIE14159PCT

<150>  US 61/471,618
<151>  2011-04-04

<160>  14    

<170>  PatentIn version 3.5

<210>  1
<211>  154
<212>  PRT
<213>  Homo sapiens

<220>  
<223>  anti-VEGF lipocalin mutein (Cys at position 91 and without C-terminal Strep-tag)

<400>  1

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


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


Ile Pro Thr Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Lys 
        35                  40                  45              


Val Thr Met His Ile Lys Gly Arg Ser Gln Glu Val Lys Ala Val Leu 
    50                  55                  60                  


Ser Lys Thr Asp Glu Pro Gly Ile Tyr Thr Ala Ile Gly Gly Ile His 
65                  70                  75                  80  


Val Ala Lys Ile Gly Arg Ser His Val Lys Cys His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Cys Leu Ser Gly Val Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Asn Leu Glu Ala Leu Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Asp 
145                 150                 


<210>  2
<211>  162
<212>  PRT
<213>  Homo sapiens

<220>  
<223>  anti-c-Met lipocalin mutein (Leu at position 123 and with C-terminal Strep-tag)

<400>  2

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


Ala Met Thr Val Asp Thr Gln Asp Pro Leu Ser Leu Tyr Val Ser Val 
            20                  25                  30          


Ser Pro Ile Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Thr 
        35                  40                  45              


Val Thr Leu Asn Gln Ile Gly Arg Ser Gln Glu Val Leu Ala Val Leu 
    50                  55                  60                  


Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Leu Tyr Gly Gly Ala His 
65                  70                  75                  80  


Val Ala Tyr Ile Gln Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Asp Thr Trp Gly Gly Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Cys Leu Glu Ala Leu Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Ala Trp Ser His Pro Gln Phe 
145                 150                 155                 160 


Glu Lys 
        


<210>  3
<211>  162
<212>  PRT
<213>  Homo sapiens

<220>  
<223>  lipocalin wt isotype control (Leu at position 123 and with C-terminal Strep-tag)

<400>  3

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


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


Thr Pro Met Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Lys 
        35                  40                  45              


Val Thr Met Leu Ile Ser Gly Arg Ser Gln Glu Val Lys Ala Val Leu 
    50                  55                  60                  


Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Ala Asp Gly Gly Lys His 
65                  70                  75                  80  


Val Ala Tyr Ile Ile Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Glu Leu His Gly Lys Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Cys Leu Glu Ala Leu Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Ala Trp Ser His Pro Gln Phe 
145                 150                 155                 160 


Glu Lys 
        


<210>  4
<211>  462
<212>  DNA
<213>  Homo sapiens

<220>  
<223>  anti-VEGF lipocalin mutein

<400>  4
gcgagcgatg aagaaattca ggatgtgagc ggcacctggt atctgaaagc catgaccgtg       60

gatgtgggcg cgctgcgttg tctggccggc agcgtgattc cgaccaccct gaccaccctg      120

gaaggcggca acctggaagc gaaagtgacc atgcatatca aaggtcgtag ccaggaagtg      180

aaagcggttc tgagcaaaac cgatgaaccg ggcatttata ccgcgattgg cggcattcat      240

gtggcgaaaa ttggtcgtag ccatgtgaaa tgccactata tcttctatag cgaaggctgc      300

ctgagcggtg ttccggtgcc gggtgtgtgg ctggttggcc gtgatccgaa aaacaatctg      360

gaagcgctgg aagattttga aaaagcggcg ggtgcgcgtg gtctgagcac cgaaagcatt      420

ctgattccgc gtcagagcga aaccagcagc ccgggcagcg at                         462


<210>  5
<211>  486
<212>  DNA
<213>  Homo sapiens

<220>  
<223>  anti-c-Met lipocalin mutein

<400>  5
gcctcagacg aggagattca ggatgtgtca gggacgtggt atctgaaggc catgacggtg       60

gacacgcagg acccgctgag cctctacgtc tcggtgtcac ccatcaccct cacgaccctg      120

gaagggggca acctggaagc cacggtcacc ttgaaccaga tcggccggtc ccaggaggtg      180

ttggccgtcc tggagaaaac tgatgagccg ggaaaataca cgttgtacgg aggtgctcac      240

gtggcataca tccagaggtc gcacgtgaag gaccactaca tcttttactc tgagggcgac      300

acctgggggg ggccggtccc aggggtgtgg ctcgtgggca gagaccccaa gaactgcctg      360

gaagccttgg aggactttga gaaagccgca ggagcccgcg gactcagcac ggagagcatc      420

ctcatcccca ggcagagcga aaccagctct ccagggagcg cttggtctca cccgcagttc      480

gaaaaa                                                                 486


<210>  6
<211>  486
<212>  DNA
<213>  Homo sapiens

<220>  
<223>  lipocalin wt isotype control

<400>  6
gcctcagacg aggagattca ggatgtgtca gggacgtggt atctgaaggc catgacggtg       60

gacagggagt tccctgagat gaatctggaa tcggtgacac ccatgaccct cacgaccctg      120

gaagggggca acctggaagc caaggtcacc atgctgataa gtggccggag ccaggaggtg      180

aaggccgtcc tggagaaaac tgacgagccg ggaaaataca cggccgacgg gggcaagcac      240

gtggcataca tcatcaggtc gcacgtgaag gaccactaca tcttttactc tgagggcgag      300

ctccacggga agccggtccc aggggtgtgg ctcgtgggca gagaccccaa gaactgcctg      360

gaagccttgg aggactttga gaaagccgca ggagcccgcg gactcagcac ggagagcatc      420

ctcatcccca ggcagagcga aaccagctct ccagggagcg cttggtctca cccgcagttc      480

gaaaaa                                                                 486


<210>  7
<211>  4
<212>  PRT
<213>  artificial

<220>
<223>  N-terminal amino acids 1 to 4 of tear lipocalin

<400>  7

His His Leu Ala 
1               


<210>  8
<211>  154
<212>  PRT
<213>  Homo sapiens

<220>
<223>  anti-VEGF lipocalin mutein (Asp at position 91 and without C-terminal Srep-tag)

<400>  8

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


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


Ile Pro Thr Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Lys 
        35                  40                  45              


Val Thr Met His Ile Lys Gly Arg Ser Gln Glu Val Lys Ala Val Leu 
    50                  55                  60                  


Ser Lys Thr Asp Glu Pro Gly Ile Tyr Thr Ala Ile Gly Gly Ile His 
65                  70                  75                  80  


Val Ala Lys Ile Gly Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Cys Leu Ser Gly Val Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Asn Leu Glu Ala Leu Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Asp 
145                 150                 


<210>  9
<211>  162
<212>  PRT
<213>  Homo sapiens

<220>
<223>  anti-c-Met lipocalin mutein (Cys at position 123 and with C-terminal Strep-tag)

<400>  9

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


Ala Met Thr Val Asp Thr Gln Asp Pro Leu Ser Leu Tyr Val Ser Val 
            20                  25                  30          


Ser Pro Ile Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Thr 
        35                  40                  45              


Val Thr Leu Asn Gln Ile Gly Arg Ser Gln Glu Val Leu Ala Val Leu 
    50                  55                  60                  


Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Leu Tyr Gly Gly Ala His 
65                  70                  75                  80  


Val Ala Tyr Ile Gln Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Asp Thr Trp Gly Gly Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Cys Leu Glu Ala Cys Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Ala Trp Ser His Pro Gln Phe 
145                 150                 155                 160 


Glu Lys 
        


<210>  10
<211>  162
<212>  PRT
<213>  Homo sapiens

<220>  
<223>  lipocalin wt isotype control (Cys at position 123 and with C-terminal Strep-tag)

<400>  10

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


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


Thr Pro Met Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Lys 
        35                  40                  45              


Val Thr Met Leu Ile Ser Gly Arg Ser Gln Glu Val Lys Ala Val Leu 
    50                  55                  60                  


Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Ala Asp Gly Gly Lys His 
65                  70                  75                  80  


Val Ala Tyr Ile Ile Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Glu Leu His Gly Lys Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Cys Leu Glu Ala Cys Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Ala Trp Ser His Pro Gln Phe 
145                 150                 155                 160 


Glu Lys 
        


<210>  11
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  Strep-tag

<400>  11

Trp Ser His Pro Gln Phe Glu Lys 
1               5               


<210>  12
<211>  162
<212>  PRT
<213>  Homo sapiens

<220>
<223>  anti-VEGF lipocalin mutein (Cys at position 91 and with C-terminal Strep-tag)

<400>  12

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


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


Ile Pro Thr Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Lys 
        35                  40                  45              


Val Thr Met His Ile Lys Gly Arg Ser Gln Glu Val Lys Ala Val Leu 
    50                  55                  60                  


Ser Lys Thr Asp Glu Pro Gly Ile Tyr Thr Ala Ile Gly Gly Ile His 
65                  70                  75                  80  


Val Ala Lys Ile Gly Arg Ser His Val Lys Cys His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Cys Leu Ser Gly Val Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Asn Leu Glu Ala Leu Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Asp Trp Ser His Pro Gln Phe 
145                 150                 155                 160 


Glu Lys 
        


<210>  13
<211>  154
<212>  PRT
<213>  Homo sapiens

<220>  
<223>  anti-c-Met lipocalin mutein (Cys at position 123 and without C-terminal Strep-tag )

<400>  13

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


Ala Met Thr Val Asp Thr Gln Asp Pro Leu Ser Leu Tyr Val Ser Val 
            20                  25                  30          


Ser Pro Ile Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Thr 
        35                  40                  45              


Val Thr Leu Asn Gln Ile Gly Arg Ser Gln Glu Val Leu Ala Val Leu 
    50                  55                  60                  


Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Leu Tyr Gly Gly Ala His 
65                  70                  75                  80  


Val Ala Tyr Ile Gln Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Asp Thr Trp Gly Gly Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Cys Leu Glu Ala Cys Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Ala 
145                 150                 


<210>  14
<211>  154
<212>  PRT
<213>  Homo sapiens

<220>  
<223>  lipocalin wt isotype control (Leu at position 123 and without C-terminal Strep-tag )

<400>  14

Ala Ser Asp Glu Glu Ile Gln Asp Val Ser Gly Thr Trp Tyr Leu Lys 
1               5                   10                  15      


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


Thr Pro Met Thr Leu Thr Thr Leu Glu Gly Gly Asn Leu Glu Ala Lys 
        35                  40                  45              


Val Thr Met Leu Ile Ser Gly Arg Ser Gln Glu Val Lys Ala Val Leu 
    50                  55                  60                  


Glu Lys Thr Asp Glu Pro Gly Lys Tyr Thr Ala Asp Gly Gly Lys His 
65                  70                  75                  80  


Val Ala Tyr Ile Ile Arg Ser His Val Lys Asp His Tyr Ile Phe Tyr 
                85                  90                  95      


Ser Glu Gly Glu Leu His Gly Lys Pro Val Pro Gly Val Trp Leu Val 
            100                 105                 110         


Gly Arg Asp Pro Lys Asn Cys Leu Glu Ala Leu Glu Asp Phe Glu Lys 
        115                 120                 125             


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


Gln Ser Glu Thr Ser Ser Pro Gly Ser Ala 
145                 150                 


