                         SEQUENCE LISTING

<110>  LEADARTIS, S.L.
 
<120>  NOVEL MULTIVALENT ANTIBODIES, METHODS FOR OBTAINING THE SAME AND 
       USES THEREOF

<130>  901 891

<150>  EP 15 382 619.3
<151>  2015-12-11

<150>  EP 16 382 003.8
<151>  2016-01-05

<160>  42    

<170>  PatentIn version 3.5

<210>  1
<211>  64
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Trimerizing structural element of collagen XV


<220>
<221>  MISC_FEATURE
<222>  (1)..(64)

<400>  1

Val Thr Ala Phe Ser Asn Met Asp Asp Met Leu Gln Lys Ala His Leu 
1               5                   10                  15      


Val Ile Glu Gly Thr Phe Ile Tyr Leu Arg Asp Ser Thr Glu Phe Phe 
            20                  25                  30          


Ile Arg Val Arg Asp Gly Trp Lys Lys Leu Gln Leu Gly Glu Leu Ile 
        35                  40                  45              


Pro Ile Pro Ala Asp Ser Pro Pro Pro Pro Ala Leu Ser Ser Asn Pro 
    50                  55                  60                  


<210>  2
<211>  59
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Trimerizing Structural Element of collagen XVIII


<220>
<221>  MISC_FEATURE
<222>  (1)..(59)

<400>  2

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


His Glu Val Pro Glu Gly Trp Leu Ile Phe Val Ala Glu Gln Glu Glu 
            20                  25                  30          


Leu Tyr Val Arg Val Gln Asn Gly Phe Arg Lys Val Gln Leu Glu Ala 
        35                  40                  45              


Arg Thr Pro Leu Pro Arg Gly Thr Asp Asn Glu 
    50                  55                  


<210>  3
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  polyglycine linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(14)

<400>  3

Ser Gly Gly Thr Ser Gly Ser Thr Ser Gly Thr Gly Ser Thr 
1               5                   10                  


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

<220>
<223>  Polyglycine linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(15)

<400>  4

Ala Gly Ser Ser Thr Gly Ser Ser Thr Gly Pro Gly Ser Thr Thr 
1               5                   10                  15  


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

<220>
<223>  polyglycine linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)

<400>  5

Gly Gly Ser Gly Gly Ala Pro 
1               5           


<210>  6
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  polyglycine linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(8)

<400>  6

Gly Gly Gly Val Glu Gly Gly Gly 
1               5               


<210>  7
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(4)

<400>  7

Gly Ser Pro Gly 
1               


<210>  8
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(13)

<400>  8

Ala Ala Ala Gly Gly Ser Gly Gly Ser Ser Gly Ser Arg 
1               5                   10              


<210>  9
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(8)

<400>  9

Gly Ser Gly Ser Gly Ser Gly Ser 
1               5               


<210>  10
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(21)

<400>  10

Ala Asn Ser Gly Ala Gly Gly Ser Gly Gly Ser Ser Gly Ser Asp Gly 
1               5                   10                  15      


Ala Ser Gly Ser Arg 
            20      


<210>  11
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(10)

<400>  11

Pro Lys Pro Ser Thr Pro Pro Gly Ser Ser 
1               5                   10  


<210>  12
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(11)

<400>  12

Ala Pro Ala Glu Thr Lys Ala Glu Pro Met Thr 
1               5                   10      


<210>  13
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(5)

<400>  13

Ala Ala Ala Leu Glu 
1               5   


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

<220>
<223>  anti-CEA1 VHH


<220>
<221>  MISC_FEATURE
<222>  (1)..(125)

<400>  14

Met Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly Ser Val Gln Ala 
1               5                   10                  15      


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Asp Thr Tyr Gly 
            20                  25                  30          


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


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


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


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


Tyr Cys Ala Ala Ser Gly Val Leu Gly Gly Leu His Glu Asp Trp Phe 
            100                 105                 110         


Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125 


<210>  15
<211>  375
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Anti-CEA1 VHH encoding sequence


<220>
<221>  misc_feature
<222>  (1)..(375)

<400>  15
atggctcagg tgcagctggt ggagtctggg ggaggctcgg tgcaggctgg agggtctctg       60

agactctcct gtgcggcctc tggagacacc tacggtagct actggatggg ctggttccgc      120

caggctccag ggaaggagcg tgagggggtc gcagctatta ataggggtgg tggctataca      180

gtctacgccg actccgtgaa gggccgattc accatctccc gagacaccgc caagaacacg      240

gtgtatctgc aaatgaacag cctgagacct gacgacacgg ccgactatta ctgtgcggct      300

agcggggtac taggtggttt acatgaggac tggtttaact actggggcca ggggacccag      360

gtcaccgtct cctca                                                       375


<210>  16
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-GFP VHH


<220>
<221>  MISC_FEATURE
<222>  (1)..(117)

<400>  16

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


Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Pro Val Asn 
            20                  25                  30          


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


Trp Val Ala Gly Met Ser Ser Ala Gly Asp Arg Ser Ser Tyr Glu Asp 
    50                  55                  60                  


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


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


Tyr Cys Asn Val Asn Val Gly Phe Glu Tyr Trp Gly Gln Gly Thr Gln 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  17
<211>  351
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Anti-GFP VHH encoding sequence


<220>
<221>  misc_feature
<222>  (1)..(351)

<400>  17
atggctcagg tgcagctggt ggagtctggg ggagccttgg tgcagccggg ggggtctctg       60

agactctcct gtgcagcctc tggattcccc gtcaatcgct atagtatgag gtggtaccgc      120

caggctccag ggaaggagcg cgagtgggtc gcgggtatga gtagtgctgg tgatcgttca      180

agttatgaag actccgtgaa gggccgattc accatctcca gagacgacgc caggaatacg      240

gtgtatctgc aaatgaacag cctgaaacct gaggacacgg ccgtgtatta ctgtaatgtc      300

aatgtgggct ttgagtactg gggccagggg acccaggtca ccgtctcctc a               351


<210>  18
<211>  132
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-EGFR VHH


<220>
<221>  MISC_FEATURE
<222>  (1)..(132)

<400>  18

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


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


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


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


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


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


Tyr Cys Ala Ala Thr Tyr Leu Ser Ser Asp Tyr Ser Arg Tyr Ala Leu 
            100                 105                 110         


Pro Gln Arg Pro Leu Asp Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val 
        115                 120                 125             


Thr Val Ser Ser 
    130         


<210>  19
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  anti-EGFR VHH encoding sequence


<220>
<221>  misc_feature
<222>  (1)..(396)

<400>  19
atggctcagg tgcagctgca ggagtctggg ggaggattgg tgcagccagg gggctcgctg       60

agactctcct gtgcagcctc tggacgcacc ttcagtagct atgccatggg ctggttccgc      120

caggctccag ggaaggagcg tgagtttgta gcagctatta ggtggagtgg tggttacaca      180

tactatacag actccgtgaa gggccgattc accatctcca gagacaacgc caagactacg      240

gtgtatctgc aaatgaacag cctgaaacct gaggacacgg ccgtttatta ctgtgcagca      300

acatacctgt cctcggacta tagccgctat gcgttgcccc aaaggccctt ggactatgac      360

tactggggcc aggggaccca ggtcaccgtc tcctca                                396


<210>  20
<211>  241
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-CD3 scFv


<220>
<221>  MISC_FEATURE
<222>  (1)..(241)

<400>  20

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


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


Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


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


Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Gly Gly Gly Gly Ser Asp Ile Asp Leu Thr Gln Ser Pro Ala Ile 
    130                 135                 140                 


Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser 
145                 150                 155                 160 


Ser Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser 
                165                 170                 175     


Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro 
            180                 185                 190         


Ala His Phe Arg Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile 
        195                 200                 205             


Ser Gly Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp 
    210                 215                 220                 


Ser Ser Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Asn 
225                 230                 235                 240 


Arg 
    


<210>  21
<211>  723
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  anti-CD3 scFv encoding sequence


<220>
<221>  misc_feature
<222>  (1)..(723)

<400>  21
caggtccagc tgcagcagtc tggcgccgag ctggctagac ctggggccag cgtgaagatg       60

agctgcaagg ccagcggcta caccttcacc cggtacacca tgcactgggt caagcagcgg      120

cctgggcagg gcctggaatg gatcggctac atcaacccca gccggggcta caccaactac      180

aaccagaagt tcaaggacaa ggccaccctg accaccgaca agagcagcag caccgcctac      240

atgcagctga gcagcctgac cagcgaggac agcgccgtgt actactgcgc ccggtactac      300

gacgaccact actgcctgga ctactggggc cagggcacca ccctgacagt gtctagcggc      360

ggaggcggat ctggcggcgg aggatctggg ggaggcggct ctgacatcga cctgacacag      420

agccccgcca tcatgagcgc cagccctggc gagaaagtga ccatgacctg cagcgccagc      480

agcagcgtgt cctacatgaa ctggtatcag cagaagtccg gcaccagccc caagcggtgg      540

atctacgaca ccagcaagct ggctagcggc gtgcccgccc actttagagg cagcggcagc      600

ggtacaagct actccctgac catcagcggc atggaagccg aggacgccgc cacctactac      660

tgccagcagt ggtccagcaa ccccttcacc ttcggctccg gcaccaagct ggaaatcaac      720

aga                                                                    723


<210>  22
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(7)

<400>  22

Gly Gly Gly Gly Ser Ser Gly 
1               5           


<210>  23
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)

<400>  23

Ser Gly Ala Gly Gly Ser Gly Gly Ser Ser Gly Ser Asp Gly Ala Ser 
1               5                   10                  15      


Gly 
    


<210>  24
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(21)

<400>  24

Lys Asn Ser Gly Ala Gly Gly Ser Gly Gly Ser Ser Gly Ser Asp Gly 
1               5                   10                  15      


Ala Ser Gly Ser Arg 
            20      


<210>  25
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ClaGFP (forward primer)


<220>
<221>  misc_feature
<222>  (1)..(31)

<400>  25
tgttgcggcc gctagggaga cggtgacctg g                                      31


<210>  26
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  NotGFP (reverse primer)


<220>
<221>  misc_feature
<222>  (1)..(30)

<400>  26
gccacatcga tggctcaggt gcagctggtg                                        30


<210>  27
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  ClaEGFR (forward primer)


<220>
<221>  misc_feature
<222>  (1)..(31)

<400>  27
gcatgatcga tgatggctca ggtgcagctc a                                      31


<210>  28
<211>  33
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  NotEGFR (reverse primer)


<220>
<221>  misc_feature
<222>  (1)..(33)

<400>  28
ttgtgcggcc gctgaggaga cggtgacctg ggt                                    33


<210>  29
<211>  32
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  XmaEGFR (forward primer)


<220>
<221>  misc_feature
<222>  (1)..(32)

<400>  29
gcatgctcga ggtatggctc aggtgcagct ca                                     32


<210>  30
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  XhoEGFR (reverse primer)


<220>
<221>  misc_feature
<222>  (1)..(31)

<400>  30
ttcccgggtg aggagacggt gacctgggtc c                                      31


<210>  31
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FwCMV (forward primer)


<220>
<221>  misc_feature
<222>  (1)..(21)

<400>  31
cgcaaatggg cggtaggcgt g                                                 21


<210>  32
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RvBGH (reverse primer)


<220>
<221>  misc_feature
<222>  (1)..(18)

<400>  32
tagaaggcac agtcgagg                                                     18


<210>  33
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  signal peptide from oncostatin M


<220>
<221>  MISC_FEATURE
<222>  (1)..(25)

<400>  33

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


Leu Leu Phe Pro Ser Met Ala Ser Met 
            20                  25  


<210>  34
<211>  68
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  signal peptide from oncostatin M encoding sequence


<220>
<221>  misc_feature
<222>  (1)..(68)

<400>  34
atgggggtac tgctcacaca gaggacgctg ctcagtctgg tccttgcact cctgtttcca       60

agcatggc                                                                68


<210>  35
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  myc-tag


<220>
<221>  MISC_FEATURE
<222>  (1)..(10)

<400>  35

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   10  


<210>  36
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  myc-tag encoding sequence


<220>
<221>  misc_feature
<222>  (1)..(30)

<400>  36
gaacaaaaac tcatctcaga agaggatctg                                        30


<210>  37
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  6xHis-tag


<220>
<221>  MISC_FEATURE
<222>  (1)..(6)

<400>  37

His His His His His His 
1               5       


<210>  38
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  6His-tag encoding sequence

<400>  38
catcatcatc accatcac                                                     18


<210>  39
<211>  15
<212>  PRT
<213>  Homo sapiens


<220>
<221>  IgG1 Core hinge sequence
<222>  (1)..(15)

<400>  39

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
1               5                   10                  15  


<210>  40
<211>  12
<212>  PRT
<213>  Homo sapiens


<220>
<221>  IgG2 Core hinge sequence
<222>  (1)..(12)

<400>  40

Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro 
1               5                   10          


<210>  41
<211>  16
<212>  PRT
<213>  Homo sapiens


<220>
<221>  IgG3 Core hinge sequence
<222>  (1)..(16)

<400>  41

Glu Leu Lys Thr Pro Leu Asp Thr Thr His Thr Cys Pro Arg Cys Pro 
1               5                   10                  15      


<210>  42
<211>  12
<212>  PRT
<213>  Homo sapiens


<220>
<221>  IgG4 Core hinge sequence
<222>  (1)..(12)

<400>  42

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Pro Cys 
1               5                   10          


