                         SEQUENCE LISTING

<110>  Micromet GmbH
 
<120>  Prevention of adverse effects caused by CD3 specific binding domains

<130>  MIM13896PCT

<150>  US 61/412,229
<151>  2010-11-10

<160>  22    

<170>  PatentIn version 3.5

<210>  1
<211>  498
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD19xCD3 bispecific single chain antibody

<400>  1

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


Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp 
            20                  25                  30          


Gly Asp Ser Tyr Leu Asn Trp Tyr Gln Gln Ile Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu Val Ser Gly Ile Pro Pro 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 
65                  70                  75                  80  


Pro Val Glu Lys Val Asp Ala Ala Thr Tyr His Cys Gln Gln Ser Thr 
                85                  90                  95      


Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


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


Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Ser Tyr Trp Met 
145                 150                 155                 160 


Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly Gln 
                165                 170                 175     


Ile Trp Pro Gly Asp Gly Asp Thr Asn Tyr Asn Gly Lys Phe Lys Gly 
            180                 185                 190         


Lys Ala Thr Leu Thr Ala Asp Glu Ser Ser Ser Thr Ala Tyr Met Gln 
        195                 200                 205             


Leu Ser Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Phe Cys Ala Arg 
    210                 215                 220                 


Arg Glu Thr Thr Thr Val Gly Arg Tyr Tyr Tyr Ala Met Asp Tyr Trp 
225                 230                 235                 240 


Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Asp 
                245                 250                 255     


Ile Lys Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala Ser 
            260                 265                 270         


Val Lys Met Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Arg Tyr Thr 
        275                 280                 285             


Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile Gly 
    290                 295                 300                 


Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
305                 310                 315                 320 


Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser Thr Ala Tyr Met 
                325                 330                 335     


Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys Ala 
            340                 345                 350         


Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp Gly Gln Gly Thr 
        355                 360                 365             


Thr Leu Thr Val Ser Ser Val Glu Gly Gly Ser Gly Gly Ser Gly Gly 
    370                 375                 380                 


Ser Gly Gly Ser Gly Gly Val Asp Asp Ile Gln Leu Thr Gln Ser Pro 
385                 390                 395                 400 


Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg 
                405                 410                 415     


Ala Ser Ser Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys Ser Gly 
            420                 425                 430         


Thr Ser Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Val Ala Ser Gly 
        435                 440                 445             


Val Pro Tyr Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu 
    450                 455                 460                 


Thr Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln 
465                 470                 475                 480 


Gln Trp Ser Ser Asn Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu 
                485                 490                 495     


Leu Lys 
        


<210>  2
<211>  1494
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CD19xCD3 bispecific single chain antibody

<400>  2
gatatccagc tgacccagtc tccagcttct ttggctgtgt ctctagggca gagggccacc       60

atctcctgca aggccagcca aagtgttgat tatgatggtg atagttattt gaactggtac      120

caacagattc caggacagcc acccaaactc ctcatctatg atgcatccaa tctagtttct      180

gggatcccac ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat      240

cctgtggaga aggtggatgc tgcaacctat cactgtcagc aaagtactga ggatccgtgg      300

acgttcggtg gagggaccaa gctcgagatc aaaggtggtg gtggttctgg cggcggcggc      360

tccggtggtg gtggttctca ggtgcagctg cagcagtctg gggctgagct ggtgaggcct      420

gggtcctcag tgaagatttc ctgcaaggct tctggctatg cattcagtag ctactggatg      480

aactgggtga agcagaggcc tggacagggt cttgagtgga ttggacagat ttggcctgga      540

gatggtgata ctaactacaa tggaaagttc aagggtaaag ccactctgac tgcagacgaa      600

tcctccagca cagcctacat gcaactcagc agcctagcat ctgaggactc tgcggtctat      660

ttctgtgcaa gacgggagac tacgacggta ggccgttatt actatgctat ggactactgg      720

ggccaaggga ccacggtcac cgtctcctcc ggaggtggtg gatccgatat caaactgcag      780

cagtcagggg ctgaactggc aagacctggg gcctcagtga agatgtcctg caagacttct      840

ggctacacct ttactaggta cacgatgcac tgggtaaaac agaggcctgg acagggtctg      900

gaatggattg gatacattaa tcctagccgt ggttatacta attacaatca gaagttcaag      960

gacaaggcca cattgactac agacaaatcc tccagcacag cctacatgca actgagcagc     1020

ctgacatctg aggactctgc agtctattac tgtgcaagat attatgatga tcattactgc     1080

cttgactact ggggccaagg caccactctc acagtctcct cagtcgaagg tggaagtgga     1140

ggttctggtg gaagtggagg ttcaggtgga gtcgacgaca ttcagctgac ccagtctcca     1200

gcaatcatgt ctgcatctcc aggggagaag gtcaccatga cctgcagagc cagttcaagt     1260

gtaagttaca tgaactggta ccagcagaag tcaggcacct cccccaaaag atggatttat     1320

gacacatcca aagtggcttc tggagtccct tatcgcttca gtggcagtgg gtctgggacc     1380

tcatactctc tcacaatcag cagcatggag gctgaagatg ctgccactta ttactgccaa     1440

cagtggagta gtaacccgct cacgttcggt gctgggacca agctggagct gaaa           1494


<210>  3
<211>  124
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH anti CD19

<400>  3

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


Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Arg Glu Thr Thr Thr Val Gly Arg Tyr Tyr Tyr Ala Met Asp 
            100                 105                 110         


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


<210>  4
<211>  372
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH anti CD19

<400>  4
caggtgcagc tgcagcagtc tggggctgag ctggtgaggc ctgggtcctc agtgaagatt       60

tcctgcaagg cttctggcta tgcattcagt agctactgga tgaactgggt gaagcagagg      120

cctggacagg gtcttgagtg gattggacag atttggcctg gagatggtga tactaactac      180

aatggaaagt tcaagggtaa agccactctg actgcagacg aatcctccag cacagcctac      240

atgcaactca gcagcctagc atctgaggac tctgcggtct atttctgtgc aagacgggag      300

actacgacgg taggccgtta ttactatgct atggactact ggggccaagg gaccacggtc      360

accgtctcct cc                                                          372


<210>  5
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL anti CD19

<400>  5

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


Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp 
            20                  25                  30          


Gly Asp Ser Tyr Leu Asn Trp Tyr Gln Gln Ile Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu Val Ser Gly Ile Pro Pro 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His 
65                  70                  75                  80  


Pro Val Glu Lys Val Asp Ala Ala Thr Tyr His Cys Gln Gln Ser Thr 
                85                  90                  95      


Glu Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110     


<210>  6
<211>  333
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL anti CD19

<400>  6
gatatccagc tgacccagtc tccagcttct ttggctgtgt ctctagggca gagggccacc       60

atctcctgca aggccagcca aagtgttgat tatgatggtg atagttattt gaactggtac      120

caacagattc caggacagcc acccaaactc ctcatctatg atgcatccaa tctagtttct      180

gggatcccac ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat      240

cctgtggaga aggtggatgc tgcaacctat cactgtcagc aaagtactga ggatccgtgg      300

acgttcggtg gagggaccaa gctcgagatc aaa                                   333


<210>  7
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH anti CD3

<400>  7

Asp Ile Lys Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Met Ser Cys Lys Thr 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 
        115                 


<210>  8
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH anti CD3

<400>  8
gatatcaaac tgcagcagtc aggggctgaa ctggcaagac ctggggcctc agtgaagatg       60

tcctgcaaga cttctggcta cacctttact aggtacacga tgcactgggt aaaacagagg      120

cctggacagg gtctggaatg gattggatac attaatccta gccgtggtta tactaattac      180

aatcagaagt tcaaggacaa ggccacattg actacagaca aatcctccag cacagcctac      240

atgcaactga gcagcctgac atctgaggac tctgcagtct attactgtgc aagatattat      300

gatgatcatt actgccttga ctactggggc caaggcacca ctctcacagt ctcctca         357


<210>  9
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL anti CD3

<400>  9

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


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


Asn Trp Tyr Gln Gln Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr 
        35                  40                  45              


Asp Thr Ser Lys Val Ala Ser Gly Val Pro Tyr Arg Phe Ser Gly Ser 
    50                  55                  60                  


Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu 
65                  70                  75                  80  


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


Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105     


<210>  10
<211>  318
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL anti CD3

<400>  10
gacattcagc tgacccagtc tccagcaatc atgtctgcat ctccagggga gaaggtcacc       60

atgacctgca gagccagttc aagtgtaagt tacatgaact ggtaccagca gaagtcaggc      120

acctccccca aaagatggat ttatgacaca tccaaagtgg cttctggagt cccttatcgc      180

ttcagtggca gtgggtctgg gacctcatac tctctcacaa tcagcagcat ggaggctgaa      240

gatgctgcca cttattactg ccaacagtgg agtagtaacc cgctcacgtt cggtgctggg      300

accaagctgg agctgaaa                                                    318


<210>  11
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  CD3 CDR-H1

<400>  11

Gly Tyr Thr Phe Thr Arg Tyr Thr Met His 
1               5                   10  


<210>  12
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  CD3 CDR-H2

<400>  12

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


Asp 
    


<210>  13
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  CD3 CDR-H3

<400>  13

Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr 
1               5                   10  


<210>  14
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  CD3 CDR-L1

<400>  14

Arg Ala Ser Ser Ser Val Ser Tyr Met Asn 
1               5                   10  


<210>  15
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  CD3 CDR-L2

<400>  15

Asp Thr Ser Lys Val Ala Ser 
1               5           


<210>  16
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  CD3 CDR-L3

<400>  16

Gln Gln Trp Ser Ser Asn Pro Leu Thr 
1               5                   


<210>  17
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  CD19 CDR-H1

<400>  17

Gly Tyr Ala Phe Ser Ser Tyr Trp Met Asn 
1               5                   10  


<210>  18
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  CD19 CDR-H2

<400>  18

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


Gly 
    


<210>  19
<211>  15
<212>  PRT
<213>  artificial

<220>
<223>  CD19 CDR-H3

<400>  19

Arg Glu Thr Thr Thr Val Gly Arg Tyr Tyr Tyr Ala Met Asp Tyr 
1               5                   10                  15  


<210>  20
<211>  15
<212>  PRT
<213>  artificial

<220>
<223>  CD19 CDR-L1

<400>  20

Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Leu Asn 
1               5                   10                  15  


<210>  21
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  CD19 CDR-L2

<400>  21

Asp Ala Ser Asn Leu Val Ser 
1               5           


<210>  22
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  CD19 CDR-L3

<400>  22

Gln Gln Ser Thr Glu Asp Pro Trp Thr 
1               5                   


