                         SEQUENCE LISTING

<110>  National Research Council of Canada
       Teva Branded Pharmaceutical Products R&D, Inc.
       Stanimirovic, Danica
       Sulea, Traian
       Kemmerich, Kristin
       Wilson, David
       Stratton, Jennifer
       Pollard, Matthew
       Clarke, Adam
 
<120>  ANTIBODY VARIANTS TRANSMIGRATING THE BLOOD-BRAIN BARRIER AND USES
        THEREOF

<130>  2016-026-02

<140>  PCT/IB2017/057844
<141>  2017-12-12

<150>  62/432,980
<151>  2016-12-12

<160>  35    

<170>  PatentIn version 3.5

<210>  1
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 FC5

<400>  1

Gly Phe Lys Ile Thr His Tyr Thr Met Gly 
1               5                   10  


<210>  2
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 consensus


<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  where X is D or K

<220>
<221>  misc_feature
<222>  (8)..(8)
<223>  where X is N or D

<220>
<221>  misc_feature
<222>  (10)..(10)
<223>  where X is F, I or L

<400>  2

Arg Ile Thr Trp Gly Gly Xaa Xaa Thr Xaa Tyr Ser Asn Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  3
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 consensus


<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  where X is T or K

<400>  3

Gly Ser Thr Ser Thr Ala Xaa Pro Leu Arg Val Asp Tyr 
1               5                   10              


<210>  4
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 FC5

<400>  4

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


Gly 
    


<210>  5
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 D56K

<400>  5

Arg Ile Thr Trp Gly Gly Lys Asn Thr Phe Tyr Ser Asn Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  6
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 N57D

<400>  6

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


Gly 
    


<210>  7
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 F59I

<400>  7

Arg Ile Thr Trp Gly Gly Asp Asn Thr Ile Tyr Ser Asn Ser Val Lys 
1               5                   10                  15      


Gly 
    


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

<220>
<223>  CDR2 F59L

<400>  8

Arg Ile Thr Trp Gly Gly Asp Asn Thr Leu Tyr Ser Asn Ser Val Lys 
1               5                   10                  15      


Gly 
    


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

<220>
<223>  CDR3 T105K

<400>  9

Gly Ser Thr Ser Thr Ala Lys Pro Leu Arg Val Asp Tyr 
1               5                   10              


<210>  10
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 FC5

<400>  10

Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr 
1               5                   10              


<210>  11
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7-T105K

<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 Gly Phe Lys Ile Thr His Tyr 
            20                  25                  30          


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


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


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 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 Gly Ser Thr Ser Thr Ala Lys Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  12
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7-D56K

<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 Phe Lys Ile Thr His Tyr 
            20                  25                  30          


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


Ser Arg Ile Thr Trp Gly Gly Lys Asn Thr Phe Tyr Ser Asn Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 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 Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  13
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7-N57D

<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 Gly Phe Lys Ile Thr His Tyr 
            20                  25                  30          


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


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


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 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 Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  14
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7-F59I

<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 Lys Ile Thr His Tyr 
            20                  25                  30          


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


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


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 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 Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  15
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7-F59L

<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 Gly Phe Lys Ile Thr His Tyr 
            20                  25                  30          


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


Ser Arg Ile Thr Trp Gly Gly Asp Asn Thr Leu Tyr Ser Asn Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 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 Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  16
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5

<400>  16

Asp Val Gln Leu Gln Ala Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Lys Ile Thr His Tyr 
            20                  25                  30          


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


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


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


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


Ala Ala Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Lys Gly Thr Gln Val Thr Val Ser Ser 
        115                 120         


<210>  17
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7

<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 Gly Phe Lys Ile Thr His Tyr 
            20                  25                  30          


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


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


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 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 Gly Ser Thr Ser Thr Ala Thr Pro Leu Arg Val Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  18
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  fdTGIII primer

<400>  18
gtgaaaaaat tattattatt cgcaattcct                                        30


<210>  19
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  96GIII primer

<400>  19
ccctcatagt tagcgtaacg                                                   20


<210>  20
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5 peptide

<400>  20

Ile Thr Trp Gly Gly Asp Asn Thr Phe Tyr Ser Asn Ser Val Lys 
1               5                   10                  15  


<210>  21
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A20.1 peptide

<400>  21

Thr Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   


<210>  22
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A20.1 peptide

<400>  22

Glu Phe Val Ala Ala Gly Ser Ser Thr Gly Arg 
1               5                   10      


<210>  23
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A20.1 peptide

<400>  23

Thr Phe Ser Met Asp Pro Met Ala Trp Phe Arg 
1               5                   10      


<210>  24
<211>  26
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A20.1 peptide

<400>  24

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


Gly Gln Ala Gly Gln Gly Ser Glu Gln Lys 
            20                  25      


<210>  25
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7 variant peptide

<400>  25

Leu Ser Cys Ala Ala Ser Gly Phe Lys 
1               5                   


<210>  26
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7 variant peptide

<400>  26

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg 
1               5                   10      


<210>  27
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FC5-H7 variant peptide

<400>  27

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


Ser Leu Arg 
            


<210>  28
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Albumin peptide

<400>  28

Ala Pro Gln Val Ser Thr Pro Thr Leu Val Glu Ala Ala Arg 
1               5                   10                  


<210>  29
<211>  232
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG1 Fc

<400>  29

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


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
            20                  25                  30          


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
        35                  40                  45              


Val Val Asp Val Ser His Glu Gly Pro Glu Val Lys Phe Asn Trp His 
    50                  55                  60                  


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
65                  70                  75                  80  


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
                85                  90                  95      


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
            100                 105                 110         


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
        115                 120                 125             


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
    130                 135                 140                 


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
145                 150                 155                 160 


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


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
            180                 185                 190         


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
        195                 200                 205             


Phe Ser Cys Ser Val Met His Glu Gly Leu His Asn His Tyr Thr Gln 
    210                 215                 220                 


Lys Ser Leu Ser Leu Ser Pro Gly 
225                 230         


<210>  30
<211>  366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FC5-H7-T105K

<400>  30
gaggtccagc tggtggaatc tggaggagga ttggtgcagc cggggggctc tctgagactc       60

tcctgtgcag cctctggatt caaaatcact cactatacca tgggctggtt ccgccaggct      120

ccagggaagg agcgtgaatt tgtatcacgt attacttggg gtggtgataa caccttctat      180

tcaaactccg tgaagggccg attcaccatt tccagagaca acagcaagaa cacgctgtat      240

ctgcaaatga acagcctgcg tgcggaggac acggccgtgt attactgtgc agcaggttcg      300

acgtcgactg cgaaaccact tagggtggac tactggggcc aggggaccct ggtcaccgtc      360

tcctca                                                                 366


<210>  31
<211>  366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FC5-H7-D56K

<400>  31
gaggtccagc tggtggaatc tggaggagga ttggtgcagc cggggggctc tctgagactc       60

tcctgtgcag cctctggatt caaaatcact cactatacca tgggctggtt ccgccaggct      120

ccagggaagg agcgtgaatt tgtatcacgt attacttggg gtggtaaaaa caccttctat      180

tcaaactccg tgaagggccg attcaccatt tccagagaca acagcaagaa cacgctgtat      240

ctgcaaatga acagcctgcg tgcggaggac acggccgtgt attactgtgc agcaggttcg      300

acgtcgactg cgacgccact tagggtggac tactggggcc aggggaccct ggtcaccgtc      360

tcctca                                                                 366


<210>  32
<211>  366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FC5-H7-N57D

<400>  32
gaggtccagc tggtggaatc tggaggagga ttggtgcagc cggggggctc tctgagactc       60

tcctgtgcag cctctggatt caaaatcact cactatacca tgggctggtt ccgccaggct      120

ccagggaagg agcgtgaatt tgtatcacgt attacttggg gtggtgatga taccttctat      180

tcaaactccg tgaagggccg attcaccatt tccagagaca acagcaagaa cacgctgtat      240

ctgcaaatga acagcctgcg tgcggaggac acggccgtgt attactgtgc agcaggttcg      300

acgtcgactg cgacgccact tagggtggac tactggggcc aggggaccct ggtcaccgtc      360

tcctca                                                                 366


<210>  33
<211>  366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FC5-H7-F59I

<400>  33
gaggtccagc tggtggaatc tggaggagga ttggtgcagc cggggggctc tctgagactc       60

tcctgtgcag cctctggatt caaaatcact cactatacca tgggctggtt ccgccaggct      120

ccagggaagg agcgtgaatt tgtatcacgt attacttggg gtggtgataa caccatctat      180

tcaaactccg tgaagggccg attcaccatt tccagagaca acagcaagaa cacgctgtat      240

ctgcaaatga acagcctgcg tgcggaggac acggccgtgt attactgtgc agcaggttcg      300

acgtcgactg cgacgccact tagggtggac tactggggcc aggggaccct ggtcaccgtc      360

tcctca                                                                 366


<210>  34
<211>  366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FC5-H7-F59L

<400>  34
gaggtccagc tggtggaatc tggaggagga ttggtgcagc cggggggctc tctgagactc       60

tcctgtgcag cctctggatt caaaatcact cactatacca tgggctggtt ccgccaggct      120

ccagggaagg agcgtgaatt tgtatcacgt attacttggg gtggtgataa caccctgtat      180

tcaaactccg tgaagggccg attcaccatt tccagagaca acagcaagaa cacgctgtat      240

ctgcaaatga acagcctgcg tgcggaggac acggccgtgt attactgtgc agcaggttcg      300

acgtcgactg cgacgccact tagggtggac tactggggcc aggggaccct ggtcaccgtc      360

tcctca                                                                 366


<210>  35
<211>  366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FC5-H7

<400>  35
gaggtccagc tggtggaatc tggaggagga ttggtgcagc cggggggctc tctgagactc       60

tcctgtgcag cctctggatt caaaatcact cactatacca tgggctggtt ccgccaggct      120

ccagggaagg agcgtgaatt tgtatcacgt attacttggg gtggtgataa caccttctat      180

tcaaactccg tgaagggccg attcaccatt tccagagaca acagcaagaa cacgctgtat      240

ctgcaaatga acagcctgcg tgcggaggac acggccgtgt attactgtgc agcaggttcg      300

acgtcgactg cgacgccact tagggtggac tactggggcc aggggaccct ggtcaccgtc      360

tcctca                                                                 366


