                         SEQUENCE LISTING

<110>  JANSSEN PHARMACEUTICA NV
 
<120>  Assays To Detect Neurodegeneration

<130>  JAB6123WOPCT

<150>  62/638,524
<151>  2018-03-05

<160>  37    

<170>  PatentIn version 3.5

<210>  1
<211>  441
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  tau protein 2N4R

<400>  1

Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly 
1               5                   10                  15      


Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His 
            20                  25                  30          


Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu 
        35                  40                  45              


Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser 
    50                  55                  60                  


Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val 
65                  70                  75                  80  


Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu 
                85                  90                  95      


Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro 
            100                 105                 110         


Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val 
        115                 120                 125             


Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly 
    130                 135                 140                 


Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro 
145                 150                 155                 160 


Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro 
                165                 170                 175     


Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly 
            180                 185                 190         


Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser 
        195                 200                 205             


Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys 
    210                 215                 220                 


Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys 
225                 230                 235                 240 


Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val 
                245                 250                 255     


Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly 
            260                 265                 270         


Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln 
        275                 280                 285             


Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly 
    290                 295                 300                 


Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser 
305                 310                 315                 320 


Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln 
                325                 330                 335     


Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser 
            340                 345                 350         


Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn 
        355                 360                 365             


Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala 
    370                 375                 380                 


Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser 
385                 390                 395                 400 


Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser 
                405                 410                 415     


Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val 
            420                 425                 430         


Ser Ala Ser Leu Ala Lys Gln Gly Leu 
        435                 440     


<210>  2
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR-H1 Sequence of PT82 mAb

<400>  2

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


<210>  3
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR-H2 Sequence of PT82 mAb

<400>  3

Gln Ile Arg Leu Gln Ser Asp Asn Tyr Ala Thr Arg Tyr Ala Glu Ser 
1               5                   10                  15      


Val Lys Gly 
            


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

<220>
<223>  CDR-H3 sequence of PT82 mAb

<400>  4

Gly Ile Thr Tyr 
1               


<210>  5
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR-L1 Sequence of PT82 mAb

<400>  5

Lys Ala Ser Gln Asn Val Gly Thr Ala Val Ala 
1               5                   10      


<210>  6
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR-L2 Sequence of PT82 mAb

<400>  6

Ser Ala Ser Ile Arg Tyr Thr 
1               5           


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

<220>
<223>  CDR-L3 Sequence of PT82 mAb

<400>  7

Gln Gln Phe Ser Ser Tyr Pro Tyr Thr 
1               5                   


<210>  8
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH sequence of PT82 mAb

<400>  8

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


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


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


Ala Gln Ile Arg Leu Gln Ser Asp Asn Tyr Ala Thr Arg Tyr Ala Glu 
    50                  55                  60                  


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


Val Tyr Leu Gln Met Asn Asn Leu Arg Thr Glu Asp Thr Gly Ile Tyr 
                85                  90                  95      


Tyr Cys Thr Gly Gly Thr Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr 
            100                 105                 110         


Val Ser Ala 
        115 


<210>  9
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL sequence of PT82 mAb

<400>  9

Asp Ile Val Met Thr Gln Ser Gln Lys Phe Met Ser Thr Ser Val Gly 
1               5                   10                  15      


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


Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile 
        35                  40                  45              


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


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Tyr Met Gln Ser 
65                  70                  75                  80  


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


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


<210>  10
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT82 mAb epitope, aa119-126 of SEQ ID NO:1

<400>  10

Ala Gly His Val Thr Gln Ala Arg 
1               5               


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

<220>
<223>  PT82 mAb epitope, aa117 to 127 of SEQ ID NO:1

<400>  11

Glu Ala Ala Gly His Val Thr Gln Ala Arg Met 
1               5                   10      


<210>  12
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR1 of HT43 mAb

<400>  12

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


<210>  13
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR2 of HT43 mAb

<400>  13

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


Gly 
    


<210>  14
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR3 of HT43 mAb

<400>  14

Ser Trp Asp Gly Ala Met Asp Tyr 
1               5               


<210>  15
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCDR1 of HT43 mAb

<400>  15

Arg Ser Ser Gln Ser Ile Leu His Ser Asn Gly Asn Thr Tyr Phe Glu 
1               5                   10                  15      


<210>  16
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCDR2 of HT43 mAb

<400>  16

Lys Val Ser Asn Arg Phe Ser 
1               5           


<210>  17
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCDR3 of HT43 mAb

<400>  17

Phe Gln Gly Ser Leu Val Pro Trp Thr 
1               5                   


<210>  18
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain variable region of HT43 mAb

<400>  18

Glu Val Lys Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly 
1               5                   10                  15      


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


Gly Met Ser Trp Val Arg Gln Thr Pro Asp Lys Arg Leu Glu Trp Val 
        35                  40                  45              


Thr Thr Ile Asn Ser Asp Gly Ser Tyr Thr Tyr Tyr Pro Asp Ser Val 
    50                  55                  60                  


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


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


Ala Val Ser Trp Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  19
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain variable region of HT43 mAb

<400>  19

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Phe Glu Trp Tyr Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


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


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


<210>  20
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HT43 mAb epitope, aa7 to 20 of SEQ ID NO:1

<400>  20

Glu Phe Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu 
1               5                   10                  


<210>  21
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hT7 mAb epitope, aa 159-163 of SEQ ID NO: 1

<400>  21

Pro Pro Gly Gln Lys 
1               5   


<210>  22
<211>  58
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  calibrant peptide pT3xhT43


<220>
<221>  dPEG4 linker
<222>  (20)..(21)

<220>
<221>  dPEG4 linker
<222>  (38)..(39)

<220>
<221>  phosphorylated threonine
<222>  (44)..(44)

<220>
<221>  phosphorylated threonine
<222>  (49)..(49)

<220>
<221>  C-terminal amide
<222>  (58)..(58)

<400>  22

Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly 
1               5                   10                  15      


Leu Gly Asp Arg Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala 
            20                  25                  30          


Pro Pro Gly Gln Lys Gly Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro 
        35                  40                  45              


Thr Pro Pro Thr Arg Glu Pro Lys Lys Val 
    50                  55              


<210>  23
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  calibrant peptide pT3xpT82


<220>
<221>  N-terminal acetyl group
<222>  (1)..(1)

<220>
<221>  dPEG4 linker
<222>  (18)..(19)

<220>
<221>  phosphorylated threonine
<222>  (24)..(24)

<220>
<221>  phosphorylated threonine
<222>  (29)..(29)

<220>
<221>  C-terminal amide
<222>  (38)..(38)

<400>  23

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


Ser Lys Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr 
            20                  25                  30          


Arg Glu Pro Lys Lys Val 
        35              


<210>  24
<211>  34
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  calibrant peptide hT7xpT82


<220>
<221>  N-terminal acetyl group
<222>  (1)..(1)

<220>
<221>  dPEG4 linker
<222>  (20)..(21)

<220>
<221>  C-terminal amide
<222>  (34)..(34)

<400>  24

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


Val Ser Lys Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala 
            20                  25                  30          


Asn Ala 
        


<210>  25
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  p217+ tau epitope


<220>
<221>  phosphorylated threonine
<222>  (2)..(2)

<400>  25

Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg 
1               5                   10      


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

<220>
<223>  p217+ tau epitope


<220>
<221>  phosphorylated threonine
<222>  (7)..(7)

<400>  26

Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg 
1               5                   10      


<210>  27
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  p217+ tau epitope


<220>
<221>  phosphorylated threonine
<222>  (2)..(2)

<220>
<221>  phosphorylated threonine
<222>  (7)..(7)

<400>  27

Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg 
1               5                   10      


<210>  28
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb VH

<400>  28

Glu Val Lys Leu Val Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Gly 
1               5                   10                  15      


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


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


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


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


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


Arg Gly Trp Gly Asp Tyr Gly Trp Phe Ala Tyr Trp Gly Gln Val Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ala 
        115             


<210>  29
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb VL

<400>  29

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


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


Leu Asn Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Thr Leu Ile 
        35                  40                  45              


Tyr Arg Ala Asn Arg Leu Leu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Gln Asp Tyr Ser Leu Thr Ile Ser Ser Leu Asp Tyr 
65                  70                  75                  80  


Glu Asp Met Gly Ile Tyr Tyr Cys Leu Gln Tyr Asp Glu Phe Pro Leu 
                85                  90                  95      


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


<210>  30
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 humanized mAb VH

<400>  30

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


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


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


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


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


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


Arg Gly Trp Gly Asp Tyr Gly Trp Phe Ala Tyr Trp Gly Gln Val Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  31
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 humanized mAb VL

<400>  31

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


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


Leu Asn Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro Lys Ser Leu Ile 
        35                  40                  45              


Tyr Arg Ala Asn Arg Leu Leu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Glu Phe Pro Leu 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  32
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb HCDR1, Kabat numbering

<400>  32

Ser Tyr Ala Met Ser 
1               5   


<210>  33
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb HCDR2, Kabat numbering

<400>  33

Ser Ile Ser Lys Gly Gly Asn Thr Tyr Tyr Pro Asn Ser Val Lys Gly 
1               5                   10                  15      


<210>  34
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb HCDR3, Kabat numbering

<400>  34

Gly Trp Gly Asp Tyr Gly Trp Phe Ala Tyr 
1               5                   10  


<210>  35
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb LCDR1, Kabat numbering

<400>  35

Lys Ala Ser Gln Asp Ile Asn Arg Tyr Leu Asn 
1               5                   10      


<210>  36
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb LCDR2, Kabat numbering

<400>  36

Arg Ala Asn Arg Leu Leu Asp 
1               5           


<210>  37
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  PT3 mouse mAb LCDR3, Kabat numbering

<400>  37

Leu Gln Tyr Asp Glu Phe Pro Leu Thr 
1               5                   


