                         SEQUENCE LISTING

<110>  Janssen Pharmaceutica NV
       Mercken, Marc
       Van Broeck, Bianca
       Vandermeeren, Marc
       Hermans, Bart
       Bottelbergs, Astrid
 
<120>  Antibodies to Pyroglutamate Amyloid-beta and Uses Thereof

<130>  PRD3410

<150>  62/416,788
<151>  2016-11-03

<160>  31    

<170>  PatentIn version 3.5

<210>  1
<211>  449
<212>  PRT
<213>  Mus musculus


<220>
<221>  CHAIN
<222>  (1)..(449)
<223>  Heavy Chain

<400>  1

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


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


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


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


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


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


Thr Arg Glu Gly Ala Tyr Ser Asp Tyr Glu Thr Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Ala Pro Ser Val Tyr 
        115                 120                 125             


Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu 
    130                 135                 140                 


Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp 
145                 150                 155                 160 


Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     


Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser 
            180                 185                 190         


Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser 
        195                 200                 205             


Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys 
    210                 215                 220                 


Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro 
225                 230                 235                 240 


Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser 
                245                 250                 255     


Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp 
            260                 265                 270         


Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr 
        275                 280                 285             


Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val 
    290                 295                 300                 


Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu 
305                 310                 315                 320 


Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg 
                325                 330                 335     


Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val 
            340                 345                 350         


Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr 
        355                 360                 365             


Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr 
    370                 375                 380                 


Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu 
385                 390                 395                 400 


Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys 
                405                 410                 415     


Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu 
            420                 425                 430         


Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly 
        435                 440                 445             


Lys 
    


<210>  2
<211>  119
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(119)
<223>  VH

<400>  2

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


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


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


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


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


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


Thr Arg Glu Gly Ala Tyr Ser Asp Tyr Glu Thr Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ala 
        115                 


<210>  3
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(5)
<223>  HCDR1 (Kabat)

<400>  3

Arg Tyr Trp Ile Asn 
1               5   


<210>  4
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(17)
<223>  HCDR2 (Kabat)

<400>  4

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


Asp 
    


<210>  5
<211>  10
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(10)
<223>  HCDR3 (Kabat)

<400>  5

Glu Gly Ala Tyr Ser Asp Tyr Glu Thr Tyr 
1               5                   10  


<210>  6
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(7)
<223>  HCDR1 (Chothia)

<400>  6

Gly Tyr Thr Phe Thr Arg Tyr 
1               5           


<210>  7
<211>  6
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(6)
<223>  HCDR2 (Chothia)

<400>  7

Arg Pro Ser Asp Ser Tyr 
1               5       


<210>  8
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(9)
<223>  HCDR3 (Chothia)

<400>  8

Glu Gly Ala Tyr Ser Asp Tyr Glu Thr 
1               5                   


<210>  9
<211>  8
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(8)
<223>  HCDR1 (IMGT)

<400>  9

Gly Tyr Thr Phe Thr Arg Tyr Trp 
1               5               


<210>  10
<211>  8
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(8)
<223>  HCDR2 (IMGT)

<400>  10

Ile Arg Pro Ser Asp Ser Tyr Thr 
1               5               


<210>  11
<211>  12
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(12)
<223>  HCDR3 (IMGT)

<400>  11

Thr Arg Glu Gly Ala Tyr Ser Asp Tyr Glu Thr Tyr 
1               5                   10          


<210>  12
<211>  219
<212>  PRT
<213>  Mus musculus


<220>
<221>  CHAIN
<222>  (1)..(219)
<223>  Light Chain

<400>  12

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser 
            20                  25                  30          


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


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


Asp Arg Phe Thr 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 Val Gln Gly 
                85                  90                  95      


Thr His Phe Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu 
        115                 120                 125             


Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
145                 150                 155                 160 


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu 
            180                 185                 190         


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
        195                 200                 205             


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
    210                 215                 


<210>  13
<211>  112
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(112)
<223>  VL

<400>  13

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser 
            20                  25                  30          


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


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


Asp Arg Phe Thr 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 Val Gln Gly 
                85                  90                  95      


Thr His Phe Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  14
<211>  16
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(16)
<223>  LCDR1 (Kabat)

<400>  14

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


<210>  15
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(7)
<223>  LCDR2 (Kabat)

<400>  15

Leu Val Ser Lys Leu Asp Ser 
1               5           


<210>  16
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(9)
<223>  LCDR3 (Kabat) and LCDR3 (IMGT)

<400>  16

Val Gln Gly Thr His Phe Pro Phe Thr 
1               5                   


<210>  17
<211>  12
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(12)
<223>  LCDR1 (Chothia)

<400>  17

Ser Gln Ser Leu Leu Asp Ser Asn Gly Lys Thr Tyr 
1               5                   10          


<210>  18
<211>  3
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(3)
<223>  LCDR2 (Chothia) and LCDR2 (IMGT)

<400>  18

Leu Val Ser 
1           


<210>  19
<211>  6
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(6)
<223>  LCDR3 (Chothia)

<400>  19

Gly Thr His Phe Pro Phe 
1               5       


<210>  20
<211>  11
<212>  PRT
<213>  Mus musculus


<220>
<221>  DOMAIN
<222>  (1)..(11)
<223>  LCDR1 (IMGT)

<400>  20

Gln Ser Leu Leu Asp Ser Asn Gly Lys Thr Tyr 
1               5                   10      


<210>  21
<211>  8
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is a pyroglutamate residue

<220>
<221>  PEPTIDE
<222>  (1)..(8)
<223>  peptide sequence from beta-amyloid

<400>  21

Xaa Phe Arg His Asp Ser Gly Cys 
1               5               


<210>  22
<211>  38
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is a pyroglutamate residue

<220>
<221>  PEPTIDE
<222>  (1)..(38)
<223>  peptide sequence from beta-amyloid

<400>  22

Xaa Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Leu Val 
1               5                   10                  15      


Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile Gly Leu 
            20                  25                  30          


Met Val Gly Gly Val Val 
        35              


<210>  23
<211>  40
<212>  PRT
<213>  Homo sapiens


<220>
<221>  PEPTIDE
<222>  (1)..(40)
<223>  peptide sequence from beta-amyloid

<400>  23

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys 
1               5                   10                  15      


Leu Val Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile 
            20                  25                  30          


Gly Leu Met Val Gly Gly Val Val 
        35                  40  


<210>  24
<211>  38
<212>  PRT
<213>  Homo sapiens


<220>
<221>  PEPTIDE
<222>  (1)..(38)
<223>  peptide sequence from beta-amyloid

<400>  24

Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Leu Val 
1               5                   10                  15      


Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile Gly Leu 
            20                  25                  30          


Met Val Gly Gly Val Val 
        35              


<210>  25
<211>  42
<212>  PRT
<213>  Homo sapiens


<220>
<221>  PEPTIDE
<222>  (1)..(42)
<223>  peptide sequence from beta-amyloid

<400>  25

Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys 
1               5                   10                  15      


Leu Val Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile 
            20                  25                  30          


Gly Leu Met Val Gly Gly Val Val Ile Ala 
        35                  40          


<210>  26
<211>  40
<212>  PRT
<213>  Homo sapiens


<220>
<221>  PEPTIDE
<222>  (1)..(40)
<223>  peptide sequence from beta-amyloid

<400>  26

Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Leu Val 
1               5                   10                  15      


Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile Gly Leu 
            20                  25                  30          


Met Val Gly Gly Val Val Ile Ala 
        35                  40  


<210>  27
<211>  30
<212>  PRT
<213>  Homo sapiens


<220>
<221>  PEPTIDE
<222>  (1)..(30)
<223>  peptide sequence from beta-amyloid

<400>  27

Glu Val His His Gln Lys Leu Val Phe Phe Ala Glu Asp Val Gly Ser 
1               5                   10                  15      


Asn Lys Gly Ala Ile Ile Gly Leu Met Val Gly Gly Val Val 
            20                  25                  30  


<210>  28
<211>  30
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is a pyroglutamate residue

<220>
<221>  PEPTIDE
<222>  (1)..(30)
<223>  peptide sequence from beta-amyloid

<400>  28

Xaa Val His His Gln Lys Leu Val Phe Phe Ala Glu Asp Val Gly Ser 
1               5                   10                  15      


Asn Lys Gly Ala Ile Ile Gly Leu Met Val Gly Gly Val Val 
            20                  25                  30  


<210>  29
<211>  32
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is a pyroglutamate residue

<220>
<221>  PEPTIDE
<222>  (1)..(32)
<223>  peptide sequence from beta-amyloid

<400>  29

Xaa Val His His Gln Lys Leu Val Phe Phe Ala Glu Asp Val Gly Ser 
1               5                   10                  15      


Asn Lys Gly Ala Ile Ile Gly Leu Met Val Gly Gly Val Val Ile Ala 
            20                  25                  30          


<210>  30
<211>  40
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Xaa at position 1 is a pyroglutamate residue

<220>
<221>  PEPTIDE
<222>  (1)..(40)
<223>  peptide sequence from beta-amyloid

<400>  30

Xaa Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Leu Val 
1               5                   10                  15      


Phe Phe Ala Glu Asp Val Gly Ser Asn Lys Gly Ala Ile Ile Gly Leu 
            20                  25                  30          


Met Val Gly Gly Val Val Ile Ala 
        35                  40  


<210>  31
<211>  443
<212>  PRT
<213>  Mus musculus


<220>
<221>  CHAIN
<222>  (1)..(443)
<223>  Murine Heavy Chain IgG1

<400>  31

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


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


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


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


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


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


Thr Arg Glu Gly Ala Tyr Ser Asp Tyr Glu Thr Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ala Ala Lys Thr Thr Pro Pro Ser Val Tyr 
        115                 120                 125             


Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu 
    130                 135                 140                 


Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp 
145                 150                 155                 160 


Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     


Glu Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Pro Ser Ser 
            180                 185                 190         


Pro Arg Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser 
        195                 200                 205             


Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys 
    210                 215                 220                 


Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser 
            260                 265                 270         


Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg 
        275                 280                 285             


Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile 
    290                 295                 300                 


Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn 
305                 310                 315                 320 


Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys 
                325                 330                 335     


Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu 
            340                 345                 350         


Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe 
        355                 360                 365             


Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala 
    370                 375                 380                 


Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asn Thr Asn Gly Ser Tyr 
385                 390                 395                 400 


Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly 
                405                 410                 415     


Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His Asn His His 
            420                 425                 430         


Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys 
        435                 440             


