                         SEQUENCE LISTING

<110>  Surrozen, Inc.
 
<120>  LIVER-SPECIFIC WNT SIGNAL ENHANCING MOLECULES AND USES THEREOF

<130>  SRZN-019/03WO 328202-2142

<150>  US 63/114,457
<151>  2020-11-16

<150>  US 63/182,106
<151>  2021-04-30

<150>  US 63/248,157
<151>  2021-09-24

<160>  62    

<170>  PatentIn version 3.5

<210>  1
<211>  215
<212>  PRT
<213>  Homo sapiens

<400>  1

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


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


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


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


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu Glu Arg Ile Gly Tyr Leu 
                85                  90                  95      


Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro 
            100                 105                 110         


Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu 
        115                 120                 125             


Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro 
    130                 135                 140                 


Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala 
145                 150                 155                 160 


Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala 
                165                 170                 175     


Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg 
            180                 185                 190         


Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 
        195                 200                 205             


Val Ala Pro Thr Glu Cys Ser 
    210                 215 


<210>  2
<211>  572
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - Fusion construct 1R34-DDNN/RA heavy chain fused to 
       RSPO2

<400>  2

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Ser Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 
        115                 120                 125             


Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys 
    130                 135                 140                 


Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser 
                165                 170                 175     


Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile 
            180                 185                 190         


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 
        195                 200                 205             


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


Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 
                245                 250                 255     


Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 
            260                 265                 270         


Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 
        275                 280                 285             


Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 
    290                 295                 300                 


Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 
305                 310                 315                 320 


Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 
                325                 330                 335     


Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
            340                 345                 350         


Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
        355                 360                 365             


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
    370                 375                 380                 


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
385                 390                 395                 400 


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
                405                 410                 415     


Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
            420                 425                 430         


Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
        435                 440                 445             


Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
    450                 455                 460                 


Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
465                 470                 475                 480 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
                485                 490                 495     


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
            500                 505                 510         


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
        515                 520                 525             


Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
    530                 535                 540                 


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
545                 550                 555                 560 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570         


<210>  3
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - Humanized VL domain modified from 8M24 antibody

<400>  3

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


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


<210>  4
<211>  244
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct heavy chain variable domain fused 
       to RSPO2

<400>  4

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys 
    130                 135                 140                 


Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Ile Asn Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Glu Ile Phe Pro Arg 
                165                 170                 175     


Ser Asp Asn Thr Phe Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile 
            180                 185                 190         


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


Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Lys Gly Arg Asp 
    210                 215                 220                 


Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
225                 230                 235                 240 


Thr Val Ser Ser 
                


<210>  5
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - Humanized VL chain modified from 8M24 antibody

<400>  5

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  6
<211>  574
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct heavy chain fused to RSPO2

<400>  6

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys 
    130                 135                 140                 


Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Ile Asn Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Glu Ile Phe Pro Arg 
                165                 170                 175     


Ser Asp Asn Thr Phe Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile 
            180                 185                 190         


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


Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Lys Gly Arg Asp 
    210                 215                 220                 


Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
225                 230                 235                 240 


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
                245                 250                 255     


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
            260                 265                 270         


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
        275                 280                 285             


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
    290                 295                 300                 


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
305                 310                 315                 320 


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
                325                 330                 335     


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
            340                 345                 350         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        355                 360                 365             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    370                 375                 380                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
385                 390                 395                 400 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                405                 410                 415     


Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val 
            420                 425                 430         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        435                 440                 445             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    450                 455                 460                 


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
465                 470                 475                 480 


Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
                485                 490                 495     


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
            500                 505                 510         


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        515                 520                 525             


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
    530                 535                 540                 


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
545                 550                 555                 560 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570                 


<210>  7
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - mutated light chain sequence

<400>  7

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


Thr Val Arg Ile Thr Cys Gln Gly Glu Ser Leu Arg Ser Tyr Tyr Ala 
            20                  25                  30          


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


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


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Thr Ser Leu Glu Arg Ile Gly Tyr Leu 
                85                  90                  95      


Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro 
            100                 105                 110         


Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu 
        115                 120                 125             


Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro 
    130                 135                 140                 


Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala 
145                 150                 155                 160 


Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala 
                165                 170                 175     


Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg 
            180                 185                 190         


Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 
        195                 200                 205             


Val Ala Pro Thr Glu Cys Ser 
    210                 215 


<210>  8
<211>  572
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct mutated EEST/EE heavy chain fused 
       to RSPO2

<400>  8

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Glu Ser Lys Asp Glu Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 
        115                 120                 125             


Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys 
    130                 135                 140                 


Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser 
                165                 170                 175     


Gly Gly Ser Thr Tyr Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile 
            180                 185                 190         


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 
        195                 200                 205             


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


Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 
                245                 250                 255     


Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 
            260                 265                 270         


Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 
        275                 280                 285             


Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 
    290                 295                 300                 


Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 
305                 310                 315                 320 


Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 
                325                 330                 335     


Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
            340                 345                 350         


Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
        355                 360                 365             


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
    370                 375                 380                 


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
385                 390                 395                 400 


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
                405                 410                 415     


Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
            420                 425                 430         


Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
        435                 440                 445             


Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
    450                 455                 460                 


Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
465                 470                 475                 480 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
                485                 490                 495     


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
            500                 505                 510         


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
        515                 520                 525             


Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
    530                 535                 540                 


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
545                 550                 555                 560 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570         


<210>  9
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - mutated 1R34-EEST/RA light chain

<400>  9

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


Thr Val Arg Ile Thr Cys Gln Gly Glu Ser Leu Arg Ser Tyr Tyr Ala 
            20                  25                  30          


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


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


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Thr Ser Leu Glu Arg Ile Gly Tyr Leu 
                85                  90                  95      


Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro 
            100                 105                 110         


Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu 
        115                 120                 125             


Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro 
    130                 135                 140                 


Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala 
145                 150                 155                 160 


Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala 
                165                 170                 175     


Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg 
            180                 185                 190         


Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 
        195                 200                 205             


Val Ala Pro Thr Glu Cys Ser 
    210                 215 


<210>  10
<211>  572
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct mutated 1R34-EEST/RA heavy chain 
       fused to RSPO2

<400>  10

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 
        115                 120                 125             


Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys 
    130                 135                 140                 


Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser 
                165                 170                 175     


Gly Gly Ser Thr Tyr Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile 
            180                 185                 190         


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 
        195                 200                 205             


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


Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 
                245                 250                 255     


Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 
            260                 265                 270         


Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 
        275                 280                 285             


Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 
    290                 295                 300                 


Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 
305                 310                 315                 320 


Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 
                325                 330                 335     


Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
            340                 345                 350         


Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
        355                 360                 365             


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
    370                 375                 380                 


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
385                 390                 395                 400 


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
                405                 410                 415     


Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
            420                 425                 430         


Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
        435                 440                 445             


Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
    450                 455                 460                 


Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
465                 470                 475                 480 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
                485                 490                 495     


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
            500                 505                 510         


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
        515                 520                 525             


Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
    530                 535                 540                 


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
545                 550                 555                 560 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570         


<210>  11
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - mutated 1R34-EEAT/EE light chain

<400>  11

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


Thr Val Arg Ile Thr Cys Gln Gly Glu Ser Leu Arg Ser Tyr Tyr Ala 
            20                  25                  30          


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


Gly Lys Ala Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser 
    50                  55                  60                  


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Thr Ser Leu Glu Arg Ile Gly Tyr Leu 
                85                  90                  95      


Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro 
            100                 105                 110         


Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu 
        115                 120                 125             


Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro 
    130                 135                 140                 


Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala 
145                 150                 155                 160 


Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala 
                165                 170                 175     


Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg 
            180                 185                 190         


Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr 
        195                 200                 205             


Val Ala Pro Thr Glu Cys Ser 
    210                 215 


<210>  12
<211>  572
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct mutated 1R34-EEAT/EE heavy chain 
       fused to RSPO2

<400>  12

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Glu Ser Lys Asp Glu Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 
        115                 120                 125             


Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys 
    130                 135                 140                 


Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser 
                165                 170                 175     


Gly Gly Ser Thr Tyr Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile 
            180                 185                 190         


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 
        195                 200                 205             


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


Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser 
                245                 250                 255     


Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys 
            260                 265                 270         


Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu 
        275                 280                 285             


Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu 
    290                 295                 300                 


Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr 
305                 310                 315                 320 


Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val 
                325                 330                 335     


Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
            340                 345                 350         


Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
        355                 360                 365             


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
    370                 375                 380                 


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
385                 390                 395                 400 


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
                405                 410                 415     


Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
            420                 425                 430         


Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
        435                 440                 445             


Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
    450                 455                 460                 


Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
465                 470                 475                 480 


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
                485                 490                 495     


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
            500                 505                 510         


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
        515                 520                 525             


Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
    530                 535                 540                 


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
545                 550                 555                 560 


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570         


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

<220>
<223>  Made in Lab - 8M24 antibody heavy chain variable domain

<400>  13

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


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


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


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


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


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


Ala Arg Lys Gly Arg Asp Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp 
            100                 105                 110         


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


<210>  14
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24 antibody light chain variable domain

<400>  14

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


Glu Thr Val Thr Ile Thr Cys Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


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


Ser Gly Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn Ser Leu Gln Ser 
65                  70                  75                  80  


Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


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


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

<220>
<223>  Made in Lab - 8M24 antibody heavy chain variable domain 
       (humanized 1)

<400>  15

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


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


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


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


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


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


Ala Arg Lys Gly Arg Asp Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp 
            100                 105                 110         


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


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

<220>
<223>  Made in Lab - 8M24 antibody heavy chain variable domain 
       (humanized 2)

<400>  16

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


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


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


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


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


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


Ala Arg Lys Gly Arg Asp Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp 
            100                 105                 110         


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


<210>  17
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24 antibody light chain variable domain 
       (humanized 1)

<400>  17

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


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


<210>  18
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24 antibod light chain variable domain (humanized
       2)

<400>  18

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala 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 Gly Thr Tyr Tyr Cys Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


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


<210>  19
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE-RA light chain variable domain

<400>  19

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala Glu 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


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


<210>  20
<211>  244
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct 8M24-EASE-RA heavy chain variable 
       domain fused to RSPO2

<400>  20

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys 
    130                 135                 140                 


Lys Ala Ser Gly Tyr Thr Phe Thr Ala Tyr Gly Ile Asn Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Glu Ile Phe Pro Arg 
                165                 170                 175     


Ser Asp Ser Thr Phe Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile 
            180                 185                 190         


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


Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Lys Gly Arg Glu 
    210                 215                 220                 


Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
225                 230                 235                 240 


Thr Val Ser Ser 
                


<210>  21
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE-EE light chain

<400>  21

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala Glu 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  22
<211>  574
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct 8M24-EASE-EE heavy chain fused to 
       RSPO2

<400>  22

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Glu Ser Lys Asp Glu Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys 
    130                 135                 140                 


Lys Ala Ser Gly Tyr Thr Phe Thr Ala Tyr Gly Ile Asn Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Glu Ile Phe Pro Arg 
                165                 170                 175     


Ser Asp Ser Thr Phe Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile 
            180                 185                 190         


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


Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Lys Gly Arg Glu 
    210                 215                 220                 


Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
225                 230                 235                 240 


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
                245                 250                 255     


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
            260                 265                 270         


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
        275                 280                 285             


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
    290                 295                 300                 


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
305                 310                 315                 320 


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
                325                 330                 335     


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
            340                 345                 350         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        355                 360                 365             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    370                 375                 380                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
385                 390                 395                 400 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                405                 410                 415     


Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val 
            420                 425                 430         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        435                 440                 445             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    450                 455                 460                 


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
465                 470                 475                 480 


Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
                485                 490                 495     


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
            500                 505                 510         


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        515                 520                 525             


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
    530                 535                 540                 


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
545                 550                 555                 560 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570                 


<210>  23
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-DDNN/RA light chain variable domain

<400>  23

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


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


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


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


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Leu Glu Arg Ile Gly Tyr Leu 
                85                  90                  95      


Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 


<210>  24
<211>  242
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct 1R34-DDNN/RA heavy chain variable 
       domain fused to RSPO2

<400>  24

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Ser Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 
        115                 120                 125             


Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys 
    130                 135                 140                 


Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser 
                165                 170                 175     


Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile 
            180                 185                 190         


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 
        195                 200                 205             


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


Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser 
        


<210>  25
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE light chain

<400>  25

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala Glu 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  26
<211>  574
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct 8M24-EASE heavy chain fused to 
       RSPO2 (human IgG1_N297G)

<400>  26

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys 
    130                 135                 140                 


Lys Ala Ser Gly Tyr Thr Phe Thr Ala Tyr Gly Ile Asn Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Glu Ile Phe Pro Arg 
                165                 170                 175     


Ser Asp Ser Thr Phe Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile 
            180                 185                 190         


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


Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Lys Gly Arg Glu 
    210                 215                 220                 


Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
225                 230                 235                 240 


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
                245                 250                 255     


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
            260                 265                 270         


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
        275                 280                 285             


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
    290                 295                 300                 


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
305                 310                 315                 320 


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
                325                 330                 335     


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
            340                 345                 350         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        355                 360                 365             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    370                 375                 380                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
385                 390                 395                 400 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                405                 410                 415     


Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val 
            420                 425                 430         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        435                 440                 445             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    450                 455                 460                 


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
465                 470                 475                 480 


Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
                485                 490                 495     


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
            500                 505                 510         


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        515                 520                 525             


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
    530                 535                 540                 


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
545                 550                 555                 560 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570                 


<210>  27
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE light chain variable domain

<400>  27

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


Thr Val Arg Ile Thr Cys Gln Gly Glu Ser Leu Arg Ser Tyr Tyr Ala 
            20                  25                  30          


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


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


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Thr Ser Leu Glu Arg Ile Gly Tyr Leu 
                85                  90                  95      


Ser Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 


<210>  28
<211>  242
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Labe - fusion construct 1R34-EEST/EE heavy chain variable
       region fused to RSPO2

<400>  28

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Glu Ser Lys Asp Glu Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu Glu 
        115                 120                 125             


Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys 
    130                 135                 140                 


Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser 
                165                 170                 175     


Gly Gly Ser Thr Tyr Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile 
            180                 185                 190         


Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu 
        195                 200                 205             


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


Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser 
        


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

<220>
<223>  Made in Lab - modified R-spondin-2

<400>  29

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu 
            100                 105         


<210>  30
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - modified R-spondin-2

<400>  30

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Ala Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu 
            100                 105         


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

<220>
<223>  Made in Lab - modified R-spondin-2

<400>  31

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Glu Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu 
            100                 105         


<210>  32
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - modified R-spondin-2

<400>  32

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Glu Ser Lys Asp Glu Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu 
            100                 105         


<210>  33
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-DDNN/RA heavy chain

<400>  33

Glu Val Gln Leu Leu 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 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              


Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp 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 Lys Asp Phe Ser Ser Arg Arg Trp Tyr Leu Glu Tyr Trp Gly Gln 
            100                 105                 110         


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


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


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


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  34
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE CDRH1

<400>  34

Ser Tyr Ala Met Ser 
1               5   


<210>  35
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE CDRH2

<400>  35

Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Glu Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  36
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE CDRH3

<400>  36

Asp Phe Ser Ser Arg Arg Trp Tyr Leu Glu Tyr 
1               5                   10      


<210>  37
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE CDRL1

<400>  37

Gln Gly Glu Ser Leu Arg Ser Tyr Tyr Ala Ser 
1               5                   10      


<210>  38
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE CDRL2

<400>  38

Tyr Gly Lys Ser Asn Arg Pro Ser 
1               5               


<210>  39
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEST/EE CDRL3

<400>  39

Cys Thr Ser Leu Glu Arg Ile Gly Tyr Leu Ser Tyr Val 
1               5                   10              


<210>  40
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 1R34-EEAT/EE CDRL2

<400>  40

Tyr Gly Lys Ala Asn Arg Pro Ser 
1               5               


<210>  41
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE CDRL1

<400>  41

Arg Ile Ser Glu Asn Ile Tyr Ser Asn Leu Ala 
1               5                   10      


<210>  42
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE CDRL2

<400>  42

Ala Ala Ile Asn Leu Ala Glu 
1               5           


<210>  43
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE CDRL3

<400>  43

Gln His Phe Trp Gly Thr Pro Phe Thr 
1               5                   


<210>  44
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE CDRH1

<400>  44

Ala Tyr Gly Ile Asn 
1               5   


<210>  45
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE CDRH2

<400>  45

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


Gly 
    


<210>  46
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24-EASE CDRH3

<400>  46

Lys Gly Arg Glu Tyr Gly Thr Ser His Tyr Phe Asp Tyr 
1               5                   10              


<210>  47
<211>  263
<212>  PRT
<213>  Homo sapiens

<400>  47

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


Leu Thr Ile Ser Ser Arg Gly Ile Lys Gly Lys Arg Gln Arg Arg Ile 
            20                  25                  30          


Ser Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu Cys Ser 
        35                  40                  45              


Glu Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile Leu Leu 
    50                  55                  60                  


Glu Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser Cys Pro 
65                  70                  75                  80  


Pro Gly Tyr Phe Asp Ala Arg Asn Pro Asp Met Asn Lys Cys Ile Lys 
                85                  90                  95      


Cys Lys Ile Glu His Cys Glu Ala Cys Phe Ser His Asn Phe Cys Thr 
            100                 105                 110         


Lys Cys Lys Glu Gly Leu Tyr Leu His Lys Gly Arg Cys Tyr Pro Ala 
        115                 120                 125             


Cys Pro Glu Gly Ser Ser Ala Ala Asn Gly Thr Met Glu Cys Ser Ser 
    130                 135                 140                 


Pro Ala Gln Cys Glu Met Ser Glu Trp Ser Pro Trp Gly Pro Cys Ser 
145                 150                 155                 160 


Lys Lys Gln Gln Leu Cys Gly Phe Arg Arg Gly Ser Glu Glu Arg Thr 
                165                 170                 175     


Arg Arg Val Leu His Ala Pro Val Gly Asp His Ala Ala Cys Ser Asp 
            180                 185                 190         


Thr Lys Glu Thr Arg Arg Cys Thr Val Arg Arg Val Pro Cys Pro Glu 
        195                 200                 205             


Gly Gln Lys Arg Arg Lys Gly Gly Gln Gly Arg Arg Glu Asn Ala Asn 
    210                 215                 220                 


Arg Asn Leu Ala Arg Lys Glu Ser Lys Glu Ala Gly Ala Gly Ser Arg 
225                 230                 235                 240 


Arg Arg Lys Gly Gln Gln Gln Gln Gln Gln Gln Gly Thr Val Gly Pro 
                245                 250                 255     


Leu Thr Ser Ala Gly Pro Ala 
            260             


<210>  48
<211>  243
<212>  PRT
<213>  Homo sapiens

<400>  48

Met Gln Phe Arg Leu Phe Ser Phe Ala Leu Ile Ile Leu Asn Cys Met 
1               5                   10                  15      


Asp Tyr Ser His Cys Gln Gly Asn Arg Trp Arg Arg Ser Lys Arg Ala 
            20                  25                  30          


Ser Tyr Val Ser Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys 
        35                  40                  45              


Asp Asn Gly Cys Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg 
    50                  55                  60                  


Arg Glu Gly Met Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser 
65                  70                  75                  80  


Gly Tyr Tyr Gly His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys 
                85                  90                  95      


Arg Ile Glu Asn Cys Asp Ser Cys Phe Ser Lys Asp Phe Cys Thr Lys 
            100                 105                 110         


Cys Lys Val Gly Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys 
        115                 120                 125             


Pro Asp Gly Phe Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly 
    130                 135                 140                 


Cys Glu Val Gly His Trp Ser Glu Trp Gly Thr Cys Ser Arg Asn Asn 
145                 150                 155                 160 


Arg Thr Cys Gly Phe Lys Trp Gly Leu Glu Thr Arg Thr Arg Gln Ile 
                165                 170                 175     


Val Lys Lys Pro Val Lys Asp Thr Ile Leu Cys Pro Thr Ile Ala Glu 
            180                 185                 190         


Ser Arg Arg Cys Lys Met Thr Met Arg His Cys Pro Gly Gly Lys Arg 
        195                 200                 205             


Thr Pro Lys Ala Lys Glu Lys Arg Asn Lys Lys Lys Lys Arg Lys Leu 
    210                 215                 220                 


Ile Glu Arg Ala Gln Glu Gln His Ser Val Phe Leu Ala Thr Asp Arg 
225                 230                 235                 240 


Ala Asn Gln 
            


<210>  49
<211>  272
<212>  PRT
<213>  Homo sapiens

<400>  49

Met His Leu Arg Leu Ile Ser Trp Leu Phe Ile Ile Leu Asn Phe Met 
1               5                   10                  15      


Glu Tyr Ile Gly Ser Gln Asn Ala Ser Arg Gly Arg Arg Gln Arg Arg 
            20                  25                  30          


Met His Pro Asn Val Ser Gln Gly Cys Gln Gly Gly Cys Ala Thr Cys 
        35                  40                  45              


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


Leu Glu Arg Ile Gly Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys 
65                  70                  75                  80  


Pro Ser Gly Tyr Tyr Gly Thr Arg Tyr Pro Asp Ile Asn Lys Cys Thr 
                85                  90                  95      


Lys Cys Lys Ala Asp Cys Asp Thr Cys Phe Asn Lys Asn Phe Cys Thr 
            100                 105                 110         


Lys Cys Lys Ser Gly Phe Tyr Leu His Leu Gly Lys Cys Leu Asp Asn 
        115                 120                 125             


Cys Pro Glu Gly Leu Glu Ala Asn Asn His Thr Met Glu Cys Val Ser 
    130                 135                 140                 


Ile Val His Cys Glu Val Ser Glu Trp Asn Pro Trp Ser Pro Cys Thr 
145                 150                 155                 160 


Lys Lys Gly Lys Thr Cys Gly Phe Lys Arg Gly Thr Glu Thr Arg Val 
                165                 170                 175     


Arg Glu Ile Ile Gln His Pro Ser Ala Lys Gly Asn Leu Cys Pro Pro 
            180                 185                 190         


Thr Asn Glu Thr Arg Lys Cys Thr Val Gln Arg Lys Lys Cys Gln Lys 
        195                 200                 205             


Gly Glu Arg Gly Lys Lys Gly Arg Glu Arg Lys Arg Lys Lys Pro Asn 
    210                 215                 220                 


Lys Gly Glu Ser Lys Glu Ala Ile Pro Asp Ser Lys Ser Leu Glu Ser 
225                 230                 235                 240 


Ser Lys Glu Ile Pro Glu Gln Arg Glu Asn Lys Gln Gln Gln Lys Lys 
                245                 250                 255     


Arg Lys Val Gln Asp Lys Gln Lys Ser Val Ser Val Ser Thr Val His 
            260                 265                 270         


<210>  50
<211>  234
<212>  PRT
<213>  Homo sapiens

<400>  50

Met Arg Ala Pro Leu Cys Leu Leu Leu Leu Val Ala His Ala Val Asp 
1               5                   10                  15      


Met Leu Ala Leu Asn Arg Arg Lys Lys Gln Val Gly Thr Gly Leu Gly 
            20                  25                  30          


Gly Asn Cys Thr Gly Cys Ile Ile Cys Ser Glu Glu Asn Gly Cys Ser 
        35                  40                  45              


Thr Cys Gln Gln Arg Leu Phe Leu Phe Ile Arg Arg Glu Gly Ile Arg 
    50                  55                  60                  


Gln Tyr Gly Lys Cys Leu His Asp Cys Pro Pro Gly Tyr Phe Gly Ile 
65                  70                  75                  80  


Arg Gly Gln Glu Val Asn Arg Cys Lys Lys Cys Gly Ala Thr Cys Glu 
                85                  90                  95      


Ser Cys Phe Ser Gln Asp Phe Cys Ile Arg Cys Lys Arg Gln Phe Tyr 
            100                 105                 110         


Leu Tyr Lys Gly Lys Cys Leu Pro Thr Cys Pro Pro Gly Thr Leu Ala 
        115                 120                 125             


His Gln Asn Thr Arg Glu Cys Gln Gly Glu Cys Glu Leu Gly Pro Trp 
    130                 135                 140                 


Gly Gly Trp Ser Pro Cys Thr His Asn Gly Lys Thr Cys Gly Ser Ala 
145                 150                 155                 160 


Trp Gly Leu Glu Ser Arg Val Arg Glu Ala Gly Arg Ala Gly His Glu 
                165                 170                 175     


Glu Ala Ala Thr Cys Gln Val Leu Ser Glu Ser Arg Lys Cys Pro Ile 
            180                 185                 190         


Gln Arg Pro Cys Pro Gly Glu Arg Ser Pro Gly Gln Lys Lys Gly Arg 
        195                 200                 205             


Lys Asp Arg Arg Pro Arg Lys Asp Arg Lys Leu Asp Arg Arg Leu Asp 
    210                 215                 220                 


Val Arg Pro Arg Gln Pro Gly Leu Gln Pro 
225                 230                 


<210>  51
<211>  574
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - fusion construct 8M24-EASE-RA heavy chain fused to 
       RSPO2

<400>  51

Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp Asn Gly Cys 
1               5                   10                  15      


Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg Glu Gly Met 
            20                  25                  30          


Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly Tyr Tyr Gly 
        35                  40                  45              


His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn 
    50                  55                  60                  


Cys Asp Ser Cys Arg Ser Lys Asp Ala Cys Thr Lys Cys Lys Val Gly 
65                  70                  75                  80  


Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe 
                85                  90                  95      


Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys 
    130                 135                 140                 


Lys Ala Ser Gly Tyr Thr Phe Thr Ala Tyr Gly Ile Asn Trp Val Arg 
145                 150                 155                 160 


Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Glu Ile Phe Pro Arg 
                165                 170                 175     


Ser Asp Ser Thr Phe Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile 
            180                 185                 190         


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


Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Lys Gly Arg Glu 
    210                 215                 220                 


Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Thr Val 
225                 230                 235                 240 


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
                245                 250                 255     


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
            260                 265                 270         


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
        275                 280                 285             


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
    290                 295                 300                 


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
305                 310                 315                 320 


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
                325                 330                 335     


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
            340                 345                 350         


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
        355                 360                 365             


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
    370                 375                 380                 


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
385                 390                 395                 400 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
                405                 410                 415     


Lys Pro Arg Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Val Val Ser Val 
            420                 425                 430         


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
        435                 440                 445             


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
    450                 455                 460                 


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
465                 470                 475                 480 


Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
                485                 490                 495     


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
            500                 505                 510         


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
        515                 520                 525             


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
    530                 535                 540                 


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
545                 550                 555                 560 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                565                 570                 


<210>  52
<211>  169
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - modified human ASGR1

<400>  52

His His His His His His His His Gly Ser Gly Ser Gly Leu Asn Asp 
1               5                   10                  15      


Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu Ser Gly Ser Gly Cys 
            20                  25                  30          


Pro Val Asn Trp Val Glu His Glu Arg Ser Cys Tyr Trp Phe Ser Arg 
        35                  40                  45              


Ser Gly Lys Ala Trp Ala Asp Ala Asp Asn Tyr Cys Arg Leu Glu Asp 
    50                  55                  60                  


Ala His Leu Val Val Val Thr Ser Trp Glu Glu Gln Lys Phe Val Gln 
65                  70                  75                  80  


His His Ile Gly Pro Val Asn Thr Trp Met Gly Leu His Asp Gln Asn 
                85                  90                  95      


Gly Pro Trp Lys Trp Val Asp Gly Thr Asp Tyr Glu Thr Gly Phe Lys 
            100                 105                 110         


Asn Trp Arg Pro Glu Gln Pro Asp Asp Trp Tyr Gly His Gly Leu Gly 
        115                 120                 125             


Gly Gly Glu Asp Cys Ala His Phe Thr Asp Asp Gly Arg Trp Asn Asp 
    130                 135                 140                 


Asp Val Cys Gln Arg Pro Tyr Arg Trp Val Cys Glu Thr Glu Leu Asp 
145                 150                 155                 160 


Lys Ala Ser Gln Glu Pro Pro Leu Leu 
                165                 


<210>  53
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24L1 Light-chain

<400>  53

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 Arg Ile Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          


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


Tyr Ala Ala Ile Asn Leu Ala 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 Gln His Phe Trp Gly Thr Pro Phe 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  54
<211>  236
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - 8M24H1 Heavy-chain

<400>  54

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


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


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


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


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


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


Ala Arg Lys Gly Arg Asp Tyr Gly Thr Ser His Tyr Phe Asp Tyr Trp 
            100                 105                 110         


Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             


Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
    130                 135                 140                 


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             


His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser 
    210                 215                 220                 


Cys Gly Ser Gly Ser Gly His His His His His His 
225                 230                 235     


<210>  55
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  55

Gly Gly Gly Gly 
1               


<210>  56
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  56

Gly Gly Gly Gly Gly 
1               5   


<210>  57
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  57

Gly Gly Gly Gly Gly Gly Gly 
1               5           


<210>  58
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  58

Gly Gly Gly Gly Ser 
1               5   


<210>  59
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  59

Gly Gly Gly Gly Gly Lys 
1               5       


<210>  60
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  60

Gly Gly Gly Gly Gly Lys Arg 
1               5           


<210>  61
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  61

Gly Gly Gly Lys Gly Gly Gly Gly 
1               5               


<210>  62
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Made in Lab - peptide linker

<400>  62

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


