                         SEQUENCE LISTING

<110>  VIB VZW
       VRIJE UNIVERSITEIT BRUSSEL
       UNIVERSITY OF COPENHAGEN
 
<120>  POSITIVE ALLOSTERIC MODULATORS OF THE CALCIUM-SENSING RECEPTOR

<130>  JaSt/CaSR_Nbs/672

<150>  EP 19211709.1
<151>  2019-11-27

<160>  34    

<170>  PatentIn version 3.5

<210>  1
<211>  1075
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Phe Tyr Ser Cys Cys Trp Val Leu Leu Ala Leu Thr Trp His 
1               5                   10                  15      


Thr Ser Ala Tyr Gly Pro Asp Gln Arg Ala Gln Lys Lys Gly Asp Ile 
            20                  25                  30          


Ile Leu Gly Gly Leu Phe Pro Ile His Phe Gly Val Ala Ala Lys Asp 
        35                  40                  45              


Gln Asp Leu Lys Ser Arg Pro Glu Ser Val Glu Cys Ile Arg Tyr Asn 
    50                  55                  60                  


Phe Arg Gly Phe Arg Trp Leu Gln Ala Met Ile Phe Ala Ile Glu Glu 
65                  70                  75                  80  


Ile Asn Ser Ser Pro Ala Leu Leu Pro Asn Leu Thr Leu Gly Tyr Arg 
                85                  90                  95      


Ile Phe Asp Thr Cys Asn Thr Val Ser Lys Ala Leu Glu Ala Thr Leu 
            100                 105                 110         


Ser Phe Val Ala Gln Asn Lys Ile Asp Ser Leu Asn Leu Asp Glu Phe 
        115                 120                 125             


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


Thr Gly Ser Gly Val Ser Thr Ala Val Ala Asn Leu Leu Gly Leu Phe 
145                 150                 155                 160 


Tyr Ile Pro Gln Val Ser Tyr Ala Ser Ser Ser Arg Leu Leu Ser Asn 
                165                 170                 175     


Lys Asn Gln Phe Lys Ser Phe Leu Arg Thr Ile Pro Asn Asp Glu His 
            180                 185                 190         


Gln Ala Thr Ala Met Ala Asp Ile Ile Glu Tyr Phe Arg Trp Asn Trp 
        195                 200                 205             


Val Gly Thr Ile Ala Ala Asp Asp Asp Tyr Gly Arg Pro Gly Ile Glu 
    210                 215                 220                 


Lys Phe Arg Glu Glu Ala Glu Glu Arg Asp Ile Cys Ile Asp Phe Ser 
225                 230                 235                 240 


Glu Leu Ile Ser Gln Tyr Ser Asp Glu Glu Glu Ile Gln His Val Val 
                245                 250                 255     


Glu Val Ile Gln Asn Ser Thr Ala Lys Val Ile Val Val Phe Ser Ser 
            260                 265                 270         


Gly Pro Asp Leu Glu Pro Leu Ile Lys Glu Ile Val Arg Arg Asn Ile 
        275                 280                 285             


Thr Gly Lys Ile Trp Leu Ala Ser Glu Ala Trp Ala Ser Ser Ser Leu 
    290                 295                 300                 


Ile Ala Met Pro Gln Tyr Phe His Val Val Gly Gly Thr Ile Gly Phe 
305                 310                 315                 320 


Ala Leu Lys Ala Gly Gln Ile Pro Gly Phe Arg Glu Phe Leu Lys Lys 
                325                 330                 335     


Val His Pro Arg Lys Ser Val His Asn Gly Phe Ala Lys Glu Phe Trp 
            340                 345                 350         


Glu Glu Thr Phe Asn Cys His Leu Gln Glu Gly Ala Lys Gly Pro Leu 
        355                 360                 365             


Pro Val Asp Thr Phe Leu Arg Gly His Glu Glu Ser Gly Asp Arg Phe 
    370                 375                 380                 


Ser Asn Ser Ser Thr Ala Phe Arg Pro Leu Cys Thr Gly Asp Glu Asn 
385                 390                 395                 400 


Ile Ser Ser Val Glu Thr Pro Tyr Ile Asp Tyr Thr His Leu Arg Ile 
                405                 410                 415     


Ser Tyr Asn Val Tyr Leu Ala Val Tyr Ser Ile Ala His Ala Leu Gln 
            420                 425                 430         


Asp Ile Tyr Thr Cys Leu Pro Gly Arg Gly Leu Phe Thr Asn Gly Ser 
        435                 440                 445             


Cys Ala Asp Ile Lys Lys Val Glu Ala Trp Gln Val Leu Lys His Leu 
    450                 455                 460                 


Arg His Leu Asn Phe Thr Asn Asn Met Gly Glu Gln Val Thr Phe Asp 
465                 470                 475                 480 


Glu Cys Gly Asp Leu Val Gly Asn Tyr Ser Ile Ile Asn Trp His Leu 
                485                 490                 495     


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


Val Tyr Ala Lys Lys Gly Glu Arg Leu Phe Ile Asn Glu Glu Lys Ile 
        515                 520                 525             


Leu Trp Ser Gly Phe Ser Arg Glu Val Pro Phe Ser Asn Cys Ser Arg 
    530                 535                 540                 


Asp Cys Leu Ala Gly Thr Arg Lys Gly Ile Ile Glu Gly Glu Pro Thr 
545                 550                 555                 560 


Cys Cys Phe Glu Cys Val Glu Cys Pro Asp Gly Glu Tyr Ser Asp Glu 
                565                 570                 575     


Thr Asp Ala Ser Ala Cys Asn Lys Cys Pro Asp Asp Phe Trp Ser Asn 
            580                 585                 590         


Glu Asn His Thr Ser Cys Ile Ala Lys Glu Ile Glu Phe Leu Ser Trp 
        595                 600                 605             


Thr Glu Pro Phe Gly Ile Ala Leu Thr Leu Phe Ala Val Leu Gly Ile 
    610                 615                 620                 


Phe Leu Thr Ala Phe Val Leu Gly Val Phe Ile Lys Phe Arg Asn Thr 
625                 630                 635                 640 


Pro Ile Lys Ala Thr Asn Arg Glu Leu Ser Tyr Leu Leu Leu Phe Ser 
                645                 650                 655     


Leu Leu Cys Cys Phe Ser Ser Ser Leu Phe Phe Ile Gly Glu Pro Gln 
            660                 665                 670         


Asp Trp Thr Cys Arg Leu Arg Gln Pro Ala Phe Gly Ile Ser Phe Val 
        675                 680                 685             


Leu Cys Ile Ser Cys Ile Leu Val Lys Thr Asn Arg Val Leu Leu Val 
    690                 695                 700                 


Phe Glu Ala Lys Ile Pro Thr Ser Phe His Arg Lys Trp Trp Gly Leu 
705                 710                 715                 720 


Asn Leu Gln Phe Leu Leu Val Phe Leu Cys Thr Phe Met Gln Ile Val 
                725                 730                 735     


Ile Cys Val Ile Trp Leu Tyr Thr Ala Pro Pro Ser Ser Tyr Arg Asn 
            740                 745                 750         


Gln Glu Leu Glu Asp Glu Ile Ile Phe Ile Thr Cys His Glu Gly Ser 
        755                 760                 765             


Leu Met Ala Leu Gly Phe Leu Ile Gly Tyr Thr Cys Leu Leu Ala Ala 
    770                 775                 780                 


Ile Cys Phe Phe Phe Ala Phe Lys Ser Arg Lys Leu Pro Glu Asn Phe 
785                 790                 795                 800 


Asn Glu Ala Lys Phe Ile Thr Phe Ser Leu Ile Phe Phe Ile Val Trp 
                805                 810                 815     


Ile Ser Phe Ile Pro Ala Tyr Ala Ser Thr Tyr Gly Lys Phe Val Ser 
            820                 825                 830         


Ala Val Glu Val Ile Ala Ile Leu Ala Ala Ser Phe Gly Leu Leu Ala 
        835                 840                 845             


Cys Ile Phe Phe Asn Lys Ile Tyr Ile Ile Leu Phe Lys Pro Ser Arg 
    850                 855                 860                 


Asn Thr Ile Glu Glu Val Arg Cys Ser Thr Ala Ala His Ala Phe Lys 
865                 870                 875                 880 


Val Ala Ala Arg Ala Thr Leu Arg Arg Ser Asn Val Ser Arg Lys Ser 
                885                 890                 895     


Ser Ser Leu Gly Gly Ser Thr Gly Ser Thr Pro Ser Ser Ser Ile Ser 
            900                 905                 910         


Ser Lys Ser Asn Ser Glu Asp Pro Phe Pro Gln Pro Glu Arg Gln Lys 
        915                 920                 925             


Gln Gln Gln Pro Leu Ala Leu Thr Gln Gln Glu Gln Gln Gln Gln Pro 
    930                 935                 940                 


Leu Thr Leu Pro Gln Gln Gln Arg Ser Gln Gln Gln Pro Arg Cys Lys 
945                 950                 955                 960 


Gln Lys Val Ile Phe Gly Ser Gly Thr Val Thr Phe Ser Leu Ser Phe 
                965                 970                 975     


Asp Glu Pro Gln Lys Asn Ala Met Ala His Arg Asn Ser Thr His Gln 
            980                 985                 990         


Asn Ser Leu Glu Ala Gln Lys Ser  Ser Asp Thr Leu Thr  Arg His Gln 
        995                 1000                 1005             


Pro Leu  Leu Pro Leu Gln Cys  Gly Glu Thr Asp Leu  Asp Leu Thr 
    1010                 1015                 1020             


Val Gln  Glu Thr Gly Leu Gln  Gly Pro Val Gly Gly  Asp Gln Arg 
    1025                 1030                 1035             


Pro Glu  Val Glu Asp Pro Glu  Glu Leu Ser Pro Ala  Leu Val Val 
    1040                 1045                 1050             


Ser Ser  Ser Gln Ser Phe Val  Ile Ser Gly Gly Gly  Ser Thr Val 
    1055                 1060                 1065             


Thr Glu  Asn Val Val Asn Ser  
    1070                 1075 


<210>  2
<211>  1079
<212>  PRT
<213>  Rattus norvegicus

<400>  2

Met Ala Ser Tyr Ser Cys Cys Leu Ala Leu Leu Ala Leu Ala Trp His 
1               5                   10                  15      


Ser Ser Ala Tyr Gly Pro Asp Gln Arg Ala Gln Lys Lys Gly Asp Ile 
            20                  25                  30          


Ile Leu Gly Gly Leu Phe Pro Ile His Phe Gly Val Ala Ala Lys Asp 
        35                  40                  45              


Gln Asp Leu Lys Ser Arg Pro Glu Ser Val Glu Cys Ile Arg Tyr Asn 
    50                  55                  60                  


Phe Arg Gly Phe Arg Trp Leu Gln Ala Met Ile Phe Ala Ile Glu Glu 
65                  70                  75                  80  


Ile Asn Ser Ser Pro Ser Leu Leu Pro Asn Met Thr Leu Gly Tyr Arg 
                85                  90                  95      


Ile Phe Asp Thr Cys Asn Thr Val Ser Lys Ala Leu Glu Ala Thr Leu 
            100                 105                 110         


Ser Phe Val Ala Gln Asn Lys Ile Asp Ser Leu Asn Leu Asp Glu Phe 
        115                 120                 125             


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


Thr Gly Ser Gly Val Ser Thr Ala Val Ala Asn Leu Leu Gly Leu Phe 
145                 150                 155                 160 


Tyr Ile Pro Gln Val Ser Tyr Ala Ser Ser Ser Arg Leu Leu Ser Asn 
                165                 170                 175     


Lys Asn Gln Tyr Lys Ser Phe Leu Arg Thr Ile Pro Asn Asp Glu His 
            180                 185                 190         


Gln Ala Thr Ala Met Ala Asp Ile Ile Glu Tyr Phe Arg Trp Asn Trp 
        195                 200                 205             


Val Gly Thr Ile Ala Ala Asp Asp Asp Tyr Gly Arg Pro Gly Ile Glu 
    210                 215                 220                 


Lys Phe Arg Glu Glu Ala Glu Glu Arg Asp Ile Cys Ile Asp Phe Ser 
225                 230                 235                 240 


Glu Leu Ile Ser Gln Tyr Ser Asp Glu Glu Glu Ile Gln Gln Val Val 
                245                 250                 255     


Glu Val Ile Gln Asn Ser Thr Ala Lys Val Ile Val Val Phe Ser Ser 
            260                 265                 270         


Gly Pro Asp Leu Glu Pro Leu Ile Lys Glu Ile Val Arg Arg Asn Ile 
        275                 280                 285             


Thr Gly Arg Ile Trp Leu Ala Ser Glu Ala Trp Ala Ser Ser Ser Leu 
    290                 295                 300                 


Ile Ala Met Pro Glu Tyr Phe His Val Val Gly Gly Thr Ile Gly Phe 
305                 310                 315                 320 


Gly Leu Lys Ala Gly Gln Ile Pro Gly Phe Arg Glu Phe Leu Gln Lys 
                325                 330                 335     


Val His Pro Arg Lys Ser Val His Asn Gly Phe Ala Lys Glu Phe Trp 
            340                 345                 350         


Glu Glu Thr Phe Asn Cys His Leu Gln Glu Gly Ala Lys Gly Pro Leu 
        355                 360                 365             


Pro Val Asp Thr Phe Val Arg Ser His Glu Glu Gly Gly Asn Arg Leu 
    370                 375                 380                 


Leu Asn Ser Ser Thr Ala Phe Arg Pro Leu Cys Thr Gly Asp Glu Asn 
385                 390                 395                 400 


Ile Asn Ser Val Glu Thr Pro Tyr Met Asp Tyr Glu His Leu Arg Ile 
                405                 410                 415     


Ser Tyr Asn Val Tyr Leu Ala Val Tyr Ser Ile Ala His Ala Leu Gln 
            420                 425                 430         


Asp Ile Tyr Thr Cys Leu Pro Gly Arg Gly Leu Phe Thr Asn Gly Ser 
        435                 440                 445             


Cys Ala Asp Ile Lys Lys Val Glu Ala Trp Gln Val Leu Lys His Leu 
    450                 455                 460                 


Arg His Leu Asn Phe Thr Asn Asn Met Gly Glu Gln Val Thr Phe Asp 
465                 470                 475                 480 


Glu Cys Gly Asp Leu Val Gly Asn Tyr Ser Ile Ile Asn Trp His Leu 
                485                 490                 495     


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


Val Tyr Ala Lys Lys Gly Glu Arg Leu Phe Ile Asn Glu Glu Lys Ile 
        515                 520                 525             


Leu Trp Ser Gly Phe Ser Arg Glu Val Pro Phe Ser Asn Cys Ser Arg 
    530                 535                 540                 


Asp Cys Gln Ala Gly Thr Arg Lys Gly Ile Ile Glu Gly Glu Pro Thr 
545                 550                 555                 560 


Cys Cys Phe Glu Cys Val Glu Cys Pro Asp Gly Glu Tyr Ser Gly Glu 
                565                 570                 575     


Thr Asp Ala Ser Ala Cys Asp Lys Cys Pro Asp Asp Phe Trp Ser Asn 
            580                 585                 590         


Glu Asn His Thr Ser Cys Ile Ala Lys Glu Ile Glu Phe Leu Ala Trp 
        595                 600                 605             


Thr Glu Pro Phe Gly Ile Ala Leu Thr Leu Phe Ala Val Leu Gly Ile 
    610                 615                 620                 


Phe Leu Thr Ala Phe Val Leu Gly Val Phe Ile Lys Phe Arg Asn Thr 
625                 630                 635                 640 


Pro Ile Val Lys Ala Thr Asn Arg Glu Leu Ser Tyr Leu Leu Leu Phe 
                645                 650                 655     


Ser Leu Leu Cys Cys Phe Ser Ser Ser Leu Phe Phe Ile Gly Glu Pro 
            660                 665                 670         


Gln Asp Trp Thr Cys Arg Leu Arg Gln Pro Ala Phe Gly Ile Ser Phe 
        675                 680                 685             


Val Leu Cys Ile Ser Cys Ile Leu Val Lys Thr Asn Arg Val Leu Leu 
    690                 695                 700                 


Val Phe Glu Ala Lys Ile Pro Thr Ser Phe His Arg Lys Trp Trp Gly 
705                 710                 715                 720 


Leu Asn Leu Gln Phe Leu Leu Val Phe Leu Cys Thr Phe Met Gln Ile 
                725                 730                 735     


Leu Ile Cys Ile Ile Trp Leu Tyr Thr Ala Pro Pro Ser Ser Tyr Arg 
            740                 745                 750         


Asn His Glu Leu Glu Asp Glu Ile Ile Phe Ile Thr Cys His Glu Gly 
        755                 760                 765             


Ser Leu Met Ala Leu Gly Ser Leu Ile Gly Tyr Thr Cys Leu Leu Ala 
    770                 775                 780                 


Ala Ile Cys Phe Phe Phe Ala Phe Lys Ser Arg Lys Leu Pro Glu Asn 
785                 790                 795                 800 


Phe Asn Glu Ala Lys Phe Ile Thr Phe Ser Met Leu Ile Phe Phe Ile 
                805                 810                 815     


Val Trp Ile Ser Phe Ile Pro Ala Tyr Ala Ser Thr Tyr Gly Lys Phe 
            820                 825                 830         


Val Ser Ala Val Glu Val Ile Ala Ile Leu Ala Ala Ser Phe Gly Leu 
        835                 840                 845             


Leu Ala Cys Ile Phe Phe Asn Lys Val Tyr Ile Ile Leu Phe Lys Pro 
    850                 855                 860                 


Ser Arg Asn Thr Ile Glu Glu Val Arg Ser Ser Thr Ala Ala His Ala 
865                 870                 875                 880 


Phe Lys Val Ala Ala Arg Ala Thr Leu Arg Arg Pro Asn Ile Ser Arg 
                885                 890                 895     


Lys Arg Ser Ser Ser Leu Gly Gly Ser Thr Gly Ser Ile Pro Ser Ser 
            900                 905                 910         


Ser Ile Ser Ser Lys Ser Asn Ser Glu Asp Arg Phe Pro Gln Pro Glu 
        915                 920                 925             


Arg Gln Lys Gln Gln Gln Pro Leu Ser Leu Thr Gln Gln Glu Gln Gln 
    930                 935                 940                 


Gln Gln Pro Leu Thr Leu His Pro Gln Gln Gln Gln Gln Pro Gln Gln 
945                 950                 955                 960 


Pro Arg Cys Lys Gln Lys Val Ile Phe Gly Ser Gly Thr Val Thr Phe 
                965                 970                 975     


Ser Leu Ser Phe Asp Glu Pro Gln Lys Asn Ala Met Ala His Arg Asn 
            980                 985                 990         


Ser Met Arg Gln Asn Ser Leu Glu  Ala Gln Arg Ser Asn  Asp Thr Leu 
        995                 1000                 1005             


Gly Arg  His Gln Ala Leu Leu  Pro Leu Gln Cys Ala  Asp Ala Asp 
    1010                 1015                 1020             


Ser Glu  Met Thr Ile Gln Glu  Thr Gly Leu Gln Gly  Pro Met Val 
    1025                 1030                 1035             


Gly Asp  His Gln Pro Glu Met  Glu Ser Ser Asp Glu  Met Ser Pro 
    1040                 1045                 1050             


Ala Leu  Val Met Ser Thr Ser  Arg Ser Phe Val Ile  Ser Gly Gly 
    1055                 1060                 1065             


Gly Ser  Ser Val Thr Glu Asn  Val Leu His Ser 
    1070                 1075                 


<210>  3
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb10

<400>  3

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


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


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


Ala Ala Met Ser Gly Thr Tyr Gly Ser Thr Ile Tyr Ser Asp Ser Met 
    50                  55                  60                  


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


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


Ala Gly Tyr Tyr Ser Gly Ala Tyr Tyr Gly Thr Pro Lys Thr Asp Tyr 
            100                 105                 110         


Thr Glu Tyr Asp Ser Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  4
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb37

<400>  4

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


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


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


Ala Ala Met Ser Gly Thr Tyr Gly Ser Thr Ile Tyr Ala Asp Ser Met 
    50                  55                  60                  


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


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


Ala Gly Tyr Tyr Ser Gly Ala Tyr Tyr Gly Thr Pro Lys Thr Asp Tyr 
            100                 105                 110         


Thr Glu Tyr Asp Ser Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  5
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb4

<400>  5

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


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


Arg Met Gly Trp Phe Arg Gln Gly Leu Gly Lys Glu Arg Glu Phe Val 
        35                  40                  45              


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


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


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


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


Thr Asp Trp Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  6
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb11

<400>  6

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


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


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


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


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


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


Ala Ala Arg Ile Lys Ala Ile Phe Thr Ala Gln Gln Ala Ala Thr Ile 
            100                 105                 110         


Thr Asp Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  7
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb36

<400>  7

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


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


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


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


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


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


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


Thr Asp Tyr Asp Asp Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  8
<211>  124
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb5

<400>  8

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


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


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


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


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


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


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


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


<210>  9
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb2

<400>  9

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


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


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


Ala Val Ile Ser Arg Gly Gly Gly Gly Ala Asp Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Arg Ile Ser Gly Phe Ser Tyr Tyr Thr Ser Val Asp Arg Tyr 
            100                 105                 110         


Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125 


<210>  10
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb15

<400>  10

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


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


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


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


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


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


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


Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125 


<210>  11
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 CaSR Nb10/Nb37

<400>  11

Gly Gly Ser Phe Arg Ser Tyr Ala 
1               5               


<210>  12
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 CaSR Nb4/Nb11

<400>  12

Gly Arg Thr Phe Ser Thr Tyr Arg 
1               5               


<210>  13
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 CaSR Nb36

<400>  13

Gly Arg Thr Phe Ser Ser Tyr Arg 
1               5               


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

<220>
<223>  CDR1 CaSR Nb5

<400>  14

Gly Leu Thr Phe Ser Asp Tyr Ser 
1               5               


<210>  15
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 CaSR Nb2

<400>  15

Gly Arg Thr Phe Ser Asn Tyr Arg 
1               5               


<210>  16
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 CaSR Nb 15

<400>  16

Gly Arg Thr Phe Asn Asn Tyr His 
1               5               


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

<220>
<223>  CDR2 CaSR Nb10/Nb37

<400>  17

Met Ser Gly Thr Tyr Gly Ser Thr 
1               5               


<210>  18
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 CaSR Nb4

<400>  18

Ile Thr Ala Asn Gly Val Arg Thr 
1               5               


<210>  19
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 CaSR Nb11

<400>  19

Ile Thr Ala Thr Gly Val Lys Thr 
1               5               


<210>  20
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 CaSR Nb36

<400>  20

Ile Thr Ala Thr Gly Val Arg Thr 
1               5               


<210>  21
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 CaSR Nb5

<400>  21

Ile Arg Arg Ser Asn Asp Ser Thr 
1               5               


<210>  22
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 CaSR Nb2

<400>  22

Ile Ser Arg Gly Gly Gly Gly Ala 
1               5               


<210>  23
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 CaSR Nb 15

<400>  23

Ile Ser Arg Arg Ala Gly Thr Thr 
1               5               


<210>  24
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 CaSR Nb10/37

<400>  24

Ala Gly Tyr Tyr Ser Gly Ala Tyr Tyr Gly Thr Pro Lys Thr Asp Tyr 
1               5                   10                  15      


Thr Glu Tyr Asp Ser 
            20      


<210>  25
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 CaSR Nb4

<400>  25

Ala Ala Arg Arg Lys Gly Ile Phe Thr Val Gln Gln Ala Ile Thr Asp 
1               5                   10                  15      


Asp Tyr 
        


<210>  26
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 CaSR Nb11

<400>  26

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


Asp Tyr 
        


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

<220>
<223>  CDR3 CaSR Nb36

<400>  27

Ala Ala Arg Arg Lys Ala Ile Phe Val Gln Gln Ala Thr Ile Thr Asp 
1               5                   10                  15      


Tyr Asp Asp 
            


<210>  28
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 CaSR Nb5

<400>  28

Ala Ala Asp Arg Gly Gly Val Gly Leu Thr Ser Ala Gln Thr Tyr Ala 
1               5                   10                  15      


Tyr 
    


<210>  29
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 CaSR Nb2

<400>  29

Ala Ala Arg Ile Ser Gly Phe Ser Tyr Tyr Thr Ser Val Asp Arg Tyr 
1               5                   10                  15      


Asp Tyr 
        


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

<220>
<223>  CDR3 CaSR Nb 15

<400>  30

Ala Ala Asp Pro Asp Thr Tyr Gly Val Ser Tyr Leu Ala Arg Lys Tyr 
1               5                   10                  15      


Asp Tyr 
        


<210>  31
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb36 humanized variant 1

<400>  31

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


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


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


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


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


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


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


Thr Asp Tyr Asp Asp Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125             


<210>  32
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb4_humanized variant 1

<400>  32

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


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


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


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


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


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


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


Thr Asp Trp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125             


<210>  33
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb2_humanized variant 1

<400>  33

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


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


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


Ala Val Ile Ser Arg Gly Gly Gly Gly Ala Asp Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Arg Ile Ser Gly Phe Ser Tyr Tyr Thr Ser Val Asp Arg Tyr 
            100                 105                 110         


Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125 


<210>  34
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CaSR Nb10 humanized variant 1

<400>  34

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


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


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


Ala Ala Met Ser Gly Thr Tyr Gly Ser Thr Ile Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Gly Tyr Tyr Ser Gly Ala Tyr Tyr Gly Thr Pro Lys Thr Asp Tyr 
            100                 105                 110         


Thr Glu Tyr Asp Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125             


