                         SEQUENCE LISTING

<110>  Amgen Inc.
 
<120>  HETEROCYCLIC QUINOLONE DERIVATIVES THAT INHIBIT PROLYL 
       HYDROXYLASE ACTIVITY

<130>  A-1280-WO-PCT

<140>  Not Assigned Yet
<141>  2008-04-25

<150>  60/927,772
<151>  2007-05-04

<160>  11    

<170>  PatentIn version 3.3

<210>  1
<211>  166
<212>  PRT
<213>  Homo sapiens

<400>  1

Met His His His His His His Glu Ala Gly Arg Pro Arg Pro Val Leu 
1               5                   10                  15      


Arg Ser Val Asn Ser Arg Glu Pro Ser Gln Val Ile Phe Cys Asn Arg 
            20                  25                  30          


Ser Pro Arg Val Val Leu Pro Val Trp Leu Asn Phe Asp Gly Glu Pro 
        35                  40                  45              


Gln Pro Tyr Pro Thr Leu Pro Pro Gly Thr Gly Arg Arg Ile His Ser 
    50                  55                  60                  


Tyr Arg Gly His Leu Trp Leu Phe Arg Asp Ala Gly Thr His Asp Gly 
65                  70                  75                  80  


Leu Leu Val Asn Gln Thr Glu Leu Phe Val Pro Ser Leu Asn Val Asp 
                85                  90                  95      


Gly Gln Pro Ile Phe Ala Asn Ile Thr Leu Pro Val Tyr Thr Leu Lys 
            100                 105                 110         


Glu Arg Cys Leu Gln Val Val Arg Ser Leu Val Lys Pro Glu Asn Tyr 
        115                 120                 125             


Arg Arg Leu Asp Ile Val Arg Ser Leu Tyr Glu Asp Leu Glu Asp His 
    130                 135                 140                 


Pro Asn Val Gln Lys Asp Leu Glu Arg Leu Thr Gln Glu Arg Ile Ala 
145                 150                 155                 160 


His Gln Arg Met Gly Asp 
                165     


<210>  2
<211>  118
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Asp Val Phe Leu Met Ile Arg Arg His Lys Thr Thr Ile Phe Thr 
1               5                   10                  15      


Asp Ala Lys Glu Ser Ser Thr Val Phe Glu Leu Lys Arg Ile Val Glu 
            20                  25                  30          


Gly Ile Leu Lys Arg Pro Pro Asp Glu Gln Arg Leu Tyr Lys Asp Asp 
        35                  40                  45              


Gln Leu Leu Asp Asp Gly Lys Thr Leu Gly Glu Cys Gly Phe Thr Ser 
    50                  55                  60                  


Gln Thr Ala Arg Pro Gln Ala Pro Ala Thr Val Gly Leu Ala Phe Arg 
65                  70                  75                  80  


Ala Asp Asp Thr Phe Glu Ala Leu Cys Ile Glu Pro Phe Ser Ser Pro 
                85                  90                  95      


Pro Glu Leu Pro Asp Val Met Lys Pro Gln Asp Ser Gly Ser Ser Ala 
            100                 105                 110         


Asn Glu Gln Ala Val Gln 
        115             


<210>  3
<211>  96
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Tyr Val Lys Leu Ile Ser Ser Asp Gly His Glu Phe Ile Val Lys 
1               5                   10                  15      


Arg Glu His Ala Leu Thr Ser Gly Thr Ile Lys Ala Met Leu Ser Gly 
            20                  25                  30          


Pro Gly Gln Phe Ala Glu Asn Glu Thr Asn Glu Val Asn Phe Arg Glu 
        35                  40                  45              


Ile Pro Ser His Val Leu Ser Lys Val Cys Met Tyr Phe Thr Tyr Lys 
    50                  55                  60                  


Val Arg Tyr Thr Asn Ser Ser Thr Glu Ile Pro Glu Phe Pro Ile Ala 
65                  70                  75                  80  


Pro Glu Ile Ala Leu Glu Leu Leu Met Ala Ala Asn Phe Leu Asp Cys 
                85                  90                  95      


<210>  4
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Biotinylation

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Carboxylation

<400>  4

Asp Leu Asp Leu Glu Ala Leu Ala Pro Tyr Ile Pro Ala Asp Asp Asp 
1               5                   10                  15      


Phe Gln Leu Arg 
            20  


<210>  5
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Biotinylation

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa at position 9 is hydroxyproline

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Carboxyamidated

<400>  5

Asp Leu Asp Leu Glu Ala Leu Ala Xaa Tyr Ile Pro Ala Asp Asp Asp 
1               5                   10                  15      


Phe Gln Leu Arg 
            20  


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

<220>
<223>  Synthetic peptide

<400>  6

Asp Leu Glu Met Leu Ala Pro Tyr Ile Pro Met Asp Asp Asp Phe Gln 
1               5                   10                  15      


Leu 
    


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

<220>
<223>  Synthetic peptide


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  Biotinylation

<400>  7

Asp Leu Glu Met Leu Ala Pro Tyr Ile Pro Met Asp Asp Asp Phe Gln 
1               5                   10                  15      


Leu 
    


<210>  8
<211>  12
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(12)
<223>  Metal affinity tag which includes histidines at positions 3 
       through 8

<400>  8

Met Ala His His His His His His Asp Glu Val Asp 
1               5                   10          


<210>  9
<211>  545
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(12)
<223>  Metal affinity tag which includes histidines at positions 3 
       through 8

<220>
<221>  MISC_FEATURE
<222>  (13)..(28)
<223>  Secretion signal sequence

<400>  9

Met Ala His His His His His His Asp Glu Val Asp Ile Trp Tyr Ile 
1               5                   10                  15      


Leu Ile Ile Gly Ile Leu Leu Pro Gln Ser Leu Ala His Pro Gly Phe 
            20                  25                  30          


Phe Thr Ser Ile Gly Gln Met Thr Asp Leu Ile His Thr Glu Lys Asp 
        35                  40                  45              


Leu Val Thr Ser Leu Lys Asp Tyr Ile Lys Ala Glu Glu Asp Lys Leu 
    50                  55                  60                  


Glu Gln Ile Lys Lys Trp Ala Glu Lys Leu Asp Arg Leu Thr Ser Thr 
65                  70                  75                  80  


Ala Thr Lys Asp Pro Glu Gly Phe Val Gly His Pro Val Asn Ala Phe 
                85                  90                  95      


Lys Leu Met Lys Arg Leu Asn Thr Glu Trp Ser Glu Leu Glu Asn Leu 
            100                 105                 110         


Val Leu Lys Asp Met Ser Asp Gly Phe Ile Ser Asn Leu Thr Ile Gln 
        115                 120                 125             


Arg Gln Tyr Phe Pro Asn Asp Glu Asp Gln Val Gly Ala Ala Lys Ala 
    130                 135                 140                 


Leu Leu Arg Leu Gln Asp Thr Tyr Asn Leu Asp Thr Asp Thr Ile Ser 
145                 150                 155                 160 


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


Asp Cys Phe Glu Leu Gly Lys Val Ala Tyr Thr Glu Ala Asp Tyr Tyr 
            180                 185                 190         


His Thr Glu Leu Trp Met Glu Gln Ala Leu Arg Gln Leu Asp Glu Gly 
        195                 200                 205             


Glu Ile Ser Thr Ile Asp Lys Val Ser Val Leu Asp Tyr Leu Ser Tyr 
    210                 215                 220                 


Ala Val Tyr Gln Gln Gly Asp Leu Asp Lys Ala Leu Leu Leu Thr Lys 
225                 230                 235                 240 


Lys Leu Leu Glu Leu Asp Pro Glu His Gln Arg Ala Asn Gly Asn Leu 
                245                 250                 255     


Lys Tyr Phe Glu Tyr Ile Met Ala Lys Glu Lys Asp Val Asn Lys Ser 
            260                 265                 270         


Ala Ser Asp Asp Gln Ser Asp Gln Lys Thr Thr Pro Lys Lys Lys Gly 
        275                 280                 285             


Val Ala Val Asp Tyr Leu Pro Glu Arg Gln Lys Tyr Glu Met Leu Cys 
    290                 295                 300                 


Arg Gly Glu Gly Ile Lys Met Thr Pro Arg Arg Gln Lys Lys Leu Phe 
305                 310                 315                 320 


Cys Arg Tyr His Asp Gly Asn Arg Asn Pro Lys Phe Ile Leu Ala Pro 
                325                 330                 335     


Ala Lys Gln Glu Asp Glu Trp Asp Lys Pro Arg Ile Ile Arg Phe His 
            340                 345                 350         


Asp Ile Ile Ser Asp Ala Glu Ile Glu Ile Val Lys Asp Leu Ala Lys 
        355                 360                 365             


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


Thr Thr Ala Gln Tyr Arg Val Ser Lys Ser Ala Trp Leu Ser Gly Tyr 
385                 390                 395                 400 


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


Gly Leu Asp Val Ser Thr Ala Glu Glu Leu Gln Val Ala Asn Tyr Gly 
            420                 425                 430         


Val Gly Gly Gln Tyr Glu Pro His Phe Asp Phe Ala Arg Lys Asp Glu 
        435                 440                 445             


Pro Asp Ala Phe Lys Glu Leu Gly Thr Gly Asn Arg Ile Ala Thr Trp 
    450                 455                 460                 


Leu Phe Tyr Met Ser Asp Val Ser Ala Gly Gly Ala Thr Val Phe Pro 
465                 470                 475                 480 


Glu Val Gly Ala Ser Val Trp Pro Lys Lys Gly Thr Ala Val Phe Trp 
                485                 490                 495     


Tyr Asn Leu Phe Ala Ser Gly Glu Gly Asp Tyr Ser Thr Arg His Ala 
            500                 505                 510         


Ala Cys Pro Val Leu Val Gly Asn Lys Trp Val Ser Asn Lys Trp Leu 
        515                 520                 525             


His Glu Arg Gly Gln Glu Phe Arg Arg Pro Cys Thr Leu Ser Glu Leu 
    530                 535                 540                 


Glu 
545 


<210>  10
<211>  544
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(12)
<223>  Metal affinity tag which includes histidines at positions 3 
       through 8

<220>
<221>  MISC_FEATURE
<222>  (13)..(32)
<223>  Secretion signal sequence

<400>  10

Met Ala His His His His His His Asp Glu Val Asp Lys Leu Trp Val 
1               5                   10                  15      


Ser Ala Leu Leu Met Ala Trp Phe Gly Val Leu Ser Cys Val Gln Ala 
            20                  25                  30          


Glu Phe Phe Thr Ser Ile Gly His Met Thr Asp Leu Ile Tyr Ala Glu 
        35                  40                  45              


Lys Glu Leu Val Gln Ser Leu Lys Glu Tyr Ile Leu Val Glu Glu Ala 
    50                  55                  60                  


Lys Leu Ser Lys Ile Lys Ser Trp Ala Asn Lys Met Glu Ala Leu Thr 
65                  70                  75                  80  


Ser Lys Ser Ala Ala Asp Ala Glu Gly Tyr Leu Ala His Pro Val Asn 
                85                  90                  95      


Ala Tyr Lys Leu Val Lys Arg Leu Asn Thr Asp Trp Pro Ala Leu Glu 
            100                 105                 110         


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


Val Gln Arg Gln Phe Phe Pro Thr Asp Glu Asp Glu Ile Gly Ala Ala 
    130                 135                 140                 


Lys Ala Leu Met Arg Leu Gln Asp Thr Tyr Arg Leu Asp Pro Gly Thr 
145                 150                 155                 160 


Ile Ser Arg Gly Glu Leu Pro Gly Thr Lys Tyr Gln Ala Met Leu Ser 
                165                 170                 175     


Val Asp Asp Cys Phe Gly Met Gly Arg Ser Ala Tyr Asn Glu Gly Asp 
            180                 185                 190         


Tyr Tyr His Thr Val Leu Trp Met Glu Gln Val Leu Lys Gln Leu Asp 
        195                 200                 205             


Ala Gly Glu Glu Ala Thr Thr Thr Lys Ser Gln Val Leu Asp Tyr Leu 
    210                 215                 220                 


Ser Tyr Ala Val Phe Gln Leu Gly Asp Leu His Arg Ala Leu Glu Leu 
225                 230                 235                 240 


Thr Arg Arg Leu Leu Ser Leu Asp Pro Ser His Glu Arg Ala Gly Gly 
                245                 250                 255     


Asn Leu Arg Tyr Phe Glu Gln Leu Leu Glu Glu Glu Arg Glu Lys Thr 
            260                 265                 270         


Leu Thr Asn Gln Thr Glu Ala Glu Leu Ala Thr Pro Glu Gly Ile Tyr 
        275                 280                 285             


Glu Arg Pro Val Asp Tyr Leu Pro Glu Arg Asp Val Tyr Glu Ser Leu 
    290                 295                 300                 


Cys Arg Gly Glu Gly Val Lys Leu Thr Pro Arg Arg Gln Lys Arg Leu 
305                 310                 315                 320 


Phe Cys Arg Tyr His His Gly Asn Arg Ala Pro Gln Leu Leu Ile Ala 
                325                 330                 335     


Pro Phe Lys Glu Glu Asp Glu Trp Asp Ser Pro His Ile Val Arg Tyr 
            340                 345                 350         


Tyr Asp Val Met Ser Asp Glu Glu Ile Glu Arg Ile Lys Glu Ile Ala 
        355                 360                 365             


Lys Pro Lys Leu Ala Arg Ala Thr Val Arg Asp Pro Lys Thr Gly Val 
    370                 375                 380                 


Leu Thr Val Ala Ser Tyr Arg Val Ser Lys Ser Ser Trp Leu Glu Glu 
385                 390                 395                 400 


Asp Asp Asp Pro Val Val Ala Arg Val Asn Arg Arg Met Gln His Ile 
                405                 410                 415     


Thr Gly Leu Thr Val Lys Thr Ala Glu Leu Leu Gln Val Ala Asn Tyr 
            420                 425                 430         


Gly Val Gly Gly Gln Tyr Glu Pro His Phe Asp Phe Ser Arg Arg Pro 
        435                 440                 445             


Phe Asp Ser Gly Leu Lys Thr Glu Gly Asn Arg Leu Ala Thr Phe Leu 
    450                 455                 460                 


Asn Tyr Met Ser Asp Val Glu Ala Gly Gly Ala Thr Val Phe Pro Asp 
465                 470                 475                 480 


Leu Gly Ala Ala Ile Trp Pro Lys Lys Gly Thr Ala Val Phe Trp Tyr 
                485                 490                 495     


Asn Leu Leu Arg Ser Gly Glu Gly Asp Tyr Arg Thr Arg His Ala Ala 
            500                 505                 510         


Cys Pro Val Leu Val Gly Cys Lys Trp Val Ser Asn Lys Trp Phe His 
        515                 520                 525             


Glu Arg Gly Gln Glu Phe Leu Arg Pro Cys Gly Ser Thr Glu Val Asp 
    530                 535                 540                 


<210>  11
<211>  514
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(17)
<223>  Secretion signal sequence

<220>
<221>  MISC_FEATURE
<222>  (18)..(23)
<223>  Six-histidine metal affinity tag

<400>  11

Met Leu Arg Arg Ala Leu Leu Cys Leu Ala Val Ala Ala Leu Val Arg 
1               5                   10                  15      


Ala His His His His His His Asp Ala Pro Glu Glu Glu Asp His Val 
            20                  25                  30          


Leu Val Leu Arg Lys Ser Asn Phe Ala Glu Ala Leu Ala Ala His Lys 
        35                  40                  45              


Tyr Leu Leu Val Glu Phe Tyr Ala Pro Trp Cys Gly His Cys Lys Ala 
    50                  55                  60                  


Leu Ala Pro Glu Tyr Ala Lys Ala Ala Gly Lys Leu Lys Ala Glu Gly 
65                  70                  75                  80  


Ser Glu Ile Arg Leu Ala Lys Val Asp Ala Thr Glu Glu Ser Asp Leu 
                85                  90                  95      


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


Asn Gly Asp Thr Ala Ser Pro Lys Glu Tyr Thr Ala Gly Arg Glu Ala 
        115                 120                 125             


Asp Asp Ile Val Asn Trp Leu Lys Lys Arg Thr Gly Pro Ala Ala Thr 
    130                 135                 140                 


Thr Leu Pro Asp Gly Ala Ala Ala Glu Ser Leu Val Glu Ser Ser Glu 
145                 150                 155                 160 


Val Ala Val Ile Gly Phe Phe Lys Asp Val Glu Ser Asp Ser Ala Lys 
                165                 170                 175     


Gln Phe Leu Gln Ala Ala Glu Ala Ile Asp Asp Ile Pro Phe Gly Ile 
            180                 185                 190         


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


Val Val Leu Phe Lys Lys Phe Asp Glu Gly Arg Asn Asn Phe Glu Gly 
    210                 215                 220                 


Glu Val Thr Lys Glu Asn Leu Leu Asp Phe Ile Lys His Asn Gln Leu 
225                 230                 235                 240 


Pro Leu Val Ile Glu Phe Thr Glu Gln Thr Ala Pro Lys Ile Phe Gly 
                245                 250                 255     


Gly Glu Ile Lys Thr His Ile Leu Leu Phe Leu Pro Lys Ser Val Ser 
            260                 265                 270         


Asp Tyr Asp Gly Lys Leu Ser Asn Phe Lys Thr Ala Ala Glu Ser Phe 
        275                 280                 285             


Lys Gly Lys Ile Leu Phe Ile Phe Ile Asp Ser Asp His Thr Asp Asn 
    290                 295                 300                 


Gln Arg Ile Leu Glu Phe Phe Gly Leu Lys Lys Glu Glu Cys Pro Ala 
305                 310                 315                 320 


Val Arg Leu Ile Thr Leu Glu Glu Glu Met Thr Lys Tyr Lys Pro Glu 
                325                 330                 335     


Ser Glu Glu Leu Thr Ala Glu Arg Ile Thr Glu Phe Cys His Arg Phe 
            340                 345                 350         


Leu Glu Gly Lys Ile Lys Pro His Leu Met Ser Gln Glu Leu Pro Glu 
        355                 360                 365             


Asp Trp Asp Lys Gln Pro Val Lys Val Leu Val Gly Lys Asn Phe Glu 
    370                 375                 380                 


Asp Val Ala Phe Asp Glu Lys Lys Asn Val Phe Val Glu Phe Tyr Ala 
385                 390                 395                 400 


Pro Trp Cys Gly His Cys Lys Gln Leu Ala Pro Ile Trp Asp Lys Leu 
                405                 410                 415     


Gly Glu Thr Tyr Lys Asp His Glu Asn Ile Val Ile Ala Lys Met Asp 
            420                 425                 430         


Ser Thr Ala Asn Glu Val Glu Ala Val Lys Val His Ser Phe Pro Thr 
        435                 440                 445             


Leu Lys Phe Phe Pro Ala Ser Ala Asp Arg Thr Val Ile Asp Tyr Asn 
    450                 455                 460                 


Gly Glu Arg Thr Leu Asp Gly Phe Lys Lys Phe Leu Glu Ser Gly Gly 
465                 470                 475                 480 


Gln Asp Gly Ala Gly Asp Asp Asp Asp Leu Glu Asp Leu Glu Glu Ala 
                485                 490                 495     


Glu Glu Pro Asp Met Glu Glu Asp Asp Asp Gln Lys Ala Val Lys Asp 
            500                 505                 510         


Glu Leu 
        


