                         SEQUENCE LISTING

<110>  Garvan Institute of Medical Research
 
<120>  Method of treating glucose metabolism disorders

<130>  512254

<150>  AU 2012902788
<151>  2012-07-29

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  399
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Lys Met Arg Phe Leu Gly Leu Val Val Cys Leu Val Leu Trp Thr 
1               5                   10                  15      


Leu His Ser Glu Gly Ser Gly Gly Lys Leu Thr Ala Val Asp Pro Glu 
            20                  25                  30          


Thr Asn Met Asn Val Ser Glu Ile Ile Ser Tyr Trp Gly Phe Pro Ser 
        35                  40                  45              


Glu Glu Tyr Leu Val Glu Thr Glu Asp Gly Tyr Ile Leu Cys Leu Asn 
    50                  55                  60                  


Arg Ile Pro His Gly Arg Lys Asn His Ser Asp Lys Gly Pro Lys Pro 
65                  70                  75                  80  


Val Val Phe Leu Gln His Gly Leu Leu Ala Asp Ser Ser Asn Trp Val 
                85                  90                  95      


Thr Asn Leu Ala Asn Ser Ser Leu Gly Phe Ile Leu Ala Asp Ala Gly 
            100                 105                 110         


Phe Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Lys 
        115                 120                 125             


His Lys Thr Leu Ser Val Ser Gln Asp Glu Phe Trp Ala Phe Ser Tyr 
    130                 135                 140                 


Asp Glu Met Ala Lys Tyr Asp Leu Pro Ala Ser Ile Asn Phe Ile Leu 
145                 150                 155                 160 


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


Thr Thr Ile Gly Phe Ile Ala Phe Ser Gln Ile Pro Glu Leu Ala Lys 
            180                 185                 190         


Arg Ile Lys Met Phe Phe Ala Leu Gly Pro Val Ala Ser Val Ala Phe 
        195                 200                 205             


Cys Thr Ser Pro Met Ala Lys Leu Gly Arg Leu Pro Asp His Leu Ile 
    210                 215                 220                 


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


Lys Trp Leu Gly Thr His Val Cys Thr His Val Ile Leu Lys Glu Leu 
                245                 250                 255     


Cys Gly Asn Leu Cys Phe Leu Leu Cys Gly Phe Asn Glu Arg Asn Leu 
            260                 265                 270         


Asn Met Ser Arg Val Asp Val Tyr Thr Thr His Ser Pro Ala Gly Thr 
        275                 280                 285             


Ser Val Gln Asn Met Leu His Trp Ser Gln Ala Val Lys Phe Gln Lys 
    290                 295                 300                 


Phe Gln Ala Phe Asp Trp Gly Ser Ser Ala Lys Asn Tyr Phe His Tyr 
305                 310                 315                 320 


Asn Gln Ser Tyr Pro Pro Thr Tyr Asn Val Lys Asp Met Leu Val Pro 
                325                 330                 335     


Thr Ala Val Trp Ser Gly Gly His Asp Trp Leu Ala Asp Val Tyr Asp 
            340                 345                 350         


Val Asn Ile Leu Leu Thr Gln Ile Thr Asn Leu Val Phe His Glu Ser 
        355                 360                 365             


Ile Pro Glu Trp Glu His Leu Asp Phe Ile Trp Gly Leu Asp Ala Pro 
    370                 375                 380                 


Trp Arg Leu Tyr Asn Lys Ile Ile Asn Leu Met Arg Lys Tyr Gln 
385                 390                 395                 


<210>  2
<211>  504
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Phe Pro Arg Glu Lys Thr Trp Asn Ile Ser Phe Ala Gly Cys Gly 
1               5                   10                  15      


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


Ala Pro Phe Leu Val Ala Asn Ala Thr His Ile Tyr Gly Ala Ser Ala 
        35                  40                  45              


Gly Ala Leu Thr Ala Thr Ala Leu Val Thr Gly Val Cys Leu Gly Glu 
    50                  55                  60                  


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


Leu Gly Pro Leu His Pro Ser Phe Asn Leu Val Lys Ile Ile Arg Ser 
                85                  90                  95      


Phe Leu Leu Lys Val Leu Pro Ala Asp Ser His Glu His Ala Ser Gly 
            100                 105                 110         


Arg Leu Gly Ile Ser Leu Thr Arg Val Ser Asp Gly Glu Asn Val Ile 
        115                 120                 125             


Ile Ser His Phe Asn Ser Lys Asp Glu Leu Ile Gln Ala Asn Val Cys 
    130                 135                 140                 


Ser Gly Phe Ile Pro Val Tyr Cys Gly Leu Ile Pro Pro Ser Leu Gln 
145                 150                 155                 160 


Gly Val Arg Tyr Val Asp Gly Gly Ile Ser Asp Asn Leu Pro Leu Tyr 
                165                 170                 175     


Glu Leu Lys Asn Thr Ile Thr Val Ser Pro Phe Ser Gly Glu Ser Asp 
            180                 185                 190         


Ile Cys Pro Gln Asp Ser Ser Thr Asn Ile His Glu Leu Arg Val Thr 
        195                 200                 205             


Asn Thr Ser Ile Gln Phe Asn Leu Arg Asn Leu Tyr Arg Leu Ser Lys 
    210                 215                 220                 


Ala Leu Phe Pro Pro Glu Pro Leu Val Leu Arg Glu Met Cys Lys Gln 
225                 230                 235                 240 


Gly Tyr Arg Asp Gly Leu Arg Phe Leu Gln Arg Asn Gly Leu Leu Asn 
                245                 250                 255     


Arg Pro Asn Pro Leu Leu Ala Leu Pro Pro Ala Arg Pro His Gly Pro 
            260                 265                 270         


Glu Asp Lys Asp Gln Ala Val Glu Ser Ala Gln Ala Glu Asp Tyr Ser 
        275                 280                 285             


Gln Leu Pro Gly Glu Asp His Val Leu Glu His Leu Pro Ala Arg Leu 
    290                 295                 300                 


Asn Glu Ala Leu Leu Glu Ala Cys Val Glu Pro Thr Asp Leu Leu Thr 
305                 310                 315                 320 


Thr Leu Ser Asn Met Leu Pro Val Arg Leu Ala Thr Ala Met Met Val 
                325                 330                 335     


Pro Tyr Thr Leu Pro Leu Glu Ser Ala Leu Ser Phe Thr Ile Cys Leu 
            340                 345                 350         


Leu Glu Trp Leu Pro Asp Val Pro Glu Asp Ile Arg Trp Met Lys Glu 
        355                 360                 365             


Gln Thr Gly Ser Ile Cys Gln Tyr Leu Val Met Arg Ala Lys Arg Lys 
    370                 375                 380                 


Leu Gly Arg His Leu Pro Ser Arg Leu Pro Glu Gln Val Glu Leu Arg 
385                 390                 395                 400 


Arg Val Gln Ser Leu Pro Ser Val Pro Leu Ser Cys Ala Ala Tyr Arg 
                405                 410                 415     


Glu Ala Pro Pro Gly Trp Met Arg Asn Asn Leu Ser Leu Gly Asp Ala 
            420                 425                 430         


Leu Ala Lys Trp Glu Glu Cys Gln Arg Gln Leu Leu Leu Gly Leu Phe 
        435                 440                 445             


Cys Thr Asn Val Ala Phe Pro Pro Glu Ala Leu Arg Met Arg Ala Pro 
    450                 455                 460                 


Ala Asp Pro Ala Pro Ala Pro Ala Asp Pro Ala Ser Pro Gln His Gln 
465                 470                 475                 480 


Leu Ala Gly Pro Ala Pro Leu Leu Ser Thr Pro Ala Pro Glu Ala Arg 
                485                 490                 495     


Pro Val Ile Gly Ala Leu Gly Leu 
            500                 


<210>  3
<211>  1076
<212>  PRT
<213>  homo sapiens

<400>  3

Met Glu Pro Gly Ser Lys Ser Val Ser Arg Ser Asp Trp Gln Pro Glu 
1               5                   10                  15      


Pro His Gln Arg Pro Ile Thr Pro Leu Glu Pro Gly Pro Glu Lys Thr 
            20                  25                  30          


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


Gln Lys Pro Ala Ser Asn Gln Arg Pro Leu Thr Gln Gln Glu Thr Pro 
    50                  55                  60                  


Ala Gln His Asp Ala Glu Ser Gln Lys Glu Pro Arg Ala Gln Gln Lys 
65                  70                  75                  80  


Ser Ala Ser Gln Glu Glu Phe Leu Ala Pro Gln Lys Pro Ala Pro Gln 
                85                  90                  95      


Gln Ser Pro Tyr Ile Gln Arg Val Leu Leu Thr Gln Gln Glu Ala Ala 
            100                 105                 110         


Ser Gln Gln Gly Pro Gly Leu Gly Lys Glu Ser Ile Thr Gln Gln Glu 
        115                 120                 125             


Pro Ala Leu Arg Gln Arg His Val Ala Gln Pro Gly Pro Gly Pro Gly 
    130                 135                 140                 


Glu Pro Pro Pro Ala Gln Gln Glu Ala Glu Ser Thr Pro Ala Ala Gln 
145                 150                 155                 160 


Ala Lys Pro Gly Ala Lys Arg Glu Pro Ser Ala Pro Thr Glu Ser Thr 
                165                 170                 175     


Ser Gln Glu Thr Pro Glu Gln Ser Asp Lys Gln Thr Thr Pro Val Gln 
            180                 185                 190         


Gly Ala Lys Ser Lys Gln Gly Ser Leu Thr Glu Leu Gly Phe Leu Thr 
        195                 200                 205             


Lys Leu Gln Glu Leu Ser Ile Gln Arg Ser Ala Leu Glu Trp Lys Ala 
    210                 215                 220                 


Leu Ser Glu Trp Val Thr Asp Ser Glu Ser Glu Ser Asp Val Gly Ser 
225                 230                 235                 240 


Ser Ser Asp Thr Asp Ser Pro Ala Thr Met Gly Gly Met Val Ala Gln 
                245                 250                 255     


Gly Val Lys Leu Gly Phe Lys Gly Lys Ser Gly Tyr Lys Val Met Ser 
            260                 265                 270         


Gly Tyr Ser Gly Thr Ser Pro His Glu Lys Thr Ser Ala Arg Asn His 
        275                 280                 285             


Arg His Tyr Gln Asp Thr Ala Ser Arg Leu Ile His Asn Met Asp Leu 
    290                 295                 300                 


Arg Thr Met Thr Gln Ser Leu Val Thr Leu Ala Glu Asp Asn Ile Ala 
305                 310                 315                 320 


Phe Phe Ser Ser Gln Gly Pro Gly Glu Thr Ala Gln Arg Leu Ser Gly 
                325                 330                 335     


Val Phe Ala Gly Val Arg Glu Gln Ala Leu Gly Leu Glu Pro Ala Leu 
            340                 345                 350         


Gly Arg Leu Leu Gly Val Ala His Leu Phe Asp Leu Asp Pro Glu Thr 
        355                 360                 365             


Pro Ala Asn Gly Tyr Arg Ser Leu Val His Thr Ala Arg Cys Cys Leu 
    370                 375                 380                 


Ala His Leu Leu His Lys Ser Arg Tyr Val Ala Ser Asn Arg Arg Ser 
385                 390                 395                 400 


Ile Phe Phe Arg Thr Ser His Asn Leu Ala Glu Leu Glu Ala Tyr Leu 
                405                 410                 415     


Ala Ala Leu Thr Gln Leu Arg Ala Leu Val Tyr Tyr Ala Gln Arg Leu 
            420                 425                 430         


Leu Val Thr Asn Arg Pro Gly Val Leu Phe Phe Glu Gly Asp Glu Gly 
        435                 440                 445             


Leu Thr Ala Asp Phe Leu Arg Glu Tyr Val Thr Leu His Lys Gly Cys 
    450                 455                 460                 


Phe Tyr Gly Arg Cys Leu Gly Phe Gln Phe Thr Pro Ala Ile Arg Pro 
465                 470                 475                 480 


Phe Leu Gln Thr Ile Ser Ile Gly Leu Val Ser Phe Gly Glu His Tyr 
                485                 490                 495     


Lys Arg Asn Glu Thr Gly Leu Ser Val Ala Ala Ser Ser Leu Phe Thr 
            500                 505                 510         


Ser Gly Arg Phe Ala Ile Asp Pro Glu Leu Arg Gly Ala Glu Phe Glu 
        515                 520                 525             


Arg Ile Thr Gln Asn Leu Asp Val His Phe Trp Lys Ala Phe Trp Asn 
    530                 535                 540                 


Ile Thr Glu Met Glu Val Leu Ser Ser Leu Ala Asn Met Ala Ser Ala 
545                 550                 555                 560 


Thr Val Arg Val Ser Arg Leu Leu Ser Leu Pro Pro Glu Ala Phe Glu 
                565                 570                 575     


Met Pro Leu Thr Ala Asp Pro Thr Leu Thr Val Thr Ile Ser Pro Pro 
            580                 585                 590         


Leu Ala His Thr Gly Pro Gly Pro Val Leu Val Arg Leu Ile Ser Tyr 
        595                 600                 605             


Asp Leu Arg Glu Gly Gln Asp Ser Glu Glu Leu Ser Ser Leu Ile Lys 
    610                 615                 620                 


Ser Asn Gly Gln Arg Ser Leu Glu Leu Trp Pro Arg Pro Gln Gln Ala 
625                 630                 635                 640 


Pro Arg Ser Arg Ser Leu Ile Val His Phe His Gly Gly Gly Phe Val 
                645                 650                 655     


Ala Gln Thr Ser Arg Ser His Glu Pro Tyr Leu Lys Ser Trp Ala Gln 
            660                 665                 670         


Glu Leu Gly Ala Pro Ile Ile Ser Ile Asp Tyr Ser Leu Ala Pro Glu 
        675                 680                 685             


Ala Pro Phe Pro Arg Ala Leu Glu Glu Cys Phe Phe Ala Tyr Cys Trp 
    690                 695                 700                 


Ala Ile Lys His Cys Ala Leu Leu Gly Ser Thr Gly Glu Arg Ile Cys 
705                 710                 715                 720 


Leu Ala Gly Asp Ser Ala Gly Gly Asn Leu Cys Phe Thr Val Ala Leu 
                725                 730                 735     


Arg Ala Ala Ala Tyr Gly Val Arg Val Pro Asp Gly Ile Met Ala Ala 
            740                 745                 750         


Tyr Pro Ala Thr Met Leu Gln Pro Ala Ala Ser Pro Ser Arg Leu Leu 
        755                 760                 765             


Ser Leu Met Asp Pro Leu Leu Pro Leu Ser Val Leu Ser Lys Cys Val 
    770                 775                 780                 


Ser Ala Tyr Ala Gly Ala Lys Thr Glu Asp His Ser Asn Ser Asp Gln 
785                 790                 795                 800 


Lys Ala Leu Gly Met Met Gly Leu Val Arg Arg Asp Thr Ala Leu Leu 
                805                 810                 815     


Leu Arg Asp Phe Arg Leu Gly Ala Ser Ser Trp Leu Asn Ser Phe Leu 
            820                 825                 830         


Glu Leu Ser Gly Arg Lys Ser Gln Lys Met Ser Glu Pro Ile Ala Glu 
        835                 840                 845             


Pro Met Arg Arg Ser Val Ser Glu Ala Ala Leu Ala Gln Pro Gln Gly 
    850                 855                 860                 


Pro Leu Gly Thr Asp Ser Leu Lys Asn Leu Thr Leu Arg Asp Leu Ser 
865                 870                 875                 880 


Leu Arg Gly Asn Ser Glu Thr Ser Ser Asp Thr Pro Glu Met Ser Leu 
                885                 890                 895     


Ser Ala Glu Thr Leu Ser Pro Ser Thr Pro Ser Asp Val Asn Phe Leu 
            900                 905                 910         


Leu Pro Pro Glu Asp Ala Gly Glu Glu Ala Glu Ala Lys Asn Glu Leu 
        915                 920                 925             


Ser Pro Met Asp Arg Gly Leu Gly Val Arg Ala Ala Phe Pro Glu Gly 
    930                 935                 940                 


Phe His Pro Arg Arg Ser Ser Gln Gly Ala Thr Gln Met Pro Leu Tyr 
945                 950                 955                 960 


Ser Ser Pro Ile Val Lys Asn Pro Phe Met Ser Pro Leu Leu Ala Pro 
                965                 970                 975     


Asp Ser Met Leu Lys Ser Leu Pro Pro Val His Ile Val Ala Cys Ala 
            980                 985                 990         


Leu Asp Pro Met Leu Asp Asp Ser  Val Met Leu Ala Arg  Arg Leu Arg 
        995                 1000                 1005             


Asn Leu  Gly Gln Pro Val Thr  Leu Arg Val Val Glu  Asp Leu Pro 
    1010                 1015                 1020             


His Gly  Phe Leu Thr Leu Ala  Ala Leu Cys Arg Glu  Thr Arg Gln 
    1025                 1030                 1035             


Ala Ala  Glu Leu Cys Val Glu  Arg Ile Arg Leu Val  Leu Thr Pro 
    1040                 1045                 1050             


Pro Ala  Gly Ala Gly Pro Ser  Gly Glu Thr Gly Ala  Ala Gly Val 
    1055                 1060                 1065             


Asp Gly  Gly Cys Gly Gly Arg  His 
    1070                 1075     


<210>  4
<211>  31
<212>  PRT
<213>  artificial

<220>
<223>  Human GLP-1

<400>  4

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 
            20                  25                  30      


<210>  5
<211>  39
<212>  PRT
<213>  artificial

<220>
<223>  Exenatide

<400>  5

His Gly Glu Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu 
1               5                   10                  15      


Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  6
<211>  31
<212>  PRT
<213>  artificial

<220>
<223>  liraglutide


<220>
<221>  MISC_FEATURE
<222>  (26)..(26)
<223>  conjugated C-16 fatty acid (palmitic acid) with a glutamic acid 
       spacer

<400>  6

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 
            20                  25                  30      


<210>  7
<211>  30
<212>  PRT
<213>  artificial

<220>
<223>  Taspoglutide


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Ala at position 2 is 2-methyl-Ala

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Ala at position 2 is 2-methyl-Ala

<400>  7

His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Ala Arg 
            20                  25                  30  


<210>  8
<211>  19
<212>  RNA
<213>  artificial

<220>
<223>  siRNA for downregulating LAL expression

<400>  8
cgcuacuguc guuauugau                                                    19


<210>  9
<211>  19
<212>  RNA
<213>  artificial

<220>
<223>  siRNA for downregulating LAL expression

<400>  9
cguuugcacu caugucaua                                                    19


<210>  10
<211>  19
<212>  RNA
<213>  artificial

<220>
<223>  siRNA for downregulating LAL expression

<400>  10
ccuggucucg gaaacauaa                                                    19


<210>  11
<211>  19
<212>  RNA
<213>  artificial

<220>
<223>  siRNA for downregulating LAL expression

<400>  11
gacuuaagcg agguauaaa                                                    19


