                               SEQUENCE LISTING

<110> QUIAPEG PHARMACEUTICALS AB
 
<120> RELEASABLE GLP-1 CONJUGATES

<130> 31152-0034WO1

<140> PCT/IB2019/057715
<141> 2019-09-12

<150> 62/771,972
<151> 2018-11-27

<150> 62/730,935
<151> 2018-09-13

<150> 62/730,341
<151> 2018-09-12

<160> 25    

<170> PatentIn version 3.5

<210> 1
<211> 37
<212> PRT
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      GLP-1 sequence"

<400> 1
His Asp Glu Phe Glu Arg His Ala Glu Gly Thr Phe Thr Ser Asp Val 
1               5                   10                  15      


Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu 
            20                  25                  30          


Val Lys Gly Arg Gly 
        35          


<210> 2
<211> 31
<212> PRT
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      GLP-1 sequence"

<400> 2
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> 3
<211> 31
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"


<220>
<221> MOD_RES
<222> (20)..(20)
<223> Lys(gamma-Glu-palmitoyl) 

<400> 3
His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


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


<210> 4
<211> 31
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<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 Arg Gly Arg Gly 
            20                  25                  30      


<210> 5
<211> 29
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<400> 5
Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala 
1               5                   10                  15      


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


<210> 6
<211> 25
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<400> 6
Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe 
1               5                   10                  15      


Ile Ala Trp Leu Val Arg Gly Arg Gly 
            20                  25  


<210> 7
<211> 13
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<400> 7
Ala Lys Glu Phe Ile Ala Trp Leu Val Arg Gly Arg Gly 
1               5                   10              


<210> 8
<211> 31
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 8
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


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


<210> 9
<211> 228
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 9
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      


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


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              


Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         


Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 


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


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


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         


Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 


Leu Ser Leu Gly 
225             


<210> 10
<211> 16
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<400> 10
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala 
1               5                   10                  15      


<210> 11
<211> 275
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 11
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Glu 
        35                  40                  45              


Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    50                  55                  60                  


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
65                  70                  75                  80  


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                85                  90                  95      


Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
            100                 105                 110         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
        115                 120                 125             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    130                 135                 140                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
145                 150                 155                 160 


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


Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val 
            180                 185                 190         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        195                 200                 205             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    210                 215                 220                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr 
225                 230                 235                 240 


Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 
                245                 250                 255     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            260                 265                 270         


Ser Leu Gly 
        275 


<210> 12
<211> 39
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 12
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> 13
<211> 30
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"


<220>
<221> MOD_RES
<222> (2)..(2)
<223> 2-methyl alanine 

<220>
<221> MOD_RES
<222> (29)..(29)
<223> 2-methyl alanine 

<400> 13
His Xaa 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 Xaa Arg 
            20                  25                  30  


<210> 14
<211> 44
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 14
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 Ser Lys Lys Lys Lys Lys Lys 
        35                  40                  


<210> 15
<211> 30
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 15
His Gly 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 
            20                  25                  30  


<210> 16
<211> 645
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 16
His Gly 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 His Gly 
            20                  25                  30          


Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala 
        35                  40                  45              


Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Asp Ala His Lys 
    50                  55                  60                  


Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys 
65                  70                  75                  80  


Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe 
                85                  90                  95      


Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr 
            100                 105                 110         


Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr 
        115                 120                 125             


Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr 
    130                 135                 140                 


Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu 
145                 150                 155                 160 


Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val 
                165                 170                 175     


Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu 
            180                 185                 190         


Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr 
        195                 200                 205             


Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala 
    210                 215                 220                 


Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro 
225                 230                 235                 240 


Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln 
                245                 250                 255     


Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys 
            260                 265                 270         


Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe 
        275                 280                 285             


Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu 
    290                 295                 300                 


Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu 
305                 310                 315                 320 


Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys 
                325                 330                 335     


Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu 
            340                 345                 350         


Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp 
        355                 360                 365             


Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp 
    370                 375                 380                 


Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp 
385                 390                 395                 400 


Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr 
                405                 410                 415     


Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys 
            420                 425                 430         


Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile 
        435                 440                 445             


Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln 
    450                 455                 460                 


Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr 
465                 470                 475                 480 


Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys 
                485                 490                 495     


Cys Cys Lys His Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr 
            500                 505                 510         


Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro 
        515                 520                 525             


Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg 
    530                 535                 540                 


Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys 
545                 550                 555                 560 


Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu 
                565                 570                 575     


Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu 
            580                 585                 590         


Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met 
        595                 600                 605             


Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys 
    610                 615                 620                 


Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln 
625                 630                 635                 640 


Ala Ala Leu Gly Leu 
                645 


<210> 17
<211> 31
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"


<220>
<221> MOD_RES
<222> (2)..(2)
<223> Alpha-aminoisobutyric acid 

<220>
<221> MOD_RES
<222> (20)..(20)
<223> Lys(AEEAc-AEEAc-gamma-Glu-17-carboxyheptadecanoyl) 

<400> 17
His Xaa Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly 
1               5                   10                  15      


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


<210> 18
<211> 33
<212> PRT
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      GLP-2 sequence"

<400> 18
His Ala Asp Gly Ser Phe Ser Asp Glu Met Asn Thr Ile Leu Asp Asn 
1               5                   10                  15      


Leu Ala Ala Arg Asp Phe Ile Asn Trp Leu Ile Gln Thr Lys Ile Thr 
            20                  25                  30          


Asp 
    


<210> 19
<211> 33
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 19
His Gly Asp Gly Ser Phe Ser Asp Glu Met Asn Thr Ile Leu Asp Asn 
1               5                   10                  15      


Leu Ala Ala Arg Asp Phe Ile Asn Trp Leu Ile Gln Thr Lys Ile Thr 
            20                  25                  30          


Asp 
    


<210> 20
<211> 33
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"


<220>
<221> MOD_RES
<222> (10)..(10)
<223> Norleucine

<220>
<221> MOD_RES
<222> (11)..(11)
<223> D-Phe

<400> 20
His Gly Asp Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Leu 
1               5                   10                  15      


Leu Ala Ala Arg Asp Phe Ile Asn Trp Leu Ile Gln Thr Lys Ile Thr 
            20                  25                  30          


Asp 
    


<210> 21
<211> 39
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 21
His Gly Glu Gly Thr Phe Ser Ser Glu Leu Ala Thr Ile Leu Asp Ala 
1               5                   10                  15      


Leu Ala Ala Arg Asp Phe Ile Ala Trp Leu Ile Ala Thr Lys Ile Thr 
            20                  25                  30          


Asp Lys Lys Lys Lys Lys Lys 
        35                  


<210> 22
<211> 39
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 22
His Gly Glu Gly Ser Phe Ser Ser Glu Leu Ser Thr Ile Leu Asp Ala 
1               5                   10                  15      


Leu Ala Ala Arg Asp Phe Ile Ala Trp Leu Ile Ala Thr Lys Ile Thr 
            20                  25                  30          


Asp Lys Lys Lys Lys Lys Lys 
        35                  


<210> 23
<211> 60
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"

<400> 23
His Gly 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 His Gly 
            20                  25                  30          


Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala 
        35                  40                  45              


Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg 
    50                  55                  60  


<210> 24
<211> 31
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"


<220>
<221> MOD_RES
<222> (2)..(2)
<223> Alpha-aminoisobutyric acid 

<400> 24
His Xaa 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 Arg Gly Arg Gly 
            20                  25                  30      


<210> 25
<211> 62
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polypeptide"


<220>
<221> NON_CONS
<222> (31)..(32)

<400> 25
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      


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


Gly Gly Lys Val Leu Trp Ala Ile Phe Glu Lys Ala Ala Gln Glu Glu 
        35                  40                  45              


Leu Tyr Ser Ser Val Asp Ser Thr Phe Arg Gly Glu Gly His 
    50                  55                  60          


