                         SEQUENCE LISTING

<110>  OPKO BIOLOGICS LTD.
 
<120>  LONG-ACTING GLP-2 ANALOGS

<130>  P-578962-PC

<150>  62/804,201
<151>  2019-02-11

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2-Gly2 Mutation

<400>  1

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>  2
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Variant #2


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Phe

<400>  2

His Gly Glu Gly Ser Phe Ser Asp Glu Xaa Xaa 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>  3
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Variant #3


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-His

<400>  3

His Gly Glu Gly Ser Phe Ser Asp Glu Xaa Xaa 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>  4
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Variant #4


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<400>  4

His Gly Glu Gly Ser Phe Ser Asp Glu Xaa Asn 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>  5
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Variant #5


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<400>  5

His Gly Glu Gly Ser Phe Ser Asp Glu Xaa Asn Thr Ile Leu Asp Tyr 
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>  6
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Variant #6


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<400>  6

His Gly Glu Gly Ser Phe Ser Asp Glu Xaa Asn 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>  7
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Variant #7


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<400>  7

His Gly Glu Gly Ser Phe Ser Asp Glu Xaa Asn Thr Ile Leu Asp Tyr 
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>  8
<211>  33
<212>  PRT
<213>  Homo sapiens

<400>  8

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>  9
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (2)..(3)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(17)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (19)..(21)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (27)..(23)
<223>  Xaa can be any amino acid

<220>
<221>  misc_feature
<222>  (27)..(33)
<223>  Xaa can be any naturally occurring amino acid

<400>  9

His Xaa Xaa Gly Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 
1               5                   10                  15      


Xaa Ala Xaa Xaa Xaa Phe Ile Xaa Trp Leu Xaa Xaa Xaa Xaa Xaa Xaa 
            20                  25                  30          


Xaa 
    


<210>  10
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (2)..(3)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..(21)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (31)..(33)
<223>  Xaa is any amino acid

<400>  10

His Xaa Xaa Gly Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 
1               5                   10                  15      


Xaa Xaa Xaa Xaa Xaa Phe Ile Xaa Trp Leu Ile Xaa Thr Lys Xaa Xaa 
            20                  25                  30          


Xaa 
    


<210>  11
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Thi

<400>  11

His Gly Asp Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Phe 
1               5                   10                  15      


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


<210>  12
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Phe

<400>  12

His Gly Asp Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Phe 
1               5                   10                  15      


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


<210>  13
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Phe

<400>  13

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>  14
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Thi

<400>  14

His Gly Asp Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Leu 
1               5                   10                  15      


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


Asp 
    


<210>  15
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Phe

<400>  15

His Gly Asp Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Phe 
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>  16
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa is Nle

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa is D-Thi

<400>  16

His Gly Asp Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Phe 
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>  17
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GLP-2 Analog


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa can be any amino acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa can be any amino acid

<400>  17

His Xaa Xaa Gly Ser Phe Ser Asp Glu Xaa Xaa Thr Ile Leu Asp Xaa 
1               5                   10                  15      


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


Asp 
    


