ÏÅÐÅ×ÅÍÜ ÏÎÑËÅÄÎÂÀÒÅËÜÍÎÑÒÅÉ

<110>  ÝËÈ ËÈËËÈ ÝÍÄ ÊÎÌÏÀÍÈ 

<120>  ÑÎÅÄÈÍÅÍÈß-ÊÎÀÃÎÍÈÑÒÛ ÃÈÏ È ÃÏÏ-1

<130>  X20448

<150>  62/101488
<151>  2015-01-09

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  42
<212>  PRT
<213>  Homo sapiens

<400>  1

Tyr Ala Glu Gly Thr Phe Ile Ser Asp Tyr Ser Ile Ala Met Asp Lys 
1               5                   10                  15      


Ile His Gln Gln Asp Phe Val Asn Trp Leu Leu Ala Gln Lys Gly Lys 
            20                  25                  30          


Lys Asn Asp Trp Lys His Asn Ile Thr Gln 
        35                  40          


<210>  2
<211>  30
<212>  PRT
<213>  Homo sapiens

<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 
            20                  25                  30  


<210>  3
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)1-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  3

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  4
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  4

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


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  5
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)1-CO-(CH2)16-CO2
       H

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  5

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  6
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)16-CO2
       H

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  6

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  7
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)18-CO2
       H

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  7

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  8
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)1-CO-(CH2)16-CO2
       H

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  8

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


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  9
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)2-CO-(CH2)16-CO2
       H

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22  is 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  9

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


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  10
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)1-CO-(CH2)18-CO2
       H

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is amidated as a C-terminal primary amide

<400>  10

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


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  11
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  Xaa at position 2 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (2)..(2)
<223>  Aib

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa at position 13 is nonnaturally occurring amino acid 
       2-Aminoisobutyric Acid

<220>
<221>  MOD_RES
<222>  (13)..(13)
<223>  Aib

<220>
<221>  MOD_RES
<222>  (20)..(20)
<223>  Lys at position 20 is chemically modified through conjugation to 
       the epsilon-amino group of the K side-chain with 
       ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(gamma-Glu)a-CO-(CH2)b-CO2H
       wherein a is 1 to 2 and b is 10 to 20

<220>
<221>  MISC_FEATURE
<222>  (22)..(22)
<223>  Xaa at position 22 is either Phe or 1-Nal

<220>
<221>  MOD_RES
<222>  (39)..(39)
<223>  Ser at position 39 is optionally amidated as a C-terminal primary
       amide

<400>  11

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


Ile Ala Gln Lys Ala Xaa Val Gln Trp Leu Ile Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35