                         SEQUENCE LISTING

<110>  Shi, Shuai
       Antochshuk, Valentyn
 
<120>  PHARMACEUTICAL FORMULATION COMPRISING INCRETIN-INSULIN CONJUGATES

<130>  24446

<140>  62/507,964
<141>  2017-05-18

<160>  20    

<170>  PatentIn version 3.5

<210>  1
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin portion of formula I


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X1 is His, Tyr, or absent

<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X3 is Glu or Gln

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X5 is Thr or Ile

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  X10 is Tyr or Lys acylated with a C16 to C20 alkyl group 
       optionally via a gamma Glu linker

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  X12 is Ile or Arg

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  X16 is Lys, Arg, or Glu

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  X17 is Gln or Arg

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  X20 is Gln or aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  X21 is Glu or Asp

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  X24 is Asn, Gln, or Ala

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  X28 is Ala or Asp

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  X29 is Ala or Gly

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  X40 is absent, or Lys, or Lys acylated with a C16 to C20 alkyl 
       group optionally via a gamma Glu

<400>  1

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


Xaa Ala Ala Xaa Xaa Phe Val Xaa Trp Leu Leu Xaa Xaa Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser Xaa 
        35                  40  


<210>  2
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  2

Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu 
1               5                   10                  15      


Glu Asn Tyr Cys Asn 
            20      


<210>  3
<211>  30
<212>  PRT
<213>  Homo sapiens

<400>  3

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr 
            20                  25                  30  


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

<220>
<223>  Incretin peptide of Compound 99


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 and X20 are each independently aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  wherein X2 and X20 are each independently aminoisobutyric acid

<400>  4

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


Gln Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu 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>  Incretin peptide of Compound 100


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  wherein X20 is aminoisobutyric acid

<400>  5

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


Gln Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  6
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 101


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  wherein X20 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  wherein X40 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  6

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


Gln Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser Xaa 
        35                  40  


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

<220>
<223>  Incretin peptide of Compound 102


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  7

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


Arg Ala Ala Gln Glu Phe Val Ala Trp Leu Leu Asp Ala Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys 
        35                  


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

<220>
<223>  Incretin peptide of Compound 103


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  8

His Xaa Gln Gly Thr Phe Thr Ser Asp Xaa Ser Arg Tyr Leu Asp Glu 
1               5                   10                  15      


Arg Ala Ala Gln Asp Phe Val Gln Trp Leu Leu Asp Ala Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys 
        35                  


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

<220>
<223>  Incretin peptide of Compound 104


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  9

His Xaa Gln Gly Thr Phe Thr Ser Asp Xaa Ser Arg Tyr Leu Asp Glu 
1               5                   10                  15      


Arg Ala Ala Gln Asp Phe Val Gln Trp Leu Leu Asp Gly Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys 
        35                  


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

<220>
<223>  Incretin peptide of Compound 105


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  10

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


Arg Ala Ala Gln Asp Phe Val Gln Trp Leu Leu Asp Gly Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys 
        35                  


<210>  11
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 106


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  wherein X1 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  wherein X9 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  wherein X19 is aminoisobutyric acid

<400>  11

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


Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser Gly 
            20                  25                  30          


Ala Pro Pro Pro Ser 
        35          


<210>  12
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 99 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  wherein X20 is aminoisobutyric acid

<400>  12

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


Gln Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser Cys 
        35                  40  


<210>  13
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 100 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  wherein X20 is aminoisobutyric acid

<400>  13

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


Gln Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser Cys 
        35                  40  


<210>  14
<211>  41
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 101 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  wherein X20 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  wherein X40 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  14

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


Gln Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser Xaa Cys 
        35                  40      


<210>  15
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 102 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  15

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


Arg Ala Ala Gln Glu Phe Val Ala Trp Leu Leu Asp Ala Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys Cys 
        35                  40  


<210>  16
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 103 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  16

His Xaa Gln Gly Thr Phe Thr Ser Asp Xaa Ser Arg Tyr Leu Asp Glu 
1               5                   10                  15      


Arg Ala Ala Gln Asp Phe Val Gln Trp Leu Leu Asp Ala Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys Cys 
        35                  40  


<210>  17
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 104 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  17

His Xaa Gln Gly Thr Phe Thr Ser Asp Xaa Ser Arg Tyr Leu Asp Glu 
1               5                   10                  15      


Arg Ala Ala Gln Asp Phe Val Gln Trp Leu Leu Asp Gly Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys Cys 
        35                  40  


<210>  18
<211>  40
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 105 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  wherein X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  wherein X10 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<400>  18

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


Arg Ala Ala Gln Asp Phe Val Gln Trp Leu Leu Asp Gly Gly Pro Ser 
            20                  25                  30          


Gly Ala Pro Pro Pro Ser Lys Cys 
        35                  40  


<210>  19
<211>  38
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of Compound 106 including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  wherein X1 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  wherein X9 is Lys acylated with a C16 fatty acyl group via 
       gamma-Glu spacer

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  wherein X19 is aminoisobutyric acid

<400>  19

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


Ala Ala Xaa Glu Phe Val Asn Trp Leu Leu Ala Gly Gly Pro Ser Gly 
            20                  25                  30          


Ala Pro Pro Pro Ser Cys 
        35              


<210>  20
<211>  41
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Incretin peptide of formula I including Cysteine of linker


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X1 is His, Tyr, or absent

<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 is aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X3 is Glu or Gln

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X5 is Thr or Ile

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  X10 is Tyr or Lys acylated with a C16 to C20 alkyl group 
       optionally via a gamma Glu linker

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  X12 is Ile or Arg

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  X16 is Lys, Arg, or Glu

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  X17 is Gln or Arg

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  X20 is Gln or aminoisobutyric acid

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  X21 is Glu or Asp

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  X24 is Asn, Gln, or Ala

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  X28 is Ala or Asp

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  X29 is Ala or Gly

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  X40 is absent, or Lys, or Lys acylated with a C16 to C20 alkyl 
       group optionally via a gamma Glu

<400>  20

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


Xaa Ala Ala Xaa Xaa Phe Val Xaa Trp Leu Leu Xaa Xaa Gly Pro Ser 
            20                  25                  30          


Ser Gly Ala Pro Pro Pro Ser Xaa Cys 
        35                  40      


