SEQUENCE LISTING


<110>  DiMarchi, Richard
      DiMarchi, Maria
      Chabenne, Joe
 
<120>  GLUCAGON ANALOGS EXHIBITING ENHANCED SOLUBILITY IN 
       PHYSIOLOGICAL PH BUFFERS

<130>  29920-201206

<160>  38    

<170>  PatentIn version 3.3

<210>  1
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  1

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr 
            20                  25                  


<210>  2
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa is Ser, Cys, Orn, homocysteine or acetyl phenyalanine

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  2

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

Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  3
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa is Arg, Cys, Orn, homocysteine or acetyl phenyalanine

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  3

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


Xaa Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  4
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa is Asp, Cys, Orn, homocysteine or acetyl phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  4

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


Arg Arg Ala Gln Xaa Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


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

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa is Gln, Cys, Orn, homocysteine or acetyl phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  5

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


Arg Arg Ala Gln Asp Phe Val Xaa Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  6
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  Xaa is Asp, Cys, Orn, homocysteine or acetyl phenyalanine

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa is Gln, Cys, Orn, homocysteine or acetyl phenyalanine

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  6

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


Arg Arg Ala Gln Xaa Phe Val Xaa Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  7
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  Xaa is Lys, Arg, His, Asp, Glu, cysteic acid or homocysteic acid

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa is Thr, Lys, Arg, His, Asp, Glu, cysteic acid or homocysteic 
       acid

<400>  7

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Xaa Xaa 
            20                  25                  


<210>  8
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  Xaa is Asp or Glu

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa is Thr, Asp or Glu

<400>  8

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Xaa Xaa 
            20                  25                  


<210>  9
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa is Asp or Glu

<400>  9

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Asn Xaa 
            20                  25                  


<210>  10
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  10

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  11
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  11

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asp Thr 
            20                  25                  


<210>  12
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa is Lys, Arg or His

<400>  12

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Xaa 
            20                  25                  


<210>  13
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  13

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asp Thr 
            20                  25                  


<210>  14
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (16)..(16)
<223>  pegylation

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  14

His Ser Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Cys 
1               5                   10                  15      


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  15
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (17)..(17)
<223>  pegylation

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  15

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


Cys Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  16
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (21)..(21)
<223>  pegylation

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa at position 27 = Met, Leu or Nle

<400>  16

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


Arg Arg Ala Gln Cys Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  17
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (24)..(24)
<223>  pegylation

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa at position 27 = Met, Leu or Nle

<400>  17

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


Arg Arg Ala Gln Asp Phe Val Cys Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  18
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (21)..(21)
<223>  pegylation

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  18

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


Arg Arg Ala Gln Lys Phe Val Gln Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  19
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (24)..(24)
<223>  pegylation

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<400>  19

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


Arg Arg Ala Gln Asp Phe Val Lys Trp Leu Xaa Asp Thr 
            20                  25                  


<210>  20
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide fragment representing the carboxy terminal 10 amino acids
       of Exendin-4

<400>  20

Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser 
1               5                   10  


<210>  21
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide fragment representing the carboxy terminal 8 amino acids 
       of oxyntomodulin

<400>  21

Lys Arg Asn Arg Asn Asn Ile Ala 
1               5               


<210>  22
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide fragment representing the amino 4 amino acids of 
       oxyntomodulin carboxy terminus of SEQ ID NO: 21

<400>  22

Lys Arg Asn Arg 
1               


<210>  23
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide fragment representing the carboxy terminal 10 amino acids
       of Exendin-4


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

<400>  23

Gly Pro Ser Ser Gly Ala Pro Pro Pro Ser 
1               5                   10  


<210>  24
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  24

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  25
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  25

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


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


Arg Asn Asn Ile Ala 
        35          


<210>  26
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  26

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


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


Arg 
    


<210>  27
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  27

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


Cys Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr 
            20                  25                  


<210>  28
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon Analogue

<400>  28

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


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

<220>
<223>  Glucagon analogue


<220>
<221>  MOD_RES
<222>  (24)..(24)
<223>  2-butyrolactone bound through thiol group of cys

<400>  29

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr 
            20                  25                  


<210>  30
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon Analogue


<220>
<221>  MOD_RES
<222>  (24)..(24)
<223>  carboxymethyl group bound through thiol group of cys

<400>  30

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asn Thr 
            20                  25                  


<210>  31
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  31

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  32
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa is Asp, Glu, Lys, Arg or His

<400>  32

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Asp Thr Xaa 
            20                  25                  30  


<210>  33
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa is Asp, Glu, cysteic acid, homoglutamic acid or homocysteic 
       acid

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  Xaa is Asn, Lys, Arg, His, Asp or Glu

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa is Thr, Lys, Arg, His, Asp or Glu

<400>  33

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Xaa Xaa 
            20                  25                  


<210>  34
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue


<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa is Asp, Glu, cysteic acid, homoglutamic acid or homocysteic 
       acid

<220>
<221>  MISC_FEATURE
<222>  (27)..(27)
<223>  Xaa is Met, Leu or Nle

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  Xaa is Asn or an acidic amino acid

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  Xaa is Thr or an acidic amino acid

<400>  34

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Xaa Xaa Xaa 
            20                  25                  


<210>  35
<211>  39
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  35

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


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


Ser Gly Ala Pro Pro Pro Ser 
        35                  


<210>  36
<211>  37
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  36

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Glu Thr Lys Arg Asn 
            20                  25                  30          


Arg Asn Asn Ile Ala 
        35          


<210>  37
<211>  33
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  37

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Glu Thr Lys Arg Asn 
            20                  25                  30          


Arg 
    


<210>  38
<211>  29
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Glucagon analogue

<400>  38

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


Arg Arg Ala Gln Asp Phe Val Gln Trp Leu Met Glu Thr 
            20                  25     
