                         SEQUENCE LISTING

<110>  Merck Sharp & Dohme Corp.
       Madsen-Duggan, Christina B.
       Feng, Danqing
       Huo, Pei
       Kekec, Ahmet
       Lin, Songnian
       Nargund, Ravi
       Moyes, Christopher  R.
       Pissarnitski, Dmitri A.
       Shi, Zhicai
       Wu, Zhicai
       Yan, Lin
       Zhu, Yuping
 
<120>  INSULIN RECEPTOR PARTIAL AGONISTS

<130>  25085-WO-PCT

<150>  63/070,384  
<151>  2020-08-26

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  1

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

<400>  2

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>  3
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  insulin A chain


<220>
<221>  MISC_FEATURE
<222>  (2)..(2)
<223>  X2 = isoleucine or threonine

<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X3=  valine, glycine, or leucine;

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  X8=threonine or histidine

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  X17=  glutamic acid or glutamine

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  X19= tyrosine, 4-methoxy-phenylalanine, alanine, or 4-amino 
       phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  X23=  asparagine or glycine

<400>  3

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


Xaa Asn Xaa Cys Xaa 
            20      


<210>  4
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  insulin B chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X25 is histidine or threonine;

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X29 is alanine, glycine or serine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  X30 is histidine, aspartic acid, glutamic acid, homocysteic acid,
       or cysteic acid;

<220>
<221>  MISC_FEATURE
<222>  (21)..(21)
<223>  X27 is phenylalanine or aspartic acid

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  X31 is aspartic acid, proline or lysine;

<220>
<221>  MISC_FEATURE
<222>  (25)..(25)
<223>  X32 is proline or lysine, with the proviso that at least one of 
       X31 or X32 is lysine

<400>  4

Xaa Leu Cys Gly Xaa Xaa Leu Val Glu Ala Leu Tyr Leu Val Cys Gly 
1               5                   10                  15      


Glu Arg Gly Phe Xaa Tyr Thr Xaa Xaa 
            20                  25  


<210>  5
<211>  32
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  insulin chain


<220>
<221>  MISC_FEATURE
<222>  (1)..(1)
<223>  X22 = is phenylalanine or desamino-phenylalanine

<220>
<221>  MISC_FEATURE
<222>  (5)..(5)
<223>  X25 =is histidine or threonine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  X26=is glycine or leucine

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  X29 =is alanine, glycine, or serine

<220>
<221>  MISC_FEATURE
<222>  (10)..(10)
<223>  X30=is histidine, aspartic acid, glutamic acid, homocysteic acid,
       or cysteic acid

<220>
<221>  MISC_FEATURE
<222>  (25)..(25)
<223>  X27 is phenylalanine or aspartic acid

<220>
<221>  MISC_FEATURE
<222>  (28)..(28)
<223>  X31 is aspartic acid, proline, or lysine

<220>
<221>  MISC_FEATURE
<222>  (29)..(29)
<223>  X32= is lysine or proline

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  X33= is threonine, alanine, or absent

<220>
<221>  MISC_FEATURE
<222>  (31)..(31)
<223>  X34= arginine or absent

<220>
<221>  MISC_FEATURE
<222>  (32)..(32)
<223>  X35 is arginine or absent;

       With the proviso at least one of X31 or X32 is lysine

<400>  5

Xaa Val Asn Gln Xaa Xaa Cys Gly Xaa Xaa Leu Val Glu Ala Leu Tyr 
1               5                   10                  15      


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


<210>  6
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  insulin lispro B chain

<400>  6

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 Lys Pro Thr 
            20                  25                  30  


<210>  7
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  insulin glargine A chain

<400>  7

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


Glu Asn Tyr Cys Gly 
            20      


<210>  8
<211>  32
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin glargine B chain

<400>  8

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 Arg Arg 
            20                  25                  30          


<210>  9
<211>  60
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Insulin aspart B chain

<400>  9

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 Asp Lys Thr Phe Val 
            20                  25                  30          


Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val 
        35                  40                  45              


Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Lys Thr 
    50                  55                  60  


<210>  10
<211>  21
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A:Y19A

<400>  10

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


Glu Asn Ala Cys Asn 
            20      


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

<220>
<223>  Insulin degludec B chain

<400>  11

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 
            20                  25                  


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

<220>
<223>  B: DesB30-K29R

<400>  12

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 Arg 
            20                  25                  


