<110>    HANMI PHARM. CO., LTD.

<120>    Novel trigonal glucagon/GLP-1/GIP receptor agonist and use
         thereof

<130>    OPA21385

<150>    KR 10-2020-0183576
<151>    2020-12-24

<160>    36

<170>    KoPatentIn 3.0

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

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    1
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Glu
  1               5                  10                  15 

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

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


<210>    2
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    2
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Glu
  1               5                  10                  15 

Gln Ala Ala Lys Glu Phe Val Gln Trp Leu Leu Asp His His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


<210>    3
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    3
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Glu
  1               5                  10                  15 

Gln Arg Ala Lys Glu Phe Ile Ala Trp Leu Leu Asp His His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


<210>    4
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    4
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Asp Glu
  1               5                  10                  15 

Gln Arg Ala Lys Glu Phe Ile Ala Trp Leu Leu Ala His His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


<210>    5
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    5
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Glu
  1               5                  10                  15 

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

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


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

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    6
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Ala Leu Asp Glu
  1               5                  10                  15 

Lys Ala Ala Lys Asp Phe Val Gln Trp Leu Leu Asp Gln His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


<210>    7
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    7
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Ala Leu Asp Glu
  1               5                  10                  15 

Lys Ala Ala Lys Asp Phe Val Gln Trp Leu Lys Asp Gln His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


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

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    8
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Cys Ser Lys Tyr Leu Asp Glu
  1               5                  10                  15 

Lys Ala Ala Lys Glu Phe Val Gln Trp Leu Leu Asp His His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser
         35                


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

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (12)..(16)
<223>    amino acids at positions 16 and 20 form a ring


<400>    9
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Glu Tyr Met Glu Lys
  1               5                  10                  15 

Glu Ala Val Arg Glu Phe Ile Cys Trp Leu Val Lys Gly Gly Pro Ser
             20                  25                  30 

Ser Gly Ala Pro Pro Pro Ser
         35                


<210>    10
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    10
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Lys Tyr Leu Asp Glu
  1               5                  10                  15 

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

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


<210>    11
<211>    40
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (16)..(20)
<223>    amino acids at positions 16 and 20 form a ring


<400>    11
Tyr Xaa Gln Gly Thr Phe Thr Ser Asp Tyr Ser Ile Tyr Leu Asp Glu
  1               5                  10                  15 

Lys Ala Ala Lys Glu Phe Val Gln Trp Leu Leu Asp Gln His Pro Ser
             20                  25                  30 

Ser Gly Gln Pro Pro Pro Ser Cys
         35                  40


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

<220>
<223>    Trigonal agonist


<220>
<221>    MISC_FEATURE
<222>    (2)
<223>    Xaa is aminoisobutyric acid (Aib)


<220>
<221>    MISC_FEATURE
<222>    (20)
<223>    Xaa is aminoisobutyric acid (Aib)


<400>    12
Tyr Xaa Glu Gly Thr Phe Thr Ser Asp Tyr Ser Ile Gln Leu Asp Lys
  1               5                  10                  15 

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

Ser Gly Ala Pro Pro Pro Ser Lys
         35                  40


<210>    13
<211>    12
<212>    PRT
<213>    HOMO SAPIENS

<400>    13
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro
  1               5                  10        


<210>    14
<211>    11
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    14
Glu Ser Lys Tyr Gly Pro Pro Pro Ser Cys Pro
  1               5                  10    


<210>    15
<211>    11
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    15
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Pro
  1               5                  10    


<210>    16
<211>    10
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    16
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser
  1               5                  10


<210>    17
<211>    10
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    17
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro
  1               5                  10


<210>    18
<211>    8
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    18
Lys Tyr Gly Pro Pro Cys Pro Ser
  1               5            


<210>    19
<211>    8
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    19
Glu Ser Lys Tyr Gly Pro Pro Cys
  1               5            


<210>    20
<211>    7
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    20
Glu Lys Tyr Gly Pro Pro Cys
  1               5        


<210>    21
<211>    6
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    21
Glu Ser Pro Ser Cys Pro
  1               5    


<210>    22
<211>    5
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    22
Glu Pro Ser Cys Pro
  1               5


<210>    23
<211>    4
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    23
Pro Ser Cys Pro
  1            


<210>    24
<211>    10
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    24
Glu Ser Lys Tyr Gly Pro Pro Ser Cys Pro
  1               5                  10


<210>    25
<211>    9
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    25
Lys Tyr Gly Pro Pro Pro Ser Cys Pro
  1               5                


<210>    26
<211>    9
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    26
Glu Ser Lys Tyr Gly Pro Ser Cys Pro
  1               5                


<210>    27
<211>    8
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    27
Glu Ser Lys Tyr Gly Pro Pro Cys
  1               5            


<210>    28
<211>    7
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    28
Lys Tyr Gly Pro Pro Cys Pro
  1               5        


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

<220>
<223>    Variant of hinge region


<400>    29
Glu Ser Lys Pro Ser Cys Pro
  1               5        


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

<220>
<223>    Variant of hinge region


<400>    30
Glu Ser Pro Ser Cys Pro
  1               5    


<210>    31
<211>    4
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    31
Glu Pro Ser Cys
  1            


<210>    32
<211>    3
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    Variant of hinge region


<400>    32
Ser Cys Pro
  1        


<210>    33
<211>    221
<212>    PRT
<213>    homo sapiens

<400>    33
Pro Ser Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
  1               5                  10                  15 

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
             20                  25                  30 

Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
         35                  40                  45 

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
     50                  55                  60 

Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
 65                  70                  75                  80 

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
                 85                  90                  95 

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
            100                 105                 110 

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
        115                 120                 125 

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
    130                 135                 140 

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
145                 150                 155                 160 

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
                165                 170                 175 

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
            180                 185                 190 

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
        195                 200                 205 

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
    210                 215                 220 




<210>    34
<211>    442
<212>    PRT
<213>    Homo sapiens

<220>
<221>    MISC_FEATURE
<222>    (1)..(442)
<223>    Amino acids at position 1 to 442 form Human Immunoglobulin G4 Fc
         Fragment (homodimer)


<220>
<221>    MISC_FEATURE
<222>    (1)..(221)
<223>    Amino acids at position 1 to 221 form one monomer


<220>
<221>    MISC_FEATURE
<222>    (222)..(442)
<223>    Amino acids at position 222 to 442 form one monomer


<220>
<221>    DISULFID
<222>    (3)..(224)
<223>    Amino acids at position 3 and position 224 form an
         inter-disulfide bond


<220>
<221>    DISULFID
<222>    (35)..(95)
<223>    Amino acids at position 35 and position 95 form an intra-chain
         disulfide bond


<220>
<221>    DISULFID
<222>    (141)..(199)
<223>    Amino acids at position 141 and position 199 form an intra-chain
         disulfide bond


<220>
<221>    DISULFID
<222>    (256)..(316)
<223>    Amino acids at position 256 and position 316 form an intra-chain
         disulfide bond


<220>
<221>    DISULFID
<222>    (362)..(420)
<223>    Amino acids at position 362 and position 420 form an intra-chain
         disulfide bond


<400>    34
Pro Ser Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
  1               5                  10                  15 

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
             20                  25                  30 

Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
         35                  40                  45 

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
     50                  55                  60 

Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
 65                  70                  75                  80 

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
                 85                  90                  95 

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
            100                 105                 110 

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
        115                 120                 125 

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
    130                 135                 140 

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
145                 150                 155                 160 

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
                165                 170                 175 

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
            180                 185                 190 

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
        195                 200                 205 

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Pro Ser Cys
    210                 215                 220 

Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
225                 230                 235                 240 

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
                245                 250                 255 

Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp
            260                 265                 270 

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
        275                 280                 285 

Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
    290                 295                 300 

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
305                 310                 315                 320 

Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
                325                 330                 335 

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu
            340                 345                 350 

Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
        355                 360                 365 

Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
    370                 375                 380 

Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
385                 390                 395                 400 

Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn
                405                 410                 415 

Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
            420                 425                 430 

Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
        435                 440        


<210>    35
<211>    4
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    partial sequecne of the trigonal agonist (X27-X30)


<400>    35
Leu Asp His His
  1            


<210>    36
<211>    4
<212>    PRT
<213>    Artificial Sequence

<220>
<223>    partial sequecne of the trigonal agonist (X27-X30)


<400>    36
Leu Asp Gln His
  1            
