                         SEQUENCE LISTING

<110>  Eli Lilly and Company
 
<120>  Neuregulin-4 Compounds and Methods of Use

<130>  X22153

<150>  US 62/827,386
<151>  2019-04-01

<160>  20    

<170>  PatentIn version 3.5

<210>  1
<211>  47
<212>  PRT
<213>  Homo sapiens

<400>  1

Asp His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn 
1               5                   10                  15      


Gly Gly Leu Cys Tyr Val Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg 
            20                  25                  30          


Cys Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
        35                  40                  45          


<210>  2
<211>  48
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct


<220>
<221>  VARIANT
<222>  (1)..(1)
<223>  Xaa at position 1 is selected from the group consisting of T, PT,
       MPT, S, GS, GGS, GGGS, and (GGGGXlambda)n wherein Xlambda is Q, 
       A, E or S and n=1-5 (SEQ ID NO:5), or is absent

<220>
<221>  VARIANT
<222>  (9)..(9)
<223>  Xaa at position 9 is E or P

<220>
<221>  VARIANT
<222>  (23)..(23)
<223>  Xaa at position 23 is Q or V

<220>
<221>  VARIANT
<222>  (27)..(27)
<223>  Xaa at position 27 is F or I

<220>
<221>  VARIANT
<222>  (36)..(36)
<223>  Xaa at position 36 or E or A

<220>
<221>  VARIANT
<222>  (45)..(45)
<223>  Xaa at position 45 is H, K or E

<400>  2

Xaa Gly His Glu Glu Pro Cys Gly Xaa Ser His Lys Ser Phe Cys Leu 
1               5                   10                  15      


Asn Gly Gly Leu Cys Tyr Xaa Ile Pro Thr Xaa Pro Ser Pro Phe Cys 
            20                  25                  30          


Arg Cys Val Xaa Asn Tyr Thr Gly Ala Arg Cys Glu Xaa Val Phe Leu 
        35                  40                  45              


<210>  3
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  3

Met Pro Thr Asp His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe 
1               5                   10                  15      


Cys Leu Asn Gly Gly Leu Cys Tyr Val Ile Pro Thr Ile Pro Ser Pro 
            20                  25                  30          


Phe Cys Arg Cys Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val 
        35                  40                  45              


Phe Leu Pro Gly Ser Ser Ile Gln Thr Lys Ser Asn Leu Phe Glu Ala 
    50                  55                  60                  


Phe Val Ala Leu Ala Val Leu Val Thr Leu Ile Ile Gly Ala Phe Tyr 
65                  70                  75                  80  


Phe Leu Cys Arg Lys Gly His Phe Gln Arg Ala Ser Ser Val Gln Tyr 
                85                  90                  95      


Asp Ile Asn Leu Val Glu Thr Ser Ser Thr Ser Ala His His Ser His 
            100                 105                 110         


Glu Gln His 
        115 


<210>  4
<211>  47
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  4

Gly His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn 
1               5                   10                  15      


Gly Gly Leu Cys Tyr Gln Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg 
            20                  25                  30          


Cys Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Lys Val Phe Leu 
        35                  40                  45          


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

<220>
<223>  Synthetic Construct


<220>
<221>  VARIANT
<222>  (1)..(5)
<223>  SEQ ID NO:5 is further represented as (GGGGXlambda)n, wherein: 
       Xlambda is Q, A, E or S; and n is 1-5.

<220>
<221>  VARIANT
<222>  (5)..(5)
<223>  Xaa at position 5 is Xlambda wherein Xlambda is Q, A, E or S

<400>  5

Gly Gly Gly Gly Xaa 
1               5   


<210>  6
<211>  221
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  6

Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  7
<211>  221
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  7

Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  8
<211>  221
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  8

Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


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


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


Asn Ala Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    210                 215                 220     


<210>  9
<211>  221
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  9

Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


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


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


Asn Ala Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    210                 215                 220     


<210>  10
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  10

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
    50                  55                  60          


<210>  11
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  11

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Glu Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
    50                  55                  60          


<210>  12
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  12

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Gln Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
    50                  55                  60          


<210>  13
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  13

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Phe Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
    50                  55                  60          


<210>  14
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  14

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Ala Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
    50                  55                  60          


<210>  15
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  15

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Phe Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Lys Val Phe Leu 
    50                  55                  60          


<210>  16
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  16

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Phe Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu His Val Phe Leu 
    50                  55                  60          


<210>  17
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  17

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Glu Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Val Ile Pro Thr Phe Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Glu Val Phe Leu 
    50                  55                  60          


<210>  18
<211>  52
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  18

Gly Gly Gly Gly Ser Gly His Glu Glu Pro Cys Gly Pro Ser His Lys 
1               5                   10                  15      


Ser Phe Cys Leu Asn Gly Gly Leu Cys Tyr Gln Ile Pro Thr Ile Pro 
            20                  25                  30          


Ser Pro Phe Cys Arg Cys Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu 
        35                  40                  45              


Lys Val Phe Leu 
    50          


<210>  19
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  19

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


His Glu Glu Pro Cys Gly Pro Ser His Lys Ser Phe Cys Leu Asn Gly 
            20                  25                  30          


Gly Leu Cys Tyr Gln Ile Pro Thr Ile Pro Ser Pro Phe Cys Arg Cys 
        35                  40                  45              


Val Glu Asn Tyr Thr Gly Ala Arg Cys Glu Lys Val Phe Leu 
    50                  55                  60          


<210>  20
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  20

Gly Gly Gly Ser 
1               


