                         SEQUENCE LISTING

<110>  SANOFI
       Joslin Diabetes Center Inc.
 
<120>  Serpins: Methods of Therapeutic Beta-Cell Regeneration and 
       Function

<130>  DE2013/025G WO PCT

<150>  EP13305204.3
<151>  2013-02-22

<150>  US61/767948
<151>  2013-02-22

<150>  EP13306284.4
<151>  2013-09-20

<150>  US61/880240
<151>  2013-09-20

<160>  10    

<170>  PatentIn version 3.5

<210>  1
<211>  1931
<212>  DNA
<213>  Mus musculus

<400>  1
acttcatcct agctgtaagt ggagccagac ctgctaagca agagacttca ccatggagca       60

gctgagttca gccaacaccc tcttcgcctt ggagctgttc caaaccctga atgaaagcag      120

ccccacagga aacatcttct tctctccctt cagcatttct tctgccttgg ccatggtcat      180

tctgggggcc aaaggcagca ctgcagctca gctttctaag acttttcatt ttgactctgt      240

tgaggacatc cattcacgct tccaaagcct gaatgctgaa gtgagcaaac gtggagcatc      300

tcacactctg aaacttgcta acagactgta tggagagaaa acctacaact tccttcctga      360

atacttggct tcaacccaga aaatgtatgg tgctgacttg gcccctgtgg attttctgca      420

tgcctctgag gatgcaagga aggagataaa ccagtgggtc aaaggtcaaa cagaagggaa      480

aatcccagaa ctgttgtctg tgggtgtggt ggacagtatg accaaacttg tgctggtgaa      540

tgccatctac tttaagggaa tgtgggagga gaaattcatg acagaggaca caacggatgc      600

tccattccga ctgagtaaga aagacacaaa aacagtgaag atgatgtatc aaaagaaaaa      660

atttccattt ggttacattt cggacctgaa gtgcaaggtg ctggagatgc cttaccaggg      720

tggagaactt agcatggtca ttctgctgcc taaagacatt gaggacgagt ccacgggtct      780

taagaagatt gaaaagcaaa taactttgga aaaactgctt gaatggacca aacgtgagaa      840

cttggaattc attgatgtcc acgtcaaact gccccggttc aagatagaag agagctatac      900

cctcaactct aacctgggcc gcctgggagt gcaggatctc tttagcagta gcaaggctga      960

tctctctggc atgtcaggat ccagagatct tttcatatca aaaattgtcc acaagtcctt     1020

tgtggaagtg aatgaggaag gaacagaggc agccgctgct acaggaggca ttgctacatt     1080

ctgtatgttg ttgcctgagg aagaattcac agtggaccat ccgttcattt tcttcattcg     1140

gcacaatccc acatctaatg tgctcttcct tggcagggtt tgttccccat agaagaagga     1200

gactttacag atacaaggca gagcttagag tttcattccc tgagatttta atagtgatta     1260

ttttcatttg tacttgacaa taaaaactct aaccagaaac caatctttct tttgtatgtt     1320

caaccctgtt agctctttat atccatgact tttggcatgg gtatgtctat tttgattgta     1380

caatgaaagc aggactcctg ttttcctcct cggcttttgc atgacctcca gagtacatca     1440

aaggttcata gctaggctga aaattctgga cgactccatc ctcaaacttt atggactgta     1500

ggtgggtgcc tgcagatgct aactgaagtc atatccatct ggggtagcgt ggataccctt     1560

aagcctcaaa tcattattac aatctgcttt tcaagtacaa catccagagt ataatcaaag     1620

ataactgttt gggtgggcag ccatggcaac agagatacaa agcagcacaa acaaaagaga     1680

aggacaacag tggaaggctc taaatgctgc tgccgcccat acaaaccaga gaacaacagt     1740

ctgtgaagat aatattgacg aaatccaagg tcagatactt tagcaggcta ttgcaaactt     1800

acaaacaaca tttcatgtct ggatgaaaag gaactagaaa ccccagagct taaacataca     1860

ataaattatt tccattgaaa acttaaataa taaagaattt gtggattttt aagtctgaaa     1920

aaaaaaaaaa a                                                          1931


<210>  2
<211>  2678
<212>  DNA
<213>  Homo sapiens

<400>  2
agaaagaagc cgcgcccctg aggagggcgc tgcccggaag ccacgctcac ttctgcttgc       60

acttaggcga cctcgggagc tcggactcct acgcagtcac cgggaagggc cgccgccccg      120

cccgcggctg ctggcccggg tgacgcttcc gcctgctata agagcagcgg ccctcggtgc      180

ctccttcctg acctcgcacc cagctcggag cccggagcgt gcctcggcgg cctgtcggtt      240

ttcaccatgg agcagctgag ctcagcaaac acccgcttcg ccttggacct gttcctggcg      300

ttgagtgaga acaatccggc tggaaacatc ttcatctctc ccttcagcat ttcatctgct      360

atggccatgg tttttctggg gaccagaggt aacacggcag cacagctgtc caagactttc      420

catttcaaca cggttgaaga ggttcattca agattccaga gtctgaatgc tgatatcaac      480

aaacgtggag cgtcttatat tctgaaactt gctaatagat tatatggaga gaaaacttac      540

aatttccttc ctgagttctt ggtttcgact cagaaaacat atggtgctga cctggccagt      600

gtggattttc agcatgcctc tgaagatgca aggaagacca taaaccagtg ggtcaaagga      660

cagacagaag gaaaaattcc ggaactgttg gcttcgggca tggttgataa catgaccaaa      720

cttgtgctag taaatgccat ctatttcaag ggaaactgga aggataaatt catgaaagaa      780

gccacgacga atgcaccatt cagattgaat aagaaagaca gaaaaactgt gaaaatgatg      840

tatcagaaga aaaaatttgc atatggctac atcgaggacc ttaagtgccg tgtgctggaa      900

ctgccttacc aaggcgagga gctcagcatg gtcatcctgc tgccggatga cattgaggac      960

gagtccacgg gcctgaagaa gattgaggaa cagttgactt tggaaaagtt gcatgagtgg     1020

actaaacctg agaatctcga tttcattgaa gttaatgtca gcttgcccag gttcaaactg     1080

gaagagagtt acactctcaa ctccgacctc gcccgcctag gtgtgcagga tctctttaac     1140

agtagcaagg ctgatctgtc tggcatgtca ggagccagag atatttttat atcaaaaatt     1200

gtccacaagt catttgtgga agtgaatgaa gagggaacag aggcggcagc tgccacagca     1260

ggcatcgcaa ctttctgcat gttgatgccc gaagaaaatt tcactgccga ccatccattc     1320

cttttcttta ttcggcataa ttcctcaggt agcatcctat tcttggggag attttcttcc     1380

ccttagaaga aagagactgt agcaatacaa aaatcaagct tagtgcttta ttacctgagt     1440

ttttaataga gccaatatgt cttatatctt taccaataaa accactgttc agaaacaagt     1500

ctttcatttt ctttgtaagt ttggctctgt tggctgttta cacccatgaa ttttggcatg     1560

ggtatctatt tttctttttt acattgaaaa aaatccagtg gttgcttttg aatgcatcaa     1620

gtaaagaaga agaaaagaat acatccgatg cgtagattct tgaccatgta gtaatctata     1680

aaattgctat atcctcctga tagccatggg aaaacatgat aagatggtca tttattttgc     1740

agttagaatt ttggaagcca caaaatagac agacaccctg actgttgaag ggaggtttaa     1800

aaacagatat tcaattgaaa tgtaagagag caccccaatt gagagcccag gttacgaaga     1860

caagcttgcc tcgcctgact tttctgtccc ttgttctgca ggattagtat tctgttacag     1920

acctctagtt tttagactct tcaattaaag ggccaatggt tataacctgc attccctttt     1980

ttgttcttct ttatgtataa tatatagttc atgtggcgct gcatgaaatc aagaagtggg     2040

tgtcttagga taaaagatac caagagtcta caaaaataac catgtagtaa gataaactgc     2100

tgaacaaagg ttttactgtt agccaccttc tcatgtgttt tcttttctct ttttcttttt     2160

ctttctttct ttcttttttt tttttttgag acagagtctt gctctgttac ccaggctgga     2220

gtgcagtggc acgatctcag ctcaccgcaa cctctgcctc ctgggttcaa gtgattctct     2280

tgcttcagcc tcctgagtag ctgggattat aggcatgcac cactaggcct ggctaatttt     2340

tgtattttta gtagagatgg ggtttttcca tgttggccag gctggtcccg aactcctgac     2400

ctcaggtgat ccgcgcacct cagcctccca aagtgctggg attacaggca tgagctacca     2460

tgcctggcct tctcatgtgt tttctgatta aggctcttga cttccaaggc tgtgtgggga     2520

gatggggtgg gggctcttgg actgatataa aactttgtca aatgtagttc tttgaatgga     2580

gcttgaaacg ccgcatattc ttgctcccac aaggatagtg ggcatcatga attaataaaa     2640

cgtcctagga ttctgcaagc taaaaaaaaa aaaaaaaa                             2678


<210>  3
<211>  379
<212>  PRT
<213>  Mus musculus

<400>  3

Met Glu Gln Leu Ser Ser Ala Asn Thr Leu Phe Ala Leu Glu Leu Phe 
1               5                   10                  15      


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


Phe Ser Ile Ser Ser Ala Leu Ala Met Val Ile Leu Gly Ala Lys Gly 
        35                  40                  45              


Ser Thr Ala Ala Gln Leu Ser Lys Thr Phe His Phe Asp Ser Val Glu 
    50                  55                  60                  


Asp Ile His Ser Arg Phe Gln Ser Leu Asn Ala Glu Val Ser Lys Arg 
65                  70                  75                  80  


Gly Ala Ser His Thr Leu Lys Leu Ala Asn Arg Leu Tyr Gly Glu Lys 
                85                  90                  95      


Thr Tyr Asn Phe Leu Pro Glu Tyr Leu Ala Ser Thr Gln Lys Met Tyr 
            100                 105                 110         


Gly Ala Asp Leu Ala Pro Val Asp Phe Leu His Ala Ser Glu Asp Ala 
        115                 120                 125             


Arg Lys Glu Ile Asn Gln Trp Val Lys Gly Gln Thr Glu Gly Lys Ile 
    130                 135                 140                 


Pro Glu Leu Leu Ser Val Gly Val Val Asp Ser Met Thr Lys Leu Val 
145                 150                 155                 160 


Leu Val Asn Ala Ile Tyr Phe Lys Gly Met Trp Glu Glu Lys Phe Met 
                165                 170                 175     


Thr Glu Asp Thr Thr Asp Ala Pro Phe Arg Leu Ser Lys Lys Asp Thr 
            180                 185                 190         


Lys Thr Val Lys Met Met Tyr Gln Lys Lys Lys Phe Pro Phe Gly Tyr 
        195                 200                 205             


Ile Ser Asp Leu Lys Cys Lys Val Leu Glu Met Pro Tyr Gln Gly Gly 
    210                 215                 220                 


Glu Leu Ser Met Val Ile Leu Leu Pro Lys Asp Ile Glu Asp Glu Ser 
225                 230                 235                 240 


Thr Gly Leu Lys Lys Ile Glu Lys Gln Ile Thr Leu Glu Lys Leu Leu 
                245                 250                 255     


Glu Trp Thr Lys Arg Glu Asn Leu Glu Phe Ile Asp Val His Val Lys 
            260                 265                 270         


Leu Pro Arg Phe Lys Ile Glu Glu Ser Tyr Thr Leu Asn Ser Asn Leu 
        275                 280                 285             


Gly Arg Leu Gly Val Gln Asp Leu Phe Ser Ser Ser Lys Ala Asp Leu 
    290                 295                 300                 


Ser Gly Met Ser Gly Ser Arg Asp Leu Phe Ile Ser Lys Ile Val His 
305                 310                 315                 320 


Lys Ser Phe Val Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala 
                325                 330                 335     


Thr Gly Gly Ile Ala Thr Phe Cys Met Leu Leu Pro Glu Glu Glu Phe 
            340                 345                 350         


Thr Val Asp His Pro Phe Ile Phe Phe Ile Arg His Asn Pro Thr Ser 
        355                 360                 365             


Asn Val Leu Phe Leu Gly Arg Val Cys Ser Pro 
    370                 375                 


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

<220>
<223>  Forward Primer SerpinB1

<400>  4
gctgctacag gaggcattgc                                                   20


<210>  5
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Reverse Primer SerpinB1

<400>  5
cggatggtcc actgtgaatt c                                                 21


<210>  6
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Forward Primer Betatrophin

<400>  6
cactgtacgg agactacaag tgc                                               23


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

<220>
<223>  Reverse Primer Betatrophin

<400>  7
gtggctctgc ttatcagctc g                                                 21


<210>  8
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Forward Primer TBP

<400>  8
acccttcacc aatgactcct atg                                               23


<210>  9
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Reverse Primer TBP

<400>  9
atgatgactg cagcaaatcg c                                                 21


<210>  10
<211>  379
<212>  PRT
<213>  Homo sapiens

<400>  10

Met Glu Gln Leu Ser Ser Ala Asn Thr Arg Phe Ala Leu Asp Leu Phe 
1               5                   10                  15      


Leu Ala Leu Ser Glu Asn Asn Pro Ala Gly Asn Ile Phe Ile Ser Pro 
            20                  25                  30          


Phe Ser Ile Ser Ser Ala Met Ala Met Val Phe Leu Gly Thr Arg Gly 
        35                  40                  45              


Asn Thr Ala Ala Gln Leu Ser Lys Thr Phe His Phe Asn Thr Val Glu 
    50                  55                  60                  


Glu Val His Ser Arg Phe Gln Ser Leu Asn Ala Asp Ile Asn Lys Arg 
65                  70                  75                  80  


Gly Ala Ser Tyr Ile Leu Lys Leu Ala Asn Arg Leu Tyr Gly Glu Lys 
                85                  90                  95      


Thr Tyr Asn Phe Leu Pro Glu Phe Leu Val Ser Thr Gln Lys Thr Tyr 
            100                 105                 110         


Gly Ala Asp Leu Ala Ser Val Asp Phe Gln His Ala Ser Glu Asp Ala 
        115                 120                 125             


Arg Lys Thr Ile Asn Gln Trp Val Lys Gly Gln Thr Glu Gly Lys Ile 
    130                 135                 140                 


Pro Glu Leu Leu Ala Ser Gly Met Val Asp Asn Met Thr Lys Leu Val 
145                 150                 155                 160 


Leu Val Asn Ala Ile Tyr Phe Lys Gly Asn Trp Lys Asp Lys Phe Met 
                165                 170                 175     


Lys Glu Ala Thr Thr Asn Ala Pro Phe Arg Leu Asn Lys Lys Asp Arg 
            180                 185                 190         


Lys Thr Val Lys Met Met Tyr Gln Lys Lys Lys Phe Ala Tyr Gly Tyr 
        195                 200                 205             


Ile Glu Asp Leu Lys Cys Arg Val Leu Glu Leu Pro Tyr Gln Gly Glu 
    210                 215                 220                 


Glu Leu Ser Met Val Ile Leu Leu Pro Asp Asp Ile Glu Asp Glu Ser 
225                 230                 235                 240 


Thr Gly Leu Lys Lys Ile Glu Glu Gln Leu Thr Leu Glu Lys Leu His 
                245                 250                 255     


Glu Trp Thr Lys Pro Glu Asn Leu Asp Phe Ile Glu Val Asn Val Ser 
            260                 265                 270         


Leu Pro Arg Phe Lys Leu Glu Glu Ser Tyr Thr Leu Asn Ser Asp Leu 
        275                 280                 285             


Ala Arg Leu Gly Val Gln Asp Leu Phe Asn Ser Ser Lys Ala Asp Leu 
    290                 295                 300                 


Ser Gly Met Ser Gly Ala Arg Asp Ile Phe Ile Ser Lys Ile Val His 
305                 310                 315                 320 


Lys Ser Phe Val Glu Val Asn Glu Glu Gly Thr Glu Ala Ala Ala Ala 
                325                 330                 335     


Thr Ala Gly Ile Ala Thr Phe Cys Met Leu Met Pro Glu Glu Asn Phe 
            340                 345                 350         


Thr Ala Asp His Pro Phe Leu Phe Phe Ile Arg His Asn Ser Ser Gly 
        355                 360                 365             


Ser Ile Leu Phe Leu Gly Arg Phe Ser Ser Pro 
    370                 375                 


