                         SEQUENCE LISTING

<110>  Santaris Pharma A/S
 
<120>  ANTI APOB ANTISENSE CONJUGATE COMPOUNDS

<130>  1143WO

<150>  EP13192930.9
<151>  2013-11-14

<150>  PCT/EP2013/073859
<151>  2013-11-14

<150>  PCT/EP2013/073858
<151>  2013-11-14

<150>  EP14153266.3
<151>  2014-01-30

<150>  EP14167879.7
<151>  2014-05-12

<160>  32    

<170>  PatentIn version 3.5

<210>  1
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  Oligonucleotide sequence motif

<400>  1
gcattggtat tca                                                          13


<210>  2
<211>  12
<212>  DNA
<213>  artificial

<220>
<223>  Oligonucleotide sequence motif

<400>  2
gttgacactg tc                                                           12


<210>  3
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  3
gcattggtat tca                                                          13


<210>  4
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' cholesterol conjugate

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  4
gcattggtat tca                                                          13


<210>  5
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  disulfide linked 5' cholesterol conjugate

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  5
gcattggtat tca                                                          13


<210>  6
<211>  16
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' cholesterol conjugate

<220>
<221>  misc_feature
<222>  (4)..(16)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (4)..(5)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (14)..(16)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  6
tcagcattgg tattca                                                       16


<210>  7
<211>  15
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' cholesterol conjugate

<220>
<221>  misc_feature
<222>  (3)..(15)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  7
cagcattggt attca                                                        15


<210>  8
<211>  14
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  phosphorodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' cholesterol conjugate

<220>
<221>  misc_feature
<222>  (2)..(14)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (12)..(14)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  8
agcattggta ttca                                                         14


<210>  9
<211>  16
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (4)..(16)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (4)..(5)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (14)..(16)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  9
tcagcattgg tattca                                                       16


<210>  10
<211>  15
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (3)..(15)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  10
cagcattggt attca                                                        15


<210>  11
<211>  14
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  phosphorodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (2)..(14)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (12)..(14)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  11
agcattggta ttca                                                         14


<210>  12
<211>  16
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (4)..(16)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (4)..(5)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (14)..(16)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  12
gacgcattgg tattca                                                       16


<210>  13
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  13
gcattggtat tca                                                          13


<210>  14
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5'folic acid conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  14
gcattggtat tca                                                          13


<210>  15
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  disulfide linked 5'folic acid conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  15
gcattggtat tca                                                          13


<210>  16
<211>  15
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' folic acid conjugate

<220>
<221>  misc_feature
<222>  (3)..(15)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  16
cagcattggt attca                                                        15


<210>  17
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' mono GalNAc conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  17
gcattggtat tca                                                          13


<210>  18
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  disulfide linked mono GalNAc conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  18
gcattggtat tca                                                          13


<210>  19
<211>  15
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' monoGalNAc conjugate

<220>
<221>  misc_feature
<222>  (3)..(15)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  19
cagcattggt attca                                                        15


<210>  20
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' GalNAc cluster conjugate Conj2a

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  20
gcattggtat tca                                                          13


<210>  21
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  21
gcattggtat tca                                                          13


<210>  22
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  disulfide linked 5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  22
gcattggtat tca                                                          13


<210>  23
<211>  15
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' FAM label conjugate

<220>
<221>  misc_feature
<222>  (3)..(15)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  23
cagcattggt attca                                                        15


<210>  24
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' tocopherol conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  24
gcattggtat tca                                                          13


<210>  25
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  disulfide linked tocopherol label conjugate

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  25
gcattggtat tca                                                          13


<210>  26
<211>  15
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' tocopherol conjugate

<220>
<221>  misc_feature
<222>  (3)..(15)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (13)..(15)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  26
cagcattggt attca                                                        15


<210>  27
<211>  12
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(12)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides

<220>
<221>  misc_feature
<222>  (11)..(12)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  27
gttgacactg tc                                                           12


<210>  28
<211>  14
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  phosphodiester lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' cholesterol conjugate

<220>
<221>  misc_feature
<222>  (3)..(14)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (3)..(4)
<223>  LNA nucleosides

<220>
<221>  misc_feature
<222>  (13)..(14)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  28
cagttgacac tgtc                                                         14


<210>  29
<211>  12
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(12)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  GalNAc cluster conjugate Conj2a

<220>
<221>  misc_feature
<222>  (11)..(12)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  29
gttgacactg tc                                                           12


<210>  30
<211>  13
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide conjugate


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  5' GalNAc cluster conjugate Conj1a

<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides, LNA C are 5-methyl C

<220>
<221>  misc_feature
<222>  (11)..(13)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  30
gcattggtat tca                                                          13


<210>  31
<211>  12
<212>  DNA
<213>  artificial

<220>
<223>  LNA antisense gapmer oligonucleotide


<220>
<221>  misc_feature
<222>  (1)..(12)
<223>  phosphorothioate lnternucleoside linkages

<220>
<221>  misc_feature
<222>  (1)..(2)
<223>  LNA nucleosides

<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  GalNAc cluster conjugate Conj1a

<220>
<221>  misc_feature
<222>  (11)..(12)
<223>  LNA nucleosides, LNA C are 5-methyl C

<400>  31
gttgacactg tc                                                           12


<210>  32
<211>  14121
<212>  DNA
<213>  Homo sapiens

<400>  32
attcccaccg ggacctgcgg ggctgagtgc ccttctcggt tgctgccgct gaggagcccg       60

cccagccagc cagggccgcg aggccgaggc caggccgcag cccaggagcc gccccaccgc      120

agctggcgat ggacccgccg aggcccgcgc tgctggcgct gctggcgctg cctgcgctgc      180

tgctgctgct gctggcgggc gccagggccg aagaggaaat gctggaaaat gtcagcctgg      240

tctgtccaaa agatgcgacc cgattcaagc acctccggaa gtacacatac aactatgagg      300

ctgagagttc cagtggagtc cctgggactg ctgattcaag aagtgccacc aggatcaact      360

gcaaggttga gctggaggtt ccccagctct gcagcttcat cctgaagacc agccagtgca      420

ccctgaaaga ggtgtatggc ttcaaccctg agggcaaagc cttgctgaag aaaaccaaga      480

actctgagga gtttgctgca gccatgtcca ggtatgagct caagctggcc attccagaag      540

ggaagcaggt tttcctttac ccggagaaag atgaacctac ttacatcctg aacatcaaga      600

ggggcatcat ttctgccctc ctggttcccc cagagacaga agaagccaag caagtgttgt      660

ttctggatac cgtgtatgga aactgctcca ctcactttac cgtcaagacg aggaagggca      720

atgtggcaac agaaatatcc actgaaagag acctggggca gtgtgatcgc ttcaagccca      780

tccgcacagg catcagccca cttgctctca tcaaaggcat gacccgcccc ttgtcaactc      840

tgatcagcag cagccagtcc tgtcagtaca cactggacgc taagaggaag catgtggcag      900

aagccatctg caaggagcaa cacctcttcc tgcctttctc ctacaagaat aagtatggga      960

tggtagcaca agtgacacag actttgaaac ttgaagacac accaaagatc aacagccgct     1020

tctttggtga aggtactaag aagatgggcc tcgcatttga gagcaccaaa tccacatcac     1080

ctccaaagca ggccgaagct gttttgaaga ctctccagga actgaaaaaa ctaaccatct     1140

ctgagcaaaa tatccagaga gctaatctct tcaataagct ggttactgag ctgagaggcc     1200

tcagtgatga agcagtcaca tctctcttgc cacagctgat tgaggtgtcc agccccatca     1260

ctttacaagc cttggttcag tgtggacagc ctcagtgctc cactcacatc ctccagtggc     1320

tgaaacgtgt gcatgccaac ccccttctga tagatgtggt cacctacctg gtggccctga     1380

tccccgagcc ctcagcacag cagctgcgag agatcttcaa catggcgagg gatcagcgca     1440

gccgagccac cttgtatgcg ctgagccacg cggtcaacaa ctatcataag acaaacccta     1500

cagggaccca ggagctgctg gacattgcta attacctgat ggaacagatt caagatgact     1560

gcactgggga tgaagattac acctatttga ttctgcgggt cattggaaat atgggccaaa     1620

ccatggagca gttaactcca gaactcaagt cttcaatcct gaaatgtgtc caaagtacaa     1680

agccatcact gatgatccag aaagctgcca tccaggctct gcggaaaatg gagcctaaag     1740

acaaggacca ggaggttctt cttcagactt tccttgatga tgcttctccg ggagataagc     1800

gactggctgc ctatcttatg ttgatgagga gtccttcaca ggcagatatt aacaaaattg     1860

tccaaattct accatgggaa cagaatgagc aagtgaagaa ctttgtggct tcccatattg     1920

ccaatatctt gaactcagaa gaattggata tccaagatct gaaaaagtta gtgaaagaag     1980

ctctgaaaga atctcaactt ccaactgtca tggacttcag aaaattctct cggaactatc     2040

aactctacaa atctgtttct cttccatcac ttgacccagc ctcagccaaa atagaaggga     2100

atcttatatt tgatccaaat aactaccttc ctaaagaaag catgctgaaa actaccctca     2160

ctgcctttgg atttgcttca gctgacctca tcgagattgg cttggaagga aaaggctttg     2220

agccaacatt ggaagctctt tttgggaagc aaggattttt cccagacagt gtcaacaaag     2280

ctttgtactg ggttaatggt caagttcctg atggtgtctc taaggtctta gtggaccact     2340

ttggctatac caaagatgat aaacatgagc aggatatggt aaatggaata atgctcagtg     2400

ttgagaagct gattaaagat ttgaaatcca aagaagtccc ggaagccaga gcctacctcc     2460

gcatcttggg agaggagctt ggttttgcca gtctccatga cctccagctc ctgggaaagc     2520

tgcttctgat gggtgcccgc actctgcagg ggatccccca gatgattgga gaggtcatca     2580

ggaagggctc aaagaatgac ttttttcttc actacatctt catggagaat gcctttgaac     2640

tccccactgg agctggatta cagttgcaaa tatcttcatc tggagtcatt gctcccggag     2700

ccaaggctgg agtaaaactg gaagtagcca acatgcaggc tgaactggtg gcaaaaccct     2760

ccgtgtctgt ggagtttgtg acaaatatgg gcatcatcat tccggacttc gctaggagtg     2820

gggtccagat gaacaccaac ttcttccacg agtcgggtct ggaggctcat gttgccctaa     2880

aagctgggaa gctgaagttt atcattcctt ccccaaagag accagtcaag ctgctcagtg     2940

gaggcaacac attacatttg gtctctacca ccaaaacgga ggtgatccca cctctcattg     3000

agaacaggca gtcctggtca gtttgcaagc aagtctttcc tggcctgaat tactgcacct     3060

caggcgctta ctccaacgcc agctccacag actccgcctc ctactatccg ctgaccgggg     3120

acaccagatt agagctggaa ctgaggccta caggagagat tgagcagtat tctgtcagcg     3180

caacctatga gctccagaga gaggacagag ccttggtgga taccctgaag tttgtaactc     3240

aagcagaagg tgcgaagcag actgaggcta ccatgacatt caaatataat cggcagagta     3300

tgaccttgtc cagtgaagtc caaattccgg attttgatgt tgacctcgga acaatcctca     3360

gagttaatga tgaatctact gagggcaaaa cgtcttacag actcaccctg gacattcaga     3420

acaagaaaat tactgaggtc gccctcatgg gccacctaag ttgtgacaca aaggaagaaa     3480

gaaaaatcaa gggtgttatt tccatacccc gtttgcaagc agaagccaga agtgagatcc     3540

tcgcccactg gtcgcctgcc aaactgcttc tccaaatgga ctcatctgct acagcttatg     3600

gctccacagt ttccaagagg gtggcatggc attatgatga agagaagatt gaatttgaat     3660

ggaacacagg caccaatgta gataccaaaa aaatgacttc caatttccct gtggatctct     3720

ccgattatcc taagagcttg catatgtatg ctaatagact cctggatcac agagtccctc     3780

aaacagacat gactttccgg cacgtgggtt ccaaattaat agttgcaatg agctcatggc     3840

ttcagaaggc atctgggagt cttccttata cccagacttt gcaagaccac ctcaatagcc     3900

tgaaggagtt caacctccag aacatgggat tgccagactt ccacatccca gaaaacctct     3960

tcttaaaaag cgatggccgg gtcaaatata ccttgaacaa gaacagtttg aaaattgaga     4020

ttcctttgcc ttttggtggc aaatcctcca gagatctaaa gatgttagag actgttagga     4080

caccagccct ccacttcaag tctgtgggat tccatctgcc atctcgagag ttccaagtcc     4140

ctacttttac cattcccaag ttgtatcaac tgcaagtgcc tctcctgggt gttctagacc     4200

tctccacgaa tgtctacagc aacttgtaca actggtccgc ctcctacagt ggtggcaaca     4260

ccagcacaga ccatttcagc cttcgggctc gttaccacat gaaggctgac tctgtggttg     4320

acctgctttc ctacaatgtg caaggatctg gagaaacaac atatgaccac aagaatacgt     4380

tcacactatc atgtgatggg tctctacgcc acaaatttct agattcgaat atcaaattca     4440

gtcatgtaga aaaacttgga aacaacccag tctcaaaagg tttactaata ttcgatgcat     4500

ctagttcctg gggaccacag atgtctgctt cagttcattt ggactccaaa aagaaacagc     4560

atttgtttgt caaagaagtc aagattgatg ggcagttcag agtctcttcg ttctatgcta     4620

aaggcacata tggcctgtct tgtcagaggg atcctaacac tggccggctc aatggagagt     4680

ccaacctgag gtttaactcc tcctacctcc aaggcaccaa ccagataaca ggaagatatg     4740

aagatggaac cctctccctc acctccacct ctgatctgca aagtggcatc attaaaaata     4800

ctgcttccct aaagtatgag aactacgagc tgactttaaa atctgacacc aatgggaagt     4860

ataagaactt tgccacttct aacaagatgg atatgacctt ctctaagcaa aatgcactgc     4920

tgcgttctga atatcaggct gattacgagt cattgaggtt cttcagcctg ctttctggat     4980

cactaaattc ccatggtctt gagttaaatg ctgacatctt aggcactgac aaaattaata     5040

gtggtgctca caaggcgaca ctaaggattg gccaagatgg aatatctacc agtgcaacga     5100

ccaacttgaa gtgtagtctc ctggtgctgg agaatgagct gaatgcagag cttggcctct     5160

ctggggcatc tatgaaatta acaacaaatg gccgcttcag ggaacacaat gcaaaattca     5220

gtctggatgg gaaagccgcc ctcacagagc tatcactggg aagtgcttat caggccatga     5280

ttctgggtgt cgacagcaaa aacattttca acttcaaggt cagtcaagaa ggacttaagc     5340

tctcaaatga catgatgggc tcatatgctg aaatgaaatt tgaccacaca aacagtctga     5400

acattgcagg cttatcactg gacttctctt caaaacttga caacatttac agctctgaca     5460

agttttataa gcaaactgtt aatttacagc tacagcccta ttctctggta actactttaa     5520

acagtgacct gaaatacaat gctctggatc tcaccaacaa tgggaaacta cggctagaac     5580

ccctgaagct gcatgtggct ggtaacctaa aaggagccta ccaaaataat gaaataaaac     5640

acatctatgc catctcttct gctgccttat cagcaagcta taaagcagac actgttgcta     5700

aggttcaggg tgtggagttt agccatcggc tcaacacaga catcgctggg ctggcttcag     5760

ccattgacat gagcacaaac tataattcag actcactgca tttcagcaat gtcttccgtt     5820

ctgtaatggc cccgtttacc atgaccatcg atgcacatac aaatggcaat gggaaactcg     5880

ctctctgggg agaacatact gggcagctgt atagcaaatt cctgttgaaa gcagaacctc     5940

tggcatttac tttctctcat gattacaaag gctccacaag tcatcatctc gtgtctagga     6000

aaagcatcag tgcagctctt gaacacaaag tcagtgccct gcttactcca gctgagcaga     6060

caggcacctg gaaactcaag acccaattta acaacaatga atacagccag gacttggatg     6120

cttacaacac taaagataaa attggcgtgg agcttactgg acgaactctg gctgacctaa     6180

ctctactaga ctccccaatt aaagtgccac ttttactcag tgagcccatc aatatcattg     6240

atgctttaga gatgagagat gccgttgaga agccccaaga atttacaatt gttgcttttg     6300

taaagtatga taaaaaccaa gatgttcact ccattaacct cccatttttt gagaccttgc     6360

aagaatattt tgagaggaat cgacaaacca ttatagttgt actggaaaac gtacagagaa     6420

acctgaagca catcaatatt gatcaatttg taagaaaata cagagcagcc ctgggaaaac     6480

tcccacagca agctaatgat tatctgaatt cattcaattg ggagagacaa gtttcacatg     6540

ccaaggagaa actgactgct ctcacaaaaa agtatagaat tacagaaaat gatatacaaa     6600

ttgcattaga tgatgccaaa atcaacttta atgaaaaact atctcaactg cagacatata     6660

tgatacaatt tgatcagtat attaaagata gttatgattt acatgatttg aaaatagcta     6720

ttgctaatat tattgatgaa atcattgaaa aattaaaaag tcttgatgag cactatcata     6780

tccgtgtaaa tttagtaaaa acaatccatg atctacattt gtttattgaa aatattgatt     6840

ttaacaaaag tggaagtagt actgcatcct ggattcaaaa tgtggatact aagtaccaaa     6900

tcagaatcca gatacaagaa aaactgcagc agcttaagag acacatacag aatatagaca     6960

tccagcacct agctggaaag ttaaaacaac acattgaggc tattgatgtt agagtgcttt     7020

tagatcaatt gggaactaca atttcatttg aaagaataaa tgacgttctt gagcatgtca     7080

aacactttgt tataaatctt attggggatt ttgaagtagc tgagaaaatc aatgccttca     7140

gagccaaagt ccatgagtta atcgagaggt atgaagtaga ccaacaaatc caggttttaa     7200

tggataaatt agtagagttg gcccaccaat acaagttgaa ggagactatt cagaagctaa     7260

gcaatgtcct acaacaagtt aagataaaag attactttga gaaattggtt ggatttattg     7320

atgatgctgt caagaagctt aatgaattat cttttaaaac attcattgaa gatgttaaca     7380

aattccttga catgttgata aagaaattaa agtcatttga ttaccaccag tttgtagatg     7440

aaaccaatga caaaatccgt gaggtgactc agagactcaa tggtgaaatt caggctctgg     7500

aactaccaca aaaagctgaa gcattaaaac tgtttttaga ggaaaccaag gccacagttg     7560

cagtgtatct ggaaagccta caggacacca aaataacctt aatcatcaat tggttacagg     7620

aggctttaag ttcagcatct ttggctcaca tgaaggccaa attccgagag accctagaag     7680

atacacgaga ccgaatgtat caaatggaca ttcagcagga acttcaacga tacctgtctc     7740

tggtaggcca ggtttatagc acacttgtca cctacatttc tgattggtgg actcttgctg     7800

ctaagaacct tactgacttt gcagagcaat attctatcca agattgggct aaacgtatga     7860

aagcattggt agagcaaggg ttcactgttc ctgaaatcaa gaccatcctt gggaccatgc     7920

ctgcctttga agtcagtctt caggctcttc agaaagctac cttccagaca cctgatttta     7980

tagtccccct aacagatttg aggattccat cagttcagat aaacttcaaa gacttaaaaa     8040

atataaaaat cccatccagg ttttccacac cagaatttac catccttaac accttccaca     8100

ttccttcctt tacaattgac tttgtagaaa tgaaagtaaa gatcatcaga accattgacc     8160

agatgctgaa cagtgagctg cagtggcccg ttccagatat atatctcagg gatctgaagg     8220

tggaggacat tcctctagcg agaatcaccc tgccagactt ccgtttacca gaaatcgcaa     8280

ttccagaatt cataatccca actctcaacc ttaatgattt tcaagttcct gaccttcaca     8340

taccagaatt ccagcttccc cacatctcac acacaattga agtacctact tttggcaagc     8400

tatacagtat tctgaaaatc caatctcctc ttttcacatt agatgcaaat gctgacatag     8460

ggaatggaac cacctcagca aacgaagcag gtatcgcagc ttccatcact gccaaaggag     8520

agtccaaatt agaagttctc aattttgatt ttcaagcaaa tgcacaactc tcaaacccta     8580

agattaatcc gctggctctg aaggagtcag tgaagttctc cagcaagtac ctgagaacgg     8640

agcatgggag tgaaatgctg ttttttggaa atgctattga gggaaaatca aacacagtgg     8700

caagtttaca cacagaaaaa aatacactgg agcttagtaa tggagtgatt gtcaagataa     8760

acaatcagct taccctggat agcaacacta aatacttcca caaattgaac atccccaaac     8820

tggacttctc tagtcaggct gacctgcgca acgagatcaa gacactgttg aaagctggcc     8880

acatagcatg gacttcttct ggaaaagggt catggaaatg ggcctgcccc agattctcag     8940

atgagggaac acatgaatca caaattagtt tcaccataga aggacccctc acttcctttg     9000

gactgtccaa taagatcaat agcaaacacc taagagtaaa ccaaaacttg gtttatgaat     9060

ctggctccct caacttttct aaacttgaaa ttcaatcaca agtcgattcc cagcatgtgg     9120

gccacagtgt tctaactgct aaaggcatgg cactgtttgg agaagggaag gcagagttta     9180

ctgggaggca tgatgctcat ttaaatggaa aggttattgg aactttgaaa aattctcttt     9240

tcttttcagc ccagccattt gagatcacgg catccacaaa caatgaaggg aatttgaaag     9300

ttcgttttcc attaaggtta acagggaaga tagacttcct gaataactat gcactgtttc     9360

tgagtcccag tgcccagcaa gcaagttggc aagtaagtgc taggttcaat cagtataagt     9420

acaaccaaaa tttctctgct ggaaacaacg agaacattat ggaggcccat gtaggaataa     9480

atggagaagc aaatctggat ttcttaaaca ttcctttaac aattcctgaa atgcgtctac     9540

cttacacaat aatcacaact cctccactga aagatttctc tctatgggaa aaaacaggct     9600

tgaaggaatt cttgaaaacg acaaagcaat catttgattt aagtgtaaaa gctcagtata     9660

agaaaaacaa acacaggcat tccatcacaa atcctttggc tgtgctttgt gagtttatca     9720

gtcagagcat caaatccttt gacaggcatt ttgaaaaaaa cagaaacaat gcattagatt     9780

ttgtcaccaa atcctataat gaaacaaaaa ttaagtttga taagtacaaa gctgaaaaat     9840

ctcacgacga gctccccagg acctttcaaa ttcctggata cactgttcca gttgtcaatg     9900

ttgaagtgtc tccattcacc atagagatgt cggcattcgg ctatgtgttc ccaaaagcag     9960

tcagcatgcc tagtttctcc atcctaggtt ctgacgtccg tgtgccttca tacacattaa    10020

tcctgccatc attagagctg ccagtccttc atgtccctag aaatctcaag ctttctcttc    10080

cagatttcaa ggaattgtgt accataagcc atatttttat tcctgccatg ggcaatatta    10140

cctatgattt ctcctttaaa tcaagtgtca tcacactgaa taccaatgct gaacttttta    10200

accagtcaga tattgttgct catctccttt cttcatcttc atctgtcatt gatgcactgc    10260

agtacaaatt agagggcacc acaagattga caagaaaaag gggattgaag ttagccacag    10320

ctctgtctct gagcaacaaa tttgtggagg gtagtcataa cagtactgtg agcttaacca    10380

cgaaaaatat ggaagtgtca gtggcaacaa ccacaaaagc ccaaattcca attttgagaa    10440

tgaatttcaa gcaagaactt aatggaaata ccaagtcaaa acctactgtc tcttcctcca    10500

tggaatttaa gtatgatttc aattcttcaa tgctgtactc taccgctaaa ggagcagttg    10560

accacaagct tagcttggaa agcctcacct cttacttttc cattgagtca tctaccaaag    10620

gagatgtcaa gggttcggtt ctttctcggg aatattcagg aactattgct agtgaggcca    10680

acacttactt gaattccaag agcacacggt cttcagtgaa gctgcagggc acttccaaaa    10740

ttgatgatat ctggaacctt gaagtaaaag aaaattttgc tggagaagcc acactccaac    10800

gcatatattc cctctgggag cacagtacga aaaaccactt acagctagag ggcctctttt    10860

tcaccaacgg agaacataca agcaaagcca ccctggaact ctctccatgg caaatgtcag    10920

ctcttgttca ggtccatgca agtcagccca gttccttcca tgatttccct gaccttggcc    10980

aggaagtggc cctgaatgct aacactaaga accagaagat cagatggaaa aatgaagtcc    11040

ggattcattc tgggtctttc cagagccagg tcgagctttc caatgaccaa gaaaaggcac    11100

accttgacat tgcaggatcc ttagaaggac acctaaggtt cctcaaaaat atcatcctac    11160

cagtctatga caagagctta tgggatttcc taaagctgga tgtaaccacc agcattggta    11220

ggagacagca tcttcgtgtt tcaactgcct ttgtgtacac caaaaacccc aatggctatt    11280

cattctccat ccctgtaaaa gttttggctg ataaattcat tattcctggg ctgaaactaa    11340

atgatctaaa ttcagttctt gtcatgccta cgttccatgt cccatttaca gatcttcagg    11400

ttccatcgtg caaacttgac ttcagagaaa tacaaatcta taagaagctg agaacttcat    11460

catttgccct caacctacca acactccccg aggtaaaatt ccctgaagtt gatgtgttaa    11520

caaaatattc tcaaccagaa gactccttga ttcccttttt tgagataacc gtgcctgaat    11580

ctcagttaac tgtgtcccag ttcacgcttc caaaaagtgt ttcagatggc attgctgctt    11640

tggatctaaa tgcagtagcc aacaagatcg cagactttga gttgcccacc atcatcgtgc    11700

ctgagcagac cattgagatt ccctccatta agttctctgt acctgctgga attgtcattc    11760

cttcctttca agcactgact gcacgctttg aggtagactc tcccgtgtat aatgccactt    11820

ggagtgccag tttgaaaaac aaagcagatt atgttgaaac agtcctggat tccacatgca    11880

gctcaaccgt acagttccta gaatatgaac taaatgtttt gggaacacac aaaatcgaag    11940

atggtacgtt agcctctaag actaaaggaa catttgcaca ccgtgacttc agtgcagaat    12000

atgaagaaga tggcaaatat gaaggacttc aggaatggga aggaaaagcg cacctcaata    12060

tcaaaagccc agcgttcacc gatctccatc tgcgctacca gaaagacaag aaaggcatct    12120

ccacctcagc agcctcccca gccgtaggca ccgtgggcat ggatatggat gaagatgacg    12180

acttttctaa atggaacttc tactacagcc ctcagtcctc tccagataaa aaactcacca    12240

tattcaaaac tgagttgagg gtccgggaat ctgatgagga aactcagatc aaagttaatt    12300

gggaagaaga ggcagcttct ggcttgctaa cctctctgaa agacaacgtg cccaaggcca    12360

caggggtcct ttatgattat gtcaacaagt accactggga acacacaggg ctcaccctga    12420

gagaagtgtc ttcaaagctg agaagaaatc tgcagaacaa tgctgagtgg gtttatcaag    12480

gggccattag gcaaattgat gatatcgacg tgaggttcca gaaagcagcc agtggcacca    12540

ctgggaccta ccaagagtgg aaggacaagg cccagaatct gtaccaggaa ctgttgactc    12600

aggaaggcca agccagtttc cagggactca aggataacgt gtttgatggc ttggtacgag    12660

ttactcaaga attccatatg aaagtcaagc atctgattga ctcactcatt gattttctga    12720

acttccccag attccagttt ccggggaaac ctgggatata cactagggag gaactttgca    12780

ctatgttcat aagggaggta gggacggtac tgtcccaggt atattcgaaa gtccataatg    12840

gttcagaaat actgttttcc tatttccaag acctagtgat tacacttcct ttcgagttaa    12900

ggaaacataa actaatagat gtaatctcga tgtataggga actgttgaaa gatttatcaa    12960

aagaagccca agaggtattt aaagccattc agtctctcaa gaccacagag gtgctacgta    13020

atcttcagga ccttttacaa ttcattttcc aactaataga agataacatt aaacagctga    13080

aagagatgaa atttacttat cttattaatt atatccaaga tgagatcaac acaatcttca    13140

gtgattatat cccatatgtt tttaaattgt tgaaagaaaa cctatgcctt aatcttcata    13200

agttcaatga atttattcaa aacgagcttc aggaagcttc tcaagagtta cagcagatcc    13260

atcaatacat tatggccctt cgtgaagaat attttgatcc aagtatagtt ggctggacag    13320

tgaaatatta tgaacttgaa gaaaagatag tcagtctgat caagaacctg ttagttgctc    13380

ttaaggactt ccattctgaa tatattgtca gtgcctctaa ctttacttcc caactctcaa    13440

gtcaagttga gcaatttctg cacagaaata ttcaggaata tcttagcatc cttaccgatc    13500

cagatggaaa agggaaagag aagattgcag agctttctgc cactgctcag gaaataatta    13560

aaagccaggc cattgcgacg aagaaaataa tttctgatta ccaccagcag tttagatata    13620

aactgcaaga tttttcagac caactctctg attactatga aaaatttatt gctgaatcca    13680

aaagattgat tgacctgtcc attcaaaact accacacatt tctgatatac atcacggagt    13740

tactgaaaaa gctgcaatca accacagtca tgaaccccta catgaagctt gctccaggag    13800

aacttactat catcctctaa ttttttaaaa gaaatcttca tttattcttc ttttccaatt    13860

gaactttcac atagcacaga aaaaattcaa actgcctata ttgataaaac catacagtga    13920

gccagccttg cagtaggcag tagactataa gcagaagcac atatgaactg gacctgcacc    13980

aaagctggca ccagggctcg gaaggtctct gaactcagaa ggatggcatt ttttgcaagt    14040

taaagaaaat caggatctga gttattttgc taaacttggg ggaggaggaa caaataaatg    14100

gagtctttat tgtgtatcat a                                              14121


