                         SEQUENCE LISTING

<110>  ELI LILLY AND COMPANY
 
<120>  COMBINATION THERAPY

<130>  X21936_WO

<150>  62/712,519
<151>  2018-07-31

<160>  13    

<170>  PatentIn version 3.5

<210>  1
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LC of exemplified anti-Tau antibody

<400>  1

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


Glu Arg Ala Thr Leu Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Asn Gln Asn Thr Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala 
        35                  40                  45              


Pro Arg Leu Leu Ile Tyr Lys Val Asp Asn Arg Phe Ser Gly Ile Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
65                  70                  75                  80  


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      


Thr Leu Val Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  2
<211>  442
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HC of exemplified anti-Tau antibody

<400>  2

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


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


Trp Ile Glu Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Glu Ile Leu Pro Gly Ser Asp Ser Ile Lys Tyr Glu Lys Asn Phe 
    50                  55                  60                  


Lys Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Asn Tyr Val Asp Asp Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
        115                 120                 125             


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


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


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 
    210                 215                 220                 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  3
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCDR1 of exemplified anti-Tau antibody

<400>  3

Arg Ser Ser Gln Ser Leu Val His Ser Asn Gln Asn Thr Tyr Leu His 
1               5                   10                  15      


<210>  4
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCDR2 of exemplified anti-Tau antibody

<400>  4

Tyr Lys Val Asp Asn Arg Phe Ser 
1               5               


<210>  5
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCDR3 of exemplified anti-Tau antibody

<400>  5

Ser Gln Ser Thr Leu Val Pro Leu Thr 
1               5                   


<210>  6
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR1 of exemplified anti-Tau antibody

<400>  6

Lys Gly Ser Gly Tyr Thr Phe Ser Asn Tyr Trp Ile Glu 
1               5                   10              


<210>  7
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR2 of exemplified anti-Tau antibody

<400>  7

Glu Ile Leu Pro Gly Ser Asp Ser Ile Lys Tyr Glu Lys Asn Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  8
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCDR3 of exemplified anti-Tau antibody

<400>  8

Ala Arg Arg Gly Asn Tyr Val Asp Asp 
1               5                   


<210>  9
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LCVR of exemplified anti-Tau antibody

<400>  9

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


Glu Arg Ala Thr Leu Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


Asn Gln Asn Thr Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala 
        35                  40                  45              


Pro Arg Leu Leu Ile Tyr Lys Val Asp Asn Arg Phe Ser Gly Ile Pro 
    50                  55                  60                  


Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 
65                  70                  75                  80  


Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      


Thr Leu Val Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


<210>  10
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HCVR of exemplified anti-Tau antibody

<400>  10

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


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


Trp Ile Glu Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Glu Ile Leu Pro Gly Ser Asp Ser Ile Lys Tyr Glu Lys Asn Phe 
    50                  55                  60                  


Lys Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Asn Tyr Val Asp Asp Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  11
<211>  1326
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide Sequence Encoding the Exemplified HC (SEQ ID NO: 2)

<400>  11
gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaagatc       60

tcctgtaagg gttctggcta cacattcagt aactactgga tagagtgggt gcgccagatg      120

cccgggaaag gcctggagtg gatgggggag attttacctg gaagtgatag tattaagtac      180

gaaaagaatt tcaagggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac      240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagaaggggg      300

aactacgtgg acgactgggg ccagggcacc ctggtcaccg tctcctcagc ttctaccaag      360

ggcccatcgg tcttcccgct agcgccctgc tccaggagca cctccgagag cacagccgcc      420

ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc      480

gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc      540

ctcagcagcg tggtgaccgt gccctccagc agcttgggca cgaagaccta cacctgcaac      600

gtagatcaca agcccagcaa caccaaggtg gacaagagag ttgagtccaa atatggtccc      660

ccatgcccac cctgcccagc acctgaggcc gccgggggac catcagtctt cctgttcccc      720

ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg      780

gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg      840

cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc      900

gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc      960

aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga     1020

gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc     1080

ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggaaagcaat     1140

gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc     1200

ttcctctaca gcaggctaac cgtggacaag agcaggtggc aggaggggaa tgtcttctca     1260

tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagagcct ctccctgtct     1320

ctgggt                                                                1326


<210>  12
<211>  657
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide Sequence Encoding the Exemplified LC (SEQ ID NO: 1)

<400>  12
gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc       60

ctctcctgca gatctagtca gagccttgta cacagtaatc agaacaccta tttacattgg      120

taccagcaga aacctggcca ggctcccagg ctcctcatct ataaagttga caaccgattt      180

tctggcatcc cagacaggtt cagtggcagt gggtctggga cagacttcac tctcaccatc      240

agcagactgg agcctgaaga ttttgcagtg tattactgtt ctcaaagtac actggttccg      300

ctcacgttcg gcggagggac caaggtggag atcaaacgga ccgtggctgc accatctgtc      360

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg      420

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa      480

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc      540

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa      600

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgc         657


<210>  13
<211>  441
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino Acid Sequence of Human, Full-Length Tau

<400>  13

Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly 
1               5                   10                  15      


Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His 
            20                  25                  30          


Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu 
        35                  40                  45              


Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser 
    50                  55                  60                  


Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val 
65                  70                  75                  80  


Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu 
                85                  90                  95      


Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro 
            100                 105                 110         


Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val 
        115                 120                 125             


Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly 
    130                 135                 140                 


Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro 
145                 150                 155                 160 


Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro 
                165                 170                 175     


Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly 
            180                 185                 190         


Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser 
        195                 200                 205             


Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys 
    210                 215                 220                 


Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys 
225                 230                 235                 240 


Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val 
                245                 250                 255     


Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly 
            260                 265                 270         


Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln 
        275                 280                 285             


Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly 
    290                 295                 300                 


Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser 
305                 310                 315                 320 


Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln 
                325                 330                 335     


Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser 
            340                 345                 350         


Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn 
        355                 360                 365             


Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala 
    370                 375                 380                 


Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser 
385                 390                 395                 400 


Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser 
                405                 410                 415     


Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val 
            420                 425                 430         


Ser Ala Ser Leu Ala Lys Gln Gly Leu 
        435                 440     


