throbber
Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 1
`
`Circulating BDNF in Women With and Without Endometriosis
`
`2500
`
`P = 0.001
`
`2000
`
`(ngmL)
`
`BDNF
`
`1 500
`
`1 000
`
`500
`
`Control
`
`Case
`
`N=25
`
`N=41
`
`1/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 2
`
`Circulating BDNF in Women With and Without Endometriosis
`
`by Stage of Disease
`
`*
`
`P = 0.001
`
`2500
`
`2000
`
`1500
`
`1000
`
`500
`
`
`
`BDNF(pglmL)
`
`Control
`
`Stage 1&2
`
`Stage 3&4
`
`N : 25
`
`N = 6
`
`N = 35
`
`2/2 1
`
`REPLACEMENT
`
`

`

`
`
`
`
`PlasmaBDNF(pg/mL)
`
`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 3
`
`Plasma BDNF in Cases
`
`1600
`
`1400
`
`1200
`
`1000
`
`800
`
`600
`
`400
`
`200
`
`
`
`Me nses
`
`Follicular
`
`Luteal
`
`3/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 4
`
`Effect of Treatment on Circulating BDNF concentrations
`
`in Women With and Without Endometriosis
`
`*
`
`*
`
`P = <o.oo1
`
`
`
`BDNF(pglmL)
`
`
`
`Control
`
`Untreated
`
`Treated
`
`N = 25
`
`N = 41
`
`N = 17
`
`4/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 5
`
`Relationship between Circulating BDNF Concentrations and Pain
`
`in Women with Untreated Endometriosis
`
`N=40
`2
`
`R = 0.0115
`
`0
`
`.
`
`P = 0.510
`
`. 5
`
`/2 1
`
`REPLACEMENT
`
`2500
`
`2000
`
`1500
`
`1000
`
`500
`
`
`
`BDNF(pg/mL)
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 6
`
`Figure iii “wad at 31 23.313
`
`
`
`
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`
`BBB? F miner
`
`Mature EDR
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`
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`
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`
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`
`3}
`
`Ntrkl Variants: ,
`
`“flaw
`
`
`
`6/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figu re 7
`
`With findemetfimis
`Wittxmt Emfiametfimig
`
`
`5
`
`if:
`
`7/2 1
`
`REPLACEMENT
`
`3
`
`3;
`
`3
`
`:3
`
`£3”
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`
`
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`323%?
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`
`8/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 9
`
`
`
`
`1 AVDMSGGTVT VLEKVPVSKG QLKQYFYETK CNPMGYTKEG CRGIDKRHWN SQCRTTQSYV
`
`61 RALTMDSKKR IG (SEQ ID NO:1)
`
`
`
`
`1 AVDMSGGTVT VLEKVPVSKG QLKQYFYETK CNPMGYTKEG CRGIDKRHWN SQCRTTQSYV
`
`61 RALTMDSKKR IG (SEQ ID NO:1)
`
`
`
`
`1 AVDMSGGTVT VLEKVPVSKG QLKQYFYETK CNPMGYTKEG CRGIDKRHWN SQCRTTQSYV
`
`61 RALTMDSKKR IG (SEQ ID NO:1)
`
`1
`
`
`1 SITLSCSVAG DPVPNMYWDV GNLVSKHMNE TSHTQGSLRI TNISSDDSGK QISCVAENLV
`
`
`61 GEDQDSVNLT (SEQ ID NO:2)
`
` L‘
`
`1 KSVTLSCSVG GDPLPTLYWD VGNLVSKHMN ETSHTQGSLR ITNISSDDSG KQISCVAENL
`
`
`61 VGEDQDSVNL T
`(SEQ ID NO:3)
`
`1
`
`
`1 SVTISCSVGG DPLPTLYWDV GNLVSKHMNE TSHTQGSLRI TNISSDDSGK QISCVAENLV
`
`
`61 GEDQDSVNLT (SEQ ID NO:4)
`
`9/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 10
`
`agtccttgaa aaggtccctg tatcaaaagg
`ngcaatccc a
`:ggg:taca caaaagaagg
`
`:cccag:gc cgaaCZaccc agtcgtacgt
`
`(SEQ I
`attggc:g
`
`
`
` D NO:5)
`
`c a
`
`agtcctagag aaagtcccgg tatccaaagg
`:gZaatccc atggthaca ccaaggaagg
`
`
`:cgcaatgc cgaaCZaccc aatcgtatgt
`at
`
`3Q ID NO:6)
`:gg (S
`
`gc a
`
`
`
`agtcctggag aaagtcccgg tatcaaaagg
`g:g:aatccc a
`:ggg:taca cgaaggaagg
`
`:cgcaa:gc cgaaCZaccc aatcgtatgt
`
`at
`:ggc:g (SEQ I
`
`
`
` D NO:7)
`
`
`
`c a
`
`61
`121
`181
`
`tgcagtggac
`ccaactgaag
`ctgcaggggc
`gcgggccctt
`
`atgtcgggcg
`caatacttct
`
`atagacaaaa
`accatggata
`
`ggacggtcac
`acgagaccaa
`ggcattggaa
`gcaaaaagag
`
`61
`121
`181
`
`tgcagtggac
`ccaactgaag
`ctgcaggggc
`tcgggccctt
`
`atgtctggcg
`cagtatttct
`atagacaaaa
`actatggata
`
`ggacggtcac
`acgagaccaa
`ggcactggaa
`gcaaaaagag
`
`61
`121
`181
`
`tgcagtggac
`ccaactgaag
`ctgcaggggc
`tcgggccctt
`
`atgtccggtg
`caatatttct
`
`atagacaaaa
`actatggata
`
`ggacggtcac
`acgagaccaa
`ggcactggaa
`gcaaaaagag
`
`61
`121
`181
`
`gtctatcaca
`tgg:aacc:g
`
`
`aac:aaca::
`
`aggagaaga:
`
`ttatcctgta
`gtt:ccaaac
`
`tca:ccga:g
`
`caagattc:g
`
`gtgtggcagg
`atatgaatga
`acagtgggaa
`tcaacctcac
`
`tgatccggtt cctaatatgt attgggatgt
`aacaagccac acacagggct
`ccttaagga
`aaaatcttg
`gcagatctct tgtgtggcgg
`
`(SEQ ID NO:8)
`
`tatccaaagg
`ccaaggaagg
`aatcgtatgt
`
`agtcctagag aaagtcccgg
`:gtaatccc atggthaca
`
`
`:cgcaatgc cgaactaccc
`(S
`3Q ID NO:6)
`attgg
`
`gc a
`
`ggacggtcac
`acgagaccaa
`ggcactggaa
`gcaaaaagag
`
`tgcagtggac
`ccaactgaag
`ctgcaggggc
`tcgggccctt
`
`atgtctggcg
`cagtatttct
`atagacaaaa
`actatggata
`
`61
`121
`181
`
`61
`121
`181
`
`tgcagtggac
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`tcgggccctt
`
`atgtccggtg
`caatatttct
`
`atagacaaaa
`actatggata
`
`ggacggtcac
`acgagaccaa
`ggcactggaa
`gcaaaaagag
`
`agtcctggag aaagtcccgg
`:taca
`ngtaatccc aZggg
`
`c:cgcaatgc cgaac
`aattggctg (SEQ I
`
`tatcaaaagg
`cgaaggaagg
`:accc aatcgtatgt
`
` D NO:7)
`
`
`
`10/21
`
`REPLACEMENT
`
`

`

`
`
`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`530%._33ggggE%\\\x23§w\\82m:8u(1&5Em88
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`
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`
`('le5d) =INCIS
`
`11/21
`
`REPLACEMENT
`
`
`
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 12
`
`6““ ‘Q :2 :
`
`ZAG <= 91.58
`Class Cases %
`.1
`m1
`izw'
`
`$3.4
`é;
`w=95.oo
`N=95
`
`m
`
`i
`
`5
`
`ZAG <— 91.58
`
`ZAG > 91.58
`
`
`
`_GLYCODELIN <= 3919;
`_Class Cases %
`5
`
`1
`
`57.1
`40
`W=70.00
`N=70
`
`:
`
`1
`
`Class Cases % ;
`:1 :\
`3
`K"
`\4‘
`=
`103.13
`2‘5
`W=25.00
`N=25
`
`
`GLYCODELIN <= 39.19
`
`GLYCODELIN > 39.19
`
`Node 4
`Class “ 1
`
`5
`
`_BDNF <= 221.51
`Class Cases %
`:1
`‘5'? a
`15‘
`"(‘52
`W=21.00
`
`1
`
`
`
`
`BDNF <=2150.13
`;...................a.................
`
`BDNF> 2150.13
`.....................................‘
`R
`
`BDNF <— 221.51
`
`BDNF > 221.51
`:ua
`
`-‘
`
`\.
`
`§Class Cases %
`
`
`
`Class Cases %
`
`1
`
`
`
`1
`-‘
`35.9%
`106.0
`15
`1C
`
`
`W=10.00
`N=1O
`
`
`1
`
`
`Class : “:
`:
`~Class Cases %
`
`4f)
`
`1 2/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 13
`
`Node 1
`(3:355 =1
`_ZAG <= 91.53
`Class Cases %
`..\\x.‘
`t.
`65
`
`ZAG <_ 91.53
`
`Node 2
`Class; == 1
`G.LYCODELIN <= 39.19
`
`=
`
`Class Cases %
`
`ZAG > 91.53
`
`:
`
`Terminal
`Node 4
`Glass = 1
`
`;,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
`
`§C|ass Cases %
`x:
`\
`:\
`n.
`:‘g :1
`
`1000
`25
`1
`‘ W: 25.00
`N = 25
`
`
`
`
`
`lssssssssss ’11111111111111111111111111111(”away/”1111111111
`
`
`GLYCODELIN <= 39.19
`
`Node 3
`3;“ x a M \
`\.,~:c:3§:: " ‘v
`
`B_DNF <= 953.90
`Class Cases %
`{3
`,t‘
`5?} (~
`1
`24
`49.0
`W= 49.00
`N = 49
`
`i.....................
`
`BDNF <— 953.90
`
`BDNF > 953.90
`
`1.\““““““““““““““““““
`
`
`1 3/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 14
`
`
`1 m‘c111t‘gv a1vcgvpamd ipqtkque‘ pkapIrvhit SI‘ptpednl eivlhrwenn
`
`
`
`61 scvekknge ktenpkkfki nytvaneat; ldtdydnflf ICqutttpi qsmmcqylar
`
`
`(SEQ ID NO: 13)
`191 v‘veddeimq gfirafrpIp rh1wy11d1k qmeepcrf
`
`
`
`
`
`1 m1c“1:1gv a‘vcgvpamd ipqtkqdle; pklagtwhsm amatnnis‘m at‘kapIrvh
`
`
`
`
`
`
`61 its-‘pred n1eiv1hrwe nnscvekkv; gektenpkkf kinytvanea tILdtdydnf
`121 1f1c1thtt piqsmmcqyl arvlveddei mqgfirafrp lprhlnyLd lkqmeepcrf
`
`(SEQ ID NO: 14)
`
`
`
`1 mlcllltlgv alvcgvpamd ipqtkqdlel pklagtwhsm amatnnislm atlkaplrvh
`61 i:sl;ptped nleivlhrwe nnscvekkvl gektenpkkf kinytvanea tlldtdydnf
`
`121 1f1c1thtt piqsmmcqyl arvlveddei mqgfirafrp lprhlwylld lkqmeepcrf
`(SEQ ID NO: 15)
`
`
`
`1 4/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 14 cont’d
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
`
`
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`
`
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`
`12“
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`18“
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`24“
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`
`:caac:a:ac
`30“
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`
`36“
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`
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`42“
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`54“
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`60“
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`
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`
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`
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`24“
`30“
`36“
`42“
`48“
`54“
`60“
`66“
`72“
`78“
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`
`
`
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`
`84“
`
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`24“
`30“
`36“
`42“
`48“
`54“
`60“
`66“
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`
`
`
`
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`
`:ccctggggg
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`
`
`
`
`
` 1|1|1|
`
`gctcagagcc
`:gg:ctgtgg
`agt:ggcagg
`cac:gaaggc
`:ggagatcg:
`agaagac:ga
`
`:gc:cga:ac
`:ccagagca:
`agggat2ca:
`aacaga:gga
`cacctccgcc
`tcctCCchc
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`acccacagcc
`:gtcccggcc
`gacctggcac
`ccc:ctgagg
`:ctgcacaga
`gaa:ccaaag
`:gac:acgac
`
`ga:g:gccag
`cagggct:tc
`agagccg:gc
`:ccaggaaga
`CZttcaaaga
`
`:chthch
`ggcagaggtt
`18)
`
`
`
`
`
`gcagccatgc
`a:ggaca:cc
`:cca:ggcca
`g:ccaca:ca
`:gggagaaca
`aag::caaga
`aa:::cc:gt
`
`
` :acc:ggcca
`
`
`
`
`aggcccc:gc
`cg:::c:agg
`
`ccagac:ccc
`a:aaccacag
`acacc:gcac
`
`aZtaaZaaac
`
`
`
`15/21
`
`REPLACEMENT
`
`tgtgcctcct
`cccagaccaa
`:ggcgaccaa
`cctcactgt:
`acagc:g:g:
`
`:caac:a:ac
`:tc:c:gcc:
`
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`:gagc:cc:g
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`
`
`
`
`
`
`
`ctcagaagac
`cacggcca:g
`ccttggagca
`
`
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 15
`
`1 mvrmvpvlls lllllgpavp qenngrysl tyiytglskh vedvpafqal gslndqufr
`karedifmet
`61 ynskdrksqp mglquvegm edwkquqlq
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`
`3Q ID NO:
`19)
`
`(S
`
`
`
`A)
`
`B)
`
`1 ccattggcct gtagattcac
`61
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`cagaaccc:c
`
`121
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`181
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`
`
`241
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`30“
`cca:gggac
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`361
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`gaggaca:c
`421
`:c:cacg:a
`acagtaacgg
`481
`gcagcggagc
`:ctggaaa
`541
`aaa:cccagc
`ggg:cccc
`60“
`acgtgcag
`cagaaccagt
`661
`:gcggaaata
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`721
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`781
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`
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`1261
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`
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`
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`
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`
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`
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`SEQ ID NO:
`
`C)
`
`1 mvpvllslpl llgpaquet gsyyltflyt glsrpskgfp rfqataflnd qaffhynsns
`61
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`301
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`3Q ID NO: 21)
`
`16/21
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`D)
`
`
`
`ataggacaag
`tctc:gcc:g
`tgggccac:g
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`
`Figure 15 cont’d
`1 tttcctgtgt agactgttct cccgggcact accgtagcaa tggtgcctgt cctgctgtcc
`61
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`121
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`241
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`301
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`361
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`481
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`541
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`gaggaggagt
`gctgaagagg
`601
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`tacctgaact
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`661
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`721
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`781
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`841
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`961
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`1081
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`
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`
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`
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`
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`
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`
`:a :a
`
`22)
`
`1 7/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 16
`
`
`+ BDNF
`
`1)
`
`e)
`
`
`[Fe(CN{6L—m— [Fe(CN>e]4-w-
`-BDNF
`
`
`\
`\\
`Vt
`6‘
`
`
`$\‘§‘\
`< MW
`
` '
`
`1 8/2 1
`
`REPLACEMENT
`
`% P
`
`otential / V
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 17
`
` 2
`
`a.»
`
`Electrade:
`
`1 9/2 1
`
`REPLACEMENT
`
`
`
`
`
`CurrentChange(‘34:)
`
`

`

`
`
`
`
`PercentageDifference(%)
`
`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 18
`
`'30
`
`(33
`
`S8
`
`4%
`
`3G
`
`20
`
`{3
`
`
`
`[BDNF](ng/mL)
`
`20/2 1
`
`REPLACEMENT
`
`

`

`Atty. Docket No. GWLG-017US-CIP
`
`USSN 15/632,497
`
`Figure 19
`
`1'0 ng/mL
`
`
`
`Praise
`
`----------- Positive Control
`
`
`
`8.0x10E-5 ,
`4
`\ 6.0x10E-5 7
`
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`
`2.0x10E-5 7
`
`0.0
`
`0.0
`
`0.2
`
`0.4
`
`0.6
`
`Potential / V
`
`0.25 ng/mL
`
`6.0x10E-5
`
`4
`: 4.0x10E-5

`
`D Z'OXIOE'S
`
`,"
`
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`
`
`
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`aE g
`
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`D
`
`2.0 ng/mL
`
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`4.0x10E-5
`
`2.0x10E-5
`
`
`
`Current/A
`
`0.0
`
`0.2
`
`0.4
`
`0.6
`
`Potential / V
`
`0'0
`
`0.2
`
`0,4
`
`0.6
`
`Potential / V
`
`21/21
`
`REPLACEMENT
`
`

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