JP 2013-508739 A 2013.3.7 10 (57)【要約】 本発明は、試料
Contents
1. JP 2013 508739 2013 3 7 16 1 12. 00000000000 00000000000 UU t golintunabH 0000 nna uu uu Ul vere T NE a SUE RSEN a DO0000000000 Ul Ul 00000000000 Hod Od Hod 000000000
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6. NS E S AES 1 1 00000000000 1 EE E E a na ee Em 1 00000000000 10 20 30 40 50 JP 2013 508739 2013 3 7 13 10 a
7. 10 1 1 1 20 F p nee ENS e MATS ENDO 30 vi di ng the ntegrati on from step c and d LL 0000 Od 0000000 00000000000 40 substrate 1 a DD U a panphl et of instructi ons 50 15 JP 2013 508739 2013 3 7 bridging HHHHHHHHHHHHHHHHHHHHHHH
8. 10 20 30 40 50 31 JP 2013 508739 2013 3 7 ri OO Q 10 20 30 40 50 JP 2013 508739 2013 3 7 32 10
9. 100 1000 cachexi a 1000 a CO shock transplant rejection 100 10000 qa Ud CO count er act Sea EN ros NES ER E Q amp amp ut utu tr iggerDOO0O00000000000000000000000000000000elici tati on 10000000000000000000 a 0000000000000 1 d E hypersensitivereaction m JP 2013 508739 2013 3 7 11 1000
10. 1 1000 1000 10 20 30 40 50 55 JP 2013 508739 2013 3 7 61 uu T amp MER 10 20 30
11. 1 20 30 40 heaver 50 stan l a 1 D
12. SE HPLC HACA HPLC 8 2 8 1 99 12 12 100 1 69ug mL HPLC 0 1 9 IFX IFX HACA n HACA HPLC 5 0 NAA NZA NZA 117 24 20 5 33 28 2 9 9 m I FX HACA I F X SE HPL C
13. 000000 0 0 E 0000000000 1 a 10 20 30 40 50 2013 508739 LJ G
14. 1 30 40 50 l Phenomenex 1 54 JP 2013 508739 A 2013
15. dw 3 2 onan x Cent ocor P rc nn S Abbott Laboratories Weth Pharnaceuticals 00 00000000 1000 osh Novartis Found Synp 263 193 205 2004 0 anti cell adhesi on l oag 1000000 El an Pharmaceuticals Bio gen dec 1000 000 um Pharmaceuticals 10 00 onocl onal anti body D PDL 8 1 100000000 000 Cent ocor 10000000000000 0000 100000000 PDL BioPharna Roche HHHHHHHHHHHHHHHHHHHHHHHHH NovartisH 0 directed 8 000000000 00000060 prim 1
16. LJ 10 20 30 40 50 JP 2013 508739 2013 3 7 4 1 1 1 10
17. oa L3 L3 di sposed 100000000 JP 2013 508739 A 2013 3 7
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20. 1000000 1000000 C difficileg 10 OO OO 0 revers 20 al uut 36 JP 2013 508739 2013 3 7 Synagis Med Immune tt RSV HIV 1 MAb Polymun Scientific HIV CCR5 MAb Hunan Genome HIV Cytolin 008 MAb NMO1 PRO 140 TNX ABthrax raxibacumab Anthim ETI 204 Sciences SRD Pharmaceuticals HIV Progenics HIV
21. 25 JP 2013 508739 A 2013 3 7 dard ga ac0000000000000 ME uu 1000000000000000 D p D detecting the presence or evel labeled complex HHHHHHHHH Ms ve nn des E 00 0 0
22. SGN 33 SGN 40 sibroturtunab Seattle Genetics Seattle Genetics Life Science Pharmaceuticals AML CLL 8 2362717 2 Tarvacin Peregrine Pharmaceuticals Pfizer TNX 650 Tanox Zevalin Biogen MLN 1202 Millennium Pharmaceuticals Alexion Pharmaceuticals
23. 20 30 40 50 JP 2013 508739 2013 3 7 26 10 1 20 30 Q 40 50
24. nul ti val ency 50 JP 2013 508739 A 2013 3 7
25. oot 10 20 30 40 50 JP 2013 508739 A 2013 3 7 66 10 u 000 Inna 0 0 1 1 looo lh 0 20 30 40 0 0 0 0 0 0 0 50 1 l 0
26. 67 JP 2013 508739 2013 3 7 i E NN T aar B oo UU 0 0 0 Oooo uu 1 0000000 artifa ILI 10 20 30 40 50 JP
27. JP 2013 508739 A 2013 3 7 1000000 0 0 D pre devel oped 0 1000000 100000000000000000 1000000 100000000000000000 secondar
28. 10 20 30 40 50 JP 2013 508739 A 2013 3 7 63 2 q 5 Q E Ei L3 Ex CI CI ol 3 3 ol O 1771 um E a m l 1 41 x
29. 10 20 30 40 50 JP 2013 508739 A 2013 3 7 61 1000 l 1000 10 20 D 1 D 1 a 30 40 50 loon l H
30. 10 20 30 40 50 46 JP 2013 508739 A 2013 3 7
31. 22 JP 2013 508739 A 2013 3 7 1000000000000 uu 00000000000 1 D Bul 100 Hod 100000 uu HO O00000 uu 1 0000000000000 uu Dansyl 000 000 5 i odoacetani da fl uoroscei n 211 100 Lucifer ow
32. nnnnnnnnnn an EDI annnnnn nnnnnonnnnnnn 0000 Od 00000 10000 transdernal Intraventr 11 DD c Hood 00000 20 30 40 50 44 JP 2013 508739 A 2013 3 7 10 REM NGTON S PHARMACEU D Mack Publishing Co Easton PA 1990 0000000 100000000000000 tissue permeati on enhancer 100000000000000 REM NGTON S PHARMACEUTI CAL SC
33. NSCLC AML CAT 3888 Cambridge Antibody Technology MAb CNTO 328 Centocor tt 00188 Peregrine Pharmaceuticals Boehringer Ingelheim Pharmaceuticals CP 751 871 Pfizer 05 1008 Daiichi Sankyo Sankyo BrevaRex Sankyo Pharma Development ViRexx Amgen Kyowa Hakko USA ecromex imab EMD 273063 EMD Lexigen tt SCLC Erbitux Bristol Myers Squibb 4 palicreatic
34. 1000 HHH 20 30 cheni cal 5 40 50 deposi t JP 2013 508739 A 2013 3 7 33 1 1000 10000 1000
35. MEDI 528 Med Immune 4 TL 9 MAb GlaxoSmithKline TL5 MAb Rsch Xolair Genentech Novartis Pharmaceuticals Raptiva Genentech 2825 CNT01275 Centocor Humira Abbott Laboratories Br RE TRX 4 TolerRx 10 20 30 40 45 JP 2013 508739 A 2013 3 7 OKT 3 Ortho Biotech CD3 Simulect Novartis Pharmaceuticals Ze
36. MDX 070 Medarex tt Bi IZ ARES MDX 214 Medarex MEDI 507 Med Immune TT MEDI 522 Med Immune Med Immune MORAb 003 Morphotek RE MORAb 009 neuradiab Bradmer Pharmaceuticals Morphotek CD20 R1594 Omnitarg YM Biosciences tt Genentech Biogen Idec tt Roche Genentech
37. DE a E nnnnmn m a 1000000000000 1000000000000 00000000000 00000000000 10 20 30 40 50 3 JP 2013 508739 2013 3 7
38. 10 20 30 40 50 8 JP 2013 508739 A 2013 3 7 um HHHHHHHH 1 1 10000 MAE 00000000 1000000000000 00000 1000000000000 10000 1100000000000 10000 1000000000000 00000 e HHHHHHHHHHH
39. ti mi t 64 2013 508739 2013 3 7
40. JP 2013 508739 2013 3 7 52 CN m st 2 da gt pe s J ss x c lt e Oo Cv 3I d RS Ea r3 st n 5 7
41. 20 fluors abel i ng 30 40 Hoechst 1 DU 50 li ssam ne JP 2013 508739 A 2013 3 7 24 10
42. 17 JP 2013 508739 A 2013 3 7 100000000000 y m 5 an ad 00 Ha Q a 6 00 10 D 1 engi neered 10000000000 D 1000000 1091 11 1 1 a 10000 10 20 30 40 50 JP 2013 508739 2013 3 7 18
43. 1000 10 1 10 1000 1 20 30 100000 1000 1000 l 40 100000
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45. 20 1 30 40 50 14 JP 2013 508739 2013 3 7
46. 1 1 1 functi onal d HHHHHHHHHH 10 20 30 40 50 10 JP 2013 508739 2013 3 7
47. HuMax CD20 Gemnab CLL HuMax EGFr Genmab 10 20 30 40 40 JP 2013 508739 A 2013 3 7 huN901 DM1 NDX M195 ImmunoGen Bristol Myers Squibb Medarex Actinium ft SCLC MCX 010 DTIC MDX 010 disomotide overmotide MDX 1379 AML 213 Pharmaceuticals M200 volocixirnab PDL BioPharma Biogen Idec tt MAb HeFi 1 MDX 060 Medarex tt
48. 1000 49 JP 2013 508739 2013 3 7 Rutgeerts N Engl Med 348 601 608 2003 1000000000 if et al Clinical Utility of Measuring Infliximab and Human Anti Chi meri ti body Levels in Patients wth Infl amatory Bowel Disease Digestive Disease Wek May 30 J une 3 2009 Chicago IL
49. 10 20 30 40 1 50 30 JP 2013 508739 A 2013 3 7 H u
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51. JP 2013 508739 2013 3 7 70 10 1000 20 30 71 0000 TNF Alexa 7 4 Humira TNF Alexa 7 I HUmira Humira TNF Alexae47 1ug TNF Alexa 1ug Humira JP 2013 508739 2013 3 7 7 Alexaa47 0000 A B TNF Alexa647 Humira 1 TNF Alexa647 Humira mAU s 0
52. AMG 706 Amgen 6GIST AMG 706 Arngen tt 61ST KARE 0023 MAb Biogen Idec CLL CD80 MAb Biogen Idec tt JER 2222 Viventia Biotech Biogen Idec tt MAb PEM MAb Somanta Pharmaceuticals Tac Fv PE38 10 20 30 40 Avastin AVE 9633 loaded CD33 MAb 39 Genentech sanofi aventis Peregrine Pharmaceuticals JP 2013 508739 2013 3 7
53. JP 2013 508739 2013 3 7 27 10 20 30 40 50 n JP 2013 508739 2013 3 7 28 1 1000 l l
54. Procter amp Gamble Pharmaceuticals MacroGenics CD3 MAb 1 OKT3 2j 7 x 1 Johnson Johnson tf 1 Pharmaceutical Research amp Development TRX 4 TolerRx 1 CD3 Remicade Centocor ABT 874 Abbott Laboratories CN 1275 Humira MDX 066 CDA 1 Centocor tL Abbott Laboratories Medarex Crolin s disease autoinunurle J 288 610 651 6000 111 847 9361189 10 20 30 40 MDX 1100 42 Millennium Pharmaceuticals tt JP 2013 508739 2013 3 7 Nuvion Tysarb
55. eor TE Biya B E cus EON _ HET NIHHHHHHHHHHHHHHHHH O Re E NUS VN 1 Hod 00000000000 variable regions dtu topographicalH 10000000000 00000000 Ser G n Val Leu Phe Lys Gl y Thr lleQ 100000 Tyr n Thr Lys Val Asn Leu Leu Ser Al a e Lys Ser Pr o Cys Gl n Ar g Gl u Thr Pro G u n Gl y Cys Pro Ser Thr Hi s Val Leu Leu Thr Hi s u Haugl and The Handbook A Gui de to Fluorescent Probes and La bel i ng Technol ogi es 10t Edition Molecular probes Inc 2005 HHHHHHHHHHHHHH 0000000000000 I I I rz
56. CR OV ProstaScint CYTOGEN Rituxan Genentech Biogen Idec t Verluma noletumomab Zevalin DuPont Pharmaceuticals IDFC Pharmaceuticals 1311 huA33 Life Science Pharmaceuticals 100963 GPC Biotech 88 UNE AGS PSCA MAb Agensys Merck AMG 102 Amgen J AMG 479 Amgen AMG 623 Amgen CLL AMG 655 Amgen
57. NSCLC OvaRex ViRexx PAM 4 Merck rlluMAb EGFr Proleukin Chiron 4 PSMA Progenics Pharmaceuticals 10 20 30 40 41 JP 2013 508739 A 2013 3 7 R1550 RadioTheraCIM Roche BioSciences RAV 12 Raven Biotechnologies Renearex Wilex Miulich tt 6250 Rituxan Genentech CLL Biogen Idec ft SGN30 Seattle Genetics MAb
58. n JP 2013 508739 A 2013 3 7 69 10 20 30 40 50 l
59. 1000 preval ence DU 1 1 38 2 ta 1 50 1 D D D warrant ed n 000 nti TNF al pha agents autoi mune di seases 3 82 9 2010 59 JP 2013 508739 2013 3 7 10000000000000000 Bendtzen et al Individual medicine in in flammatory bowel disease monitoring bi oavailability pharmacoki netics and i mun ogenicity of anti tunour necrosis factor alpha anti bodies Scand Gastroente rol 44 7 774 81 2009 Afif et al Clinical utility of measuring i nfli xi mab and human anti chi meri c anti body concentrations in patients wth nfl amratory b owel disease Am J Gastroenterol 1
60. 61 262 877 2 21 11 19 2009 11 19 3 OS 61 324 635 32 22 4 15 2010 4 15 33 05 54 TNF 57 1 Preparation of Alexa5 labeled Remicade 2 Incubation with patient serum HAGA to form the complex 3 Quantification of the complex by SE HPLC 4 Assay works In the presence of remicade il 21 E Alexa Remicade Pow M v E b SE HPLC Analysis 1 e j a E m HACA Ooo OOO OOO OOO OOO OOO ET rr OOO OOO OOO OOOOH OOOO OOOO MW 150kD MW 150kD MW 300kD 2 JP 2013 508739 A 2013 3 7
61. IMMU 106 Immunomedics tt hCD20 LymphoStat B Human Genome SLE Sciences MEDI 545 Medarex RE MDX 1103 MedImmune tt MLN 1202 Millennium Pharmaceuticals Genentech CD20 R1594 0KT3 1 Rituxan Biogen Idec 4 Roche Johnson amp Johnson Pharmaceutical Research amp Development Genentech Biogen Idec 4 2 15888 DMARD Pa SLE
62. 50 Propri etary JP 2013 508739 A 2013 3 7 58 10 20 30 10000 40 munogeni city of xg Rev Allergy Inmunol Ai kawa et a Clin 1000
63. CO c c ooo oo lt a 4 ot c o I I 21 JP 2013 508739 2013 3 7 MISES m s E PE WEN ERE EAE A EEE annon za a 00 a 00 10000
64. 72 72 40085 AA4 EEO1 GDl 4 86 AAO1 AAO2 CBO9 7833 2835 2837 20 2402 2466 27496 287 211 2856
65. 1000000 1000000000000 H 1000000000000 1000000000000 1 11111 111 1 1 1 HHHHHHHHHHHH 1100000000000 0 1 10 20 30 40 50 9 JP 2013 508739 2013 3 7
66. 5897 16 18 min 0 3 4 6 8 0 2 CH mi 7 96 42 uuu SL03246013 HAHA L JL iho ic ts ERN 9 9 0 52 Humira 16 9 ug mL H i e i 58 sj 4 Hh T E 3 8 SP 8 14 H e ig i vis i 0 ee m NN 10 12 14 16 18 min We A lia 5 Us nea TMNT 9 10 421 8 HAHA i 250 Humira i i 1 c i H L 50 8 S c i gt UO A 0 2 4 6 8 0 1 14 8 cm oy 00000 2013508739000001 xni 85 2013 508739 2013 3 7 INTERNATIONAL SEARCH REPORT International application No PCT US2010 054125 CLASSIFICATION OF SUBJECT MATTER INV 6G01N33 50 G01N33 564 ADD Anoording to Intemational Patent Classifioation IPC or to both national classification and IPC B FIELDS SEARCHED Minimum documentation searched classification eystem followed by classification symbole GO1N Documentation searched other than minimum documentation to the extent that such documents are included in the fielde searched Electronic data
67. 2848 ELISA za i HACA Remicade HACA Remicade 192275 Soo Remicade 00000 4 NHS 4 NHS 37 Sng IFX FI a i 25 b x 7 CUR 24 mn 0 596 HPS 3 596 NHS 37 5ng IFX FI 2 HPS 4 236 NHS 37 Sng eere gem i 5 125 d 20 IFX FI A i5 C2 C1 4 i 1519 21455 C1 77 JP 2013 508739 A 2013 3 7 b 1 11 4 IFX FI a 21 IFX FI 70 IFX FI D wi S 5 aS 9 S S N 4 NHS 4 NHS 100ng TNFo FI 23 995 2 17 TNFa FI TNFa FI 8 TNFa FI 24 007 MO 8 r 23 971 24 78 JP 2013 508739 A 2013 3 7 110 s 7 TNF FI D 100 TNF F 6 6 4 4 R 2 0 15 10 05 00 05 10 15 20 15 10 05 00 05 10 15 Log IFX ug ml Log IFX ug ml IFX IFX HACA IFX 0 3 a 3i 0 30 negr 6
68. gt N C o 3 k a ea 3 gt 5 1 C 4 C c o C D 4 SeS 5 8 T ES C c o o Oo o i CI 4 C o B C 1 5 i al rm i m 3 N 4 3 Q ea i 4 JP 2013 508739 A 2013 3 7 53 10 20 1 81
69. Pharmaceuticals 355 Tanox MAb HIV 355 Tanox MAb HIV Please 11 Human Genome RE Sciences ad hsp90 MAb NeuTec Pharma staph MAb Med Immune Aurexis Inhibitex Peregrine C Pharmaceuticals MDX 1303 Medarex 11 RE Numax PharmAthene Tarvacin XTL 6865 Humira Med Immune tt Peregrine Pharmaceuti Pharmaceuticals tk cals Pharmaceuticals tk XTL Biopharmaceuticals poU Abbott Laboratories tt Remicade Centocor Rituxan Genentech ritiximab Biogen Idec Tysarbi Biogen Idec Multiple scleorisis ART 874 Abbott Laboratories Acte
70. TRX 1 TolerRx tt CD4 cutaneous lupus erythetnatosus ReoPro Centocor Eli Lilly PTCA PTCA Teijin Pharma hemolytic uremic Abbot Laboratories Alexion Pharmaceuticals E Avastin Genentech tt A 2013 3 7 10 20 30 40 Bexxar 38 GlaxoSmithKIine JP 2013 508739 2013 3 7 1131 Campath Berlex Laboratories Genzyme Erbitux Bristol Myers Squibb Medarex Herceptin Genentech HER 2 Mylotarg Wyeth tt OncoScint CYTOGEN
71. 00 05 10 15 20 2 5 3 0 00 0 5 10 15 20 25 3 0 Log Humira ng Log Humira ng mAUs 1 RA TNF Alexa647 Humira 100 mAU s 75 mAUS 9 50 2 0 0 0 5 1 0 1 5 2 0 2 5 3 0 Log Humira ng 72 JP 2013 508739 2013 3 7 0000 lt gt 3 gt 2 gt A HACA co V 0000 1 Alexa 47 Remicade 2 HACA 3 SE HPLC 4 remicade Alexa 7 Remicade SE HPLC wv _ gt 2 3 Alexa647 Remicade MW 150kD MW 150kD MW 300kD 0000 A 1X PBS pH 7 4 0 1 14 16 18 20 22 24 min N 49 677 20 22 24min 2 18 20 me 3 9ng lgG A 6 25ng Remicade N N 9 43 2623 Q0 12 4 16 18 30 2 6 15 6ng IgG 6 25ng Remicade Alexa57 ss 36 6918 10 872 l g 5 9 Nm F laG 6 25 6 Remicade A
72. 1000 100000 10 20 30 l 40 418 1000 nst Di seas 50 000000 a 000 n species 0 Bi otechnol ogy Medi ci nes in Testi ng Promise to Bolster the Arsenal 2006 PhRMA Report el DU 1000 34 JP 2013 508739 2013 3 7
73. l 1000 30 40 50 1000 JP 2013 508739 2013 3 7 20
74. 10000000 100000000000000 D HO m B TEE p m D DU OO 00000000 0000 00000000 z ood ood 2 E 11 11 11 HB LD B H 0 3 S uHHHHHHHHH E aqata _ 0 ood equilibrate 10 20 30 40 50 JP 2013 508739 2013 3 7 51 10 20 ow 30 40 0 50 ser um cont ent
75. 2013 508739 A 2013 3 7 19 JP A 11 2013 508739 P2013 508739A 43 25 3 7 2013 3 61 Int Cl GO7A 30 88 2006 01 GO1N 30 88 J 4CO85 GO1N 30 06 2006 01 GOIN 30 88 201G 4CO86 GOIN 30 66 2006 01 GOIN 30 06 E GOIN 30 04 200 01 GOIN 30 86 E A61K 39 35 2006 01 GOIN 30 04 P 88 2012 536962 P2012 536962 22 22 10 26 2010 10 26 24 6 25 2012 6 25 PCT US2010 054125 W02011 056590 23 5 12 2011 5 12 21 71 599132904 86 85 86 87 87 31 61 255 048 32 33 31 32 33 31 5 5 74 100088155 74 100114270 5 74 100128381 RE 74 100107456 100140453 21 10 26 2009 10 26 05
76. conaulted during the intemational search name of data base and where practical search terms used EPO Internal BIOSIS C DOCUMENTS CONSIDERED TO BE RELEVANT Citation of document with indication where appropriate of the relevant passages Relevant to claim No US 2009 035216 A1 SVENSON MORTEN DK ET 1 84 AL 5 February 2009 2009 02 05 abstract figure 1 paragraph 6 last sentence paragraph 0057 paragraph 0059 paragraph 0082 paragraph 0097 paragraph 0138 examples See patent family annex later dooument published after the international filing date X Further documents are listed the continuation of Box C Special categories of cited documents A document defining the general state of the art whioh is not considered to be of particular relevance E earlier document but published on or after the intemational filing date L document which may throw doubts on priority olaim s or which is cited to establish the publication date of another citation or other special reason ae specified dooument referring to an oral disclosure use exhibition or other means document published prior to the intemational filing date but later than the priority date claimed Date of the actual completion of the intemational search 15 March 2011 Name and mailing address of the ISA European Patent Office 5818 Patentlaan 2 NL 2280 HV Rijswijk Tel 31 70 340 2040 Fax
77. 1 1 1 11 11 1 11 LO MC m m Anthroyl fatty acid 00 00 00000000000 00000000060 10 Merocyanine 0000 00 0000000000 lt nec r1 r1 11 n n n 1 r1 pt hal ocyani nes JP 2013 508739 A 2013 3 7 23 10 1000 1
78. 10 20 30 1000 a H 40 50 1000 1 H H 00000 JP 2013 508739 A 2013 3 7 29 1 H HO
79. 10 E e 109035 lecso 187 4 0 0 5 0 0 Log 7 196 nM 0 5 75 JP 2013 508739 2013 3 7 uuu A 496 B 4 4 2nM Remicade Alexa mAU 8 eS 12 12 S b 08 08 06 06 5 eg E 04 a 04 6 S SN E 02 A 02 ie P 0 T 12 14 16 18 2 22 24min 10 12 14 16 18 20 2 24 min C 4 D 4 4 2nM Remicade Alexa mAU 12 12 4 Ae 1 1 gt 2 05 Dy N oy 08 3 06 06 041 5 9 s 04 5 8 Sx x 02 JE AM 02 5 8 24 min ELISA 4 _ 5807010477 22 77779008 26 me dup SK07110085 _ u 3 16 unes mm we oe 56 Me me 2 59 seems 88 SK08260093 5 me m amp oe 16 20 me me 05 625meRemcade 67 J 3 76 JP 2013 508739 2013 3 7 DIG HACA HACA
80. B je 2 35 Tu 3 NHS 5 25 3769 FI ADL sie 02210 Ab pa F z L 00 2 4 8 8 10 12 1i 16 mi NHS 37 5ng FI ADL 0 0249 Ab 82 JP 2013 508739 2013 3 7 5 2 a 8 tt FI ADL FI BioCyt 0001 001 04 1 10 400 5 F IgG pg ml FLTNF 003ugADL Aer detach 8 0 14 1 00000 C 9 83 JP 2013 508739 2013 3 7 0 75 te FI TNF FI BioCyt 0 00 001 041 1 10 100 pgiml 4 NHS IFX FI 4 NHS 37 5ng IFX FI Wie 9 Ej LU 4 HPC 13996 HPC 237 NHS 37 5ng IPX 16 18 min u 0 44 HPC 3 56 bakeri Leas ej 55 8 5 8 SE f i nr n oe 0 2 4 6 8 10 12 14 16 18 min 0 049 HPC 3 951 NHS 37 5ng IFX FI U 10265 102558 8 BC 17 T 274 10 2 1 16 imn 0 2 4 6 8 10 12 8 16 18 min 84 JP 2013 508739 2013 3 7 00000 4 NHS 37 5ng ADLF ADL B K wa 6 8 E 14 16 18 min 0 2 4 6 8 42 14 16 18 min 0 2 4 6 8 10 i2 14 16 18 min 622 8 lgG1 37 5ng ADL FI F 1861 37 Sng ADL FI 0 yoy 6 8 10 12 14 16 18 min a ADL FI F lgG1 37 5ng ADLFI
81. 31 70 340 3016 Fom PCT ISA 210 second aheet April 2005 or priority date and not in conflict with the application but cited to understand the principle or theory underlying the invention X document of particular relevance the claimed invention oannot be considered novel or cannot be oonsidered to involve an inventive step when the document is taken alone Y document of particular relevance the claimed invention cannot be considered to involve an inventive step when the dooument is combined with one or more other suoh doou mente euch combination being obvious to a person skilled inthe art amp dooument member of the same patent family Date of mailing of the intemational search report 29 03 2011 Authorized officer Luis Alves Dulce page 1 of 2 86 JP 2013 508739 2013 3 7 International application No PCT US2010 054125 Citation of document with indication where appropriate of the relevant passages X BENDTZEN KLAUS ET AL Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab ARTHRITIS amp RHEUMATISM vol 54 no 12 December 2006 2006 12 pages 3782 3789 XP002626408 ISSN 0004 3591 abstract p 3782 Serum testing page 3783 left hand column INTERNATIONAL SEARCH REPORT CHEIFETZ A ET AL MONOCLONAL ANTIBODIES IMMUNOGENICITY AND ASSOCIATED I
82. 40 50 56 JP 2013 508739 2013 3 7 w a nna ER 10 20 30 40 50 JP 2013 508739 A 2013 3 7 57 10 20 30 l 1 40
83. AJ u gt lt AJ D gt lt V2 V10 V14 V2 V10 V14 79 IFX 1 FX 11 HACA HACA 0 350 8 am LDC 0 35 b 0325 G 0 30 9 0 300 0275 1 2020 0 15 0 225 T gt ZS 0 200 0 19 4a i 0175 00 0 150 2 V10 V14 RSJAG 52 583 JMM 2013 508739 2013 3 7 IFX 11 ed gt in uglml n e V10 V14 80 JP 2013 508739 A 2013 3 7 00000 HACA F1 Remicade Fi Remicade F2 TNF a HACA F1 Remicade 2 F2 TNF a B HACA F1 Remicade F1 Remicade F2 TNF c F1 Remicade 81 JP 2013 508739 2013 3 7 uuu HACA F1 Remicade HACA Aun 4 21 F1 Remicade F1 Remicade F2 TNF o 2 s HACA 3 2 2 FLADL FA IC 101428 13 56 25 375ngFLADL 06Tug Ab
84. 000 2900 2006 01 3700 2006 01 0000 3 12 2006 01 0000 3y 2006 01 0000 3700 2006 01 0000 3 00 2006 01 0000 250 2006 01 0000 1902 2006 01 000 2006 01 31 000 61 345 567 32 22 8 170 2010 5 17 33 U5 31 61 351 269 32 22 61 31 2010 6 3 33 U5 31 61 389 672 32 22 100 4 2010 10 4 33 5 31 61 393 581 32 22 100 19 2010 10 15 33 U5 81 ZA MAN 88 JP 2013 508739 2013 3 7 39 395 31 519 29 00 37 00 31 2 31 04 33 00 35 00 25 00 19 02 1 04 AP BWGH KE LR 5 SD SL SZ TZ UG M ZW EX AZ BY KG KZ RJ TJ T EP AL AT BG CH CY CZ OK EE ES FR HJ E IS LT LT LU LV NT NQ PL ROR S SE 9 5 SM TR OX BF QN GQ GWM M SN TD TG AG AL AQ AT BA BB BG BH BR BWBY BZ CH G CN Q QJ CZ IK EM DO EE EG ES Fl GB Q G H GM GI D IL IN IS KG KM KN KP KR KZ LA LG LK LR LS LT LU LY M M ME MG MK W MyMK ME NN NG NO COM PE PG PH PL RS RU SG SD SE SG SK SL M ST SV SY TH TJ TM TN TR TT TZ UG US VG VN 72
85. 00 uu uu 00000000000 1 Ul 1 t Muil ti ple scleorisisH 1000 10000000000 er yt hemat osus 0 Hod juvenile idiop at hriti 10000000000000 00000000000 10 20 30 40 50 35 JP 2013 508739 A 2013 3 7
86. 0000000000000 1 HHHHHHHHHHHHHH 1000000000000 10 20 30 40 50 7 JP 2013 508739 A 2013 3 7 1 UU 1 U 1 1 1 Ul 1 1 1000 1000 1000 1 Ul EN Se ES 1 1 1 O 11 11 E 1 1 1 Ul 1 UU
87. 05 5 1133 9 2010 UU UU UU HHHHHHHHHHHHHHHHHHHHHHH um HHHHHHHHHHHHH um ua E m E HHHHHHHHHHHHHHHHHH HHHHHHHIH HHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHIH HHHHHHHHHHHHHHHHHHHHHHHHHHI
88. 10 20 30 40 50 6 JP 2013 508739 A 2013 3 7 um HHHHHHHH 1000000 000 HHHHHHHHHHHHH ue VE oe 000 1
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92. H HHHHHHHHHHHHHHHHHHHHHHHHHHHHH uu HHHHHHHHHHHHHHHHHHHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHHHHHHHHIH 1000000000000000000000000000 10000000 0000000000000000000 aldehyde fixable 000000000000000 1 IlHHHHHHHHHHH HHHHHHHHHHHHHHHHHHHInvit rogenl HHHHHHHHHHHHHHHHH 1 UU Q 1 1 1 HHHHHHH Oh uu 00 a 0 HHHHHHHH 1 uu HHHHHHHHHHHH 10 20 30 40 50 60 JP 2013 508739 A 2013 3 7 E En n EH E Mp 000000n Mp Nes EOJ D ME z HH
93. HHHHHHHH HHHHHHHHHH HHHHLHHHHHH ADA ADL n ADA ADL ug mL 100 38 62 18 62 0 0 76 37 1 1 00 A DL 1 1 4 51 763 20 69 5 4 3 10 80 39 9 17 80 1 BD W SS S SSS asi DNE DEMOS Bes AEN MS unn 2 o unnm ADA ADL ADL ADA n gmL 100 38 62 18 62 0 761 0 37 1 00 ADL 114 51 63 20 69 10 80 1 O 4ug mL ADL 39 9 7 80 42323949 5206 I BD ah gt HHHHLuH Hi MEE s a na Q j 3 5 e T
94. NFUSION REACTIONS MOUNT SINAI JOURNAL OF MEDICINE JOHN WILEY amp SONS INC NEW YORK NY US vol 72 no 4 1 July 2005 2005 07 01 pages 250 256 XP008059895 ISSN 0027 2507 abstract page 251 left hand column last paragraph right hand column paragraph 1 CANAN AYBAY ET AL Demonstration of specific antibodies against infliximab induced during treatment of a patient with ankylosing spondylitis RHEUMATOLOGY INTERNATIONAL CLINICAL AND EXPERIMENTAL INVESTIGATIONS SPRINGER BERLIN DE vol 26 no 5 1 March 2006 2006 03 01 pages 473 480 XP019335344 ISSN 1437 160X DOI D01 10 1007 500296 005 0085 0 abstract page 475 right hand column paragraph 3 page 476 left hand column paragraph 1 Fom PCT ISA 210 continuation of aecond aheet April 2005 page 2 of 2 87 JP 2013 508739 A 2013 3 7 International application No PCT US2010 054125 Patent document Publication Patent family Publication cited in search report date member s date US 2009035216 Al 05 02 2009 NONE INTERNATIONAL SEARCH REPORT Information on patent family members Forn PCT ISA 210 patent farnily annex April 2005 51 Irt d 31519 200601
95. NSCLC 8 NSCLC J GMK Campath Progenies Pharmaceuticals Berlex Laboratories primacy Herceptin Genentech HER2 HER2 Taxotere HGS ETR1 HGS ETR2 Human Genome Sciences HGS TR2J Human Genome Sciences HuC242 DM4 ImmunoGen NSCLC HuMax CD4 Genmab Serono tt
96. i Soliris PDT BioPharma tt Biogen Idec tt Centocor Alexion Pharmaceuticals lt 1 V PNH RN624 RN1219 Rinat Neuroscience Rinat Neuroscience ABN 912 Novartis Pharmaceuticals COPD ABX 1L8 Amgen 11 GOPD AMG 317 CD25 WMAb Amgen Protein Design Labs Roche
97. lexa fr S amp BIR 188633 22 24 min 24 min 73 125ng v 3c E F IgG 22 Amn 7 8ng eH IgG 6 25ng Remicade Alexa647 8 37 5833 10 12 14 20 22 24min 31 219 IgG 6 25ng Remicade Alexat47 12 FJ 8 m 8 49008 10 12 20 22 24min JP 2013 508739 A 2013 3 7 74 62 5ng Remicade Alexa647 10 12 14 16 18 mAUj 12 14 08 06 04 02 0 10 12 14 62 5ng Remicade Alexa647 7 8ng fi lg JP 2013 508739 2013 3 7 20 108 20 _ 28 min LS e 20 1 min 14 08 0 64 0 44 0 24 8 10 124 14 08 064 04 02 03 10 D S P 17 029 16 2 14 1 0000 A lgG Remicade Alexa647 C m 1718 550 3359 Remicade Alexa647 5 1 00 0 75 0 50 0 25 0 00 0 25 0 50 0 75 1 00 Log 7 196 nM uH 62 5ng Remicade Alexa647 15 6ng lgG 5 Immunocomplex of Remicade Alexa647 e 26 28 mihn 62 5ng Remicade Alexa647 31 25ng tii IgG 02 28 IgG Remicade Alexa647
98. mra Roche AME 527 Applied Molecular AMG 108 Amgen AMG 714 Amgen CD16 MAb CNTO 1275 MacroGenics thrombocytopenic Centocor Horham 10 20 30 40 37 JP 2013 508739 PDL BioPharma CD25 MAb Biogen Idec denosumah Amgen AMG 162 ETI 201 Elusys Therapeutics tt SLE Centocor tt HuMax CD20 Genmab tt Humira Abbott Laboratories HuZAF PDL BioPharma Biogen ldec tt
99. napax Roche Protein Design Labs OKT3 1 Johnson amp Johnson NeutroSpec Palatin Technologies 99m Tc CR 0002 CuraGen Bk Amgen tt BORER AMG 162 GlaxoSmithKIIne anti IL5 MAb Xolair Genentech tt Tanox
100. y response failure catastrophi c all clear0 DO HHHHHHHHHHH 10000000000 HHHHHHHHHH 10000000000 uu HHHHHHHHHHH 1000000 100000000000 00 0100 1000000 100000000000000000 1000000 100000000000000000 10 20 30 40 50 JP 2013 508739 A 2013 3 7 48 100000 10 20 30 40 50
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