WO 2012/160678 A 1
Contents
1. GxcR4 GxKGR4 1 GGR5 HIV 1 Rs GXGR4 HIV 1 x4 8 GGR5 GxGR4 HIV 1 R5xX4 1 2 GxGR42. CA BIOSIS MEDLINE WPIDS STN JSTPlus JMEDPlus JST7580 JDreamll c k TANAKA R et al Unique extracellular loop of CXCR4 human enhances immunodeficiency formation and productive infection p 11534 11543 CARNEC X overlapping Anti CXCR4 epitopes differ significantly et al human immunodeficiency virus XI Y XI Y MW CM ORS C tX BL PIS EN TV Do ra re re
3. HIV HIV 1 HIV 2 2 HIV 1 GD4 T HIV 1 GD4 Gp4 ep 4 GD4 LA GD4 GD4 HIV 1 GD4 VVO 2012 160678 2 PCT JP2011 062007
4. GXGR4 GxXGR4 GxGR4 1 2 3 1 2 GxGR4 GXGR4 GxKGR4 VVO 2012 160678 21 PCT JP2011 062007 GxGR4 1 2
5. GxcR4 Gx lt GR4 GxGR4 exc VVO 2012 160678 5 PCT JP2011 062007 001 4 001 5 001 6 CH o SDF 10 8 TAG GGR5 HIV 1 R579 GxGR4 HIV 1 X4 GGR5 GxGR4 HIV 1 R5X4 GxGR4 GXKGR4 GxGR4
6. GXGR4 1 2 3 1 2 1 2 JL Z 1 2 GxGR4 1 2 120 Ant i GXGR4 ECL 182 12G5 3 A80 Ant i GXGR4 ECL 3 CHS 2
7. R5 GxG Anti_GxGR4 ECL 1 amp 2 F C 120 GxGR4 xX4 HB IST SE TCE lt A120 Ri GxGR4 YI X4 X4 Rs
8. A120 PlMe 8_ GD3 GD28 PMG ep1 9 B GD4 T GD8 T G p14 mock PBM G 10 U glml A120 24 ELISA 1 2 1 2 GD14 89 GD4 T GD8 T ept9 B
9. A120 EGL2 G XGR4 X4 exGR4 Rs A120 EGL2 ecRs ER MP 1 0 GGR5 Rs GexG A120 Anti CXCR4 EGL 18251 X4 Rs Alps VVO 2012 160678 20 PCT JP2011 062007 1 2 3 4 5
10. ps_sss1 1101 34 4 8 02009 7 PCT JP2011 062007 C p 1930 1933 A Hiv 0x40 Al 1 5 2010 11 20 Vol 12 No 4 p 305 SY10 1 RRPCT ISA 210 2 200 9 7
11. HIV 1 HIV 1 Rs5 GGR5 MIP 1 MIP 1 8 RANTES X4 cGxGR4 SDF 1 eeRs exGR4 HIV 1 HIV 1 1 2 1 2006_ 188445 2 2006 503849 eGRs5 Marav iroc Vicriviroc LA exGR4 AMD3100
12. R 14 PBMe R5 xX4 GXGR4 15 PMe A120 MAB173 VVO 2012 160678 8 PCT JP2011 062007 001 9 0020 0021 GGR5 101A120 X4 R5 1 X4 ER X4 gp120 GD4
13. gp120 gp120 GxGR4 GxGR4 exGR 4 3 A80 3 MAB171 MAB1 72 MAB173 exGR4 X4 0 PBMG R5 PeMe in vitro 1 2 A120
14. R 5 X4 R5 X4 R5 VVO 2012 160678 7 PCT JP2011 062007 0018 1X4 2 PBMG HIV 1 3 PBMG R5 G XGR4 514 A120 9 D JL T KOM 7 JL Z K OU R5 5 PeMe A120 HIV 1 6 PlMe Rs X4
15. A120 5 b A120 R5 x4 G xGR4 xi20 4 PMe Rs x4 A120 x4 Rs x4 Rs PeMe A120 4 VVO 2012 160678 15 PCT JP2011 062007 0045 0046 0047 0048 HIV 1 D24 ELISA
16. SHIVA cGxGR4 x4 VVO 2012 160678 4 PCT JP2011 062007 001 1 001 2 001 3 GGR5 GxXGR4 ecGRs Rs cxo X4 R5 exc Ant i_GxGR4 ECL 3 AA80 Anti CXCR4 ECL 2 MAB171 MAB172 MAB173 GxGR4 X4
17. pBMe A145 A120 1 1 PMG A120 417 Is eeGR5 MP 1 o MP 1 RANTFES GD3 GD28 PBMG A120 xX4 R5 VVO 2012 160678 17 PCT JP2011 062007 0054 0055 0056 0057 X4 GxGR4 R5 MIP 1 MIP 1 BB 0 k 5 coRs fs S PE p 8 A120
18. PFA FAGS Galibur Cell Quest softwear BD HIV 1 4 PFA PBS 5 0 1 FAGS 2mgml c Fc 15 HIV 1 p 26G2 Alexa Fluo 488 TRE LE RB 303 o VVO 2012 160678 13 PCT JP2011 062007 0037 0038 0039 0040 0041 FAGS p24 BD FeuM 6 Prism software Graph Pad 2 1 PBMG A R5 x4 GxXGR4 10 g ml GxGR4 amp 145
19. A120 817 HIV 1 HTLV 1 A120 8 ppBus A120 cGR5 91A120 eccR5 ecR 10 A120 ecR5 ecR 1 1A120 ecR5 ecR 12 A120 8 13 HIV 1 A120
20. T A120 9 HIV 1 A120 A120 GD3 GD28 Peme 15 HIV 1 10 gml A120 lge 5 p24 1 3 VVO 2012 160678 18 PCT JP2011 062007 0058 0059 0060 13 A120 10 R5 3 X4 2 R5 X4 p24 10 GxGR4 12G5 MAaB171 MAB172 MAB173 14
21. GGR5 HIV 1 Rs 1 2 KX 1 RX 2 1 RX gt K 2 A120 HIV 1 x4 HIV 1 R5 HIV 1 GxGR4 x4 exGR4 1 2 A12 0 GxGR4
22. SA Z p 1o 0 8 9 1 5 4 3 pc sA 2 10 2 monoclonal induces virus J Virol monoclonal type 1 J Virol the third agglutination antibodv recognizing lymphocyte and type 1 mediated 2001 12 Vol 75 syncytium No 23 antibodies recognizing in their ability to mnibit entry of 2005 02 Vol 79 No 3 r ki ry 1 r amp
23. M AB171 MAB172 MAB173 GxGR4 GxGR4 Gx GR4 cGx GR4 1 2 VVO 2012 160678 6 PCT JP2011 062007 0017 GxKGR4 GxGR4 GXGR4 HIV 1 xX4 GxGR4 HIV 1 X4 7 Gx lt GR4 cGx GR4 GoR5
24. GGR5 EGL2 X4 Rs EGL3 Nin E GxGR4 A80 EGL2 VVO 2012 160678 19 PCT JP2011 062007 GxGR4 MB173 MB171 MB172 Rep X4 PMG EGL1 EGL2 G XCR4 A120 R5 x4 PMG 1 6 X4 A120 EGL 2 X4 GxGR4
25. cxcR CH cxcR4 WO 2012 160678 A 1 EX EAIA 21 3 VVO 2012 160678 1 PCT JP2011 062007 0001 0002 0003 0004 A UAlps A IDS UF PFHIV T
26. A1 20 A80 GD3 GD28 PBMe R5 x4 QR FL R ON L4 3 PBMc 0 005 0 01 HIV 1 3 3 A120 A80 R5 X4 HIV 1 P24 A145 2 A120 A120 HIV 1 A120 HIV 1 R5 HIV 1 JR F R5 HIV 1 JR GsF X4 HIV 1 NL4 3 X4 HIV 1 IIIB 4
27. 4 R5 HIV 1 JR F R5 HIV 1 JR GSF X4 HIV 1 NL4 3 X4 HIV 1 IIIB A120 HIV 1 VVO 2012 160678 14 PCT JP2011 062007 0042 0043 0044 3 PMce A1z2o Hiv 1 PaMG A120 R 5 HIV 1 JR FL X4 HIV 1 NL4 3 6 peMoG OkT 3 GD28 R5 HIV 1 JR FL X4 HIV 1 NL4 3 RR 0 01m 0 i o A120 rat isotype 4 ABB LE pz24 1 5 FeMu LE 5 5 R5 HIV 1 JR FL X4 HIV 1 NL4 3
28. 6 6 A120 R5 5 gt gt g ml X4 0 6 gml 5 A120 R 5 x4 5 HIV 1 HTLV 1 A120 A120 A120 A120 HIV 1 Mo 4 IIIB HTLV 1 MT 2 HIV 1 Mo 11 4 111BR HTLV 1 MT 2 A120 10ug ml 1
29. HIV 1 p24 HTLV 1 p24 ELISA 7 7 A120 6 PMe A120 ecR5 E ONMIP 1 0 E BIP A B RANTES Rs A120 6 PBeMG OKT 3 GD28 A120 fat isotype 1 VVO 2012 160678 16 PCT JP2011 062007 0049 0050 0051 0052 0053 ELISA 8 8 A120 Rs MMP 1
30. PBMG 20U ml IL 2 RPM A120 24 1x 10cellsm 5 ELISA HIV 1 HIV 1 core p24 HIV 1 P2 4 ELISA HIV 1 P24 E A Bio Ac ademi a Canada 1 A ELISA Y KK Biosource Gamer illo Biolegend LE 5 Flow Cytometry roms FGM 3 UR 2mgml gG Fc RB 153 y RR 8303 o FAGS 2 FGS 0 1 PBS FAGS 1
31. A120 GxGR4 X4 PBMG R5 PMG in vitro VVO 2012 160678 9 PCT JP2011 062007 0022 0023 0024 1 1 RPMI 1640 18m3 A 1 DT I dE Inc St Lou is MO IC 1047 Z f R mis FGS 1 oUm 100 gml AF RPMI o jP E hCD3 clone OKT 3 GD28 clone 28 2 American Ty pe Culture Gollect ion Rockv i lle Yo X O Bio1s8e 1d 3101ego GA 2 GXGR4 WKA A145 lgG1 A120 lgG2b A80 lge1 1 runiqe monoc lona I ant i body recogn izing the third extrace Ilular loop of CXCR4 induces ymphocyte agglut inat ion and enhances human immunodef ic iency virus type 1 med ia ted syncyt ium format ion and product iVe infect
32. HIV 1 GpD4 HIV 1 ep4 T T HIV 1 HIV 1 GGR5 HIV 1 GxGR4 HIV 1 GoGRs HIV 1 Rs GxGR4 HIV 1 x4 VVO 2012 160678 3 PCT JP2011 062007 0007 0008 0009 001 0 eoGR5 ecxGR4 R5x4 HIV 1
33. MP 1 RANTES 7 A120 ecR5 ceR A120 oxGR4 MIP 1 o MP 1 8 RANT ES 1 A4120 9 1 1 9 A120 GD3 GD28 PMeG MP 1 MIP 1 RANTES 10 A120 PBMG GGR5 GD4 T GeGR5 GD4rT GxGR4
34. BAT SET 80 C 0031 4 PBMC HIV 1 ORR PBMG 3 2 00321 AF HistoPAQUE 1 077 Sigma A Idfich PBMG RPM RE 2x 106cells ml OKT3 5 gml TT 1m we I 24wel BD 0 1 gml NHG D28 2 4 5 0033 PEMG HIV 1 RHSBEO 005 0 0 1m 0 i 2x 106 p24 10ng 2 20Uml IL 2 RPM BE VVO 2012 160678 12 PCT JP2011 062007 0034 0035 0036 1x 106cellsml 0 5m we 110 Z L F 48we BD KOSH LT 2 GXKGR4 GD3 GD28 iday
35. 15 1 PBMG NO R5 xX4 GxGR4 7 A120 ccGR5 ccR 12G5 EGL1 EGL2 MAaB171 MAB172 MAB173 EGL2 14 a 14 b 12G5 MAB171 MAB172 MAB173 R5 X4 15 MaB173 A 120 ecR5 M IP 1
36. 160678 12 1000 750 500 MIP 1 1a pg ml 250 58 OF SS KKK KS ECR x SL lt x X SK MIP 1 18 pg ml XX lt CX 00706 SOO ER 250 200 RA SS XD RR 5 SS 2 AS S RLS 150 7 Q 100 XXXXXXX KKK KX L SES RANTES pg ml 77 2 SS 50 XX X 5 SS gt D DA K 11 14 CD4 CD4 CD4 CD8 CD8 CD8 PCT JP2011 062007 CD4 8 CD4 8 CD4 8 CD4 8 14 CD4 8 14 CD4 8 14 12 14 VVO 2012 160678 PCT JP2011 062007 13 R5 HIV 1 1000 100 10 p 0 0065 lt a 4 0 1 control A120 X4 HIV 1 1000 100 10 p 0 0065 lt 2 1 0 1 control A120 X4R5 HIV 1 100 p 0 0065 0 1 p24 ng ml 5 0 01 control A120 13 14 VVO 2012 160678 PCT JP2011 062007 14 a R5 HIV 1 JR FL d5 N o 2 Control A120 1265 MAB171 MAB172 MAB173 Antibody b X4 HIV 1 NL4 3 d5 175 150 125 100 G 75 a 50 25 0 Control A120 12G5 MAB171 MAB172 MAB173 Antibody 14 14 VVO 2012 160678 PCT JP2011 062007 15 1100 1000 900 800 700 600 500 400 300 200 100 MIP 1 pg ml Antibody 16 A120 A120 Activated PBMC humanized Clinical traials INTERNATIONAL SEARCH REPORT International application No PCT JP2
37. Dynaland 12G5 GxGR4 Bi oLegend and R amp D 0029 3 HIVA E HIV 1 JR FL HIV 1 JR_GSF HIV 1 NL4 3 HIV 1 DNA 293T VVO 2012 160678 11 PCT JP2011 062007 4 induct ion of protect iVe immune responses aga inst R5 human immunodef iciency virus type 1 HIV 1 infect ion in hu PBL SCI D mice by intrasp lenic immunizat ion with HIV 1 pu Ised dendr it ic cells p oss ible invo lvement of nove factor of human CD4 T ce 11 originj Jou rna of Vifology 2003 77 16 871 9 8728 Prepub lished on 2003 07 30 as DO I Yosh ida A Tanaka R Murakami T et a 0030 RPM 4 ABB LE in vitro o L Z El 4 HIV 1 111B Molt4 111 cell Iine HIV 1 HIV subtype infect iVity pane PRD320 BB I Diagnost i cs West Bridgewater MA USA HIV 1 E
38. GXGR4 GxGR4 El GxGR4 El HIV 1 X4 GxGR4 HIV 1 X4 GxGR4 GxGR4 GGSR5s A GGR5s HIV 1 Rs 1 3 1 14 VVO 2012 160678 PCT JP2011 062007 1 X4 HIV 1 e e e Cytoplasmic y E 2 gt R WIR oo OOO AR 2 14 WO 2012 160678 PCT JP2011 062007 2 HIV 1 infection method Fresh PBMCs 2 x 10 cel Is ml OKT 3 coated plate soluble antipCD28 mAb 24hr Wash amp infection with HIV 1 at a m o i of 0 01 R5 HIV 1 JR FL X4 HIV 1 NL4 3 Cultivation at 0 571 x 10 cel ls mi Anti CXCR4 mAb
39. 00 GE polymixin B columm 31 LPS LAL LPS 0026 IgG Alexa Fluo r 488 Alexa Fluor 647 InVitrogen Gy5 GE horserad ishperox daselz Doj in Kumamoto Japan o FITC PE gt GD4 GD8 GD14 GD19 Beckman GoiH t er BioLegend 0027 HIV 1 P24 SHH R 3 Suppression of CCR5 trop ic HIV type 1 infect ion by 0X40 st imulat ion via enhanced product ion of beta_chemok ines 4 AIDS res earch and human retrov iruses 2010 26 10 1147 1 154 Prepub lished on 20 100922 as pol 10 1089 a id 2010 0043 Tanaka R Takahash i Y Kodama A S aito M Ansar i AA Tanaka Y 0028 jP NoD4 GD8 GD14 GD19
40. 011 062007 A CLASSIFICATION OF SUBJECT MATTER CO 7K1 6 28 2006 01 i C12P21 08 2006 01 n According to International Patent Classification IPC or to both national classification and IPC FIELDS SEARCHED Minimum documentation searched classification system followed by classification symbols Co7K16 28 C12P21 08 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Koho 1922 1 996 Koho 1996 2011 Shinan 1 971 2011 Koho 1994 2011 Jitsuyo Shinan Shinan Toroku Kokai Jitsuyo Jitsuyo Koho Toroku Jitsuyo Shinan Electronic data base consulted during the international search name of data base and where practicable search terms used CA BI OS I S MEDLINE WPI DS STN JST Plus JMEDPlus I JST 7580 JDreaml 1 o DOCUMENTS CONSIDERED TO BE RELEVANT i CONSIDERED TO BE RELEVANT Category Citation of document with indication where appropriate of the relevant passages Relevant to claim No TANAKA R ue the thi r d monoclonal antibody recogni med lular of CXCR4 enhance zing loop and type product 75 i nduce s ymphocyte aggluti nati on s human immunode f i ciency virus ive ee oe and Vol f o rmati 2001 ium Virol 1 mediated on 12 syncyt i nfecti on ayy J No p 11534 11543 CARNEC X ibodie s Ant z ing i CXCR4 ove r appi thei r monoclonal ng epi abi
41. 2012 1606 A1 JUD 12 19 arees JU M I TI Hl A LRH 10 43 2012 11 A 29 B 29 11 2012 w 4 S WO 2012 160678 A 1 61 81 BEB G amp R Q UA BE lt TOD OO CO7K 16 28 2006 01 C12P 21 08 2006 01 EE JH E AE AG AL AM AO AT AU AZ BA El BB BG BH BR BVV BY BZ CA CH CL CN CO 21 le cd CR CU CZ DE DK DM DO DZ EC EE EG ES Fl ea 201 1 5 A 25 25 05 201 1 GB GD GE GH GM GT HN HR HU ID YL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS 25 LT LU LY MA MD ME MG MK MN MW MX 26 MY MZ NA NG NI NO NZ OM PE PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY 71 E E lt lt Q J E E IC V lt TH TJ TM TN TR TT TZ UA UG US UZ VC VN iit University of the Ryukyus ZA ZM ZW VPP T 9030243 PRR rh s RAR SSR okinawa JP Ry EN AN OE Be SD NOIA EE RE EE ARPO BW GH GM KE LR LS MW ukvu Immunology Corporation JP JP T 9042234 SE ss GR SSH EM i 5
42. GxXGR4 GGR5 GXGR4 GGR5 chemokine GPGR 0005 HIV 1 gp120 GD4 gp120 gp120 G xGR4 GeGR5 gp41 NN REM gp41 2 HIV 1 HIV 1 0006
43. blocking CXCR4 functioning as a coreceptor and stopping infection by X4 vir us whilst also providing a substance for inhibiting infection by human immunodeficiency virus whicn is effective not just against X 4 virus but also against RS virus and thus effectively stopping the onset of human immunodeficiency syndromes Solution An in hibitory substance which inhibits the infection of a target cell by human immunodeficiency virus This inhibitory substance is a monoclonal antibody having binding specincity for an chemokine receptor appearing in a target cell This chemokine receptor is CXCR4 and the monoclonal antibody which is an inhibitory substance is an anti CXCR4 monoclonal antibody 67 cxcR4 xa x4 Rs BRIM
44. gt D 15 40 CN k cN 1 1 0 T z 58 10 0 0 0 Control A120 Control A120 6 14 VVO 2012 160678 PCT JP2011 062007 46 140 e R5 HIV 1 100 E bn 80 a Q 60 gt 40 20 0 0 001 0 01 0 1 1 10 100 A120 concentration 4 g ml 7 Molt 4 1IB cells MT 2 cells 2500 E Ao 2000 E o G 1500 A gt 2 1000 gt 500 0 Control A120 7 14 WO 2012 160678 PCT JP2011 062007 8 96 control 96 control 96 control anti MIP 1 a 125 100 75 50 p 0 004 25 control C MIP 1 0 anti MIP 1 8 30 20 10 0 control a MIP 1 8 ant i RANTES 20 15 10 p 0 49 5 0 control a RANTES 8 14 VVO 2012 160678 PCT JP2011 062007 9 MIP 1 0 3000 gt 2500 E 2000 1500 p 0 008 CN 1000 gt 500 0 Control A120 MIP 1 8 60000 50000 E 40000 30000 p 0 019 S 20000 10000 0 B Control A120 RANTES 500 400 300 p 0 069 lt 200 E 100 0 Control A120 9 14 VVO 2012 160678 PCT JP2011 062007 10 Control A120 CXCR4 CXCR4 MFI 28 1 CXCR4 MFI 45 9 CCR5 MFI 60 8 CCR5 MFI 51 7 10 14 VVO 2012 160678 PCT JP2011 062007 611 Cultured with Donor 1 Donor 2 me ES pa Au alone AE PES A120 anti RANTES 16 4 34 9 re 5 A120 anti MIP 1 q L Pa A A120 all anti 8 chem Abs 16 4 Con Ab pa all anti 8 chem Abs CCR5 Cell number WO 2012
45. h Okinawa JP Mz NA SD SL SZ TZ UG ZM zw I E 7 4 AM AZ BY KG KZ MD RU TJ TM 72 AL AT BE BG CH CY CZ DE DK EE ES Fl FR 75 BH 45 GB GR HR HU IE IS IT LT LU LV MC MK MT TANAKA Yuetsu JP JP 79030215 XP 4 IR rh s EP NL NO PL PT RO RS SE SI SK SM TR OAPI 207 BF BJ CF CG Cl CM GA GN GQ GW ML MR Okinawa JP NE SN TD TG ra RM AKIYAMA Atsushi et al T 417 1050001 3 5 Pa3 7 Toko JP BR 4 470 54 Title SUBSTANCE FOR INHIBITING INFECTION BY HUMAN IMMUNODEFICIENCY VIRUS 64 813 Rs HIV 1 JR FL x4 HIV 1 NL4 3 RX A 2 x 335 p24 ng ml Xs TE gt 0 XA lt Te SS lt gt lt SOS 2 gt lt XX HIV 1 p24 ng ml N I 3 22 HIV es 926264 Control a145 A120 A80 Control A145 A120 A80 57 Abstract Problem To provide a substance for
46. ionj Journa of virology 2001 75 23 11534 1 1543 Prepub lished on 2001 1 1 02 as DOI 10 1128 Jv 1 75 23 11534 4 1543 2001 Tanaka R Yosh ida A Murakami T et a Eo 1 12G5 MAB171 MAB172T MAB173 R amp D LE gG ilgG2b ant i HTLV 1 gp46 LAT 27 lgG1 ant i HCV enve Iope2 Mo 8 gt 2 New monoc lona ant ibod ies aga inst a r ecomb inant second enve lope prote in of Hepat it is C v i rusj Microb iol IM VVO 2012 160678 10 PCT JP2011 062007 muno 1988 42 12 875 877 Prepub ished on 1999 02 26 as DOI Inudoh M Kato N Tanaka Y CCR5 T312 rat Ilge1 1 0025 eB 17 SGI D Superdex G2
47. it y f ciency 79 et al ant differ i nhibit type Ves id p 1930 1933 r e cogni tope s 1gni f i cantl y in to ry Vi rol oe human immunode 2005 02 ent of virus Vol No 3 Further documents are listed in the continuation of Box C L See patent family annex Special categories of cited documents T later document published after the international filing date or priority document defining the general state of the art which isnot considered to be of particular relevance earlier application or patent but published on or after the international filing date document which may throw doubts on priority claim s or which is cited to establish the publication date of another citation or other special reason as specified document referring to an oral disclosure use exhibnion or other means document published prior to the international filing date but later than the priority date claimed Date of the actual completion of the international search 02 Augu st 2011 02 08 11 Name and mailing address of the ISA Japane se Patent Office Facsimile No Form PCT ISA 210 second sheet July 2009 x y date and not in conflict with the application but cited to understand the principle or theory underlying tiie invention document of particular relevance the claimed invention cannot be considered novel or cannot be considered to involve an inventive step when the document is taken alo
48. ne document of particular relevance the claimed invention cannot be considered to involve an inventive step when the document is combined with one or more other such documents such combination being obvious to a person skilled in the art document member of the same patent family Date of mailing of the international search report 09 Augu st 2011 09 08 11 Authorized officer Telephone No INTERNATIONAL SEARCH REPORT International application No PCT JP2 011 062007 Continuation DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document with indication where appropriate of the relevant passages Relevant to claim No Yuet su TANAKA HIV Kans en Zosho ku o Yokus ei 1 5 suru Futat su no Hoho Jujo Saibo Vacc ne to 0X40 Shigeki The Journal of Al DS Research 20 November 2010 20 11 2010 vol 12 no 4 page 305 SY1 0 1 Form PCT ISA 2 10 continuation of second sheet July 2009 i pc Int CI CO07K16 28 2006 01 i C12P21 08 2006 01 n pcT p2o11 062007 B C12P21 08 PC Int CI CO07K16 28 BA
49. s 10 y g ml HIV 1 p24 quatitation p24 ELISA culture supernatants intra cellular p24 FCM 3 14 WO 2012 160678 PCT JP2011 062007 3 R5 HIV 1 JR FL X4 HIV 1 NL4 3 17 5 Ce SS oS 22 252 gt A RR 5 SS lt gt A lt x SO 5 Co SA X SS SS lt gt A SS 5 BS 5 SAS S 2 O lt gt A 0 9 Oo SA R gt SS HIV 1 p24 ng ml x S gt EN SS LLS xX X 5 SS X oS Ks ROSS KR o 5 ct x Oo gt b gt o gt o gt Co o Control A145 A120 A80 4 14 WO 2012 160678 PCT JP2011 062007 B14 R5 HIV 1 JR FL X4 HIV 1 NL4 3 120 gt Control 2007 o Control P E 1004 A120 A120 i 0 150 lt lt CN N e 100 1 al R5 HIV 1 JR CSF X4 HIV 1 IIIB 90 Control 2005 o Control A120 gt S e A120 we S 150 lt CN N S 2 100 gt gt a o 5 14 VVO 2012 160678 PCT JP2011 062007 45 a HIV 1 p24 production R5 HIV 1 JR FL X4 HIV 1 NL4 3 0 007 Ib 0 032 p ds _ 120 Zn E 6 a 100 5 80 4 lt N N 2 40 x 1 20 0 0 Control A120 Control A120 b FCM infected cells R5 HIV 1 JR FL X4 HIV 1 NL4 3 2 5 60 p 0 026 p 0 013 ae 2 50
Download Pdf Manuals
Related Search