WO1991005546A1 - Solid tumor treatment method and composition - Google Patents
Solid tumor treatment method and composition Download PDFInfo
- Publication number
- WO1991005546A1 WO1991005546A1 PCT/US1990/006211 US9006211W WO9105546A1 WO 1991005546 A1 WO1991005546 A1 WO 1991005546A1 US 9006211 W US9006211 W US 9006211W WO 9105546 A1 WO9105546 A1 WO 9105546A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- liposomes
- liposome
- tumor
- drug
- lipid
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 131
- 239000000203 mixture Substances 0.000 title claims abstract description 105
- 238000000034 method Methods 0.000 title claims description 61
- 238000011282 treatment Methods 0.000 title description 31
- 239000002502 liposome Substances 0.000 claims abstract description 341
- 150000002632 lipids Chemical class 0.000 claims abstract description 168
- 239000003814 drug Substances 0.000 claims abstract description 129
- 229940079593 drug Drugs 0.000 claims abstract description 128
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 30
- 229920001477 hydrophilic polymer Polymers 0.000 claims abstract description 16
- 239000003817 anthracycline antibiotic agent Substances 0.000 claims abstract description 12
- 238000001990 intravenous administration Methods 0.000 claims abstract description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 116
- 239000008280 blood Substances 0.000 claims description 78
- 210000004369 blood Anatomy 0.000 claims description 78
- 239000002202 Polyethylene glycol Substances 0.000 claims description 69
- 229920001223 polyethylene glycol Polymers 0.000 claims description 67
- 229960004679 doxorubicin Drugs 0.000 claims description 59
- -1 epiru¬ bicin Chemical compound 0.000 claims description 32
- 238000002347 injection Methods 0.000 claims description 31
- 239000007924 injection Substances 0.000 claims description 31
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 30
- 229960001904 epirubicin Drugs 0.000 claims description 29
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 28
- 239000000463 material Substances 0.000 claims description 23
- 238000011068 loading method Methods 0.000 claims description 18
- 239000003550 marker Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 14
- 239000002246 antineoplastic agent Substances 0.000 claims description 12
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 9
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 9
- 229960000975 daunorubicin Drugs 0.000 claims description 9
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 8
- 229920000954 Polyglycolide Polymers 0.000 claims description 8
- 229940041181 antineoplastic drug Drugs 0.000 claims description 7
- 239000004633 polyglycolic acid Substances 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 6
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 3
- 208000002352 blister Diseases 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 claims 1
- 229950008885 polyglycolic acid Drugs 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 62
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 60
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 49
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 48
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 45
- 241001465754 Metazoa Species 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
- 229920000362 Polyethylene-block-poly(ethylene glycol) Polymers 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- 229960001701 chloroform Drugs 0.000 description 31
- 229940107161 cholesterol Drugs 0.000 description 31
- 235000012000 cholesterol Nutrition 0.000 description 30
- 238000009472 formulation Methods 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- 239000007787 solid Substances 0.000 description 26
- 238000002360 preparation method Methods 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 229940067631 phospholipid Drugs 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 23
- 150000003904 phospholipids Chemical class 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000012071 phase Substances 0.000 description 22
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- 239000012528 membrane Substances 0.000 description 20
- 210000004379 membrane Anatomy 0.000 description 20
- 210000004881 tumor cell Anatomy 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 18
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 18
- 239000000306 component Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000010168 coupling process Methods 0.000 description 14
- 210000004185 liver Anatomy 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 238000005859 coupling reaction Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 206010003445 Ascites Diseases 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000012530 fluid Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 230000008878 coupling Effects 0.000 description 11
- 206010009944 Colon cancer Diseases 0.000 description 10
- 206010015866 Extravasation Diseases 0.000 description 10
- 230000036251 extravasation Effects 0.000 description 10
- 210000002216 heart Anatomy 0.000 description 10
- 229940086542 triethylamine Drugs 0.000 description 10
- 229920001202 Inulin Polymers 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 238000001125 extrusion Methods 0.000 description 8
- 229940029339 inulin Drugs 0.000 description 8
- 229920001427 mPEG Polymers 0.000 description 8
- 229920000747 poly(lactic acid) Polymers 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 238000004513 sizing Methods 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 238000012800 visualization Methods 0.000 description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 7
- 241000196324 Embryophyta Species 0.000 description 7
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 7
- 229930013930 alkaloid Natural products 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 210000003722 extracellular fluid Anatomy 0.000 description 7
- 239000012216 imaging agent Substances 0.000 description 7
- 238000002513 implantation Methods 0.000 description 7
- 230000004807 localization Effects 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000004626 polylactic acid Substances 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 230000008685 targeting Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 241000256844 Apis mellifera Species 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 206010025323 Lymphomas Diseases 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000004698 Polyethylene Substances 0.000 description 6
- 240000002825 Solanum vestissimum Species 0.000 description 6
- 235000018259 Solanum vestissimum Nutrition 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 210000002469 basement membrane Anatomy 0.000 description 6
- 239000002738 chelating agent Substances 0.000 description 6
- 150000001841 cholesterols Chemical class 0.000 description 6
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 6
- 229940099217 desferal Drugs 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 239000010408 film Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 229920000151 polyglycol Polymers 0.000 description 6
- 239000010695 polyglycol Substances 0.000 description 6
- 239000011148 porous material Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229940123150 Chelating agent Drugs 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000010432 diamond Substances 0.000 description 5
- 229960004756 ethanol Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 150000008105 phosphatidylcholines Chemical class 0.000 description 5
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 5
- 229960004528 vincristine Drugs 0.000 description 5
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 150000003905 phosphatidylinositols Chemical class 0.000 description 4
- 229920000515 polycarbonate Polymers 0.000 description 4
- 229920000573 polyethylene Polymers 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000004576 sand Substances 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- NTRLSGIBUFLYST-VFTWSTDHSA-N (8s,10s,13s,14s,16r,17s)-17-[2-[4-(2,6-dipyrrolidin-1-ylpyrimidin-4-yl)piperazin-1-yl]acetyl]-10,13,16-trimethyl-6,7,8,12,14,15,16,17-octahydrocyclopenta[a]phenanthren-3-one;methanesulfonic acid;hydrate Chemical compound O.CS(O)(=O)=O.O=C([C@@H]1[C@@]2(C)CC=C3[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)CN(CC1)CCN1C(N=1)=CC(N2CCCC2)=NC=1N1CCCC1 NTRLSGIBUFLYST-VFTWSTDHSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 229920005654 Sephadex Polymers 0.000 description 3
- 239000012507 Sephadex™ Substances 0.000 description 3
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- KDJVUTSOHYQCDQ-UHFFFAOYSA-N carbamic acid;1h-imidazole Chemical compound NC([O-])=O.[NH2+]1C=CN=C1 KDJVUTSOHYQCDQ-UHFFFAOYSA-N 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000008497 endothelial barrier function Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 230000036571 hydration Effects 0.000 description 3
- 238000006703 hydration reaction Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000005298 paramagnetic effect Effects 0.000 description 3
- 239000004417 polycarbonate Substances 0.000 description 3
- 229920000570 polyether Polymers 0.000 description 3
- 229940093430 polyethylene glycol 1500 Drugs 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000010409 thin film Substances 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 2
- BIABMEZBCHDPBV-MPQUPPDSSA-N 1,2-palmitoyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-MPQUPPDSSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 239000000232 Lipid Bilayer Substances 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000004721 Polyphenylene oxide Substances 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000012062 aqueous buffer Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 229940031098 ethanolamine Drugs 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 230000000887 hydrating effect Effects 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000002584 immunomodulator Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 description 2
- 125000003473 lipid group Chemical group 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229960003540 oxyquinoline Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- LMGGOGHEVZMZCU-FGJMKEJPSA-N (2s,4s)-4-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,7,12-tetrahydroxy-6,11-dioxo-3,4-dihydro-1h-tetracene-2-carboxylic acid Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(O)=O)C1 LMGGOGHEVZMZCU-FGJMKEJPSA-N 0.000 description 1
- YGPZWPHDULZYFR-DPAQBDIFSA-N (3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-amine Chemical compound C1C=C2C[C@@H](N)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 YGPZWPHDULZYFR-DPAQBDIFSA-N 0.000 description 1
- LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- WQTCTMDKQPZJES-UHFFFAOYSA-N 2-aminoethyl dihydrogen phosphate;nonane Chemical compound NCCOP(O)(O)=O.CCCCCCCCC.CCCCCCCCC WQTCTMDKQPZJES-UHFFFAOYSA-N 0.000 description 1
- TZGPACAKMCUCKX-UHFFFAOYSA-N 2-hydroxyacetamide Chemical compound NC(=O)CO TZGPACAKMCUCKX-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 241000427202 Adria Species 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- 241000182988 Assa Species 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 240000001546 Byrsonima crassifolia Species 0.000 description 1
- 235000003197 Byrsonima crassifolia Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000237074 Centris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- BHYOQNUELFTYRT-UHFFFAOYSA-N Cholesterol sulfate Natural products C1C=C2CC(OS(O)(=O)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 BHYOQNUELFTYRT-UHFFFAOYSA-N 0.000 description 1
- 241000272470 Circus Species 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 240000003550 Eusideroxylon zwageri Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241001669573 Galeorhinus galeus Species 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- YEEGWNXDUZONAA-RYDPDVNUSA-K Gallium Citrate (67 Ga) Chemical compound [67Ga+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YEEGWNXDUZONAA-RYDPDVNUSA-K 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
- RJECHNNFRHZQKU-UHFFFAOYSA-N Oelsaeurecholesterylester Natural products C12CCC3(C)C(C(C)CCCC(C)C)CCC3C2CC=C2C1(C)CCC(OC(=O)CCCCCCCC=CCCCCCCCC)C2 RJECHNNFRHZQKU-UHFFFAOYSA-N 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 241001503951 Phoma Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940046545 animal allergen extract Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 208000027697 autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency Diseases 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 229930183167 cerebroside Natural products 0.000 description 1
- 150000001784 cerebrosides Chemical class 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- BHYOQNUELFTYRT-DPAQBDIFSA-N cholesterol sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 BHYOQNUELFTYRT-DPAQBDIFSA-N 0.000 description 1
- WLNARFZDISHUGS-MIXBDBMTSA-N cholesteryl hemisuccinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 WLNARFZDISHUGS-MIXBDBMTSA-N 0.000 description 1
- RJECHNNFRHZQKU-RMUVNZEASA-N cholesteryl oleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)C1 RJECHNNFRHZQKU-RMUVNZEASA-N 0.000 description 1
- 239000012568 clinical material Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 239000011363 dried mixture Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- WCHFOOKTKZYYAE-UHFFFAOYSA-N ethoxyperoxyethane Chemical compound CCOOOCC WCHFOOKTKZYYAE-UHFFFAOYSA-N 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000006481 glucose medium Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- NKAAEMMYHLFEFN-UHFFFAOYSA-M monosodium tartrate Chemical compound [Na+].OC(=O)C(O)C(O)C([O-])=O NKAAEMMYHLFEFN-UHFFFAOYSA-M 0.000 description 1
- 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- ZVVSSOQAYNYNPP-UHFFFAOYSA-N olaflur Chemical group F.F.CCCCCCCCCCCCCCCCCCN(CCO)CCCN(CCO)CCO ZVVSSOQAYNYNPP-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- 239000000088 plastic resin Substances 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical group C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 1
- 229960000641 zorubicin Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/5537—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom the heteroring containing the structure -C(=O)-N-C(=O)- (both carbon atoms belong to the heteroring)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- Fiel ⁇ of the Invention relates to a liposome composi ⁇ tion and method, particularly for use in tumor diagnos ⁇ tics and/or therapeutics.
- Liposomes have been proposed as a drug carrier for intravenously (IV) administered compounds, including both imaging and therapeutic compounds.
- IV intravenously
- the use of liposomes for site-specific targeting via the bloodstream has been severely restricted by the rapid clearance of liposomes by cells of the reticuloendothelial system (RES) .
- the RES will remove 80-95% of a dose of IV injected liposomes within one hour, effectively out-competing the selected target site for uptake of the liposomes.
- One general object of the invention is to provide a liposome composition and method which is effective for tumor targeting, for localizing an imaging or anti-tumor agent selectively at therapeutic dose levels in systemic, extravascular tumors.
- the invention includes, in one aspect, a liposome composition for use in localizing a compound in a solid tumor, as defined in Section IV below, via the blood- stream comprising: The liposomes forming the composition
- (i) are composed of vesicle-forming lipids and between 1-
- vesicle-forming lipid is defined as any lipid that by itself or in combination with other lipids forms bilayer structures.
- the hydrophilic polymer is polyethyleneglycol, poly lactic poly glycoloc acid having a molecular weight between about 1,000-5,000 daltons, and is derivatized to a phospholipid.
- the compound in one embodiment is an anthracycline antibiotic or plant alka ⁇ loid, at least about 80% of the compound is in liposome- entrapped form, and the drug is present in the liposomes at a concentration of at least about 20 ⁇ g compound/ ⁇ mole liposome lipid in the case of the anthracycline antibio ⁇ tics and and 1 ⁇ g/ ⁇ moles lipid in the case of the plant alkaloids.
- the invention includes a com- position of liposomes characterized by:
- the agent is carried through the bloodstream
- the method includes entrap ⁇ ping the agent in liposomes of the type characterize above.
- One liposome composition preferred for transpor - ing anthracycline antibiotic or plant alkaloid anti-tumor agents to systemic solid tumors would contain high phase transition phospholipids and cholesterol as this type o liposome does not tend to release these drugs while circulating through the bloodstream during the first 24- 48 hours following administration.
- the invention includes a metho for localizing a compound in a solid tumor in a subject.
- the method includes preparing a composition of liposo.nes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an vesicle-forming lipid derivatized wit a hydrophilic polymer, (ii) having an average size in selected size range between about 0.07-0.12 microns, an (iii) containing the compound in liposome-entrapped form.
- the composition is injected IV in the subject in a amount sufficient to localize a therapeutically effectiv dose of the agent in the solid tumor.
- Figure 1 illustrates a general reaction scheme for derivatizing a vesicle-forming lipid amine with a polyal- kylether
- Figure 2 is a reaction scheme for preparing phospha- tidylethanolamine (PE) derivatized with polyethylene- glycol via a cyanuric chloride linking agent
- Figure 3 illustrates a reaction scheme for preparing phosphatidylethanolamine (PE) derivatized with polyethy- leneglycol by - ⁇ ieans of a diimidazole activating reagent
- Figure 4 illustrates a reaction scheme for preparing phosphatidylethanolamine (PE) derivatized with polyethy- leneglycol by means of a trifluoromethane sulfonate reagent
- Figure 5 illustrates a vesicle-forming lipid deriva ⁇ tized with polyethyleneglycol through a peptide (A) , ester (B) , and disulfide (C) linkage;
- Figure 6 illustrates a reaction scheme for preparing phosphatidylethanolamine (PE) derivatized with poly lactic acid;
- Figure 7 is a plot of liposome residence times in the blood, expressed in terms of percent injected dose as a function of hours after IV injection, for PEG-PE lipo ⁇ somes containing different amounts of phosphatidylglyce- rol;
- Figure 8 is a plot similar to that of Figure 7, showing blood residence times of liposomes composed of predominantly unsaturated phospholipid components;
- Figure 9 is a plot similar to that of Figure 7, showing the blood residence times of PEG-coated liposomes (solid triangles) and conventional, uncoated liposomes (solid circles) ;
- SUBSTITUTE SHEET Figure 10 is a plot similar to that of Figure 7, showing the blood residence time of polylactic acid- coated liposomes (solid squares) polyglycolic acid-coated liposomes (open triangles) ;
- Figure 11 is a plot showing the kinetics of doxoru ⁇ bicin clearance from the blood of beagle dogs, for drug administered IV in free form (open circles) , in liposomes formulated with saturated phospholipids and hydrogenated phosphatidylinositol (HPI) (open squares) , and in lipo- somes coated, with PEG (open triangles) ;
- HPI hydrogenated phosphatidylinositol
- Figures 12A and 12B are plots of the time course of doxorubicin uptake from the bloodstream by heart (solid diamonds), muscle (solid circles), and tumor (solid triangles) for drug administered IV in free (12A) and PEG-liposomal (12B) form;
- Figure 13 is a plot of the time course of uptake of doxorubicin from the bloodstream by J-6456 tumor cells implanted interperitoneally (IP) in mice, as measured as total drug (filled diamonds) as drag associated with tumor cells (solid circles) and liposome-associated form (solid triangles) ;
- Figures 14A-14D are light micrographs showing loca ⁇ lization of liposomes (small dark stained particles) in Kupfer cells in normal liver (14A) , in the interstitial fluid of a C-26 colon carcinoma implanted in liver in the region of a capillary supplying the tumor cells (14B) and in the region of actively dividing C-26 tumor cells implanted in liver (14C) or subcutaneously (14D) ;
- Figure 15A-C are plots showing tumor size growth in days following subcutaneous implantation of a C-26 colon carcinoma, for mice treated with a saline control (open circles), doxorubicin at 6 mg/kg (filled circles), epiru- bicin at 6 mg/kg (open triangles) , or PEG-liposome-en- trapped epirubicin at two doses, 6mg/kg (filled trian-
- Figure 16 is a plot showing percent survivors, in days following interperitoneal implantation of a J-6456 lymphoma, for animals treated with doxorubicin in free form (closed circles) or PEG-liposomal form (solid tri ⁇ angles) , or untreated animals (open triangles) ; and
- Figure 17 is a plot similar to that in Figure 15, showing tumor size growth, in days following subcutaneous implantation of a C-26 colon carcinoma, for animals treated with a saline control (filled circles) , or ani ⁇ mals treated with 10 mg/kg doxorubicin in free form (filled squares) , or in conventional liposomes (open circles) .
- Figure 1 shows a general reaction scheme for prepa- ring a vesicle-forming lipid derivatized a biocompatible, hydrophilic polymer, as exemplified by polyethylene glycol (PEG) , polylactic acid, and polyglycolic acid, all of which are readily water soluble, can be coupled to vesicle-forming lipids, and are tolerated in vivo without toxic effects.
- the hydrophilic polymer which is em ⁇ ployed, e.g., PEG is preferably capped by a methoxy, ethoxy or other unreactive group at one end or, alterna ⁇ tively, has a chemical group that is more highly reactive at one end than the other.
- the polymer is activated at
- SUBSTITUTE SHEET one of its ends by reaction with a suitable activatin agent, such as cyanuric acid, diimadozle, anhydrid reagent, or the like, as described below.
- a suitable activatin agent such as cyanuric acid, diimadozle, anhydrid reagent, or the like, as described below.
- the activate compound is then reacted with a vesicle-forming lipid, such as a diacyl glycerol, including diacyl phosphogly cerols, where the two hydrocarbon chains are typicall between 14-22 carbon atoms in length and have varyin degrees of saturation, to produce the derivatized lipid.
- Phosphatidylethanol-amine (PE) is an example of a phos- pholipid which is preferred for this purpose since it contains a reactive amino group which is convenient for coupling to the activated polymers.
- the lipid group may be activated for reaction with the poly ⁇ mer, or the two groups may be joined in a concerte coupling reaction, according to known coupling methods.
- PEG capped at one end with a methoxy or ethoxy group can be obtained commercially in a variety of polymer sizes, e.g., 500-20,000 dalton molecular weights.
- the vesicle-forming lipid is preferably one having two hydrocarbon chains, typically acyl chains, and a polar head group.
- phos- pholipids such as phosphatidylcholine (PC) , PE, phos phatidic acid (PA), phosphatidylinositol (PI), and sphin- gomyelin (SM) , where the two hydrocarbon chains ar typically between about 14-22 carbon atoms in length, an have varying degrees of unsaturation.
- the glycolipids such as cerebrosides an gangliosides.
- vesicle-forming lipid which may be employe is cholesterol and related sterols.
- choles terol may be less tightly anchored to a lipid bilaye membrane, particularly when derivatized with a hig molecular weight polymers, such as polyalkylether, an therefore be less effective in promoting liposome evasio
- vesicle forming lipid is intended to include any amphipathi lipid having hydrophobic and polar head group moieties, and which (a) by itself can form spontaneously int bilayer vesicles in water, as exemplified by phospholi pids, or (b) is stably incorporated into lipid bilayer in combination with phospholipids, with its hydrophobi moiety in contact with the interior, hydrophobic regio of the bilayer membrane, and its polar head group moiet oriented toward the exterior, polar surface of the mem brane.
- the vesicle-forming lipid may be a relatively flui lipid, typically meaning that the lipid phase has relatively low liquid to liquid-crystalline meltin temperature, e.g., at or below room temperature, o relatively rigid lipid, meaning that the lipid has relatively high melting temperature, e.g., up to 60°C.
- the more rigid, i.e., saturated lipids con tribute to greater membrane rigidity in a lipid bilaye structure and also contribute to greater bilayer stabi lity in serum.
- lipid components such as choleste ⁇ rol
- choleste ⁇ rol are also known to contribute to membrane rigidity and stability in lipid bilayer structures.
- a long chai (e.g. C-18) saturated lipid plus cholesterol is on preferred composition for delivering anthracycline anti biotic and plant alkaloids anti-tumor agents to soli tumors since these liposomes do not tend to release th drugs into the plasma as they circulate through th bloodstream and enter the tumor during the first 48 hour following injection.
- Phospholipids whose acyl chain have a variety of degrees of saturation can be obtained commercially, or prepared according to published methods.
- Figure 2 shows a reaction scheme for producing a PE- PEG lipid in which the PEG is derivatized to PE through a cyanuric chloride group. Details of the reaction are provided in Example 1. Briefly, methoxy-capped PEG is activated with cyanuric chloride in the presence in sodium carbonate under conditions which produced the activated PEG compound shown in the figure. This mate- rial is purified to remove unreacted cyanuric acid. The activated PEG compound is reacted with PE in the presence of triethyl amine to produce the desired PE-PEG compound shown in the figure. The yield is about 8-10% with respect to initial quantities of PEG. The method just described may be applied to a vari ⁇ ety of lipid amines, including PE, cholesteryl amine, and glycolipids with sugar-amine groups.
- a second method of coupling a polyalkylether, such as capped PEG to a lipid amine is illustrated in Figure 3.
- the capped PEG is activated with a carbonyl diimidazole coupling reagent, to form the activated imidazole compound shown in Figure 3.
- Reaction with a lipid amine, such as PE leads to PEG coupling to the lipid through an amide linkage, as illustrated in the PEG-PE compound shown in the figure. Details of the reaction are given in Example 2.
- a third reaction method for coupling a capped poly ⁇ alkylether to a lipid amine is shown in Figure 4.
- PEG is first protected at its OH end by a trimethylsilane group.
- the end-protection reaction is shown in the figure, and involves the reaction of trimethylsilylchlo- ride with PEG in the presence of triethylamine.
- the protected PEG is then reacted with the anhydride of trifluoromethyl sulfonate to form the PEG compound acti-
- SUBSTITUTE SHEET vated with trifluoromethyl sulfonate Reaction of the activated compound with a lipid amine, such as PE, in the presence of triethylamine, gives the desired derivatized lipid product, such as the PEG-PE compound, in which the lipid amine group is coupled to the polyether through the terminal methylene carbon in the polyether polymer.
- the trimethylsilyl protective group can be released by acid treatment, as indicated in the figure, or, alternatively, by reaction with a quaternary amine fluoride salt, such as the fluoride salt of tetrabutylamine.
- the acid group of phosphatidi-; acid can be activated to form an active lipid anhydride, by reaction with a suitable anhydride, such as acetic anhydride, and the reactive lipid can then be joined to a protected polyalkylamine by reaction in the presence of an isothio- cyanate reagent.
- a suitable anhydride such as acetic anhydride
- the derivatized lipid com ⁇ ponents are prepared to include a labile lipid-polymer linkage, such as a peptide, ester, or disulfide linkage, which can be cleaved under selective physiological condi ⁇ tions, such as in the presence of peptidase or esterase enzymes or reducing agents such as glutathione present in the bloodstream.
- Figure 5 shows exemplary lipids which are linked through (A) peptide, (B) , ester, and (C) ,
- the peptide-linked com pound can be prepared, for example, by first coupling polyalkylether with the N-terminal amine of the tripep tide shown, e.g., via the reaction shown in Figure 3.
- the peptide carboxyl group can then be coupled to a lipi amine group through a carbodiimide coupling reagent con ventionally.
- the ester linked compound can be prepared, for example, by coupling, a lipid acid, such as phosphati dic acid, to the terminal alcohol group of a polyalkyl ether, using alcohol via an anhydride coupling agent.
- an short linkage fragment containing a internal ester bond and suitable end groups, such a primary amine groups can be used to couple the polyalkyl ether to the amphipathic lipid through amide or carbamat linkages.
- the linkage fragment may contain a internal disulfide linkage, for use in forming the com pound shown at C in Figure 5.
- Polymers coupled to phos pholipids via such reversible linkages are useful t provide high blood levels of liposomes which contain the for the first few hours post injection. After thi period, plasma components cleave the reversible bond releasing the polymers and the "unprotected" liposome are rapidly taken up by the RES.
- Figure 6 illustrates a method for derivatizin polylactic acid with PE.
- the polylactic acid is reacted, in the presence of PE, with dicyclohexylcarboimid (DCCI) , as detailed in Example 4.
- DCCI dicyclohexylcarboimid
- a vesicle forming lipid derivatized with polyglycolic acid may b formed by reaction of polyglycolic acid or glycolic aci with PE in the presence of a suitable coupling agent, such as DCCI, also as detailed in Example 4.
- the vesi cle-forming lipids derivatized with either polylacti acid or polyglycolic acid form part of the inventio herein.
- liposome containing these derivatized lipids in a 1-20 mole percent.
- the lipid components used in forming the liposomes of the invention may be selected from a variety of vesi ⁇ cle-forming lipids, typically including phospholipids, sphingolipids and sterols.
- lipid components used in forming the liposomes of the invention may be selected from a variety of vesi ⁇ cle-forming lipids, typically including phospholipids, sphingolipids and sterols.
- one require- ment of the liposomes of the present invention is long blood circulation lifetime. It is therefore useful to establish a standardized measure of blood lifetime which can be used for evaluating the effect of lipid components on blood halflife.
- One method used for evaluating liposome circulation time in vivo measures the distribution of IV injected liposomes in the bloodstream and the primary organs of the RES at selected times after injection.
- RES uptake is mea- sured by the ratio of total liposomes in the bloodstream to total liposomes in the liver and spleen, the principal organs of the RES.
- age and sex matched mice are injected IV through the tail vein with a radiolabtled liposome composition, and each time point is determined by measuring total blood and combined liver and spleen radiolabel counts, as detailed in Example 5.
- the blood- /RES ratio just described provides a good approximation of the extent of uptake from the blood to the RE3 in vivo. For example, a ratio of about 1 or greater indi ⁇ cates a predominance of injected liposomes remaining in the bloodstream, and a ratio below about 1, a predomi ⁇ nance of liposomes in the RES. For most of the lipid
- the liposomes of the present invention include 1-2 mole percent of the vesicle-forming lipid derivatize with a hydrophilic polymer, described in Section I.
- a hydrophilic polymer described in Section I.
- the phospholipid components may b composed of predominantly of fluidic, relatively unsatu rated, acyl chains, or of more saturated, rigidifyin acyl chain components.
- This feature of the invention i seen in Example 6, which examines blood/RES ratios i liposomes formed with PEG-PE, cholesterol, and PC havin varying degrees of saturation (Table 4)-.
- the vesicle-forming lipids may b selected to achieve a selected degree of fluidity o rigidity, to control the stability of the liposomes i serum and the rate of release of entrapped drug from th liposomes in the bloodstream and/or tumor.
- the vesicle forming lipids may also be selected, in lipid saturatio characteristics, to achieve desired liposome preparatio properties. It is generally the case, for example, tha more fluidic lipids are easier to formulate and down-siz by extrusion and homogenization methods than more rigi lipid compositions.
- Liposomes suspensions which con- tain negative charge tend to be less sensitive to aggre ⁇ gation in high ionic strength buffers and h nce physical stability is enhanced. Also, negative charge present in the liposome membrane can be used as a formulation tool to effectively bind high amounts of cationic drugs.
- the vesicle-forming lipid derivatized with a hydro ⁇ philic polymer is.present in an amount preferably between about 1-20 mole percent, on the basis of moles of deriva ⁇ tized lipid as a percentage of total moles of vesicle- forming lipids.
- a lower mole ratio such as 0.0 mole percent
- a lipid derivative with a large molecular weight polymer such as one having a molecular weight of 100 kilodaltons.
- the hydrophilic polymer in the derivatized lipid preferably has a molecular weight between about 200-20,000 daltons, and more preferabl between about 500-5,000 daltons.
- Example 7B whic examines the effect of very short ethoxy ether moietie on blood/RES ratios indicates that polyether moieties o greater than about 5 carbon ethers are required t achieve significant enhancement of blood/RES ratios.
- the liposomes may be prepared by a variety of tech niques, such as those detailed in Szoka et al, 1980.
- On method for preparing drug-containing liposomes is th reverse phase evaporation method described by Szoka et a and in U.S. Patent No. 4,235,871.
- the reverse phas evaporation vesicles (REVs) have typical average size between about 2-4 microns and are predominantly oligo lamellar, that is, contain one or a few lipid bilaye shells. The method is detailed in Example 4A.
- Multilamellar vesicles can be formed b simple lipid-film hydration techniques.
- the lipid film hydrates to form MLVs typically wit sizes between about 0.1 to 10 microns.
- the liposomes are prepared to have substan tially homogeneous sizes in a selected size range betwee about 0.07 and 0.12 microns.
- liposomes in this size range are readil able to extravasate into solid tumors, as discussed i Section III below, and at the same time, are capable o carrying a substantial drug load to a tumor (unlike smal unilamellar vesicles, which are severely restricted i drug-loading capacity) .
- the pore size of the membrane corresponds roughly to the largest sizes of liposomes produced by extrusion through that membrane, particularly where the preparation is extruded two or more times through the same membrane.
- This method of liposome sizing is used in preparing homogeneous-size REV and MLV compositions described in the examples below.
- a more recent method involves extru ⁇ sion through an asymmetric ceramic filter. The method is detailed in U.S. patent No. 4,737,323 for Liposome Extru ⁇ sion issued April 12, 1988. Homogenization methods are also useful for down-sizing liposomes to sizes of lOOnm or less (Martin) .
- the composition of t ⁇ e invention is used for localizing an imaging agent, such as radio- isotopes including 67 Ga and U1 ln, or paramagnetic com ⁇ pounds at the tumor site.
- an imaging agent such as radio- isotopes including 67 Ga and U1 ln, or paramagnetic com ⁇ pounds at the tumor site.
- the radiolabel can be detected at relatively low concentra ⁇ tion, it is generally sufficient to encapsulate the imaging agent by passive loading, i.e., during liposome formation. This may be done, for example, by hydrating lipids with an aqueous solution of the agent to be encap- sulated.
- radiolabeled agents are radioisotopic metals in chelated form, such as 67 Ga-desferal, and are retained in the liposomes substantially in entrapped form. After liposome formation and sizing, non-encapsu ⁇ lated material may be removed by one of a variety of
- SUBSTITUTE SHEET methods such as by ion exchange or gel filtration chro matography.
- concentration of chelated metal whic can be achieved by passive loading is limited b th concentration of the agent in the hydrating medium.
- Active loading of radioimaging agents is also pos sible by entrapping a high affinity, water soluble chela ting agent (such as EDTA or desferoxa ine) within th aqueous compartment of liposomes, removing any unen trapped chelating agent by dialysis or gel exclusio column chromatography and incubating the liposomes in th presence of the metal radioisotope chelated to a lowe affinity, lipid soluble chelating agent such as 8-hydr oxyquinoline.
- the metal radioisotope is carried into th liposome by the lipid soluble chelating agent. Once i the liposome, the radioisotope is chelated by the en trapped, water soluble chelating agent - effectivel trapping the radioisotope in the liposome interior (Gabi zon) .
- Passive loading may also be employed for th amphipathic anti-tumor compounds, such as the alkaloid vinblastine and vincristine, which are the.rapeuticall active at relatively low drug doses, e.g., about 1-1 mg/m 2 .
- the drug is either dissolved in the aqueou phase used to hydrate the lipid or included with th lipids in liposome formation process, depending on th solubility of the compound.
- an sizing, free (unbound) drug can be removed, as above, fo example, by ion exchange or gel exclusion chro atographi methods.
- the anti-tumor compound includes a peptide o protein drug, such as interleukin-2 (IL-2) or tissu necrosis factor (TNF) , or where the liposomes are formu lated to contain a peptide immunomodulator, such a muramyl di- or tri-peptide derivatives or a protei
- IL-2 interleukin-2
- TNF tissu necrosis factor
- the liposomes are preferably prepared b the above reverse phase method or by rehydrating a freez dried mixture of the protein and a suspension of smal unilamellar vesicles with water (Kirby) . Both method combine passive loading with relatively high encapsu lation efficiency, e.g., up to 50% efficiency. Nonencap sulated material can be readily removed from the liposom suspension, e.g., by dialysis, diafiltration or exclusio chromatography.
- M-CSF macrophage colony stimulatin factor
- the concentration of hydrophobic drug which can b accommodated in the liposomes will depend on drug/lipi interactions in the membrane, but is generally limited t a drug concentration of less than about 20 ⁇ g drug/m lipid. More specifically, for a variety of anthracyclin antibiotics, such as doxorubicin and epirubicin, th highest concentration of encapsulated material which ca be achieved by passive loading into the aqueous compart ment of the liposome is about 10-20 ⁇ g/ ⁇ moles lipid (du to the low intrinsic water solubility of thes compounds) .
- suc charged complexed anthracycline formulations have range utility in the context of the present invention (whic requires that the drug be carried through the bloodstrea for the first 24-48 hours following IV administration i liposome entrapped form) because the drugs tend to b rapidly released from the liposome membrane when intro Jerusalem into plasma.
- SUBSTITUTE SHEET In accordance with another aspect of the inventio it has been found essential, for delivery of an therape tically effective dose of a variety of amphipathic ant tumor drugs to tumors, to load the liposomes to a hi drug concentration by active drug loading methods.
- anthracycline antibiotic drugs such as doxorubicin, epirubicin, daunorubicin, carcinomycin, acetyladriamycin, rubidazone, 5-imidodaunomycin, and acetyldaunomycin
- a final concentration of liposom entrapped drug of greater than about 25 ⁇ g/ ⁇ mole lip and preferably 50 ⁇ g/ ⁇ mole lipid is desired.
- liposomes are prepared in the presence a relatively high concentration of ammonium ion, such 0.125 M ammonium sulfate. After sizing the liposomes t a desired size, the liposome suspension is treated t create an inside-to-outside ammonium ion gradient acros the liposomal membranes.
- the gradient may be created dialysis against a non-ammonium containing medium, su as an isotonic glucose medium, or by gel filtration, su as on a Sephadex G-50 column equilibrated with 0.15M Na or KC1, effectively replacing ammonium ions in the ext rior phase with sodium or potassium ions.
- the liposome suspension may be diluted with a non-a monium solution, thereby reducing the exterior-pha concentration of ammonium ions.
- the ammonium concentr tion inside the liposomes is preferably at least times, and more preferably at least 100 to 1000 tim that in the external liposome phase.
- SUBSTITUTE SHEET The ammonium ion gradient across the liposomes in turn creates a pH gradient, as ammonia is released across the liposome membrane, and protons are trapped in the internal aqueous phase of the liposome.
- a suspension of the lipo ⁇ somes e.g., about 20-200 mg/ml lipid, is mixed with an aqueous solution of the drug, and the mixture is allowed to equilibrate over an period of time, e.g., several hours, at temperatures ranging from room temperature to 60°C - depending on the phase transition temperature of the lipids used to form the liposome.
- a suspension of liposomes having a lipid con ⁇ centration of 50 ⁇ moles/ml is mixed with an equal volume of anthracycline drug at a concentration of about 5-8 mg/ml.
- anthracycline drug is mixed with an equal volume of anthracycline drug at a concentration of about 5-8 mg/ml.
- the suspen ⁇ sion is treated to remove free (unbound) drug.
- an ion exchange resin such S Dowex 50 WX-4, which is capable of binding the drug.
- the plant alkaloids such as vincristine do not require high loading factors in liposomes due to their intrinsically high anti-tumor activity, and thus can be loaded by passive ntrapment techniques, it also possible to load these drug by active methods. Since vincristine is amphipathic and a weak base, it and similar molecules can be loaded into lipo ⁇ somes using a pH gradient formed by entrapping ammonium sulfate as described above for the anthracycline antibio ⁇ tics.
- the remote loading method just described is illus ⁇ trated in Example 10, which describes the preparation of 0.1 micron MLVs loaded with doxorubicin, to a final drug concentration of about 80-100 ⁇ g/ ⁇ moles lipid.
- SUBSTITUTE SHEET somes show a very low rate of drug leakage when stored a 4°C.
- One of the requirements for liposome localization i a target tumor is a extended liposome lifetime in the bloodstream followin IV liposome administration.
- One measure of liposom lifetime in the bloodstream in the blood/RES ratio deter mined at a selected time after liposome administration as discussed above.
- Blood/RES ratios for a variety o liposome compositions are given in Table 3 of Example 5 In the absence of PEG-derivatized lipids, blood/RE ratios were 0.03 or less.
- the blood/RES ratio ranged from 0.2, fo low-molecular weight PEG, to between 1.7-4 for several o the formulations, one of which lacks cholesterol, an three of which lack an added charged phospholipid (e.g. PG) .
- the blood/RES values reported above can be compar with blood/RES values reported in co-owned U.S. Pate No. 4,920,016, which used blood/RES measurement metho identical to those used in generating the data present in Tables 3 and 5.
- Plasma pharmacokinetics of a liposomal marker in th bloodstream can provide another measure of the enhance liposome lifetime which is achieved by the liposom formulations of the present invention.
- Figure 7 and discussed above show the slow loss of liposomal marke from the bloodstream over a 24 hour period in typica PEG-liposome formulations, substantially independent o whether the marker is a lipid or an encapsulated water soluble compound ( Figure 8) . In both plots, the amoun of liposomal marker present 24 hours after liposom injection is greater than 10% of the originally injecte material.
- Figure 9 shows the kinetics of liposome- loss fro the blood stream for a typical PEG-liposome formulatio and the same liposomes in the absence of a I- ' G-deriva tized lipid. After 24 hours, the percent marker remain ing in the PEG-liposomes was greater than about 20% whereas the conventional liposomes showed less than 5 retention in the blood after 3 hours, and virtually n detectable marker at 24 hours.
- the ability of the liposomes to retain an amp pathic anti-tumor drug in the bloodstream over the 24 period required to provide an opportunity for the li some to reach and enter a systemic tumor has also b investigated.
- plasma pharmacokinetics of doxorubicin loaded in P liposomes, doxorubicin given in free form, and doxoru cin loaded into liposomes containing hydrogenated ph phatidylinositol (HPI) was invested in beagle dogs.
- HPI liposomes were formulated with a predominantly sa rated PC lipid and cholesterol, and represents one of optimal formulations described in the above co-owned U. patent.
- liposome extravasation into Tumors Another required feature for high-activity liposome targeting to a solid tumor, in accordance with the inven ⁇ tion, is liposome extravasation into the tumor through the endothelial cell barrier and underlying basement membrane separating a capillary from the tumor cells supplied by the capillary. This feature is optimized in liposomes having sizes between 0.07 and 0.12 microns.
- SUBSTITUTE SHEET by contrast, lower than with free drug.
- the tumor contained 8 ti more drug compared with healthy muscle and 6 times t amount in heart at 24 hours post injection.
- groups of mi were injected IP with 10 6 J-6456 ly phoma cells. Aft five days the IP tumor had been established, and t animals were treated IV with lO g/kg doxorubicin, eit in free drug form or entrapped in PEG-containing li somes. Tissue distribution of the drug is tabulated Table 9, Example 12.
- the tumor/heart ratio about 272 greater for liposome delivery than for f drug at 24 hours, and about 47 times greater at 48 hour
- the tumor tissue was separat into cellular and supernatant (intercellular flui fractions, and the presence of liposome-associated free drug in both fractions was assayed.
- Figure 13 sh the total amount of drug (filled diamonds) anc' the amo of drug present in tumor cells (solid circles) and sup natant (solid diamonds) over a 48-hour post injecti period.
- the sup natant was passed through an ion-exchange resin to rem free drug, and the drug remaining in the supernatant assayed (solid triangles) . As seen, most of the drug the tumor is liposome-associated.
- FIG. 14 shows the distribution of liposomes (small, . dar stained bodies) in normal liver tissue 24 hours after injection of PEG-liposomes.
- the liposomes are confine exclusively to the Kupfer cells and are not presen either in hepatocytes or in the intercellular fluid o the normal liver tissue.
- Figure 14B shows a region of C-26 colon carcinom implanted in the liver of mice, 24 hours after injectio of PEG-liposomes.
- Liposomes Concentrations of liposomes are clear ly evident in the region of the capillary in the figure on the tumor tissue side of the endothelial barrier an basement membrane. Liposomes are also abundant in th intercellular fluid of the tumor cells, further eviden cing passage from the capillary lumen into the tumor.
- the Figure 14C photomicrograph shows another region o the tumor, where an abundance of liposomes in the inter cellular fluid is also evident.
- a similar finding wa made with liposome extravasation into a region of C-2 colon carcinoma cells injected subcutaneously, as seen i Figure 14D.
- the liposomes of the inventio are effective to localize specifically in a solid tumo region by virtue of the extended lifetime of the lipo somes in the bloodstream and a liposome size which allow both extravasation into tumors, a relatively high dru carrying capacity and minimal leakage of the entrappe drug during the time required for the liposomes to dis tribute to and enter the tumor (the first 24-48 hour following injection) .
- the liposomes thus provide a effective method for localizing a compound selectively t a solid tumor, by entrapping the compound in such lipo somes and injecting the liposomes IV into a subject.
- a solid tumor is defined as one that grow in an anatomical site outside the bloodstream (in con trast, for example, to blood-born tumors such as leuke mias) and requires the formation of small blood vessel and capillaries to supply nutrients, etc. to the growin tumor mass.
- an IV injected liposo and its entrapped anti-tumor drug
- the method is used for tumor treatmen by localizing an anti-tumor drug selectively in th tumor.
- the anti-tumor drug which may be used is an compound, including the ones listed below, which can b stably entrapped in liposomes at a suitable loadin factor and administered at a therapeutically effectiv dose (indicated below in parentheses after eac compound) .
- These include amphipathic anti-tumor com pounds such as the plant alkaloids vincristine (1. mg/m 2 ) , .
- vinblastine (4-18 mg/m 2 ) and etoposide (35-10 mg/m 2 )
- anthracycline antibiotics including doxo rubicin (60-75 mg/m 2 ), epirubicin (60-120 mg/m 2 ) an daunorubicin (25-45 mg/m 2 ) .
- the water-soluble anti-meta bolites such as methotrexate 3 mg/m 2 ) , cytosine arabino side (100 mg/m 2 ), and fluorouracil (10-15 mg/kg), th antibiotics such as bleomycin (10-20 units/m 2 ) , mitomyci (20 mg/m 2 ) , plicamycin (25-30 ⁇ g/m 2 ) and dactincycin (1 ⁇ g/m 2 ) , and the alkylating agents including cyclophospha mide (3-25 mg/kg), thiotepa (0.3-0.4 mg/Kg) and BCN (150-200 mg/m 2 ) are also useful in this context.
- th antibiotics such as bleomycin (10-20 units/m 2 ) , mitomyci (20 mg/m 2 ) , plicamycin (25-30 ⁇ g/m 2 ) and dactincycin (1 ⁇ g/m 2 )
- the plant alkaloids exemplified by vincris tine and the anthracycline antibiotics including doxoru bicin, daunorubicin and epirubicin are preferably active ly loaded into liposomes, to achieve drug/lipid ratio which are several times greater than can be achieved wit passive loading.
- the liposomes ma contain encapsulated tumor-therapeutic peptides a protein drugs , such as IL-2, and/or TNF, and/or immun modulators, such as M-CSF, which are present alone or i combination with anti-tumor drugs, such as an anthracy cline antibiotic drug.
- Example 15 compares the rate of tumor growth in animal with implanted subcutaneously with a C-26 colon carci noma. Treatment was with epirubicin, either in fre form, or entrapped in PEG-liposomes, in accordance wit the invention, with the results shown in Figures 15A- As seen, and discussed more fully in Example 15, treat ment with epirubicin loaded PEG-liposomes produced marked supression of tumor growth and lead to long ter survivors among groups of animals inoculated with normally lethal dose of tumor cells.
- the tumor-treatment method allows both high levels of drug to be administered, due to reduced dr toxicity in liposomes, and greater drug efficacy, due selective liposome localization in the intercellul fluid of the tumor.
- t imaging agent typically a radioisotope in chelated for or a paramagnetic molecule is entrapped in liposome which are then administered IV to the subject bei examined. After a selected period, typically 24- hours, the subject is then monitored, for example gamma scintillation radiography in the case of radiois tope or by NMR in the case of the paramagnetic agent, detect regions of local uptake of the imaging agent.
- PC lecithin or PC
- partially hydrogenated PC having t composition IV40, IV30, IV20, IV10, and IV1, phosphati dylglycerol (PG) , phosphatidylethanolamine (PE) , dipalmi toyl-phosphatidyl glycerol (DPPG) , dipalmitoyl PC (DPPC) dioleyl PC (DOPC) and distearoyl PC (DSPC) were obtain from Avanti Polar Lipids (Birmingham, AL) or Aust Chemical Company (Chicago, IL) .
- PG phosphati dylglycerol
- PE phosphatidylethanolamine
- DPPG dipalmi toyl-phosphatidyl glycerol
- DOPC dipalmitoyl PC
- DOPC dioleyl PC
- DSPC distearoyl PC
- [ 125 I]-tyraminyl-inulin was made according to pu lished procedures. 67 Gallium-8-hydroxyquinoline was su plied by NEN Neoscan (Boston, MA) .
- Doxorubicin HC1 a Epirubicin HCL were obtained from Adria Laboratori (Columbus. OH) or Farmitalia Carlo Erba (Milan, Italy) .
- Cyanuric chloride (5.5 g; 0.03 mol) was dissolved 400 ml of anhydrous benzene containing 10 g of anhydr sodium carbonate, and PEG-1900 (19 g; 0.01 mol) was ad and the mixture was stirred overnight at room tempe ture. The solution was filtered, and 600 ml of petrol ether (boiling range, 35-60°) was added slowly with st ring. The finely divided precipitate was collected on filter and redissolved in 400 ml of benzene.
- the solid compound was taken up in 24 ml of etha nol/chloroform; 50/50 chloroform and centrifuged t remove insoluble material. Evaporation of the clarifie solution to dryness under vacuum afforded 21 mg (7.6 micromoles) of colorless solid.
- Example 2 Preparation of Carbamate and Amide Linked Hydrophilic Polymers with PE A. Preparation of the imidazole carbamate of poly ethylene glycol methyl ether 1900.
- reaction mixture was cooled and the clear solu tion formed at room temperature.
- the solution was dilu ted to 50.0 ml with dry benzene and stored in the refri gerator as a 100 micromole/ml stock solution of th imidazole carbamate of PEG ether 1900.
- B Preparation of the phosphatidylethanolamine ca bamate of polyethylene glycol methyl ether 1900.
- Phosphate analysis suggests a molecular weight o 924,000.
- the desired N-1-trimethylsilyloxy polyethylene glyco 1500 PE was a chief constituent of the 170-300 ml por tions of column effluent. When evaporated to drynes under vacuum these portions afforded 111 mg of pal yellow oil of compound.
- PE compound was dissolved in 2 m of tetrahydrofuran. To this, 6 ml acetic acid and 2 m water was added. The resulting solution was let to stan for 3 days at 23°C. The solvent from the reaction mix ture was evaporated under vacuum and dried to constan weight to obtain 75 mg of pale yellow wax. TLC on Si-C1 reversed-phase plates, developed with a mixture of volumes ethanol, 1 volume water, indicated that some fre PE and some polyglycol-like material formed during th hydrolysis.
- SUBSTITUTE SHEET The product prepared was used for a preparation of PEG-P liposomes.
- the wax was re-dissolved in 5 ml chloroform and trans ⁇ ferred to the top of a 21 X 270 mm column of silica gel moistened with chloroform.
- the column was developed by passing 100 ml of solvent through the column.
- the Table 2 solvents were used in sequence:
- Example 4 Preparation of REVs and MLVs A. Sized REVs A total of 15 ⁇ moles of the selected lip components, in the mole ratios indicated in the exampl below, were dissolved in chloroform and dried as a t film by rotary evaporation. This lipid f lm was di solved in 1 ml of diethyl ether washed with distill water. To this lipid solution was added 0.34 ml of aqueous buffer solution containing 5 mM Tris, 100 NaCl, 0.1 mM EDTA, pH 7.4, and the mixture was emulsifi by sonication for 1 minute, maintaining the temperat of the solution at or below room temperature. Where t liposomes were prepared to contain encapsulated [ 1Z tyraminyl-inulin, such was included in the phosph buffer at a concentration of about 4 ⁇ Ci/ml buffer.
- the ether solvent was removed under reduced pr sure at room temperature, and the resulting gel was ta up in 0.1 ml of the above buffer, and shaken vigorousl
- the resulting REV suspension had particle sizes, determined by microscopic examination, of between abo 0.1 to 20 microns, and was composed predominantly relatively large (greater than 1 micron) vesicles havi one or only a few bilayer lamellae.
- the liposomes were extruded twice through a pol carbonate filter (Szoka, 1978), having a selected po size of 0.4 microns or 0.2 microns. Liposomes extrude through the 0.4 micron filter averaged 0.17 ⁇ (0.05 micron diameters, and through the 0.2 micron filter, 0.1 (0.05) micron diameters. Non-encapsulated [ 12S I] tyr aminyl-inulin was removed by passing the extruded lipo somes through Sephadex G-50 (Pharmacia) .
- Multilamellar vesicle (MLV) liposomes were pre pared according to standard procedures by dissolving mixture of lipids in an organic solvent containing prima rily CHC1 3 and drying the lipids as a thin film by rota tion under reduced pressure.
- a radioactiv label for the lipid phase was added to the lipid solutio before drying.
- the lipid film was hydrated by additio of the desired aqueous phase and 3 mm glass beads fol lowed by agitation with a vortex and shaking above th phase transition temperature of the phospholipid com ponent for at least 1 hour.
- a radioactiv label for the aqueous phase was included in the buffer
- the hydrated lipid was repeatedly froze and thawed three times to provide for ease of the follow ing extrusion step.
- the size of the liposome samples was controlled b extrusion through defined pore polycarbonate filter using pressurized nitrogen gas.
- th liposomes were extruded one time through a filter w pores of 0.4 ⁇ m and then ten times through a filter w pores of 0.1 ⁇ m.
- the liposo were extruded three times through a filter with 0.2 pores followed by repeated extrusion with 0.05 ⁇ m po until the mean diameter of the particles was below 100 as determined by DLS.
- Unencapsulated aqueous compone were removed by passing the extruded sample through a permeation column separating the liposomes in the v volume from the small molecules in the included volume.
- Liposome particle size distribution measureme were obtained by DLS using a NICOMP Model 200 *-*ith Brookhaven Instruments BI-2030AT autocorrelator attach The instruments were operated according to the manuf turer's instructions. The NICOMP results were expres as the mean diameter and standard deviation of a Gauss distribution of vesicles by relative volume.
- Liposome Blood Lifetime Measurements A. Measuring Blood Circulation Time and Bloo RES Ratios
- Swiss-Webster mice at 25 each and laboratory rats .at 200-300 g each.
- the quiet in mice involved tail vein injection of liposome sampl at 1 ⁇ M phospholipid/mouse followed by animal sacrifi after a defined time and tissue removal for label qua titation by gamma counting. The weight and percent the injected dose in each tissue were determined.
- PEG-PE composed of methoxy PEG, molecular weig 1900 and l-palmitoyl-2-oleyl-PE (POPE) was prepared as Example 2.
- the PEG-POPE lipid was combined with a partially hydrogenated egg PC (PHEPC) in a lipid:lip mole ratio of about 0.1:2, and the lipid mixture w hydrated and extruded through a 0.1 micron polycarbona membrane, as described in Example 4, to produce MLV with average size about 0.1 micron.
- the MLV lipi included a small amount of radiolabeled lipid marker 14 cholesteryl oleate, and the encapsulated marker 3 H-i ulin.
- FIG. 7 is a plot of percent injected dose f encapsulated inulin (solid circles) , inulin marker cor rected to the initial injection point of 100% (ope circles) , and lipid marker (closed triangles) , over a 24 hour period post injection. As seen, both lipid an encapsulated markers showed greater than 10% of origina injected dose after 24 hours.
- PEG-PE composed of methoxy PEG, molecular weight 19 and distearylPE (DSPE) was prepared as in Example 2.
- T PEG-PE lipids were formulated with selected lipids fr among sphingomyelin (SM) , fully hydrogenated soy PC (PC cholesterol (Choi) , partially hydrogenated soy (PHSPC) , and partially hydrogenated PC lipids identifi as PC IV1, IV10, IV20, IV30, and IV40 in Table 4.
- SM sphingomyelin
- PC cholesterol Choi
- PHSPC partially hydrogenated soy
- PC lipids identifi as PC IV1, IV10, IV20, IV30, and IV40 in Table 4.
- T lipid components were mixed in the molar ratios shown the left in Table 5, and used to form MLVs sized to 0 micron as described in Example 4.
- the percent material injected (as measured by percent of 14 C-cholesteryl ole- ate) remaining the blood and in the liver (L) and spleen (S) were determined, and these values are shown in the two data columns at the left in Table 4.
- the blood and L+S (RES) values were used to calculate a blood/RES ⁇ -slue for each composition.
- the column at the right in Table 4 shows total amount of radioactivity recovered.
- the two low total recovery values in the table indicate anomalous clearance behavior.
- the results from the table demonstrate that t blood/RES ratios are largely independent of the fluidit or degree of saturation of the phospholipid componen forming the liposomes.
- PEG-PE composed of methoxy PEG, molecular weig
- the PEG-PE lipids were formulated with selected lipi from among sphingomyelin (SM) , fully hydrogenated soy
- Methoxy-ethyoxy-cholesterol was prepared by coupling methoxy ethanol to cholesterol via the trifluorosulfonate coupling method described in Section I.
- PEG-PE composed of methoxy PEG, molecular weight 1900 and was derivatized DSPE as described in Example 6.
- the PEG-PE lipids were formulated with selected lipids from among distearylPC (DSPC) , partially hydrogenated soy ,PC (PHSPC) , choleste ⁇ rol, and ethoxylated cholesterol, as indicated at the right in Table 7.
- DSPC distearylPC
- PHSPC partially hydrogenated soy ,PC
- choleste ⁇ rol choleste ⁇ rol
- ethoxylated cholesterol as indicated at the right in Table 7.
- the data show that (a) ethoxylated cholesterol, in combination with PEG-PE, gives about the same degree of enhancement of liposome lifetime in th blood as PEG-PE alone.
- Example 8 Effect of Charged Lipid Components on Blood/RES Ratios in PEG-PE Liposomes
- PEG-PE composed of methoxy PEG, molecular v: ⁇ e.igh 1900 and was derivatized DSPE as described in Example 6
- the PEG-PE lipids were formulated with lipids selecte from among egg PG (PG) , partially hydrogenated egg P (PHEPC) , and cholesterol (Choi) , as indicated in th Figure 7.
- the two formulations shown in the figur contained about 4.7 mole percent (triangles) or 14 mol percent (circles) PG.
- the lipids were prepared as MLVs sized to 0.1 micron as in Example 4.
- SUBSTITUTESHEET in the composition had little or no effect on liposom retention in the bloodstream.
- the rate of loss of encap sulated marker seen is also similar to that observed fo similarly prepared liposomes containing no PG.
- Example 9 Plasma Kinetics of PEG-Coated and Uncoated Liposomes
- PEG-PE composed of methoxy PEG, molecular weight 1900 and distearylPE (DSPE) was prepared as in Example 2.
- the PEG-PE lipids were formulated with PHEPC, and choles ⁇ terol, in a mole ratio of 0.15:1.85:1.
- a second lipid mixture contained the same lipids, but without PEG-PE.
- Liposomes were prepared from the two lipid mixtures as described in Example 5, by lipid hydration in the pre- sence of desferal mesylate, followed by sizing to 0.1 micron, and removal of non-entrapped desferal by gel filtration with subsequent loading of 67 Ga-oxine into the liposomes.
- the unencapsulated 67 Ga was removed during passage through a Sephadex G-50 gel exclusion cloumn. Both compositions contained 10 ⁇ moles/ml in 0.15 M NaCl, 0.5 mM desferal.
- the two liposome compositions (0.4 ml) were injected IV in animals, as described in Example 6. At time 0.25, 1, 3 or 5 and 24 hours after injection, blood samples. were removed and assayed for amount inulin remaining in the blood, expressed as a percentage of the amount mea ⁇ sured immediately after injection. The results are shown in Figure 9. As seen, the PEG-coated liposomes have a blood halflife of about 11 hours, and nearly 30% o the injected material is present in the blood after 24 hours. By contrast, uncoated liposomes showed a halflife in the blood of less than 1 hour. At 24 hours, the amount of injected material was undetectable.
- Example 10 Example 10
- Vesicle-forming lipids containing PEG-PE, PG, PHEP and cholesterol, in a mole ratio of 0.3: 0.3: 1.4: 1 we dissolved in chloroform to a final lipid concentration
- phospholipid/ml 25 ⁇ mol phospholipid/ml.
- Alpha-tocopherol ( ⁇ -TC) in fr base form was added in chloroform.-methanol (2:1) soluti to a final mole ratio of 0.5%.
- the lipid solution w dried to a thin lipid film, then hydrated with a wa (60°C) solution of 125 mM ammonium sulfate containing mM desferal. Hydration was carried out with 1 ml aqueous solution per 50 ⁇ mole phospholipid.
- the lip material was hydrated with 10 freeze/thaw cycles, usi liquid nitrogen and a warm water bath.
- Liposome sizing was performed by extrusion throu two Nuclepore polycarbonate membranes, 3 cycles throu 0.2 microns filters, and ten cycles through 0.05 micr filters. The final liposome size was 100 nm. The siz liposomes were then dialyzed against 50-100 volumes of glucose three times during a 24 hour period. A four cycle was carried out against 5% glucose titered to 6.5-7.0 for 1 hour.
- the co centration of drug in the mixture was about 5 mg/ml dr 50 ⁇ moles/ml phospholipid.
- the mixture was incubated f 1 hours at 60°C in a water bath with shaking. Untrapp drug was removed by passage through a Dowex 50 WX .es packed in a small column. The column was centrifuged a bench top centrifuge for 5 minutes to completely elu the liposome suspension. Sterilization of the mixtu was by passage through a 0.45 micron membrane, and t liposomes were stored at 5°C
- PEG-PE composed of methoxy PEG, molecular weigh 1900 and distearylPE (DSPE) was prepared as in Example 2.
- the PEG-PE lipids were formulated with hydrogenated so bean PC (HSPC) and cholesterol, in a mole ratio o
- a second lipid mixture containe hydrogenated phosphatidylinositol (HPI), HSPC choleste rol, in a mole ratio of 1:10:5 (HPI-Dox) .
- HPI hydrogenated phosphatidylinositol
- HPI-Dox hydrogenated phosphatidylinositol
- Each lipi formulation was used in preparing sized MLVs containin an ammonium ion gradient, as in Example 10.
- the liposomes were loaded with doxorubicin, by mixing with an equal volume of a doxorubicin solution, 10 mg/ml plus 1 mM desferal, as in Example 15.
- the two compositions are indicated in Figure 11 and Table 7 belo as PEG-DOX and HPI-DOX liposomes, respectively.
- a doxo ⁇ rubicin HC1 solution (the marketed product. Free Dox) was obtained from the hospital pharmacy. Free DOX, PEG-Dox and HPI-Dox were diluted to the same concentration (1.8 mg/ml) using unbuffered 5% glucose on the day of injec ⁇ tion. Dogs were randomized into three groups (2 females, 1 male) and weighed.
- Venflon IV catheter was inserted in a superficial limb vein in each animal.
- the drug and liposome suspensions were injected by quick bolus (15 seconds) .
- Four ml bllod samples were before injection and at 5, 10, 15, 30, 45 min, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 hours post injection.
- blood was also drawn after 96, 120, 144,. and 168 hours.
- Plasma was separated from the formed elements of the whole blood by centrifugation and doxorubicin concentrations assayed by standard fluorescence tech ⁇ niques. The amount of doxorubicin remaining in the bloo was expressed as a percentage of peak concentration o labeled drug, measured immediately after injection.
- PEG-liposomes loaded with doxorubicin were prepare as in Example 11 (PEG-DOX liposomes) . Free drug used wa clinical material obtained from the hospital pharmacy.
- mice Two groups of twelve mice were injected subcutane ously with 10 6 J-6456 tumor cells. After 14 days th tumors had grown to about 1 cm 3 in size in the subcu ⁇ taneous space and the animals were injected IV (tail vein) with 10 mg/kg doxorubicin as free drug (group 1) or encapsulated in PEG liposomes (group 2) .
- group 1 free drug
- group 2 encapsulated in PEG liposomes
- four animal in each group were sacrificed, and sections of tumor, heart, and muscle tissue were excised. Each tissue was weighed, then homo ⁇ genized and extracted for determination of doxorubicin concentration using a standard florescence assay proce- dure (Gabizon, 1989) . The total drug measured in each homogenate was expressed as ⁇ g drug per gram tissue.
- FIGs 12A and 12B The data for drug distribution in heart, muscle, and liver are plotted in Figures 12A and 12B for free and liposome-associated doxorubicin, respectively.
- Figure 12A it is seen that all three tissue types take up about the same amount of drug/g tissue, although initially the drug is taken up preferentially in the heart.
- trast when entrapped in PEG-liposomes, the drug shows a strong selective localization in the tumor, with reduced levels in heart and muscle tissue.
- mice Two groups of 15 mice were injected interperitoneal- ly with 10 ⁇ J-6456 lymphoma cells. The tumor was allowed to grow for one-two weeks at which time 5 ml of ascites fluid had accumulated. The mice were then injected IV with 10 mg/kg doxorubicin either in free drug form (group 1) or entrapped in PEG liposomes as described in Example 11 (group 2) . Ascites fluid was withdrawn from three animals in each group at 1, 4, 15, 24 and 48 hours post treatment. The ascites tumor was further fractionated into cellular and fluid components by centrifugation (15 min. 5000 rpm) .
- Free and liposome-bound drug in the supernatant was determined by passing the fluid through a Dowex WX resin, as above, to remove free drug.
- the doxorubicin concentrations in the ascites fluid, tumo cells, supernatant, and resin-treated supernatant were then determined, and from these values, ⁇ g doxorubicin/ gram tissue was calculated.
- the values for total ascite fluid supernatant (solid diamonds) , supernatant afte removal of free drug (solid triangles) , and isolate tumor cells (solid circles) are plotted in Figure 13. A seen, the total doxorubicin in the ascites fluid in creased steadily up to about 24 hours, then droppe slightly over the next 24 hours. Most of the doxorubici in the tumor is in liposome-entrapped form, demonstratin that liposomes are able to extravasate into solid tumor in intact form.
- mice Two groups of 6 mice were injected subcutaneously with 10 s -10 s C-26 colon carcinoma cells and the tumor was allowed to grow in the subcutaneous space until it reached a size of about 1 cm (about two weeks following injection)
- Each group of animals was then injected with 0.5 mg of eithe conventional liposomes (100 nm DSPC/Chol, 1:1) or PEG lipo somes (100 nm DSPC/Chol/PEG-DSPE, 10:3:1) which had bee loaded with radioactive gallium as described in Example
- Three mice from each group were sacrificed at 2, 24 and 4 hours post treatment, the tumors excised and weighed and th amount of radioactivity quantified using a gamma counter The results are presented in the following table and ar expressed as the percent of the injected dose per gra tissue.
- PEG-PE composed of methoxy PEG, molecular weigh 1900 and distearylPE (DSPE) was prepared as in Example 2
- the PEG-PE lipids were formulated with HSPC, and choles terol, in a mole ratio of 0.15:1.85:1.
- PEG-liposome were prepared to contain colloidal gold particles (Hong)
- the resulting MLVs were sized by extrusion, as above, t an average 0.1 micron size. Non-entrapped material wa removed by gel filtration. The final concentration o liposomes in the suspension was about 10 ⁇ mol/ml.
- SUBSTITUTESHEET In a first study, a normal mouse was injected IV with 0.4 ml of the above liposome formulation. Twenty four hours after injection, the animal was sacrificed, and sections of the liver removed fixed in a standard water-soluble plastic resin. Thick sections were cut with a microtome and the sections stained with a solution of silver nitrate according to instructions provided with the "Intense 2" System kit supplied by Jannsen Life Sciences, Inc. (Kingsbridge, Piscataway, N.J.). The sections were further stained with eosin and hemotoxylin.
- Figure 14A is a photomicrograph of a typically liver section, showing smaller, irregularly shaped Kupfer cells, such as cells 20, among larger, more regular shaped hepatocytes, such as hepatocyes 22.
- the Kupfer cells show large concentrations of intact liposomes, seen as small, darkly stained bodies, such at 24 in Figure 14A.
- the hepatocytes are largely free of liposomes, as would be expected.
- a C-26 colon carcinoma (about 10 6 c ⁇ U) was implanted in a mouse liver. Fourteen days post implantation, the animal was injected IV with 0.5 mg of the above liposomes.
- FIG. 14B shows a capillary 26 feeding a region of carcinoma cells, such as cells 28. These cells have characteristic staining patterns, and often include darkly stained nuclii in various stages of mitosis.
- the capillary in the figure is lined by an endothelial barrier 30, and just below that, a basement membrane 32.
- liposomes such as liposomes 34
- liposomes 34 are heavily concentrated in the tumor re ⁇ gion, adjacent the capillary on the tumor side of the endothelial barrier and basement membrane, and many lipo- somes are also dispersed throughout the intercellular fluid surrounding the tumor cells.
- Figure 14C shows another region of the liver tumor from the above animal. Liposomes are seen throughout the intercellular fluid bathing the carcinoma cells.
- C26 colon carcinoma cells were injected subcutaneously into an animal, and allowed to grow in the animal for 28 days. Thereafter, the animal was injected IV with 0.5 mg of the above liposomes. Twenty four hours later, the animal was sacrificed, and the tumor mass was excised. After embeding, tumor mass was sectioned on a microtome and stained as above.
- Figure 14D shows a region of the tumor cells, including a cell 36 in the center of the figure which is in late stage mitosis. Small, darkly stained liposomes are seen throughout the intercellular fluid.
- Example 15 Tumor Treatment Method
- Vesicle-forming lipids containing PEG-PE, PG, PHEPC, and cholesterol and ⁇ -TC in a mole ratio of 0.3: 0.3: 1.4: 1: 0.2 were dissolved in chloroform to a final lipid concentration of 25 ⁇ ol phospholipid/ml.
- the lipid mix ⁇ ture was dried into a thin film under reduced pressure.
- the film was hydrated with a solution of .125M ammcnium sulfate to form MLVs.
- the MLV suspension was frozen in a dry ice acetone bath and thawed three times and sized to 80-100 nm.
- An ammonium ion gradient was created substan ⁇ tially as described in Example 10.
- the liposomes were loaded with epirubicin, and free (unbound drug) removed also as described in Example 10 for doxorubicin.
- the final concentration of entrapped drug was about 50-100 ⁇ g drug/ ⁇ mol lipid.
- Epirubicin HC1 and doxorubicin HCL, the commercial products, were obtained from the hospital pharmacy.
- C-26 colon carcinoma cells were injected subcutaneously into three groups of 35 mice. The groups were subdivided into 5 7-animal subgroups.
- each subgroup was injected IV with 0.5 ml of either saline vehicle control (open circles) , 6 mg/kg epirubicin (open triangles) , 6 mg/kg doxorubicin (filled circles) , or the drug-loaded liposomes (PEG-DOX liposomes) at two doses, 6mg/kg (filled triangles) and 12 mg/kg (open squares) on days 1, 8 and 15 following tumor cell implan ⁇ tation. Each group was followed for 28 days. Tumor size was measured for each animal on days 5,7,12,14,17,21,24 and 28. The growth of the tumor in each subgroup (ex ⁇ pressed as the mean tumor size of the individual animals) at each time point is plotted in Figure 15A.
- Figure 15B and 15C The results of delayed treatment experiments using the same tumor model are presented in Figure 15B and 15C The same number of animals were inoculated with the same number of tumor cells as described above.
- the treatment groups in Figures 15B and 15C consisted of saline (solid line), 6 mg/kg epirubicin (filled triangles), 6 mg/kg free epirubicin plus empty PEG liposomes (open circles) and two doses of epirubicin entrapped in PEG liposomes, 6 mg/kg (filled triangles) and 9 mg/kg (open squares) .
- Example 16 Tumor Treatment Method PEG-DOX liposomes were prepared as in Example 15 except that doxorubicin was loaded in the liposomes to a final level of 60-80 ⁇ g/ ⁇ moles total lipid.
- a doxorubi ⁇ cin HC1 solution to be used as the free drug control was obtained from a hospital pharmacy.
- a total of 30 mice were injected IP with 10 6 J-6456 lymphoma cells.
- the animals were divided into three 10-animal groups, each of which was injected IV with 0.4 ml of either saline vehi ⁇ cle, 10 mg/kg doxorubicin solution or the doxorubicin- loaded liposomes at 10 mg/kg.
- Each group was followed for 100 days for number of surviving animals. The per- cent survivors for each treatment group is plotted in Figure 16.
- Example 17 Reduced Toxicity of PEG-Liposomes Solutions of free doxorubicin HC1, epirubicin HC1 were obtained as above. PEG-liposome formulations con- taining either doxorubicin or epirubicin, at a drug concentration of 70-90 ⁇ g compound/ ⁇ mole liposome lipid, were prepared as described in Example 16. Conventional liposomes (no PEG-derivatized lipid) were loaded with doxorubicin to a drug concentration of 40 ⁇ g/ ⁇ mole lipid using standard techniques.
- Each of the five formulations was administered to 35 mice, at a dose between 10 and 40 mg drug/kg body weight, in 5 mg/kG increments, with five receiving each dosage.
- the maximum tolerated dose given in Table 11 below is highest dose which did not cause death or dramatic weight loss in the injected animals within 14 days.
- both DOX-liposomes and PEG-DOX liposomes more than doubled the tolerated dose of doxorubicin over the drug in free form, with the PEG-DOX liposomes giving a slightly higher tolerated dose.
- a similar result was obtained for doses of tolerated epirubicin in free and PEG-liposomal form.
- Example 18 Tumor Treatment Method Conventional doxorubicin liposomes (L-DOX) were pre pared according to published methods. Briefly, a mixtur of eggPG, Egg,PC, cholesterol and a-TC in a mole ratio o 0.3: 1.4: 1: 0.2 was made in chloroform. The solvent wa removed under reduced presssure and the dry lipid fil hydrated with a solution of 155 mM NaCl containing 2-5 m doxorubicin HC1. The resulting MLV preparation was down sized by extrusion through a series of polycarbonat membranes to a final size of about 250 nm. The fre (unentrapped) drug was removed by passing the suspensio over a bed of Dowex resin. The final doxorubicin con centration was about 40 per ⁇ mole lipid.
- mice Three groups of 7 mice were inoculated subcutaneous ly with 10 5 - 10 6 C-26 colon carcinoma cells as detaile in Example 15.
- the animals were divided into three, 7 animal treatment groups, one of which receivd 0.5 ml o saline vehicle as a control.
- the other two groups were treated with doxorubicin either as a free drug solutio or in the form of L-DOX liposomes at a dose of 10 mg/kg.
- the treatments were given on days 8, 15 and 22 afte tumor cell inoculation. Tumor size was measured on th days treatments were given and day 28.
- the free drug filled circles
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Separation By Low-Temperature Treatments (AREA)
- Control Of El Displays (AREA)
- Wire Bonding (AREA)
- Saccharide Compounds (AREA)
- Colloid Chemistry (AREA)
Abstract
Description
Claims
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19675048C DE19675048I2 (en) | 1989-10-20 | 1990-10-19 | METHOD AND COMPOSITION FOR THE TREATMENT OF SOLID TUMORS. |
DE69019366T DE69019366T2 (en) | 1989-10-20 | 1990-10-19 | METHOD AND COMPOSITION FOR TREATING SOLID TUMORS. |
EP91900513A EP0496835B1 (en) | 1989-10-20 | 1990-10-19 | Solid tumor treatment method and composition |
AU68982/91A AU654120B2 (en) | 1989-10-20 | 1990-10-19 | Solid tumor treatment method and composition |
NO920996A NO304637B1 (en) | 1989-10-20 | 1992-03-27 | Process for the preparation of a liposome composition |
FI921764A FI105151B (en) | 1989-10-20 | 1992-04-21 | A method of making a liposome composition for locating a tumor imaging agent or an antitumor agent |
GR950402186T GR3017060T3 (en) | 1989-10-20 | 1995-08-09 | Solid tumor treatment method and composition. |
LU88854C LU88854I2 (en) | 1989-10-20 | 1996-12-13 | Pgylated liposomal doxorubicin optionally in the form of a salt for pharmaceutical use |
NL960031C NL960031I2 (en) | 1989-10-20 | 1996-12-18 | Fixed tumor treatment, method and composition. |
HK14097A HK14097A (en) | 1989-10-20 | 1997-02-05 | Solid tumor treatment method and composition |
NO1999003C NO1999003I1 (en) | 1989-10-20 | 1999-02-23 | Pegylated liposomal doxorubicin |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US425,224 | 1989-10-20 | ||
US07/425,224 US5013556A (en) | 1989-10-20 | 1989-10-20 | Liposomes with enhanced circulation time |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1991005546A1 true WO1991005546A1 (en) | 1991-05-02 |
Family
ID=23685679
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1990/006034 WO1991005545A1 (en) | 1989-10-20 | 1990-10-19 | Liposome microreservoir composition and method |
PCT/US1990/006211 WO1991005546A1 (en) | 1989-10-20 | 1990-10-19 | Solid tumor treatment method and composition |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1990/006034 WO1991005545A1 (en) | 1989-10-20 | 1990-10-19 | Liposome microreservoir composition and method |
Country Status (18)
Country | Link |
---|---|
US (2) | US5013556A (en) |
EP (2) | EP0496835B1 (en) |
JP (4) | JP2667051B2 (en) |
KR (2) | KR0134982B1 (en) |
AT (2) | ATE122229T1 (en) |
AU (2) | AU654120B2 (en) |
CA (2) | CA2067178C (en) |
DE (3) | DE19675048I2 (en) |
DK (1) | DK0496835T3 (en) |
ES (1) | ES2071976T3 (en) |
FI (2) | FI105151B (en) |
GR (1) | GR3017060T3 (en) |
HK (1) | HK14097A (en) |
IL (2) | IL96069A (en) |
LU (1) | LU88854I2 (en) |
NL (1) | NL960031I2 (en) |
NO (3) | NO921213L (en) |
WO (2) | WO1991005545A1 (en) |
Cited By (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993019738A1 (en) * | 1992-03-27 | 1993-10-14 | Liposome Technology, Inc. | Method of treatment of infected tissues |
EP0526700A3 (en) * | 1991-05-23 | 1994-01-26 | Mitsubishi Chem Ind | |
WO1994022429A1 (en) * | 1993-03-31 | 1994-10-13 | Liposome Technology, Inc. | Solid-tumor treatment method |
EP0656368A1 (en) * | 1992-08-05 | 1995-06-07 | Meito Sangyo Kabushiki Kaisha | Small-diameter composite composed of water-soluble carboxypolysaccharide and magnetic iron oxide |
US5556948A (en) * | 1993-01-22 | 1996-09-17 | Mitsubishi Chemical Corporation | Phospholipid derivatized with PEG bifunctional linker and liposome containing it |
WO1996034598A1 (en) * | 1995-05-03 | 1996-11-07 | Polymasc Pharmaceuticals Plc | Tissue entrapment |
WO1998007409A1 (en) * | 1996-08-23 | 1998-02-26 | Sequus Pharmaceuticals, Inc. | Liposomes containing a cisplatin compound |
US5820873A (en) * | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
US5827533A (en) * | 1997-02-06 | 1998-10-27 | Duke University | Liposomes containing active agents aggregated with lipid surfactants |
US5885613A (en) * | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
WO1999027908A1 (en) * | 1997-12-04 | 1999-06-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
WO2000067760A1 (en) * | 1999-05-11 | 2000-11-16 | Sankyo Company, Limited | Liposome preparation of fat-soluble antitumor drug |
WO2001011069A1 (en) | 1999-08-06 | 2001-02-15 | Celltech R&D Limited | Freeze/thawed lipid complexes and their preparation |
WO2001041738A2 (en) * | 1999-12-10 | 2001-06-14 | Celator Technologies Inc. | Lipid carrier compositions with protected surface reactive functions |
EP1179340A2 (en) * | 1994-09-30 | 2002-02-13 | INEX Pharmaceutical Corp. | Compositions for the introduction of polyanionic materials into cells |
US6673364B1 (en) | 1995-06-07 | 2004-01-06 | The University Of British Columbia | Liposome having an exchangeable component |
WO2004019913A1 (en) * | 2002-08-29 | 2004-03-11 | Monte Verde S.A. | A pharmaceutical composition of small-sized liposomes and method of preparation |
US6734171B1 (en) | 1997-10-10 | 2004-05-11 | Inex Pharmaceuticals Corp. | Methods for encapsulating nucleic acids in lipid bilayers |
EP1435231A1 (en) * | 2002-12-31 | 2004-07-07 | Bharat Serums & Vaccines Ltd. | Non-pegylated long-circulating liposomes |
WO2004063216A1 (en) * | 2003-01-10 | 2004-07-29 | Yamanouchi Pharmaceutical Co., Ltd. | Conjugate for retention in blood and cancer tissue-specific drug delivery |
US7169892B2 (en) | 2003-01-10 | 2007-01-30 | Astellas Pharma Inc. | Lipid-peptide-polymer conjugates for long blood circulation and tumor specific drug delivery systems |
EP2382996A2 (en) | 2005-02-18 | 2011-11-02 | The University of Tokushima | Lipid Film Structure Containing a Polyoxyalkylene Chain-Containing Lipid Derivative. |
EP2535347A1 (en) * | 2002-09-30 | 2012-12-19 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
US8895557B2 (en) | 2004-10-29 | 2014-11-25 | Pharma Mar, S.A., Sociedad Unipersonal | Pharmaceutical formulations of ecteinascidin compounds |
US8926955B2 (en) | 2008-12-22 | 2015-01-06 | Creabilis S.A. | Synthesis of polymer conjugates of indolocarbazole compounds |
US8961929B2 (en) | 2010-01-08 | 2015-02-24 | Fujifilm Corporation | Targeting agent for tumor site |
US9192568B2 (en) | 2005-10-31 | 2015-11-24 | Pharma Mar, S.A. | Formulations comprising jorumycin-, renieramycin-, safracin- or saframycin-related compounds for treating proliferative diseases |
US9566238B2 (en) | 2010-06-19 | 2017-02-14 | Western University Of Health Sciences | Formulation of PEGylated-liposome encapsulated glycopeptide antibiotics |
WO2020055929A1 (en) * | 2018-09-11 | 2020-03-19 | Memorial Sloan Kettering Cancer Center | Bone marrow-, reticuloendothelial system-, and/or lymph node-targeted radiolabeled liposomes and methods of their diagnostic and therapeutic use |
US11633502B2 (en) | 2016-03-07 | 2023-04-25 | Memorial Sloan Kettering Cancer Center | Bone marrow-, reticuloendothelial system-, and/or lymph node-targeted radiolabeled liposomes and methods of their diagnostic and therapeutic use |
Families Citing this family (1576)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5882330A (en) * | 1984-05-25 | 1999-03-16 | Lemelson; Jerome H. | Drugs and methods for treating diseases |
US5456663A (en) * | 1984-05-25 | 1995-10-10 | Lemelson; Jerome H. | Drugs and methods for treating diseases |
US5925375A (en) * | 1987-05-22 | 1999-07-20 | The Liposome Company, Inc. | Therapeutic use of multilamellar liposomal prostaglandin formulations |
JPH0720857B2 (en) * | 1988-08-11 | 1995-03-08 | テルモ株式会社 | Liposome and its manufacturing method |
US6132763A (en) * | 1988-10-20 | 2000-10-17 | Polymasc Pharmaceuticals Plc | Liposomes |
GB8824593D0 (en) * | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Liposomes |
US5153000A (en) * | 1988-11-22 | 1992-10-06 | Kao Corporation | Phosphate, liposome comprising the phosphate as membrane constituent, and cosmetic and liposome preparation comprising the liposome |
US5356633A (en) * | 1989-10-20 | 1994-10-18 | Liposome Technology, Inc. | Method of treatment of inflamed tissues |
US20010051183A1 (en) * | 1989-10-20 | 2001-12-13 | Alza Corporation | Liposomes with enhanced circulation time and method of treatment |
US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5620689A (en) * | 1989-10-20 | 1997-04-15 | Sequus Pharmaceuuticals, Inc. | Liposomes for treatment of B-cell and T-cell disorders |
US6088613A (en) * | 1989-12-22 | 2000-07-11 | Imarx Pharmaceutical Corp. | Method of magnetic resonance focused surgical and therapeutic ultrasound |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5773024A (en) * | 1989-12-22 | 1998-06-30 | Imarx Pharmaceutical Corp. | Container with multi-phase composition for use in diagnostic and therapeutic applications |
US6551576B1 (en) | 1989-12-22 | 2003-04-22 | Bristol-Myers Squibb Medical Imaging, Inc. | Container with multi-phase composition for use in diagnostic and therapeutic applications |
US5733572A (en) * | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
US5542935A (en) * | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US5705187A (en) * | 1989-12-22 | 1998-01-06 | Imarx Pharmaceutical Corp. | Compositions of lipids and stabilizing materials |
US5352435A (en) * | 1989-12-22 | 1994-10-04 | Unger Evan C | Ionophore containing liposomes for ultrasound imaging |
US5469854A (en) * | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
US5305757A (en) * | 1989-12-22 | 1994-04-26 | Unger Evan C | Gas filled liposomes and their use as ultrasonic contrast agents |
US6146657A (en) | 1989-12-22 | 2000-11-14 | Imarx Pharmaceutical Corp. | Gas-filled lipid spheres for use in diagnostic and therapeutic applications |
US5776429A (en) * | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US5441746A (en) * | 1989-12-22 | 1995-08-15 | Molecular Bioquest, Inc. | Electromagnetic wave absorbing, surface modified magnetic particles for use in medical applications, and their method of production |
US5580575A (en) * | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US6001335A (en) * | 1989-12-22 | 1999-12-14 | Imarx Pharmaceutical Corp. | Contrasting agents for ultrasonic imaging and methods for preparing the same |
US5922304A (en) * | 1989-12-22 | 1999-07-13 | Imarx Pharmaceutical Corp. | Gaseous precursor filled microspheres as magnetic resonance imaging contrast agents |
US5656211A (en) * | 1989-12-22 | 1997-08-12 | Imarx Pharmaceutical Corp. | Apparatus and method for making gas-filled vesicles of optimal size |
US5882678A (en) * | 1990-01-12 | 1999-03-16 | The Liposome Co, Inc. | Interdigitation-fusion liposomes containing arachidonic acid metabolites |
US5162361A (en) * | 1990-04-10 | 1992-11-10 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Method of treating diseases associated with elevated levels of interleukin 1 |
US6465188B1 (en) * | 1990-06-11 | 2002-10-15 | Gilead Sciences, Inc. | Nucleic acid ligand complexes |
US20060084797A1 (en) * | 1990-06-11 | 2006-04-20 | Gilead Sciences, Inc. | High affinity TGFbeta nucleic acid ligands and inhibitors |
US20030113369A1 (en) * | 1991-01-16 | 2003-06-19 | Martin Francis J. | Liposomes with enhanced circulation time and method of treatment |
US5874062A (en) * | 1991-04-05 | 1999-02-23 | Imarx Pharmaceutical Corp. | Methods of computed tomography using perfluorocarbon gaseous filled microspheres as contrast agents |
US5205290A (en) | 1991-04-05 | 1993-04-27 | Unger Evan C | Low density microspheres and their use as contrast agents for computed tomography |
GB9111611D0 (en) * | 1991-05-30 | 1991-07-24 | Sandoz Ltd | Liposomes |
ES2221920T3 (en) | 1992-04-03 | 2005-01-16 | The Regents Of The University Of California | SELF-ASSEMBLY POLYUCLEOTID RELEASE SYSTEM THAT INCLUDES AN AMPHIPATIC CATIONIC PEPTIDE. |
ZA933926B (en) * | 1992-06-17 | 1994-01-03 | Amgen Inc | Polyoxymethylene-oxyethylene copolymers in conjuction with blomolecules |
NL9201722A (en) * | 1992-10-05 | 1994-05-02 | Stichting Tech Wetenschapp | Pharmaceutical composition for the site-bound release of a clot dissolving protein and method for its preparation. |
DE4236237A1 (en) * | 1992-10-27 | 1994-04-28 | Behringwerke Ag | Prodrugs, their preparation and use as medicines |
US6764693B1 (en) * | 1992-12-11 | 2004-07-20 | Amaox, Ltd. | Free radical quenching composition and a method to increase intracellular and/or extracellular antioxidants |
US5395619A (en) * | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
AU6368394A (en) * | 1993-03-23 | 1994-10-11 | Liposome Technology, Inc. | Polymer-polypeptide composition and method |
US6326353B1 (en) * | 1993-03-23 | 2001-12-04 | Sequus Pharmaceuticals, Inc. | Enhanced circulation effector composition and method |
US6180134B1 (en) * | 1993-03-23 | 2001-01-30 | Sequus Pharmaceuticals, Inc. | Enhanced ciruclation effector composition and method |
WO1994026251A1 (en) * | 1993-05-07 | 1994-11-24 | Sequus Pharmaceuticals, Inc. | Subcutaneous liposome delivery method |
US6191105B1 (en) | 1993-05-10 | 2001-02-20 | Protein Delivery, Inc. | Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin |
US5681811A (en) * | 1993-05-10 | 1997-10-28 | Protein Delivery, Inc. | Conjugation-stabilized therapeutic agent compositions, delivery and diagnostic formulations comprising same, and method of making and using the same |
US5359030A (en) * | 1993-05-10 | 1994-10-25 | Protein Delivery, Inc. | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
US20050181976A1 (en) * | 1993-05-10 | 2005-08-18 | Ekwuribe Nnochiri N. | Amphiphilic oligomers |
WO1994027580A1 (en) * | 1993-05-21 | 1994-12-08 | The Liposome Company, Inc. | Reduction of liposome-induced adverse physiological reactions |
US5744155A (en) * | 1993-08-13 | 1998-04-28 | Friedman; Doron | Bioadhesive emulsion preparations for enhanced drug delivery |
US5514670A (en) * | 1993-08-13 | 1996-05-07 | Pharmos Corporation | Submicron emulsions for delivery of peptides |
DK0725629T3 (en) * | 1993-10-25 | 2000-08-07 | Liposome Co Inc | Liposomal defensins |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
US5468499A (en) * | 1993-11-15 | 1995-11-21 | Ohio State University | Liposomes containing the salt of phosphoramide mustard and related compounds |
US7083572B2 (en) * | 1993-11-30 | 2006-08-01 | Bristol-Myers Squibb Medical Imaging, Inc. | Therapeutic delivery systems |
JPH09506866A (en) * | 1993-12-14 | 1997-07-08 | ジョーンズ ホプキンス ユニバーシティー スクール オブ メディシン | Controlled release of pharmaceutically active substances for immunotherapy |
US6773719B2 (en) * | 1994-03-04 | 2004-08-10 | Esperion Luv Development, Inc. | Liposomal compositions, and methods of using liposomal compositions to treat dislipidemias |
US6312719B1 (en) * | 1994-03-04 | 2001-11-06 | The University Of British Columbia | Liposome compositions and methods for the treatment of atherosclerosis |
US20010055581A1 (en) * | 1994-03-18 | 2001-12-27 | Lawrence Tamarkin | Composition and method for delivery of biologically-active factors |
US5736121A (en) * | 1994-05-23 | 1998-04-07 | Imarx Pharmaceutical Corp. | Stabilized homogenous suspensions as computed tomography contrast agents |
DE4423131A1 (en) * | 1994-07-01 | 1996-01-04 | Bayer Ag | New hIL-4 mutant proteins as antagonists or partial agonists of human interleukin 4 |
US5626862A (en) | 1994-08-02 | 1997-05-06 | Massachusetts Institute Of Technology | Controlled local delivery of chemotherapeutic agents for treating solid tumors |
US5512294A (en) * | 1994-08-05 | 1996-04-30 | Li; King C. | Targeted polymerized liposome contrast agents |
US6132764A (en) | 1994-08-05 | 2000-10-17 | Targesome, Inc. | Targeted polymerized liposome diagnostic and treatment agents |
US6471956B1 (en) | 1994-08-17 | 2002-10-29 | The Rockefeller University | Ob polypeptides, modified forms and compositions thereto |
US6350730B1 (en) | 1994-08-17 | 2002-02-26 | The Rockefeller University | OB polypeptides and modified forms as modulators of body weight |
US6124439A (en) * | 1994-08-17 | 2000-09-26 | The Rockefeller University | OB polypeptide antibodies and method of making |
US6124448A (en) * | 1994-08-17 | 2000-09-26 | The Rockfeller University | Nucleic acid primers and probes for the mammalian OB gene |
US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
US6048837A (en) * | 1994-08-17 | 2000-04-11 | The Rockefeller University | OB polypeptides as modulators of body weight |
US6001968A (en) * | 1994-08-17 | 1999-12-14 | The Rockefeller University | OB polypeptides, modified forms and compositions |
JPH10507450A (en) * | 1994-10-14 | 1998-07-21 | ザ リポソーム カンパニー、インコーポレーテッド | Ether lipid liposomes and their therapeutic use |
CN1080575C (en) * | 1994-10-14 | 2002-03-13 | 蛋白质传送股份有限公司 | Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same |
US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
US6743779B1 (en) | 1994-11-29 | 2004-06-01 | Imarx Pharmaceutical Corp. | Methods for delivering compounds into a cell |
US5827531A (en) * | 1994-12-02 | 1998-10-27 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Microcapsules and methods for making |
US6008202A (en) * | 1995-01-23 | 1999-12-28 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
US5795587A (en) * | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
US5830430A (en) * | 1995-02-21 | 1998-11-03 | Imarx Pharmaceutical Corp. | Cationic lipids and the use thereof |
IL112834A (en) * | 1995-03-01 | 2000-12-06 | Yeda Res & Dev | Pharmaceutical compositions for controlled release of soluble receptors |
US5658588A (en) * | 1995-03-31 | 1997-08-19 | University Of Cincinnati | Fibrinogen-coated liposomes |
US8071737B2 (en) * | 1995-05-04 | 2011-12-06 | Glead Sciences, Inc. | Nucleic acid ligand complexes |
US5997898A (en) * | 1995-06-06 | 1999-12-07 | Imarx Pharmaceutical Corp. | Stabilized compositions of fluorinated amphiphiles for methods of therapeutic delivery |
US6420549B1 (en) | 1995-06-06 | 2002-07-16 | Isis Pharmaceuticals, Inc. | Oligonucleotide analogs having modified dimers |
US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
US6139819A (en) | 1995-06-07 | 2000-10-31 | Imarx Pharmaceutical Corp. | Targeted contrast agents for diagnostic and therapeutic use |
US6231834B1 (en) | 1995-06-07 | 2001-05-15 | Imarx Pharmaceutical Corp. | Methods for ultrasound imaging involving the use of a contrast agent and multiple images and processing of same |
US5981501A (en) * | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
US6521211B1 (en) | 1995-06-07 | 2003-02-18 | Bristol-Myers Squibb Medical Imaging, Inc. | Methods of imaging and treatment with targeted compositions |
JP4335310B2 (en) * | 1995-06-07 | 2009-09-30 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | Lipid-nucleic acid particles prepared through hydrophobic lipid-nucleic acid complex intermediates and use for gene transfer |
US6033645A (en) * | 1996-06-19 | 2000-03-07 | Unger; Evan C. | Methods for diagnostic imaging by regulating the administration rate of a contrast agent |
JPH11511128A (en) * | 1995-08-01 | 1999-09-28 | ノバルティス・アクチエンゲゼルシャフト | Liposome oligonucleotide composition |
US6107332A (en) | 1995-09-12 | 2000-08-22 | The Liposome Company, Inc. | Hydrolysis-promoting hydrophobic taxane derivatives |
US6051600A (en) * | 1995-09-12 | 2000-04-18 | Mayhew; Eric | Liposomal hydrolysis-promoting hydrophobic taxane derivatives |
US5834025A (en) | 1995-09-29 | 1998-11-10 | Nanosystems L.L.C. | Reduction of intravenously administered nanoparticulate-formulation-induced adverse physiological reactions |
US5858397A (en) * | 1995-10-11 | 1999-01-12 | University Of British Columbia | Liposomal formulations of mitoxantrone |
EA199800279A1 (en) * | 1995-10-11 | 1999-04-29 | Талариа Терапьютикс, Инк | LIPOSOMIC COMPOSITIONS AND METHODS OF THEIR APPLICATION |
US6936439B2 (en) * | 1995-11-22 | 2005-08-30 | Amgen Inc. | OB fusion protein compositions and methods |
US20030040467A1 (en) * | 1998-06-15 | 2003-02-27 | Mary Ann Pelleymounter | Ig/ob fusions and uses thereof. |
US5626654A (en) | 1995-12-05 | 1997-05-06 | Xerox Corporation | Ink compositions containing liposomes |
US5817856A (en) * | 1995-12-11 | 1998-10-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Radiation-protective phospholipid and method |
US5789244A (en) * | 1996-01-08 | 1998-08-04 | Canji, Inc. | Compositions and methods for the treatment of cancer using recombinant viral vector delivery systems |
US6392069B2 (en) | 1996-01-08 | 2002-05-21 | Canji, Inc. | Compositions for enhancing delivery of nucleic acids to cells |
US20040014709A1 (en) * | 1996-01-08 | 2004-01-22 | Canji, Inc. | Methods and compositions for interferon therapy |
CA2241564C (en) | 1996-01-08 | 2013-09-03 | Genentech, Inc. | Wsx receptor and ligands |
US7002027B1 (en) | 1996-01-08 | 2006-02-21 | Canji, Inc. | Compositions and methods for therapeutic use |
US6096336A (en) * | 1996-01-30 | 2000-08-01 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
US5908624A (en) * | 1996-06-27 | 1999-06-01 | Albany Medical College | Antigenic modulation of cells |
US5965159A (en) | 1996-02-16 | 1999-10-12 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
US6007839A (en) * | 1996-02-16 | 1999-12-28 | The Liposome Company, Inc. | Preparation of pharmaceutical compositions containing etherlipid-containing multiple lipid liposomes |
USRE39042E1 (en) * | 1996-02-16 | 2006-03-28 | The Liposome Company, Inc. | Etherlipid-containing multiple lipid liposomes |
US5942246A (en) * | 1996-02-16 | 1999-08-24 | The Liposome Company, Inc. | Etherlipid containing multiple lipid liposomes |
US6667053B1 (en) | 1996-02-16 | 2003-12-23 | Elan Pharmaceuticals, Inc. | D and L etherlipid stereoisomers and liposomes |
AU2549297A (en) | 1996-03-28 | 1997-10-17 | Board Of Trustees Of The University Of Illinois, The | Materials and methods for making improved echogenic liposome compositions |
ATE345682T1 (en) | 1996-05-01 | 2006-12-15 | Imarx Pharmaceutical Corp | IN VITRO METHOD FOR INTRODUCING NUCLEIC ACIDS INTO A CELL |
US20070275921A1 (en) * | 1996-06-06 | 2007-11-29 | Isis Pharmaceuticals, Inc. | Oligomeric Compounds That Facilitate Risc Loading |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US20050042647A1 (en) * | 1996-06-06 | 2005-02-24 | Baker Brenda F. | Phosphorous-linked oligomeric compounds and their use in gene modulation |
US9096636B2 (en) | 1996-06-06 | 2015-08-04 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
US7812149B2 (en) | 1996-06-06 | 2010-10-12 | Isis Pharmaceuticals, Inc. | 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations |
US5919480A (en) | 1996-06-24 | 1999-07-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Liposomal influenza vaccine composition and method |
US8007784B1 (en) | 1996-06-27 | 2011-08-30 | Albany Medical College | Antigenic modulation of cells |
US6284267B1 (en) | 1996-08-14 | 2001-09-04 | Nutrimed Biotech | Amphiphilic materials and liposome formulations thereof |
US7368129B1 (en) | 1996-08-14 | 2008-05-06 | Nutrimed Biotech | Amphiphilic materials and liposome formulations thereof |
US5851984A (en) * | 1996-08-16 | 1998-12-22 | Genentech, Inc. | Method of enhancing proliferation or differentiation of hematopoietic stem cells using Wnt polypeptides |
US6159462A (en) * | 1996-08-16 | 2000-12-12 | Genentech, Inc. | Uses of Wnt polypeptides |
ATE252891T1 (en) * | 1996-08-26 | 2003-11-15 | Transgene Sa | CATIONIC LIPID-NUCLIC ACID COMPLEXES |
US6414139B1 (en) | 1996-09-03 | 2002-07-02 | Imarx Therapeutics, Inc. | Silicon amphiphilic compounds and the use thereof |
US5846517A (en) * | 1996-09-11 | 1998-12-08 | Imarx Pharmaceutical Corp. | Methods for diagnostic imaging using a renal contrast agent and a vasodilator |
AU736056B2 (en) * | 1996-09-11 | 2001-07-26 | Imarx Pharmaceutical Corp. | Improved methods for diagnostic imaging using a contrast agent and a vasodilator |
WO1998016201A1 (en) * | 1996-10-11 | 1998-04-23 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
TW520297B (en) * | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
US6224903B1 (en) | 1996-10-11 | 2001-05-01 | Sequus Pharmaceuticals, Inc. | Polymer-lipid conjugate for fusion of target membranes |
NZ336539A (en) * | 1996-10-15 | 2000-09-29 | Liposome Co Inc | Peptide-lipid conjugates, liposomes and liposomal drug delivery |
US6339069B1 (en) * | 1996-10-15 | 2002-01-15 | Elan Pharmaceuticalstechnologies, Inc. | Peptide-lipid conjugates, liposomes and lipsomal drug delivery |
US6261537B1 (en) | 1996-10-28 | 2001-07-17 | Nycomed Imaging As | Diagnostic/therapeutic agents having microbubbles coupled to one or more vectors |
US20070036722A1 (en) * | 1996-10-28 | 2007-02-15 | Pal Rongved | Separation processes |
DE69735354T2 (en) * | 1996-10-28 | 2006-11-30 | Amersham Health As | IMPROVEMENTS AT OR RELATED TO DIAGNOSTIC / THERAPEUTIC COMPOUNDS |
US6331289B1 (en) | 1996-10-28 | 2001-12-18 | Nycomed Imaging As | Targeted diagnostic/therapeutic agents having more than one different vectors |
WO1998035828A1 (en) * | 1997-02-14 | 1998-08-20 | The Regents Of The University Of California | Lamellar gels and methods for making and regulating |
US6090800A (en) | 1997-05-06 | 2000-07-18 | Imarx Pharmaceutical Corp. | Lipid soluble steroid prodrugs |
US6537246B1 (en) | 1997-06-18 | 2003-03-25 | Imarx Therapeutics, Inc. | Oxygen delivery agents and uses for the same |
US6143276A (en) * | 1997-03-21 | 2000-11-07 | Imarx Pharmaceutical Corp. | Methods for delivering bioactive agents to regions of elevated temperatures |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
HUP0001256A3 (en) | 1997-04-03 | 2002-12-28 | Univ Johns Hopkins Med | Biodegradable terephthalate polyester-poly(phosphate) polymers, compositions, method for making the same and using them |
AU743758B2 (en) | 1997-04-07 | 2002-02-07 | Genentech Inc. | Anti-VEGF antibodies |
SI1695985T1 (en) | 1997-04-07 | 2011-06-30 | Genentech Inc | Methods for forming humanised antibodies by random mutagenesis |
AU7104598A (en) * | 1997-04-09 | 1998-10-30 | Philipp Lang | New technique to monitor drug delivery noninvasively (in vivo) |
US20020039594A1 (en) * | 1997-05-13 | 2002-04-04 | Evan C. Unger | Solid porous matrices and methods of making and using the same |
US6416740B1 (en) | 1997-05-13 | 2002-07-09 | Bristol-Myers Squibb Medical Imaging, Inc. | Acoustically active drug delivery systems |
JP4656675B2 (en) * | 1997-05-14 | 2011-03-23 | ユニバーシティー オブ ブリティッシュ コロンビア | High rate encapsulation of charged therapeutic agents in lipid vesicles |
DE19724796A1 (en) * | 1997-06-06 | 1998-12-10 | Max Delbrueck Centrum | Antitumor therapy agents |
US6663899B2 (en) | 1997-06-13 | 2003-12-16 | Genentech, Inc. | Controlled release microencapsulated NGF formulation |
US6113947A (en) * | 1997-06-13 | 2000-09-05 | Genentech, Inc. | Controlled release microencapsulated NGF formulation |
US6217886B1 (en) | 1997-07-14 | 2001-04-17 | The Board Of Trustees Of The University Of Illinois | Materials and methods for making improved micelle compositions |
US6548047B1 (en) | 1997-09-15 | 2003-04-15 | Bristol-Myers Squibb Medical Imaging, Inc. | Thermal preactivation of gaseous precursor filled compositions |
JP4467789B2 (en) | 1997-09-18 | 2010-05-26 | パシラ ファーマシューティカルズ インコーポレーテッド | Sustained release liposome anesthetic composition |
US6083923A (en) * | 1997-10-31 | 2000-07-04 | Isis Pharmaceuticals Inc. | Liposomal oligonucleotide compositions for modulating RAS gene expression |
US7229841B2 (en) * | 2001-04-30 | 2007-06-12 | Cytimmune Sciences, Inc. | Colloidal metal compositions and methods |
ES2384094T3 (en) | 1997-11-14 | 2012-06-29 | Pacira Pharmaceuticals, Inc. | Production of multivesicular liposomes |
US7192589B2 (en) | 1998-09-16 | 2007-03-20 | Genentech, Inc. | Treatment of inflammatory disorders with STIgMA immunoadhesins |
EP2014677A1 (en) | 1997-11-21 | 2009-01-14 | Genentech, Inc. | A-33 related antigens and their pharmacological uses |
US6787132B1 (en) * | 1997-12-04 | 2004-09-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
EP1947119A3 (en) | 1997-12-12 | 2012-12-19 | Genentech, Inc. | Treatment of cancer with anti-erb2 antibodies in combination with a chemotherapeutic agent |
US6123923A (en) | 1997-12-18 | 2000-09-26 | Imarx Pharmaceutical Corp. | Optoacoustic contrast agents and methods for their use |
US20010003580A1 (en) | 1998-01-14 | 2001-06-14 | Poh K. Hui | Preparation of a lipid blend and a phospholipid suspension containing the lipid blend |
ATE438720T1 (en) | 1998-02-04 | 2009-08-15 | Genentech Inc | USE OF HEREGULIN AS AN EPITHELIAL CELL GROWTH FACTOR |
WO1999039738A1 (en) * | 1998-02-09 | 1999-08-12 | Bracco Research S.A. | Targeted delivery of biologically active media |
US6942859B2 (en) | 1998-03-13 | 2005-09-13 | University Of Southern California | Red blood cells covalently bound with polymers |
US6312685B1 (en) | 1998-03-13 | 2001-11-06 | Timothy C. Fisher | Red blood cells covalently bound with two different polyethylene glycol derivatives |
ES2313778T3 (en) | 1998-03-17 | 2009-03-01 | Genentech, Inc. | VEGF AND BMP1 HOMOLOGICAL POLYPEPTIDES. |
US6433012B1 (en) * | 1998-03-25 | 2002-08-13 | Large Scale Biology Corp. | Method for inhibiting inflammatory disease |
WO1999048495A1 (en) * | 1998-03-25 | 1999-09-30 | Biosource Technologies, Inc. | Benzoates derivatives for inhibiting angiogenesis |
US6858706B2 (en) * | 1998-04-07 | 2005-02-22 | St. Jude Children's Research Hospital | Polypeptide comprising the amino acid of an N-terminal choline binding protein a truncate, vaccine derived therefrom and uses thereof |
US6593294B1 (en) * | 1998-04-27 | 2003-07-15 | Opperbas Holding B.V. | Pharmaceutical composition comprising Factor VIII and neutral liposomes |
US6986902B1 (en) * | 1998-04-28 | 2006-01-17 | Inex Pharmaceuticals Corporation | Polyanionic polymers which enhance fusogenicity |
US6331407B1 (en) | 1998-05-06 | 2001-12-18 | St. Jude Children's Research Hospital | Antibiotics and methods of using the same |
US6448224B1 (en) | 1998-05-06 | 2002-09-10 | St. Jude Children's Research Hospital | Antibiotics and methods of using the same |
US6169078B1 (en) * | 1998-05-12 | 2001-01-02 | University Of Florida | Materials and methods for the intracellular delivery of substances |
EP1865061A3 (en) | 1998-05-15 | 2007-12-19 | Genentech, Inc. | IL-17 homologous polypeptides and therapeutic uses thereof |
EP3112468A1 (en) | 1998-05-15 | 2017-01-04 | Genentech, Inc. | Il-17 homologous polypeptides and therapeutic uses thereof |
EP1076703B2 (en) | 1998-05-15 | 2010-12-15 | Genentech, Inc. | Therapeutic uses of il-17 homologous polypeptides |
ES2395693T3 (en) | 1998-06-12 | 2013-02-14 | Genentech, Inc. | Monoclonal antibodies, cross-reactive antibodies and process for manufacturing them |
US6726925B1 (en) * | 1998-06-18 | 2004-04-27 | Duke University | Temperature-sensitive liposomal formulation |
US6200598B1 (en) * | 1998-06-18 | 2001-03-13 | Duke University | Temperature-sensitive liposomal formulation |
US20040229363A1 (en) * | 1998-06-24 | 2004-11-18 | Ed Nolan | High efficiency transfection based on low electric field strength, long pulse length |
US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
US6693086B1 (en) * | 1998-06-25 | 2004-02-17 | National Jewish Medical And Research Center | Systemic immune activation method using nucleic acid-lipid complexes |
US20040247662A1 (en) * | 1998-06-25 | 2004-12-09 | Dow Steven W. | Systemic immune activation method using nucleic acid-lipid complexes |
US6277413B1 (en) | 1998-07-17 | 2001-08-21 | Skyepharma, Inc. | Biodegradable compositions for the controlled release of encapsulated substances |
US20020172678A1 (en) | 2000-06-23 | 2002-11-21 | Napoleone Ferrara | EG-VEGF nucleic acids and polypeptides and methods of use |
US6703381B1 (en) | 1998-08-14 | 2004-03-09 | Nobex Corporation | Methods for delivery therapeutic compounds across the blood-brain barrier |
EP1121102B1 (en) * | 1998-09-16 | 2003-04-23 | Alza Corporation | Liposome-entrapped topoisomerase inhibitors |
US6077709A (en) | 1998-09-29 | 2000-06-20 | Isis Pharmaceuticals Inc. | Antisense modulation of Survivin expression |
US6419709B1 (en) | 1998-10-02 | 2002-07-16 | Guilford Pharmaceuticals, Inc. | Biodegradable terephthalate polyester-poly(Phosphite) compositions, articles, and methods of using the same |
US6153212A (en) * | 1998-10-02 | 2000-11-28 | Guilford Pharmaceuticals Inc. | Biodegradable terephthalate polyester-poly (phosphonate) compositions, articles, and methods of using the same |
KR100719202B1 (en) * | 1998-10-23 | 2007-05-16 | 키린-암젠 인코포레이티드 | A COMPOUND BINDING TO MPl RECEPTOR AND A PHARMACEUTICAL COMPOSITION THEREOF |
US6660843B1 (en) * | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
SI1135498T1 (en) | 1998-11-18 | 2008-06-30 | Genentech Inc | Antibody variants with higher binding affinity compared to parent antibodies |
CA2350599A1 (en) * | 1998-11-20 | 2000-06-02 | Genentech, Inc. | Method of inhibiting angiogenesis |
US6773911B1 (en) * | 1998-11-23 | 2004-08-10 | Amgen Canada Inc. | Apoptosis-inducing factor |
DK1140173T4 (en) | 1998-12-22 | 2013-06-10 | Genentech Inc | Vascular endothelial cell growth factor antagonists and applications thereof |
EP2075335A3 (en) | 1998-12-22 | 2009-09-30 | Genentech, Inc. | Methods and compositions for inhibiting neoplastic cell growth |
US6350464B1 (en) * | 1999-01-11 | 2002-02-26 | Guilford Pharmaceuticals, Inc. | Methods for treating ovarian cancer, poly (phosphoester) compositions, and biodegradable articles for same |
US6818227B1 (en) * | 1999-02-08 | 2004-11-16 | Alza Corporation | Liposome composition and method for administration of a radiosensitizer |
US6537585B1 (en) | 1999-03-26 | 2003-03-25 | Guilford Pharmaceuticals, Inc. | Methods and compositions for treating solid tumors |
US6379698B1 (en) | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
US7098192B2 (en) | 1999-04-08 | 2006-08-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of STAT3 expression |
US7112337B2 (en) | 1999-04-23 | 2006-09-26 | Alza Corporation | Liposome composition for delivery of nucleic acid |
ATE259231T1 (en) * | 1999-04-29 | 2004-02-15 | Alza Corp | LIPOSOME COMPOSITIONS FOR IMPROVED ACTIVE RETENTION |
CA2270600A1 (en) | 1999-05-03 | 2000-11-03 | Infectio Recherche Inc. | Method and formulations for the treatment of diseases, particularly those caused by human immunodeficiency virus and leishmania |
EP1645290A1 (en) | 1999-05-07 | 2006-04-12 | Genentech, Inc. | Treatment of autoimmune diseases with antagonists which bind to B cell surface markers |
US20040023874A1 (en) * | 2002-03-15 | 2004-02-05 | Burgess Catherine E. | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US6974684B2 (en) * | 2001-08-08 | 2005-12-13 | Curagen Corporation | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US20040229779A1 (en) * | 1999-05-14 | 2004-11-18 | Ramesh Kekuda | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US20040067490A1 (en) * | 2001-09-07 | 2004-04-08 | Mei Zhong | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
DE60043367D1 (en) | 1999-06-15 | 2009-12-31 | Genentech Inc | Secreted and transmembrane polypeptides and nucleic acids for their coding |
US20030021792A1 (en) * | 2001-06-08 | 2003-01-30 | Roben Paul W. | Tissue-specific endothelial membrane proteins |
US7169889B1 (en) | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
US6309633B1 (en) | 1999-06-19 | 2001-10-30 | Nobex Corporation | Amphiphilic drug-oligomer conjugates with hydroyzable lipophile components and methods for making and using the same |
CA2376849C (en) * | 1999-06-24 | 2008-10-14 | Kyowa Hakko Kogyo Co., Ltd. | Method of inhibiting leakage of drug encapsulated in liposomes |
AT500848B1 (en) | 1999-06-25 | 2008-01-15 | Genentech Inc | HUMANIZED ANTI-ERBB2 ANTIBODIES |
US6352996B1 (en) | 1999-08-03 | 2002-03-05 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
BR0013814A (en) | 1999-08-27 | 2002-04-23 | Genentech Inc | Methods of treating a human patient susceptible to or diagnosed with a disease with anti-erbb2 antibodies, industrialized articles, methods of treating cancer in human patients and uses of anti-erbb2 antibody |
NZ523206A (en) * | 1999-08-31 | 2004-12-24 | Genentech Inc | Antibodies that bind to tumor gene sequences |
CA2349406C (en) * | 1999-09-03 | 2011-01-11 | Amgen Inc. | Compositions and methods for the prevention or treatment of cancer and bone loss associated with cancer |
WO2001026625A2 (en) | 1999-10-08 | 2001-04-19 | Alza Corp | Neutral-cationic lipid for nucleic acid and drug delivery |
IT1315253B1 (en) * | 1999-10-22 | 2003-02-03 | Novuspharma Spa | LIPOSOMIAL PREPARATION OF 6,9-BIS- (2-AMINOXYL) AMINO | BENZOG | ISOCHINOLIN-5,10-DIONE DIMALEATO |
US7067111B1 (en) * | 1999-10-25 | 2006-06-27 | Board Of Regents, University Of Texas System | Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging |
US6511676B1 (en) * | 1999-11-05 | 2003-01-28 | Teni Boulikas | Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes |
WO2001039722A2 (en) | 1999-11-30 | 2001-06-07 | Mayo Foundation For Medical Education And Research | B7-h1, a novel immunoregulatory molecule |
CA2391455A1 (en) | 1999-12-01 | 2001-06-07 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
US6593308B2 (en) | 1999-12-03 | 2003-07-15 | The Regents Of The University Of California | Targeted drug delivery with a hyaluronan ligand |
DK1897945T3 (en) | 1999-12-23 | 2012-05-07 | Genentech Inc | IL-17 homologous polypeptides and therapeutic uses thereof. |
CA2395132A1 (en) * | 2000-01-05 | 2001-07-12 | Imarx Therapeutics, Inc. | Pharmaceutical formulations for the delivery of drugs having low aqueous solubility |
US20040009229A1 (en) * | 2000-01-05 | 2004-01-15 | Unger Evan Charles | Stabilized nanoparticle formulations of camptotheca derivatives |
CN1425066B (en) * | 2000-01-13 | 2010-05-26 | 杰南技术公司 | Novel stra6 polypeptides |
US20020055479A1 (en) | 2000-01-18 | 2002-05-09 | Cowsert Lex M. | Antisense modulation of PTP1B expression |
US6261840B1 (en) | 2000-01-18 | 2001-07-17 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
JP2003521366A (en) * | 2000-01-28 | 2003-07-15 | アルザ・コーポレーション | Liposomes containing compounds entrapped in supersaturated solutions |
US20030176385A1 (en) * | 2000-02-15 | 2003-09-18 | Jingfang Ju | Antisense modulation of protein expression |
JP4922824B2 (en) * | 2000-04-03 | 2012-04-25 | 参天製薬株式会社 | Delivery substance and drug delivery system using the same |
AU2001247616B2 (en) | 2000-04-11 | 2007-06-14 | Genentech, Inc. | Multivalent antibodies and uses therefor |
ATE382333T1 (en) * | 2000-04-12 | 2008-01-15 | Liplasome Pharma As | LIPIDE-BASED DRUG DELIVERY SYSTEMS AGAINST PARASITIC INFECTIONS |
ATE319737T1 (en) | 2000-04-21 | 2006-03-15 | Amgen Inc | PEPTIDE DERIVATIVES OF APOLIPOPROTEIN-A1/AII |
US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
US6677136B2 (en) | 2000-05-03 | 2004-01-13 | Amgen Inc. | Glucagon antagonists |
WO2001085131A2 (en) * | 2000-05-11 | 2001-11-15 | Celator Technologies Inc. | Lipid carrier compositions for improved drug retention |
US6680172B1 (en) | 2000-05-16 | 2004-01-20 | Regents Of The University Of Michigan | Treatments and markers for cancers of the central nervous system |
AU6531101A (en) | 2000-06-02 | 2001-12-17 | Genentech Inc | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
CA2410906C (en) | 2000-06-02 | 2012-10-02 | Board Of Regents, The University Of Texas System | Ethylenedicysteine (ec)-drug conjugates |
US20030072794A1 (en) * | 2000-06-09 | 2003-04-17 | Teni Boulikas | Encapsulation of plasmid DNA (lipogenes™) and therapeutic agents with nuclear localization signal/fusogenic peptide conjugates into targeted liposome complexes |
JP2004512262A (en) | 2000-06-20 | 2004-04-22 | アイデック ファーマスーティカルズ コーポレイション | Non-radioactive anti-CD20 antibody / radiolabeled anti-CD22 antibody combination |
CA2709771A1 (en) | 2000-06-23 | 2002-01-03 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
EP2042597B1 (en) | 2000-06-23 | 2014-05-07 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
US20040023259A1 (en) * | 2000-07-26 | 2004-02-05 | Luca Rastelli | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
ATE412009T1 (en) | 2000-08-24 | 2008-11-15 | Genentech Inc | METHOD FOR INHIBITING IL-22 INDUCED PAP1 |
EP1944317A3 (en) | 2000-09-01 | 2008-09-17 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
US20030133972A1 (en) * | 2000-10-11 | 2003-07-17 | Targesome, Inc. | Targeted multivalent macromolecules |
EP1421174B1 (en) | 2000-10-18 | 2009-12-23 | The Brigham And Women's Hospital, Inc. | Hematopoietic cell e-selectin/l-selectin ligand polypeptides and methods of use thereof |
US7045283B2 (en) | 2000-10-18 | 2006-05-16 | The Regents Of The University Of California | Methods of high-throughput screening for internalizing antibodies |
AU2002225878A1 (en) * | 2000-11-02 | 2002-05-15 | Smith Kline Beecham Corporation | Receptor antagonist-lipid conjugates and delivery vehicles containing same |
DE10056136A1 (en) * | 2000-11-07 | 2002-05-16 | Nemod New Modalities | Inhibiting leukocyte or tumor cell adhesion to vascular endothelial cells e.g. for combating inflammation or metastasis, using e.g. pregnancy proteins or selectin binding liposomes containing calcium-binding compound |
AU2002239607A1 (en) * | 2000-11-30 | 2002-06-11 | Baxter Healthcare Corporation | Ahf associated dispersion system and method for preparation |
US7625584B2 (en) * | 2000-11-30 | 2009-12-01 | The Research Foundation Of State University Of New York | Method of complexing a protein by the use of a dispersed system and proteins thereof |
US8110218B2 (en) * | 2000-11-30 | 2012-02-07 | The Research Foundation Of State University Of New York | Compositions and methods for less immunogenic protein-lipid complexes |
WO2002061036A2 (en) * | 2000-11-30 | 2002-08-08 | The Research Foundation Of State University Of New York | Method of complexing a protein by the use of a dispersed system and proteins thereof |
US20060014674A1 (en) | 2000-12-18 | 2006-01-19 | Dennis Keith | Methods for preparing purified lipopeptides |
EP1343811A4 (en) * | 2000-12-18 | 2004-12-08 | Cubist Pharm Inc | Methods for preparing purified lipopeptides |
WO2002059145A1 (en) * | 2000-12-18 | 2002-08-01 | Cubist Pharmaceuticals, Inc. | Methods for preparing purified lipopeptides |
US20040077604A1 (en) * | 2001-12-19 | 2004-04-22 | Lenard Lichtenberger | Method and compositions employing formulations of lecithin oils and nsaids for protecting the gastrointestinal tract and providingenhanced therapeutic activity |
US6964849B2 (en) | 2001-01-11 | 2005-11-15 | Curagen Corporation | Proteins and nucleic acids encoding same |
US20040043928A1 (en) * | 2001-08-02 | 2004-03-04 | Ramesh Kekuda | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US20020159996A1 (en) | 2001-01-31 | 2002-10-31 | Kandasamy Hariharan | Use of CD23 antagonists for the treatment of neoplastic disorders |
AR035779A1 (en) | 2001-02-06 | 2004-07-14 | Genetics Inst Llc | FUSION POLYPEPTIDES DERIVED FROM GLICOPROTEIN IB PLATE ALFA AND METHODS OF USE OF THE SAME |
US6867183B2 (en) * | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
US7087726B2 (en) | 2001-02-22 | 2006-08-08 | Genentech, Inc. | Anti-interferon-α antibodies |
CA2439953A1 (en) * | 2001-03-08 | 2002-09-19 | Mark D. Bednarski | Stabilized therapeutic and imaging agents |
AU2002305094B2 (en) * | 2001-03-26 | 2007-01-11 | Alza Corporation | Liposome composition for improved intracellular delivery of a therapeutic agent |
US20040126900A1 (en) * | 2001-04-13 | 2004-07-01 | Barry Stephen E | High affinity peptide- containing nanoparticles |
EP1383480A4 (en) * | 2001-04-30 | 2006-05-24 | Targeted Genetics Corp | Lipid-comprising drug delivery complexes and methods for their production |
US20030077829A1 (en) * | 2001-04-30 | 2003-04-24 | Protiva Biotherapeutics Inc.. | Lipid-based formulations |
GB0111279D0 (en) * | 2001-05-10 | 2001-06-27 | Nycomed Imaging As | Radiolabelled liposomes |
EA010435B1 (en) | 2001-05-11 | 2008-08-29 | Амген, Инк. | Binding to tall-1 molecules and use thereof |
JP2004528384A (en) * | 2001-05-15 | 2004-09-16 | トランジェーヌ、ソシエテ、アノニム | Complex for introducing target substances into cells |
US20020197253A1 (en) * | 2001-05-22 | 2002-12-26 | Cheek Dennis J. | Compositions and methods for promoting or inhibiting NDPK |
CA2448018A1 (en) * | 2001-05-22 | 2002-11-28 | Duke University | Compositions and methods for inhibiting metastasis |
EP2340849A1 (en) | 2001-05-30 | 2011-07-06 | Genentech, Inc. | Anti-NGF antibodies for the treatment of various disorders |
IL158819A0 (en) * | 2001-05-31 | 2004-05-12 | Skyepharma Inc | Encapsulation of nanosuspensions in liposomes and microspheres |
US6858580B2 (en) * | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US6828297B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US7713932B2 (en) | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
US6713452B2 (en) | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US6835802B2 (en) * | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
US6828305B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
US20070160576A1 (en) | 2001-06-05 | 2007-07-12 | Genentech, Inc. | IL-17A/F heterologous polypeptides and therapeutic uses thereof |
US20050107595A1 (en) * | 2001-06-20 | 2005-05-19 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
KR100628425B1 (en) | 2001-06-20 | 2006-09-28 | 제넨테크, 인크. | Compositions and Methods for the Diagnosis and Treatment of Tumor |
US7803915B2 (en) * | 2001-06-20 | 2010-09-28 | Genentech, Inc. | Antibody compositions for the diagnosis and treatment of tumor |
WO2003000707A2 (en) | 2001-06-21 | 2003-01-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of superoxide dismutase 1, soluble expression |
CN1827766B (en) | 2001-06-28 | 2010-08-25 | 徐荣祥 | In vitro cell cultivation method |
US20030087274A1 (en) * | 2001-07-05 | 2003-05-08 | Anderson David W. | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US20040029790A1 (en) * | 2001-07-05 | 2004-02-12 | Meera Patturajan | Novel human proteins, polynucleotides encoding them and methods of using the same |
WO2003007915A2 (en) * | 2001-07-19 | 2003-01-30 | Guilford Pharmaceuticals, Inc. | Compositions for treatment of head and neck cancers, and methods of making and using the same |
US20030133903A1 (en) * | 2001-07-19 | 2003-07-17 | Wenbin Dang | Compositions for treatment of prostate cancers and methods of making and using the same |
US7425545B2 (en) | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
US6964950B2 (en) | 2001-07-25 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of C-reactive protein expression |
CN1310672C (en) * | 2001-07-29 | 2007-04-18 | 耶路撒冷希伯来大学伊森姆研究发展公司 | Osteogenis oligopeptide as blood-formation stimulation articles |
US20030096772A1 (en) | 2001-07-30 | 2003-05-22 | Crooke Rosanne M. | Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression |
US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
US20040030096A1 (en) * | 2001-08-02 | 2004-02-12 | Linda Gorman | Novel human proteins, polynucleotides encoding them and methods of using the same |
US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
EP1424889A4 (en) * | 2001-08-20 | 2008-04-02 | Transave Inc | Method for treating lung cancers |
IL160307A0 (en) | 2001-08-31 | 2004-07-25 | Univ Rockefeller | Phosphodiesterase activity and regulation of phosphodiesterase 1-b-mediated signaling in brain |
US20040235068A1 (en) * | 2001-09-05 | 2004-11-25 | Levinson Arthur D. | Methods for the identification of polypeptide antigens associated with disorders involving aberrant cell proliferation and compositions useful for the treatment of such disorders |
US7196059B2 (en) * | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
US6913903B2 (en) * | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US7166571B2 (en) * | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US7312192B2 (en) * | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
US7547673B2 (en) * | 2001-09-13 | 2009-06-16 | The Johns Hopkins University | Therapeutics for cancer using 3-bromopyruvate and other selective inhibitors of ATP production |
NZ573831A (en) | 2001-09-18 | 2010-07-30 | Genentech Inc | Compositions and methods for the diagnosis and treatment of tumor, particularly breast tumor - TAT193 |
US7981863B2 (en) | 2001-09-19 | 2011-07-19 | Neuronova Ab | Treatment of Parkinson's disease with PDGF |
YU26304A (en) * | 2001-09-28 | 2006-08-17 | Esperion Therapeutics Inc. | Method and apparatus for extrusion of vesicles at high pressure |
DE10148065A1 (en) * | 2001-09-28 | 2003-04-17 | Max Planck Gesellschaft | (Ester) -lysolecithins in liposomes |
US20030199442A1 (en) * | 2001-10-09 | 2003-10-23 | Alsobrook John P. | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
US6750019B2 (en) | 2001-10-09 | 2004-06-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of insulin-like growth factor binding protein 5 expression |
NZ566396A (en) | 2001-10-09 | 2009-07-31 | Isis Pharmaceuticals Inc | Antisense modulation of insulin-like growth factor binding protein 5 expressions |
US7332474B2 (en) * | 2001-10-11 | 2008-02-19 | Amgen Inc. | Peptides and related compounds having thrombopoietic activity |
AU2002368202B2 (en) | 2001-11-02 | 2008-06-05 | Insert Therapeutics, Inc | Methods and compositions for therapeutic use of RNA interference |
WO2003039595A2 (en) * | 2001-11-07 | 2003-05-15 | Inex Pharmaceuticals Corporation | Mucosal adjuvants comprising an oligonucleotide and a cationic lipid |
US20040219201A1 (en) * | 2001-12-06 | 2004-11-04 | Yechezkel Barenholz | Tempamine compositions and methods of use |
US6965025B2 (en) | 2001-12-10 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of connective tissue growth factor expression |
MXPA04006554A (en) | 2002-01-02 | 2005-03-31 | Genentech Inc | Compositions and methods for the diagnosis and treatment of tumor. |
US7910586B2 (en) | 2002-01-04 | 2011-03-22 | The Rockefeller University | Compositions and methods for prevention and treatment of amyloid-β peptide-related disorders |
US7781396B2 (en) * | 2002-01-31 | 2010-08-24 | Tel Aviv University Future Technology Development L.P. | Peptides directed for diagnosis and treatment of amyloid-associated disease |
US20040052928A1 (en) * | 2002-09-06 | 2004-03-18 | Ehud Gazit | Peptides and methods using same for diagnosing and treating amyloid-associated diseases |
US6929798B2 (en) | 2002-02-13 | 2005-08-16 | Immunology Laboratories, Inc. | Compositions and methods for treatment of microbial infections |
CA2476518A1 (en) | 2002-02-22 | 2003-09-04 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
US20100311954A1 (en) * | 2002-03-01 | 2010-12-09 | Xencor, Inc. | Optimized Proteins that Target Ep-CAM |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
US20090042291A1 (en) * | 2002-03-01 | 2009-02-12 | Xencor, Inc. | Optimized Fc variants |
US20030180712A1 (en) | 2002-03-20 | 2003-09-25 | Biostratum Ab | Inhibition of the beta3 subunit of L-type Ca2+ channels |
US20040009216A1 (en) * | 2002-04-05 | 2004-01-15 | Rodrigueza Wendi V. | Compositions and methods for dosing liposomes of certain sizes to treat or prevent disease |
EP1571968A4 (en) | 2002-04-16 | 2007-10-17 | Genentech Inc | Compositions and methods for the diagnosis and treatment of tumor |
AU2003233008B2 (en) * | 2002-04-22 | 2008-04-24 | Recopharma Ab | Fusion polypeptides and methods for inhibiting microbial adhesion |
US20040009944A1 (en) * | 2002-05-10 | 2004-01-15 | Inex Pharmaceuticals Corporation | Methylated immunostimulatory oligonucleotides and methods of using the same |
US7199107B2 (en) | 2002-05-23 | 2007-04-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of kinesin-like 1 expression |
WO2005056606A2 (en) * | 2003-12-03 | 2005-06-23 | Xencor, Inc | Optimized antibodies that target the epidermal growth factor receptor |
EP2305710A3 (en) | 2002-06-03 | 2013-05-29 | Genentech, Inc. | Synthetic antibody phage libraries |
US7601688B2 (en) * | 2002-06-13 | 2009-10-13 | Biocon Limited | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
JP4722481B2 (en) | 2002-06-28 | 2011-07-13 | プロティバ バイオセラピューティクス リミテッド | Liposome production method and apparatus |
DE60335469D1 (en) * | 2002-07-02 | 2011-02-03 | Univ Texas | RADIOACTIVELY MARKED COMPOUNDS AND LIPOSOME AND THEIR MANUFACTURING AND APPLICATION METHOD |
US20050169979A1 (en) * | 2002-07-03 | 2005-08-04 | Dov Michaeli | Liposomal vaccine |
US20040247661A1 (en) * | 2002-07-03 | 2004-12-09 | Dov Michaeli | Liposomal vaccine |
EP1528915A2 (en) * | 2002-07-03 | 2005-05-11 | Aphton Corporation | Liposomal vaccine |
EP2383278A1 (en) | 2002-07-08 | 2011-11-02 | Genentech, Inc. | Method to determine B cell mediated diseases |
US7622118B2 (en) * | 2002-07-15 | 2009-11-24 | Board Of Regents, The University Of Texas System | Cancer treatment methods using selected antibodies to aminophospholipids |
US7714109B2 (en) * | 2002-07-15 | 2010-05-11 | Board Of Regents, The University Of Texas System | Combinations and kits for cancer treatment using selected antibodies to aminophospholipids |
US7572448B2 (en) * | 2002-07-15 | 2009-08-11 | Board Of Regents, The University Of Texas System | Combined cancer treatment methods using selected antibodies to aminophospholipids |
US7615223B2 (en) * | 2002-07-15 | 2009-11-10 | Board Of Regents, The University Of Texas System | Selected immunoconjugates for binding to aminophospholipids |
US7678386B2 (en) * | 2002-07-15 | 2010-03-16 | Board Of Regents The University Of Texas | Liposomes coated with selected antibodies that bind to aminophospholipids |
US7625563B2 (en) * | 2002-07-15 | 2009-12-01 | Board Of Regents, The University Of Texas System | Cancer treatment methods using selected immunoconjugates for binding to aminophospholipids |
SI2269656T1 (en) * | 2002-07-15 | 2014-11-28 | Board Of Regents, The University Of Texas System | Selected antibodies binding to aminophospholipids and their use in treatment, such as cancer |
CA2490758C (en) | 2002-07-15 | 2014-09-23 | Genentech, Inc. | Dosage form of recombinant humanized monoclonal antibody 2c4 |
WO2004007693A2 (en) * | 2002-07-16 | 2004-01-22 | University Of South Florida | Human immunosuppressive protein |
US20040161423A1 (en) * | 2002-07-18 | 2004-08-19 | Sanjeev Kumar (Mendiratta) | Polymer modified anti-angiogenic serpins |
CA2494673A1 (en) * | 2002-08-02 | 2004-07-01 | Transave, Inc. | Platinum aggregates and process for producing the same |
US9186322B2 (en) * | 2002-08-02 | 2015-11-17 | Insmed Incorporated | Platinum aggregates and process for producing the same |
PT1534335E (en) | 2002-08-14 | 2012-02-28 | Macrogenics Inc | Fcgammariib-specific antibodies and methods of use thereof |
EP1393720A1 (en) * | 2002-08-27 | 2004-03-03 | Universiteit Utrecht | Vesicle-encapsulated corticosteroids for treatment of cancer |
MXPA05002219A (en) | 2002-08-28 | 2005-07-05 | Immunex Corp | Compositions and methods for treating cardiovascular disease. |
US20070231379A1 (en) * | 2002-08-29 | 2007-10-04 | Slater James L | Liposome-entrapped topoisomerase inhibitors |
US20080214437A1 (en) * | 2002-09-06 | 2008-09-04 | Mohapatra Shyam S | Methods and compositions for reducing activity of the atrial natriuretic peptide receptor and for treatment of diseases |
WO2004022003A2 (en) | 2002-09-06 | 2004-03-18 | University Of South Florida | Materials and methods for treatment of allergic diseases |
US8071560B2 (en) * | 2004-02-17 | 2011-12-06 | University Of South Florida | Materials and methods for reducing inflammation by inhibition of the atrial natriuretic peptide receptor |
ATE493433T1 (en) | 2002-09-11 | 2011-01-15 | Genentech Inc | NEW COMPOSITION AND METHOD FOR TREATING IMMUNE DISEASES |
EP1578373A4 (en) | 2002-09-11 | 2007-10-24 | Genentech Inc | Novel compositions and methods for the treatment of immune related diseases |
AU2003267785C1 (en) * | 2002-09-13 | 2009-12-24 | Replicor, Inc. | Non-sequence complementary antiviral oligonucleotides |
US20050196382A1 (en) * | 2002-09-13 | 2005-09-08 | Replicor, Inc. | Antiviral oligonucleotides targeting viral families |
EP1578364A4 (en) | 2002-09-16 | 2011-06-08 | Genentech Inc | Compositions and methods for the treatmentof immune related diseases |
US6919426B2 (en) | 2002-09-19 | 2005-07-19 | Amgen Inc. | Peptides and related molecules that modulate nerve growth factor activity |
EP1585482A4 (en) | 2002-09-25 | 2009-09-09 | Genentech Inc | Nouvelles compositions et methodes de traitement du psoriasis |
EP2272958A1 (en) | 2002-09-26 | 2011-01-12 | ISIS Pharmaceuticals, Inc. | Modulation of forkhead box O1A expression |
DK2345671T3 (en) | 2002-09-27 | 2016-02-15 | Xencor Inc | Optimized Fc variants and methods for their formation |
US8129330B2 (en) * | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
CA2500901A1 (en) * | 2002-10-04 | 2004-04-22 | Rinat Neuroscience Corp. | Methods for treating cardiac arrhythmia and preventing death due to cardiac arrhythmia using ngf antagonists |
US7432351B1 (en) | 2002-10-04 | 2008-10-07 | Mayo Foundation For Medical Education And Research | B7-H1 variants |
AU2003285864C1 (en) | 2002-10-08 | 2010-07-01 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering a nerve growth factor antagonist and compositions containing the same |
UA80447C2 (en) * | 2002-10-08 | 2007-09-25 | Methods for treating pain by administering nerve growth factor antagonist and opioid analgesic | |
WO2005000194A2 (en) | 2002-10-08 | 2005-01-06 | Rinat Neuroscience Corp. | Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody and compositions containing the same |
EP1633786A4 (en) * | 2002-10-09 | 2007-07-25 | Rinat Neuroscience Corp | Methods of treating alzheimer s disease using antibodies directed against amyloid beta peptide and compositions thereof |
JP2006517785A (en) | 2002-10-29 | 2006-08-03 | ジェネンテック・インコーポレーテッド | Novel compositions and methods for the treatment of immune related diseases |
WO2004110345A2 (en) * | 2002-10-29 | 2004-12-23 | Pharmacia Corporation | Differentially expressed genes involved in cancer, the polypeptides encoded thereby, and methods of using the same |
CA2505330A1 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
AU2003287505A1 (en) | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
AU2003295401B2 (en) | 2002-11-08 | 2010-04-29 | Genentech, Inc. | Compositions and methods for the treatment of natural killer cell related diseases |
US20040093198A1 (en) * | 2002-11-08 | 2004-05-13 | Carbon Design Systems | Hardware simulation with access restrictions |
US20040152769A1 (en) * | 2002-11-09 | 2004-08-05 | Ekwuribe Nnochiri Nkem | Modified carbamate-containing prodrugs and methods of synthesizing same |
EP1569695B1 (en) | 2002-11-13 | 2013-05-15 | Genzyme Corporation | Antisense modulation of apolipoprotein b expression |
DK1569695T3 (en) | 2002-11-13 | 2013-08-05 | Genzyme Corp | ANTISENSE MODULATION OF APOLIPOPROTEIN-B EXPRESSION |
US20050158375A1 (en) * | 2002-11-15 | 2005-07-21 | Toshikiro Kimura | Pharmaceutical composition containing liposomes for treating cancer |
US7144999B2 (en) | 2002-11-23 | 2006-12-05 | Isis Pharmaceuticals, Inc. | Modulation of hypoxia-inducible factor 1 alpha expression |
US7648962B2 (en) * | 2002-11-26 | 2010-01-19 | Biocon Limited | Natriuretic compounds, conjugates, and uses thereof |
US20070048301A1 (en) | 2002-11-26 | 2007-03-01 | Bodary-Winter Sarah C | Compositions and methods for the treatment of immune related diseases |
SG159387A1 (en) | 2002-11-26 | 2010-03-30 | Biocon Ltd In | Modified natriuretic compounds, conjugates, and uses thereof |
US7491699B2 (en) * | 2002-12-09 | 2009-02-17 | Ramot At Tel Aviv University Ltd. | Peptide nanostructures and methods of generating and using the same |
EP1587484A4 (en) * | 2002-12-19 | 2008-11-12 | Alza Corp | Method of treating angiogenic tissue growth |
US7569364B2 (en) | 2002-12-24 | 2009-08-04 | Pfizer Inc. | Anti-NGF antibodies and methods using same |
NZ587852A (en) | 2002-12-24 | 2012-02-24 | Rinat Neuroscience Corp | Anti-NGF antibodies and methods using same |
US9498530B2 (en) | 2002-12-24 | 2016-11-22 | Rinat Neuroscience Corp. | Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same |
US8980310B2 (en) * | 2002-12-31 | 2015-03-17 | Bharat Serums and Vaccines, Ltd. | Non-pegylated long-circulating liposomes |
ATE426575T1 (en) * | 2003-01-07 | 2009-04-15 | Univ Ramot | PEPTIDE ANOSTRUCTURES CONTAINING FOREIGN MATERIAL AND METHOD FOR PRODUCING THE SAME |
DK1597366T3 (en) | 2003-02-11 | 2013-02-25 | Antisense Therapeutics Ltd | Modulation of expression of insulin-like growth factor receptor I |
KR20050111598A (en) * | 2003-02-19 | 2005-11-25 | 리나트 뉴로사이언스 코퍼레이션 | Methods for treating pain by administering a nerve growth factor antagonist and an nsaid and compositions containing the same |
US7803781B2 (en) | 2003-02-28 | 2010-09-28 | Isis Pharmaceuticals, Inc. | Modulation of growth hormone receptor expression and insulin-like growth factor expression |
US7968115B2 (en) | 2004-03-05 | 2011-06-28 | Board Of Regents, The University Of Texas System | Liposomal curcumin for treatment of cancer |
WO2004087097A2 (en) * | 2003-03-31 | 2004-10-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Stable liposomes or micelles comprising a sphinolipid and a peg-lipopolymer |
US20040185559A1 (en) | 2003-03-21 | 2004-09-23 | Isis Pharmaceuticals Inc. | Modulation of diacylglycerol acyltransferase 1 expression |
KR20060034215A (en) | 2003-03-31 | 2006-04-21 | 알자 코포레이션 | Lipid particles having asymmetric lipid coating and method of preparing same |
CN1798575A (en) | 2003-04-04 | 2006-07-05 | 健泰科生物技术公司 | High concentration antibody and protein formulations |
ME00426B (en) | 2003-04-09 | 2011-10-10 | Genentech Inc | Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor |
ES2307009T3 (en) * | 2003-04-15 | 2008-11-16 | Opperbas Holding B.V. | PHARMACEUTICAL COMPOSITION CONTAINING PROTEINS AND / OR COLOID POLYPEPTIDES AND PARTICLES. |
US20060246104A1 (en) * | 2003-04-16 | 2006-11-02 | Massia Stephen P | Stable rgd peptidomimetic composition |
US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
EP1620112A4 (en) * | 2003-04-17 | 2007-04-25 | Univ Columbia | Desmoglein 4 is a novel gene involved in hair growth |
US7399853B2 (en) | 2003-04-28 | 2008-07-15 | Isis Pharmaceuticals | Modulation of glucagon receptor expression |
US7919118B2 (en) | 2003-05-12 | 2011-04-05 | Affymax, Inc. | Spacer moiety for poly (ethylene glycol) modified peptide based compounds |
EA010016B1 (en) | 2003-05-12 | 2008-06-30 | Афимакс, Инк. | Novel polyethyleneglycol modified compounds and uses thereof |
AU2004251161A1 (en) * | 2003-05-30 | 2005-01-06 | Genentech, Inc. | Polypeptides that bind an anti-tissue factor antibody and uses thereof |
WO2005000900A1 (en) | 2003-05-30 | 2005-01-06 | Genentech, Inc. | Treatment with anti-vegf antibodies |
WO2005002507A2 (en) | 2003-06-03 | 2005-01-13 | Isis Pharmaceuticals, Inc. | Modulation of survivin expression |
JP2006526661A (en) * | 2003-06-04 | 2006-11-24 | カンジ,インコーポレイテッド | Methods and compositions for interferon therapy |
PT1636593E (en) | 2003-06-06 | 2009-06-03 | Genentech Inc | Modulating the interaction between hgf beta chain and c-met |
CN100436480C (en) | 2003-06-11 | 2008-11-26 | 韦思公司 | Platelet glycoprotein IB-alpha variant fusion polypeptides and methods of use thereof |
US7939058B2 (en) | 2003-07-03 | 2011-05-10 | University Of Southern California | Uses of IL-12 in hematopoiesis |
ES2354238T3 (en) | 2003-07-03 | 2011-03-11 | University Of Medicine And Dentistry Of New Jersey | GENES AS A DIAGNOSTIC TOOL FOR AUTISM. |
ES2424353T3 (en) | 2003-07-08 | 2013-10-01 | Genentech, Inc. | Heterologous IL-17 A / F polypeptides and therapeutic uses thereof |
CA2532228C (en) * | 2003-07-16 | 2017-02-14 | Protiva Biotherapeutics, Inc. | Lipid encapsulated interfering rna |
CN100431525C (en) * | 2003-07-17 | 2008-11-12 | 台湾东洋药品工业股份有限公司 | Production method of liposome suspended liquid and products thereof |
CA2534234C (en) * | 2003-07-31 | 2011-02-22 | The Board Of Regents Of The University Of Texas System | Sterile preparations of phospholipids and anti-inflammatory pharmaceuticals and methods for making and using same |
WO2005013901A2 (en) | 2003-07-31 | 2005-02-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding rnas |
WO2005019258A2 (en) | 2003-08-11 | 2005-03-03 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
WO2005016348A1 (en) * | 2003-08-14 | 2005-02-24 | Icos Corporation | Method of inhibiting immune responses stimulated by an endogenous factor |
US20050054614A1 (en) * | 2003-08-14 | 2005-03-10 | Diacovo Thomas G. | Methods of inhibiting leukocyte accumulation |
US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
US8986731B2 (en) * | 2003-08-26 | 2015-03-24 | Biolitec Pharma Marketing Ltd | Pegylated liposomal formulations of hydrophobic photosensitizers for photodynamic therapy |
ATE422880T1 (en) * | 2003-08-26 | 2009-03-15 | Smithkline Beecham Corp | HETEROFUNCTIONAL COPOLYMERS OF GLYCEROL AND POLYETHYLENE GLYCOL, THEIR CONJUGATES AND COMPOSITIONS |
US20060115523A1 (en) * | 2004-12-01 | 2006-06-01 | Konduri Kameswari S | Sterically stabilized liposome and triamcinolone composition for treating the respiratory tract of a mammal |
US8846079B1 (en) | 2004-12-01 | 2014-09-30 | Vgsk Technologies, Inc. | Sterically stabilized carrier for aerosol therapeutics, compositions and methods for treating the respiratory tract of a mammal |
US11324698B2 (en) | 2003-08-28 | 2022-05-10 | Vgsk Technologies, Inc. | Sterically stabilized carrier for aerosol therapeutics, compositions and methods for treating the respiratory tract of a mammal |
EP1666486A4 (en) * | 2003-09-03 | 2006-12-06 | Kyowa Hakko Kogyo Kk | Compound modified with glycerol derivative |
US20050233435A1 (en) * | 2003-09-04 | 2005-10-20 | Nyu Medical Center | Plasmodium axenic liver stages as a noninfectious whole organism malaria vaccine |
US20070123480A1 (en) * | 2003-09-11 | 2007-05-31 | Replicor Inc. | Oligonucleotides targeting prion diseases |
CN1882693B (en) * | 2003-09-15 | 2012-08-15 | 普洛体维生物治疗公司 | Polyethyleneglycol-modified lipid compounds and uses thereof |
NZ545134A (en) | 2003-09-18 | 2009-06-26 | Lilly Co Eli | Modulation of eIF4E expression |
JP4917889B2 (en) * | 2003-09-25 | 2012-04-18 | テル アヴィヴ ユニヴァーシティ フューチャー テクノロジー ディヴェロップメント エル.ピー. | Compositions for treating amyloid-related diseases and methods of use thereof |
US8101720B2 (en) * | 2004-10-21 | 2012-01-24 | Xencor, Inc. | Immunoglobulin insertions, deletions and substitutions |
US7625707B2 (en) * | 2003-10-02 | 2009-12-01 | Ramot At Tel Aviv University Ltd. | Antibacterial agents and methods of identifying and utilizing same |
ES2437491T3 (en) | 2003-10-10 | 2014-01-10 | Alchemia Oncology Pty Limited | Modulation of the synthesis and degradation of hyaluronan in the treatment of disease |
WO2005034979A2 (en) * | 2003-10-11 | 2005-04-21 | Inex Pharmaceuticals Corporation | Methods and compositions for enhancing innate immunity and antibody dependent cellular cytotoxicity |
TW200517114A (en) | 2003-10-15 | 2005-06-01 | Combinatorx Inc | Methods and reagents for the treatment of immunoinflammatory disorders |
US7960350B2 (en) | 2003-10-24 | 2011-06-14 | Ader Enterprises, Inc. | Composition and method for the treatment of eye disease |
CA2542804A1 (en) * | 2003-10-24 | 2005-05-06 | Alza Corporation | Preparation of lipid particles |
WO2005040163A1 (en) * | 2003-10-28 | 2005-05-06 | Dr. Reddy's Laboratories Ltd | Heterocyclic compounds that block the effects of advanced glycation end products (age) |
US20050191653A1 (en) | 2003-11-03 | 2005-09-01 | Freier Susan M. | Modulation of SGLT2 expression |
US20050129753A1 (en) * | 2003-11-14 | 2005-06-16 | Gabizon Alberto A. | Method for drug loading in liposomes |
DE602004021713D1 (en) * | 2003-11-14 | 2009-08-06 | Het Nl Kanker I The Netherland | Pharmaceutical Formulations with Short Chain Sphingolipids and Their Use |
JP4901478B2 (en) | 2003-11-17 | 2012-03-21 | ジェネンテック, インコーポレイテッド | Compositions and methods for the treatment of tumors of hematopoietic origin |
CN1914226B (en) * | 2003-11-25 | 2012-02-01 | 达纳-法伯癌症研究院有限公司 | Antibodies against SARS-COV and methods of use thereof |
US7312320B2 (en) | 2003-12-10 | 2007-12-25 | Novimmune Sa | Neutralizing antibodies and methods of use thereof |
US9050378B2 (en) * | 2003-12-10 | 2015-06-09 | Board Of Regents, The University Of Texas System | N2S2 chelate-targeting ligand conjugates |
EP1692178A1 (en) | 2003-12-11 | 2006-08-23 | Genentech, Inc. | Methods and compositions for inhibiting c-met dimerization and activation |
WO2005062955A2 (en) | 2003-12-23 | 2005-07-14 | Rinat Neuroscience Corp. | Agonist anti-trkc antibodies and methods using same |
MXPA06007856A (en) | 2004-01-07 | 2007-03-23 | Chiron Corp | M-csf-specific monoclonal antibody and uses thereof. |
JP2007520481A (en) * | 2004-01-15 | 2007-07-26 | アルザ・コーポレーシヨン | Liposome composition for delivering therapeutic agents |
US20050164271A1 (en) | 2004-01-20 | 2005-07-28 | Sanjay Bhanot | Modulation of glucocorticoid receptor expression |
US7468431B2 (en) | 2004-01-22 | 2008-12-23 | Isis Pharmaceuticals, Inc. | Modulation of eIF4E-BP2 expression |
WO2005094420A2 (en) * | 2004-02-17 | 2005-10-13 | University Of South Florida | Materials and methods for treatment of inflammatory and cell proliferation disorders |
US20050181035A1 (en) * | 2004-02-17 | 2005-08-18 | Dow Steven W. | Systemic immune activation method using non CpG nucleic acids |
ATE452147T1 (en) | 2004-02-19 | 2010-01-15 | Genentech Inc | ANTIBODIES WITH CORRECTED CDR |
US8784881B2 (en) | 2004-03-05 | 2014-07-22 | Board Of Regents, The University Of Texas System | Liposomal curcumin for treatment of diseases |
US8569474B2 (en) | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
EP1735009A4 (en) * | 2004-03-12 | 2011-03-30 | Alnylam Pharmaceuticals Inc | iRNA AGENTS TARGETING VEGF |
EP2700720A3 (en) | 2004-03-15 | 2015-01-28 | Isis Pharmaceuticals, Inc. | Compositions and methods for optimizing cleavage of RNA by RNASE H |
EP1579850A3 (en) * | 2004-03-15 | 2009-12-16 | Nipro Corporation | A pharmaceutical composition containing liposomes for treating a cancer |
CA2559722A1 (en) * | 2004-03-18 | 2005-09-29 | Transave, Inc. | Administration of cisplatin by inhalation |
US20070065522A1 (en) * | 2004-03-18 | 2007-03-22 | Transave, Inc. | Administration of high potency platinum compound formulations by inhalation |
US8241663B2 (en) * | 2004-03-26 | 2012-08-14 | Terumo Kabushiki Kaisha | Liposome preparation |
ES2707393T3 (en) * | 2004-03-26 | 2019-04-03 | Curis Inc | RNA interference modulators of hedgehog signaling and uses thereof |
US20050244869A1 (en) * | 2004-04-05 | 2005-11-03 | Brown-Driver Vickie L | Modulation of transthyretin expression |
PL1732949T3 (en) | 2004-04-07 | 2010-06-30 | Rinat Neuroscience Corp | Methods for treating bone cancer pain by administering a nerve growth factor antagonist |
US7794713B2 (en) | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
US20150017671A1 (en) | 2004-04-16 | 2015-01-15 | Yaping Shou | Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity |
US20060002930A1 (en) * | 2004-04-16 | 2006-01-05 | Genentech, Inc. | Treatment of disorders |
US8658203B2 (en) * | 2004-05-03 | 2014-02-25 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for drug delivery to the brain |
EP1746976B1 (en) | 2004-05-03 | 2017-01-11 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for drug delivery |
USRE44638E1 (en) | 2004-05-13 | 2013-12-10 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
ATE450251T1 (en) * | 2004-05-17 | 2009-12-15 | Tekmira Pharmaceuticals Corp | LIPOSOMAL FORMULATIONS CONTAINING DIHYDROSPHINGOMYELIN AND METHODS OF USE THEREOF |
US20060292554A1 (en) * | 2004-05-18 | 2006-12-28 | Genentech, Inc. | Major coat protein variants for C-terminal and bi-terminal display |
US20050260260A1 (en) * | 2004-05-19 | 2005-11-24 | Edward Kisak | Liposome compositions for the delivery of macromolecules |
AU2005245018A1 (en) * | 2004-05-21 | 2005-12-01 | Transave, Inc. | Treatment of lung diseases and pre-lung disease conditions |
EP1749000A4 (en) * | 2004-05-25 | 2009-12-30 | Metabolex Inc | Bicyclic, substituted triazoles as modulators of ppar and methods of their preparation |
BRPI0511510A (en) * | 2004-05-25 | 2007-12-26 | Metabolex Inc | pharmaceutically acceptable compound, salts, solvates, hydrates and prodrugs thereof, composition, and methods for modulating a peroxisome proliferator-activated receptor, for treating disease, for modulating insulin resistance, for treating one or more risk factors for cardiovascular disease, to decrease fibrinogen levels, to decrease ldlc, to suppress appetite, and to modulate leptin levels in an individual |
CA2567883A1 (en) * | 2004-05-25 | 2005-12-15 | Icos Corporation | Methods for treating and/or preventing aberrant proliferation of hematopoietic cells |
US8481501B2 (en) * | 2004-05-28 | 2013-07-09 | Human Biomolecular Research Institute | Synthesis of metabolically stable analgesics, pain medications and other agents |
WO2005121372A2 (en) * | 2004-06-03 | 2005-12-22 | Isis Pharmaceuticals, Inc. | Double strand compositions comprising differentially modified strands for use in gene modulation |
JP2008501335A (en) * | 2004-06-03 | 2008-01-24 | アイシス ファーマシューティカルズ、インク. | Chimeric gapped oligomer composition |
US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
US20090048192A1 (en) * | 2004-06-03 | 2009-02-19 | Isis Pharmaceuticals, Inc. | Double Strand Compositions Comprising Differentially Modified Strands for Use in Gene Modulation |
MXPA06014069A (en) | 2004-06-04 | 2007-04-25 | Genentech Inc | Method for treating multiple sclerosis. |
JP4796062B2 (en) * | 2004-06-07 | 2011-10-19 | プロチバ バイオセラピューティクス インコーポレイティッド | Lipid-encapsulating interfering RNA |
EP1781593B1 (en) | 2004-06-07 | 2011-12-14 | Protiva Biotherapeutics Inc. | Cationic lipids and methods of use |
CA2579756C (en) * | 2004-06-19 | 2013-04-30 | Human Biomolecular Research Institute | Modulators of central nervous system neurotransmitters |
CA2571243A1 (en) | 2004-06-21 | 2006-01-05 | The Board Of Trustees Of The Leland Stanford Junior University | Genes and pathways differentially expressed in bipolar disorder and/or major depressive disorder |
US20060019893A1 (en) * | 2004-07-02 | 2006-01-26 | Genentech, Inc. | Factor VIIa variants |
WO2006002538A1 (en) | 2004-07-02 | 2006-01-12 | Protiva Biotherapeutics, Inc. | Immunostimulatory sirna molecules and uses therefor |
US8143380B2 (en) * | 2004-07-08 | 2012-03-27 | Amgen Inc. | Therapeutic peptides |
CN101014619B (en) | 2004-07-15 | 2010-11-03 | 赞科股份有限公司 | Optimized fc variants |
WO2006006172A2 (en) * | 2004-07-15 | 2006-01-19 | Ramot At Tel Aviv University Ltd. | Use of anti-amyloid agents for treating and typing pathogen infections |
WO2006007712A1 (en) * | 2004-07-19 | 2006-01-26 | Protiva Biotherapeutics, Inc. | Methods comprising polyethylene glycol-lipid conjugates for delivery of therapeutic agents |
UA91512C2 (en) * | 2004-07-19 | 2010-08-10 | Биокон Лимитед | Insulin-oligomer conjugates, formulations and uses thereof |
CN102641503A (en) | 2004-07-20 | 2012-08-22 | 健泰科生物技术公司 | Inhibitors of angiopoietin-like 4 protein, combinations, and their use |
JP5226308B2 (en) | 2004-07-26 | 2013-07-03 | ジェネンテック, インコーポレイテッド | Methods and compositions for controlling hepatocyte growth factor activation |
JP5042828B2 (en) * | 2004-07-30 | 2012-10-03 | ライナット ニューロサイエンス コーポレイション | Antibodies directed against amyloid-beta peptide and methods using the antibodies |
EP1781310B1 (en) | 2004-08-02 | 2015-10-14 | Ramot at Tel Aviv University Ltd. | Articles of peptide nanostructures and method of forming the same |
US9132116B2 (en) * | 2004-08-02 | 2015-09-15 | Willowcroft Pharm Inc. | Mast cell stabilizers to prevent or treat laminitis |
ES2356748T3 (en) | 2004-08-17 | 2011-04-12 | Tyco Healthcare Group Lp | ANTI-ADHESION BARRIER. |
JP2006056807A (en) * | 2004-08-18 | 2006-03-02 | Konica Minolta Medical & Graphic Inc | Preparation for use in photodynamic therapy |
US7732479B2 (en) | 2004-08-19 | 2010-06-08 | Tel Aviv University Future Technology Development L.P. | Compositions for treating amyloid associated diseases |
JP4715133B2 (en) * | 2004-08-26 | 2011-07-06 | コニカミノルタエムジー株式会社 | Anti-tumor liposome preparation and production method thereof |
JP2006069929A (en) * | 2004-08-31 | 2006-03-16 | Konica Minolta Medical & Graphic Inc | Preparation for treating mycosis and method for producing the same |
US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
US7786086B2 (en) * | 2004-09-08 | 2010-08-31 | Ramot At Tel-Aviv University Ltd. | Peptide nanostructures containing end-capping modified peptides and methods of generating and using the same |
EP1793805A1 (en) * | 2004-09-09 | 2007-06-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Liposomal formulations comprising an amphipathic weak base like tempamine for treatment of neurodegenerative conditions |
JP2008512445A (en) * | 2004-09-09 | 2008-04-24 | イッスム・リサーチ・ディベロップメント・カンパニー・オブ・ザ・ヘブルー・ユニバーシティ・オブ・エルサレム | Use of liposomal glucocorticoids for the treatment of inflammatory conditions |
US6998028B1 (en) * | 2004-09-24 | 2006-02-14 | Superpower, Inc. | Methods for forming superconducting conductors |
DK1797127T3 (en) * | 2004-09-24 | 2017-10-02 | Amgen Inc | Modified Fc molecules |
EP1804824B1 (en) | 2004-09-29 | 2017-01-04 | Icahn School of Medicine at Mount Sinai | Fsh and fsh receptor modulator compositions and methods for inhibiting osteoclastic bone resorption and bone loss in osteoporosis |
US20060110387A1 (en) | 2004-10-05 | 2006-05-25 | Genentech, Inc. | Method for treating vasculitis |
WO2006042112A2 (en) | 2004-10-05 | 2006-04-20 | California Institute Of Technology | Aptamer regulated nucleic acids and uses thereof |
AU2005295038B2 (en) | 2004-10-06 | 2012-05-17 | Mayo Foundation For Medical Education And Research | B7-H1 and methods of diagnosis, prognosis, and treatment of cancer |
TW200612993A (en) * | 2004-10-08 | 2006-05-01 | Alza Corp | Lipopolymer conjugates |
US7985417B2 (en) * | 2004-10-08 | 2011-07-26 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of lipid structure preparation |
JO3000B1 (en) | 2004-10-20 | 2016-09-05 | Genentech Inc | Antibody Formulations. |
UA87877C2 (en) * | 2004-10-26 | 2009-08-25 | Фарма Мар С.А., Сосьедад Униперсональ | Pegylated liposomal doxorubicin in combination with ecteinescidin 743 |
JP2008518951A (en) * | 2004-10-28 | 2008-06-05 | アルザ コーポレイション | Lyophilized liposome formulations and methods |
EP1807051A2 (en) | 2004-11-05 | 2007-07-18 | Inex Pharmaceuticals Corporation | Compositions and methods for stabilizing liposomal camptothecin formulations |
TW200618820A (en) * | 2004-11-05 | 2006-06-16 | Alza Corp | Liposome formulations of boronic acid compounds |
US20060246124A1 (en) * | 2004-11-08 | 2006-11-02 | Pilkiewicz Frank G | Methods of treating cancer with lipid-based platinum compound formulations administered intraperitoneally |
WO2006060148A2 (en) * | 2004-11-11 | 2006-06-08 | Affymax, Inc. | Novel peptides that bind to the erythropoietin receptor |
EP1817004A2 (en) * | 2004-11-15 | 2007-08-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combination therapy associating preferably a ceramide with a cytotoxic drug |
US20060134189A1 (en) * | 2004-11-17 | 2006-06-22 | Protiva Biotherapeutics, Inc | siRNA silencing of apolipoprotein B |
US20070298094A1 (en) * | 2004-11-18 | 2007-12-27 | Terumo Kabushiki Kaisha | Medicinal Composition, Preparation and Combined Preparation |
CA2590768A1 (en) * | 2004-12-14 | 2006-06-22 | Alnylam Pharmaceuticals, Inc. | Rnai modulation of mll-af4 and uses thereof |
JP2008526883A (en) | 2005-01-07 | 2008-07-24 | ディアデクサス インコーポレーテッド | Ovr110 antibody compositions and methods of use |
US20080207505A1 (en) * | 2005-01-12 | 2008-08-28 | James Kenneth D | Bna Conjugates and Methods of Use |
KR20180080371A (en) | 2005-01-21 | 2018-07-11 | 제넨테크, 인크. | Fixed dosing of her antibodies |
JP5221126B2 (en) * | 2005-01-28 | 2013-06-26 | 協和発酵キリン株式会社 | Method for producing fine particles surface-modified with water-soluble substances |
EP1853289A4 (en) | 2005-01-31 | 2008-04-09 | Vaxinnate Corp | Novel polypeptide ligands for toll-like receptor 2 (tlr2) |
US8029783B2 (en) | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
ES2852549T3 (en) | 2005-02-09 | 2021-09-13 | Sarepta Therapeutics Inc | Antisense composition for treatment of muscle atrophy |
EP2548575A1 (en) | 2005-02-15 | 2013-01-23 | Duke University | Anti-CD19 antibodies that mediate ADCC for use in treating autoimmune diseases |
CA2598409A1 (en) * | 2005-02-17 | 2006-08-24 | Icos Corporation | Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation |
CA2597717C (en) | 2005-02-18 | 2014-10-21 | Dana-Farber Cancer Institute | Antibodies against cxcr4 and methods of use thereof |
SI1850874T1 (en) | 2005-02-23 | 2014-01-31 | Genentech, Inc. | Extending time to disease progression or survival in ovarian cancer patients using pertuzumab |
TW200714289A (en) * | 2005-02-28 | 2007-04-16 | Genentech Inc | Treatment of bone disorders |
US20060204505A1 (en) * | 2005-03-08 | 2006-09-14 | Sliwkowski Mark X | Methods for identifying tumors responsive to treatment with HER dimerization inhibitors (HDIs) |
JP2006248978A (en) * | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | New liposome preparation |
BRPI0607985A2 (en) | 2005-03-10 | 2009-10-27 | Genentech Inc | dscr1 modulator, treatment methods, side effect amelioration method and tumor growth inhibition method |
EP1861072A2 (en) * | 2005-03-14 | 2007-12-05 | Massachusetts Institute Of Technology | Nanocells for diagnosis and treatment of diseases and disorders |
JP2008538351A (en) | 2005-03-21 | 2008-10-23 | メタボレックス インコーポレーティッド | Method for avoiding edema in the treatment or prevention of PPARγ-responsive diseases including cancer |
CN1840193B (en) * | 2005-03-29 | 2010-05-12 | 中国科学院生物物理研究所 | Nanometer capsule of anthracene nucleus anticancer antibiotic with polyethylene glycol-phospholipid |
WO2006105361A2 (en) | 2005-03-31 | 2006-10-05 | Calando Pharmaceuticals, Inc. | Inhibitors of ribonucleotide reductase subunit 2 and uses thereof |
MY148086A (en) | 2005-04-29 | 2013-02-28 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide and methods using same |
CA2607281C (en) | 2005-05-05 | 2023-10-03 | Duke University | Anti-cd19 antibody therapy for autoimmune disease |
WO2006122079A1 (en) | 2005-05-06 | 2006-11-16 | Zymogenetics, Inc. | Il-31 monoclonal antibodies and methods of use |
US8124084B2 (en) | 2005-05-17 | 2012-02-28 | University Of Connecticut | Compositions and methods for immunomodulation in an organism using IL-15 and soluble IL-15Ra |
US7919461B2 (en) * | 2005-06-03 | 2011-04-05 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
US7550433B2 (en) | 2005-06-03 | 2009-06-23 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
US8324159B2 (en) * | 2005-06-03 | 2012-12-04 | Affymax, Inc. | Erythropoietin receptor peptide formulations and uses |
JP2008541781A (en) | 2005-06-06 | 2008-11-27 | ジェネンテック・インコーポレーテッド | Transgenic animals for different genes and their use for characterizing genes |
US20070014845A1 (en) * | 2005-07-01 | 2007-01-18 | Yuanpeng Zhang | Liposomal delivery vehicle for hydrophobic drugs |
EP2004695A2 (en) | 2005-07-08 | 2008-12-24 | Xencor, Inc. | Optimized anti-ep-cam antibodies |
AU2006272713A1 (en) * | 2005-07-22 | 2007-02-01 | Y's Therapeutics Co, Ltd. | Anti-CD26 antibodies and methods of use thereof |
US8652469B2 (en) * | 2005-07-28 | 2014-02-18 | Novartis Ag | M-CSF-specific monoclonal antibody and uses thereof |
JP5657862B2 (en) * | 2005-07-28 | 2015-01-21 | ノバルティス アーゲー | Use of antibodies against M-CSF |
US20070055199A1 (en) | 2005-08-10 | 2007-03-08 | Gilbert Scott J | Drug delivery device for buccal and aural applications and other areas of the body difficult to access |
US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
ZA200800970B (en) | 2005-08-15 | 2009-10-28 | Genentech Inc | Gene disruptions, compositions and methods relating thereto |
US20070054873A1 (en) * | 2005-08-26 | 2007-03-08 | Protiva Biotherapeutics, Inc. | Glucocorticoid modulation of nucleic acid-mediated immune stimulation |
US7700567B2 (en) | 2005-09-29 | 2010-04-20 | Supergen, Inc. | Oligonucleotide analogues incorporating 5-aza-cytosine therein |
EP1973928A2 (en) * | 2005-10-11 | 2008-10-01 | Ramot at Tel-Aviv University Ltd. | Self-assembled fmoc-ff hydrogels |
TW200732350A (en) * | 2005-10-21 | 2007-09-01 | Amgen Inc | Methods for generating monovalent IgG |
US7875602B2 (en) * | 2005-10-21 | 2011-01-25 | Sutter West Bay Hospitals | Camptothecin derivatives as chemoradiosensitizing agents |
HUE031122T2 (en) | 2005-10-31 | 2017-07-28 | Oncomed Pharm Inc | Compositions and methods for treating cancer based on human fzd receptors |
WO2007053696A2 (en) | 2005-11-01 | 2007-05-10 | Alnylam Pharmaceuticals, Inc. | Rnai inhibition of influenza virus replication |
EP2395012B8 (en) * | 2005-11-02 | 2018-06-06 | Arbutus Biopharma Corporation | Modified siRNA molecules and uses thereof |
US7879212B2 (en) * | 2005-11-03 | 2011-02-01 | Ramot At Tel-Aviv University Ltd. | Peptide nanostructure-coated electrodes |
DE102005053066A1 (en) | 2005-11-04 | 2007-05-10 | Basf Ag | Use of copolymers as solubilizers for sparingly water-soluble compounds |
US20070190182A1 (en) * | 2005-11-08 | 2007-08-16 | Pilkiewicz Frank G | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally |
US9107824B2 (en) | 2005-11-08 | 2015-08-18 | Insmed Incorporated | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally |
WO2007056236A2 (en) * | 2005-11-08 | 2007-05-18 | Transave, Inc. | Methods of treating cancer with lipid-based platinum compound formulations administered intravenously |
US20070190180A1 (en) * | 2005-11-08 | 2007-08-16 | Pilkiewicz Frank G | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intravenously |
CA2629299C (en) | 2005-11-12 | 2017-08-22 | The Board Of Trustees Of The Leland Stanford Junior University | Fgf2-related methods for diagnosing and treating depression |
PL2380592T3 (en) | 2005-11-14 | 2018-07-31 | Teva Pharmaceuticals International Gmbh | Antagonist antibody directed against calcitonin gene-related peptide |
AR056806A1 (en) | 2005-11-14 | 2007-10-24 | Amgen Inc | RANKL- PTH / PTHRP ANTIBODY CHEMICAL MOLECULES |
MY149159A (en) | 2005-11-15 | 2013-07-31 | Hoffmann La Roche | Method for treating joint damage |
EP1948798B1 (en) | 2005-11-18 | 2015-04-01 | Glenmark Pharmaceuticals S.A. | Anti-alpha2 integrin antibodies and their uses |
ZA200804162B (en) | 2005-11-21 | 2009-12-30 | Genentech Inc | Novel gene disruptions, compositions and methods relating thereto |
CA2630602A1 (en) | 2005-11-21 | 2007-05-31 | Isis Pharmaceuticals, Inc. | Modulation of eif4e-bp2 expression |
WO2007064658A2 (en) * | 2005-11-30 | 2007-06-07 | Transave, Inc. | Safe and effective methods of administering therapeutic agents |
AU2006342792A1 (en) | 2005-12-02 | 2007-11-08 | Genentech, Inc. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to IL-22 and IL-22R |
US8466263B2 (en) * | 2005-12-02 | 2013-06-18 | Dana-Farber Cancer Institute, Inc. | Carbonic anhydrase IX (G250) anitbodies |
US20090155345A1 (en) * | 2005-12-08 | 2009-06-18 | Ben Gurion University Of The Negev Research And Development Authority | Methods for affecting liposome composition ultrasound irradiation |
US20080300320A1 (en) * | 2005-12-09 | 2008-12-04 | Basf Se | Use of Polyvinyl Lactam-Polyalkylene Block Copolymers as Solubilisers for Poorly Water-Soluble Compounds |
WO2007070705A2 (en) | 2005-12-15 | 2007-06-21 | The Trustees Of The University Of Pennsylvania | Cationic lipid-mediated vectors |
US20090246208A1 (en) | 2006-01-05 | 2009-10-01 | Novartis Ag | Methods for preventing and treating cancer metastasis and bone loss associated with cancer metastasis |
WO2007082154A2 (en) * | 2006-01-05 | 2007-07-19 | Mayo Foundation For Medical Education And Research | B7-h1 and b7-h4 in cancer |
US20100015642A1 (en) * | 2006-01-05 | 2010-01-21 | Kwon Eugene D | B7-h1 and survivin in cancer |
AU2007251256B2 (en) * | 2006-01-26 | 2013-03-07 | Recopharma Ab | Compositions and methods for inhibiting viral adhesion |
CA2638908C (en) | 2006-01-26 | 2021-04-27 | Susan M. Freier | Compositions and their uses directed to huntingtin |
US7829097B2 (en) * | 2006-02-06 | 2010-11-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Use of HMGB1 for protection against ischemia reperfusion injury |
ZA200807714B (en) | 2006-02-17 | 2010-01-27 | Genentech Inc | Gene disruptions, compositions and methods relating thereto |
US8389688B2 (en) | 2006-03-06 | 2013-03-05 | Aeres Biomedical, Ltd. | Humanized anti-CD22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
US20070218116A1 (en) * | 2006-03-14 | 2007-09-20 | Schwendener Reto A | Compositions and methods for the treatment of tumors and tumor metastases |
US9119782B2 (en) * | 2006-03-20 | 2015-09-01 | Mary P. McCourt | Drug delivery means |
BRPI0709338A2 (en) | 2006-03-21 | 2011-07-12 | Genentech Inc | antibody, isolated nucleic acid molecule, cell, compositions, alpha5beta1 protein detection method, antibody use, treatment methods, kit, use of a composition, use of an alpha5beta antagonist, and use of a vegf antagonist |
EP2004221A2 (en) | 2006-03-23 | 2008-12-24 | Novartis Pharma AG | Anti-tumor cell antigen antibody therapeutics |
KR20170061189A (en) | 2006-03-31 | 2017-06-02 | 알닐람 파마슈티칼스 인코포레이티드 | DsRNA for inhibiting expression of Eg5 gene |
WO2007126455A2 (en) | 2006-04-05 | 2007-11-08 | Genentech, Inc. | Method for using boc/cdo to modulate hedgehog signaling |
CA2649387A1 (en) | 2006-04-19 | 2008-03-27 | Genentech, Inc. | Novel gene disruptions, compositions and methods relating thereto |
US8758723B2 (en) | 2006-04-19 | 2014-06-24 | The Board Of Regents Of The University Of Texas System | Compositions and methods for cellular imaging and therapy |
WO2007124361A2 (en) * | 2006-04-20 | 2007-11-01 | Mayo Foundation For Medical Education And Research | Soluble b7-h1 |
EP2881468B1 (en) | 2006-04-21 | 2017-04-12 | Intervet International B.V. | Pestivirus species |
EP2013222B1 (en) | 2006-04-28 | 2013-02-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of a gene from the jc virus |
US8298818B2 (en) * | 2006-04-28 | 2012-10-30 | University Of Florida Research Foundation, Inc. | Self-complementary adeno-associated virus having a truncated CMV-chicken β-actin promoter |
US8697120B2 (en) * | 2006-05-01 | 2014-04-15 | Johns Hopkins University | Method and use of nano-scale devices for reduction of tissue injury in ischemic and reperfusion injury |
CA2651031A1 (en) * | 2006-05-03 | 2007-11-08 | Baltic Technology Development, Ltd. | Antisense agents combining strongly bound base - modified oligonucleotide and artificial nuclease |
US20070264322A1 (en) * | 2006-05-10 | 2007-11-15 | Huang Ken S | Method for making liposomes conjugated with temperature-sensitive ligands |
JP2009537147A (en) | 2006-05-15 | 2009-10-29 | シー レーン バイオテクノロジーズ, エルエルシー | Neutralizing antibody against influenza virus |
WO2007133801A2 (en) * | 2006-05-15 | 2007-11-22 | Dmitri B Kirpotin | Magnetic microparticles comprising organic substances |
CN101489566B (en) | 2006-05-19 | 2012-04-18 | 阿尔尼拉姆医药品有限公司 | Rnai modulation of aha and therapeutic uses thereof |
EP2029157A4 (en) * | 2006-05-19 | 2009-11-18 | Georgia Tech Res Inst | Abc transporter ligand |
CA2653451C (en) * | 2006-05-22 | 2015-12-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of ikk-b gene |
EP2023938A4 (en) * | 2006-05-23 | 2010-11-10 | Isis Pharmaceuticals Inc | Modulation of chrebp expression |
US8598333B2 (en) * | 2006-05-26 | 2013-12-03 | Alnylam Pharmaceuticals, Inc. | SiRNA silencing of genes expressed in cancer |
US7862812B2 (en) | 2006-05-31 | 2011-01-04 | Lpath, Inc. | Methods for decreasing immune response and treating immune conditions |
US7915399B2 (en) * | 2006-06-09 | 2011-03-29 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
KR101376634B1 (en) | 2006-06-19 | 2014-03-27 | 더 존스 홉킨스 유니버시티 | Tumor-specific delivery of therapeutic agents via liposomase |
US7981425B2 (en) * | 2006-06-19 | 2011-07-19 | Amgen Inc. | Thrombopoietic compounds |
ATE540681T1 (en) | 2006-06-26 | 2012-01-15 | Amgen Inc | METHOD FOR TREATING ATHEROSCLERosis |
EP2029173B1 (en) | 2006-06-26 | 2016-07-20 | MacroGenics, Inc. | Fc riib-specific antibodies and methods of use thereof |
JP5072275B2 (en) | 2006-07-03 | 2012-11-14 | テルモ株式会社 | Method for separating closed vesicles, method for producing preparation and evaluation method |
AU2007314477B2 (en) | 2006-07-11 | 2012-03-29 | Rutgers, The State University Of New Jersey | MG53 compositions and methods of use |
US8324158B2 (en) * | 2006-07-14 | 2012-12-04 | Georgia Tech Research Corporation | Methods for inhibiting CLC-2 channel with GATX2 |
WO2008008523A1 (en) | 2006-07-14 | 2008-01-17 | Regents Of The University Of Minnesota | COMPOUNDS THAT BIND α5β1 INTEGRIN AND METHODS OF USE |
JP2009543579A (en) | 2006-07-19 | 2009-12-10 | ザ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルバニア | WSX-1 / p28 as a target for anti-inflammatory response |
US8198253B2 (en) | 2006-07-19 | 2012-06-12 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to HBXIP |
JP4936312B2 (en) * | 2006-07-20 | 2012-05-23 | 株式会社島津製作所 | Novel amphiphile, drug delivery system and molecular imaging system using the same |
WO2008013918A2 (en) * | 2006-07-26 | 2008-01-31 | Myelin Repair Foundation, Inc. | Cell cycle regulation and differentiation |
CA2659820A1 (en) | 2006-08-04 | 2008-02-14 | Novartis Ag | Ephb3-specific antibody and uses thereof |
CA2660286A1 (en) | 2006-08-09 | 2008-02-21 | Homestead Clinical Corporation | Organ-specific proteins and methods of their use |
DK2383297T5 (en) | 2006-08-14 | 2022-07-04 | Xencor Inc | Optimized antibodies directed against CD19 |
US7867493B2 (en) | 2006-08-18 | 2011-01-11 | Novartis Ag | PRLR-specific antibody and uses thereof |
EP2061900A2 (en) | 2006-08-25 | 2009-05-27 | Oncotherapy Science, Inc. | Prognostic markers and therapeutic targets for lung cancer |
WO2008027338A2 (en) | 2006-08-28 | 2008-03-06 | Kyowa Hakko Kirin Co., Limited | Antagonistic human light-specific human monoclonal antibodies |
SG174753A1 (en) | 2006-08-29 | 2011-10-28 | Genentech Inc | Use of tenecteplase for treating acute ischemic stroke |
RU2009111884A (en) | 2006-09-01 | 2010-10-10 | Займоджинетикс, Инк. (Us) | SEQUENCES OF VARIABLE AREAS OF MONOCLONAL ANTIBODIES AGAINST IL-31 AND METHODS OF USE |
CA2600220C (en) * | 2006-09-07 | 2014-12-09 | Canadian Blood Services | Surface cross-linked lipidic particles, methods of production and uses therefor |
ME02371B (en) | 2006-09-29 | 2016-06-20 | Oncomed Pharm Inc | Compositions and methods for diagnosing and treating cancer |
EP2099467B1 (en) | 2006-10-03 | 2017-05-10 | University Of Medicine And Dentistry Of New Jersey | Atap peptides, nucleic acids encoding the same and associated methods of use |
US10925977B2 (en) * | 2006-10-05 | 2021-02-23 | Ceil>Point, LLC | Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications |
CA2667678A1 (en) | 2006-10-25 | 2008-07-24 | Amgen Inc. | Toxin peptide therapeutic agents |
CA2667574A1 (en) * | 2006-10-27 | 2008-06-12 | Roger A. Sabbadini | Compositions and methods for binding sphingosine-1-phosphate |
AU2007313822A1 (en) | 2006-10-27 | 2008-05-08 | Lpath, Inc. | Compositions and methods for treating ocular diseases and conditions |
WO2008058291A2 (en) | 2006-11-09 | 2008-05-15 | California Institute Of Technology | Modular aptamer-regulated ribozymes |
AU2007317204A1 (en) * | 2006-11-10 | 2008-05-15 | Dimerix Bioscience Pty Ltd | Thyrotropin releasing hormone receptor-orexin receptor hetero-dimers/-oligomers |
AU2007323836B2 (en) | 2006-11-13 | 2013-04-18 | Icos Corporation | Thienopyrimidinones for treatment of inflammatory disorders and cancers |
EP2104513B1 (en) | 2006-11-27 | 2015-05-20 | diaDexus, Inc. | Ovr110 antibody compositions and methods of use |
WO2008070780A1 (en) | 2006-12-07 | 2008-06-12 | Novartis Ag | Antagonist antibodies against ephb3 |
EP1932517A3 (en) * | 2006-12-11 | 2008-07-16 | Universiteit Utrecht Holding B.V. | Liposomes containing a polyphenol derivative such as caffeic acid and a method of post-loading thereof |
US20100203110A1 (en) * | 2006-12-18 | 2010-08-12 | The Johns Hopkins University | Therapeutics for Cancer Using 3-Bromopyruvate and Other Selective Inhibitors of ATP Production |
WO2008079973A2 (en) * | 2006-12-21 | 2008-07-03 | Centocor, Inc. | Egfr binding peptides and uses thereof |
WO2008079976A2 (en) | 2006-12-21 | 2008-07-03 | Centocor, Inc. | Dimeric high affinity egfr constructs and uses thereof |
US8834920B2 (en) | 2006-12-21 | 2014-09-16 | Alza Corporation | Liposome composition for targeting egfr receptor |
EP2913341A1 (en) | 2006-12-22 | 2015-09-02 | University of Utah Research Foundation | Method of detecting ocular diseases and pathologic conditions and treatment of same |
WO2008083169A2 (en) * | 2006-12-26 | 2008-07-10 | The Johns Hopkins University | Compositions and methods for the treatment of immunologic disorders |
CA2673659A1 (en) * | 2006-12-27 | 2008-07-10 | The Johns Hopkins University | Methods of detecting and diagnosing inflamatory responses and disorders by determining the level of soluble b7-h4 |
US20090142342A1 (en) * | 2006-12-27 | 2009-06-04 | Johns Hopkins University | B7-h4 receptor agonist compositions and methods for treating inflammation and auto-immune diseases |
US7989173B2 (en) | 2006-12-27 | 2011-08-02 | The Johns Hopkins University | Detection and diagnosis of inflammatory disorders |
US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
EP2118118B1 (en) * | 2007-01-19 | 2017-09-27 | Exiqon A/S | Mediated cellular delivery of lna oligonucleotides |
WO2008091655A2 (en) * | 2007-01-23 | 2008-07-31 | The Regents Of The University Of California | Methods, compositions and device for directed and controlled heating and release of agents |
EP2641971A1 (en) | 2007-01-29 | 2013-09-25 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating protein expression |
WO2008094275A1 (en) | 2007-01-30 | 2008-08-07 | New York University | Peptides for treatment of conditions associated with nitric oxide |
MX2009008736A (en) | 2007-02-22 | 2009-08-24 | Genentech Inc | Methods for detecting inflammatory bowel disease. |
ES2477497T3 (en) | 2007-03-02 | 2014-07-17 | Genentech, Inc. | Prediction of the response to an HER dimerization inhibitor based on low HER3 expression |
CA2681302C (en) * | 2007-03-19 | 2013-07-23 | Dhiraj Khattar | Proliposomal and liposomal compositions of poorly water-soluble compounds |
JP4510842B2 (en) * | 2007-03-26 | 2010-07-28 | キヤノン株式会社 | Polyhydroxyalkanoate-coated liposome |
CA2682161A1 (en) | 2007-03-29 | 2008-10-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a gene from ebola virus |
SG194368A1 (en) | 2007-05-04 | 2013-11-29 | Technophage Investigacao E Desenvolvimento Em Biotecnologia Sa | Engineered rabbit antibody variable domains and uses thereof |
RU2549701C2 (en) | 2007-05-07 | 2015-04-27 | Медиммун, Ллк | Anti-icos antibodies and their application in treatment of oncological, transplantation-associated and autoimmune diseases |
WO2008141278A1 (en) * | 2007-05-11 | 2008-11-20 | Centocor, Inc. | Method for preparing antibody conjugates |
US20090196913A1 (en) * | 2007-05-11 | 2009-08-06 | Ken Shi Kun Huang | Anti-Alpha-V Immunoliposome Composition, Methods, and Uses |
US20090175784A1 (en) * | 2007-05-11 | 2009-07-09 | Joshua Goldstein | Anti-Alpha V Immunoliposome Composition, Methods, and Uses |
EP2650018A3 (en) | 2007-05-14 | 2014-09-03 | The University of Chicago | Antibody-LIGHT fusion products for cancer therapeutics |
EP2173381B1 (en) | 2007-05-14 | 2013-10-02 | NovImmune SA | Fc receptor-binding polypeptides with modified effector functions |
CA2840407A1 (en) * | 2007-05-22 | 2008-12-18 | Amgen Inc. | Compositions and methods for producing bioactive fusion proteins |
WO2008148023A2 (en) * | 2007-05-23 | 2008-12-04 | Medical College Of Georgia Research Institute, Inc. | Compositions and methods for treating neurological disorders |
EP3486653A1 (en) | 2007-05-24 | 2019-05-22 | The United States Government as represented by The Department of Veterans Affairs | Treatment of skeletal muscle disorder using ent2 |
JP5989299B2 (en) | 2007-05-30 | 2016-09-07 | エルパス・インコーポレイテッドLpath, Inc. | Compositions and methods for lysophosphatidic acid binding |
EP2708557A1 (en) | 2007-05-30 | 2014-03-19 | Xencor, Inc. | Method and compositions for inhibiting CD32B expressing cells |
US9163091B2 (en) * | 2007-05-30 | 2015-10-20 | Lpath, Inc. | Compositions and methods for binding lysophosphatidic acid |
AR066984A1 (en) | 2007-06-15 | 2009-09-23 | Novartis Ag | INHIBITION OF THE EXPRESSION OF THE ALFA SUBUNITY OF THE SODIUM EPITELIAL CHANNEL (ENAC) THROUGH ARNI (INTERFERENCE RNA) |
TW200916094A (en) * | 2007-06-27 | 2009-04-16 | Poniard Pharmaceuticals Inc | Stabilized picoplatin dosage form |
WO2009029342A2 (en) | 2007-07-13 | 2009-03-05 | The Johns Hopkins University | B7-dc variants |
CA2692819A1 (en) | 2007-07-16 | 2009-01-22 | Genentech, Inc. | Humanized anti-cd79b antibodies and immunoconjugates and methods of use |
SI2176296T1 (en) | 2007-07-16 | 2012-05-31 | Genentech Inc | Anti-cd79b antibodies and immunoconjugates and methods of use |
US20090082217A1 (en) * | 2007-07-16 | 2009-03-26 | California Institute Of Technology | Selection of nucleic acid-based sensor domains within nucleic acid switch platform |
US8183381B2 (en) * | 2007-07-19 | 2012-05-22 | Metabolex Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
JP2010534730A (en) * | 2007-07-26 | 2010-11-11 | ビーエーエスエフ ソシエタス・ヨーロピア | Process for the preparation of solid-form copolymers based on polyethers obtained by graft polymerization in solution |
EP2522721B1 (en) | 2007-07-26 | 2016-05-04 | Amgen, Inc | Modified lecithin-cholesterol acyltransferase enzymes |
US7666973B2 (en) | 2007-07-30 | 2010-02-23 | Tyco Healthcare Group Lp | Carbonate copolymers |
CA2693208A1 (en) | 2007-08-02 | 2009-02-05 | Victoria Smith | Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis |
WO2009020093A1 (en) * | 2007-08-09 | 2009-02-12 | Daiichi Sankyo Company, Limited | Immunoliposome inducing apoptosis into cell expressing death domain-containing receptor |
US20090048423A1 (en) * | 2007-08-15 | 2009-02-19 | Tyco Healthcare Group Lp | Phospholipid Copolymers |
US8268958B2 (en) | 2007-08-15 | 2012-09-18 | Tyco Healthcare Group Ip | Phospholipid copolymers |
US8367815B2 (en) * | 2007-08-28 | 2013-02-05 | California Institute Of Technology | Modular polynucleotides for ligand-controlled regulatory systems |
US20120165387A1 (en) | 2007-08-28 | 2012-06-28 | Smolke Christina D | General composition framework for ligand-controlled RNA regulatory systems |
JP2010539089A (en) * | 2007-09-07 | 2010-12-16 | ゲンシア コーポレーション | Mitochondrial composition and uses thereof |
US8865667B2 (en) * | 2007-09-12 | 2014-10-21 | California Institute Of Technology | Higher-order cellular information processing devices |
US20110014118A1 (en) * | 2007-09-21 | 2011-01-20 | Lawrence Tamarkin | Nanotherapeutic colloidal metal compositions and methods |
CA2700378A1 (en) * | 2007-09-21 | 2009-03-29 | Cytimmune Sciences, Inc. | Nanotherapeutic colloidal metal compositions and methods |
CN106310293A (en) | 2007-09-27 | 2017-01-11 | 免疫疫苗技术有限公司 | Use of liposomes in a carrier comprising a continuous hydrophobic phase for delivery of polynucleotides in vivo |
CA2700810A1 (en) | 2007-09-28 | 2009-04-02 | Universitatsspital Basel | Immunoliposomes for treatment of cancer |
EP2205741A2 (en) | 2007-10-02 | 2010-07-14 | Amgen Inc. | Increasing erythropoietin using nucleic acids hybridizable to micro-rna and precursors thereof |
US20100209452A1 (en) * | 2007-10-03 | 2010-08-19 | Immunovaccine Technologies, Inc | Compositions comprising an antigen, an amphipathic compound and a hydrophobic carrier, and uses thereof |
UA114700C2 (en) * | 2007-10-16 | 2017-07-25 | Біокон Лімітед | SOLID PHARMACEUTICAL FORM FOR ORAL APPLICATION AND MANUFACTURING PROCESS |
US8361465B2 (en) * | 2007-10-26 | 2013-01-29 | Lpath, Inc. | Use of anti-sphingosine-1-phosphate antibodies in combination with chemotherapeutic agents |
AU2008324068A1 (en) * | 2007-11-05 | 2009-05-14 | Baltic Technology Development, Ltd. | Use of oligonucleotides with modified bases in hybridization of nucleic acids |
AU2008324800B2 (en) | 2007-11-05 | 2014-03-27 | Astrazeneca Ab | Methods of treating scleroderma |
DK2514436T3 (en) | 2007-11-07 | 2018-03-12 | Genentech Inc | IL-22 FOR USE IN TREATMENT OF MICROBIAL DISEASES |
US20110033476A1 (en) * | 2007-11-12 | 2011-02-10 | Theraclone Sciences Inc. | Compositions and methods for the therapy and diagnosis of influenza |
MX2010005244A (en) * | 2007-11-12 | 2010-10-25 | Theraclone Sciences Inc | Compositions and methods for the therapy and diagnosis of influenza. |
US8598165B2 (en) | 2007-11-26 | 2013-12-03 | University Of Kansas | Morpholines as selective inhibitors of cytochrome P450 2A13 |
CA2708221C (en) | 2007-12-06 | 2017-07-25 | Wayne A. Marasco | Antibodies against influenza virus and methods of use thereof |
KR101603109B1 (en) | 2007-12-07 | 2016-03-25 | 지모제넥틱스, 인코포레이티드 | Humanized antibody molecules specific for il-31 |
US9029524B2 (en) * | 2007-12-10 | 2015-05-12 | California Institute Of Technology | Signal activated RNA interference |
EP2617828B1 (en) | 2007-12-10 | 2014-09-24 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of factor VII gene |
KR101499278B1 (en) | 2007-12-17 | 2015-03-06 | 화이자 리미티드 | Treatment of interstitial cystitis |
US8962806B2 (en) | 2007-12-28 | 2015-02-24 | Dana-Farber Cancer Institute, Inc. | Humanized monoclonal antibodies and methods of use |
EP2224912B1 (en) | 2008-01-02 | 2016-05-11 | TEKMIRA Pharmaceuticals Corporation | Improved compositions and methods for the delivery of nucleic acids |
US20090181094A1 (en) * | 2008-01-15 | 2009-07-16 | Eric Yueh-Lang Sheu | Molecular Cage for Sustained Release Control of Pharmaceutical and Cosmetic Agents |
AR070141A1 (en) * | 2008-01-23 | 2010-03-17 | Glenmark Pharmaceuticals Sa | SPECIFIC HUMANIZED ANTIBODIES FOR VON WILLEBRAND FACTOR |
TWI472339B (en) | 2008-01-30 | 2015-02-11 | Genentech Inc | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
SI2247620T1 (en) | 2008-01-31 | 2016-09-30 | Genentech, Inc. | Anti-cd79b antibodies and immunoconjugates and methods of use |
US20110020325A1 (en) * | 2008-02-29 | 2011-01-27 | Kwon Eugene D | Methods for reducing granulomatous inflammation |
KR101397407B1 (en) | 2008-03-05 | 2014-06-19 | 알닐람 파마슈티칼스 인코포레이티드 | Compositions and methods for inhibiting expression of Eg5 and VEGF genes |
JP5544309B2 (en) | 2008-03-10 | 2014-07-09 | セラクローン サイエンシーズ, インコーポレイテッド | Compositions and methods for treatment and diagnosis of cytomegalovirus infection |
EP2105145A1 (en) * | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
AU2009228058A1 (en) | 2008-03-28 | 2009-10-01 | Sea Lane Biotechnologies, Llc | Neutralizing molecules to viral antigens |
US20090270404A1 (en) * | 2008-03-31 | 2009-10-29 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
BRPI0911332A2 (en) | 2008-04-04 | 2019-09-24 | Calando Pharmaceuticals Inc | compositions and use of epas1 inhibitors |
BRPI0906550B8 (en) | 2008-04-09 | 2022-01-11 | Genentech Inc | Anti-tigit antibody, uses of an anti-tigit antibody, and in vitro methods to stimulate the cd226-pvr interaction and/or the cd96-pvr interaction, to enhance or stimulate the proliferation of a T cell or the release of proinflammatory cytokines by a dendritic cell, to enhance or stimulate the immune response of the T cell to enhance or stimulate the production of proinflammatory cytokines by a dendritic cell |
EP3023502A1 (en) | 2008-04-10 | 2016-05-25 | Cell Signaling Technology, Inc. | Compositions and methods for detecting egfr mutations in cancer |
PT2279254T (en) | 2008-04-15 | 2017-09-04 | Protiva Biotherapeutics Inc | Novel lipid formulations for nucleic acid delivery |
CA2722668A1 (en) * | 2008-04-29 | 2009-11-05 | Wyeth Llc | Methods for treating inflammation |
US8324366B2 (en) | 2008-04-29 | 2012-12-04 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for delivering RNAI using lipoproteins |
WO2009136297A2 (en) * | 2008-05-09 | 2009-11-12 | Recopharma Ab | Compositions and methods for inhibiting toxin a from clostridium difficile |
US20090280104A1 (en) * | 2008-05-09 | 2009-11-12 | Recopharma Ab | Compositions and methods for inhibiting shiga toxin and shiga-like toxin |
MX2010012368A (en) | 2008-05-16 | 2010-12-06 | Genentech Inc | Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7integrin antagonists. |
US8093018B2 (en) | 2008-05-20 | 2012-01-10 | Otsuka Pharmaceutical Co., Ltd. | Antibody identifying an antigen-bound antibody and an antigen-unbound antibody, and method for preparing the same |
WO2009140853A1 (en) * | 2008-05-23 | 2009-11-26 | The University Of Hong Kong | Combination therapy for the treatment of influenza |
CA2723918C (en) | 2008-06-05 | 2018-01-09 | Immunovaccine Technologies Inc. | Compositions comprising liposomes, an antigen, a polynucleotide and a carrier comprising a continuous phase of a hydrophobic substance |
WO2009148121A1 (en) | 2008-06-05 | 2009-12-10 | 株式会社 島津製作所 | Novel molecular assembly, molecular probe for molecular imaging and molecular probe for drug delivery system using the same, and molecular imaging system and drug delivery system |
US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
WO2009150623A1 (en) | 2008-06-13 | 2009-12-17 | Pfizer Inc | Treatment of chronic prostatitis |
US20110104074A1 (en) * | 2008-06-18 | 2011-05-05 | University Of Louisville Research Foundation, Inc. | Methods for targeted cancer treatment and detection |
US20100003315A1 (en) * | 2008-07-02 | 2010-01-07 | Willeford Kenneth L | Method and Composition for the Treatment of Skin Conditions |
RS53924B1 (en) | 2008-07-08 | 2015-08-31 | Oncomed Pharmaceuticals, Inc. | Notch-binding agents and antagonists and methods of use thereof |
EP2310440A4 (en) * | 2008-07-10 | 2013-06-05 | Serina Therapeutics Inc | Polyoxazolines with inert terminating groups, polyoxazolines prepared from protected initiating groups and related compounds |
US20100008900A1 (en) * | 2008-07-14 | 2010-01-14 | The University Of Hong Kong | Annexin ii compositions for treating or monitoring inflammation or immune-mediated disorders |
US8815818B2 (en) | 2008-07-18 | 2014-08-26 | Rxi Pharmaceuticals Corporation | Phagocytic cell delivery of RNAI |
US20110237646A1 (en) * | 2008-08-07 | 2011-09-29 | Isis Pharmaceuticals, Inc. | Modulation of transthyretin expression for the treatment of cns related disorders |
WO2010019702A2 (en) | 2008-08-12 | 2010-02-18 | Oncomed Pharmaceuticals, Inc. | Ddr1-binding agents and methods of use thereof |
CA2734225A1 (en) | 2008-08-15 | 2010-02-18 | Georgetown University | Fluorescent regulators of rassf1a expression and human cancer cell proliferation |
EP2331092B1 (en) | 2008-08-21 | 2014-03-19 | The Johns Hopkins University | Methods and compositions for administration of 3-halopyruvate and related compounds for the treatment of cancer |
MX2011001135A (en) | 2008-08-22 | 2011-03-21 | Sanofi Aventis | [4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-[7-fluoro-1-( 2-methoxy-ethyl)-4-trifluoromethoxy-1h-indol-3-yl]-methan one as an inhibitor of mast cell tryptase. |
EP3301116A1 (en) | 2008-08-25 | 2018-04-04 | Dana Farber Cancer Institute, Inc. | Conserved influenza hemagglutinin epitope and antibodies thereto |
US8252762B2 (en) | 2008-08-25 | 2012-08-28 | Excaliard Pharmaceuticals, Inc. | Antisense oligonucleotides directed against connective tissue growth factor and uses thereof |
KR20110050529A (en) | 2008-08-25 | 2011-05-13 | 앰플리뮨, 인크. | Compositions of pd-1 antagonists and methods of use |
EA201170375A1 (en) * | 2008-08-25 | 2012-03-30 | Эмплиммьюн, Инк. | PD-1 ANTAGONISTS AND METHODS OF THEIR APPLICATION |
EP2331690B1 (en) | 2008-09-02 | 2016-01-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of mutant egfr gene |
RU2530583C2 (en) | 2008-09-10 | 2014-10-10 | Дженентек, Инк. | Methods of inhibiting ocular angiogenesis |
TWI445716B (en) | 2008-09-12 | 2014-07-21 | Rinat Neuroscience Corp | Pcsk9 antagonists |
TW201438738A (en) | 2008-09-16 | 2014-10-16 | Genentech Inc | Methods for treating progressive multiple sclerosis |
AU2009293658A1 (en) | 2008-09-22 | 2010-03-25 | James Cardia | Reduced size self-delivering RNAi compounds |
EP3109321B1 (en) | 2008-09-25 | 2019-05-01 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene |
BRPI0920552A2 (en) | 2008-10-09 | 2019-09-24 | Univ Northeastern | multifunctional self-organizing polymeric nanosystems |
CN104119242B (en) | 2008-10-09 | 2017-07-07 | 泰米拉制药公司 | The amino lipids of improvement and the method for delivering nucleic acid |
IL281434B2 (en) | 2008-10-20 | 2023-09-01 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhabiting expression of transthyretin |
US8147847B2 (en) * | 2008-10-21 | 2012-04-03 | International Vaccine Institute | Shigella protein antigens and methods |
WO2010048207A2 (en) * | 2008-10-21 | 2010-04-29 | Metabolex, Inc. | Aryl gpr120 receptor agonists and uses thereof |
US8871202B2 (en) | 2008-10-24 | 2014-10-28 | Lpath, Inc. | Prevention and treatment of pain using antibodies to sphingosine-1-phosphate |
CA2742899A1 (en) * | 2008-11-06 | 2010-05-14 | Glenmark Pharmaceuticals, S.A. | Treatment with anti-alpha2 integrin antibodies |
WO2010054401A1 (en) | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Novel lipids and compositions for the delivery of therapeutics |
ES2674719T3 (en) | 2008-11-13 | 2018-07-03 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
SI2752189T1 (en) | 2008-11-22 | 2017-02-28 | F. Hoffmann-La Roche Ag | Use of anti-vegf antibody in combination with chemotherapy for treating breast cancer |
WO2010068414A2 (en) * | 2008-11-25 | 2010-06-17 | Bowen Richard L | Methods for treating obesity related disease |
US20110160222A1 (en) * | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
KR101749352B1 (en) | 2008-12-04 | 2017-06-20 | 큐알엔에이, 인크. | Treatment of sirtuin 1(sirt1) related diseases by inhibition of natural antisense transcript to sirtuin 1 |
ES2637063T3 (en) | 2008-12-04 | 2017-10-10 | Curna, Inc. | Treatment of diseases related to tumor suppressor genes by inhibiting the natural antisense transcript to the gene |
CA2745329C (en) | 2008-12-04 | 2022-07-12 | Opko Curna, Llc | Treatment of erythropoietin (epo) related diseases by inhibition of natural antisense transcript to epo |
US8628762B2 (en) | 2008-12-10 | 2014-01-14 | Icahn School Of Medicine At Mount Sinai | T-helper cell type 17 lineage-specific adjuvants, compositions and methods |
CA2746514C (en) | 2008-12-10 | 2018-11-27 | Alnylam Pharmaceuticals, Inc. | Gnaq targeted dsrna compositions and methods for inhibiting expression |
AR074760A1 (en) | 2008-12-18 | 2011-02-09 | Metabolex Inc | GPR120 RECEIVER AGONISTS AND USES OF THE SAME IN MEDICINES FOR THE TREATMENT OF DIABETES AND METABOLIC SYNDROME. |
AR074776A1 (en) | 2008-12-18 | 2011-02-09 | Sanofi Aventis | METHOD TO TREAT MACULAR DEGENERATION; MODULATING THE PATIENT'S IMMUNE SYSTEM |
WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
PT2376088T (en) | 2008-12-23 | 2017-05-02 | Gilead Pharmasset Llc | 6-o-substituted-2-amino-purine nucleoside phosphoramidates |
BRPI0923815A2 (en) | 2008-12-23 | 2015-07-14 | Pharmasset Inc | Purine nucleoside synthesis |
NZ593649A (en) | 2008-12-23 | 2013-11-29 | Gilead Pharmasset Llc | Nucleoside analogs |
US9493774B2 (en) | 2009-01-05 | 2016-11-15 | Rxi Pharmaceuticals Corporation | Inhibition of PCSK9 through RNAi |
EP3243504A1 (en) | 2009-01-29 | 2017-11-15 | Arbutus Biopharma Corporation | Improved lipid formulation |
WO2010086828A2 (en) | 2009-02-02 | 2010-08-05 | Rinat Neuroscience Corporation | Agonist anti-trkb monoclonal antibodies |
WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
JP6066035B2 (en) | 2009-02-12 | 2017-01-25 | クルナ・インコーポレーテッド | Treatment of glial cell-derived neurotrophic factor (GDNF) -related diseases by suppression of natural antisense transcripts against GDNF |
PL2396038T3 (en) | 2009-02-12 | 2016-05-31 | Curna Inc | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
US8329882B2 (en) | 2009-02-18 | 2012-12-11 | California Institute Of Technology | Genetic control of mammalian cells with synthetic RNA regulatory systems |
US20120041051A1 (en) | 2009-02-26 | 2012-02-16 | Kevin Fitzgerald | Compositions And Methods For Inhibiting Expression Of MIG-12 Gene |
US8975389B2 (en) | 2009-03-02 | 2015-03-10 | Alnylam Pharmaceuticals, Inc. | Nucleic acid chemical modifications |
JP6250263B2 (en) | 2009-03-04 | 2017-12-20 | クルナ・インコーポレーテッド | Treatment of SIRT1-related diseases by suppression of natural antisense transcripts against sirtuin 1 (SIRT1) |
EP2228059A1 (en) | 2009-03-12 | 2010-09-15 | Universitätsspital Basel | Chemotherapeutic composition for the treatment of cancer |
AU2010223967B2 (en) | 2009-03-12 | 2015-07-30 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes |
MX2011009751A (en) | 2009-03-16 | 2011-09-29 | Opko Curna Llc | Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2. |
SI3260136T1 (en) | 2009-03-17 | 2021-05-31 | Theraclone Sciences, Inc. | Human immunodeficiency virus (hiv) -neutralizing antibodies |
WO2010107740A2 (en) | 2009-03-17 | 2010-09-23 | Curna, Inc. | Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1 |
NZ595307A (en) | 2009-03-24 | 2013-11-29 | Gilead Calistoga Llc | Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use |
DK2411411T3 (en) | 2009-03-25 | 2016-11-07 | Hoffmann La Roche | New anti-alpha5beta1 antibodies and uses thereof |
JP6132548B2 (en) | 2009-04-01 | 2017-05-24 | ジェネンテック, インコーポレイテッド | Anti-FcRH5 antibodies and immunoconjugates and methods of use |
UA105384C2 (en) | 2009-04-01 | 2014-05-12 | Дженентек, Инк. | Treatment of insulin-resistant disorders |
US9145555B2 (en) | 2009-04-02 | 2015-09-29 | California Institute Of Technology | Integrated—ligand-responsive microRNAs |
JP2012524126A (en) * | 2009-04-20 | 2012-10-11 | ギリアド カリストガ リミテッド ライアビリティ カンパニー | Method for treating solid tumors |
EP3524275A1 (en) | 2009-04-22 | 2019-08-14 | Massachusetts Institute Of Technology | Innate immune supression enables repeated delivery of long rna molecules |
US8609101B2 (en) | 2009-04-23 | 2013-12-17 | Theraclone Sciences, Inc. | Granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibodies |
AU2010245011B2 (en) * | 2009-04-27 | 2015-09-03 | Oncomed Pharmaceuticals, Inc. | Method for making heteromultimeric molecules |
EP2248903A1 (en) | 2009-04-29 | 2010-11-10 | Universitat Autònoma De Barcelona | Methods and reagents for efficient and targeted gene transfer to monocytes and macrophages |
US8524784B2 (en) | 2009-04-30 | 2013-09-03 | Intezyne Technologies, Incorporated | Polymer micelles containing anthracylines for the treatment of cancer |
EP2424359A4 (en) | 2009-04-30 | 2014-01-15 | Intezyne Technologies Inc | Polymer micelles containing anthracylines for the treatment of cancer |
CN102639151B (en) | 2009-05-01 | 2017-03-22 | 库尔纳公司 | Treatment of hemoglobin (HBF/HBG) related diseases inhibition of natural antisense transcript to HBF/HBG |
JP5889783B2 (en) | 2009-05-05 | 2016-03-22 | テクミラ ファーマシューティカルズ コーポレイションTekmira Pharmaceuticals Corporation | Methods for delivering oligonucleotides to immune cells |
NZ596186A (en) | 2009-05-05 | 2014-03-28 | Alnylam Pharmaceuticals Inc | Lipid compositions |
MX348013B (en) | 2009-05-05 | 2017-05-23 | Novimmune Sa | Anti-il-17f antibodies and methods of use thereof. |
CA2761142C (en) | 2009-05-06 | 2021-06-08 | Opko Curna, Llc | Treatment of tristetraproline (ttp) related diseases by inhibition of natural antisense transcript to ttp |
US9155754B2 (en) | 2009-05-06 | 2015-10-13 | Curna, Inc. | Treatment of ABCA1 gene related diseases by inhibition of a natural antisense transcript to ABCA1 |
ES2664590T3 (en) | 2009-05-18 | 2018-04-20 | Curna, Inc. | Treatment of diseases related to reprogramming factors by inhibition of the natural antisense transcript to a reprogramming factor |
EP2432499A2 (en) | 2009-05-20 | 2012-03-28 | Schering Corporation | Modulation of pilr receptors to treat microbial infections |
TWI583692B (en) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | Nucleoside phosphoramidates |
CA2762302A1 (en) | 2009-05-20 | 2010-11-25 | Theraclone Sciences, Inc. | Compositions and methods for the therapy and diagnosis of influenza |
CN102549158B (en) | 2009-05-22 | 2017-09-26 | 库尔纳公司 | By suppressing to treat the disease that TFE3 is related to IRS albumen 2 (IRS2) for transcription factor E3 (TFE3) natural antisense transcript |
US8791085B2 (en) | 2009-05-28 | 2014-07-29 | Curna, Inc. | Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene |
TR201811076T4 (en) | 2009-06-10 | 2018-08-27 | Arbutus Biopharma Corp | Improved lipid formulation. |
WO2010143193A1 (en) | 2009-06-11 | 2010-12-16 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Targeted liposomes comprising n-containing bisphosphonates and uses thereof |
US8951981B2 (en) | 2009-06-16 | 2015-02-10 | Curna, Inc. | Treatment of paraoxonase 1 (PON1) related diseases by inhibition of natural antisense transcript to PON1 |
US20120171170A1 (en) | 2009-06-16 | 2012-07-05 | Opko Curna, Llc | Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene |
WO2010146511A1 (en) | 2009-06-17 | 2010-12-23 | Pfizer Limited | Treatment of overactive bladder |
WO2010151671A2 (en) | 2009-06-24 | 2010-12-29 | Curna, Inc. | Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2 |
US8921330B2 (en) | 2009-06-26 | 2014-12-30 | Curna, Inc. | Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene |
WO2010151808A1 (en) | 2009-06-26 | 2010-12-29 | Sea Lane Biotechnologies, Llc | Expression of surrogate light chains |
EP2450055B1 (en) | 2009-06-30 | 2018-01-03 | Obshestvo S OgranichennoyOtvetstvennostiu"OncoMax" | Method for suppressing renal tumor growth by blocking fibroblast growth factor receptor |
WO2011000107A1 (en) | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for delivery of therapeutic agents to solid tumors |
US9018187B2 (en) | 2009-07-01 | 2015-04-28 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
WO2011000106A1 (en) | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Improved cationic lipids and methods for the delivery of therapeutic agents |
KR20120051002A (en) | 2009-07-07 | 2012-05-21 | 제넨테크, 인크. | Diagnosis and treatment of autoimmune demyelinating diseases |
CA2768444A1 (en) * | 2009-07-17 | 2011-01-20 | Rigshospitalet | Loading technique for preparing radionuclide and ionophore containing liposomes in which the ionophore is 2-hydroxyquionoline (carbostyril) or structurally related 2-hydroxyquinolines |
EA201270184A1 (en) | 2009-07-21 | 2012-08-30 | ГИЛИЭД КАЛИСТОГА ЭлЭлСи | TREATMENT OF LIVER DISORDERS PI3K INHIBITORS |
US9937128B2 (en) | 2009-08-03 | 2018-04-10 | The University Of North Carolina At Chapel Hill | Liposomes comprising a calcium phosphate-containing precipitate |
EP2462229B1 (en) | 2009-08-05 | 2016-05-11 | CuRNA, Inc. | Treatment of insulin gene (ins) related diseases by inhibition of natural antisense transcript to an insulin gene (ins) |
AP3574A (en) | 2009-08-14 | 2016-02-08 | Alnylam Pharmaceuticals Inc | Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus |
TWI451875B (en) | 2009-08-15 | 2014-09-11 | 建南德克公司 | Anti-angiogenesis therapy for the treatment of previously treated breast cancer |
FR2955324A1 (en) | 2010-01-15 | 2011-07-22 | Sanofi Aventis | DISUBSTITUTED 4- (5-AMINOMETHYL-PHENYL) -PIPERIDIN-1-YL] -1H-INDOL-3-YL] -METHANONES |
WO2011031482A2 (en) | 2009-08-25 | 2011-03-17 | Curna, Inc. | Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap |
US9011853B2 (en) | 2009-08-31 | 2015-04-21 | Amplimmune, Inc. | B7-H4 fusion proteins and methods of use thereof |
US20110059111A1 (en) | 2009-09-01 | 2011-03-10 | Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center | Mammalian receptors as targets for antibody and active vaccination therapy against mold infections |
EP2473522B1 (en) | 2009-09-02 | 2016-08-17 | Genentech, Inc. | Mutant smoothened and methods of using the same |
CN102666553B (en) | 2009-10-01 | 2015-05-06 | 赛马拜制药公司 | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
US20130079382A1 (en) | 2009-10-12 | 2013-03-28 | Larry J. Smith | Methods and Compositions for Modulating Gene Expression Using Oligonucleotide Based Drugs Administered in vivo or in vitro |
MX368790B (en) * | 2009-10-15 | 2019-10-16 | Genentech Inc | Chimeric fibroblast growth factors with altered receptor specificity. |
EP3485908B1 (en) | 2009-10-16 | 2021-08-18 | Mereo BioPharma 5, Inc. | Therapeutic combination and use of dll4 antagonist antibodies and anti-hypertensive agents |
WO2011049625A1 (en) | 2009-10-20 | 2011-04-28 | Mansour Samadpour | Method for aflatoxin screening of products |
ES2564207T3 (en) | 2009-10-22 | 2016-03-18 | F. Hoffmann-La Roche Ag | Methods and compositions for modulating hepsin activation of macrophage stimulating protein |
WO2011053468A1 (en) | 2009-10-30 | 2011-05-05 | Sanofi-Aventis | Amino-benzoic acid derivatives for use in the treatment of dihydrogenase-related disorders |
CN105801550B (en) | 2009-11-05 | 2019-06-14 | 理森制药股份公司 | Novel chromene kinase modulator |
WO2011056234A1 (en) | 2009-11-06 | 2011-05-12 | Fibrogen, Inc. | Treatment for radiation-induced disorders |
EP3037435B1 (en) | 2009-11-17 | 2019-08-07 | MUSC Foundation for Research Development | Human monoclonal antibodies to human nucleolin |
EP2507264A2 (en) | 2009-11-30 | 2012-10-10 | F. Hoffmann-La Roche AG | Antibodies for treating and diagnosing tumors expressing slc34a2 (tat211 = seqid 2) |
EP3296398A1 (en) | 2009-12-07 | 2018-03-21 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
EP2509997B1 (en) | 2009-12-07 | 2017-08-30 | i2 Pharmaceuticals, Inc. | Conjugates comprising an antibody surrogate scaffold with improved pharmacokinetic properties |
JP2013513588A (en) | 2009-12-11 | 2013-04-22 | ジーンコード エーエス | Method for facilitating survival of neural cells using mimic or RET signaling pathway activators of GDNF family ligand (GFL) |
US20130004490A1 (en) | 2009-12-14 | 2013-01-03 | The United States of America, as represented by the Secretary, Department | Delivery of transthyretin across the blood-brain barrier as a treatment for alzheimer's disease |
US9173895B2 (en) | 2009-12-16 | 2015-11-03 | Curna, Inc. | Treatment of membrane bound transcription factor peptidase, site 1 (MBTPS1) related diseases by inhibition of natural antisense transcript to MBTPS1 |
US8691227B2 (en) | 2009-12-17 | 2014-04-08 | Merck Sharp & Dohme Corp. | Methods of treating multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease using agonists antibodies to PILR-α |
WO2011075656A1 (en) | 2009-12-18 | 2011-06-23 | The University Of British Columbia | Methods and compositions for delivery of nucleic acids |
CA2782375C (en) | 2009-12-23 | 2023-10-31 | Opko Curna, Llc | Treatment of uncoupling protein 2 (ucp2) related diseases by inhibition of natural antisense transcript to ucp2 |
DK2516468T3 (en) | 2009-12-23 | 2016-05-23 | Synimmune Gmbh | ANTI-FLT3 ANTIBODIES AND METHODS FOR USING THESE |
KR101891352B1 (en) | 2009-12-23 | 2018-08-24 | 큐알엔에이, 인크. | Treatment of hepatocyte growth factor (hgf) related diseases by inhibition of natural antisense transcript to hgf |
SG181501A1 (en) | 2009-12-23 | 2012-07-30 | Sanofi Sa | Prodrugs of [4[4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(1h-pyrrolo-pyridin-yl)-methanones and synthesis thereof |
MX2012007080A (en) | 2009-12-23 | 2012-07-20 | Sanofi Sa | [4[4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-(1h- pyrrolo-pyridin-yl)-methanones and synthesis thereof. |
DK2519542T3 (en) | 2009-12-28 | 2019-01-14 | Onco Therapy Science Inc | ANTI-CDH3 ANTIBODIES AND APPLICATIONS THEREOF. |
RU2611186C2 (en) | 2009-12-29 | 2017-02-21 | Курна, Инк. | TREATMENT OF TUMOR PROTEIN 63 (p63) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO p63 |
ES2657452T3 (en) | 2009-12-29 | 2018-03-05 | Curna, Inc. | Treatment of diseases related to nuclear respiratory factor 1 (NRF1) by inhibition of natural antisense transcript to NRF1 |
WO2011082187A1 (en) | 2009-12-30 | 2011-07-07 | Genentech, Inc. | Methods for modulating a pdgf-aa mediated biological response |
JP5886757B2 (en) | 2010-01-04 | 2016-03-16 | カッパーアールエヌエー,インコーポレイテッド | Treatment of interferon regulatory factor 8 (IRF8) related diseases by inhibition of natural antisense transcripts against interferon regulatory factor 8 (IRF8) |
CN102822342B (en) | 2010-01-06 | 2017-05-10 | 库尔纳公司 | Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene |
CA2786535C (en) | 2010-01-11 | 2019-03-26 | Curna, Inc. | Treatment of sex hormone binding globulin (shbg) related diseases by inhibition of natural antisense transcript to shbg |
TWI535445B (en) | 2010-01-12 | 2016-06-01 | 安可美德藥物股份有限公司 | Wnt antagonists and methods of treatment and screening |
WO2011088215A2 (en) | 2010-01-13 | 2011-07-21 | Oncomed Pharmaceuticals, Inc. | Notch1 binding agents and methods of use thereof |
WO2011090971A2 (en) | 2010-01-19 | 2011-07-28 | The Trustees Of Columbia University In The City Of New York | Osteocalcin as a treatment for male reproductive disorders |
WO2011089211A1 (en) | 2010-01-22 | 2011-07-28 | Synimmune Gmbh | Anti-cd133 antibodies and methods of using the same |
NO2529015T3 (en) | 2010-01-25 | 2018-04-14 | ||
US8198337B2 (en) * | 2010-01-27 | 2012-06-12 | Momentive Performance Materials Inc. | Demulsifier compositions and methods for separating emulsions using the same |
EP2531175A2 (en) | 2010-02-01 | 2012-12-12 | Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd. | Liposomes comprising amphipathic drugs and method for their preparation |
US8962586B2 (en) | 2010-02-22 | 2015-02-24 | Curna, Inc. | Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related diseases by inhibition of natural antisense transcript to PYCR1 |
TWI457135B (en) | 2010-02-23 | 2014-10-21 | Genentech Inc | Combination of carboplatin,gemcitabine and anti-vegf antibody for the treatment of recurrent platinum-sensitive advanced epithelial ovarian,fallopian tube or primary peritoneal cancer |
US8877897B2 (en) | 2010-02-23 | 2014-11-04 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
RU2545401C2 (en) | 2010-02-23 | 2015-03-27 | Санофи | Anti-integrin alpha-2 antibodies and using them |
US8298535B2 (en) | 2010-02-24 | 2012-10-30 | Rinat Neuroscience Corp. | Anti-IL-7 receptor antibodies |
EP2538929A4 (en) | 2010-02-25 | 2014-07-09 | Univ Johns Hopkins | Sustained delivery of therapeutic agents to an eye compartment |
SG183867A1 (en) | 2010-03-11 | 2012-10-30 | Rinat Neuroscience Corp | ANTIBODIES WITH pH DEPENDENT ANTIGEN BINDING |
SI2550018T1 (en) | 2010-03-22 | 2019-05-31 | F. Hoffmann-La Roche Ag | Compositions and methods useful for stabilizing protein-containing formulations |
EP2550000A4 (en) | 2010-03-24 | 2014-03-26 | Advirna Inc | Reduced size self-delivering rnai compounds |
ES2625406T3 (en) | 2010-03-25 | 2017-07-19 | Oregon Health & Science University | CMV glycoproteins and recombinant vectors |
EP3329924B1 (en) | 2010-03-29 | 2021-05-05 | Alnylam Pharmaceuticals, Inc. | Dsrna therapy for transthyretin (ttr) related ocular amyloidosis |
CN102971340A (en) | 2010-03-29 | 2013-03-13 | 酵活有限公司 | Antibodies with enhanced or suppressed effector function |
PL3290428T3 (en) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tablet comprising crystalline (s)-isopropyl 2-(((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2h)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate |
KR101760242B1 (en) | 2010-03-31 | 2017-07-21 | 베링거 인겔하임 인터내셔날 게엠베하 | Anti-cd40 antibodies |
EP2609923B1 (en) | 2010-03-31 | 2017-05-24 | Gilead Pharmasset LLC | Process for the crystallisation of (s)-isopropyl 2-(((s)-(perfluorophenoxy)(phenoxy)phosphoryl)amino)propanoate |
DK2552930T3 (en) | 2010-03-31 | 2015-12-07 | Gilead Pharmasset Llc | Crystalline (S) -isopropyl 2 - (((S) - (((2R, 3R, 4R, 5R) -5- (2,4-dioxo-3,4-DIHYDROPYRIMIDIN- 1- (2 H) -yl) - 4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphoryl) amino) propanoate |
WO2011123621A2 (en) | 2010-04-01 | 2011-10-06 | Alnylam Pharmaceuticals Inc. | 2' and 5' modified monomers and oligonucleotides |
WO2011125015A2 (en) | 2010-04-05 | 2011-10-13 | Bar-Ilan University | Protease-activatable pore-forming polypeptides |
JP2013523162A (en) | 2010-04-06 | 2013-06-17 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Compositions and methods for inhibiting the expression of the CD274 / PD-L1 gene |
CN102858979B (en) | 2010-04-09 | 2018-01-26 | 库尔纳公司 | FGF21 relevant diseases are treated by suppressing the natural antisense transcript of FGF2 1 (FGF21) |
US9725479B2 (en) | 2010-04-22 | 2017-08-08 | Ionis Pharmaceuticals, Inc. | 5′-end derivatives |
WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
WO2011133868A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Conformationally restricted dinucleotide monomers and oligonucleotides |
US9096660B2 (en) | 2010-04-26 | 2015-08-04 | Abraxis Bioscience, Llc | SPARC binding antibodies and uses thereof |
WO2011135905A1 (en) * | 2010-04-28 | 2011-11-03 | 国立大学法人北海道大学 | Lipid membrane structure |
WO2011139911A2 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
US20110294868A1 (en) | 2010-04-29 | 2011-12-01 | Monia Brett P | Modulation of transthyretin expression |
ES2552954T3 (en) | 2010-04-30 | 2015-12-03 | Alexion Pharmaceuticals, Inc. | Anti-C5a antibodies and methods for the use of antibodies |
MX2012012743A (en) | 2010-05-03 | 2012-11-23 | Genentech Inc | Compositions and methods useful for reducing the viscosity of protein-containing formulations. |
CN102933711B (en) | 2010-05-03 | 2018-01-02 | 库尔纳公司 | Sirtuin (SIRT) relevant disease is treated by suppressing the natural antisense transcript of Sirtuin (SIRT) |
WO2011139985A1 (en) | 2010-05-03 | 2011-11-10 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
DK2569430T3 (en) | 2010-05-12 | 2019-02-04 | Univ Columbia | PROCEDURES FOR MANUFACTURING ENTEROENDOCRIN CELLS WHICH MANUFACTURE AND SECRET INSULIN |
TWI531370B (en) | 2010-05-14 | 2016-05-01 | 可娜公司 | Treatment of par4 related diseases by inhibition of natural antisense transcript to par4 |
DK2571878T3 (en) | 2010-05-17 | 2019-02-11 | Indian Incozen Therapeutics Pvt Ltd | Hitherto unknown 3,5-DISUBSTITUTED-3H-IMIDAZO [4,5-B] PYRIDINE AND 3,5- DISUBSTITUTED -3H- [1,2,3] TRIAZOL [4,5-B] PYRIDINE COMPOUNDS AS MODULATORS OF PROTEIN CHINES |
WO2011146574A1 (en) | 2010-05-18 | 2011-11-24 | Neumedicines, Inc. | Il-12 formulations for enhancing hematopoiesis |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
US8895528B2 (en) | 2010-05-26 | 2014-11-25 | Curna, Inc. | Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1 |
EP3957653A1 (en) | 2010-06-02 | 2022-02-23 | Dana Farber Cancer Institute, Inc. | Humanized monoclonal antibodies and methods of use |
WO2011153243A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Anti-angiogenesis therapy for treating gastric cancer |
CA2801066C (en) | 2010-06-02 | 2021-02-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods directed to treating liver fibrosis |
DK2575764T3 (en) | 2010-06-03 | 2017-08-07 | Alnylam Pharmaceuticals Inc | BIODEGRADABLE LIPIDS FOR THE ACTIVATION OF ACTIVE AGENTS |
CA2801182A1 (en) | 2010-06-16 | 2011-12-22 | Metabolex, Inc. | Gpr120 receptor agonists and uses thereof |
US8299117B2 (en) | 2010-06-16 | 2012-10-30 | Metabolex Inc. | GPR120 receptor agonists and uses thereof |
CN103037843A (en) | 2010-06-23 | 2013-04-10 | 麦它波莱克斯股份有限公司 | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-Yl-phenoxymethyl)-thiazol-2-Yl]-piperidin-1-Yl}-pyrimidine |
AU2011270828B2 (en) | 2010-06-24 | 2015-09-24 | Genentech, Inc. | Compositions and methods containing alkylgycosides for stabilizing protein- containing formulations |
CN102309448B (en) * | 2010-06-29 | 2014-07-09 | 中国人民解放军军事医学科学院毒物药物研究所 | Pulmonary delivery ciprofloxacin pharmaceutical composition and preparation method thereof |
US9006417B2 (en) | 2010-06-30 | 2015-04-14 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
AU2011276234B2 (en) | 2010-07-06 | 2016-02-25 | Glaxosmithkline Biologicals S.A. | Liposomes with lipids having an advantageous pKa- value for RNA delivery |
PL2591114T3 (en) | 2010-07-06 | 2017-08-31 | Glaxosmithkline Biologicals Sa | Immunisation of large mammals with low doses of rna |
WO2012006377A2 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Delivery of rna to trigger multiple immune pathways |
HRP20221522T1 (en) | 2010-07-06 | 2023-02-17 | Glaxosmithkline Biologicals S.A. | Virion-like delivery particles for self-replicating rna molecules |
KR20130050966A (en) | 2010-07-12 | 2013-05-16 | 씨오브이엑스 테크놀로지스 아일랜드 리미티드 | Multifunctional antibody conjugates |
EP2593547B1 (en) | 2010-07-14 | 2017-11-15 | CuRNA, Inc. | Treatment of discs large homolog (dlg) related diseases by inhibition of natural antisense transcript to dlg |
EP3696195B1 (en) | 2010-07-23 | 2024-02-14 | Trustees of Boston University | Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery |
US20130202652A1 (en) | 2010-07-30 | 2013-08-08 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
WO2012016184A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
US8906943B2 (en) | 2010-08-05 | 2014-12-09 | John R. Cashman | Synthetic compounds and methods to decrease nicotine self-administration |
AU2011289275A1 (en) | 2010-08-12 | 2013-02-21 | Theraclone Sciences, Inc. | Anti-hemagglutinin antibody compositions and methods of use thereof |
EP2420250A1 (en) | 2010-08-13 | 2012-02-22 | Universitätsklinikum Münster | Anti-Syndecan-4 antibodies |
EP3970742B1 (en) * | 2010-08-31 | 2022-05-25 | GlaxoSmithKline Biologicals S.A. | Pegylated liposomes for delivery of immunogen-encoding rna |
EP3556396B1 (en) | 2010-08-31 | 2022-04-20 | Theraclone Sciences, Inc. | Human immunodeficiency virus (hiv)-neutralizing antibodies |
ES2935542T3 (en) | 2010-08-31 | 2023-03-07 | Glaxosmithkline Biologicals Sa | Small liposomes for delivery of RNA encoding immunogen |
US8551479B2 (en) | 2010-09-10 | 2013-10-08 | Oncomed Pharmaceuticals, Inc. | Methods for treating melanoma |
DK2625197T3 (en) | 2010-10-05 | 2016-10-03 | Genentech Inc | Smoothened MUTANT AND METHODS OF USING THE SAME |
ES2640755T3 (en) | 2010-10-06 | 2017-11-06 | Curna, Inc. | Treatment of diseases related to Sialidase 4 (neu4) by inhibition of the natural antisense transcript to the neu4 gene |
EP3520813B1 (en) | 2010-10-11 | 2023-04-19 | GlaxoSmithKline Biologicals S.A. | Antigen delivery platforms |
RU2597972C2 (en) | 2010-10-22 | 2016-09-20 | Курна Инк. | Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua |
US20120201821A1 (en) | 2010-10-25 | 2012-08-09 | Gonzalez Jr Lino | Treatment of Gastrointestinal Inflammation and Psoriasis and Asthma |
DK2633052T3 (en) | 2010-10-27 | 2018-07-16 | Curna Inc | TREATMENT OF INTERFERON-RELATED DEVELOPMENT REGULATOR 1 (IFRD1) -RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPT TO IFRD1 |
CA3017116A1 (en) | 2010-11-04 | 2012-05-10 | Boehringer Ingelheim International Gmbh | Anti-il-23 antibodies |
WO2012061811A2 (en) | 2010-11-05 | 2012-05-10 | Fibrogen, Inc. | Treatment method for lung remodeling diseases |
US9339513B2 (en) | 2010-11-09 | 2016-05-17 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes |
WO2012065044A2 (en) | 2010-11-12 | 2012-05-18 | Purdue Research Foundation | Treating bladder tumor cells using fibronectin attachment protein as a target |
EP2640831A1 (en) | 2010-11-17 | 2013-09-25 | Sea Lane Biotechnologies,llc. | Influenza virus neutralizing agents that mimic the binding site of an influenza neutralizing antibody |
EP2640359A4 (en) | 2010-11-18 | 2015-11-04 | Gen Hospital Corp | Novel compositions and uses of anti-hypertension agents for cancer therapy |
EP2643463B1 (en) | 2010-11-23 | 2017-09-27 | CuRNA, Inc. | Treatment of nanog related diseases by inhibition of natural antisense transcript to nanog |
US8841275B2 (en) | 2010-11-30 | 2014-09-23 | Gilead Pharmasset Llc | 2′-spiro-nucleosides and derivatives thereof useful for treating hepatitis C virus and dengue virus infections |
EP2649182A4 (en) | 2010-12-10 | 2015-05-06 | Alnylam Pharmaceuticals Inc | Compositions and methods for increasing erythropoietin (epo) production |
EP2648763A4 (en) | 2010-12-10 | 2014-05-14 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of klf-1 and bcl11a genes |
KR20140092226A (en) | 2010-12-14 | 2014-07-23 | 테크니칼 유니버시티 오브 덴마크 | Entrapment of radionuclides in nanoparticle compositions |
EP2468259A1 (en) * | 2010-12-23 | 2012-06-27 | Traslational Cancer Drugs Pharma, S.L. | Pharmaceutical compositions of pyridinium and quinolinium derivatives |
CA2834968C (en) | 2011-01-05 | 2018-01-09 | Livon Laboratories | Methods of making liposomes, liposome compositions made by the methods, and methods of using the same |
CA2821985C (en) | 2011-01-11 | 2019-07-09 | Dimerix Bioscience Pty Ltd | Combination therapy |
CA2824526C (en) | 2011-01-11 | 2020-07-07 | Alnylam Pharmaceuticals, Inc. | Pegylated lipids and their use for drug delivery |
MX365647B (en) | 2011-02-02 | 2019-06-10 | Excaliard Pharmaceuticals Inc | Method of treating keloids or hypertrophic scars using antisense compounds targeting connective tissue growth factor (ctgf). |
RU2440142C1 (en) | 2011-02-07 | 2012-01-20 | Общество С Ограниченной Ответственностью "Онкомакс" | Antibody, stopping or retarding tumour growth (versions), method of suppressing tumour growth, method of diagnosing malignant lesions |
WO2012109495A1 (en) | 2011-02-09 | 2012-08-16 | Metabolic Solutions Development Company, Llc | Cellular targets of thiazolidinediones |
MX2013009357A (en) | 2011-02-14 | 2014-02-17 | Theraclone Sciences Inc | Compositions and methods for the therapy and diagnosis of influenza. |
PL226015B1 (en) * | 2011-03-03 | 2017-06-30 | Wrocławskie Centrum Badań Eit + Spółka Z Ograniczoną | Liposome preparation containing anticancer active substance, process for the preparation thereof and pharmaceutical compositions containing thereof |
US9920110B2 (en) | 2011-03-09 | 2018-03-20 | Cell Signaling Technology, Inc. | Methods and reagents for creating monoclonal antibodies |
JP2014509591A (en) | 2011-03-15 | 2014-04-21 | セラクローン サイエンシーズ, インコーポレイテッド | Compositions and methods for the treatment and diagnosis of influenza |
SG193434A1 (en) | 2011-03-16 | 2013-10-30 | Amgen Inc | Potent and selective inhibitors of nav1.3 and nav1.7 |
US10184942B2 (en) | 2011-03-17 | 2019-01-22 | University Of South Florida | Natriuretic peptide receptor as a biomarker for diagnosis and prognosis of cancer |
WO2012134975A1 (en) | 2011-03-28 | 2012-10-04 | St. Jude Children's Research Hospital | Methods and compositions employing immunogenic fusion proteins |
MX343008B (en) | 2011-03-29 | 2016-10-21 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of tmprss6 gene. |
CN114642731A (en) | 2011-03-31 | 2022-06-21 | 豪夫迈·罗氏有限公司 | Methods of administering beta7 integrin antagonists |
EP2508176A1 (en) | 2011-04-08 | 2012-10-10 | Lipotarg Gmbh | Novel combination treatment of cancer |
CA2832972C (en) | 2011-04-13 | 2019-04-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of ptp1b expression |
KR101589135B1 (en) | 2011-04-20 | 2016-01-29 | 주식회사 셀앤바이오 | Humanized anti-EMAPII antibodies and uses thereof |
PT2699264T (en) | 2011-04-20 | 2018-05-23 | Medimmune Llc | Antibodies and other molecules that bind b7-h1 and pd-1 |
JP6118314B2 (en) | 2011-05-04 | 2017-04-19 | ライゼン・ファーマシューティカルズ・エスアー | Novel compounds as modulators of protein kinases |
CN107936121B (en) | 2011-05-16 | 2022-01-14 | 埃泰美德(香港)有限公司 | Multispecific FAB fusion proteins and methods of use thereof |
JP6662566B2 (en) | 2011-06-02 | 2020-03-11 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | Methods and uses for ex vivo tissue culture systems |
KR102043422B1 (en) | 2011-06-09 | 2019-11-11 | 큐알엔에이, 인크. | Treatment of frataxin (fxn) related diseases by inhibition of natural antisense transcript to fxn |
HUE037408T2 (en) | 2011-06-10 | 2018-08-28 | Univ Oregon Health & Science | Cmv glycoproteins and recombinant vectors |
CN103597074A (en) | 2011-06-16 | 2014-02-19 | Isis制药公司 | Antisense modulation of fibroblast growth factor receptor 4 expression |
WO2012177949A2 (en) | 2011-06-21 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibition of expression of protein c (proc) genes |
US20140275211A1 (en) | 2011-06-21 | 2014-09-18 | Alnylam Pharmaceuticals, Inc. | Assays and methods for determining activity of a therapeutic agent in a subject |
KR20230084331A (en) | 2011-06-21 | 2023-06-12 | 알닐람 파마슈티칼스 인코포레이티드 | Compositions and methods for inhibition of expression of apolipoprotein c-iii(apoc3) genes |
EP2537532A1 (en) | 2011-06-22 | 2012-12-26 | J. Stefan Institute | Cathepsin-binding compounds bound to a nanodevice and their diagnostic and therapeutic use |
EP3597750B1 (en) | 2011-06-23 | 2022-05-04 | Alnylam Pharmaceuticals, Inc. | Serpina1 sirnas: compositions of matter and methods of treatment |
WO2013003112A1 (en) | 2011-06-27 | 2013-01-03 | The Jackson Laboratory | Methods and compositions for treatment of cancer and autoimmune disease |
WO2013003647A2 (en) | 2011-06-28 | 2013-01-03 | Sea Lane Biotechnologies, Llc | Multispecific stacked variable domain binding proteins |
CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
LT2731591T (en) | 2011-07-13 | 2020-12-28 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Liposomes co-encapsulating a bisphosphonate and an amphipathic agent |
EP2731623A1 (en) | 2011-07-14 | 2014-05-21 | Pfizer Inc | Treatment with anti-pcsk9 antibodies |
US9120858B2 (en) | 2011-07-22 | 2015-09-01 | The Research Foundation Of State University Of New York | Antibodies to the B12-transcobalamin receptor |
US20130022551A1 (en) | 2011-07-22 | 2013-01-24 | Trustees Of Boston University | DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS |
WO2013015821A1 (en) | 2011-07-22 | 2013-01-31 | The Research Foundation Of State University Of New York | Antibodies to the b12-transcobalamin receptor |
WO2013019857A2 (en) | 2011-08-01 | 2013-02-07 | Alnylam Pharmaceuticals, Inc. | Method for improving the success rate of hematopoietic stem cell transplants |
WO2013025779A1 (en) | 2011-08-15 | 2013-02-21 | Amplimmune, Inc. | Anti-b7-h4 antibodies and their uses |
FR2979239A1 (en) * | 2011-08-25 | 2013-03-01 | Trophos | LIPOSOME COMPRISING AT LEAST ONE CHOLESTEROL DERIVATIVE |
US8822651B2 (en) | 2011-08-30 | 2014-09-02 | Theraclone Sciences, Inc. | Human rhinovirus (HRV) antibodies |
US9399791B2 (en) | 2011-08-31 | 2016-07-26 | St. Jude Children's Research Hospital | Methods of treating alzheimer's disease by administration of protective protein/cathepsin A |
AU2012305807B2 (en) | 2011-09-09 | 2015-08-20 | Department of Medical Sciences (DMSc) | Dengue-virus serotype neutralizing antibodies |
CA2789539A1 (en) | 2011-09-12 | 2013-03-12 | International Aids Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies |
CA2849073A1 (en) | 2011-09-19 | 2013-03-28 | Gencia Corporation | Modified creatine compounds |
ES2796556T3 (en) | 2011-09-20 | 2020-11-27 | Ionis Pharmaceuticals Inc | Antisense modulation of GCGR expression |
HRP20230078T1 (en) | 2011-09-23 | 2023-05-12 | Mereo Biopharma 5, Inc. | Vegf/dll4 binding agents and uses thereof |
CA2846432A1 (en) | 2011-09-23 | 2013-03-28 | Amgen Research (Munich) Gmbh | Bispecific binding molecules for 5t4 and cd3 |
SG11201400879SA (en) | 2011-09-23 | 2014-04-28 | Technophage Investigação E Desenvolvimento Em Biotecnologia Sa | Anti-tumor necrosis factor-alpha agents and uses thereof |
JP6250543B2 (en) | 2011-09-27 | 2017-12-20 | アルニラム・ファーマシューティカルズ・インコーポレーテッド | Dialiphatic substituted PEGylated lipids |
WO2013049749A2 (en) | 2011-09-29 | 2013-04-04 | Plx Pharma Inc. | pH DEPENDENT CARRIERS FOR TARGETED RELEASE OF PHARMACEUTICALS ALONG THE GASTROINTESTINAL TRACT, COMPOSITIONS THEREFROM, AND MAKING AND USING SAME |
US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
CN103998058B (en) | 2011-10-06 | 2021-11-05 | 免疫疫苗技术有限公司 | Liposome composition comprising adjuvant for activating or increasing TLR2 activity and application thereof |
CA2850032C (en) | 2011-10-14 | 2022-06-07 | Genentech, Inc. | Anti-htra1 antibodies and methods of use |
US8883989B2 (en) | 2011-10-18 | 2014-11-11 | Regents Of The University Of Minnesota | Fractalkine binding polynucleotides and methods of use |
AU2012328680A1 (en) | 2011-10-25 | 2014-05-01 | Ionis Pharmaceuticals, Inc. | Antisense modulation of GCCR expression |
US9402894B2 (en) | 2011-10-27 | 2016-08-02 | International Aids Vaccine Initiative | Viral particles derived from an enveloped virus |
AR088509A1 (en) | 2011-10-28 | 2014-06-11 | Genentech Inc | THERAPEUTIC COMBINATIONS AND METHODS TO TREAT MELANOMA |
EP2773662A4 (en) | 2011-10-31 | 2015-07-01 | Hoffmann La Roche | Antibody formulations |
JP6205095B2 (en) * | 2011-11-03 | 2017-09-27 | タイワン リポサム カンパニー、エルティーディー. | Pharmaceutical composition of hydrophobic camptothecin derivative |
US10980798B2 (en) | 2011-11-03 | 2021-04-20 | Taiwan Liposome Company, Ltd. | Pharmaceutical compositions of hydrophobic camptothecin derivatives |
CA2954166A1 (en) | 2011-11-11 | 2013-05-16 | Rinat Neuroscience Corp. | Antibodies specific for trop-2 and their uses |
TWI679212B (en) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | Binding molecules for e3 of bcma and cd3 |
US9023995B2 (en) | 2011-11-16 | 2015-05-05 | Boehringer Ingelheim International Gmbh | Anti IL-36R antibodies |
EP2790730B1 (en) | 2011-12-15 | 2019-01-23 | The University of Chicago | Methods and compositions for cancer therapy using mutant light molecules with increased affinity to receptors |
RU2014123030A (en) | 2011-12-22 | 2016-02-20 | Ринат Ньюросайенс Корп. | ANTAGONISTIC ANTIBODIES AGAINST THE HUMAN GROWTH HORMONE RECEPTOR AND WAYS OF THEIR APPLICATION |
WO2013093693A1 (en) | 2011-12-22 | 2013-06-27 | Rinat Neuroscience Corp. | Staphylococcus aureus specific antibodies and uses thereof |
EP3539982A3 (en) | 2011-12-23 | 2020-01-15 | Pfizer Inc | Engineered antibody constant regions for site-specific conjugation and methods and uses therefor |
WO2013101771A2 (en) | 2011-12-30 | 2013-07-04 | Genentech, Inc. | Compositions and method for treating autoimmune diseases |
WO2013105013A1 (en) | 2012-01-09 | 2013-07-18 | Covx Technologies Ireland Limited | Mutant antibodies and conjugation thereof |
EP2804620A4 (en) | 2012-01-18 | 2016-04-13 | Neumedicines Inc | Il-12 for radiation protection and radiation-induced toxicity mitigation |
AU2013209512B2 (en) | 2012-01-20 | 2017-08-03 | I2 Pharmaceuticals, Inc. | Surrobody cojugates |
WO2013114377A1 (en) | 2012-02-02 | 2013-08-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd | Stable liposomes for drug delivery |
BR112014019331A2 (en) | 2012-02-06 | 2022-07-12 | Inhibrx Inc | cd47 antibodies and methods of use of these |
MX2014009827A (en) * | 2012-02-17 | 2014-09-22 | Celsion Corp | Thermosensitive nanoparticle formulations and method of making the same. |
US9138492B2 (en) * | 2012-02-23 | 2015-09-22 | Canon Kabushiki Kaisha | Particle containing hydrophobic dye having cyanine structure, and contrast agent containing the particle |
US20150037334A1 (en) | 2012-03-01 | 2015-02-05 | Amgen Research (Munich) Gmbh | Long life polypeptide binding molecules |
AR090253A1 (en) | 2012-03-05 | 2014-10-29 | Gilead Calistoga Llc | Polymorphic forms of (S) -2- (1- (9H-PURIN-6-ILAMINO) PROPIL) -5-FLUOR-3-PHENYLQUINAZOLIN-4 (3H) -ONA |
TR201815503T4 (en) | 2012-03-15 | 2018-11-21 | Curna Inc | Treatment of brain-mediated neurotrophic factor (bknf) related diseases by inhibition of the native antisense transcript to bknf. |
WO2013149111A2 (en) | 2012-03-29 | 2013-10-03 | Novimmune S.A. | Anti-tlr4 antibodies and uses thereof |
KR20140144726A (en) | 2012-03-30 | 2014-12-19 | 리젠 파마슈티컬스 소시에떼 아노님 | Novel 3,5-disubstitued-3h-imidazo[4,5-b]pyridine and 3,5-disubstitued -3h-[1,2,3]triazolo[4,5-b] pyridine compounds as modulators of c-met protein kinases |
WO2013151649A1 (en) | 2012-04-04 | 2013-10-10 | Sialix Inc | Glycan-interacting compounds |
US9133461B2 (en) | 2012-04-10 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the ALAS1 gene |
CA2871462A1 (en) | 2012-04-24 | 2013-10-31 | University Of Miami | Perforin 2 defense against invasive and multidrug resistant pathogens |
EP4039275A1 (en) | 2012-05-03 | 2022-08-10 | Boehringer Ingelheim International GmbH | Anti-il-23p19 antibodies |
JP6392209B2 (en) * | 2012-05-04 | 2018-09-19 | ザ・ジョンズ・ホプキンス・ユニバーシティー | Lipid-based drug carriers for rapid permeation through the mucus lining |
WO2013166500A1 (en) | 2012-05-04 | 2013-11-07 | Dana-Farber Cancer Institute, Inc. | Affinity matured anti-ccr4 humanized monoclonal antibodies and methods of use |
AU2013202947B2 (en) | 2012-06-13 | 2016-06-02 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan |
US9717724B2 (en) | 2012-06-13 | 2017-08-01 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies |
BR112014031421A2 (en) | 2012-06-15 | 2017-06-27 | Brigham & Womens Hospital Inc | cancer treatment compositions and methods for producing them |
US9856314B2 (en) | 2012-06-22 | 2018-01-02 | Cytomx Therapeutics, Inc. | Activatable antibodies having non-binding steric moieties and methods of using the same |
EP2679596B1 (en) | 2012-06-27 | 2017-04-12 | International Aids Vaccine Initiative | HIV-1 env glycoprotein variant |
US20150209281A1 (en) * | 2012-07-18 | 2015-07-30 | Onyx Therapeutics, Inc. | Liposomal compositions of epoxyketone-based proteasome inhibitors |
US8603470B1 (en) | 2012-08-07 | 2013-12-10 | National Cheng Kung University | Use of IL-20 antagonists for treating liver diseases |
CN103565745A (en) * | 2012-08-10 | 2014-02-12 | 德克萨斯州大学系统董事会 | Neuroprotective liposome compositions and methods for treatment of stroke |
SG11201408340SA (en) | 2012-08-14 | 2015-01-29 | Univ Nanyang Tech | Angiopoietin-like 4 antibody and a method of its use in cancer treatment |
US11291644B2 (en) | 2012-09-04 | 2022-04-05 | Eleison Pharmaceuticals, Llc | Preventing pulmonary recurrence of cancer with lipid-complexed cisplatin |
EP2943194A1 (en) | 2012-09-17 | 2015-11-18 | Chemedest Ltd. | Treatment of peripheral neuropathy using gfr(alpha)3 type receptor agonists |
CN107892719B (en) | 2012-10-04 | 2022-01-14 | 达纳-法伯癌症研究所公司 | Human monoclonal anti-PD-L1 antibodies and methods of use |
CA2884368C (en) | 2012-10-05 | 2022-01-18 | Genentech, Inc. | Methods for diagnosing and treating inflammatory bowel disease |
EP2911691B1 (en) | 2012-10-23 | 2018-10-10 | OncoMed Pharmaceuticals, Inc. | Methods of treating neuroendocrine tumors using wnt pathway-binding agents |
US9599620B2 (en) | 2012-10-31 | 2017-03-21 | Oncomed Pharmaceuticals, Inc. | Methods and monitoring of treatment with a DLL4 antagonist |
JP6392770B2 (en) | 2012-12-03 | 2018-09-19 | ノビミューン エスアー | Anti-CD47 antibody and method of use thereof |
AU2013360302C1 (en) | 2012-12-12 | 2019-01-24 | Temple University - Of The Commonwealth System Of Higher Education | Compositions and methods for treatment of cancer |
CA2894879A1 (en) | 2012-12-19 | 2014-06-26 | Amplimmune, Inc. | B7-h4 specific antibodies, and compositions and methods of use thereof |
EP2934303B1 (en) | 2012-12-19 | 2019-09-04 | The Research Foundation for the State University of New York | Compositions and method for light triggered release of materials from nanovesicles |
GB201223053D0 (en) | 2012-12-20 | 2013-02-06 | Medical Res Council | Receptor |
EP3907237A1 (en) | 2012-12-20 | 2021-11-10 | Amgen Inc. | Apj receptor agonists and uses thereof |
CA2896091C (en) | 2012-12-21 | 2018-06-19 | Amplimmune, Inc. | Anti-h7cr antibodies |
DK2941269T3 (en) | 2013-01-07 | 2021-01-11 | Mucosal Vaccine Tech Llc | Therapeutic vaccines for the treatment of herpes simplex virus type 2 infections |
JO3519B1 (en) | 2013-01-25 | 2020-07-05 | Amgen Inc | Antibody constructs for CDH19 and CD3 |
EP2948478B1 (en) | 2013-01-25 | 2019-04-03 | Amgen Inc. | Antibodies targeting cdh19 for melanoma |
US10568975B2 (en) | 2013-02-05 | 2020-02-25 | The Johns Hopkins University | Nanoparticles for magnetic resonance imaging tracking and methods of making and using thereof |
EP2953643B1 (en) | 2013-02-06 | 2023-02-22 | Inhibrx, Inc. | Non-platelet depleting and non-red blood cell depleting cd47 antibodies and methods of use thereof |
EP2956169B1 (en) | 2013-02-12 | 2018-04-11 | THE UNITED STATES OF AMERICA, represented by the S | Monoclonal antibodies that neutralize norovirus |
EP2970408B1 (en) | 2013-03-12 | 2018-01-10 | Amgen Inc. | Potent and selective inhibitors of nav1.7 |
WO2014152795A2 (en) | 2013-03-14 | 2014-09-25 | Schentag Jerome J | Cholestosome vesicles for incorporation of molecules into chylomicrons |
US9302005B2 (en) | 2013-03-14 | 2016-04-05 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
US10052364B2 (en) | 2013-03-15 | 2018-08-21 | The Trustees Of Columbia University In The City Of New York | Osteocalcin as a treatment for cognitive disorders |
KR20150132473A (en) | 2013-03-15 | 2015-11-25 | 다이액스 코포레이션 | Anti-plasma kallikrein antibodies |
WO2014145037A1 (en) * | 2013-03-15 | 2014-09-18 | M. Alphabet 3, L.L.C. | Methods and compositions for enhancing oxygen levels in tissues |
TW201525001A (en) | 2013-03-15 | 2015-07-01 | Amgen Res Munich Gmbh | Single chain binding molecules comprising N-terminal ABP |
US20140283157A1 (en) | 2013-03-15 | 2014-09-18 | Diadexus, Inc. | Lipoprotein-associated phospholipase a2 antibody compositions and methods of use |
BR112015023664A2 (en) | 2013-03-15 | 2017-10-24 | Gencia Corp | compositions and methods for treating conditions affecting the epidermis |
EP2970446A1 (en) | 2013-03-15 | 2016-01-20 | Amgen Research (Munich) GmbH | Antibody constructs for influenza m2 and cd3 |
WO2014145654A1 (en) | 2013-03-15 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Method for the site-specific covalent cross-linking of antibodies to surfaces |
JP6427552B2 (en) | 2013-03-15 | 2018-11-21 | デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド | Flavivirus neutralizing antibody and method of using the same |
AR095374A1 (en) | 2013-03-15 | 2015-10-14 | Amgen Res (Munich) Gmbh | UNION MOLECULES FOR BCMA AND CD3 |
SG11201507974RA (en) | 2013-03-27 | 2015-10-29 | Genentech Inc | Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists |
EP3708184A1 (en) | 2013-03-27 | 2020-09-16 | The General Hospital Corporation | Methods and agents for treating alzheimer s disease |
WO2014169272A1 (en) | 2013-04-12 | 2014-10-16 | Icahn School Of Medicine At Mount Sinai | Method for treating post-traumatic stress disorder |
EP2992000B1 (en) | 2013-05-03 | 2020-07-08 | The Regents of The University of California | Cyclic di-nucleotide induction of type i interferon |
SG10201913751RA (en) | 2013-05-06 | 2020-03-30 | Scholar Rock Inc | Compositions and methods for growth factor modulation |
EP2994167B1 (en) | 2013-05-06 | 2020-05-06 | Alnylam Pharmaceuticals, Inc. | Dosages and methods for delivering lipid formulated nucleic acid molecules |
CN105189560A (en) | 2013-05-07 | 2015-12-23 | 瑞纳神经科学公司 | Anti-glucagon receptor antibodies and methods of use thereof |
WO2014183052A1 (en) | 2013-05-09 | 2014-11-13 | The United States Of America, As Represented By The Secretary, Depart Of Health And Human Services | Single-domain vhh antibodies directed to norovirus gi.1 and gii.4 and their use |
BR112015029395A2 (en) | 2013-05-24 | 2017-09-19 | Medimmune Llc | ANTI-B7-H5 ANTIBODIES AND THEIR USES |
EP3381939A1 (en) | 2013-05-31 | 2018-10-03 | Genentech, Inc. | Anti-wall teichoic antibodies and conjugates |
MX369758B (en) | 2013-05-31 | 2019-11-20 | Genentech Inc | Anti-wall teichoic antibodies and conjugates. |
SG11201509982UA (en) | 2013-06-06 | 2016-04-28 | Igenica Biotherapeutics Inc | |
JP6869720B2 (en) | 2013-06-13 | 2021-05-12 | アンチセンス セラピューティクス リミテッド | Combination therapy |
US10208125B2 (en) | 2013-07-15 | 2019-02-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Anti-mucin 1 binding agents and uses thereof |
WO2015013671A1 (en) | 2013-07-25 | 2015-01-29 | Cytomx Therapeutics, Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
WO2015017807A1 (en) * | 2013-08-01 | 2015-02-05 | University Of Georgia Research Foundation, Inc. | Liposomal formulations for the treatment of bacterial infections |
PE20160671A1 (en) | 2013-08-02 | 2016-07-09 | Pfizer | ANTI-CXCR4 ANTIBODIES AND ANTIBODY AND DRUG CONJUGATES |
MX2016001854A (en) | 2013-08-12 | 2016-09-06 | Genentech Inc | Compositions and method for treating complement-associated conditions. |
JP6617239B2 (en) | 2013-08-14 | 2019-12-11 | サイドゥ サチデーブ | Antibodies against Frizzled protein and methods of use thereof |
JP2016529284A (en) * | 2013-08-27 | 2016-09-23 | ノースイースタン ユニバーシティ | Nanoparticle drug delivery system and method for treating cancer and neurotrauma |
EP3690048A1 (en) | 2013-09-04 | 2020-08-05 | Cold Spring Harbor Laboratory | Reducing nonsense-mediated mrna decay |
CA2922838A1 (en) | 2013-09-05 | 2015-03-12 | Sarepta Therapeutics, Inc. | Antisense-induced exon2 inclusion in acid alpha-glucosidase |
US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
TWI688401B (en) | 2013-09-13 | 2020-03-21 | 美商安進公司 | Combination of epigenetic factors and bispecific compounds targeting cd33 and cd3 in the treatment of myeloid leukemia |
PT3046537T (en) * | 2013-09-16 | 2021-10-07 | Glycomine Inc | Pharmaceutical preparation of carbohydrates for therapeutic use |
DE102013015334A1 (en) * | 2013-09-17 | 2015-03-19 | Fresenius Medical Care Deutschland Gmbh | Magnesium-liposome complexes |
WO2015042466A2 (en) | 2013-09-19 | 2015-03-26 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Compositions and methods for inhibiting jc virus (jcv) |
WO2015048329A2 (en) | 2013-09-25 | 2015-04-02 | Cytomx Therapeutics, Inc. | Matrix metalloproteinase substrates and other cleavable moieties and methods of use thereof |
US10259875B2 (en) | 2013-10-01 | 2019-04-16 | Mayo Foundation For Medical Education And Research | Methods for treating cancer in patients with elevated levels of BIM |
TWI669393B (en) | 2013-10-02 | 2019-08-21 | 艾爾妮蘭製藥公司 | Compositions and methods for inhibiting expression of the lect2 gene |
EP3052628B1 (en) | 2013-10-04 | 2020-02-26 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the alas1 gene |
US10058604B2 (en) | 2013-10-07 | 2018-08-28 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
JPWO2015068781A1 (en) | 2013-11-06 | 2017-03-09 | 国立大学法人大阪大学 | Antibodies with broad neutralizing activity against group 1 of influenza virus type A |
WO2015087187A1 (en) | 2013-12-10 | 2015-06-18 | Rinat Neuroscience Corp. | Anti-sclerostin antibodies |
JP2017505756A (en) | 2013-12-13 | 2017-02-23 | ザ ジェネラル ホスピタル コーポレイション | Soluble high molecular weight (HMW) tau species and uses thereof |
AU2014364414A1 (en) | 2013-12-20 | 2016-06-30 | Gilead Calistoga Llc | Polymorphic forms of a hydrochloride salt of (S) -2-(1-(9H-purin-6-ylamino) propyl) -5-fluoro-3-phenylquinazolin-4 (3H) -one |
EA201690990A1 (en) | 2013-12-20 | 2016-11-30 | Джилид Калистога Ллс | METHODS OF OBTAINING PHOSPHATIDYLINOSITOL-3-KINASE INHIBITORS |
CN106102725A (en) | 2014-01-14 | 2016-11-09 | 约翰斯·霍普金斯大学 | The cyclodextrin composite of the selective ATP inhibitor of encapsulating and application thereof |
AU2015315834B2 (en) | 2014-01-31 | 2019-12-12 | Boehringer Ingelheim International Gmbh | Novel anti-BAFF antibodies |
WO2015116902A1 (en) | 2014-01-31 | 2015-08-06 | Genentech, Inc. | G-protein coupled receptors in hedgehog signaling |
IL302642A (en) | 2014-01-31 | 2023-07-01 | Cytomx Therapeutics Inc | Matriptase and U-Plasminogen Activator Polypeptide Substrates and Other Cleanable Moieties, Compositions Comprising Same and Uses Thereof |
WO2015120075A2 (en) | 2014-02-04 | 2015-08-13 | Genentech, Inc. | Mutant smoothened and methods of using the same |
JP6870988B2 (en) | 2014-02-24 | 2021-05-19 | セルジーン コーポレイション | How to use cereblon activators for neuronal amplification and treatment of central nervous system disorders |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
NZ711451A (en) | 2014-03-07 | 2016-05-27 | Alexion Pharma Inc | Anti-c5 antibodies having improved pharmacokinetics |
EP4043489A1 (en) | 2014-03-19 | 2022-08-17 | Dana-Farber Cancer Institute, Inc. | Immunogenetic restriction on elicitation of antibodies |
WO2015143409A1 (en) | 2014-03-21 | 2015-09-24 | Labrys Biologics, Inc. | Antagonist antibodies directed against calcitonin gene-related peptide and methods using same |
CN113604543A (en) | 2014-03-27 | 2021-11-05 | 豪夫迈·罗氏有限公司 | Methods for diagnosing and treating inflammatory bowel disease |
AU2015241198A1 (en) | 2014-04-03 | 2016-11-17 | Invictus Oncology Pvt. Ltd. | Supramolecular combinatorial therapeutics |
KR20160145813A (en) | 2014-04-25 | 2016-12-20 | 다나-파버 캔서 인스티튜트 인크. | Middle east respiratory syndrome coronavirus neutralizing antibodies and methods of use thereof |
EP3139955B1 (en) | 2014-04-30 | 2024-03-20 | President and Fellows of Harvard College | Fusion proteins for treating cancer and related methods |
EP3137114B8 (en) | 2014-04-30 | 2021-08-04 | Pfizer Inc. | Anti-ptk7 antibody-drug conjugates |
WO2015171918A2 (en) | 2014-05-07 | 2015-11-12 | Louisiana State University And Agricultural And Mechanical College | Compositions and uses for treatment thereof |
EP3143043B1 (en) | 2014-05-16 | 2022-12-14 | Pfizer Inc. | Bispecific antibodies with engineered ch1-cl interfaces |
US10302653B2 (en) | 2014-05-22 | 2019-05-28 | Mayo Foundation For Medical Education And Research | Distinguishing antagonistic and agonistic anti B7-H1 antibodies |
EA028614B1 (en) | 2014-05-22 | 2017-12-29 | Общество С Ограниченной Ответственностью "Русские Фармацевтические Технологии" | Selective inhibitors interfering with fibroblast growth factor receptor and frs2 interaction for the prevention and treatment of cancer |
TWI689520B (en) | 2014-05-30 | 2020-04-01 | 漢霖生技股份有限公司 | Anti-epidermal growth factor receptor (egfr) antibodies |
WO2015191781A2 (en) | 2014-06-10 | 2015-12-17 | Amgen Inc. | Apelin polypeptides |
EA201692202A1 (en) | 2014-06-11 | 2017-06-30 | Джилид Сайэнс, Инк. | METHODS OF TREATING CARDIOVASCULAR DISEASES |
CA2952012A1 (en) | 2014-06-13 | 2015-12-17 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
TWI695011B (en) | 2014-06-18 | 2020-06-01 | 美商梅爾莎納醫療公司 | Monoclonal antibodies against her2 epitope and methods of use thereof |
US10562946B2 (en) | 2014-06-20 | 2020-02-18 | Genentech, Inc. | Chagasin-based scaffold compositions, methods, and uses |
EP3160503B1 (en) | 2014-06-26 | 2021-02-17 | The Trustees of Columbia University in the City of New York | Inhibition of serotonin expression in gut enteroendocrine cells results in conversion to insulin-positive cells |
US10517875B2 (en) | 2014-07-23 | 2019-12-31 | Mayo Foundation for Medical Engineering and Research | Targeting DNA-PKcs and B7-H1 to treat cancer |
BR112017001579A2 (en) | 2014-07-25 | 2017-11-21 | Cytomx Therapeutics Inc | anti-cd3 antibodies, activatable anti-cd3 antibodies, multispecific anti-cd3 antibodies, multispecific activatable cd3 antibodies and methods of use |
AR101669A1 (en) | 2014-07-31 | 2017-01-04 | Amgen Res (Munich) Gmbh | ANTIBODY CONSTRUCTS FOR CDH19 AND CD3 |
AR101936A1 (en) | 2014-07-31 | 2017-01-25 | Amgen Res (Munich) Gmbh | SPECIFIC BIESPECIFIC CHAIN ANTIBODY CONSTRUCTS SPECIFIED FOR OPTIMIZED CROSSED SPECIES |
WO2016020798A1 (en) | 2014-08-06 | 2016-02-11 | Rinat Neuroscience Corp. | Methods for reducing ldl-cholesterol |
WO2016020799A1 (en) | 2014-08-06 | 2016-02-11 | Rinat Neuroscience Corp. | Methods for reducing ldl-cholesterol |
WO2016033424A1 (en) | 2014-08-29 | 2016-03-03 | Genzyme Corporation | Methods for the prevention and treatment of major adverse cardiovascular events using compounds that modulate apolipoprotein b |
WO2016034968A1 (en) | 2014-09-02 | 2016-03-10 | Pfizer Inc. | Therapeutic antibody |
EP3197492A1 (en) | 2014-09-23 | 2017-08-02 | Pfizer Inc | Treatment with anti-pcsk9 antibodies |
RU2017115315A (en) | 2014-10-03 | 2018-11-08 | Дана-Фарбер Кэнсер Инститьют, Инк. | ANTIBODIES TO A GLUCCORTICOID-INDUCED TUMOR NECROSIS FACTOR (GITR) RECEPTOR AND METHODS OF APPLICATION |
GB201417589D0 (en) | 2014-10-06 | 2014-11-19 | Cantab Biopharmaceuticals Patents Ltd | Pharmaceutical Formulations |
EP3699196A1 (en) | 2014-10-06 | 2020-08-26 | Dana Farber Cancer Institute, Inc. | Humanized cc chemokine receptor 4 (ccr4) antibodies and methods of use thereof |
CN107530419B (en) | 2014-10-31 | 2021-05-18 | 昂考梅德药品有限公司 | Combination therapy for treating disease |
FI3218005T3 (en) | 2014-11-12 | 2023-03-31 | Seagen Inc | Glycan-interacting compounds and methods of use |
WO2016077566A1 (en) | 2014-11-12 | 2016-05-19 | Research Institute At Nationwide Children's Hospital | Modulation of alternative mdm2 splicing |
US9879087B2 (en) | 2014-11-12 | 2018-01-30 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
WO2016081728A1 (en) | 2014-11-19 | 2016-05-26 | The Trustees Of Columbia University In The City Of New York | Osteocalcin as a treatment for frailty associated with aging |
KR20170086536A (en) | 2014-12-03 | 2017-07-26 | 제넨테크, 인크. | Anti-staphylococcus aureus antibody rifamycin conjugates and uses thereof |
RU2017118792A (en) | 2014-12-03 | 2019-01-09 | Дженентек, Инк. | ANTIBODY CONJUGATES TO STAPHYLOCOCCUS AUREUS WITH RIFAMICINE AND THEIR APPLICATION |
WO2016090170A1 (en) | 2014-12-05 | 2016-06-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A potent anti-influenza a neuraminidase subtype n1 antibody |
TWI595006B (en) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | Anti-pd-1 antibodies and methods of use thereof |
NZ733055A (en) | 2014-12-11 | 2023-03-31 | Pf Medicament | Anti-c10orf54 antibodies and uses thereof |
TW201702218A (en) | 2014-12-12 | 2017-01-16 | 美國杰克森實驗室 | Compositions and methods relating to the treatment of cancer, autoimmune disease, and neurodegenerative disease |
EA201791337A1 (en) | 2014-12-15 | 2017-11-30 | Дзе Джонс Хопкинс Юниверсити | COMPOSITIONS OF SUITINIBA AND METHODS OF THEIR APPLICATION IN THE TREATMENT OF EYE DISTURBANCES |
CA2970795A1 (en) | 2014-12-18 | 2016-06-23 | Alnylam Pharmaceuticals, Inc. | Reversir compounds |
MA41374A (en) | 2015-01-20 | 2017-11-28 | Cytomx Therapeutics Inc | MATRIX METALLOPROTEASE CLIVABLE AND SERINE PROTEASE CLIVABLE SUBSTRATES AND METHODS OF USE THEREOF |
CA2974369A1 (en) | 2015-01-20 | 2016-07-28 | The Children's Medical Center Corporation | Anti-net compounds for treating and preventing fibrosis and for facilitating wound healing |
EP3250184A1 (en) | 2015-01-27 | 2017-12-06 | The Johns Hopkins University | Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces |
JP2018506275A (en) | 2015-01-28 | 2018-03-08 | ジェネンテック, インコーポレイテッド | Gene expression markers and treatment of multiple sclerosis |
JP2018506526A (en) | 2015-01-29 | 2018-03-08 | ボード オブ トラスティーズ オブ ミシガン ステイト ユニバーシティBoard Of Trustees Of Michigan State University | Cryptic polypeptides and uses thereof |
WO2016134066A1 (en) * | 2015-02-17 | 2016-08-25 | Mallinckrodt Llc | Modified docetaxel liposome formulations and uses thereof |
LT3653221T (en) | 2015-02-19 | 2022-11-10 | Compugen Ltd. | Anti-pvrig antibodies and methods of use |
DK3259597T3 (en) | 2015-02-19 | 2022-05-09 | Compugen Ltd | PVRIG POLYPEPTIDES AND METHODS OF TREATMENT |
AU2016222683A1 (en) | 2015-02-26 | 2017-07-13 | Genentech, Inc. | Integrin beta7 antagonists and methods of treating crohn's disease |
LT3265123T (en) | 2015-03-03 | 2023-01-25 | Kymab Limited | Antibodies, uses & methods |
US9895313B2 (en) | 2015-03-03 | 2018-02-20 | Cureport, Inc. | Combination liposomal pharmaceutical formulations |
CN107530291A (en) * | 2015-03-03 | 2018-01-02 | 奎尔波特股份有限公司 | Double heavy duty liposomal pharmaceutical preparations |
BR112017019559B1 (en) | 2015-03-13 | 2020-08-04 | Cytomx Therapeutics, Inc | ANTI-PDL1 ANTIBODIES, ACTIVABLE ANTI-PDL1 ANTIBODIES, AND METHODS OF USE OF THESE |
JP6859275B2 (en) | 2015-03-17 | 2021-04-14 | リポメディックス・ファーマシューティカルズ・リミテッドLipomedix Pharmaceuticals Ltd. | How to treat bladder cancer |
MA41795A (en) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | EXCLUSION OF AN EXON INDUCED BY ANTISENSE COMPOUNDS IN MYOSTATIN |
US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
US9758575B2 (en) | 2015-04-06 | 2017-09-12 | Yung Shin Pharmaceutical Industrial Co. Ltd. | Antibodies which specifically bind to canine vascular endothelial growth factor and uses thereof |
CN107750253B (en) | 2015-04-08 | 2022-10-04 | 达纳-法伯癌症研究所公司 | Humanized influenza monoclonal antibodies and methods of use thereof |
CA3219684A1 (en) | 2015-04-13 | 2016-10-13 | Pfizer Inc. | Anti-bcma antibodies, anti-cd3 antibodies and bi-specific antibodies binding to bcma and cd3 |
LT3283524T (en) | 2015-04-17 | 2023-05-25 | Amgen Research (Munich) Gmbh | Bispecific antibody constructs for cdh3 and cd3 |
EP3288977B1 (en) | 2015-05-01 | 2021-11-17 | Dana-Farber Cancer Institute, Inc. | Methods of mediating cytokine expression with anti ccr4 antibodies |
MX2017014136A (en) | 2015-05-04 | 2018-07-06 | Cytomx Therapeutics Inc | Anti-cd166 antibodies, activatable anti-cd166 antibodies, and methods of use thereof. |
RS62956B1 (en) | 2015-05-04 | 2022-03-31 | Cytomx Therapeutics Inc | Activatable anti-cd71 antibodies, and methods of use thereof |
BR112017023868A2 (en) | 2015-05-04 | 2018-07-24 | Cytomx Therapeutics Inc | anti-itga3 antibodies, activatable anti-itga3 antibodies, and methods of use thereof |
EP3294334B1 (en) | 2015-05-11 | 2020-07-08 | The Johns Hopkins University | Autoimmune antibodies for use in inhibiting cancer cell growth |
WO2016180986A1 (en) | 2015-05-14 | 2016-11-17 | Fundación Centro Nacional De Investigaciones Cardiovasculares Carlos Iii (Cnic) | Mirna compositions for the treatment of mature b-cell neoplasms |
US11318131B2 (en) | 2015-05-18 | 2022-05-03 | Ipsen Biopharm Ltd. | Nanoliposomal irinotecan for use in treating small cell lung cancer |
WO2016196381A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Pd-l1 promoter methylation in cancer |
MA50829A (en) | 2015-06-01 | 2018-04-11 | Sarepta Therapeutics Inc | EXCLUSION OF EXON INDUCED BY ANTISEN TECHNOLOGY IN TYPE VII COLLAGEN |
ES2932801T3 (en) | 2015-06-10 | 2023-01-26 | Elysium Health Inc | Nicotinamide Riboside and Pterostilbene Compositions and Methods for Treatment of Skin Disorders |
CN108024535A (en) | 2015-07-02 | 2018-05-11 | 大塚制药株式会社 | Freeze-drying medicinal composition |
SG10201913303XA (en) | 2015-07-13 | 2020-03-30 | Cytomx Therapeutics Inc | Anti-pd-1 antibodies, activatable anti-pd-1 antibodies, and methods of use thereof |
CA2991980A1 (en) | 2015-07-13 | 2017-01-19 | Compugen Ltd. | Hide1 compositions and methods |
WO2017015109A1 (en) | 2015-07-17 | 2017-01-26 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
CA2993026A1 (en) | 2015-07-21 | 2017-01-26 | Dyax Corp. | A monoclonal antibody inhibitor of factor xiia |
EP3328886B1 (en) | 2015-07-29 | 2020-09-16 | Allergan, Inc. | Heavy chain only antibodies to ang-2 |
TWI829617B (en) | 2015-07-31 | 2024-01-21 | 德商安美基研究(慕尼黑)公司 | Antibody constructs for flt3 and cd3 |
TWI793062B (en) | 2015-07-31 | 2023-02-21 | 德商安美基研究(慕尼黑)公司 | Antibody constructs for dll3 and cd3 |
TWI796283B (en) | 2015-07-31 | 2023-03-21 | 德商安美基研究(慕尼黑)公司 | Antibody constructs for msln and cd3 |
TWI744242B (en) | 2015-07-31 | 2021-11-01 | 德商安美基研究(慕尼黑)公司 | Antibody constructs for egfrviii and cd3 |
TWI717375B (en) | 2015-07-31 | 2021-02-01 | 德商安美基研究(慕尼黑)公司 | Antibody constructs for cd70 and cd3 |
JP2018523673A (en) | 2015-08-14 | 2018-08-23 | アラーガン、インコーポレイテッドAllergan,Incorporated | Heavy chain only antibody against PDGF |
WO2017031442A1 (en) | 2015-08-20 | 2017-02-23 | Merrimack Pharmaceuticals, Inc. | Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment |
CN108495629A (en) | 2015-08-21 | 2018-09-04 | 益普生生物制药有限公司 | Use the method comprising liposome Irinotecan and the combination therapy to treat metastatic cancer of pancreas of oxaliplatin |
US20170058038A1 (en) | 2015-09-01 | 2017-03-02 | Boehringer Ingelheim International Gmbh | Use of anti-cd40 antibodies for treatment of lupus nephritis |
WO2017048843A1 (en) | 2015-09-14 | 2017-03-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the alas1 gene |
LT3350220T (en) | 2015-09-15 | 2021-09-27 | Scholar Rock, Inc. | Anti-pro/latent-myostatin antibodies and uses thereof |
TWI799366B (en) | 2015-09-15 | 2023-04-21 | 美商建南德克公司 | Cystine knot scaffold platform |
US11339213B2 (en) | 2015-09-23 | 2022-05-24 | Mereo Biopharma 5, Inc. | Methods and compositions for treatment of cancer |
WO2017058881A1 (en) | 2015-09-28 | 2017-04-06 | The Trustees Of Columbia University In The City Of New York | Use of pentoxifylline with immune checkpoint-blockade therapies for the treatment of melanoma |
WO2017055966A1 (en) | 2015-10-01 | 2017-04-06 | Pfizer Inc. | Low viscosity antibody compositions |
CN108431038A (en) | 2015-10-06 | 2018-08-21 | 豪夫迈·罗氏有限公司 | The method for treating multiple sclerosis |
MA45819A (en) | 2015-10-09 | 2018-08-15 | Sarepta Therapeutics Inc | COMPOSITIONS AND METHODS FOR TREATING DUCHENNE MUSCLE DYSTROPHY AND RELATED DISORDERS |
GB201518170D0 (en) | 2015-10-14 | 2015-11-25 | Cantab Biopharmaceuticals Patents Ltd | Colloidal particles for subcutaneous administration with intravenous administration of therapeutic agent |
GB201518171D0 (en) | 2015-10-14 | 2015-11-25 | Cantab Biopharmaceuticals Patents Ltd | Colloidal particles for topical administration with therapeutic agent |
GB201518172D0 (en) | 2015-10-14 | 2015-11-25 | Cantab Biopharmaceuticals Patents Ltd | Colloidal particles for use in medicine |
WO2017066726A1 (en) | 2015-10-16 | 2017-04-20 | Merrimack Pharmaceuticals, Inc. | Stabilizing camptothecin pharmaceutical compositions |
WO2017066714A1 (en) | 2015-10-16 | 2017-04-20 | Compugen Ltd. | Anti-vsig1 antibodies and drug conjugates |
WO2017075037A1 (en) | 2015-10-27 | 2017-05-04 | Scholar Rock, Inc. | Primed growth factors and uses thereof |
US10875923B2 (en) | 2015-10-30 | 2020-12-29 | Mayo Foundation For Medical Education And Research | Antibodies to B7-H1 |
SG10202001808VA (en) | 2015-10-30 | 2020-04-29 | Genentech Inc | Anti-htra1 antibodies and methods of use thereof |
CA3007424A1 (en) | 2015-11-05 | 2017-05-11 | Children's Hospital Los Angeles | "mobilizing leukemia cells" |
EP3370712A4 (en) | 2015-11-06 | 2019-10-09 | The Johns Hopkins University | Methods of treating liver fibrosis by administering 3-bromopyruvate |
US11116726B2 (en) | 2015-11-10 | 2021-09-14 | Childrens Research Institute, Childrens National Medical Center | Echinomycin formulation, method of making and method of use thereof |
CA3004886A1 (en) | 2015-11-12 | 2017-05-18 | Graybug Vision, Inc. | Aggregating microparticles for medical therapy |
CA3002097A1 (en) | 2015-11-12 | 2017-05-18 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
TWI778491B (en) | 2015-11-30 | 2022-09-21 | 美商輝瑞股份有限公司 | Site specific her2 antibody drug conjugates |
TWI812873B (en) | 2015-11-30 | 2023-08-21 | 美商輝瑞股份有限公司 | Antibodies and antibody fragments for site-specific conjugation |
EP3383908A1 (en) | 2015-12-02 | 2018-10-10 | Stsciences, Inc. | Antibodies specific to glycosylated btla (b- and t- lymphocyte attenuator) |
WO2017096051A1 (en) | 2015-12-02 | 2017-06-08 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
US20190307857A1 (en) | 2015-12-09 | 2019-10-10 | Modernatx, Inc. | MODIFIED mRNA ENCODING A URIDINE DIPHOPSPHATE GLUCURONOSYL TRANSFERASE AND USES THEREOF |
WO2017105990A1 (en) | 2015-12-14 | 2017-06-22 | Massachusetts Institute Of Technology | Ph-responsive mucoadhesive polymeric encapsulated microorganisms |
US11433136B2 (en) | 2015-12-18 | 2022-09-06 | The General Hospital Corporation | Polyacetal polymers, conjugates, particles and uses thereof |
JPWO2017110772A1 (en) | 2015-12-21 | 2018-09-13 | 富士フイルム株式会社 | Liposomes and liposome compositions |
CA3009378A1 (en) | 2015-12-23 | 2017-06-29 | Queensland University Of Technology | Nucleic acid oligomers and uses therefor |
US11719704B2 (en) | 2015-12-30 | 2023-08-08 | Momenta Pharmaceuticals, Inc. | Methods related to biologics |
MX2018008369A (en) | 2016-01-08 | 2019-05-15 | Scholar Rock Inc | Anti-pro/latent myostatin antibodies and methods of use thereof. |
WO2017127750A1 (en) | 2016-01-22 | 2017-07-27 | Modernatx, Inc. | Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof |
TWI797073B (en) | 2016-01-25 | 2023-04-01 | 德商安美基研究(慕尼黑)公司 | Pharmaceutical composition comprising bispecific antibody constructs |
EA039859B1 (en) | 2016-02-03 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Bispecific antibody constructs binding egfrviii and cd3 |
BR112018015415A2 (en) | 2016-02-03 | 2018-12-18 | Amgen Res Munich Gmbh | psma and cd3 bispecific t cell of antibody construct coupling |
TWI748984B (en) | 2016-02-03 | 2021-12-11 | 德商安美基研究(慕尼黑)公司 | Bcma and cd3 bispecific t cell engaging antibody constructs |
AU2017213826A1 (en) | 2016-02-04 | 2018-08-23 | Curis, Inc. | Mutant smoothened and methods of using the same |
JP7157981B2 (en) | 2016-03-07 | 2022-10-21 | チャールストンファーマ, エルエルシー | anti-nucleolin antibody |
KR20230088508A (en) | 2016-03-11 | 2023-06-19 | 스칼러 락, 인크. | TGFβ1-BINDING IMMUNOGLOBULINS AND USE THEREOF |
CN109476756B (en) | 2016-03-15 | 2022-05-31 | 埃泰美德(香港)有限公司 | Multi-specificity Fab fusion protein and application thereof |
MX2018012695A (en) | 2016-04-18 | 2019-06-20 | Sarepta Therapeutics Inc | Antisense oligomers and methods of using the same for treating diseases associated with the acid alpha-glucosidase gene. |
CN109069473B (en) | 2016-04-21 | 2022-09-16 | 港大科桥有限公司 | Compositions and methods for lightening skin and reducing hyperpigmentation |
CA3026880A1 (en) | 2016-06-08 | 2017-12-14 | Paul Foster | Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b |
ITUA20164630A1 (en) | 2016-06-23 | 2017-12-23 | Paolo Blasi | PHARMACOLOGICAL ADIUVANTS FOR TUMOR THERMAL WELDING |
ES2887573T3 (en) | 2016-06-27 | 2021-12-23 | Alexion Pharma Inc | Methods for treating hypophosphatasia in children and adolescents |
WO2018005657A1 (en) | 2016-06-28 | 2018-01-04 | Verily Life Sciences Llc | Serial filtration to generate small cholesterol-containing liposomes |
BR112019001262A2 (en) | 2016-07-22 | 2019-05-07 | Dana-Farber Cancer Institute, Inc. | antibodies to the glucocorticoid-induced tumor necrosis factor receptor (gitr) and methods of use thereof |
KR20240035633A (en) | 2016-08-03 | 2024-03-15 | 넥스트큐어 인코포레이티드 | Compositions and methods for modulating lair signal transduction |
WO2018026890A1 (en) | 2016-08-03 | 2018-02-08 | Cymabay Therapeutics | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
TWI754659B (en) | 2016-08-08 | 2022-02-11 | 台灣微脂體股份有限公司 | Delivery vehicle, method and kit for preparing a liposomal composition containing mild acidic agent |
EP3507305A1 (en) | 2016-09-02 | 2019-07-10 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating b cell disorders |
BR112019004214A2 (en) | 2016-09-06 | 2019-05-28 | Dana Farber Cancer Inst Inc | Methods to Treat or Prevent Zika Virus Infection |
WO2018049275A1 (en) | 2016-09-09 | 2018-03-15 | Genentech, Inc. | Selective peptide inhibitors of frizzled |
WO2018049261A1 (en) | 2016-09-09 | 2018-03-15 | Icellhealth Consulting Llc | Oncolytic virus expressing immune checkpoint modulators |
CA3036829A1 (en) | 2016-09-14 | 2018-03-22 | The Trustees Of The University Of Pennsylvania | Proximity-based sortase-mediated protein purification and ligation |
AU2017327828B2 (en) | 2016-09-16 | 2023-11-16 | Shanghai Henlius Biotech, Inc. | Anti-PD-1 antibodies |
CA3037661A1 (en) | 2016-09-23 | 2018-03-29 | Teva Pharmaceuticals International Gmbh | Treating cluster headache |
BR112019005823A2 (en) | 2016-09-23 | 2019-06-25 | Teva Pharmaceuticals Int Gmbh | treatment for refractory migraine |
EP3532070A1 (en) | 2016-10-26 | 2019-09-04 | Modernatx, Inc. | Messenger ribonucleic acids for enhancing immune responses and methods of use thereof |
MA46709A (en) | 2016-11-02 | 2019-09-11 | Ipsen Biopharm Ltd | TREATMENT OF GASTRIC CANCER USING POLYTHERAPIES INCLUDING OXALIPLATIN, 5-FLUORURACIL (AND LEUCOVORIN) AND IRINOTECAN IN LIPOSOMAL FORM |
WO2018083248A1 (en) | 2016-11-03 | 2018-05-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
CA3040812A1 (en) | 2016-11-04 | 2018-05-11 | Novimmune Sa | Anti-cd19 antibodies and methods of use thereof |
JP2020500020A (en) | 2016-11-14 | 2020-01-09 | ノバルティス アーゲー | Compositions, methods, and therapeutic uses related to the fusogenic protein MINION |
US11401330B2 (en) | 2016-11-17 | 2022-08-02 | Seagen Inc. | Glycan-interacting compounds and methods of use |
WO2018106738A1 (en) | 2016-12-05 | 2018-06-14 | Massachusetts Institute Of Technology | Brush-arm star polymers, conjugates and particles, and uses thereof |
GEP20217265B (en) | 2016-12-16 | 2021-06-25 | Pfizer | Glp-1 receptor agonists and uses thereof |
US10772926B2 (en) | 2016-12-16 | 2020-09-15 | Nutragen Health Innovations, Inc. | Natural drugs for the treatment of inflammation and melanoma |
FI3565592T3 (en) | 2017-01-06 | 2023-05-10 | Scholar Rock Inc | Treating metabolic diseases by inhibiting myostatin activation |
CA3049005A1 (en) | 2017-01-06 | 2018-07-12 | Scholar Rock, Inc. | Isoform-specific, context-permissive tgf.beta.1 inhibitors and use thereof |
PT3565592T (en) | 2017-01-06 | 2023-05-31 | Scholar Rock Inc | Methods for treating metabolic diseases by inhibiting myostatin activation |
CN117224710A (en) | 2017-02-01 | 2023-12-15 | 莫得纳特斯公司 | Immunomodulatory therapeutic MRNA compositions encoding mutant peptides that activate oncogenes |
JOP20190189A1 (en) | 2017-02-02 | 2019-08-01 | Amgen Res Munich Gmbh | Low ph pharmaceutical composition comprising t cell engaging antibody constructs |
WO2018152496A1 (en) | 2017-02-17 | 2018-08-23 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Compositions and methods for the diagnosis and treatment of zika virus infection |
PE20191487A1 (en) | 2017-03-03 | 2019-10-18 | Rinat Neuroscience Corp | ANTI-GITR ANTIBODIES AND METHODS OF USE OF THEM |
SG11201907889YA (en) | 2017-03-03 | 2019-09-27 | Seattle Genetics Inc | Glycan-interacting compounds and methods of use |
WO2018165619A1 (en) | 2017-03-09 | 2018-09-13 | Cytomx Therapeutics, Inc. | Cd147 antibodies, activatable cd147 antibodies, and methods of making and use thereof |
EP3601350A1 (en) | 2017-03-27 | 2020-02-05 | Boehringer Ingelheim International GmbH | Anti il-36r antibodies combination therapy |
US11359200B2 (en) | 2017-04-09 | 2022-06-14 | The Cleveland Clinic Foundation | Cancer treatment by MALAT1 inhibition |
US20230192839A1 (en) | 2017-04-12 | 2023-06-22 | Pfizer Inc. | Antibodies having conditional affinity and methods of use thereof |
WO2018191548A2 (en) | 2017-04-14 | 2018-10-18 | Kodiak Sciences Inc. | Complement factor d antagonist antibodies and conjugates thereof |
EP3612625A4 (en) | 2017-04-21 | 2021-08-18 | Mellitus, LLC | Methods and antibodies for diabetes-related applications |
US11236151B2 (en) | 2017-04-25 | 2022-02-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of Epstein Barr virus infection |
BR112019022751A2 (en) | 2017-05-05 | 2020-05-19 | Amgen Inc | pharmaceutical composition comprising bispecific antibody constructs for improved storage and administration |
US11318190B2 (en) | 2017-05-05 | 2022-05-03 | United States Government As Represented By The Department Of Veterans Affairs | Methods and compositions for treating liver disease |
US11160870B2 (en) | 2017-05-10 | 2021-11-02 | Graybug Vision, Inc. | Extended release microparticles and suspensions thereof for medical therapy |
SG11201909751TA (en) | 2017-05-12 | 2019-11-28 | Augusta University Research Institute Inc | Human alpha fetoprotein-specific t cell receptors and uses thereof |
WO2018209288A1 (en) | 2017-05-12 | 2018-11-15 | Massachusetts Institute Of Technology | Argonaute protein-double stranded rna complexes and uses related thereto |
US11260117B2 (en) | 2017-05-26 | 2022-03-01 | Novimmune Sa | Anti-CD47 x anti-mesothelin antibodies and methods of use thereof |
CA3065300A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that immunospecifically bind to btn1a1 |
EP3630835A1 (en) | 2017-05-31 | 2020-04-08 | STCube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
BR112019025188A2 (en) | 2017-06-01 | 2020-06-23 | Cytomx Therapeutics, Inc. | ACTIVABLE ANTI-PDL1 ANTIBODIES AND METHODS OF USE OF THE SAME |
EP3635007A1 (en) | 2017-06-06 | 2020-04-15 | STCube & Co., Inc. | Methods of treating cancer using antibodies and molecules that bind to btn1a1 or btn1a1-ligands |
GB201710838D0 (en) | 2017-07-05 | 2017-08-16 | Ucl Business Plc | Bispecific antibodies |
CA3061752A1 (en) | 2017-07-06 | 2019-01-10 | Arrowhead Pharmaceuticals, Inc. | Rnai agents for inhibiting expression of alpha-enac and methods of use |
EP3651799A1 (en) | 2017-07-13 | 2020-05-20 | Massachusetts Institute of Technology | Targeting the hdac2-sp3 complex to enhance synaptic function |
KR20200027971A (en) | 2017-07-14 | 2020-03-13 | 싸이톰스 테라퓨틱스, 인크. | Anti-CD166 antibodies and uses thereof |
EP3655430A1 (en) | 2017-07-19 | 2020-05-27 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Antibodies and methods for the diagnosis and treatment of hepatitis b virus infection |
US20210025877A1 (en) | 2017-07-20 | 2021-01-28 | CytomX Therapeutices, Inc. | Methods of qualitatively and/or quantitatively analyzing properties of activatable antibodies and uses thereof |
WO2019016784A1 (en) | 2017-07-21 | 2019-01-24 | Universidade De Coimbra | Anti-nucleolin antibody |
WO2019018765A1 (en) | 2017-07-21 | 2019-01-24 | Modernatx, Inc. | Modified mrna encoding a propionyl-coa carboxylase and uses thereof |
US20200179494A1 (en) | 2017-07-24 | 2020-06-11 | Modernatx, Inc. | Modified mRNA Encoding a Glucose 6 Phosphatase and Uses Thereof |
PT3658184T (en) | 2017-07-27 | 2023-11-29 | Alexion Pharma Inc | High concentration anti-c5 antibody formulations |
EP3658583A1 (en) | 2017-07-28 | 2020-06-03 | Scholar Rock, Inc. | Ltbp complex-specific inhibitors of tgf-beta 1 and uses thereof |
CA3071755A1 (en) | 2017-08-03 | 2019-02-07 | Otsuka Pharmaceutical Co., Ltd. | Drug compound and purification methods thereof |
US11135187B2 (en) | 2017-08-22 | 2021-10-05 | National Institutes Of Health (Nih) | Compositions and methods for treating diabetic retinopathy |
WO2019046652A1 (en) | 2017-08-30 | 2019-03-07 | Cytomx Therapeutics, Inc. | Activatable anti-cd166 antibodies and methods of use thereof |
WO2019051164A1 (en) | 2017-09-07 | 2019-03-14 | Augusta University Research Institute, Inc. | Antibodies to programmed cell death protein 1 |
US11999953B2 (en) | 2017-09-13 | 2024-06-04 | The Children's Medical Center Corporation | Compositions and methods for treating transposon associated diseases |
US11364303B2 (en) | 2017-09-29 | 2022-06-21 | Pfizer Inc. | Cysteine engineered antibody drug conjugates |
JP2020536967A (en) | 2017-10-12 | 2020-12-17 | イミュノウェイク インコーポレイテッド | VEGFR-antibody light chain fusion protein |
WO2019075405A1 (en) | 2017-10-14 | 2019-04-18 | Cytomx Therapeutics, Inc. | Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof |
AU2018353533A1 (en) | 2017-10-17 | 2020-05-28 | Rhizen Pharmaceuticals Sa | CRAC channel modulators for treating esophageal cancer |
WO2019079637A2 (en) | 2017-10-18 | 2019-04-25 | Sarepta Therapeutics, Inc. | Antisense oligomer compounds |
WO2019082124A1 (en) | 2017-10-26 | 2019-05-02 | Rhizen Pharmaceuticals Sa | Composition and method for treating diffuse large b-cell lymphoma |
CN111556876A (en) | 2017-10-27 | 2020-08-18 | 辉瑞公司 | Antibodies and antibody-drug conjugates specific for CD123 and uses thereof |
WO2019087047A1 (en) | 2017-10-30 | 2019-05-09 | Rhizen Pharmaceuticals Sa | Calcium release-activated calcium channel modulators for treating hematological and solid cancers |
WO2019086626A1 (en) | 2017-11-03 | 2019-05-09 | Centro Nacional De Investigaciones Cardiovasculares Carlos Iii (F.S.P.) | MIRNAs AND COMBINATIONS THEREOF FOR USE IN THE TREATMENT OF HUMAN B CELL NEOPLASIAS |
EA202091082A1 (en) | 2017-12-06 | 2020-10-23 | Ризен Фармасьютикалз Са | COMPOSITION AND METHOD FOR TREATMENT OF PERIPHERAL T-CELL LYMPHOMA AND SKIN T-CELL LYMPHOMA |
US11946094B2 (en) | 2017-12-10 | 2024-04-02 | Augusta University Research Institute, Inc. | Combination therapies and methods of use thereof |
CN111315780A (en) | 2017-12-11 | 2020-06-19 | 安进公司 | Continuous manufacturing process for bispecific antibody products |
TW201940518A (en) | 2017-12-29 | 2019-10-16 | 美商安進公司 | Bispecific antibody construct directed to MUC17 and CD3 |
WO2019165101A1 (en) | 2018-02-22 | 2019-08-29 | Verily Life Sciences Llc | Combining orthogonal chemistries for preparation of multiplexed nanoparticles |
WO2019166946A1 (en) | 2018-02-28 | 2019-09-06 | Pfizer Inc. | Il-15 variants and uses thereof |
WO2019173771A1 (en) | 2018-03-09 | 2019-09-12 | Cytomx Therapeutics, Inc. | Activatable cd147 antibodies and methods of making and use thereof |
CA3093330A1 (en) | 2018-03-14 | 2019-09-19 | Novimmune Sa | Anti-cd3 epsilon antibodies and methods of use thereof |
BR112020014591A2 (en) | 2018-03-14 | 2020-12-01 | Beijing Xuanyi Pharmasciences Co., Ltd. | anticlaudin antibodies 18.2 |
US20210000936A1 (en) | 2018-03-21 | 2021-01-07 | Colorado State University Research Foundation | Cancer vaccine compositions and methods of use thereof |
US10722528B2 (en) | 2018-03-28 | 2020-07-28 | Augusta University Research Institute, Inc. | Compositions and methods for inhibiting metastasis |
WO2019195738A1 (en) | 2018-04-06 | 2019-10-10 | Children's Medical Center Corporation | Compositions and methods for somatic cell reprogramming and modulating imprinting |
CN112334485A (en) | 2018-04-06 | 2021-02-05 | 百进生物科技公司 | Anti-tetraspanin 33agents and compositions thereof and methods of making and using |
WO2019197607A1 (en) | 2018-04-13 | 2019-10-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fc-engineered anti-human ige antibodies and methods of use |
WO2019213416A1 (en) | 2018-05-02 | 2019-11-07 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Antibodies and methods for the diagnosis, prevention, and treatment of epstein barr virus infection |
US11434292B2 (en) | 2018-05-23 | 2022-09-06 | Pfizer Inc. | Antibodies specific for CD3 and uses thereof |
AU2019274655B2 (en) | 2018-05-23 | 2023-03-09 | Pfizer Inc. | Antibodies specific for GUCY2c and uses thereof |
WO2019234680A1 (en) | 2018-06-08 | 2019-12-12 | Pfizer Inc. | Methods of treating iron metabolic disease with a neutralizing antibody binding erhythroferrone |
TWI707683B (en) | 2018-06-13 | 2020-10-21 | 美商輝瑞股份有限公司 | Glp-1 receptor agonists and uses thereof |
DK3806855T5 (en) | 2018-06-15 | 2023-05-22 | Pfizer | GLP-1 receptor agonists and uses thereof |
EP3810189A1 (en) | 2018-06-19 | 2021-04-28 | Armo Biosciences, Inc. | Compositions and methods of use of il-10 agents in conjunction with chimeric antigen receptor cell therapy |
AU2019293286A1 (en) | 2018-06-28 | 2021-01-07 | Crispr Therapeutics Ag | Compositions and methods for genomic editing by insertion of donor polynucleotides |
EA202190094A1 (en) | 2018-06-29 | 2021-04-21 | Бёрингер Ингельхайм Интернациональ Гмбх | ANTIBODIES AGAINST CD40 FOR USE IN THE TREATMENT OF AUTOIMMUNE DISEASE |
CA3105161C (en) | 2018-07-06 | 2022-11-15 | Pfizer Inc. | Manufacturing process and intermediates for a pyrrolo[2,3- d]pyrimidine compound and use thereof |
WO2020014460A1 (en) | 2018-07-11 | 2020-01-16 | Scholar Rock, Inc. | HIGH-AFFINITY, ISOFORM-SELECTIVE TGFβ1 INHIBITORS AND USE THEREOF |
TW202019957A (en) | 2018-07-11 | 2020-06-01 | 美商供石公司 | Tgfβ1 inhibitors and use thereof |
EP3677278B1 (en) | 2018-07-11 | 2021-11-10 | Scholar Rock, Inc. | Isoform selective tgfbeta1 inhibitors and use thereof |
MA53160A (en) | 2018-07-20 | 2021-05-26 | Pf Medicament | RECEIVER FOR VISTA |
EP3837367A1 (en) | 2018-08-16 | 2021-06-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
CN113365697A (en) | 2018-09-25 | 2021-09-07 | 百进生物科技公司 | anti-TLR9 agents and compositions and methods of making and using the same |
JP2022513328A (en) | 2018-09-27 | 2022-02-07 | フォスフォガム, インコーポレイテッド | Methods and Compositions for Proliferation and Use of Allogeneic Gamma / Delta T Cells |
JP2022503961A (en) | 2018-09-28 | 2022-01-12 | リビジェン バイオファーマ カンパニー リミテッド | Anti-CD40 binding molecule with engineered Fc domain and its therapeutic uses |
KR20210074341A (en) | 2018-10-10 | 2021-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | Methods for membrane gas transfer in high-density bioreactor cultures |
CN112789058A (en) | 2018-10-11 | 2021-05-11 | 安进公司 | Downstream processing of bispecific antibody constructs |
US11427591B2 (en) | 2018-10-17 | 2022-08-30 | Insilico Medicine Ip Limited | Kinase inhibitors |
SG11202104010PA (en) | 2018-10-23 | 2021-05-28 | Scholar Rock Inc | Rgmc-selective inhibitors and use thereof |
CN113260383A (en) | 2018-11-02 | 2021-08-13 | 西托姆克斯治疗公司 | Activatable anti-CD 166 antibodies and methods of use thereof |
KR20210106447A (en) | 2018-11-22 | 2021-08-30 | 치루 레고르 테라퓨틱스 인코포레이티드 | GLP-1R agonists and uses thereof |
EP3887516A1 (en) | 2018-11-29 | 2021-10-06 | Flagship Pioneering Innovations V, Inc. | Methods of modulating rna |
KR20210102318A (en) | 2018-12-06 | 2021-08-19 | 싸이톰스 테라퓨틱스, 인크. | Matrix metalloprotease-cleavable substrates and serine or cysteine protease-cleavable substrates and methods of use thereof |
BR112021012172A2 (en) | 2018-12-12 | 2021-08-31 | Kite Pharma, Inc. | CHIMERIC AND T-CELL ANTIGEN RECEPTORS AND METHODS OF USE |
WO2020154374A1 (en) | 2019-01-22 | 2020-07-30 | Massachusetts Institute Of Technology | In vitro human blood brain barrier |
JP2020117502A (en) | 2019-01-28 | 2020-08-06 | ファイザー・インク | Method of treating signs and symptoms of osteoarthritis |
CA3128042A1 (en) | 2019-01-30 | 2020-08-06 | Scholar Rock, Inc. | Ltbp complex-specific inhibitors of tgf.beta. and uses thereof |
US20220144846A1 (en) | 2019-02-15 | 2022-05-12 | Pfizer Inc. | Crystalline pyrimidinyl-3,8-diazabicyclo[3.2.1]octanylmethanone compound and use thereof |
EP3927430A1 (en) | 2019-02-18 | 2021-12-29 | Pfizer Inc. | Method of treatment of chronic low back pain |
US20220275059A1 (en) | 2019-02-20 | 2022-09-01 | Harbour Antibodies Bv | Antibodies |
US11795160B2 (en) | 2019-02-22 | 2023-10-24 | Insilico Medicine Ip Limited | Kinase inhibitors |
CN113677372A (en) | 2019-02-26 | 2021-11-19 | 西托姆克斯治疗公司 | Combination therapy of activatable immune checkpoint inhibitors and conjugated activatable antibodies |
US20200283796A1 (en) | 2019-03-05 | 2020-09-10 | Massachusetts Institute Of Technology | Dna launched rna replicon system (drep) and uses thereof |
WO2020185293A1 (en) | 2019-03-08 | 2020-09-17 | Massachusetts Institute Of Technology | Synthetic oncolytic lnp-replicon rna and uses for cancer immunotherapy |
WO2020197400A1 (en) | 2019-03-27 | 2020-10-01 | Umc Utrecht Holding B.V. | Engineered iga antibodies and methods of use |
AR118536A1 (en) | 2019-04-01 | 2021-10-20 | Genentech Inc | COMPOSITIONS AND METHODS TO STABILIZE FORMULATIONS CONTAINING PROTEIN |
EP3947367A1 (en) | 2019-04-02 | 2022-02-09 | Array Biopharma, Inc. | Protein tyrosine phosphatase inhibitors |
TW202115086A (en) | 2019-06-28 | 2021-04-16 | 美商輝瑞大藥廠 | Bckdk inhibitors |
JP7498199B2 (en) | 2019-06-28 | 2024-06-11 | ファイザー・インク | 5-(thiophen-2-yl)-1H-tetrazole derivatives as BCKDK inhibitors useful for treating various diseases - Patents.com |
LT6699B (en) | 2019-07-15 | 2020-02-10 | UAB "Valentis" | Method for production of proliposomes by using up to 5% ethanol and the use thereof for encapsulation of lipophilic substances |
CN112300279A (en) | 2019-07-26 | 2021-02-02 | 上海复宏汉霖生物技术股份有限公司 | Methods and compositions directed to anti-CD 73 antibodies and variants |
US10758329B1 (en) | 2019-08-20 | 2020-09-01 | Raymond L. Wright, III | Hydrating mouth guard |
MX2022002689A (en) | 2019-09-03 | 2022-04-07 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of the lect2 gene. |
JP2022548310A (en) | 2019-09-23 | 2022-11-17 | シートムエックス セラピューティクス,インコーポレイテッド | Anti-CD47 antibodies, activatable anti-CD47 antibodies, and methods of use thereof |
CN114729045A (en) | 2019-09-26 | 2022-07-08 | 斯特库比公司 | Antibodies specific for glycosylated CTLA-4 and methods of use thereof |
WO2021062092A1 (en) | 2019-09-26 | 2021-04-01 | Massachusetts Institute Of Technology | Trans-activated functional rna by strand displacement and uses thereof |
WO2021062096A1 (en) | 2019-09-26 | 2021-04-01 | Massachusetts Institute Of Technology | Microrna-based logic gates and uses thereof |
WO2021067526A1 (en) | 2019-10-02 | 2021-04-08 | Alexion Pharmaceuticals, Inc. | Complement inhibitors for treating drug-induced complement-mediated response |
TWI771766B (en) | 2019-10-04 | 2022-07-21 | 美商輝瑞股份有限公司 | Diacylglycerol acyltransferase 2 inhibitor |
WO2021067747A1 (en) | 2019-10-04 | 2021-04-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing ugt1a1 gene expression |
WO2021071830A1 (en) | 2019-10-07 | 2021-04-15 | University Of Virginia Patent Foundation | Modulating lymphatic vessels in neurological disease |
US20220356248A1 (en) | 2019-10-09 | 2022-11-10 | Stcube & Co | Antibodies specific to glycosylated lag3 and methods of use thereof |
US11912784B2 (en) | 2019-10-10 | 2024-02-27 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
EP4041773A1 (en) | 2019-10-11 | 2022-08-17 | Beth Israel Deaconess Medical Center, Inc. | Anti-tn antibodies and uses thereof |
JP2023501912A (en) | 2019-10-21 | 2023-01-20 | ライゼン ファーマシューティカルズ アーゲー | Compositions containing DHODH inhibitors for the treatment of acute myeloid leukemia |
EP4051796A1 (en) | 2019-11-01 | 2022-09-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajb1-prkaca fusion gene expression |
WO2021116874A1 (en) | 2019-12-10 | 2021-06-17 | Pfizer Inc. | Solid forms of 2-((4-((s)-2-(5-chloropyridin-2-yl)-2-methylbenzo[d] [1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-benzo[d] imidazole-6-carboxylic acid, 1,3-dihydroxy-2-(hydroxymethyl)propan-2-amine salt |
EP4087649A1 (en) | 2020-01-11 | 2022-11-16 | Scholar Rock, Inc. | Tgfbeta inhibitors and use thereof |
WO2021142448A2 (en) | 2020-01-11 | 2021-07-15 | Scholar Rock,Inc. | Tgf-beta inhibitors and use thereof |
CA3166420A1 (en) | 2020-01-14 | 2021-07-22 | Synthekine, Inc. | Il2 orthologs and methods of use |
EP4090681A1 (en) | 2020-01-17 | 2022-11-23 | Biolegend, Inc. | Anti-tlr7 agents and compositions and methods for making and using the same |
US20230067811A1 (en) | 2020-01-24 | 2023-03-02 | University Of Virginia Patent Foundation | Modulating lymphatic vessels in neurological disease |
TW202140786A (en) | 2020-02-10 | 2021-11-01 | 美商艾爾妮蘭製藥公司 | Compositions and methods for silencing vegf-a expression |
JP2022058085A (en) | 2020-02-24 | 2022-04-11 | ファイザー・インク | Combination of inhibitors of diacylglycerol acyltransferase 2 and inhibitors of acetyl-coa carboxylase |
AU2021232062A1 (en) | 2020-03-06 | 2022-09-29 | Colorado State University Research Foundation | Production of vaccines comprising inactivated SARS-CoV-2 viral particles |
CA3174908A1 (en) | 2020-03-09 | 2021-09-16 | Pfizer Inc. | Fusion proteins and uses thereof |
GB202003632D0 (en) | 2020-03-12 | 2020-04-29 | Harbour Antibodies Bv | SARS-Cov-2 (SARS2, COVID-19) antibodies |
US20230095383A1 (en) | 2020-03-17 | 2023-03-30 | Dst Pharma, Inc. | Methods and compositions for treating viral infections |
AU2021244695A1 (en) | 2020-03-26 | 2022-11-10 | Plx Opco Inc. | Pharmaceutical carriers capable of pH dependent reconstitution and methods for making and using same |
CA3176569A1 (en) | 2020-03-27 | 2021-09-30 | Pfizer Inc. | Treatment of type 2 diabetes or obesity or overweight with 2-[(4-{6-[(4-cyano-2-fluorobenzyl)oxy]pyridin-2-yl} piperidin-1-yl)methyl]-1-[(2s)-oxetan-2-ylmethyl]-1h-benzimidazole-6-carboxylic acid or a pharmaceutically salt thereof |
WO2021202443A2 (en) | 2020-03-30 | 2021-10-07 | Alnylam Pharmaceucticals, Inc. | Compositions and methods for silencing dnajc15 gene expression |
MX2022012493A (en) | 2020-04-06 | 2022-10-27 | Alnylam Pharmaceuticals Inc | Compositions and methods for silencing myoc expression. |
AU2021251754A1 (en) | 2020-04-07 | 2022-11-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing SCN9A expression |
EP4132931A1 (en) | 2020-04-08 | 2023-02-15 | Pfizer Inc. | Crystalline forms of 3-cyano-1-[4-[6-(1-methyl-1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]-1h-pyrazol-1-yl]cyclobutaneacetonitrile, and use thereof |
CA3176425A1 (en) | 2020-04-24 | 2021-10-28 | Millennium Pharmaceuticals, Inc. | Anti-cd19 antibodies and uses thereof |
WO2021224850A1 (en) | 2020-05-06 | 2021-11-11 | Crispr Therapeutics Ag | Mask peptides and masked anti-ptk7 antibodies comprising such |
CA3178965A1 (en) | 2020-05-15 | 2021-11-18 | Christian COBAUGH | Messenger rna encoding cas9 for use in genome-editing systems |
WO2021237097A1 (en) | 2020-05-21 | 2021-11-25 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting marc1 gene expression |
CN115867546A (en) | 2020-05-27 | 2023-03-28 | 上海齐鲁锐格医药研发有限公司 | Salts and crystalline forms of GLP-1R agonists and uses thereof |
MX2022015706A (en) | 2020-06-09 | 2023-01-24 | Pfizer | Spiro compounds as melanocortin 4 receptor antagonists and uses thereof. |
EP4171632A2 (en) | 2020-06-26 | 2023-05-03 | Pfizer Inc. | Methods of treating inflammatory bowel disease with tl1a antibodies |
WO2022006562A1 (en) | 2020-07-03 | 2022-01-06 | Dana-Farber Cancer Institute, Inc. | Multispecific coronavirus antibodies |
PE20231565A1 (en) | 2020-07-17 | 2023-10-04 | Pfizer | THERAPEUTIC ANTIBODIES AND THEIR USES |
WO2022020811A1 (en) | 2020-07-24 | 2022-01-27 | Strand Therapeutics, Inc. | Lipidnanoparticle comprising modified nucleotides |
CA3187393A1 (en) | 2020-07-28 | 2022-02-03 | Andrew BELFIELD | Chiral synthesis of fused bicyclic raf inhibitors |
CA3187514A1 (en) | 2020-07-28 | 2022-02-03 | Andrew BELFIELD | Fused bicyclic raf inhibitors and methods for use thereof |
JP2023536654A (en) | 2020-08-05 | 2023-08-28 | シンセカイン インコーポレイテッド | IL10Ra binding molecules and methods of use |
JP2023536652A (en) | 2020-08-05 | 2023-08-28 | シンセカイン インコーポレイテッド | IL27Rα binding molecules and methods of use |
US20230272090A1 (en) | 2020-08-05 | 2023-08-31 | Sandro Vivona | Il2rb binding molecules and methods of use |
EP4192877A1 (en) | 2020-08-05 | 2023-06-14 | Synthekine, Inc. | Il2rb/il2rg synthetic cytokines |
AR123156A1 (en) | 2020-08-06 | 2022-11-02 | Qilu Regor Therapeutics Inc | GLP-1R AGONISTS AND THEIR USES |
IL299911A (en) | 2020-08-14 | 2023-03-01 | Kite Pharma Inc | Improving immune cell function |
AU2021340793A1 (en) | 2020-09-14 | 2023-05-11 | Vor Biopharma Inc. | Single domain antibodies against cd33 |
EP4213939A1 (en) | 2020-09-21 | 2023-07-26 | Boehringer Ingelheim International GmbH | Use of anti-cd40 antibodies for treatment of inflammatory conditions |
AU2021357805A1 (en) | 2020-10-06 | 2023-05-04 | Xencor, Inc. | Biomarkers, methods, and compositions for treating autoimmune disease including systemic lupus erythematous (sle) |
CA3195264A1 (en) | 2020-10-14 | 2022-04-21 | Wenge Zhong | Crystal forms of glp-1r agonists and uses thereof |
WO2022093640A1 (en) | 2020-10-30 | 2022-05-05 | BioLegend, Inc. | Anti-nkg2c agents and compositions and methods for making and using the same |
WO2022093641A1 (en) | 2020-10-30 | 2022-05-05 | BioLegend, Inc. | Anti-nkg2a agents and compositions and methods for making and using the same |
US11058637B1 (en) * | 2020-11-25 | 2021-07-13 | King Abdulaziz University | Surface-modified emulsomes for intranasal delivery of drugs |
IL303195A (en) | 2020-11-25 | 2023-07-01 | Akagera Medicines Inc | Lipid nanoparticles for delivery of nucleic acids, and related methods of use |
TW202241946A (en) | 2020-12-18 | 2022-11-01 | 美商健生生物科技公司 | Antibodies against integrin alpha 11 beta 1 |
EP4274846A1 (en) | 2021-01-08 | 2023-11-15 | Strand Therapeutics Inc. | Expression constructs and uses thereof |
US11357727B1 (en) | 2021-01-22 | 2022-06-14 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
US11033495B1 (en) | 2021-01-22 | 2021-06-15 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
US11278494B1 (en) | 2021-01-22 | 2022-03-22 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
CN117062836A (en) | 2021-02-05 | 2023-11-14 | 勃林格殷格翰国际有限公司 | anti-IL 1RAP antibodies |
CA3208490A1 (en) | 2021-02-24 | 2022-09-01 | Aleksandrs Zavoronkovs | Analogs for the treatment of disease |
IL305571A (en) | 2021-03-11 | 2023-10-01 | Kite Pharma Inc | Improving immune cell function |
WO2022195504A1 (en) | 2021-03-19 | 2022-09-22 | Pfizer Inc. | Method of treating osteoarthritis pain with an anti ngf antibody |
CA3212056A1 (en) | 2021-03-22 | 2022-09-29 | Xavier CHAUCHET | Bispecific antibodies targeting cd47 and pd-l1 and methods of use thereof |
US11952461B2 (en) | 2021-03-22 | 2024-04-09 | Sunbio, Inc. | Siloxy polyethylene glycol and derivatives thereof |
AU2022241935A1 (en) | 2021-03-22 | 2023-09-28 | Novimmune S.A. | Bispecific antibodies targeting cd47 and pd-l1 and methods of use thereof |
WO2022204581A2 (en) | 2021-03-26 | 2022-09-29 | Scholar Rock, Inc. | Tgf-beta inhibitors and use thereof |
EP4320149A1 (en) | 2021-04-09 | 2024-02-14 | Takeda Pharmaceutical Company Limited | Antibodies targeting complement factor d and uses therof |
AU2022261124A1 (en) | 2021-04-22 | 2023-10-05 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating cancer |
IL307939A (en) | 2021-04-26 | 2023-12-01 | Millennium Pharm Inc | Anti-clec12a antibodies and uses thereof |
IL307940A (en) | 2021-04-26 | 2023-12-01 | Millennium Pharm Inc | Anti-adgre2 antibodies and uses thereof |
EP4334354A1 (en) | 2021-05-06 | 2024-03-13 | Dana-Farber Cancer Institute, Inc. | Antibodies against alk and methods of use thereof |
WO2022245859A1 (en) | 2021-05-17 | 2022-11-24 | Curia Ip Holdings, Llc | Sars-cov-2 spike protein antibodies |
US20230115257A1 (en) | 2021-05-17 | 2023-04-13 | Curia Ip Holdings, Llc | Sars-cov-2 spike protein antibodies |
WO2022256723A2 (en) | 2021-06-03 | 2022-12-08 | Scholar Rock, Inc. | Tgf-beta inhibitors and therapeutic use thereof |
EP4358995A1 (en) | 2021-06-23 | 2024-05-01 | Scholar Rock, Inc. | A myostatin pathway inhibitor in combination with a glp-1 pathway activator for use in treating metabolic disorders |
EP4367237A2 (en) | 2021-07-09 | 2024-05-15 | Alnylam Pharmaceuticals, Inc. | Bis-rnai compounds for cns delivery |
TW202306985A (en) | 2021-07-12 | 2023-02-16 | 美商建南德克公司 | Structures for reducing antibody-lipase binding |
WO2023288277A1 (en) | 2021-07-14 | 2023-01-19 | Scholar Rock, Inc. | Ltbp complex-specific inhibitors of tgfb1 and uses thereof |
WO2023007374A1 (en) | 2021-07-27 | 2023-02-02 | Pfizer Inc. | Method of treatment of cancer pain with tanezumab |
GB202111757D0 (en) | 2021-08-17 | 2021-09-29 | Cantab Biopharmaceuticals Patents Ltd | Modified colloidal particles for use in the treatment of haemophilia A |
GB202111758D0 (en) | 2021-08-17 | 2021-09-29 | Cantab Biopharmaceuticals Patents Ltd | Modified colloidal particles for use in the treatment of haemophilia A |
GB202111759D0 (en) | 2021-08-17 | 2021-09-29 | Cantab Biopharmaceuticals Patents Ltd | Modified colloidal particles |
CN117940422A (en) | 2021-08-31 | 2024-04-26 | 辉瑞大药厂 | Solid forms of 2- [ (4- {6- [ (4-cyano-2-fluorobenzyl) oxy ] pyridin-2-yl } piperidin-1-yl) methyl ] -1- [ (2S) -oxetan-2-ylmethyl ] -1H-benzimidazole-6-carboxylic acid, 1, 3-dihydroxy-2- (hydroxymethyl) propan-2-amine salt |
WO2023034901A1 (en) | 2021-09-01 | 2023-03-09 | The Broad Institute, Inc. | Tumor avatar vaccine compositions and uses thereof |
WO2023036982A1 (en) | 2021-09-10 | 2023-03-16 | Harbour Antibodies Bv | Anti-sars2-s antibodies |
GB202112935D0 (en) | 2021-09-10 | 2021-10-27 | Harbour Antibodies Bv | Sars-cov-2 (sars2, covid-19) heavy chain only antibodies |
WO2023068382A2 (en) | 2021-10-20 | 2023-04-27 | Takeda Pharmaceutical Company Limited | Compositions targeting bcma and methods of use thereof |
WO2023077148A1 (en) | 2021-11-01 | 2023-05-04 | Tome Biosciences, Inc. | Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo |
AU2022383057A1 (en) | 2021-11-05 | 2024-05-16 | Abviro Llc | Human broadly crossreactive influenza monoclonal antibodies and methods of use thereof |
CA3238936A1 (en) | 2021-11-24 | 2023-06-01 | Wayne A. Marasco | Antibodies against ctla-4 and methods of use thereof |
AU2022403203A1 (en) | 2021-12-01 | 2024-05-02 | Pfizer Inc. | 3-phenyl-1-benzothiophene-2-carboxylic acid derivatives as branched-chain alpha keto acid dehydrogenase kinase inhibitors for the treatment of diabetes, kidney diseases, nash and heart failure |
WO2023105387A1 (en) | 2021-12-06 | 2023-06-15 | Pfizer Inc. | Melanocortin 4 receptor antagonists and uses thereof |
AU2022403854A1 (en) | 2021-12-08 | 2024-05-23 | Array Biopharma Inc. | Crystalline form of n-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)-3-fluoroazetidine-1-sulfonamide |
WO2023114544A1 (en) | 2021-12-17 | 2023-06-22 | Dana-Farber Cancer Institute, Inc. | Antibodies and uses thereof |
WO2023114543A2 (en) | 2021-12-17 | 2023-06-22 | Dana-Farber Cancer Institute, Inc. | Platform for antibody discovery |
WO2023111817A1 (en) | 2021-12-17 | 2023-06-22 | Pfizer Inc. | Crystalline forms of [(1r,5s,6r)-3-{2-[(2s)-2-methylazetidin-1-yl]-6-(trifluoromethyl) pyrimidin-4-yl}-3-azabicyclo[3.1.0]hex-6-yl]acetic acid |
WO2023122764A1 (en) | 2021-12-22 | 2023-06-29 | Tome Biosciences, Inc. | Co-delivery of a gene editor construct and a donor template |
WO2023178357A1 (en) | 2022-03-18 | 2023-09-21 | Evolveimmune Therapeutics, Inc. | Bispecific antibody fusion molecules and methods of use thereof |
WO2023201238A1 (en) | 2022-04-11 | 2023-10-19 | Vor Biopharma Inc. | Binding agents and methods of use thereof |
WO2023205744A1 (en) | 2022-04-20 | 2023-10-26 | Tome Biosciences, Inc. | Programmable gene insertion compositions |
WO2023212618A1 (en) | 2022-04-26 | 2023-11-02 | Strand Therapeutics Inc. | Lipid nanoparticles comprising venezuelan equine encephalitis (vee) replicon and uses thereof |
WO2023215831A1 (en) | 2022-05-04 | 2023-11-09 | Tome Biosciences, Inc. | Guide rna compositions for programmable gene insertion |
WO2023220641A2 (en) | 2022-05-11 | 2023-11-16 | Juno Therapeutics, Inc. | Methods and uses related to t cell therapy and production of same |
WO2023225670A2 (en) | 2022-05-20 | 2023-11-23 | Tome Biosciences, Inc. | Ex vivo programmable gene insertion |
WO2023228023A1 (en) | 2022-05-23 | 2023-11-30 | Pfizer Inc. | Treatment of type 2 diabetes or weight management control with 2-((4-((s)-2-(5-chloropyridin-2-yl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-benzo[d]imidazole-6-carboxylic acid or a pharmaceutically salt thereof |
WO2023235852A1 (en) | 2022-06-03 | 2023-12-07 | Zenas Biopharma, Inc. | Methods and compositions for treating igg4- related diseases |
WO2024020051A1 (en) | 2022-07-19 | 2024-01-25 | BioLegend, Inc. | Anti-cd157 antibodies, antigen-binding fragments thereof and compositions and methods for making and using the same |
WO2024030829A1 (en) | 2022-08-01 | 2024-02-08 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal antibodies that bind to the underside of influenza viral neuraminidase |
WO2024030843A1 (en) | 2022-08-01 | 2024-02-08 | Cytomx Therapeutics, Inc. | Protease-cleavable moieties and methods of use thereof |
WO2024030845A1 (en) | 2022-08-01 | 2024-02-08 | Cytomx Therapeutics, Inc. | Protease-cleavable moieties and methods of use thereof |
WO2024030847A1 (en) | 2022-08-01 | 2024-02-08 | Cytomx Therapeutics, Inc. | Protease-cleavable moieties and methods of use thereof |
WO2024030858A1 (en) | 2022-08-01 | 2024-02-08 | Cytomx Therapeutics, Inc. | Protease-cleavable substrates and methods of use thereof |
WO2024030850A1 (en) | 2022-08-01 | 2024-02-08 | Cytomx Therapeutics, Inc. | Protease-cleavable substrates and methods of use thereof |
WO2024039672A2 (en) | 2022-08-15 | 2024-02-22 | Dana-Farber Cancer Institute, Inc. | Antibodies against msln and methods of use thereof |
WO2024039670A1 (en) | 2022-08-15 | 2024-02-22 | Dana-Farber Cancer Institute, Inc. | Antibodies against cldn4 and methods of use thereof |
WO2024040114A2 (en) | 2022-08-18 | 2024-02-22 | BioLegend, Inc. | Anti-axl antibodies, antigen-binding fragments thereof and methods for making and using the same |
WO2024059165A1 (en) | 2022-09-15 | 2024-03-21 | Alnylam Pharmaceuticals, Inc. | 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof |
WO2024075051A1 (en) | 2022-10-07 | 2024-04-11 | Pfizer Inc. | Hsd17b13 inhibitors and/or degraders |
WO2024084360A1 (en) | 2022-10-18 | 2024-04-25 | Pfizer Inc. | Patatin-like phospholipase domain-containing protein 3 (pnpla3) modifiers |
US20240182468A1 (en) | 2022-10-18 | 2024-06-06 | Pfizer Inc. | Compounds for the activation of ampk |
WO2024084363A1 (en) | 2022-10-18 | 2024-04-25 | Pfizer Inc. | Use of patatin-like phospholipase domain-containing protein 3 compounds |
WO2024084052A1 (en) | 2022-10-21 | 2024-04-25 | Novimmune Sa | Pd-l1xcd28 bispecific antibodies for immune checkpoint-dependent t cell activation |
GB202216284D0 (en) | 2022-11-02 | 2022-12-14 | Ucl Business Ltd | Self-regulation |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0072111A1 (en) * | 1981-07-20 | 1983-02-16 | Lipid Specialties, Inc. | Synthetic phospholipid compounds and their preparation |
EP0118316A2 (en) * | 1983-03-07 | 1984-09-12 | Lipid Specialties, Inc. | Synthetic phospholipid compounds, their preparation and use |
GB2185397A (en) * | 1986-01-17 | 1987-07-22 | Cosmas Damian Ltd | Drug delivery system |
WO1988004924A1 (en) * | 1986-12-24 | 1988-07-14 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
EP0354855A2 (en) * | 1988-08-11 | 1990-02-14 | Terumo Kabushiki Kaisha | Liposomes on which adsorption of proteins is inhibited |
WO1990004384A1 (en) * | 1988-10-20 | 1990-05-03 | Royal Free Hospital School Of Medicine | Liposomes |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3993754A (en) * | 1974-10-09 | 1976-11-23 | The United States Of America As Represented By The United States Energy Research And Development Administration | Liposome-encapsulated actinomycin for cancer chemotherapy |
US4501728A (en) * | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
JPS60100516A (en) * | 1983-11-04 | 1985-06-04 | Takeda Chem Ind Ltd | Preparation of sustained release microcapsule |
US4885172A (en) * | 1985-06-26 | 1989-12-05 | The Liposome Company, Inc. | Composition for targeting, storing and loading of liposomes |
IE58981B1 (en) * | 1985-10-15 | 1993-12-15 | Vestar Inc | Anthracycline antineoplastic agents encapsulated in phospholipid micellular particles |
US4797285A (en) * | 1985-12-06 | 1989-01-10 | Yissum Research And Development Company Of The Hebrew University Of Jerusalem | Lipsome/anthraquinone drug composition and method |
US4837028A (en) * | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US4863739A (en) * | 1987-05-19 | 1989-09-05 | Board Of Regents, The University Of Texas System | Liposome compositions of anthracycline derivatives |
JPH0696636B2 (en) * | 1988-03-30 | 1994-11-30 | 富士写真フイルム株式会社 | 2,4-bis (o-methoxypolyethylene glycol) -6-cholesteryl-S-triazine compound |
AU616040B2 (en) * | 1988-08-11 | 1991-10-17 | Terumo Kabushiki Kaisha | Agents for inhibiting adsorption of proteins on the liposome surface |
US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
-
1989
- 1989-10-20 US US07/425,224 patent/US5013556A/en not_active Expired - Lifetime
-
1990
- 1990-10-19 CA CA002067178A patent/CA2067178C/en not_active Expired - Lifetime
- 1990-10-19 DK DK91900513.2T patent/DK0496835T3/en active
- 1990-10-19 KR KR1019920700918A patent/KR0134982B1/en not_active IP Right Cessation
- 1990-10-19 WO PCT/US1990/006034 patent/WO1991005545A1/en not_active Application Discontinuation
- 1990-10-19 WO PCT/US1990/006211 patent/WO1991005546A1/en active IP Right Grant
- 1990-10-19 CA CA002067133A patent/CA2067133C/en not_active Expired - Lifetime
- 1990-10-19 KR KR1019920700919A patent/KR920703013A/en not_active Application Discontinuation
- 1990-10-19 DE DE19675048C patent/DE19675048I2/en active Active
- 1990-10-19 AU AU68982/91A patent/AU654120B2/en not_active Expired
- 1990-10-19 DE DE69015207T patent/DE69015207T2/en not_active Revoked
- 1990-10-19 AU AU66374/90A patent/AU642679B2/en not_active Expired
- 1990-10-19 ES ES91900513T patent/ES2071976T3/en not_active Expired - Lifetime
- 1990-10-19 EP EP91900513A patent/EP0496835B1/en not_active Expired - Lifetime
- 1990-10-19 DE DE69019366T patent/DE69019366T2/en not_active Expired - Lifetime
- 1990-10-19 JP JP3501034A patent/JP2667051B2/en not_active Expired - Lifetime
- 1990-10-19 AT AT91900513T patent/ATE122229T1/en active
- 1990-10-19 JP JP51523890A patent/JP3571335B2/en not_active Expired - Fee Related
- 1990-10-19 EP EP90916409A patent/EP0496813B1/en not_active Revoked
- 1990-10-19 AT AT90916409T patent/ATE115401T1/en not_active IP Right Cessation
- 1990-10-21 IL IL9606990A patent/IL96069A/en not_active IP Right Cessation
- 1990-10-21 IL IL9607090A patent/IL96070A/en not_active IP Right Cessation
-
1991
- 1991-01-15 US US07/642,321 patent/US5213804A/en not_active Expired - Lifetime
-
1992
- 1992-03-27 NO NO92921213A patent/NO921213L/en unknown
- 1992-03-27 NO NO920996A patent/NO304637B1/en not_active IP Right Cessation
- 1992-04-21 FI FI921764A patent/FI105151B/en active Protection Beyond IP Right Term
- 1992-04-21 FI FI921763A patent/FI921763A0/en not_active Application Discontinuation
-
1995
- 1995-08-09 GR GR950402186T patent/GR3017060T3/en unknown
-
1996
- 1996-12-13 LU LU88854C patent/LU88854I2/en unknown
- 1996-12-18 NL NL960031C patent/NL960031I2/en unknown
-
1997
- 1997-02-05 HK HK14097A patent/HK14097A/en not_active IP Right Cessation
- 1997-03-17 JP JP9063661A patent/JP2889549B2/en not_active Expired - Lifetime
-
1999
- 1999-02-23 NO NO1999003C patent/NO1999003I1/en unknown
-
2001
- 2001-01-11 JP JP2001004291A patent/JP3921050B2/en not_active Expired - Fee Related
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0072111A1 (en) * | 1981-07-20 | 1983-02-16 | Lipid Specialties, Inc. | Synthetic phospholipid compounds and their preparation |
EP0118316A2 (en) * | 1983-03-07 | 1984-09-12 | Lipid Specialties, Inc. | Synthetic phospholipid compounds, their preparation and use |
GB2185397A (en) * | 1986-01-17 | 1987-07-22 | Cosmas Damian Ltd | Drug delivery system |
WO1988004924A1 (en) * | 1986-12-24 | 1988-07-14 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
EP0354855A2 (en) * | 1988-08-11 | 1990-02-14 | Terumo Kabushiki Kaisha | Liposomes on which adsorption of proteins is inhibited |
WO1990004384A1 (en) * | 1988-10-20 | 1990-05-03 | Royal Free Hospital School Of Medicine | Liposomes |
Non-Patent Citations (2)
Title |
---|
Derwent FIle Supplier WPIL, 1989, AN 89-335922 (46), Derwent Publications Ltd, (London, GB), & JP-A-1249798 (FUJI PHOTO FILM CO., LTD) 5 October 1989 * |
Patent Abstracts of Japan, vol. 13, no. 592 (C-671)(3940), 26 December 1989; & JP-A-1249717 (FUJI PHOTO FILM CO., LTD) 5 October 1989 * |
Cited By (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0526700A3 (en) * | 1991-05-23 | 1994-01-26 | Mitsubishi Chem Ind | |
WO1993019738A1 (en) * | 1992-03-27 | 1993-10-14 | Liposome Technology, Inc. | Method of treatment of infected tissues |
US5766572A (en) * | 1992-08-05 | 1998-06-16 | Meito Sangyo Kabushiki Kaisha | Water-soluble carboxypolysaccharide-magnetic iron oxide complex having a small particle diameter |
EP0656368A1 (en) * | 1992-08-05 | 1995-06-07 | Meito Sangyo Kabushiki Kaisha | Small-diameter composite composed of water-soluble carboxypolysaccharide and magnetic iron oxide |
EP0656368A4 (en) * | 1992-08-05 | 1996-05-08 | Meito Sangyo Kk | Small-diameter composite composed of water-soluble carboxypolysaccharide and magnetic iron oxide. |
US5556948A (en) * | 1993-01-22 | 1996-09-17 | Mitsubishi Chemical Corporation | Phospholipid derivatized with PEG bifunctional linker and liposome containing it |
US5686101A (en) * | 1993-01-22 | 1997-11-11 | Mitsubishi Chemical Corporation | Phospholipid derivative and liposome containing it |
WO1994022429A1 (en) * | 1993-03-31 | 1994-10-13 | Liposome Technology, Inc. | Solid-tumor treatment method |
EP1179340A2 (en) * | 1994-09-30 | 2002-02-13 | INEX Pharmaceutical Corp. | Compositions for the introduction of polyanionic materials into cells |
US5885613A (en) * | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
US5820873A (en) * | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
EP1179340A3 (en) * | 1994-09-30 | 2003-05-07 | INEX Pharmaceutical Corp. | Compositions for the introduction of polyanionic materials into cells |
WO1996034598A1 (en) * | 1995-05-03 | 1996-11-07 | Polymasc Pharmaceuticals Plc | Tissue entrapment |
US6673364B1 (en) | 1995-06-07 | 2004-01-06 | The University Of British Columbia | Liposome having an exchangeable component |
WO1998007409A1 (en) * | 1996-08-23 | 1998-02-26 | Sequus Pharmaceuticals, Inc. | Liposomes containing a cisplatin compound |
US5945122A (en) * | 1996-08-23 | 1999-08-31 | Sequus Pharmaceuticals, Inc. | Liposomes containing a cisplatin compound |
AU714992B2 (en) * | 1996-08-23 | 2000-01-13 | Alza Corporation | Liposomes containing a cisplatin compound |
US6126966A (en) * | 1996-08-23 | 2000-10-03 | Sequus Pharmaceuticals, Inc. | Liposomes containing a cisplatin compound |
US5882679A (en) * | 1997-02-06 | 1999-03-16 | Duke University | Liposomes containing active agents aggregated with lipid surfactants |
US6296870B1 (en) | 1997-02-06 | 2001-10-02 | Duke University | Liposomes containing active agents |
US5827533A (en) * | 1997-02-06 | 1998-10-27 | Duke University | Liposomes containing active agents aggregated with lipid surfactants |
US6734171B1 (en) | 1997-10-10 | 2004-05-11 | Inex Pharmaceuticals Corp. | Methods for encapsulating nucleic acids in lipid bilayers |
WO1999027908A1 (en) * | 1997-12-04 | 1999-06-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
WO2000067760A1 (en) * | 1999-05-11 | 2000-11-16 | Sankyo Company, Limited | Liposome preparation of fat-soluble antitumor drug |
WO2001011069A1 (en) | 1999-08-06 | 2001-02-15 | Celltech R&D Limited | Freeze/thawed lipid complexes and their preparation |
WO2001041738A2 (en) * | 1999-12-10 | 2001-06-14 | Celator Technologies Inc. | Lipid carrier compositions with protected surface reactive functions |
WO2001041738A3 (en) * | 1999-12-10 | 2001-11-29 | Celator Technologies Inc | Lipid carrier compositions with protected surface reactive functions |
WO2004019913A1 (en) * | 2002-08-29 | 2004-03-11 | Monte Verde S.A. | A pharmaceutical composition of small-sized liposomes and method of preparation |
EP2535347A1 (en) * | 2002-09-30 | 2012-12-19 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
EP1435231A1 (en) * | 2002-12-31 | 2004-07-07 | Bharat Serums & Vaccines Ltd. | Non-pegylated long-circulating liposomes |
WO2004063216A1 (en) * | 2003-01-10 | 2004-07-29 | Yamanouchi Pharmaceutical Co., Ltd. | Conjugate for retention in blood and cancer tissue-specific drug delivery |
US7169892B2 (en) | 2003-01-10 | 2007-01-30 | Astellas Pharma Inc. | Lipid-peptide-polymer conjugates for long blood circulation and tumor specific drug delivery systems |
US8895557B2 (en) | 2004-10-29 | 2014-11-25 | Pharma Mar, S.A., Sociedad Unipersonal | Pharmaceutical formulations of ecteinascidin compounds |
US10322183B2 (en) | 2004-10-29 | 2019-06-18 | Pharma Mar, S.A., Sociedad Unipersonal | Pharmaceutical formulations of ecteinascidin compounds |
EP2382996A2 (en) | 2005-02-18 | 2011-11-02 | The University of Tokushima | Lipid Film Structure Containing a Polyoxyalkylene Chain-Containing Lipid Derivative. |
US9192568B2 (en) | 2005-10-31 | 2015-11-24 | Pharma Mar, S.A. | Formulations comprising jorumycin-, renieramycin-, safracin- or saframycin-related compounds for treating proliferative diseases |
US8926955B2 (en) | 2008-12-22 | 2015-01-06 | Creabilis S.A. | Synthesis of polymer conjugates of indolocarbazole compounds |
EP2522366A4 (en) * | 2010-01-08 | 2016-06-15 | Fujifilm Corp | Targeting agent for tumor site |
US8961929B2 (en) | 2010-01-08 | 2015-02-24 | Fujifilm Corporation | Targeting agent for tumor site |
US9566238B2 (en) | 2010-06-19 | 2017-02-14 | Western University Of Health Sciences | Formulation of PEGylated-liposome encapsulated glycopeptide antibiotics |
US11633502B2 (en) | 2016-03-07 | 2023-04-25 | Memorial Sloan Kettering Cancer Center | Bone marrow-, reticuloendothelial system-, and/or lymph node-targeted radiolabeled liposomes and methods of their diagnostic and therapeutic use |
WO2020055929A1 (en) * | 2018-09-11 | 2020-03-19 | Memorial Sloan Kettering Cancer Center | Bone marrow-, reticuloendothelial system-, and/or lymph node-targeted radiolabeled liposomes and methods of their diagnostic and therapeutic use |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU654120B2 (en) | Solid tumor treatment method and composition | |
EP0662820B1 (en) | Compositions for treatmewnt of inflamed tissues | |
EP0632719B1 (en) | Method of treatment of infected tissues | |
US5225212A (en) | Microreservoir liposome composition and method | |
AU718460B2 (en) | Ionophore-mediated liposome loading of weakly basic drug | |
DE60122304T2 (en) | LIPIDEN BASED SYSTEM FOR TARGETED ADMINISTRATION OF DIAGNOSTIC ACTIVE SUBSTANCES | |
IE58981B1 (en) | Anthracycline antineoplastic agents encapsulated in phospholipid micellular particles | |
JP2012122075A (en) | Cationic peg-lipid and method of use | |
EP0699068A1 (en) | Reduction of liposome-induced adverse physiological reactions | |
US20030113369A1 (en) | Liposomes with enhanced circulation time and method of treatment | |
CA2559800A1 (en) | Drug delivery system based on immune response system | |
US20010051183A1 (en) | Liposomes with enhanced circulation time and method of treatment |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA FI JP KR NO |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LU NL SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2067178 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 921764 Country of ref document: FI |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1991900513 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1991900513 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 1991900513 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 921764 Country of ref document: FI |