DE69922189T2 - Pharmazeutische zusammensetzungen enthaltend faktor viii und neutrale liposomen - Google Patents
Pharmazeutische zusammensetzungen enthaltend faktor viii und neutrale liposomen Download PDFInfo
- Publication number
- DE69922189T2 DE69922189T2 DE69922189T DE69922189T DE69922189T2 DE 69922189 T2 DE69922189 T2 DE 69922189T2 DE 69922189 T DE69922189 T DE 69922189T DE 69922189 T DE69922189 T DE 69922189T DE 69922189 T2 DE69922189 T2 DE 69922189T2
- Authority
- DE
- Germany
- Prior art keywords
- fviii
- pharmaceutical composition
- composition according
- particles
- colloidal particles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229960000301 factor viii Drugs 0.000 title claims abstract description 115
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
- 230000007935 neutral effect Effects 0.000 title claims abstract description 10
- 239000002502 liposome Substances 0.000 title description 54
- 102000001690 Factor VIII Human genes 0.000 claims abstract description 117
- 108010054218 Factor VIII Proteins 0.000 claims abstract description 117
- 239000002245 particle Substances 0.000 claims abstract description 42
- 150000002632 lipids Chemical class 0.000 claims abstract description 35
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 30
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 29
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 25
- 229920001184 polypeptide Polymers 0.000 claims abstract description 23
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 23
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 21
- 229920001477 hydrophilic polymer Polymers 0.000 claims abstract description 13
- 239000003112 inhibitor Substances 0.000 claims abstract description 11
- 238000007911 parenteral administration Methods 0.000 claims abstract description 6
- 150000003904 phospholipids Chemical class 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 14
- 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 claims description 12
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 9
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 9
- 208000009292 Hemophilia A Diseases 0.000 claims description 8
- 208000031220 Hemophilia Diseases 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 229940105778 coagulation factor viii Drugs 0.000 claims description 3
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 239000004633 polyglycolic acid Substances 0.000 claims 1
- 239000004626 polylactic acid Substances 0.000 claims 1
- 210000002966 serum Anatomy 0.000 abstract description 3
- 239000000969 carrier Substances 0.000 abstract 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 39
- 102000057593 human F8 Human genes 0.000 description 36
- 241000699670 Mus sp. Species 0.000 description 33
- 230000000694 effects Effects 0.000 description 32
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 28
- 229940047434 kogenate Drugs 0.000 description 27
- 239000007924 injection Substances 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
- 238000003556 assay Methods 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 8
- 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 6
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 6
- 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 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229920000515 polycarbonate Polymers 0.000 description 5
- 239000004417 polycarbonate Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000013459 approach Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 102100026735 Coagulation factor VIII Human genes 0.000 description 3
- 206010053567 Coagulopathies Diseases 0.000 description 3
- 108010074860 Factor Xa Proteins 0.000 description 3
- 229940087168 alpha tocopherol Drugs 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 238000007820 coagulation assay Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960000984 tocofersolan Drugs 0.000 description 3
- 239000002076 α-tocopherol Substances 0.000 description 3
- 235000004835 α-tocopherol Nutrition 0.000 description 3
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 201000003542 Factor VIII deficiency Diseases 0.000 description 2
- 108010014173 Factor X Proteins 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 102100027378 Prothrombin Human genes 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229940039716 prothrombin Drugs 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 210000003462 vein Anatomy 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 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 101001082397 Human adenovirus B serotype 3 Hexon-associated protein Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101001120093 Pseudoalteromonas phage PM2 Protein P8 Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- -1 activated imidazole compound Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical group ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000018592 inherited blood coagulation disease Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
-
- 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—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL12422498 | 1998-04-27 | ||
| IL12422498 | 1998-04-27 | ||
| PCT/IL1999/000217 WO1999055306A1 (en) | 1998-04-27 | 1999-04-23 | Pharmaceutical composition comprising factor viii and neutral liposomes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69922189D1 DE69922189D1 (de) | 2004-12-30 |
| DE69922189T2 true DE69922189T2 (de) | 2005-11-10 |
Family
ID=11071435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69922189T Expired - Lifetime DE69922189T2 (de) | 1998-04-27 | 1999-04-23 | Pharmazeutische zusammensetzungen enthaltend faktor viii und neutrale liposomen |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6593294B1 (enExample) |
| EP (1) | EP1079805B1 (enExample) |
| JP (1) | JP4545928B2 (enExample) |
| AT (1) | ATE283034T1 (enExample) |
| AU (1) | AU747391B2 (enExample) |
| BR (1) | BR9909978A (enExample) |
| CA (1) | CA2329768C (enExample) |
| DE (1) | DE69922189T2 (enExample) |
| ES (1) | ES2233036T3 (enExample) |
| MX (1) | MXPA00010241A (enExample) |
| PT (1) | PT1079805E (enExample) |
| WO (1) | WO1999055306A1 (enExample) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US20020132982A1 (en) * | 2000-11-30 | 2002-09-19 | Balasubramanian Sathyamangalam V. | AHF associated dispersion system and method for preparation |
| 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 |
| US7718160B2 (en) * | 2002-07-02 | 2010-05-18 | The Board Of Regents Of The University Of Texas System | Radiolabeled compounds and liposomes and their method of making and using same |
| US7351688B2 (en) * | 2003-02-05 | 2008-04-01 | The Research Foundation Of State University Of New York | Compositions and methods for less immunogenic protein formulations |
| DE602004013769D1 (de) * | 2003-04-15 | 2008-06-26 | Opperbas Holding Bv | Pharmazeutische zusammensetzung, enthaltend proteine und/oder polypeptide sowie kolloidpartikel |
| US20050069578A1 (en) * | 2003-08-05 | 2005-03-31 | Balasubramanian Sathyamangalam V. | Reconstitution medium for protein and peptide formulations |
| US20070003607A1 (en) * | 2003-09-02 | 2007-01-04 | Vibhudutta Awasthi | Neutral liposome-encapsulated compounds and methods of making and using thereof |
| US7208174B2 (en) * | 2003-12-18 | 2007-04-24 | Hoffmann-La Roche Inc. | Liposome compositions |
| JP4966018B2 (ja) * | 2004-01-23 | 2012-07-04 | カムルス エービー | 三元非ラメラ脂質組成物 |
| SI1824988T1 (sl) | 2004-11-12 | 2017-11-30 | Bayer Healthcare Llc | Usmerjena modifikacija FVIII |
| US8895717B2 (en) * | 2005-04-15 | 2014-11-25 | The Board Of Regents Of The University Of Texas System | Delivery of siRNA by neutral lipid compositions |
| JP2008544990A (ja) * | 2005-06-29 | 2008-12-11 | ザ リサーチ ファウンデイション オブ ステイト ユニバーシティー オブ ニューヨーク | 低免疫原性蛋白質−脂質複合体に関する組成物および方法 |
| WO2007021822A2 (en) | 2005-08-09 | 2007-02-22 | The Research Foundation Of State Of University Of New York At Buffalo | Compositions and methods of preparation of liposomal microparticulate il-12 |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| WO2007117469A2 (en) | 2006-03-30 | 2007-10-18 | The Research Foundation Of State University Of New York | Compositions of less immunogenic and long-circulating protein-lipid complexes |
| US7875288B2 (en) | 2006-03-30 | 2011-01-25 | The Research Foundation Of State University Of New York | Method for treating blood coagulation disorders |
| CN105838699A (zh) * | 2006-12-15 | 2016-08-10 | 巴克斯艾尔塔公司 | 具有延长的体内半衰期的因子VIIa-聚唾液酸结合物 |
| EP3231440A1 (en) | 2006-12-22 | 2017-10-18 | CSL Behring GmbH | Modified coagulation factors with prolonged in vivo half-life |
| CN103739712B (zh) | 2008-06-24 | 2016-10-05 | 德国杰特贝林生物制品有限公司 | 具有延长的体内半衰期的因子viii、冯·维勒布兰德因子或它们的复合物 |
| PL2299953T3 (pl) | 2008-07-14 | 2017-10-31 | Polypid Ltd | Kompozycja nośnika leku o przedłużonym uwalnianiu |
| WO2010135714A2 (en) | 2009-05-22 | 2010-11-25 | The Methodist Hospital Research Institute | Methods for modulating adipocyte expression using microrna compositions |
| IN2012DN00570A (enExample) | 2009-07-14 | 2015-06-12 | Polypid Ltd | |
| US10058837B2 (en) | 2009-08-28 | 2018-08-28 | The Trustees Of Columbia University In The City Of New York | Systems, methods, and devices for production of gas-filled microbubbles |
| WO2011084610A1 (en) | 2009-12-16 | 2011-07-14 | Children Medical Center Corporation | Liposomes for preventing the spread of hiv |
| EP2512588A4 (en) | 2009-12-16 | 2014-06-04 | Univ Columbia | METHODS, DEVICES AND SYSTEMS FOR ULTRASOUND-RELEASED ON-DEMAND AGGREGATE FREEZING |
| AU2011208374B2 (en) | 2010-01-19 | 2016-09-08 | Polypid Ltd. | Sustained-release nucleic acid matrix compositions |
| US8637448B2 (en) | 2010-09-14 | 2014-01-28 | University Of Rochester | Recombinant factor VIII having enhanced stability following mutation at the A1-C2 domain interface |
| DE102010043733A1 (de) | 2010-11-10 | 2012-05-10 | Oxprotect Gmbh | Unbeladene PEGylierte Liposomen zur Verwendung als Arzneimittel zur Prophylaxe und Therapie von hämorrhagischen und thrombo- embolischen Erkrankungen |
| ES2651523T3 (es) | 2012-02-15 | 2018-01-26 | Csl Behring Gmbh | Variantes del Factor de von Willebrand que tienen afinidad de unión al Factor VIII mejorada |
| DK2796145T3 (da) | 2013-04-22 | 2018-01-29 | Csl Ltd | Et kovalent kompleks af von Willebrand-faktor og faktor VIII linket af en disulfidbro |
| AU2015283822B2 (en) | 2014-07-02 | 2019-10-03 | CSL Behring Lengnau AG | Modified von willebrand factor |
| GB201417589D0 (en) | 2014-10-06 | 2014-11-19 | Cantab Biopharmaceuticals Patents Ltd | Pharmaceutical Formulations |
| DK3265483T3 (da) | 2015-03-06 | 2020-03-02 | CSL Behring Lengnau AG | Modificeret von Willebrand-faktor med forbedret halveringstid |
| SG11201708755WA (en) | 2015-05-22 | 2017-12-28 | Csl Behring Recombinant Facility Ag | Truncated von willebrand factor polypeptides for treating hemophilia |
| CN107810194B (zh) | 2015-05-22 | 2021-10-08 | 康诺贝林伦瑙有限公司 | 用于制备经修饰的血管性血友病因子的方法 |
| GB201518172D0 (en) | 2015-10-14 | 2015-11-25 | Cantab Biopharmaceuticals Patents Ltd | Colloidal particles for use in medicine |
| GB201518171D0 (en) | 2015-10-14 | 2015-11-25 | Cantab Biopharmaceuticals Patents Ltd | Colloidal particles for topical administration with therapeutic agent |
| GB201518170D0 (en) | 2015-10-14 | 2015-11-25 | Cantab Biopharmaceuticals Patents Ltd | Colloidal particles for subcutaneous administration with intravenous administration of therapeutic agent |
| SG10201912857XA (en) | 2016-01-07 | 2020-02-27 | CSL Behring Lengnau AG | Mutated von willebrand factor |
| SG11201805497QA (en) | 2016-01-07 | 2018-07-30 | Csl Behring Recombinant Facility Ag | Mutated truncated von willebrand factor |
| WO2017220099A1 (en) | 2016-06-24 | 2017-12-28 | Statens Serum Institut | Adjuvants with modified drainage properties |
| US11246832B2 (en) * | 2016-06-28 | 2022-02-15 | Verily Life Sciences Llc | Serial filtration to generate small cholesterol-containing liposomes |
| AU2017358865A1 (en) | 2016-11-11 | 2019-05-09 | CSL Behring Lengnau AG | Truncated von willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder |
| TW201828975A (zh) | 2016-11-11 | 2018-08-16 | 瑞士商Ｃｓｌ貝林重組技能公司 | 用於治療血友病之截短型類血友病因子（ｖｏｎ Ｗｉｌｌｅｂｒａｎｄ ｆａｃｔｏｒ）多肽類 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7900459A (nl) | 1979-01-19 | 1980-07-22 | Hendrik Coenraad Hemker Prof D | Farmaceutisch preparaat en werkwijze ter bereiding daarvan. |
| JPS56127307A (en) * | 1980-03-11 | 1981-10-06 | Green Cross Corp:The | Blood-coagulation factor 8 pharmaceutical for oral administration |
| US4348384A (en) | 1980-10-17 | 1982-09-07 | Dainippon Pharmaceutical Co., Ltd. | Pharmaceutical composition for oral administration containing coagulation factor VIII or IX |
| US5527528A (en) * | 1989-10-20 | 1996-06-18 | Sequus Pharmaceuticals, Inc. | Solid-tumor treatment method |
| US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| AU7217891A (en) * | 1990-02-13 | 1991-09-03 | Oxford Virology Plc | Therapeutic agents, and intermediates for the synthesis thereof |
| US6326353B1 (en) | 1993-03-23 | 2001-12-04 | Sequus Pharmaceuticals, Inc. | Enhanced circulation effector composition and method |
-
1999
- 1999-04-23 MX MXPA00010241A patent/MXPA00010241A/es active IP Right Grant
- 1999-04-23 US US09/673,412 patent/US6593294B1/en not_active Expired - Lifetime
- 1999-04-23 ES ES99916022T patent/ES2233036T3/es not_active Expired - Lifetime
- 1999-04-23 CA CA002329768A patent/CA2329768C/en not_active Expired - Fee Related
- 1999-04-23 BR BR9909978-0A patent/BR9909978A/pt not_active Application Discontinuation
- 1999-04-23 AU AU34414/99A patent/AU747391B2/en not_active Ceased
- 1999-04-23 AT AT99916022T patent/ATE283034T1/de active
- 1999-04-23 JP JP2000545506A patent/JP4545928B2/ja not_active Expired - Fee Related
- 1999-04-23 DE DE69922189T patent/DE69922189T2/de not_active Expired - Lifetime
- 1999-04-23 EP EP99916022A patent/EP1079805B1/en not_active Expired - Lifetime
- 1999-04-23 PT PT99916022T patent/PT1079805E/pt unknown
- 1999-04-23 WO PCT/IL1999/000217 patent/WO1999055306A1/en not_active Ceased
-
2002
- 2002-12-26 US US10/327,970 patent/US6930087B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69922189D1 (de) | 2004-12-30 |
| EP1079805B1 (en) | 2004-11-24 |
| EP1079805A1 (en) | 2001-03-07 |
| MXPA00010241A (es) | 2004-09-06 |
| AU3441499A (en) | 1999-11-16 |
| JP2002512947A (ja) | 2002-05-08 |
| ES2233036T3 (es) | 2005-06-01 |
| ATE283034T1 (de) | 2004-12-15 |
| PT1079805E (pt) | 2005-03-31 |
| WO1999055306A1 (en) | 1999-11-04 |
| JP4545928B2 (ja) | 2010-09-15 |
| CA2329768A1 (en) | 1999-11-04 |
| US6593294B1 (en) | 2003-07-15 |
| BR9909978A (pt) | 2000-12-26 |
| US20030134778A1 (en) | 2003-07-17 |
| AU747391B2 (en) | 2002-05-16 |
| US6930087B2 (en) | 2005-08-16 |
| CA2329768C (en) | 2008-06-10 |
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Owner name: ZILIP PHARMA B.V., ALKMAAR, NL |