DE69225757T2 - Lyophilische monoklonale antikörperpräparationen - Google Patents
Lyophilische monoklonale antikörperpräparationenInfo
- Publication number
- DE69225757T2 DE69225757T2 DE69225757T DE69225757T DE69225757T2 DE 69225757 T2 DE69225757 T2 DE 69225757T2 DE 69225757 T DE69225757 T DE 69225757T DE 69225757 T DE69225757 T DE 69225757T DE 69225757 T2 DE69225757 T2 DE 69225757T2
- Authority
- DE
- Germany
- Prior art keywords
- freeze
- solution
- monoclonal antibodies
- gelatin
- monoclonal antibody
- 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 - Fee Related
Links
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- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 235000014705 isoleucine Nutrition 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012514 monoclonal antibody product Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 108010014241 oxypolygelatine Proteins 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 235000008729 phenylalanine Nutrition 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229960004109 potassium acetate Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- SHPKCSFVQGSAJU-SEPHDYHBSA-L potassium fumarate Chemical compound [K+].[K+].[O-]C(=O)\C=C\C([O-])=O SHPKCSFVQGSAJU-SEPHDYHBSA-L 0.000 description 1
- 235000019295 potassium fumarate Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229960004249 sodium acetate Drugs 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
- 229940039790 sodium oxalate Drugs 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000011426 transformation method Methods 0.000 description 1
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
- C07K16/1214—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Pseudomonadaceae (F)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4343191 | 1991-03-08 | ||
| PCT/JP1992/000226 WO1992015331A1 (en) | 1991-03-08 | 1992-02-28 | Lyophilized monoclonal antibody preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69225757D1 DE69225757D1 (de) | 1998-07-09 |
| DE69225757T2 true DE69225757T2 (de) | 1998-12-03 |
Family
ID=12663510
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69225757T Expired - Fee Related DE69225757T2 (de) | 1991-03-08 | 1992-02-28 | Lyophilische monoklonale antikörperpräparationen |
| DE69232617T Expired - Fee Related DE69232617T2 (de) | 1991-03-08 | 1992-02-28 | Gefriergetrocknete Zubereitung, die einen monoklonalen Antikörper enthält |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69232617T Expired - Fee Related DE69232617T2 (de) | 1991-03-08 | 1992-02-28 | Gefriergetrocknete Zubereitung, die einen monoklonalen Antikörper enthält |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5908826A (OSRAM) |
| EP (2) | EP0531539B1 (OSRAM) |
| JP (1) | JPH0565233A (OSRAM) |
| AU (1) | AU645187B2 (OSRAM) |
| CA (1) | CA2082169A1 (OSRAM) |
| DE (2) | DE69225757T2 (OSRAM) |
| DK (2) | DK0531539T3 (OSRAM) |
| FI (1) | FI924982A7 (OSRAM) |
| NO (1) | NO924279L (OSRAM) |
| WO (1) | WO1992015331A1 (OSRAM) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6800738B1 (en) | 1991-06-14 | 2004-10-05 | Genentech, Inc. | Method for making humanized antibodies |
| GB9122820D0 (en) * | 1991-10-28 | 1991-12-11 | Wellcome Found | Stabilised antibodies |
| JP2014148555A (ja) * | 1995-07-27 | 2014-08-21 | Genentech Inc | タンパク質の処方 |
| MX9800684A (es) * | 1995-07-27 | 1998-04-30 | Genentech Inc | Formulacion de proteinas liofilizadas isotonicas estables. |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| JP3624543B2 (ja) * | 1996-05-02 | 2005-03-02 | 東ソー株式会社 | 免疫反応試薬及びその製造方法 |
| EP0852951A1 (de) | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
| WO1999037329A1 (en) * | 1998-01-22 | 1999-07-29 | Astrazeneca Ab | Pharmaceutical formulation comprising an antibody and a citrate buffer |
| US6750330B1 (en) * | 1998-05-14 | 2004-06-15 | Ashley Davis | Lyophilized tubulins |
| JP4516711B2 (ja) * | 1999-12-28 | 2010-08-04 | 中外製薬株式会社 | 安定な抗体組成物及び注射製剤 |
| JP5490972B2 (ja) * | 2000-08-04 | 2014-05-14 | 中外製薬株式会社 | タンパク質注射製剤 |
| JP4340062B2 (ja) | 2000-10-12 | 2009-10-07 | ジェネンテック・インコーポレーテッド | 粘度の減少した濃縮タンパク質製剤 |
| US8703126B2 (en) | 2000-10-12 | 2014-04-22 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| GB0113179D0 (en) * | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
| US20030113316A1 (en) * | 2001-07-25 | 2003-06-19 | Kaisheva Elizabet A. | Stable lyophilized pharmaceutical formulation of IgG antibodies |
| US20040002451A1 (en) * | 2002-06-20 | 2004-01-01 | Bruce Kerwin | Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| EP2335725B1 (en) | 2003-04-04 | 2016-10-12 | Genentech, Inc. | High concentration antibody and protein formulations |
| ATE490787T1 (de) | 2003-07-15 | 2010-12-15 | Chugai Pharmaceutical Co Ltd | Produktion von igm durch transformierte zellen und verfahren zur quantifizierung dieser igm- produktion |
| US8496930B2 (en) * | 2003-10-01 | 2013-07-30 | Kyowa Hakko Kirin Co., Ltd | Method of stabilizing antibody and stabilized solution-type antibody preparation |
| JP4762717B2 (ja) * | 2003-10-09 | 2011-08-31 | 中外製薬株式会社 | ＩｇＭ高濃度安定化溶液 |
| EP1686137A4 (en) * | 2003-10-09 | 2009-10-28 | Chugai Pharmaceutical Co Ltd | PROCESS FOR STABILIZING PROTEIN SOLUTIONS |
| WO2005063291A1 (ja) * | 2003-12-25 | 2005-07-14 | Kirin Beer Kabushiki Kaisha | 抗体を含有する安定な水性医薬製剤 |
| CA2607663C (en) * | 2005-05-19 | 2014-08-12 | Amgen Inc. | Compositions and methods for increasing the stability of antibodies |
| ES2776657T3 (es) | 2005-06-14 | 2020-07-31 | Amgen Inc | Formulaciones de proteínas autotamponantes |
| WO2007074880A1 (ja) * | 2005-12-28 | 2007-07-05 | Chugai Seiyaku Kabushiki Kaisha | 抗体含有安定化製剤 |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| ES2827180T3 (es) * | 2006-10-06 | 2021-05-20 | Amgen Inc | Formulaciones de anticuerpos estables |
| US7705132B2 (en) * | 2006-10-20 | 2010-04-27 | Amgen Inc. | Stable polypeptide formulations |
| UA96473C2 (ru) * | 2007-03-22 | 2011-11-10 | Имклоун Ллк | Жидкая стойкая композиция, которая содержит антитело imc-а12 |
| JP5322405B2 (ja) * | 2007-06-07 | 2013-10-23 | 小林製薬株式会社 | タンパク質含有組成物 |
| SG174258A1 (en) | 2009-03-06 | 2011-10-28 | Genentech Inc | Antibody formulation |
| DK3345615T3 (da) | 2010-03-01 | 2020-01-20 | Bayer Healthcare Llc | Optimerede monoklonale antistoffer mod inhibitor af vævsfaktoraktiveringsvejen (tfpi) |
| WO2012028683A1 (en) | 2010-09-02 | 2012-03-08 | Novartis Ag | Antibody gel system for sustained drug delivery |
| KR20180129991A (ko) | 2010-11-05 | 2018-12-05 | 노파르티스 아게 | Ｉｌ-１７ 길항제를 사용한 류마티스성 관절염의 치료 방법 |
| HRP20161753T1 (hr) | 2010-11-11 | 2017-02-10 | Abbvie Biotechnology Ltd | Tekuće formulacije protutijela anti-tnf-alfa s visokom koncentracijom |
| JP2012158615A (ja) * | 2012-05-28 | 2012-08-23 | Kobayashi Pharmaceutical Co Ltd | 還元糖によるタンパク質変性を抑制する方法 |
| US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
| US8613919B1 (en) | 2012-08-31 | 2013-12-24 | Bayer Healthcare, Llc | High concentration antibody and protein formulations |
| WO2015185998A2 (en) | 2014-04-11 | 2015-12-10 | Acerta Pharma B.V. | Methods of blocking the cxcr-4/sdf-1 signaling pathway with inhibitors of bone marrow x kinase |
| WO2015181633A2 (en) | 2014-04-11 | 2015-12-03 | Acerta Pharma B.V. | Methods of blocking the cxcr-4/sdf-1 signaling pathway with inhibitors of bruton's tyrosine kinase |
| US20170231995A1 (en) | 2014-08-11 | 2017-08-17 | Acerta Pharma B.V. | BTK Inhibitors to Treat Solid Tumors Through Modulation of the Tumor Microenvironment |
| WO2016055982A1 (en) | 2014-10-10 | 2016-04-14 | Acerta Pharma B.V. | Quinoline and quinazoline compounds |
| WO2016087994A1 (en) | 2014-12-05 | 2016-06-09 | Acerta Pharma B.V. | Btk inhibitors to treat solid tumors through modulation of the tumor microenvironment |
| LT3334747T (lt) | 2015-08-13 | 2023-12-27 | Amgen Inc. | Įkrautas giluminis antigeną surišančio baltymo filtravimas |
| EP3371189A1 (en) | 2015-11-06 | 2018-09-12 | Acerta Pharma B.V. | Imidazopyrazine inhibitors of bruton's tyrosine kinase |
| US20240417445A1 (en) * | 2023-06-13 | 2024-12-19 | Grifols Worldwide Operations Limited | Method for producing a lyophilized composition comprising polyclonal igm and composition obtained |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2149304A (en) * | 1936-04-20 | 1939-03-07 | Sharp & Dohme Inc | Lyophilic biologically active substances |
| SU700132A1 (ru) * | 1978-06-30 | 1979-11-30 | Томский Ордена Трудового Красного Знамени Научно-Исследовательский Институт Вакцин И Сывороток | Способ получени сухого препарата иммуноглобулина |
| JPS57140724A (en) * | 1981-02-25 | 1982-08-31 | Green Cross Corp:The | Heat-treatment of aqueous solution containing cold insoluble globulin |
| JPS58167518A (ja) * | 1982-03-29 | 1983-10-03 | Nippon Sekijiyuujishiya | ゼラチン誘導体添加静注用人免疫グロブリンの製造法 |
| JPS6035263A (ja) * | 1983-08-05 | 1985-02-23 | Wako Pure Chem Ind Ltd | 不溶性担体に固定化された免疫活性物質の安定化法及び該物質を構成単位として含む生理活性物質測定用試薬 |
| JPS60146833A (ja) * | 1984-01-10 | 1985-08-02 | Green Cross Corp:The | モノクロ−ナル抗体製剤 |
| JP2565303B2 (ja) * | 1984-05-25 | 1996-12-18 | 三井東圧化学株式会社 | 緑膿菌感染症の予防治療剤 |
| US4650772A (en) * | 1984-08-09 | 1987-03-17 | Abbott Laboratories | Monoclonal antibody stabilization |
| JPH0669961B2 (ja) * | 1984-09-25 | 1994-09-07 | 株式会社ミドリ十字 | 免疫グロブリンの加熱処理方法 |
| JPS61176532A (ja) * | 1985-01-30 | 1986-08-08 | Green Cross Corp:The | プラスミノ−ゲンアクチベ−タ−前駆体の安定化方法 |
| JPH0825902B2 (ja) * | 1985-02-21 | 1996-03-13 | 株式会社ミドリ十字 | γ−グロブリンの加熱処理方法 |
| JPH0825903B2 (ja) * | 1985-05-16 | 1996-03-13 | 株式会社ミドリ十字 | γ―グロブリン含有水溶液 |
| JPS6178731A (ja) * | 1985-05-20 | 1986-04-22 | Green Cross Corp:The | 加熱処理免疫グロブリン製剤 |
| DE3619565A1 (de) * | 1986-06-11 | 1987-12-17 | Behringwerke Ag | Verfahren zur herstellung einer pasteurisierten immunglobulinpraeparation |
| JPS6388197A (ja) * | 1986-09-30 | 1988-04-19 | Tosoh Corp | モノクロナル抗体の安定化方法 |
| KR910004868B1 (ko) * | 1986-12-15 | 1991-07-15 | 미츠이 도아츠 가가쿠 가부시기가이샤 | 인체 단일 클론항체 및 그것을 활성성분으로 함유하는 감염증의 예방 및 치료용 약학적 제제 |
| ATE82136T1 (de) * | 1987-08-10 | 1992-11-15 | Miles Inc | Gereinigtes igm. |
| EP0417191B1 (en) * | 1988-05-27 | 1993-03-10 | Centocor, Inc. | Formulation for antibody reagents |
| EP0465513A1 (en) * | 1989-03-27 | 1992-01-15 | Centocor, Inc. | FORMULATIONS FOR STABILIZING OF IgM ANTIBODIES |
| JPH0384461A (ja) * | 1989-08-28 | 1991-04-10 | Green Cross Corp:The | 免疫学的凝集反応試薬及びその製法 |
| JPH0911350A (ja) * | 1995-06-30 | 1997-01-14 | Olympus Optical Co Ltd | エネルギー硬化型樹脂を用いた光学素子の製造方法 |
-
1992
- 1992-02-27 JP JP4041015A patent/JPH0565233A/ja active Pending
- 1992-02-28 EP EP92906211A patent/EP0531539B1/en not_active Expired - Lifetime
- 1992-02-28 DE DE69225757T patent/DE69225757T2/de not_active Expired - Fee Related
- 1992-02-28 DE DE69232617T patent/DE69232617T2/de not_active Expired - Fee Related
- 1992-02-28 DK DK92906211T patent/DK0531539T3/da active
- 1992-02-28 AU AU13375/92A patent/AU645187B2/en not_active Ceased
- 1992-02-28 DK DK97120255T patent/DK0841067T3/da active
- 1992-02-28 WO PCT/JP1992/000226 patent/WO1992015331A1/ja not_active Ceased
- 1992-02-28 EP EP97120255A patent/EP0841067B1/en not_active Revoked
- 1992-02-28 FI FI924982A patent/FI924982A7/fi not_active Application Discontinuation
- 1992-02-28 CA CA002082169A patent/CA2082169A1/en not_active Abandoned
- 1992-11-06 NO NO92924279A patent/NO924279L/no unknown
-
1994
- 1994-11-14 US US08/340,319 patent/US5908826A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| FI924982A0 (fi) | 1992-11-04 |
| NO924279D0 (no) | 1992-11-06 |
| CA2082169A1 (en) | 1992-09-09 |
| DE69225757D1 (de) | 1998-07-09 |
| JPH0565233A (ja) | 1993-03-19 |
| AU1337592A (en) | 1992-10-06 |
| EP0531539A1 (en) | 1993-03-17 |
| FI924982L (fi) | 1992-11-04 |
| DK0841067T3 (da) | 2002-07-15 |
| WO1992015331A1 (en) | 1992-09-17 |
| DK0531539T3 (da) | 1998-10-12 |
| DE69232617T2 (de) | 2002-10-31 |
| AU645187B2 (en) | 1994-01-06 |
| EP0841067B1 (en) | 2002-05-22 |
| EP0531539B1 (en) | 1998-06-03 |
| NO924279L (no) | 1992-11-06 |
| EP0531539A4 (OSRAM) | 1995-04-05 |
| DE69232617D1 (de) | 2002-06-27 |
| EP0841067A1 (en) | 1998-05-13 |
| FI924982A7 (fi) | 1992-11-04 |
| US5908826A (en) | 1999-06-01 |
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