CA2185859C - Preparation of virally inactivated intravenously injectable immune serum globulin - Google Patents
Preparation of virally inactivated intravenously injectable immune serum globulin Download PDFInfo
- Publication number
- CA2185859C CA2185859C CA2185859A CA2185859A CA2185859C CA 2185859 C CA2185859 C CA 2185859C CA 2185859 A CA2185859 A CA 2185859A CA 2185859 A CA2185859 A CA 2185859A CA 2185859 C CA2185859 C CA 2185859C
- Authority
- CA
- Canada
- Prior art keywords
- antibody solution
- aca
- antibody
- solution
- incubation
- 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
- 238000002360 preparation method Methods 0.000 title claims description 27
- 108010045362 Serum Globulins Proteins 0.000 title description 15
- 102000005686 Serum Globulins Human genes 0.000 title description 15
- 238000000034 method Methods 0.000 claims abstract description 74
- STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 claims abstract description 50
- 239000003599 detergent Substances 0.000 claims abstract description 35
- 230000003612 virological effect Effects 0.000 claims abstract description 30
- 230000000694 effects Effects 0.000 claims abstract description 28
- 230000002391 anti-complement effect Effects 0.000 claims abstract description 22
- 108010008730 anticomplement Proteins 0.000 claims abstract description 22
- 241000700605 Viruses Species 0.000 claims abstract description 15
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims description 26
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 6
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- 150000002632 lipids Chemical class 0.000 claims description 5
- 239000004471 Glycine Substances 0.000 claims description 4
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims 2
- 125000003071 maltose group Chemical group 0.000 claims 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims 1
- 229940068968 polysorbate 80 Drugs 0.000 claims 1
- 238000011534 incubation Methods 0.000 abstract description 54
- 230000002779 inactivation Effects 0.000 abstract description 31
- -1 sodium cholate Chemical compound 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 41
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 38
- 229940099352 cholate Drugs 0.000 description 37
- 230000008569 process Effects 0.000 description 34
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- 230000000295 complement effect Effects 0.000 description 14
- 239000007858 starting material Substances 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 230000009467 reduction Effects 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 239000012460 protein solution Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 108010074605 gamma-Globulins Proteins 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000010836 blood and blood product Substances 0.000 description 4
- 229940125691 blood product Drugs 0.000 description 4
- 238000013329 compounding Methods 0.000 description 4
- 238000005194 fractionation Methods 0.000 description 4
- 230000000521 hyperimmunizing effect Effects 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 241000710780 Bovine viral diarrhea virus 1 Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000001627 detrimental effect Effects 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000013101 initial test Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011026 diafiltration Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000001223 reverse osmosis Methods 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- 230000001256 tonic effect Effects 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 108010032597 Cohn fraction II Proteins 0.000 description 1
- 108010044316 Cohn fraction III Proteins 0.000 description 1
- 238000000665 Cohn process Methods 0.000 description 1
- 241001137251 Corvidae Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010006464 Hemolysin Proteins Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000003228 hemolysin Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 235000015108 pies Nutrition 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012420 spiking experiment Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000003253 viricidal 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
- A61L2/0088—Liquid substances
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/53211 | 1995-09-22 | ||
| US08/532,211 US6686191B1 (en) | 1995-09-22 | 1995-09-22 | Preparation of virally inactivated intravenously injectable immune serum globulin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2185859A1 CA2185859A1 (en) | 1997-03-23 |
| CA2185859C true CA2185859C (en) | 2011-04-19 |
Family
ID=24120836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2185859A Expired - Fee Related CA2185859C (en) | 1995-09-22 | 1996-09-18 | Preparation of virally inactivated intravenously injectable immune serum globulin |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6686191B1 (enExample) |
| EP (2) | EP1356829A3 (enExample) |
| JP (1) | JP4036494B2 (enExample) |
| AT (1) | ATE257016T1 (enExample) |
| AU (1) | AU709608B2 (enExample) |
| CA (1) | CA2185859C (enExample) |
| DE (1) | DE69631229T2 (enExample) |
| DK (1) | DK0764447T3 (enExample) |
| ES (1) | ES2213760T3 (enExample) |
| PT (1) | PT764447E (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998044948A2 (en) * | 1997-04-07 | 1998-10-15 | Cangene Corporation | Intravenous immune globulin formulation containing a non-ionic surface active agent with improved pharmacokinetic properties |
| AT405608B (de) * | 1997-04-08 | 1999-10-25 | Immuno Ag | Verfahren zur inaktivierung von pathogenen, insbesondere von viren, in einem biologischen material |
| BR9807936A (pt) | 1997-04-08 | 2000-02-22 | Baxter Ag | Preparação farmacêutica imuno-tolerante de complexo de pró-trombina, processo para a produção de uma preparação, e, utilização de uma preparação |
| US6717116B1 (en) * | 1999-08-10 | 2004-04-06 | Ibiden Co., Ltd. | Semiconductor production device ceramic plate |
| US8703126B2 (en) | 2000-10-12 | 2014-04-22 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| IL155002A0 (en) | 2000-10-12 | 2003-10-31 | Genentech Inc | Reduced-viscosity concentrated protein formulations |
| KR100791502B1 (ko) * | 2006-09-29 | 2008-01-03 | 한스바이오메드 주식회사 | 바이러스 불활화된 무세포 인체 이식재 생산방법 |
| EP2077118A1 (en) * | 2008-01-07 | 2009-07-08 | Gwo Rei Biomedical Technology Corp. | Clottable concentrate of platelet growth factors and preparation method thereof |
| TW201039854A (en) | 2009-03-06 | 2010-11-16 | Genentech Inc | Antibody formulation |
| LT3345615T (lt) | 2010-03-01 | 2020-02-10 | Bayer Healthcare Llc | Optimizuoti monokloniniai antikūnai prieš audinių faktoriaus kelio slopiklį (tfpi) |
| CN102357259A (zh) * | 2011-07-28 | 2012-02-22 | 王珊珊 | 一种生物蛋白海绵及其制备方法 |
| EP3981873A1 (en) | 2012-06-29 | 2022-04-13 | EMD Millipore Corporation | Methods for inactivating viruses during a protein purification process |
| US8613919B1 (en) | 2012-08-31 | 2013-12-24 | Bayer Healthcare, Llc | High concentration antibody and protein formulations |
| US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4396608A (en) * | 1981-08-24 | 1983-08-02 | Cutter Laboratories | Intravenously injectable immune serum globulin |
| US4540573A (en) * | 1983-07-14 | 1985-09-10 | New York Blood Center, Inc. | Undenatured virus-free biologically active protein derivatives |
| US4762714A (en) * | 1986-04-08 | 1988-08-09 | Miles Laboratories, Inc. | Preparation of retrovirus-free immunoglobulins |
| GB8628104D0 (en) * | 1986-11-25 | 1986-12-31 | Connaught Lab | Pasteurization of immunoglobin solutions |
| EP0523406B1 (en) * | 1991-07-05 | 1998-12-09 | Bayer Corporation | Use of tri(n-butyl) phosphate at low pH in solutions of biologically active proteins for enhanced virucidal activity |
-
1995
- 1995-09-22 US US08/532,211 patent/US6686191B1/en not_active Expired - Fee Related
-
1996
- 1996-09-10 ES ES96114439T patent/ES2213760T3/es not_active Expired - Lifetime
- 1996-09-10 EP EP03016677A patent/EP1356829A3/en not_active Withdrawn
- 1996-09-10 DK DK96114439T patent/DK0764447T3/da active
- 1996-09-10 EP EP96114439A patent/EP0764447B1/en not_active Expired - Lifetime
- 1996-09-10 AT AT96114439T patent/ATE257016T1/de active
- 1996-09-10 PT PT96114439T patent/PT764447E/pt unknown
- 1996-09-10 DE DE69631229T patent/DE69631229T2/de not_active Expired - Lifetime
- 1996-09-17 JP JP26508496A patent/JP4036494B2/ja not_active Expired - Lifetime
- 1996-09-18 AU AU65690/96A patent/AU709608B2/en not_active Expired
- 1996-09-18 CA CA2185859A patent/CA2185859C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1356829A2 (en) | 2003-10-29 |
| DE69631229T2 (de) | 2004-12-02 |
| EP0764447B1 (en) | 2004-01-02 |
| JP4036494B2 (ja) | 2008-01-23 |
| EP0764447A2 (en) | 1997-03-26 |
| ATE257016T1 (de) | 2004-01-15 |
| AU6569096A (en) | 1997-03-27 |
| AU709608B2 (en) | 1999-09-02 |
| EP1356829A3 (en) | 2003-12-17 |
| CA2185859A1 (en) | 1997-03-23 |
| EP0764447A3 (en) | 1997-07-30 |
| ES2213760T3 (es) | 2004-09-01 |
| PT764447E (pt) | 2004-04-30 |
| JPH09124507A (ja) | 1997-05-13 |
| US6686191B1 (en) | 2004-02-03 |
| DE69631229D1 (de) | 2004-02-05 |
| DK0764447T3 (da) | 2004-05-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150918 |