MD20150126A2 - Letermovir amorf şi forme preparative farmaceutice solide ale acestuia pentru administrare orală - Google Patents
Letermovir amorf şi forme preparative farmaceutice solide ale acestuia pentru administrare orală Download PDFInfo
- Publication number
- MD20150126A2 MD20150126A2 MDA20150126A MD20150126A MD20150126A2 MD 20150126 A2 MD20150126 A2 MD 20150126A2 MD A20150126 A MDA20150126 A MD A20150126A MD 20150126 A MD20150126 A MD 20150126A MD 20150126 A2 MD20150126 A2 MD 20150126A2
- Authority
- MD
- Moldova
- Prior art keywords
- amorphous letermovir
- amorphous
- solid pharmaceutical
- pharmaceutical formulations
- immediate release
- Prior art date
Links
- FWYSMLBETOMXAG-QHCPKHFHSA-N letermovir Chemical compound COC1=CC=CC(N2CCN(CC2)C=2N([C@@H](CC(O)=O)C3=CC=CC(F)=C3N=2)C=2C(=CC=C(C=2)C(F)(F)F)OC)=C1 FWYSMLBETOMXAG-QHCPKHFHSA-N 0.000 title abstract 7
- 229950010668 letermovir Drugs 0.000 title abstract 7
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 239000007787 solid Substances 0.000 title abstract 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 abstract 3
- 238000001035 drying Methods 0.000 abstract 2
- 238000009472 formulation Methods 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 2
- 241000701022 Cytomegalovirus Species 0.000 abstract 1
- 241000700586 Herpesviridae Species 0.000 abstract 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 abstract 1
- 239000012296 anti-solvent Substances 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 239000003960 organic solvent Substances 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 238000011282 treatment Methods 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Biotechnology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Invenţia se referă la Letermovir amorf şi formele sale preparative farmaceutice solide, administrabile oral (formă preparativă cu eliberare imediată). Letermovirul amorf menţionat este obţinut prin izolarea dintr-o soluţie organică fie prin metoda uscării cu role a soluţiei organice respective într-un solvent organic volatil, în special acetonă, la o temperatură de 30...60°C, cu uscarea ulterioară a Letermovirului amorf obţinut, fie prin metoda izolării Letermovirului amorf menţionat prin precipitare din solvenţi miscibili cu apa, selectaţi din acetonă sau acetonitril, în exces de apă în calitate de antisolvent, cu filtrarea sau centrifugarea ulterioară a Letermovirului amorfobţinut.Formele preparative de Letermovir amorf cu eliberare imediată sunt destinate utilizării în metodele de profilaxie sau de tratament al bolilor asociate cu grupa Herpesviridae, preferabil asociate cu citomegalovirusul, mai preferabil asociate cu citomegalovirusul uman.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13003120 | 2013-06-19 | ||
| EP14165027 | 2014-04-16 | ||
| PCT/EP2014/062974 WO2014202737A1 (en) | 2013-06-19 | 2014-06-19 | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| MD20150126A2 true MD20150126A2 (ro) | 2016-06-30 |
| MD4673B1 MD4673B1 (ro) | 2020-02-29 |
| MD4673C1 MD4673C1 (ro) | 2020-11-30 |
Family
ID=50982905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MDA20150126A MD4673C1 (ro) | 2013-06-19 | 2014-06-19 | Letermovir amorf şi forme preparative farmaceutice solide ale acestuia pentru administrare orală |
Country Status (34)
| Country | Link |
|---|---|
| US (1) | US10442773B2 (ro) |
| EP (1) | EP3010891B1 (ro) |
| JP (2) | JP6445546B2 (ro) |
| KR (1) | KR101953270B1 (ro) |
| CN (2) | CN105555771B (ro) |
| AU (1) | AU2014283231B2 (ro) |
| BR (1) | BR112015031979B1 (ro) |
| CA (1) | CA2916143C (ro) |
| CU (1) | CU24619B1 (ro) |
| CY (1) | CY1121732T1 (ro) |
| DK (1) | DK3010891T3 (ro) |
| DO (1) | DOP2015000303A (ro) |
| EA (1) | EA036131B1 (ro) |
| ES (1) | ES2730958T3 (ro) |
| HR (1) | HRP20190936T1 (ro) |
| HU (1) | HUE043721T2 (ro) |
| IL (2) | IL243228B (ro) |
| LT (1) | LT3010891T (ro) |
| MD (1) | MD4673C1 (ro) |
| ME (1) | ME03483B (ro) |
| MX (1) | MX373764B (ro) |
| MY (1) | MY179502A (ro) |
| NZ (1) | NZ715387A (ro) |
| PE (1) | PE20160659A1 (ro) |
| PH (1) | PH12015502821B1 (ro) |
| PL (1) | PL3010891T3 (ro) |
| PT (1) | PT3010891T (ro) |
| RS (1) | RS58882B1 (ro) |
| SG (1) | SG11201510426PA (ro) |
| SI (1) | SI3010891T1 (ro) |
| SM (1) | SMT201900327T1 (ro) |
| UA (1) | UA117755C2 (ro) |
| WO (1) | WO2014202737A1 (ro) |
| ZA (1) | ZA201509239B (ro) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10319612A1 (de) | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE102012101673A1 (de) | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| US10442773B2 (en) * | 2013-06-19 | 2019-10-15 | Aicuris Anti-Infective Cures Gmbh | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
| CN109152787A (zh) | 2016-03-31 | 2019-01-04 | 英特塞普特医药品公司 | 具有优越的溶出性的口服制剂 |
| AU2020237505B2 (en) * | 2019-03-12 | 2023-02-02 | Microbiotix, Inc. | Combination drug treatment for human cytomegalovirus |
| CN111024861A (zh) * | 2019-12-31 | 2020-04-17 | 山东省药学科学院 | 一种莱特莫韦及含莱特莫韦的制剂中有关物质的检测方法 |
| EP3906929A1 (en) | 2020-05-08 | 2021-11-10 | AiCuris GmbH & Co. KG | Letermovir for use in the prevention and the treatment of coronavirus infections |
| US20230312485A1 (en) * | 2020-08-17 | 2023-10-05 | Lupin Limited | A precipitation process for amorphous letermovir |
| US20240041882A1 (en) * | 2020-12-16 | 2024-02-08 | Merck Sharp & Dohme Llc | Mini-tablet dosage form of a viral terminase inhibitor and uses thereof |
| CN115403528B (zh) * | 2021-05-27 | 2025-01-07 | 南京正大天晴制药有限公司 | 无定形3,4-二氢喹唑啉衍生物的制备方法 |
| CN114942278B (zh) * | 2022-04-12 | 2023-09-08 | 山东诚创蓝海医药科技有限公司 | 来特莫韦中间体二d-(+)-二对甲基苯甲酰酒石酸乙酸乙酯络合物有关物质的分析方法 |
| WO2024037485A1 (zh) * | 2022-08-15 | 2024-02-22 | 上海迪赛诺化学制药有限公司 | 一种来特莫韦无定形的制备方法 |
| CN116338119B (zh) * | 2023-02-24 | 2026-03-13 | 重庆希韦医药科技有限公司 | 一种来特莫韦包合物溶液体外释放度的测定方法 |
| WO2025133248A1 (en) | 2023-12-21 | 2025-06-26 | Aic246 Ag & Co. Kg | Diastereomeric aminoalcohol and aminoether salts of 2-[(4r,s)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl]acetic acid and their use for enantiomeric separation |
| JP2025161786A (ja) * | 2024-04-12 | 2025-10-24 | 東和薬品株式会社 | レテルモビル含有医薬組成物ならびにその製造方法および用途 |
| CN119745803A (zh) * | 2024-12-30 | 2025-04-04 | 上海奥科达医药科技股份有限公司 | 一种来特莫韦制剂组合物及其制备方法 |
| CN120927867B (zh) * | 2025-10-11 | 2026-01-06 | 成都诺和晟欣生物医药有限公司 | 一种来特莫韦注射液中对映异构体的hplc检测方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10207026A1 (de) * | 2002-02-20 | 2003-08-28 | Boehringer Ingelheim Kg | Pulverinhalativum, enthaltend den CGRP-Antagonisten BIBN4096 und Verfahren zu dessen Herstellung |
| DE10319612A1 (de) * | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE10305785A1 (de) * | 2003-02-12 | 2004-08-26 | Bayer Healthcare Ag | Dihydrochinazoline |
| DE10338402A1 (de) * | 2003-08-18 | 2005-03-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Sprühgetrocknetes, amorphes BIBN 4096, Verfahren zu dessen Herstellung sowie dessen Verwendung als Inhalativum |
| BRPI0607537A2 (pt) * | 2005-04-12 | 2009-09-15 | Elan Pharma Int Ltd | formulações de derivado de quinazolina nanoparticulado |
| DE102005027517A1 (de) | 2005-06-15 | 2006-12-21 | Bayer Healthcare Ag | Verfahren zur Herstellung von Dihydrochinazolinen |
| US20140044759A1 (en) * | 2011-05-04 | 2014-02-13 | Dimitrios Zarkadas | Drug substances, pharmaceutical compositions and methods for preparing the same |
| DE102012101680A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Pharmazeutische Zubereitung enthaltend ein antiviral wirksames Dihydrochinazolinderivat |
| DE102012101659A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| DE102012101673A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Salze eines Dihydrochinazolinderivats |
| WO2014047562A2 (en) * | 2012-09-21 | 2014-03-27 | Epiphany Biosciences | Method of treating and/or preventing shingles and method of treating and/or preventing zoster associated pain |
| US10442773B2 (en) * | 2013-06-19 | 2019-10-15 | Aicuris Anti-Infective Cures Gmbh | Amorphous letermovir and solid pharmaceutical formulations thereof for oral administration |
-
2014
- 2014-06-19 US US14/899,178 patent/US10442773B2/en active Active
- 2014-06-19 WO PCT/EP2014/062974 patent/WO2014202737A1/en not_active Ceased
- 2014-06-19 BR BR112015031979-3A patent/BR112015031979B1/pt active IP Right Grant
- 2014-06-19 SG SG11201510426PA patent/SG11201510426PA/en unknown
- 2014-06-19 DK DK14732545.0T patent/DK3010891T3/da active
- 2014-06-19 MD MDA20150126A patent/MD4673C1/ro active IP Right Grant
- 2014-06-19 EA EA201600024A patent/EA036131B1/ru unknown
- 2014-06-19 HR HRP20190936TT patent/HRP20190936T1/hr unknown
- 2014-06-19 JP JP2016520499A patent/JP6445546B2/ja active Active
- 2014-06-19 MY MYPI2015002983A patent/MY179502A/en unknown
- 2014-06-19 SM SM20190327T patent/SMT201900327T1/it unknown
- 2014-06-19 LT LTEP14732545.0T patent/LT3010891T/lt unknown
- 2014-06-19 HU HUE14732545A patent/HUE043721T2/hu unknown
- 2014-06-19 SI SI201431243T patent/SI3010891T1/sl unknown
- 2014-06-19 CN CN201480040969.XA patent/CN105555771B/zh active Active
- 2014-06-19 CU CU2015000179A patent/CU24619B1/es unknown
- 2014-06-19 NZ NZ715387A patent/NZ715387A/en unknown
- 2014-06-19 KR KR1020167001010A patent/KR101953270B1/ko active Active
- 2014-06-19 CN CN202510264255.7A patent/CN120097924A/zh active Pending
- 2014-06-19 ES ES14732545T patent/ES2730958T3/es active Active
- 2014-06-19 AU AU2014283231A patent/AU2014283231B2/en active Active
- 2014-06-19 PL PL14732545T patent/PL3010891T3/pl unknown
- 2014-06-19 MX MX2015017758A patent/MX373764B/es active IP Right Grant
- 2014-06-19 ME MEP-2019-149A patent/ME03483B/me unknown
- 2014-06-19 CA CA2916143A patent/CA2916143C/en active Active
- 2014-06-19 EP EP14732545.0A patent/EP3010891B1/en active Active
- 2014-06-19 PE PE2015002639A patent/PE20160659A1/es unknown
- 2014-06-19 RS RS20190686A patent/RS58882B1/sr unknown
- 2014-06-19 UA UAA201600339A patent/UA117755C2/uk unknown
- 2014-06-19 PT PT14732545T patent/PT3010891T/pt unknown
-
2015
- 2015-12-18 DO DO2015000303A patent/DOP2015000303A/es unknown
- 2015-12-18 ZA ZA2015/09239A patent/ZA201509239B/en unknown
- 2015-12-18 PH PH12015502821A patent/PH12015502821B1/en unknown
- 2015-12-20 IL IL243228A patent/IL243228B/en active IP Right Grant
-
2018
- 2018-09-07 JP JP2018168220A patent/JP6770035B2/ja active Active
- 2018-12-26 IL IL263978A patent/IL263978B/en active IP Right Grant
-
2019
- 2019-06-11 CY CY20191100607T patent/CY1121732T1/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG4A | Patent for invention issued | ||
| PD4A | Change of proprietorship (patent for invention) |
Owner name: AIC246 GMBH & CO. KG, DE FRIEDRICH-EBERT-STR. 475, 42117 WUPPERTAL, GERMANIA Free format text: PREVIOUS PROPRIETOR: AICURIS ANTI-INFECTIVE CURES GMBH, DE FRIEDRICH-EBERT-STR. 475, 42117 WUPPERTAL, GERMANIA |
|
| TC4A | Change of name of proprietor (patent for invention) |
Owner name: AIC246 AG & CO. KG, DE FRIEDRICH-EBERT-STR. 475, 42117 WUPPERTAL, GERMANIA Free format text: PREVIOUS NAME OF PROPRIETOR: AIC246 GMBH & CO. KG, DE FRIEDRICH-EBERT-STR. 475, 42117 WUPPERTAL, GERMANIA |