SI9300603B - Novi postopki za pridobivanje finasterida - Google Patents

Novi postopki za pridobivanje finasterida Download PDF

Info

Publication number: SI9300603B
Authority: SI; Slovenia
Prior art keywords: mixture; finasteride; water; solvent; organic solvent
Prior art date: 1992-11-19

Application number

SI9300603A

Other languages

English (en)

Slovenian (sl)

Other versions

SI9300603A (en

Inventor

Ulf H. Dolling

James A. Mccauley

Richard J. Varsalona

Original Assignee

Merck & Co., Inc.

Priority date (The priority date 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 date listed.)

1992-11-19

Filing date

1993-11-19

Publication date

2004-06-30

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26681536&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SI9300603(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1993-11-19 Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.

1994-06-30 Publication of SI9300603A publication Critical patent/SI9300603A/sl

2004-06-30 Publication of SI9300603B publication Critical patent/SI9300603B/sl

Links

DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 title claims abstract 12
229960004039 finasteride Drugs 0.000 title claims abstract 10
238000000034 method Methods 0.000 title claims abstract 9
238000004519 manufacturing process Methods 0.000 title abstract 2
239000003960 organic solvent Substances 0.000 claims abstract 7
238000010438 heat treatment Methods 0.000 claims abstract 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 10
239000000203 mixture Substances 0.000 claims 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 6
239000011877 solvent mixture Substances 0.000 claims 5
239000007787 solid Substances 0.000 claims 3
239000000126 substance Substances 0.000 claims 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 2
238000002425 crystallisation Methods 0.000 claims 2
230000008025 crystallization Effects 0.000 claims 2
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 2
229940011051 isopropyl acetate Drugs 0.000 claims 2
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 2
239000002904 solvent Substances 0.000 claims 2
229960000583 acetic acid Drugs 0.000 claims 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
239000012362 glacial acetic acid Substances 0.000 claims 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
-1 magnesium halide salt Chemical class 0.000 abstract 2
125000001931 aliphatic group Chemical group 0.000 abstract 1
150000004792 aryl magnesium halides Chemical class 0.000 abstract 1
150000002148 esters Chemical class 0.000 abstract 1
229910052749 magnesium Inorganic materials 0.000 abstract 1
239000011777 magnesium Substances 0.000 abstract 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 abstract 1

Classifications

- 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
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N5/00—Details of television systems
- H04N5/74—Projection arrangements for image reproduction, e.g. using eidophor
- H04N5/7416—Projection arrangements for image reproduction, e.g. using eidophor involving the use of a spatial light modulator, e.g. a light valve, controlled by a video signal
- H04N5/7458—Projection arrangements for image reproduction, e.g. using eidophor involving the use of a spatial light modulator, e.g. a light valve, controlled by a video signal the modulator being an array of deformable mirrors, e.g. digital micromirror device [DMD]

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Multimedia (AREA)
Signal Processing (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Dermatology (AREA)
Urology & Nephrology (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Confectionery (AREA)
Dental Preparations (AREA)
Seasonings (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

SI9300603A 1992-11-19 1993-11-19 Novi postopki za pridobivanje finasterida SI9300603B (sl)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US97853592A	1992-11-19	1992-11-19
US08/010,734 US5468860A (en)	1992-11-19	1993-01-29	New finasteride processes

Publications (2)

Publication Number	Publication Date
SI9300603A SI9300603A (en)	1994-06-30
SI9300603B true SI9300603B (sl)	2004-06-30

Family

ID=26681536

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SI9300603A SI9300603B (sl)	1992-11-19	1993-11-19	Novi postopki za pridobivanje finasterida

Country Status (33)

Country	Link
US (3)	US5468860A (is)
EP (3)	EP0599376B2 (is)
JP (2)	JPH07110875B2 (is)
CN (1)	CN1058018C (is)
AT (2)	ATE177112T1 (is)
AU (1)	AU658774B2 (is)
BG (2)	BG62362B1 (is)
CA (1)	CA2103107C (is)
CY (1)	CY2135B1 (is)
CZ (3)	CZ301160B6 (is)
DE (4)	DE69317856T2 (is)
DK (2)	DK0599376T4 (is)
DZ (1)	DZ1733A1 (is)
ES (2)	ES2052476T5 (is)
FI (4)	FI107450B (is)
GR (4)	GR940300045T1 (is)
HK (1)	HK1008338A1 (is)
HR (2)	HRP931410B1 (is)
HU (2)	HU216195B (is)
IL (1)	IL107574A (is)
IS (2)	IS1692B (is)
LV (2)	LV12212B (is)
MX (1)	MX9307222A (is)
MY (2)	MY110410A (is)
NO (3)	NO305912B1 (is)
PH (1)	PH31120A (is)
RO (2)	RO115164B1 (is)
RU (1)	RU2120445C1 (is)
SI (1)	SI9300603B (is)
SK (2)	SK286488B6 (is)
TW (1)	TW257766B (is)
UA (1)	UA41341C2 (is)
WO (1)	WO1994011387A2 (is)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5468860A (en) *	1992-11-19	1995-11-21	Merck & Co., Inc.	New finasteride processes
IT1270660B (it) *	1994-10-13	1997-05-07	Poli Ind Chimica Spa	Procedimento microbiologico per la preparazione di 3-oxo-4-azasteroidi-17beta-carbossi sostituiti e uso dei prodotti come inibitori dell'enzima 5alfa-riduttasi
US5670643A (en) *	1995-03-16	1997-09-23	Glaxo Wellcome Inc.	Method for preparing finasteride
US5585383A (en) *	1995-05-03	1996-12-17	Merck & Co., Inc.	Process for crystallizing a 4-azasteroid 5alpha-reductase inhibitor
WO1997010217A1 (en) *	1995-09-15	1997-03-20	Merck & Co., Inc.	4-azasteroids for treatment of hyperandrogenic conditions
GB2338234B (en) *	1998-06-10	2000-05-03	Torcan Chemical Ltd	Preparation of finasteride
ES2153789B1 (es) *	1999-07-05	2001-10-16	Raga Consultores S L	Procedimiento para la obtencion de 178-(n-terc-butlcarbamoil)-3-ona-4-aza-esteroides
EP1228084A1 (en) *	1999-11-01	2002-08-07	TORCAN CHEMICAL Ltd	Production of polymorphic forms i and ii of finasteride by complexation with group i or ii metal salts
SK2732003A3 (en) *	2000-09-07	2004-01-08	Reddys Lab Ltd Dr	Novel polymorphic form of 17-beta-(N-ter.butyl carbamoyl)-4-aza- 5-alpha-androst-1-en-3-one and a process for preparing it
MXPA03002031A (es) *	2000-09-07	2004-12-13	Reddys Lab Ltd Dr	Forma polimorfica novedosa de 17-beta-(n-tercbutil carbamoil)-4-aza-5-alfa-androst-1-en-3-ona y proceso para preparar la misma.
NZ525116A (en) *	2000-09-07	2004-11-26	Dr	Novel polymorphic form of 17- beta -(N-ter.butyl carbamoyl)-4-AZA-5- alpha -androst-1-en-3-one and a process for preparing it
KR100415858B1 (ko) *	2001-09-22	2004-01-24	한미약품 주식회사	17베타-(엔-3차-부틸카바모일)-3-온 스테로이드 화합물의제조방법
CN100428897C (zh) *	2002-08-16	2008-10-29	浙江寿峰堂生物工程有限公司	抗疲劳改善亚健康的保健食品及其制备方法
ES2206065B1 (es) *	2002-10-31	2005-08-16	Ragactives, S.L.	Procedimiento para la obtencion de la forma polimorfica i de finasterida.
WO2004083230A1 (en) *	2003-03-19	2004-09-30	Hetero Drugs Limited	Novel crystalline forms of finasteride
ATE406376T1 (de) *	2003-07-03	2008-09-15	Cipla Ltd	Verfahren zur herstellung von finasterid form i
US20050136015A1 (en) *	2003-12-17	2005-06-23	McKie Derrick B.	Topical use of halosalicylic acid derivatives
US20070167477A1 (en) *	2006-01-13	2007-07-19	Mandava Venkata Naga Brahmeswa	Processes to prepare finasteride polymorphs
US7531658B2 (en) *	2006-01-20	2009-05-12	Apotex Pharmachem Inc.	Process for the preparation of 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones
US7897800B2 (en)	2006-02-03	2011-03-01	Jr Chem, Llc	Chemical compositions and methods of making them
WO2007089267A1 (en)	2006-02-03	2007-08-09	Jr Chem, Llc	Anti-aging treatment using copper and zinc compositions
US7687650B2 (en)	2006-02-03	2010-03-30	Jr Chem, Llc	Chemical compositions and methods of making them
US7867522B2 (en)	2006-09-28	2011-01-11	Jr Chem, Llc	Method of wound/burn healing using copper-zinc compositions
US20090076058A1 (en) *	2007-09-17	2009-03-19	Protia, Llc	Deuterium-enriched finasteride
US8273791B2 (en)	2008-01-04	2012-09-25	Jr Chem, Llc	Compositions, kits and regimens for the treatment of skin, especially décolletage
US9004752B2 (en) *	2008-05-05	2015-04-14	Abbvie, Inc.	Method for evaluating the solubility of a crystalline substance in a polymer
CA2750636C (en)	2009-01-23	2017-07-25	Jr Chem, Llc	Rosacea treatments and kits for performing them
US8952057B2 (en)	2011-01-11	2015-02-10	Jr Chem, Llc	Compositions for anorectal use and methods for treating anorectal disorders

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ211145A (en) *	1984-02-27	1988-10-28	Merck & Co Inc	4-aza-5-alpha-androst-1-en-3-ones and pharmaceutical compositions
US4760071A (en) *	1984-02-27	1988-07-26	Merck & Co., Inc.	17β-N-monosubstituted carbamoyl-4-aza-5α-androst-1-en-3-ones which are active as testosterone 5α-reductase inhibitors
DE3888378T2 (de) *	1987-04-03	1994-09-29	Merck & Co Inc	Behandlung von Prostatacarcinoma mit 17-beta-n-monosubstituierten-Carbamoyl-4-aza-5-alpha-Androst-1-en-3-onen.
NZ225100A (en) *	1987-06-29	1991-09-25	Merck & Co Inc	Reaction of steroids (including 4-azasteroids) with a silylating agent in the presence of a quinone to introduce a delta' double bond and silylated intermediates
US5084574A (en) *	1988-04-18	1992-01-28	Merck & Co., Inc.	Dehydrogenation process
US5237061A (en) *	1988-10-31	1993-08-17	Merck & Co., Inc.	Methods of synthesizing benign prostatic hypertropic agents and their intermediates
US5021575A (en) *	1989-11-13	1991-06-04	Merck & Co., Inc.	Method for introducing a 1,2 double bond into azasteroids
EP0461930B1 (en) *	1990-06-15	1995-09-13	Merck & Co. Inc.	A crystallization method to improve crystal structure and size
EP0462662A3 (en) *	1990-06-20	1992-08-19	Merck & Co. Inc.	17beta-n-monosubstituted adamantyl/norbornanyl carbamoyl-4-aza-5alpha-androst-1-en-3-ones and androstan-3-ones
US5120847A (en) †	1990-08-27	1992-06-09	Merck & Co., Inc.	Process for iodinating or brominating the α-methylenic carbon of a secondary amide
US5091534A (en)	1990-08-27	1992-02-25	Merck & Co., Inc.	Trialkylsilyl trifluoromethanesulfonate mediated α-methylenic carbon functionalization of 4-AZA-5α-androstan-3-one steroids
CA2050824A1 (en) *	1990-09-24	1992-03-25	John M. Williams	Process for making 3-oxo-4-aza-androst-1-ene 17-.beta.-ketones
US5061801A (en) *	1990-09-24	1991-10-29	Merck & Co., Inc.	Intermediate for making 3-oxo-4-aza-androst-1-ene 17β-ketones
US5468860A (en) *	1992-11-19	1995-11-21	Merck & Co., Inc.	New finasteride processes

1993
- 1993-01-29 US US08/010,734 patent/US5468860A/en not_active Expired - Fee Related
- 1993-11-05 RO RO95-00940A patent/RO115164B1/ro unknown
- 1993-11-05 SK SK1897-2000A patent/SK286488B6/sk not_active IP Right Cessation
- 1993-11-05 UA UA95058438A patent/UA41341C2/uk unknown
- 1993-11-05 SK SK659-95A patent/SK281765B6/sk unknown
- 1993-11-05 WO PCT/US1993/010659 patent/WO1994011387A2/en active IP Right Grant
- 1993-11-05 CZ CZ20003685A patent/CZ301160B6/cs not_active IP Right Cessation
- 1993-11-05 CZ CZ19951268A patent/CZ287842B6/cs not_active IP Right Cessation
- 1993-11-05 RU RU95112521A patent/RU2120445C1/ru active
- 1993-11-05 CZ CZ20003686A patent/CZ301191B6/cs not_active IP Right Cessation
- 1993-11-05 RO RO99-00785A patent/RO115165B1/ro unknown
- 1993-11-05 IS IS4286A patent/IS1692B/is unknown
- 1993-11-05 US US08/411,685 patent/US5652365A/en not_active Expired - Lifetime
- 1993-11-11 MY MYPI93002365A patent/MY110410A/en unknown
- 1993-11-11 MY MYPI96001019A patent/MY110411A/en unknown
- 1993-11-11 IL IL10757493A patent/IL107574A/xx not_active IP Right Cessation
- 1993-11-11 TW TW082109464A patent/TW257766B/zh not_active IP Right Cessation
- 1993-11-12 DE DE69317856T patent/DE69317856T2/de not_active Expired - Lifetime
- 1993-11-12 EP EP93203163A patent/EP0599376B2/en not_active Expired - Lifetime
- 1993-11-12 EP EP95200270A patent/EP0655458B1/en not_active Expired - Lifetime
- 1993-11-12 ES ES93203163T patent/ES2052476T5/es not_active Expired - Lifetime
- 1993-11-12 DK DK93203163T patent/DK0599376T4/da active
- 1993-11-12 DE DE69323754T patent/DE69323754T2/de not_active Expired - Fee Related
- 1993-11-12 AT AT95200270T patent/ATE177112T1/de not_active IP Right Cessation
- 1993-11-12 EP EP97201712A patent/EP0823436A3/en not_active Withdrawn
- 1993-11-12 DK DK95200270T patent/DK0655458T3/da active
- 1993-11-12 DE DE0599376T patent/DE599376T1/de active Pending
- 1993-11-12 DE DE0655458T patent/DE655458T1/de active Pending
- 1993-11-12 AT AT93203163T patent/ATE164850T1/de active
- 1993-11-12 ES ES95200270T patent/ES2072848T3/es not_active Expired - Lifetime
- 1993-11-15 CA CA2103107A patent/CA2103107C/en not_active Expired - Lifetime
- 1993-11-16 IS IS4094A patent/IS1671B/is unknown
- 1993-11-17 DZ DZ930120A patent/DZ1733A1/fr active
- 1993-11-18 HU HU9303275A patent/HU216195B/hu unknown
- 1993-11-18 HR HR931410A patent/HRP931410B1/xx not_active IP Right Cessation
- 1993-11-18 AU AU50787/93A patent/AU658774B2/en not_active Expired
- 1993-11-18 JP JP5289536A patent/JPH07110875B2/ja not_active Expired - Fee Related
- 1993-11-18 MX MX9307222A patent/MX9307222A/es not_active IP Right Cessation
- 1993-11-19 PH PH47298A patent/PH31120A/en unknown
- 1993-11-19 CN CN93114530A patent/CN1058018C/zh not_active Expired - Lifetime
- 1993-11-19 SI SI9300603A patent/SI9300603B/sl unknown
1994
- 1994-07-29 GR GR940300045T patent/GR940300045T1/el unknown
- 1994-11-07 HU HU94P/P00041P patent/HU210535A9/hu unknown
1995
- 1995-05-16 BG BG99637A patent/BG62362B1/bg unknown
- 1995-05-18 FI FI952422A patent/FI107450B/fi not_active IP Right Cessation
- 1995-05-19 NO NO951986A patent/NO305912B1/no not_active IP Right Cessation
- 1995-07-31 GR GR950300043T patent/GR950300043T1/el unknown
1996
- 1996-09-30 JP JP8259373A patent/JP2742409B2/ja not_active Expired - Lifetime
1997
- 1997-03-26 US US08/824,426 patent/US5886184A/en not_active Expired - Lifetime
1998
- 1998-04-09 GR GR980400749T patent/GR3026577T3/el unknown
- 1998-07-21 HK HK98109309A patent/HK1008338A1/xx not_active IP Right Cessation
- 1998-10-26 LV LVP-98-236A patent/LV12212B/en unknown
1999
- 1999-02-01 NO NO19990468A patent/NO307888B3/no not_active IP Right Cessation
- 1999-02-11 BG BG103170A patent/BG64464B1/bg unknown
- 1999-03-04 GR GR990400546T patent/GR3029554T3/el unknown
- 1999-05-28 NO NO992580A patent/NO307609B1/no not_active IP Right Cessation
- 1999-09-07 CY CY9900028A patent/CY2135B1/xx unknown
2000
- 2000-02-23 LV LVP-00-26A patent/LV12460B/en unknown
- 2000-05-12 HR HR20000295A patent/HRP20000295B1/xx not_active IP Right Cessation
2001
- 2001-02-15 FI FI20010289A patent/FI114800B/fi not_active IP Right Cessation
- 2001-02-15 FI FI20010290A patent/FI114215B/fi not_active IP Right Cessation
2004
- 2004-04-21 FI FI20040559A patent/FI116941B/fi not_active IP Right Cessation

Also Published As

Publication number	Publication date
ES2052476T5 (es)	2008-11-01
DZ1733A1 (fr)	2002-02-17
IS1671B (is)	1997-12-19
PH31120A (en)	1998-02-23
NO307888B1 (no)	2000-06-13
SK65995A3 (en)	1995-10-11
IS4286A (is)	1994-05-20
LV12460A (lv)	2000-04-20
NO990468D0 (no)	1999-02-01
CN1090583A (zh)	1994-08-10
SK286488B6 (sk)	2008-11-06
TW257766B (is)	1995-09-21
LV12212A (lv)	1999-01-20
RU95112521A (ru)	1997-02-10
CA2103107A1 (en)	1994-05-20
WO1994011387A3 (en)	1994-09-29
NO307609B1 (no)	2000-05-02
US5886184A (en)	1999-03-23
GR950300043T1 (en)	1995-07-31
EP0823436A3 (en)	1998-11-25
ES2052476T3 (es)	1998-06-16
NO990468L (no)	1995-05-19
JPH07110875B2 (ja)	1995-11-29
NO305912B1 (no)	1999-08-16
GR940300045T1 (en)	1994-07-29
ATE164850T1 (de)	1998-04-15
WO1994011387A2 (en)	1994-05-26
ES2072848T1 (es)	1995-08-01
HRP20000295A2 (en)	2000-08-31
GR3029554T3 (en)	1999-06-30
IL107574A0 (en)	1994-02-27
DK0599376T4 (da)	2008-07-28
BG99637A (bg)	1996-04-30
DE69323754T2 (de)	1999-10-07
EP0655458A2 (en)	1995-05-31
AU658774B2 (en)	1995-04-27
NO992580D0 (no)	1999-05-28
ATE177112T1 (de)	1999-03-15
HU216195B (hu)	1999-05-28
CZ287842B6 (en)	2001-02-14
NO951986D0 (no)	1995-05-19
CA2103107C (en)	2010-09-28
EP0655458A3 (en)	1996-07-10
US5652365A (en)	1997-07-29
EP0599376A2 (en)	1994-06-01
CY2135B1 (en)	2002-05-21
FI20040559A (fi)	2004-04-21
BG103170A (en)	1999-09-30
SK281765B6 (sk)	2001-07-10
DE69317856D1 (de)	1998-05-14
IS4094A (is)	1994-05-20
FI107450B (fi)	2001-08-15
HU210535A9 (en)	1995-04-28
BG62362B1 (bg)	1999-09-30
RU2120445C1 (ru)	1998-10-20
DE69317856T2 (de)	1998-11-05
EP0599376A3 (en)	1994-09-28
BG64464B1 (bg)	2005-03-31
LV12212B (en)	1999-03-20
FI114215B (fi)	2004-09-15
ES2072848T3 (es)	1999-05-01
JP2742409B2 (ja)	1998-04-22
GR3026577T3 (en)	1998-07-31
MY110411A (en)	1998-05-30
AU5078793A (en)	1994-06-16
CN1058018C (zh)	2000-11-01
DE655458T1 (de)	1995-11-30
EP0655458B1 (en)	1999-03-03
CZ301160B6 (cs)	2009-11-18
EP0599376B1 (en)	1998-04-08
JPH06199889A (ja)	1994-07-19
FI20010289A (fi)	2001-02-15
UA41341C2 (uk)	2001-09-17
RO115164B1 (ro)	1999-11-30
HK1008338A1 (en)	1999-05-07
DE69323754D1 (de)	1999-04-08
LV12460B (en)	2000-09-20
IL107574A (en)	2000-07-16
RO115165B1 (ro)	1999-11-30
MY110410A (en)	1998-05-30
CZ126895A3 (en)	1995-12-13
FI952422A (fi)	1995-05-18
MX9307222A (es)	1994-07-29
HRP931410B1 (en)	2000-06-30
NO951986L (no)	1995-05-19
CZ301191B6 (cs)	2009-12-02
ES2052476T1 (es)	1994-07-16
EP0823436A2 (en)	1998-02-11
SI9300603A (en)	1994-06-30
HRP20000295B1 (en)	2002-08-31
IS1692B (is)	1998-04-20
HUT66973A (en)	1995-01-30
EP0599376B2 (en)	2008-04-16
FI114800B (fi)	2004-12-31
FI116941B (fi)	2006-04-13
HRP931410A2 (en)	1996-06-30
HU9303275D0 (en)	1994-03-28
JPH09235294A (ja)	1997-09-09
US5468860A (en)	1995-11-21
FI952422A0 (fi)	1995-05-18
FI20010290A (fi)	2001-02-15
DK0655458T3 (da)	1999-09-27
DE599376T1 (de)	1994-12-08
NO307888B3 (no)	2000-06-13
NO992580L (no)	1995-05-19

Legal Events

Date

Code

Title

Description

2005-01-10

IF

Valid on the event date

2010-05-31

SP73

Change of data on owner

Owner name: MERCK SHARP & DOHME CORP.; US

Effective date: 20100330

2013-01-31