AU2012299218A1 - Crystal forms of a HCV protease inhibitor - Google Patents
Crystal forms of a HCV protease inhibitor Download PDFInfo
- Publication number
- AU2012299218A1 AU2012299218A1 AU2012299218A AU2012299218A AU2012299218A1 AU 2012299218 A1 AU2012299218 A1 AU 2012299218A1 AU 2012299218 A AU2012299218 A AU 2012299218A AU 2012299218 A AU2012299218 A AU 2012299218A AU 2012299218 A1 AU2012299218 A1 AU 2012299218A1
- Authority
- AU
- Australia
- Prior art keywords
- hydrate
- compound
- diffraction pattern
- radiation
- powder diffraction
- 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.)
- Abandoned
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C35/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic
- C07C35/04—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic containing a three or four-membered rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/32—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C271/34—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/013—Esters of alcohols having the esterified hydroxy group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/16—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
- C07K5/126—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Cephalosporin Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161525462P | 2011-08-19 | 2011-08-19 | |
| US61/525,462 | 2011-08-19 | ||
| US201161533439P | 2011-09-12 | 2011-09-12 | |
| US61/533,439 | 2011-09-12 | ||
| US201161533915P | 2011-09-13 | 2011-09-13 | |
| US61/533,915 | 2011-09-13 | ||
| US201161539540P | 2011-09-27 | 2011-09-27 | |
| US61/539,540 | 2011-09-27 | ||
| PCT/US2012/051168 WO2013028465A1 (en) | 2011-08-19 | 2012-08-16 | Crystal forms of a hcv protease inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2012299218A1 true AU2012299218A1 (en) | 2014-02-20 |
Family
ID=47746773
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012299218A Abandoned AU2012299218A1 (en) | 2011-08-19 | 2012-08-16 | Crystal forms of a HCV protease inhibitor |
| AU2012299223A Abandoned AU2012299223A1 (en) | 2011-08-19 | 2012-08-16 | Process and intermediates for preparing macrolactams |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012299223A Abandoned AU2012299223A1 (en) | 2011-08-19 | 2012-08-16 | Process and intermediates for preparing macrolactams |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US9242917B2 (https=) |
| EP (3) | EP2744331A4 (https=) |
| JP (2) | JP2014521750A (https=) |
| KR (2) | KR20140059236A (https=) |
| CN (2) | CN103889439A (https=) |
| AU (2) | AU2012299218A1 (https=) |
| BR (2) | BR112014003798A2 (https=) |
| CA (2) | CA2844388A1 (https=) |
| MX (2) | MX2014001944A (https=) |
| RU (2) | RU2014110400A (https=) |
| WO (3) | WO2013028471A1 (https=) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8828930B2 (en) | 2009-07-30 | 2014-09-09 | Merck Sharp & Dohme Corp. | Hepatitis C virus NS3 protease inhibitors |
| US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2744331A4 (en) | 2011-08-19 | 2015-01-21 | Merck Sharp & Dohme | METHOD AND INTERMEDIATE PRODUCTS FOR THE MANUFACTURE OF MACROLACTAMEN |
| UA119315C2 (uk) | 2012-07-03 | 2019-06-10 | Гіліад Фармассет Елелсі | Інгібітори вірусу гепатиту с |
| EA025560B1 (ru) | 2012-10-19 | 2017-01-30 | Бристол-Майерс Сквибб Компани | Ингибиторы вируса гепатита с |
| WO2014070964A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014071007A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2914614B1 (en) | 2012-11-05 | 2017-08-16 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| EP2764866A1 (en) | 2013-02-07 | 2014-08-13 | IP Gesellschaft für Management mbH | Inhibitors of nedd8-activating enzyme |
| WO2014137869A1 (en) | 2013-03-07 | 2014-09-12 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9617310B2 (en) | 2013-03-15 | 2017-04-11 | Gilead Sciences, Inc. | Inhibitors of hepatitis C virus |
| US9873707B2 (en) | 2013-10-18 | 2018-01-23 | Merck Sharp & Dohme Corp. | Methods and intermediates for preparing macrolactams |
| WO2015095437A1 (en) * | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Methods and intermediates for the preparation of macrolactams |
| PL3636649T3 (pl) | 2014-01-24 | 2024-05-06 | Turning Point Therapeutics, Inc. | Diaryle makrocykliczne jako modulatory kinaz białkowych |
| EP3151850A4 (en) * | 2014-06-06 | 2017-11-29 | AbbVie Inc. | Crystal forms |
| ES2864839T3 (es) | 2015-07-02 | 2021-10-14 | Turning Point Therapeutics Inc | Macrociclos de diarilo quirales como moduladores de proteína quinasas |
| JP6917974B2 (ja) * | 2015-07-06 | 2021-08-11 | ターニング・ポイント・セラピューティクス・インコーポレイテッドTurning Point Therapeutics,Inc. | ジアリール大環状多形 |
| FI3733187T3 (fi) * | 2015-07-21 | 2024-12-18 | Turning Point Therapeutics Inc | Kiraalinen diaryylimakrosykli ja sen käyttö syövän hoidossa |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| CN109641874A (zh) | 2016-05-10 | 2019-04-16 | C4医药公司 | 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体 |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| EP4491236A3 (en) | 2016-05-10 | 2025-04-02 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| BR112019001607A2 (pt) | 2016-07-28 | 2019-04-30 | Tp Therapeutics, Inc. | inibidores macrocíclicos de quinases |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| EP4717317A2 (en) | 2017-06-20 | 2026-04-01 | C4 Therapeutics, Inc. | N/o-linked degrons and degronimers for protein degradation |
| US11286264B2 (en) | 2017-07-28 | 2022-03-29 | Turning Point Therapeutics, Inc. | Macrocyclic compounds and uses thereof |
| LT3728271T (lt) | 2017-12-19 | 2022-12-12 | Turning Point Therapeutics, Inc. | Makrocikliniai junginiai, skirti ligų gydymui |
| CN111057045A (zh) * | 2019-12-18 | 2020-04-24 | 安徽红杉生物医药科技有限公司 | Hcv ns3/4a蛋白酶抑制剂中间体及其合成方法、应用 |
| CN112174982A (zh) * | 2020-09-10 | 2021-01-05 | 上海希迈医药科技有限公司 | 一种洛普替尼晶型及其制备方法 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4871868A (en) | 1987-03-11 | 1989-10-03 | Takeda Chemical Industries, Ltd. | Production of substituted acetylenic compounds |
| GB9207987D0 (en) | 1992-04-10 | 1992-05-27 | Smithkline Beecham Plc | Novel container and closure |
| US5716960A (en) * | 1995-01-13 | 1998-02-10 | U.S. Bioscience Inc. And Individuals | Crystalline trimetrexate salts and the process for making the same |
| ZA98879B (en) * | 1997-02-04 | 1998-08-03 | Ono Pharmaceutical Co | Omega-cycloalkyl-prostaglandin e2 derivatives |
| NO317155B1 (no) | 1997-02-04 | 2004-08-30 | Ono Pharmaceutical Co | <omega>-cykloalkyl-prostagladin-E<N>2</N>-derivater |
| CN102372704B (zh) * | 2005-02-18 | 2014-10-08 | 田边三菱制药株式会社 | 脯氨酸衍生物的盐,其溶剂合物,及其生产方法 |
| WO2006102087A2 (en) | 2005-03-22 | 2006-09-28 | Merck & Co., Inc. | Hcv protease substrates |
| CA2606195C (en) | 2005-05-02 | 2015-03-31 | Merck And Co., Inc. | Hcv ns3 protease inhibitors |
| UA90909C2 (en) * | 2005-07-20 | 2010-06-10 | Мерк Шарп Энд Домэ Корп. | Hcv ns3 protease inhibitors |
| AR057456A1 (es) | 2005-07-20 | 2007-12-05 | Merck & Co Inc | Inhibidores de la proteasa ns3 del vhc |
| NZ565269A (en) | 2005-08-01 | 2010-03-26 | Merck & Co Inc | Macrocyclic peptides as HCV NS3 protease inhibitors |
| EP2018146A2 (en) | 2006-03-07 | 2009-01-28 | The Procter and Gamble Company | Compositions for oxidatively dyeing keratin fibers and methods for using such compositions |
| GB0609492D0 (en) | 2006-05-15 | 2006-06-21 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| GB0612423D0 (en) | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| AU2007309488B2 (en) | 2006-10-24 | 2012-10-11 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| AU2007309546A1 (en) | 2006-10-24 | 2008-05-02 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | HCV NS3 protease inhibitors |
| US8377874B2 (en) | 2006-10-27 | 2013-02-19 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| BRPI0718161A2 (pt) * | 2006-10-27 | 2013-11-26 | Merck & Co Inc | Composto, composição farmacêutica, e, uso do composto. |
| SG174809A1 (en) | 2007-05-03 | 2011-10-28 | Intermune Inc | Macrocyclic compounds useful as inhibitors of hepatitis c virus |
| AU2008277377B2 (en) | 2007-07-19 | 2013-08-01 | Msd Italia S.R.L. | Macrocyclic compounds as antiviral agents |
| CA2714604A1 (en) | 2008-02-25 | 2009-09-03 | Merck Sharp & Dohme Corp. | Macrocyclic hcv ns3 protease inhibitors |
| WO2009131196A1 (ja) * | 2008-04-24 | 2009-10-29 | 武田薬品工業株式会社 | 置換ピロリジン誘導体およびその用途 |
| WO2009132202A2 (en) * | 2008-04-24 | 2009-10-29 | Incyte Corporation | Macrocyclic compounds and their use as kinase inhibitors |
| WO2009134624A1 (en) | 2008-04-28 | 2009-11-05 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
| EA019327B1 (ru) | 2008-07-22 | 2014-02-28 | Мерк Шарп Энд Домэ Корп. | Макроциклическое хиноксалиновое соединение в качестве ингибитора протеазы вгс ns3 |
| US8828930B2 (en) | 2009-07-30 | 2014-09-09 | Merck Sharp & Dohme Corp. | Hepatitis C virus NS3 protease inhibitors |
| EP2470189A4 (en) * | 2009-08-27 | 2013-01-23 | Merck Sharp & Dohme | METHOD FOR PRODUCING PROTEASE INHIBITORS OF HEPATITIS C VIRUS |
| EP2744331A4 (en) | 2011-08-19 | 2015-01-21 | Merck Sharp & Dohme | METHOD AND INTERMEDIATE PRODUCTS FOR THE MANUFACTURE OF MACROLACTAMEN |
-
2012
- 2012-08-16 EP EP12825726.8A patent/EP2744331A4/en not_active Withdrawn
- 2012-08-16 AU AU2012299218A patent/AU2012299218A1/en not_active Abandoned
- 2012-08-16 CA CA2844388A patent/CA2844388A1/en not_active Abandoned
- 2012-08-16 EP EP12825540.3A patent/EP2744507A4/en not_active Withdrawn
- 2012-08-16 CN CN201280050382.8A patent/CN103889439A/zh active Pending
- 2012-08-16 JP JP2014526217A patent/JP2014521750A/ja active Pending
- 2012-08-16 WO PCT/US2012/051182 patent/WO2013028471A1/en not_active Ceased
- 2012-08-16 US US14/239,389 patent/US9242917B2/en active Active
- 2012-08-16 WO PCT/US2012/051168 patent/WO2013028465A1/en not_active Ceased
- 2012-08-16 RU RU2014110400/04A patent/RU2014110400A/ru not_active Application Discontinuation
- 2012-08-16 US US14/239,391 patent/US9073825B2/en active Active
- 2012-08-16 CN CN201280050361.6A patent/CN103874414A/zh active Pending
- 2012-08-16 JP JP2014526215A patent/JP2014524442A/ja active Pending
- 2012-08-16 RU RU2014110399/04A patent/RU2014110399A/ru not_active Application Discontinuation
- 2012-08-16 MX MX2014001944A patent/MX2014001944A/es unknown
- 2012-08-16 KR KR1020147006888A patent/KR20140059236A/ko not_active Withdrawn
- 2012-08-16 BR BR112014003798A patent/BR112014003798A2/pt not_active IP Right Cessation
- 2012-08-16 BR BR112014003802A patent/BR112014003802A2/pt not_active IP Right Cessation
- 2012-08-16 AU AU2012299223A patent/AU2012299223A1/en not_active Abandoned
- 2012-08-16 KR KR1020147006858A patent/KR20140053330A/ko not_active Withdrawn
- 2012-08-16 EP EP12826404.1A patent/EP2744336B1/en not_active Not-in-force
- 2012-08-16 MX MX2014001945A patent/MX2014001945A/es unknown
- 2012-08-16 WO PCT/US2012/051177 patent/WO2013028470A1/en not_active Ceased
- 2012-08-16 CA CA2844386A patent/CA2844386A1/en not_active Abandoned
- 2012-08-16 US US14/239,393 patent/US9238604B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2012299223A1 (en) | 2014-02-27 |
| KR20140053330A (ko) | 2014-05-07 |
| EP2744336A4 (en) | 2014-12-31 |
| WO2013028471A1 (en) | 2013-02-28 |
| CN103874414A (zh) | 2014-06-18 |
| MX2014001945A (es) | 2014-03-27 |
| US9073825B2 (en) | 2015-07-07 |
| US9238604B2 (en) | 2016-01-19 |
| US20140243519A1 (en) | 2014-08-28 |
| US9242917B2 (en) | 2016-01-26 |
| JP2014524442A (ja) | 2014-09-22 |
| EP2744507A1 (en) | 2014-06-25 |
| EP2744331A4 (en) | 2015-01-21 |
| RU2014110400A (ru) | 2015-09-27 |
| CA2844388A1 (en) | 2013-02-28 |
| BR112014003802A2 (pt) | 2017-06-13 |
| US20140200343A1 (en) | 2014-07-17 |
| KR20140059236A (ko) | 2014-05-15 |
| JP2014521750A (ja) | 2014-08-28 |
| BR112014003798A2 (pt) | 2017-03-01 |
| WO2013028465A1 (en) | 2013-02-28 |
| CA2844386A1 (en) | 2013-02-28 |
| EP2744336A1 (en) | 2014-06-25 |
| MX2014001944A (es) | 2014-03-27 |
| EP2744331A1 (en) | 2014-06-25 |
| RU2014110399A (ru) | 2015-09-27 |
| EP2744336B1 (en) | 2017-07-05 |
| WO2013028470A1 (en) | 2013-02-28 |
| US20140206605A1 (en) | 2014-07-24 |
| EP2744507A4 (en) | 2015-01-28 |
| CN103889439A (zh) | 2014-06-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |