CA2641769C - Succinic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(r)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl) ethyl] piperidin-4-yl ester and its use for the treatment of pulmonary disorders - Google Patents
Succinic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(r)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl) ethyl] piperidin-4-yl ester and its use for the treatment of pulmonary disorders Download PDFInfo
- Publication number
- CA2641769C CA2641769C CA2641769A CA2641769A CA2641769C CA 2641769 C CA2641769 C CA 2641769C CA 2641769 A CA2641769 A CA 2641769A CA 2641769 A CA2641769 A CA 2641769A CA 2641769 C CA2641769 C CA 2641769C
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- Canada
- Prior art keywords
- hydroxy
- salt
- ester
- succinic acid
- chloro
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- 238000011282 treatment Methods 0.000 title claims description 18
- URWYQGVSPQJGGB-DHUJRADRSA-N [1-[3-[2-chloro-4-[[[(2r)-2-hydroxy-2-(8-hydroxy-2-oxo-1h-quinolin-5-yl)ethyl]amino]methyl]-5-methoxyanilino]-3-oxopropyl]piperidin-4-yl] n-(2-phenylphenyl)carbamate Chemical compound ClC=1C=C(CNC[C@H](O)C=2C=3C=CC(=O)NC=3C(O)=CC=2)C(OC)=CC=1NC(=O)CCN(CC1)CCC1OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 URWYQGVSPQJGGB-DHUJRADRSA-N 0.000 title claims 5
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- IXTCZMJQGGONPY-XJAYAHQCSA-N rofleponide Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3O[C@@H](CCC)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O IXTCZMJQGGONPY-XJAYAHQCSA-N 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 229960004499 scopolamine hydrobromide Drugs 0.000 description 1
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- SBIBMFFZSBJNJF-UHFFFAOYSA-N selenium;zinc Chemical compound [Se]=[Zn] SBIBMFFZSBJNJF-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229950004351 telenzepine Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- XJGONMZLEDGBRM-UHFFFAOYSA-M tridihexethyl chloride Chemical compound [Cl-].C=1C=CC=CC=1C(O)(CC[N+](CC)(CC)CC)C1CCCCC1 XJGONMZLEDGBRM-UHFFFAOYSA-M 0.000 description 1
- 229960001205 tridihexethyl chloride Drugs 0.000 description 1
- 229960004479 trihexyphenidyl hydrochloride Drugs 0.000 description 1
- QDWJJTJNXAKQKD-UHFFFAOYSA-N trihexyphenidyl hydrochloride Chemical compound Cl.C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 QDWJJTJNXAKQKD-UHFFFAOYSA-N 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 239000002750 tryptase inhibitor Substances 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0602778.3 | 2006-02-10 | ||
| GBGB0602778.3A GB0602778D0 (en) | 2006-02-10 | 2006-02-10 | Novel compound |
| PCT/EP2007/051196 WO2007090859A1 (en) | 2006-02-10 | 2007-02-08 | Succinic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{ [ (r)-2-hydroxy-2- (8-hydroxy-2-oxo-1, 2-dihydroquinolin-5-yl) eth ylaminoimethyl] } -5-methoxyphenylcarbamoyl) ethyl] piperidin-4-yl ester and its use for the treatment of pulmonary disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2641769A1 CA2641769A1 (en) | 2007-08-16 |
| CA2641769C true CA2641769C (en) | 2014-02-04 |
Family
ID=36119909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2641769A Active CA2641769C (en) | 2006-02-10 | 2007-02-08 | Succinic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(r)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl) ethyl] piperidin-4-yl ester and its use for the treatment of pulmonary disorders |
Country Status (33)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2535326T3 (es) | 2009-04-14 | 2015-05-08 | Glaxo Group Limited | Procedimiento de preparación de un éster de ácido bifenil-2-ilcarbámico |
| AU2015234331B2 (en) * | 2009-04-23 | 2017-08-03 | Theravance Biopharma R&D Ip, Llc | Diamide compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| CN103936716B (zh) | 2009-04-23 | 2016-09-07 | 施万呼吸有限责任公司 | 具蕈毒碱受体拮抗剂和β2肾上腺素受体激动剂活性的二酰胺化合物 |
| WO2011081937A1 (en) | 2009-12-15 | 2011-07-07 | Gilead Sciences, Inc. | Corticosteroid-beta-agonist-muscarinic antagonist compounds for use in therapy |
| EP2386555A1 (en) | 2010-05-13 | 2011-11-16 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and m3 muscarinic antagonist activities |
| ITRM20110083U1 (it) | 2010-05-13 | 2011-11-14 | De La Cruz Jose Antonio Freire | Piastra per la costruzione di carrelli per aeroplani |
| AR083115A1 (es) * | 2010-09-30 | 2013-01-30 | Theravance Inc | Sales oxalato cristalinas de un compuesto diamida |
| KR101966630B1 (ko) * | 2011-08-02 | 2019-04-09 | 알파시그마 에스.피.에이. | 흡입에 적당한 산화된 아비딘의 약제학적 조성물 |
| EP2592078A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
| BR112015013628A2 (pt) | 2012-12-18 | 2017-07-11 | Almirall Sa | derivados de carbamato de ciclo-hexila e quinuclidinila tendo atividades agonista adrenérgica de beta2 e antagonista muscarínica de m3 |
| TWI643853B (zh) | 2013-02-27 | 2018-12-11 | 阿爾米雷爾有限公司 | 同時具有β2腎上腺素受體促效劑和M3毒蕈鹼受體拮抗劑活性之2-氨基-1-羥乙基-8-羥基喹啉-2(1H)-酮衍生物之鹽類 |
| TW201517906A (zh) | 2013-07-25 | 2015-05-16 | Almirall Sa | 含有ｍａｂａ化合物和皮質類固醇之組合 |
| TWI641373B (zh) | 2013-07-25 | 2018-11-21 | 阿爾米雷爾有限公司 | 具有蕈毒鹼受體拮抗劑和β２腎上腺素受體促效劑二者之活性的２－胺基－１－羥乙基－８－羥基喹啉－２（１Ｈ）－酮衍生物之鹽 |
| TW201617343A (zh) | 2014-09-26 | 2016-05-16 | 阿爾米雷爾有限公司 | 具有β２腎上腺素促效劑及Ｍ３蕈毒拮抗劑活性之新穎雙環衍生物 |
| GB201500447D0 (en) * | 2015-01-12 | 2015-02-25 | Glaxosmithkline Ip Dev Ltd | Novel Combination Product |
| CN106632257B (zh) * | 2016-12-15 | 2019-02-12 | 上海市奉贤区中心医院 | Gsk961081及其中间体的合成方法 |
| US11484531B2 (en) | 2018-08-30 | 2022-11-01 | Theravance Biopharma R&D Ip, Llc | Methods for treating chronic obstructive pulmonary disease |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4026897A (en) | 1974-01-31 | 1977-05-31 | Otsuka Pharmaceutical Company | 5-[1-Hydroxy-2-(substituted-amino)]alkyl-8-hydroxycarbostyril derivatives |
| DE3134590A1 (de) | 1981-09-01 | 1983-03-10 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue benzo-heterocyclen |
| US4460581A (en) | 1982-10-12 | 1984-07-17 | Boehringer Ingelheim Kg | (1-Hydroxy-2-amino-alkyl)-substituted benzoxazinones and benzoxazolinones |
| ZW6584A1 (en) | 1983-04-18 | 1985-04-17 | Glaxo Group Ltd | Phenethanolamine derivatives |
| US4894219A (en) | 1988-03-29 | 1990-01-16 | University Of Florida | Beta-agonist carbostyril derivatives, assay method and pharmacological composition |
| DK443489D0 (da) | 1989-09-08 | 1989-09-08 | Ferrosan As | Substituerede urinstofforbindelser, deres fremstilling og anvendelse |
| ES2141763T3 (es) | 1992-03-31 | 2000-04-01 | Glaxo Group Ltd | Fenilcarbonatos y fenilureas sustituidos, su preparacion y su uso como antagonistas de 5-ht4. |
| CA2123728A1 (en) | 1993-05-21 | 1994-11-22 | Noriyoshi Sueda | Urea derivatives and their use as acat inhibitors |
| WO1995006635A1 (en) | 1993-09-02 | 1995-03-09 | Yamanouchi Pharmaceutical Co., Ltd. | Carbamate derivative and medicine containing the same |
| KR970701174A (ko) | 1994-02-10 | 1997-03-17 | 오노다 마사요시 | 신규한 카바메이트 유도체 및 이의 의약 조성물(Novel carbamate derivative and medicinal composition containing the same) |
| WO1997013766A1 (en) | 1995-10-13 | 1997-04-17 | Banyu Pharmaceutical Co., Ltd. | Substituted heteroaromatic derivatives |
| PE92198A1 (es) | 1996-08-01 | 1999-01-09 | Banyu Pharma Co Ltd | Derivados de 1,4-piperidina disustituida que contienen fluor |
| US6040344A (en) | 1996-11-11 | 2000-03-21 | Sepracor Inc. | Formoterol process |
| CA2313125A1 (en) | 1997-12-12 | 1999-06-24 | Laramie Mary Gaster | Quinolinepiperazine and quinolinepiperidine derivatives, their preparation and their use as combined 5-ht1a, 5-ht1b and 5-ht1d receptor antagonists |
| EP1086066A4 (en) | 1998-06-08 | 2001-08-08 | Advanced Medicine Inc | MUSCARINIC RECEPTOR ANTAGONISTS |
| US6541669B1 (en) | 1998-06-08 | 2003-04-01 | Theravance, Inc. | β2-adrenergic receptor agonists |
| US6713651B1 (en) | 1999-06-07 | 2004-03-30 | Theravance, Inc. | β2-adrenergic receptor agonists |
| US6693202B1 (en) | 1999-02-16 | 2004-02-17 | Theravance, Inc. | Muscarinic receptor antagonists |
| GB9913083D0 (en) | 1999-06-04 | 1999-08-04 | Novartis Ag | Organic compounds |
| US6593497B1 (en) | 1999-06-02 | 2003-07-15 | Theravance, Inc. | β2-adrenergic receptor agonists |
| JP2003516390A (ja) | 1999-12-07 | 2003-05-13 | セラヴァンス インコーポレーテッド | ムスカリンレセプターアンタゴニスト活性を有するカルバメート誘導体 |
| UA73543C2 (uk) | 1999-12-07 | 2005-08-15 | Тераванс, Інк. | Похідні сечовини, фармацевтична композиція та застосування похідного при приготуванні лікарського засобу для лікування захворювання, яке опосередковується мускариновим рецептором |
| UA73965C2 (en) | 1999-12-08 | 2005-10-17 | Theravance Inc | b2 ADRENERGIC RECEPTOR ANTAGONISTS |
| MXPA02006660A (es) * | 2000-01-07 | 2002-12-13 | Transform Pharmaceuticals Inc | Formacion, identificacion y analisis de diversas formas solidas de alto rendimiento. |
| KR20030031907A (ko) | 2000-06-05 | 2003-04-23 | 알타나 파마 아게 | β-2-아드레날린 수용체 작동물질로서 뿐만 아니라ＰＤＥ4-억제제로서 효과적인 화합물 |
| EP1345937B1 (en) | 2000-12-22 | 2005-09-28 | Almirall Prodesfarma AG | Quinuclidine carbamate derivatives and their use as m3 antagonists |
| GB0103630D0 (en) | 2001-02-14 | 2001-03-28 | Glaxo Group Ltd | Chemical compounds |
| US20030018019A1 (en) | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
| TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| US6653323B2 (en) | 2001-11-13 | 2003-11-25 | Theravance, Inc. | Aryl aniline β2 adrenergic receptor agonists |
| AU2003232201B2 (en) | 2002-04-12 | 2009-06-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments containing betamimetic drugs and a novel anticholinesterase drug |
| JP2005527618A (ja) | 2002-05-28 | 2005-09-15 | セラヴァンス インコーポレーテッド | アルコキシアリールβ２アドレナリン作動性レセプターアゴニスト |
| GB0217225D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicinal compounds |
| AR040779A1 (es) | 2002-08-06 | 2005-04-20 | Glaxo Group Ltd | Compuesto de tiazol anilina su uso para preparar una formulacion farmaceutica dicha formulacion recipiente que la contiene y dispositivo adaptado para la administracion intranasal de la formulacion |
| PE20040950A1 (es) * | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| JP4767842B2 (ja) | 2003-04-01 | 2011-09-07 | セラヴァンス， インコーポレーテッド | β２アドレナリン作用性レセプターアゴニスト活性およびムスカリン性レセプターアンタゴニスト活性を有するジアリールメチル化合物および関連化合物 |
| ATE435862T1 (de) | 2003-05-28 | 2009-07-15 | Theravance Inc | Azabicycloalkanverbindungen als muscarinrezeptor antagonisten |
| DE602004021959D1 (de) | 2003-11-21 | 2009-08-20 | Theravance Inc | Verbindungen mit agonistischer wirkung am beta2-adrenergen rezeptor und am muscarinischen rezeptor |
| WO2005080375A1 (en) | 2004-02-13 | 2005-09-01 | Theravance, Inc. | Crystalline form of a biphenyl compound |
| TWI374883B (en) * | 2004-08-16 | 2012-10-21 | Theravance Inc | Crystalline form of a biphenyl compound |
| WO2006023460A2 (en) | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| WO2006023457A1 (en) | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
-
2006
- 2006-02-10 GB GBGB0602778.3A patent/GB0602778D0/en not_active Ceased
-
2007
- 2007-02-08 WO PCT/EP2007/051196 patent/WO2007090859A1/en not_active Ceased
- 2007-02-08 JP JP2008553758A patent/JP5616021B2/ja not_active Expired - Fee Related
- 2007-02-08 LT LTEP07704449.3T patent/LT1981872T/lt unknown
- 2007-02-08 BR BRPI0707559A patent/BRPI0707559B8/pt not_active IP Right Cessation
- 2007-02-08 CN CN2007800050282A patent/CN101379057B/zh not_active Expired - Fee Related
- 2007-02-08 NZ NZ570242A patent/NZ570242A/en not_active IP Right Cessation
- 2007-02-08 EP EP07704449.3A patent/EP1981872B1/en active Active
- 2007-02-08 HR HRP20171304TT patent/HRP20171304T1/hr unknown
- 2007-02-08 HU HUE07704449A patent/HUE034315T2/en unknown
- 2007-02-08 PE PE2007000135A patent/PE20071249A1/es not_active Application Discontinuation
- 2007-02-08 ES ES07704449.3T patent/ES2640226T3/es active Active
- 2007-02-08 CA CA2641769A patent/CA2641769C/en active Active
- 2007-02-08 PT PT77044493T patent/PT1981872T/pt unknown
- 2007-02-08 PE PE2010000996A patent/PE20110120A1/es active IP Right Grant
- 2007-02-08 TW TW096104636A patent/TWI401251B/zh not_active IP Right Cessation
- 2007-02-08 JO JOP/2007/0037A patent/JO3389B1/ar active
- 2007-02-08 KR KR20087022160A patent/KR101488691B1/ko not_active Expired - Fee Related
- 2007-02-08 AR ARP070100537A patent/AR059409A1/es not_active Application Discontinuation
- 2007-02-08 AU AU2007213767A patent/AU2007213767B2/en not_active Ceased
- 2007-02-08 DK DK07704449.3T patent/DK1981872T3/en active
- 2007-02-08 SI SI200731963T patent/SI1981872T1/sl unknown
- 2007-02-08 SG SG201100933-9A patent/SG169404A1/en unknown
- 2007-02-08 PL PL07704449T patent/PL1981872T3/pl unknown
- 2007-02-08 EA EA200801691A patent/EA016580B1/ru unknown
- 2007-02-08 US US11/672,536 patent/US7960551B2/en active Active
- 2007-08-02 UA UAA200809940A patent/UA100364C2/ru unknown
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2008
- 2008-07-29 IL IL193103A patent/IL193103A/en active IP Right Grant
- 2008-08-05 ZA ZA200806782A patent/ZA200806782B/xx unknown
- 2008-08-05 NO NO20083425A patent/NO341343B1/no unknown
- 2008-08-08 MY MYPI20083025A patent/MY153656A/en unknown
- 2008-08-20 CR CR10227A patent/CR10227A/es not_active Application Discontinuation
- 2008-09-10 MA MA31228A patent/MA30273B1/fr unknown
-
2016
- 2016-04-15 AR ARP160101036A patent/AR104288A2/es not_active Application Discontinuation
-
2017
- 2017-08-22 CY CY20171100887T patent/CY1119238T1/el unknown
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