BRPI0513982A - inibidores de sinalização de receptor de vegf e receptor de hgf - Google Patents
inibidores de sinalização de receptor de vegf e receptor de hgfInfo
- Publication number
- BRPI0513982A BRPI0513982A BRPI0513982-1A BRPI0513982A BRPI0513982A BR PI0513982 A BRPI0513982 A BR PI0513982A BR PI0513982 A BRPI0513982 A BR PI0513982A BR PI0513982 A BRPI0513982 A BR PI0513982A
- Authority
- BR
- Brazil
- Prior art keywords
- hgf
- receptor signaling
- vegf
- receptor
- signaling inhibitors
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4355—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- C07D498/02—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 two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59291304P | 2004-07-30 | 2004-07-30 | |
| US68303805P | 2005-05-20 | 2005-05-20 | |
| PCT/CA2005/001177 WO2006010264A1 (en) | 2004-07-30 | 2005-07-28 | Inhibitors of vegf receptor and hgf receptor signaling |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0513982A true BRPI0513982A (pt) | 2007-11-27 |
Family
ID=35785877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0513982-1A BRPI0513982A (pt) | 2004-07-30 | 2005-07-28 | inibidores de sinalização de receptor de vegf e receptor de hgf |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7772247B2 (https=) |
| EP (1) | EP1781664B1 (https=) |
| JP (1) | JP5096142B2 (https=) |
| KR (1) | KR101257343B1 (https=) |
| CN (1) | CN101031570B (https=) |
| AU (1) | AU2005266803B2 (https=) |
| BR (1) | BRPI0513982A (https=) |
| CA (1) | CA2573538C (https=) |
| ES (1) | ES2438017T3 (https=) |
| IL (1) | IL180788A0 (https=) |
| MX (1) | MX2007001216A (https=) |
| RU (1) | RU2007107167A (https=) |
| WO (1) | WO2006010264A1 (https=) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2569016C (en) * | 2004-06-02 | 2012-11-27 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
| ES2438017T3 (es) | 2004-07-30 | 2014-01-15 | Methylgene Inc. | Inhibidores de la señalización del receptor del VEGF y del receptor del HGF |
| AU2006229343A1 (en) * | 2005-03-28 | 2006-10-05 | Kirin Pharma Kabushiki Kaisha | Thienopyridine derivative, or quinoline derivative, or quinazoline derivative, having c-Met autophosphorylation inhibiting potency |
| JP2008536932A (ja) * | 2005-04-18 | 2008-09-11 | サイード・アール・カーン | チューブリン重合阻害剤:ボンゾイルフェニル尿素(bpu)硫黄類似体の設計及び合成 |
| KR101378716B1 (ko) * | 2005-05-20 | 2014-04-10 | 메틸진 인코포레이티드 | Vegf 수용체 및 hgf 수용체 신호전달의 억제제 |
| AU2006313456B2 (en) | 2005-05-20 | 2011-06-23 | Methylgene Inc. | Inhibitors of VEGF receptor and HGF receptor signaling |
| TW200730527A (en) * | 2005-12-02 | 2007-08-16 | Takeda Pharmaceuticals Co | Fused heterocyclic compound |
| JP2009526761A (ja) * | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| AR060061A1 (es) * | 2006-03-22 | 2008-05-21 | Methylgene Inc | Inhibidores de la actividad de la proteina tirosina quinasa |
| JP2009539878A (ja) * | 2006-06-08 | 2009-11-19 | アレイ バイオファーマ、インコーポレイテッド | キノリン化合物および使用方法 |
| ES2593279T3 (es) | 2007-08-29 | 2016-12-07 | Methylgene Inc. | Procesos e intermedios para preparar inhibidores de cinasa heterocíclicos condensados |
| PL2183254T3 (pl) | 2007-08-29 | 2017-10-31 | Methylgene Inc | Inhibitory aktywności białkowej kinazy tyrozynowej |
| NZ588355A (en) | 2008-03-05 | 2012-03-30 | Methylgene Inc | Inhibitors of protein tyrosine kinase activity |
| ES2599458T3 (es) * | 2008-10-14 | 2017-02-01 | Sunshine Lake Pharma Co., Ltd. | Compuestos y métodos de uso |
| EP2408300B1 (en) * | 2009-03-21 | 2016-05-11 | Sunshine Lake Pharma Co., Ltd. | Amino ester derivatives, salts thereof and methods of use |
| JP2013525286A (ja) * | 2010-04-16 | 2013-06-20 | メチルジーン・インコーポレイテッド | タンパク質チロシンキナーゼ活性の阻害剤 |
| US20130225581A1 (en) | 2010-07-16 | 2013-08-29 | Kyowa Hakko Kirin Co., Ltd | Nitrogen-containing aromatic heterocyclic derivative |
| TW201217387A (en) | 2010-09-15 | 2012-05-01 | Hoffmann La Roche | Azabenzothiazole compounds, compositions and methods of use |
| RU2568258C2 (ru) | 2011-02-28 | 2015-11-20 | Саншайн Лейк Фарма Ко., Лтд | Замещенные соединения хинолина и способы их использования |
| HUE056194T2 (hu) | 2012-02-21 | 2022-01-28 | Towa Pharmaceutical Europe S L | Dabigatrán-etexilát orális gyógyszerészeti készítményei |
| TWI520962B (zh) * | 2012-06-29 | 2016-02-11 | As the c-Met tyrosine kinase inhibitors novel fused pyridine derivatives | |
| JP6342392B2 (ja) | 2012-07-28 | 2018-06-13 | カリター・サイエンシーズ・エルエルシー | 置換型ピラゾロン化合物及び使用方法 |
| TWI574962B (zh) | 2012-11-14 | 2017-03-21 | 加拓科學公司 | 作爲pi3激酶調節劑的芳雜環化合物及其使用方法和用途 |
| MX2015010700A (es) | 2013-02-21 | 2017-01-23 | Calitor Sciences Llc | Compuestos heteroaromaticos como moduladores de la p13 cinasa. |
| RS58361B1 (sr) * | 2013-07-31 | 2019-03-29 | Merck Patent Gmbh | Piridini, pirimidini i pirazini, kao inhibitori btk i njihova upotreba |
| US10308658B2 (en) | 2015-10-19 | 2019-06-04 | Sunshine Lake Pharma Co., Ltd. | Salt of EGFR inhibitor, crystalline form and uses thereof |
| EP3646887A4 (en) | 2017-06-30 | 2021-03-24 | Korea Advanced Institute of Science and Technology | CONJUGATE OF VEGF GRAB PROTEIN AND MEDICINAL PRODUCTS AND USES THEREOF |
| US11623923B2 (en) | 2017-11-24 | 2023-04-11 | Medshine Discovery, Inc. | Uracil compound as c-MET/AXL inhibitor |
| WO2020132384A1 (en) | 2018-12-21 | 2020-06-25 | Celgene Corporation | Thienopyridine inhibitors of ripk2 |
| US20250188147A1 (en) | 2022-03-04 | 2025-06-12 | Panalos Bioscience, Inc. | Composition for combi-therapy comprising vegf-grab and pd-1 or pd-l1 antagonist |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6107300A (en) * | 1996-03-27 | 2000-08-22 | Dupont Pharmaceuticals | Arylamino fused pyrimidines |
| EP1028964A1 (en) * | 1997-11-11 | 2000-08-23 | Pfizer Products Inc. | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
| US6232320B1 (en) * | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| AU4231299A (en) | 1998-06-04 | 1999-12-20 | Abbott Laboratories | Cell adhesion-inhibiting antinflammatory compounds |
| WO2000075145A1 (en) | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| BR0111377A (pt) | 2000-06-06 | 2003-06-03 | Pfizer Prod Inc | Derivados de tiofeno úteis como agentes anticancerìgenos |
| US20020004511A1 (en) * | 2000-06-28 | 2002-01-10 | Luzzio Michael Joseph | Thiophene derivatives useful as anticancer agents |
| AU9598601A (en) * | 2000-10-20 | 2002-04-29 | Eisai Co Ltd | Nitrogenous aromatic ring compounds |
| WO2003000194A2 (en) | 2001-06-21 | 2003-01-03 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
| GB0115109D0 (en) * | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| AU2002313249B2 (en) * | 2001-06-22 | 2008-08-21 | Kirin Pharma Kabushiki Kaisha | Quinoline derivative and quinazoline derivate inhibiting self-phosphorylation of hepatocytus proliferator receptor, and medicinal composition containing the same |
| GB0119249D0 (en) * | 2001-08-07 | 2001-10-03 | Novartis Ag | Organic compounds |
| AU2003206068A1 (en) | 2002-03-01 | 2003-09-16 | Pfizer Inc. | Indolyl-urea derivatives of thienopyridines useful as anti-angiogenic agents |
| US20030199525A1 (en) * | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
| CL2003002287A1 (es) * | 2002-11-25 | 2005-01-14 | Wyeth Corp | COMPUESTOS DERIVADOS DE TIENO[3,2-b]-PIRIDINA-6-CARBONITRILOS Y TIENEO[2,3-b]-PIRIDINA-5-CARBONITRILOS, COMPOSICION FARMACEUTICA, PROCEDIMIENTO DE PREPARACION Y COMPUESTOS INTERMEDIARIOS, Y SU USO EN EL TRATAMIENTO DEL CANCER, APOPLEJIA, OSTEOPOROSIS |
| DE10335598A1 (de) | 2003-08-04 | 2005-02-24 | Robert Bosch Gmbh | Pedal-Vorrichtung für Kraftfahrzeuge |
| ES2314444T3 (es) | 2003-08-29 | 2009-03-16 | Pfizer Inc. | Tienopiridina-fenilacetaminasy sus derivados utiles como nuevos agentes antiangiogenicos. |
| WO2005052872A1 (en) * | 2003-11-21 | 2005-06-09 | Facil, Llc | Financial transaction system and method |
| JP2007518823A (ja) * | 2004-01-23 | 2007-07-12 | アムゲン インコーポレイテッド | キノリン、キナゾリン、ピリジン、及びピリミジン化合物と炎症、血管新生、及び癌に対する治療におけるそれら化合物の用途 |
| US7459562B2 (en) | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| TW200538453A (en) * | 2004-04-26 | 2005-12-01 | Bristol Myers Squibb Co | Bicyclic heterocycles as kinase inhibitors |
| WO2005121125A1 (en) | 2004-06-09 | 2005-12-22 | Pfizer Inc. | Ether-linked heteroaryl compounds |
| US7439246B2 (en) * | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US7173031B2 (en) | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| US7977345B2 (en) | 2004-07-02 | 2011-07-12 | Exelixis, Inc. | c-MET modulators and method of use |
| MX2007000631A (es) | 2004-07-16 | 2007-03-30 | Sunesis Pharmaceuticals Inc | Tienopirimidinas utiles como inhibidores de aurora cinasa. |
| ES2438017T3 (es) | 2004-07-30 | 2014-01-15 | Methylgene Inc. | Inhibidores de la señalización del receptor del VEGF y del receptor del HGF |
| AU2006229343A1 (en) | 2005-03-28 | 2006-10-05 | Kirin Pharma Kabushiki Kaisha | Thienopyridine derivative, or quinoline derivative, or quinazoline derivative, having c-Met autophosphorylation inhibiting potency |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| AU2006313456B2 (en) * | 2005-05-20 | 2011-06-23 | Methylgene Inc. | Inhibitors of VEGF receptor and HGF receptor signaling |
| KR101378716B1 (ko) | 2005-05-20 | 2014-04-10 | 메틸진 인코포레이티드 | Vegf 수용체 및 hgf 수용체 신호전달의 억제제 |
-
2005
- 2005-07-28 ES ES05770304.3T patent/ES2438017T3/es not_active Expired - Lifetime
- 2005-07-28 AU AU2005266803A patent/AU2005266803B2/en not_active Ceased
- 2005-07-28 CA CA2573538A patent/CA2573538C/en not_active Expired - Fee Related
- 2005-07-28 KR KR1020077005060A patent/KR101257343B1/ko not_active Expired - Fee Related
- 2005-07-28 EP EP05770304.3A patent/EP1781664B1/en not_active Expired - Lifetime
- 2005-07-28 WO PCT/CA2005/001177 patent/WO2006010264A1/en not_active Ceased
- 2005-07-28 CN CN2005800331963A patent/CN101031570B/zh not_active Expired - Fee Related
- 2005-07-28 US US11/191,617 patent/US7772247B2/en active Active
- 2005-07-28 BR BRPI0513982-1A patent/BRPI0513982A/pt not_active Application Discontinuation
- 2005-07-28 JP JP2007522886A patent/JP5096142B2/ja not_active Expired - Fee Related
- 2005-07-28 MX MX2007001216A patent/MX2007001216A/es active IP Right Grant
- 2005-07-28 RU RU2007107167/04A patent/RU2007107167A/ru not_active Application Discontinuation
-
2007
- 2007-01-18 IL IL180788A patent/IL180788A0/en unknown
-
2010
- 2010-05-06 US US12/775,090 patent/US8470850B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005266803B2 (en) | 2011-10-27 |
| US20100216766A1 (en) | 2010-08-26 |
| JP5096142B2 (ja) | 2012-12-12 |
| MX2007001216A (es) | 2007-03-23 |
| KR101257343B1 (ko) | 2013-04-23 |
| WO2006010264A1 (en) | 2006-02-02 |
| US20060074056A1 (en) | 2006-04-06 |
| IL180788A0 (en) | 2007-06-03 |
| EP1781664A1 (en) | 2007-05-09 |
| EP1781664B1 (en) | 2013-09-04 |
| ES2438017T3 (es) | 2014-01-15 |
| KR20070051876A (ko) | 2007-05-18 |
| US7772247B2 (en) | 2010-08-10 |
| EP1781664A4 (en) | 2010-06-02 |
| CN101031570B (zh) | 2012-09-05 |
| AU2005266803A1 (en) | 2006-02-02 |
| JP2008508192A (ja) | 2008-03-21 |
| CA2573538C (en) | 2014-11-25 |
| US8470850B2 (en) | 2013-06-25 |
| RU2007107167A (ru) | 2008-09-10 |
| CA2573538A1 (en) | 2006-02-02 |
| CN101031570A (zh) | 2007-09-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B06T | Formal requirements before examination [chapter 6.20 patent gazette] | ||
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] |
Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
|
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] | ||
| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B11B | Dismissal acc. art. 36, par 1 of ipl - no reply within 90 days to fullfil the necessary requirements |