BR112017011530A2 - polipeptídeos que compreendem uma sequência de aminoácidos g3p de bacteriófago modificada sem sinal de glicosilação - Google Patents
polipeptídeos que compreendem uma sequência de aminoácidos g3p de bacteriófago modificada sem sinal de glicosilaçãoInfo
- Publication number
- BR112017011530A2 BR112017011530A2 BR112017011530A BR112017011530A BR112017011530A2 BR 112017011530 A2 BR112017011530 A2 BR 112017011530A2 BR 112017011530 A BR112017011530 A BR 112017011530A BR 112017011530 A BR112017011530 A BR 112017011530A BR 112017011530 A2 BR112017011530 A2 BR 112017011530A2
- Authority
- BR
- Brazil
- Prior art keywords
- polypeptides
- amino acid
- acid sequence
- modified
- amyloid
- Prior art date
Links
- 229920001184 polypeptide Polymers 0.000 title abstract 5
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract 5
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract 5
- 230000013595 glycosylation Effects 0.000 title abstract 2
- 238000006206 glycosylation reaction Methods 0.000 title abstract 2
- 241001515965 unidentified phage Species 0.000 title 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 2
- 238000006467 substitution reaction Methods 0.000 abstract 2
- 101150090724 3 gene Proteins 0.000 abstract 1
- 241000724791 Filamentous phage Species 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 238000004220 aggregation Methods 0.000 abstract 1
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 230000037430 deletion Effects 0.000 abstract 1
- 238000012217 deletion Methods 0.000 abstract 1
- 230000006806 disease prevention Effects 0.000 abstract 1
- 239000012634 fragment Substances 0.000 abstract 1
- 230000002163 immunogen Effects 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 230000037431 insertion Effects 0.000 abstract 1
- 238000003780 insertion Methods 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1716—Amyloid plaque core protein
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2795/00—Bacteriophages
- C12N2795/00011—Details
- C12N2795/14011—Details ssDNA Bacteriophages
- C12N2795/14022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Marine Sciences & Fisheries (AREA)
- Psychology (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462087052P | 2014-12-03 | 2014-12-03 | |
| PCT/US2015/063476 WO2016090022A1 (en) | 2014-12-03 | 2015-12-02 | Polypeptides comprising a modified bacteriophage g3p amino acid sequence lacking a gylcosylation signal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112017011530A2 true BR112017011530A2 (pt) | 2018-03-13 |
Family
ID=55273507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112017011530A BR112017011530A2 (pt) | 2014-12-03 | 2015-12-02 | polipeptídeos que compreendem uma sequência de aminoácidos g3p de bacteriófago modificada sem sinal de glicosilação |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US10722551B2 (https=) |
| EP (1) | EP3227313B1 (https=) |
| JP (2) | JP6730988B2 (https=) |
| KR (1) | KR20170085132A (https=) |
| CN (1) | CN107250154A (https=) |
| AR (1) | AR102890A1 (https=) |
| AU (1) | AU2015358504A1 (https=) |
| BR (1) | BR112017011530A2 (https=) |
| CA (1) | CA2969128A1 (https=) |
| DK (1) | DK3227313T3 (https=) |
| EA (1) | EA201791212A1 (https=) |
| ES (1) | ES2910017T3 (https=) |
| IL (1) | IL252426A0 (https=) |
| MX (1) | MX2017007059A (https=) |
| PH (1) | PH12017501004A1 (https=) |
| PL (1) | PL3227313T3 (https=) |
| PT (1) | PT3227313T (https=) |
| SG (1) | SG11201704427YA (https=) |
| TW (1) | TW201632542A (https=) |
| WO (1) | WO2016090022A1 (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114748605A (zh) | 2011-11-29 | 2022-07-15 | 普罗克拉拉生物科学股份有限公司 | 噬菌体基因3蛋白组合物及作为淀粉样蛋白结合剂的用途 |
| CN104870008B (zh) | 2012-10-02 | 2019-10-01 | 普罗克拉拉生物科学股份有限公司 | 噬菌体的p3融合蛋白作为淀粉样蛋白结合剂的用途 |
| KR20160010618A (ko) | 2013-05-28 | 2016-01-27 | 뉴로페이지 파마슈티컬즈, 인크. | 감소된 면역원성을 갖는 개질된 박테리오파아지 g3p 아미노산 서열을 포함하는 폴리펩티드 |
| PL3227313T3 (pl) | 2014-12-03 | 2022-05-09 | Proclara Biosciences, Inc. | Polipeptydy zawierające zmodyfikowaną sekwencję aminokwasową bakteriofaga g3p pozbawioną sygnału glikozylacji |
| EP3806884B1 (en) * | 2018-06-15 | 2023-08-02 | Amyl Therapeutics | General amyloid interaction motif (gaim) |
| CN120641092A (zh) | 2022-12-02 | 2025-09-12 | 阿尔泽恩股份有限公司 | 用于用曲米沙特治疗神经变性病症的方法 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3941763A (en) | 1975-03-28 | 1976-03-02 | American Home Products Corporation | PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates |
| US4215051A (en) | 1979-08-29 | 1980-07-29 | Standard Oil Company (Indiana) | Formation, purification and recovery of phthalic anhydride |
| EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
| EP0401384B1 (en) | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
| ATE194384T1 (de) | 1989-09-12 | 2000-07-15 | Hoffmann La Roche | Tnf-bindende proteine |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| US5252714A (en) | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| DK0575545T3 (da) | 1991-03-15 | 2003-09-15 | Amgen Inc | Pegylering af polypeptider |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| DE69334070T2 (de) | 1992-05-26 | 2007-01-04 | Immunex Corp., Thousand Oaks | Neue zytokine die cd30 binden |
| WO1998052976A1 (en) | 1997-05-21 | 1998-11-26 | Biovation Limited | Method for the production of non-immunogenic proteins |
| WO2000034317A2 (en) | 1998-12-08 | 2000-06-15 | Biovation Limited | Method for reducing immunogenicity of proteins |
| US20020052311A1 (en) | 1999-09-03 | 2002-05-02 | Beka Solomon | Methods and compostions for the treatment and/or diagnosis of neurological diseases and disorders |
| US8022270B2 (en) | 2000-07-31 | 2011-09-20 | Biolex Therapeutics, Inc. | Expression of biologically active polypeptides in duckweed |
| US7189830B2 (en) | 2001-02-19 | 2007-03-13 | Merck Patent Gmbh | Anti-KSA/IL-2 fusion proteins with reduced immunogenicity |
| MXPA03008032A (es) | 2001-03-08 | 2003-12-04 | Merck Patent Gmbh | Factor de estimulacion de colonias de granulocitos- macrofagos modificado con inmunogenicidad reducida. |
| DE10238846A1 (de) | 2002-08-20 | 2004-03-04 | Nemod Immuntherapie Ag | Aktive Fusionsproteine und Verfahren zu ihrer Herstellung |
| EP1853285B1 (en) | 2005-02-01 | 2011-03-16 | Ramot at Tel-Aviv University Ltd. | Method for treating inflammation associated with amyloid deposits and brain inflammation involving activated microglia |
| MX2008010612A (es) | 2006-02-15 | 2009-03-20 | Ramot At Tel Aviv University | Bacteriofago filamentoso que exhibe proteina a como aglutinante de anticuerpos e inmunocomplejos para el suministro hacia el cerebro. |
| US20090304726A1 (en) | 2006-02-15 | 2009-12-10 | Ramot At Tel Aviv University Ltd. | Viral display vehicles for treating multiple sclerosis |
| WO2007109733A2 (en) | 2006-03-21 | 2007-09-27 | The Johns Hopkins University | Diagnostic and prognostic markers and treatment strategies for multiple sclerosis |
| WO2007114139A1 (ja) | 2006-04-06 | 2007-10-11 | Fumiaki Uchiyama | 新規繊維状ファージによるファージディスプレイ |
| EP2054515B1 (en) | 2006-07-21 | 2012-01-11 | Ramot at Tel-Aviv University Ltd. | Use of a phage displaying a peptide from an adhesion protein for treating a disease associated with intracellular formation of protein fibrillar inclusions or aggregates |
| EP2080138A2 (en) | 2006-10-11 | 2009-07-22 | Antitope Limited | T cell epitope databases |
| WO2009143470A1 (en) | 2008-05-22 | 2009-11-26 | Ramot At Tel Aviv University Ltd. | Method for treating disease characterized by plaque |
| RU2011125971A (ru) | 2008-11-24 | 2012-12-27 | Рамот Эт Тель-Авив Юниверсити Лтд. | Способ лечения болезни паркинсона |
| WO2011084714A2 (en) | 2009-12-17 | 2011-07-14 | Biogen Idec Ma Inc. | STABILIZED ANTI-TNF-ALPHA scFv MOLECULES OR ANTI-TWEAK scFv MOLECULES AND USES THEREOF |
| BR112013023040A2 (pt) | 2011-03-11 | 2018-10-23 | Univ Ramot | bacteriófago filamentoso, composição farmacêutica, e, métodos para reduzir a formação de fibrilas de proteína tau ou para desagregar fibrilas pré-formadas de proteína tau em um paciente, e para tratar uma tauopatia degenerativa. |
| CN114748605A (zh) | 2011-11-29 | 2022-07-15 | 普罗克拉拉生物科学股份有限公司 | 噬菌体基因3蛋白组合物及作为淀粉样蛋白结合剂的用途 |
| CN104870008B (zh) | 2012-10-02 | 2019-10-01 | 普罗克拉拉生物科学股份有限公司 | 噬菌体的p3融合蛋白作为淀粉样蛋白结合剂的用途 |
| KR20160010618A (ko) * | 2013-05-28 | 2016-01-27 | 뉴로페이지 파마슈티컬즈, 인크. | 감소된 면역원성을 갖는 개질된 박테리오파아지 g3p 아미노산 서열을 포함하는 폴리펩티드 |
| PL3227313T3 (pl) | 2014-12-03 | 2022-05-09 | Proclara Biosciences, Inc. | Polipeptydy zawierające zmodyfikowaną sekwencję aminokwasową bakteriofaga g3p pozbawioną sygnału glikozylacji |
-
2015
- 2015-12-02 PL PL15831011T patent/PL3227313T3/pl unknown
- 2015-12-02 CA CA2969128A patent/CA2969128A1/en not_active Abandoned
- 2015-12-02 SG SG11201704427YA patent/SG11201704427YA/en unknown
- 2015-12-02 AU AU2015358504A patent/AU2015358504A1/en not_active Abandoned
- 2015-12-02 US US15/532,820 patent/US10722551B2/en active Active
- 2015-12-02 PT PT158310110T patent/PT3227313T/pt unknown
- 2015-12-02 KR KR1020177017763A patent/KR20170085132A/ko not_active Withdrawn
- 2015-12-02 TW TW104140347A patent/TW201632542A/zh unknown
- 2015-12-02 EP EP15831011.0A patent/EP3227313B1/en active Active
- 2015-12-02 MX MX2017007059A patent/MX2017007059A/es unknown
- 2015-12-02 EA EA201791212A patent/EA201791212A1/ru unknown
- 2015-12-02 DK DK15831011.0T patent/DK3227313T3/da active
- 2015-12-02 JP JP2017529043A patent/JP6730988B2/ja not_active Expired - Fee Related
- 2015-12-02 WO PCT/US2015/063476 patent/WO2016090022A1/en not_active Ceased
- 2015-12-02 ES ES15831011T patent/ES2910017T3/es active Active
- 2015-12-02 CN CN201580065696.9A patent/CN107250154A/zh active Pending
- 2015-12-02 BR BR112017011530A patent/BR112017011530A2/pt not_active Application Discontinuation
- 2015-12-03 AR ARP150103956A patent/AR102890A1/es unknown
-
2017
- 2017-05-22 IL IL252426A patent/IL252426A0/en unknown
- 2017-05-31 PH PH12017501004A patent/PH12017501004A1/en unknown
-
2020
- 2020-02-19 JP JP2020026300A patent/JP2020073610A/ja not_active Withdrawn
- 2020-06-18 US US16/905,128 patent/US11723951B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016090022A9 (en) | 2016-08-25 |
| CA2969128A1 (en) | 2016-06-09 |
| US20180207231A1 (en) | 2018-07-26 |
| AU2015358504A8 (en) | 2017-07-13 |
| CN107250154A (zh) | 2017-10-13 |
| JP6730988B2 (ja) | 2020-07-29 |
| IL252426A0 (en) | 2017-07-31 |
| JP2020073610A (ja) | 2020-05-14 |
| AR102890A1 (es) | 2017-03-29 |
| DK3227313T3 (da) | 2022-04-19 |
| AU2015358504A1 (en) | 2017-06-29 |
| PH12017501004A1 (en) | 2017-12-18 |
| ES2910017T3 (es) | 2022-05-11 |
| EP3227313B1 (en) | 2022-02-09 |
| SG11201704427YA (en) | 2017-06-29 |
| TW201632542A (zh) | 2016-09-16 |
| WO2016090022A1 (en) | 2016-06-09 |
| KR20170085132A (ko) | 2017-07-21 |
| US11723951B2 (en) | 2023-08-15 |
| PT3227313T (pt) | 2022-04-12 |
| JP2017538407A (ja) | 2017-12-28 |
| MX2017007059A (es) | 2018-05-02 |
| US10722551B2 (en) | 2020-07-28 |
| US20210015895A1 (en) | 2021-01-21 |
| PL3227313T3 (pl) | 2022-05-09 |
| EA201791212A1 (ru) | 2018-01-31 |
| WO2016090022A8 (en) | 2017-06-22 |
| EP3227313A1 (en) | 2017-10-11 |
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| Date | Code | Title | Description |
|---|---|---|---|
| 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. |
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| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] | ||
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 5A ANUIDADE. |
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| B11B | Dismissal acc. art. 36, par 1 of ipl - no reply within 90 days to fullfil the necessary requirements |