DE69326069T2 - Zusammensetzungen die die hiv replikation inhibieren - Google Patents
Zusammensetzungen die die hiv replikation inhibierenInfo
- Publication number
- DE69326069T2 DE69326069T2 DE69326069T DE69326069T DE69326069T2 DE 69326069 T2 DE69326069 T2 DE 69326069T2 DE 69326069 T DE69326069 T DE 69326069T DE 69326069 T DE69326069 T DE 69326069T DE 69326069 T2 DE69326069 T2 DE 69326069T2
- Authority
- DE
- Germany
- Prior art keywords
- hiv
- compositions
- inhibit hiv
- methods
- hiv replication
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/16011—Orthomyxoviridae
- C12N2760/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18522—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/806—Antigenic peptides or proteins
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US91654092A | 1992-07-20 | 1992-07-20 | |
US92753292A | 1992-08-07 | 1992-08-07 | |
PCT/US1993/006769 WO1994002505A1 (en) | 1992-07-20 | 1993-07-19 | Compounds which inhibit hiv replication |
Publications (2)
Publication Number | Publication Date |
---|---|
DE69326069D1 DE69326069D1 (de) | 1999-09-23 |
DE69326069T2 true DE69326069T2 (de) | 2000-03-23 |
Family
ID=27129697
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69326069T Expired - Fee Related DE69326069T2 (de) | 1992-07-20 | 1993-07-19 | Zusammensetzungen die die hiv replikation inhibieren |
Country Status (11)
Country | Link |
---|---|
US (3) | US5656480A (de) |
EP (1) | EP0652895B1 (de) |
JP (1) | JP4010560B2 (de) |
KR (1) | KR100358209B1 (de) |
AT (1) | ATE183515T1 (de) |
AU (1) | AU688733B2 (de) |
CA (1) | CA2140663C (de) |
DE (1) | DE69326069T2 (de) |
ES (1) | ES2139017T3 (de) |
NZ (1) | NZ254640A (de) |
WO (1) | WO1994002505A1 (de) |
Families Citing this family (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ254640A (en) * | 1992-07-20 | 1997-04-24 | Univ Duke | Hiv protein fragments of transmembrane glycoprotein gp41 (dp-107) with antiviral activity and their use |
US5464933A (en) * | 1993-06-07 | 1995-11-07 | Duke University | Synthetic peptide inhibitors of HIV transmission |
US6479055B1 (en) * | 1993-06-07 | 2002-11-12 | Trimeris, Inc. | Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission |
NZ311319A (en) * | 1995-06-07 | 2000-01-28 | Trimeris Inc | The treatment of HIV and other viral infections using the peptide DP-178 or DP-107 in combination therapy |
US6271198B1 (en) | 1996-11-06 | 2001-08-07 | Genentech, Inc. | Constrained helical peptides and methods of making same |
AU6649698A (en) * | 1997-01-28 | 1998-08-18 | Regents Of The University Of California, The | Peptide probes to coil proteins and methods for making the same |
US6818740B1 (en) | 1997-04-17 | 2004-11-16 | Whitehead Institute For Biomedical Research | Inhibitors of HIV membrane fusion |
US6150088A (en) | 1997-04-17 | 2000-11-21 | Whitehead Institute For Biomedical Research | Core structure of gp41 from the HIV envelope glycoprotein |
US6841657B2 (en) | 1997-04-17 | 2005-01-11 | Whitehead Institute For Biomedical Research | Inhibitors of HIV membrane fusion |
FR2771011B1 (fr) | 1997-11-17 | 2000-01-28 | Hippocampe | Obtention de vaccins destines a prevenir les effets pathogenes associes a une infection retrovirale |
GB9801070D0 (en) * | 1998-01-19 | 1998-03-18 | Andaris Ltd | HIV inhibition |
US6281331B1 (en) * | 1998-03-23 | 2001-08-28 | Trimeris, Inc. | Methods and compositions for peptide synthesis |
US6656906B1 (en) | 1998-05-20 | 2003-12-02 | Trimeris, Inc. | Hybrid polypeptides with enhanced pharmacokinetic properties |
US6258782B1 (en) | 1998-05-20 | 2001-07-10 | Trimeris, Inc. | Hybrid polypeptides with enhanced pharmacokinetic properties |
EP1100818B1 (de) * | 1998-07-30 | 2013-01-02 | Whitehead Institute For Biomedical Research | Inhibitoren der membranfusion von hiv |
US7960504B2 (en) | 1998-07-30 | 2011-06-14 | Whitehead Institute For Biomedical Research | Inhibitors of HIV membrane fusion |
US6747126B1 (en) | 1998-07-30 | 2004-06-08 | Whitehead Institute For Biomedical Research | Peptide inhibitors of HIV entry |
AU2604200A (en) * | 1999-01-08 | 2000-07-24 | Panacos Pharmaceuticals, Inc. | Methods of eliciting broadly neutralizing antibodies targeting hiv-1 gp41 |
BR0010757A (pt) * | 1999-05-17 | 2002-02-19 | Conjuchem Inc | Inibidores de peptìdeo de fusão de longa duração de infecção viral |
US6469136B1 (en) * | 1999-07-07 | 2002-10-22 | Trimeris, Inc. | Methods and composition for peptide synthesis |
US6750008B1 (en) | 1999-07-09 | 2004-06-15 | Trimeris, Inc. | Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission |
US6541020B1 (en) * | 1999-07-09 | 2003-04-01 | Trimeris, Inc. | Methods and compositions for administration of therapeutic reagents |
US20030082525A1 (en) * | 1999-12-16 | 2003-05-01 | Whitehead Institute For Biomedical Research | Five-Helix protein |
WO2001044286A2 (en) | 1999-12-16 | 2001-06-21 | Whitehead Institute For Biomedical Research | Five-helix protein |
AU3334001A (en) | 2000-02-10 | 2001-08-20 | Panacos Pharmaceuticals Inc | Assay for detection of viral fusion inhibitors |
US6623741B1 (en) | 2000-02-29 | 2003-09-23 | Trimeris, Inc. | Methods and compositions for inhibition of membrane fusion-associated events including RSV transmission |
US6528308B1 (en) * | 2000-03-16 | 2003-03-04 | Duke University | Suppressor of HIV replication and transcription |
NZ521977A (en) * | 2000-03-17 | 2004-05-28 | Panacos Pharmaceuticals Inc | A method for generating immunogens that elicit neutralizing antibodies against fusion-active regions of HIV envelope proteins |
WO2002096935A2 (en) * | 2001-05-31 | 2002-12-05 | Conjuchem, Inc. | Long lasting fusion peptide inhibitors for hiv infection |
EP1752469B1 (de) * | 2001-05-31 | 2008-10-29 | ConjuChem Biotechnologies Inc. | Langwirkende Fusionspeptidinhibitoren gegen HIV-Infektion |
WO2002103026A2 (en) * | 2001-06-15 | 2002-12-27 | F. Hoffmann-La Roche Ag | Method for the recombinant production of peptidic antiviral fusion inhibitors, and acetylation of gb41 fragments |
WO2003006056A2 (en) * | 2001-07-11 | 2003-01-23 | Genfa Zhou | End-locked five-helix protein |
CN1100564C (zh) * | 2001-08-29 | 2003-02-05 | 周根发 | 用于治疗hiv感染的药物、其组合物及其用途 |
WO2003048187A2 (en) * | 2001-11-29 | 2003-06-12 | Mymetics, Corp. | Peptides and use thereof in therapeutic agents against hiv infection |
US20060241027A1 (en) * | 2002-02-07 | 2006-10-26 | Hans-Peter Hauser | Hiv inhibiting proteins |
US20040076637A1 (en) * | 2002-09-27 | 2004-04-22 | Delmedico Mary Kay | HIV-derived HR1 peptides modified to form stable trimers, and their use in therapy to inhibit transmission of human immunodeficiency virus |
US7556813B2 (en) * | 2002-09-27 | 2009-07-07 | Trimeris, Inc. | Antiviral peptide-polymer conjugate comprising a polymer covalently attached to two or more synthetic HIV gp41 HR1 and/or HR2 peptides |
US7045552B2 (en) * | 2002-09-27 | 2006-05-16 | Trimeris, Inc. | Pharmaceutical composition for improved administration of HIV gp41-derived peptides, and its use in therapy |
WO2004035808A2 (en) * | 2002-10-16 | 2004-04-29 | Panacos Pharmaceuticals, Inc. | Method for detecting viral inactivating agents |
CA2443365C (en) * | 2002-11-19 | 2010-01-12 | F. Hoffmann-La Roche Ag | Methods for the recombinant production of antifusogenic peptides |
EP1578461A4 (de) * | 2002-12-18 | 2008-09-03 | Univ Maryland Biotech Inst | Impfstoffe gegen hiv-tat-protein zur erzeugung von neutralisierenden antikörpern |
WO2004108886A2 (en) * | 2003-05-08 | 2004-12-16 | Anderson Porter W | Anti-hiv-1 compounds based upon a conserved amino acid sequence shared by gp160 and the human cd4 protein |
WO2005018666A1 (en) * | 2003-08-14 | 2005-03-03 | The Government Of The United States Of America, As Represented By The Department Of Health And Human Services | Polypeptide multimers having antiviral activity |
KR20050024730A (ko) * | 2003-09-01 | 2005-03-11 | 코바이오텍 (주) | T―20 펩타이드 코딩 유전자를 포함하는 재조합대장균의 고농도 세포 배양 방법 및 이로부터 생산된t―20 펩타이드의 분리 및 정제 방법 |
US7744897B2 (en) | 2003-12-23 | 2010-06-29 | Dillon Susan B | Human immunodeficiency virus gp41 mimetibody polypeptides |
EP1701972B1 (de) * | 2003-12-31 | 2008-10-08 | F. Hoffmann-La Roche Ag | Verfahren und systeme zur rückgewinnung von peptiden |
WO2005063800A2 (en) * | 2003-12-31 | 2005-07-14 | F. Hoffmann-La Roche Ag | Peptide synthesis using decanting filter |
WO2005063799A2 (en) * | 2003-12-31 | 2005-07-14 | F.Hoffmann-La Roche Ag | Peptide synthesis and deprotection with co-solvent |
DE602004009710T2 (de) * | 2003-12-31 | 2008-08-07 | F. Hoffmann-La Roche Ag | Verfahren zur peptidsynthese unter verwendung einer reduzierten menge an entschützungsmittel |
WO2005063792A2 (en) * | 2003-12-31 | 2005-07-14 | F. Hoffmann-La Roche Ag | Methods for recovering cleaved peptide from a support |
CA2551082A1 (en) * | 2004-01-07 | 2005-07-28 | Trimeris, Inc. | Hiv gp41 hr2-derived synthetic peptides, and their use in therapy to inhibit transmission of human immunodeficiency virus |
US20080039532A1 (en) * | 2004-05-06 | 2008-02-14 | Dominique Bridon | Compounds For Specific Viral Target |
JP5069558B2 (ja) | 2004-06-01 | 2012-11-07 | メルク・シャープ・エンド・ドーム・コーポレイション | HIVgp41融合中間物質の安定したペプチド模倣薬 |
ATE516048T1 (de) * | 2004-06-01 | 2011-07-15 | Merck Sharp & Dohme | Mit hiv gp41 in wechselwirkung stehende menschliche antikörper |
WO2006069779A1 (en) * | 2004-12-30 | 2006-07-06 | F. Hoffmann-La Roche Ag | Preparing of peptides with excellent solubility |
CN101133077B (zh) * | 2004-12-30 | 2012-09-05 | 弗·哈夫曼-拉罗切有限公司 | 使用肽中间片段合成肽t-20 |
WO2006069697A1 (en) * | 2004-12-30 | 2006-07-06 | F. Hoffmann-La Roche Ag | Colorimetrically assessing peptide characteristics |
ES2329270T3 (es) * | 2004-12-30 | 2009-11-24 | F. Hoffmann-La Roche Ag | Sintesis del peptido t-1249 utilizando fragmentos intermediarios del ipeptido. |
EP1868652A2 (de) * | 2005-04-05 | 2007-12-26 | Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. | Verfahren zur abschirmung von funktionalen stellen oder epitopen auf proteinen |
AR059300A1 (es) | 2006-02-02 | 2008-03-26 | Trimeris Inc | Peptidos inhibidores de la fusion de vih con propiedades biologicas mejoradas |
JP2008005838A (ja) * | 2006-05-31 | 2008-01-17 | Wataru Sakamoto | 新規ペルオキシダーゼ検出用試薬組成物及びこれを用いた炎症疾患等の判定法および抗酸化活性測定法 |
TW200817438A (en) * | 2006-08-17 | 2008-04-16 | Hoffmann La Roche | A conjugate of an antibody against CCR5 and an antifusogenic peptide |
MX2009001204A (es) | 2006-08-17 | 2009-02-11 | Hoffmann La Roche | Conjugado de un anticuerpo cointra ccr5 y un peptido antifusogenico. |
KR20090098880A (ko) | 2006-12-12 | 2009-09-17 | 바이오렉시스 파마슈티칼 코포레이션 | 트랜스페린 융합 단백질 라이브러리 |
US20090088378A1 (en) * | 2007-01-12 | 2009-04-02 | Omar Quraishi | Long lasting inhibitors of viral infection |
TW200902544A (en) * | 2007-03-13 | 2009-01-16 | Hoffmann La Roche | Peptide-complement conjugates |
MX2009010689A (es) * | 2007-04-03 | 2009-12-14 | Trimeris Inc | Formulaciones novedosas para el suministro de agentes terapeuticos de peptidos antivirales. |
BRPI0811864A2 (pt) * | 2007-05-16 | 2014-11-18 | Conjuchem Biotechnologies Inc | Derivados de ácido cistéico de peptídeos antivirais |
AR067584A1 (es) | 2007-07-20 | 2009-10-14 | Hoffmann La Roche | Un conjugado de un anticuerpo contra la cd4 y peptidos antifusogenicos |
WO2009042194A2 (en) * | 2007-09-25 | 2009-04-02 | Trimeris, Inc. | Methods of synthesis for therapeuthic anti-hiv peptides |
WO2011133948A2 (en) | 2010-04-22 | 2011-10-27 | Longevity Biotech, Inc. | Highly active polypeptides and methods of making and using the same |
EP2616487B1 (de) | 2010-09-14 | 2015-03-25 | F.Hoffmann-La Roche Ag | Serpin-finger-fusionspolypeptid |
WO2013150532A1 (en) | 2012-04-04 | 2013-10-10 | Yeda Research And Development Co. Ltd. | Lipopeptide conjugates comprising sphingolipid and hiv gp41 derived peptides |
WO2014145718A2 (en) | 2013-03-15 | 2014-09-18 | Longevity Biotech, Inc. | Peptides comprising non-natural amino acids and methods of making and using the same |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8305985D0 (en) * | 1983-03-04 | 1983-04-07 | Szelke M | Enzyme inhibition |
ATE98376T1 (de) * | 1986-03-24 | 1993-12-15 | Ortho Pharma Corp | Synthetische htlv-iii-peptid-zusammensetzungen und ihre verwendung. |
US5030449A (en) * | 1988-07-21 | 1991-07-09 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Synthetic vaccine against AIDS virus |
EP0323157A3 (de) * | 1987-12-24 | 1990-07-25 | The University Of Melbourne | Antivirale Verbindungen und Methoden |
DE3854425T2 (de) * | 1987-12-28 | 1996-03-07 | Yamaha Corp | Elfenbeinartiges Tastenmaterial und Verfahren zur Herstellung. |
GB8828097D0 (en) * | 1988-12-01 | 1989-01-05 | Wellcome Found | Peptides |
US5444044A (en) * | 1992-03-26 | 1995-08-22 | New York Blood Center | Synthetic polypeptides as inhibitors of HIV-1 |
NZ254640A (en) * | 1992-07-20 | 1997-04-24 | Univ Duke | Hiv protein fragments of transmembrane glycoprotein gp41 (dp-107) with antiviral activity and their use |
WO1994016109A1 (en) | 1993-01-15 | 1994-07-21 | Whitehead Institute For Biomedical Research | Membrane fusion events and means for altering same |
-
1993
- 1993-07-19 NZ NZ254640A patent/NZ254640A/en not_active IP Right Cessation
- 1993-07-19 DE DE69326069T patent/DE69326069T2/de not_active Expired - Fee Related
- 1993-07-19 JP JP50462594A patent/JP4010560B2/ja not_active Expired - Fee Related
- 1993-07-19 CA CA002140663A patent/CA2140663C/en not_active Expired - Fee Related
- 1993-07-19 EP EP93917272A patent/EP0652895B1/de not_active Expired - Lifetime
- 1993-07-19 AU AU46837/93A patent/AU688733B2/en not_active Ceased
- 1993-07-19 KR KR1019950700214A patent/KR100358209B1/ko not_active IP Right Cessation
- 1993-07-19 AT AT93917272T patent/ATE183515T1/de not_active IP Right Cessation
- 1993-07-19 WO PCT/US1993/006769 patent/WO1994002505A1/en active IP Right Grant
- 1993-07-19 ES ES93917272T patent/ES2139017T3/es not_active Expired - Lifetime
-
1995
- 1995-01-27 US US08/374,666 patent/US5656480A/en not_active Expired - Lifetime
- 1995-06-02 US US08/464,003 patent/US6573078B1/en not_active Expired - Fee Related
-
2003
- 2003-04-15 US US10/414,192 patent/US20030181382A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
KR950702575A (ko) | 1995-07-29 |
US5656480A (en) | 1997-08-12 |
ATE183515T1 (de) | 1999-09-15 |
NZ254640A (en) | 1997-04-24 |
AU4683793A (en) | 1994-02-14 |
AU688733B2 (en) | 1998-03-19 |
EP0652895B1 (de) | 1999-08-18 |
JPH08500342A (ja) | 1996-01-16 |
US20030181382A1 (en) | 2003-09-25 |
CA2140663A1 (en) | 1994-02-03 |
ES2139017T3 (es) | 2000-02-01 |
KR100358209B1 (ko) | 2003-01-24 |
JP4010560B2 (ja) | 2007-11-21 |
US6573078B1 (en) | 2003-06-03 |
EP0652895A1 (de) | 1995-05-17 |
CA2140663C (en) | 2004-01-27 |
DE69326069D1 (de) | 1999-09-23 |
EP0652895A4 (de) | 1997-02-05 |
WO1994002505A1 (en) | 1994-02-03 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
8364 | No opposition during term of opposition | ||
8339 | Ceased/non-payment of the annual fee |