DK164392C - Anvendelse af 3'-azido-3'-desoxythymidin til fremstilling af et laegemiddel til behandling af eller profylakse for en human retrovirusinfektion - Google Patents

Anvendelse af 3'-azido-3'-desoxythymidin til fremstilling af et laegemiddel til behandling af eller profylakse for en human retrovirusinfektion

Info

Publication number
DK164392C
DK164392C DK118086A DK118086A DK164392C DK 164392 C DK164392 C DK 164392C DK 118086 A DK118086 A DK 118086A DK 118086 A DK118086 A DK 118086A DK 164392 C DK164392 C DK 164392C
Authority
DK
Denmark
Prior art keywords
desoxythymidine
prophylaxy
azido
medicine
prepare
Prior art date
Application number
DK118086A
Other languages
Danish (da)
English (en)
Other versions
DK118086A (da
DK118086D0 (da
DK164392B (da
Inventor
Janet Litster Rideout
David Walter Barry
Sandra Nusinoff Lehrman
Clair Martha Heider St
Phillip Allen Furman
George Andrew Freeman
Original Assignee
Wellcome Found
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27516579&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DK164392(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB858506869A external-priority patent/GB8506869D0/en
Priority claimed from GB858511774A external-priority patent/GB8511774D0/en
Priority claimed from US06/776,899 external-priority patent/US4724232A/en
Priority claimed from GB858523881A external-priority patent/GB8523881D0/en
Priority claimed from GB868603450A external-priority patent/GB8603450D0/en
Application filed by Wellcome Found filed Critical Wellcome Found
Publication of DK118086D0 publication Critical patent/DK118086D0/da
Publication of DK118086A publication Critical patent/DK118086A/da
Priority to DK199102026A priority Critical patent/DK175122B1/da
Priority to DK199102027A priority patent/DK175192B1/da
Publication of DK164392B publication Critical patent/DK164392B/da
Publication of DK164392C publication Critical patent/DK164392C/da
Application granted granted Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/21Interferons [IFN]
    • A61K38/212IFN-alpha
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06Pyrimidine radicals
    • C07H19/10Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
DK118086A 1985-03-16 1986-03-14 Anvendelse af 3'-azido-3'-desoxythymidin til fremstilling af et laegemiddel til behandling af eller profylakse for en human retrovirusinfektion DK164392C (da)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DK199102027A DK175192B1 (da) 1985-03-16 1991-12-18 Farmaceutisk præparat med indhold af 3'-azido-3'-desoxythymidin som aktiv ingrediens samt 3'-azido-3'-desoxythymidin til anvendelse mod en human retrovirusinfektion
DK199102026A DK175122B1 (da) 1985-03-16 1991-12-18 Farmaceutisk præparat omfattende et farmaceutisk acceptabelt derivat af 3'azido-3'-desoxythymidin samt fremgangsmåde til fremstilling deraf

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
GB858506869A GB8506869D0 (en) 1985-03-16 1985-03-16 Antiviral compound
GB858511774A GB8511774D0 (en) 1985-05-09 1985-05-09 Antiviral compounds
US77689985 1985-09-17
US06/776,899 US4724232A (en) 1985-03-16 1985-09-17 Treatment of human viral infections
GB858523881A GB8523881D0 (en) 1985-09-27 1985-09-27 Antiviral compounds
GB8506869 1986-02-12
GB868603450A GB8603450D0 (en) 1986-02-12 1986-02-12 Antiviral compounds
GB8603450 1986-02-12
GB8523881 1986-02-12
GB8511774 1986-02-12

Publications (4)

Publication Number Publication Date
DK118086D0 DK118086D0 (da) 1986-03-14
DK118086A DK118086A (da) 1986-09-17
DK164392B DK164392B (da) 1992-06-22
DK164392C true DK164392C (da) 1992-11-09

Family

ID=27516579

Family Applications (1)

Application Number Title Priority Date Filing Date
DK118086A DK164392C (da) 1985-03-16 1986-03-14 Anvendelse af 3'-azido-3'-desoxythymidin til fremstilling af et laegemiddel til behandling af eller profylakse for en human retrovirusinfektion

Country Status (21)

Country Link
EP (2) EP0291633B1 (de)
JP (1) JPH0780898B2 (de)
AP (1) AP11A (de)
AT (4) ATE44464T1 (de)
AU (1) AU572019B2 (de)
CA (1) CA1238277A (de)
CS (1) CS385191A3 (de)
CY (2) CY1508A (de)
DE (4) DE3650130T3 (de)
DK (1) DK164392C (de)
FI (1) FI85978C (de)
GR (1) GR860712B (de)
HK (2) HK85789A (de)
IE (1) IE56503B1 (de)
IL (1) IL78158A (de)
MC (1) MC1742A1 (de)
MY (1) MY102693A (de)
NZ (1) NZ215486A (de)
PH (1) PH24388A (de)
PT (1) PT82199B (de)
SG (1) SG62889G (de)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE190064T1 (de) * 1985-09-17 2000-03-15 Wellcome Found Kombination therapeutische nukleoside mit weiteren therapeutisch wirksamen komponenten.
US5077279A (en) * 1986-05-01 1991-12-31 University Of Georgia Research Foundation, Inc. 3'-azido-2',3'-dideoxy-5-methylcytidine anti-viral composition
US4916122A (en) * 1987-01-28 1990-04-10 University Of Georgia Research Foundation, Inc. 3'-Azido-2',3'-dideoxyuridine anti-retroviral composition
US4841039A (en) * 1986-05-01 1989-06-20 Emory University 2',3'-dideoxy-5-substituted uridines and related compounds as antiviral agents
US5084445A (en) * 1986-05-01 1992-01-28 University Of Georgia Research Foundation, Inc. 3'-azido-2',3'-dideoxy-5-methylcytidine
EP0332626A1 (de) * 1986-11-21 1989-09-20 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Zubereitungen zur behandlung viraler infektionen bei menschen
US4880782A (en) * 1986-11-21 1989-11-14 Max-Planck-Gesellschaft Zur Foederung Der Wissenschaften E.V. Method of treating viral infections in humans and compositions therefor
SE8605503D0 (sv) * 1986-12-19 1986-12-19 Astra Laekemedel Ab Novel medicinal use
US5190926A (en) * 1987-01-28 1993-03-02 University Of Georgia Research Foundation, Inc. 3'-azido-2',3'-dideoxypyrimidines and related compounds as antiviral agents
HU199865B (en) * 1987-03-16 1990-03-28 Wellcome Found Process for production of healing nucleosides and medical compositions containing them
EP0286825A3 (de) * 1987-03-18 1989-04-12 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Verwendung von 3'-fluro-3'-deoxythymidine zur Herstellung von medicamenten zur Behandlung von Viruskrankheiten
EP0282618A1 (de) * 1987-03-18 1988-09-21 Vereniging Het Nederlands Kanker Instituut 1-Deoxynojirimycin als Anti-HIV-Therapeutikum
US4950652A (en) * 1987-03-23 1990-08-21 Hem Research, Inc. dsRNAs for combination therapy in the treatment of viral diseases
EP0292101A3 (de) * 1987-03-25 1990-01-31 The Wellcome Foundation Limited Verfahren zur Herstellung von 3'-Azido-3'-deoxythymidin und Zwischenverbindungen
GB8707421D0 (en) * 1987-03-27 1987-04-29 Wellcome Found Pharmaceutical formulations
US5185437A (en) * 1987-04-09 1993-02-09 Burroughs Wellcome Co. Therapeutic nucleosides
IL86007A0 (en) * 1987-04-09 1988-09-30 Wellcome Found 6-substituted purine nucleosides,their preparation and pharmaceutical compositions containing them
IL86009A (en) * 1987-04-10 1991-09-16 Us Health Liposome-encapsulated phosphorylated nucleosides for treatment of retroviral diseases
US5215970A (en) * 1987-04-16 1993-06-01 Medivir Ab Nucleosides and nucleotide analogues, pharmaceutical composition and processes for the preparation of the compounds
SE8701605D0 (sv) * 1987-04-16 1987-04-16 Astra Ab Novel medicinal compounds
JPS63280026A (ja) * 1987-04-24 1988-11-17 ザ ウエルカム フアウンデーション リミテッド 抗ウイルス配合組成物
US4863927A (en) * 1987-05-11 1989-09-05 Merck & Co., Inc. 1-(2-hydroxymethyl)cycloalkylmethyl)-5-substituted uracils
YU110888A (en) * 1987-06-10 1989-08-31 Wellcome Found Process for obtaining timine derivatives
USRE33887E (en) * 1987-06-22 1992-04-14 Hoffmann-La Roche Inc. Anti-retroviral compounds
SU1548182A1 (ru) * 1987-12-29 1990-03-07 Институт молекулярной биологии АН СССР 5 @ -Фосфонаты 3 @ -азидо-2 @ ,3 @ -дидезоксинуклеозидов, вл ющиес специфическими ингибиторами вируса СПИД в культуре лимфоцитов человека Н9/ШВ
US5384396A (en) * 1988-02-23 1995-01-24 The University Of Georgia Research Foundation, Inc. Process for the deoxygenation of nucleosides
DE3824669C2 (de) * 1988-07-20 1999-05-06 Wondrak Ewald M Verwendung von Trinatrium-Phosphonoformat
US4987224A (en) * 1988-08-02 1991-01-22 University Of Georgia Research Foundation, Inc. Method of preparation of 2',3'-dideoxynucleosides
EP0355245A1 (de) * 1988-08-26 1990-02-28 Michel Vandevelde Anwendung von Inhibitoren der reversen Transcriptase von Retroviren
HU205089B (en) * 1989-05-31 1992-03-30 Biogal Gyogyszergyar Process for producing new thymine derivatives and pharmaceutical compositions comprising same
IE67874B1 (en) * 1989-11-09 1996-05-01 Asta Medica Ag Medicaments containing as active substance sulphur-containing carboxylic acids and their use in combating retroviruses
DE69102764T2 (de) * 1990-04-19 1995-02-09 Previsan S.A., Luxemburg/Luxembourg Azoische derivate, pharmazeutische und desinfektierende zusammensetzungen diese substanzen enthaltend, und deren verwendung gegen aids.
US5585367A (en) * 1990-04-19 1996-12-17 Previsan S.A. Method of treating humans and animals infected with viruses of the retrovirus group
US6812233B1 (en) 1991-03-06 2004-11-02 Emory University Therapeutic nucleosides
GB9104740D0 (en) * 1991-03-06 1991-04-17 Wellcome Found Antiviral nucleoside combination
IL102548A (en) * 1991-08-02 1998-08-16 Medivir Ab Use of painting derivatives in the preparation of drugs for VIH inhibition and treatment of SDIA and new compounds
US5593993A (en) * 1991-08-02 1997-01-14 Medivir Ab Method for inhibition of HIV related viruses
EP0639971B1 (de) * 1992-05-13 1999-09-22 The Wellcome Foundation Limited Therapeutische kombinationen
US6177435B1 (en) 1992-05-13 2001-01-23 Glaxo Wellcome Inc. Therapeutic combinations
GR920100326A (el) * 1992-07-21 1994-03-31 Medivir Ag Ενώσεις και μέ?οδοι αναστολής του HIV και των σχετικών ιών.
DE4336640A1 (de) * 1993-10-22 1995-04-27 Deutsches Rheuma Forschungszen Neue Metallchelate, Verfahren zu deren Herstellung sowie deren Verwendung als antivirale Arzneimittel
CA2270600A1 (en) 1999-05-03 2000-11-03 Infectio Recherche Inc. Method and formulations for the treatment of diseases, particularly those caused by human immunodeficiency virus and leishmania
CN102219750B (zh) 2001-10-26 2013-05-29 P.安杰莱蒂分子生物学研究所 关于hiv整合酶的n-取代的羟基嘧啶酮甲酰胺抑制剂
IL163666A0 (en) 2002-02-22 2005-12-18 New River Pharmaceuticals Inc Active agent delivery systems and methods for protecting and administering active agents
US8980894B2 (en) 2004-03-25 2015-03-17 Boehringer Ingelheim Vetmedica Gmbh Use of PDE III inhibitors for the treatment of asymptomatic (occult) heart failure
EP1579862A1 (de) 2004-03-25 2005-09-28 Boehringer Ingelheim Vetmedica Gmbh Verwendung von PDE III Ihibitoren zur Reduktion der Herzgrösse in an Herzversagen leidenden Säugern
WO2022008025A1 (en) * 2020-07-05 2022-01-13 Since & Technology Development Fund Authority 2-hydroxyiminopyrimidine nucleosides and derivitives and antiviral uses thereto

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0199451B1 (de) * 1985-03-16 1996-03-06 The Wellcome Foundation Limited Therapeutische Nukleoside

Also Published As

Publication number Publication date
AU572019B2 (en) 1988-04-28
CA1238277A (en) 1988-06-21
EP0196185B1 (de) 1989-07-12
AP11A (en) 1987-12-22
DE3650130D1 (de) 1994-12-08
DE3650130T2 (de) 1995-03-16
EP0291633A1 (de) 1988-11-23
FI861069A0 (fi) 1986-03-14
EP0196185A2 (de) 1986-10-01
NZ215486A (en) 1988-09-29
SG62889G (en) 1990-01-26
DE3650130T3 (de) 2003-07-24
EP0196185A3 (en) 1988-01-13
HK85789A (en) 1989-11-03
DE196185T1 (de) 1987-04-30
PH24388A (en) 1990-06-13
DK118086A (da) 1986-09-17
AU5475886A (en) 1986-09-18
ATA68386A (de) 1989-08-15
ATE81978T1 (de) 1992-11-15
MY102693A (en) 1992-09-30
MC1742A1 (fr) 1987-02-26
EP0291633B1 (de) 1992-11-04
CY1508A (en) 1990-08-03
DK118086D0 (da) 1986-03-14
IL78158A0 (en) 1986-07-31
JPS63290895A (ja) 1988-11-28
IE56503B1 (en) 1991-08-14
FI861069A (fi) 1986-09-17
FI85978B (fi) 1992-03-13
AT390000B (de) 1990-02-26
IE860677L (en) 1986-09-16
DE3687069T2 (de) 1993-03-25
CY1889A (en) 1996-11-22
ATE44464T1 (de) 1989-07-15
ATE113603T1 (de) 1994-11-15
FI85978C (fi) 1992-06-25
DE3687069D1 (de) 1992-12-10
DE3608606A1 (de) 1986-09-18
DK164392B (da) 1992-06-22
PT82199A (en) 1986-04-01
IL78158A (en) 1988-04-29
GR860712B (en) 1986-07-16
AP8600027A0 (en) 1986-02-01
PT82199B (pt) 1990-11-07
HK164395A (en) 1995-10-27
CS385191A3 (en) 1992-05-13
JPH0780898B2 (ja) 1995-08-30

Similar Documents

Publication Publication Date Title
DK164392C (da) Anvendelse af 3'-azido-3'-desoxythymidin til fremstilling af et laegemiddel til behandling af eller profylakse for en human retrovirusinfektion
BR8705931A (pt) Ventilador que ministra respiracao artificial a um paciente
DK333788D0 (da) Farmaceutisk praeparat til behandling af oedelagt bruskvaev
FI102182B1 (fi) Menetelmä ihmisen insuliinianalogien valmistamiseksi
DK674389A (da) Anvendelse af nalmefen eller naltrexon til fremstilling af et laegemiddel til behandling af artritiske og inflammatoriske sygdomme
DK395789D0 (da) Anvendelse af alfa-aminoboronsyrederivater til fremstilling af et laegemiddel til terapi eller profylakse af virussygdomme
DK254887D0 (da) Salve til behandling af hudsygdomme
ZA872359B (en) Treatment of diseases caused by retroviruses
DK503886D0 (da) Fastgaerelse af stive emner saasom en dentalprotese
NO873923D0 (no) Fremgangsmaate for fremstilling av et medisinsk hudpreparat
DK115390A (da) Anvendelse af interferon-gamma og/eller interleukin-6 til fremstilling af et laegemiddel til behandling af blodtrauma
DK464687A (da) Nucleosid-analoger og deres farmaceutiske anvendelse
DK599986D0 (da) Terapeutisk middel i form af et hudplaster
DK31386D0 (da) Behandling af proliferative hudsygdomme
DK87888A (da) Terapeutisk anvendelse af tindijoddeuteroporfyrin
FR2580175B1 (fr) Utilisation therapeutique nouvelle de l'urogastrone humaine
DK593086A (da) Mono-, di- og triestere af 1,8-dihydroxy-10-phenyl-9-anthron eller -9-anthranol, deres fremstilling og deres anvendelse til human- eller veterinaermedicinske og kosmetiske formaal
DK38986D0 (da) Medicinsk inhalationsapparat
DK125687D0 (da) Patientkran-chassis
DK476887D0 (da) Middel til behandling af neurotisk forstyrrelse eller sygdom
DK83688D0 (da) Anvendelse af kendte forbindelser til fremstilling af et laegemiddel til behandling af hjertesygdomme eller organisk hjernesyndrom
DK639088A (da) Laegemiddel til behandling af iskaemiske hjertesygdomme
DK469487A (da) Laegemiddel til behandling af fedme
DK207686D0 (da) Medicinsk inhalationsapparat
KR890002236U (ko) 의료용 가아제의 증살통

Legal Events

Date Code Title Description
PUP Patent expired