ATE314860T1 - Verwendung des copolymer-1 peptids sowie von damit verwandten peptiden und polypeptiden und von damit behandelten t-zellen zur neuroprotektion vor glutamattoxizitaet - Google Patents

Verwendung des copolymer-1 peptids sowie von damit verwandten peptiden und polypeptiden und von damit behandelten t-zellen zur neuroprotektion vor glutamattoxizitaet

Info

Publication number
ATE314860T1
ATE314860T1 AT01906632T AT01906632T ATE314860T1 AT E314860 T1 ATE314860 T1 AT E314860T1 AT 01906632 T AT01906632 T AT 01906632T AT 01906632 T AT01906632 T AT 01906632T AT E314860 T1 ATE314860 T1 AT E314860T1
Authority
AT
Austria
Prior art keywords
cop
nervous system
peptide
polypeptide
polypeptides
Prior art date
Application number
AT01906632T
Other languages
English (en)
Inventor
Michal Eisenbach-Schwartz
Eti Yoles
Jonathan Kipnis
Original Assignee
Yeda Res & Dev
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
Application filed by Yeda Res & Dev filed Critical Yeda Res & Dev
Application granted granted Critical
Publication of ATE314860T1 publication Critical patent/ATE314860T1/de

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/0005Vertebrate antigens
    • A61K39/0008Antigens related to auto-immune diseases; Preparations to induce self-tolerance
    • 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
    • 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
    • A61K38/1703Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/46Cellular immunotherapy
    • A61K39/461Cellular immunotherapy characterised by the cell type used
    • A61K39/4611T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/46Cellular immunotherapy
    • A61K39/464Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643Vertebrate antigens
    • A61K39/46432Nervous system antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/02Nutrients, e.g. vitamins, minerals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515Animal cells
    • A61K2039/5158Antigen-pulsed cells, e.g. T-cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/31Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/38Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00Indexing codes associated with cellular immunotherapy of group A61K39/46
    • A61K2239/46Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
    • A61K2239/47Brain; Nervous system

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Zoology (AREA)
  • Addiction (AREA)
  • Ophthalmology & Optometry (AREA)
  • Obesity (AREA)
  • Rheumatology (AREA)
  • Psychology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Nutrition Science (AREA)
  • Pain & Pain Management (AREA)
  • Emergency Medicine (AREA)
AT01906632T 2000-06-07 2001-01-22 Verwendung des copolymer-1 peptids sowie von damit verwandten peptiden und polypeptiden und von damit behandelten t-zellen zur neuroprotektion vor glutamattoxizitaet ATE314860T1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US20979900P 2000-06-07 2000-06-07
US62021600A 2000-07-20 2000-07-20

Publications (1)

Publication Number Publication Date
ATE314860T1 true ATE314860T1 (de) 2006-02-15

Family

ID=26904524

Family Applications (1)

Application Number Title Priority Date Filing Date
AT01906632T ATE314860T1 (de) 2000-06-07 2001-01-22 Verwendung des copolymer-1 peptids sowie von damit verwandten peptiden und polypeptiden und von damit behandelten t-zellen zur neuroprotektion vor glutamattoxizitaet

Country Status (17)

Country Link
US (1) US20020037848A1 (de)
EP (1) EP1294390B1 (de)
JP (1) JP4328090B2 (de)
KR (1) KR20030007397A (de)
CN (1) CN100438906C (de)
AT (1) ATE314860T1 (de)
AU (1) AU783031B2 (de)
CA (1) CA2398277C (de)
CY (1) CY1105263T1 (de)
DE (1) DE60116467T2 (de)
DK (1) DK1294390T3 (de)
ES (1) ES2256200T3 (de)
HK (1) HK1058892A1 (de)
IL (2) IL150801A0 (de)
MX (1) MXPA02007109A (de)
NZ (1) NZ520282A (de)
WO (1) WO2001093893A2 (de)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1098902A4 (de) 1998-07-23 2002-07-24 Yeda Res & Dev Behandlung von autoimmunkrankheiten mittels copolymer 1 und ähnlichen copolymeren und peptiden
ES2527760T3 (es) * 1998-07-23 2015-01-29 Yeda Research And Development Co., Ltd. Tratamiento de enfermedad de Crohn con copolímero 1 y polipéptidos
US6800287B2 (en) 1998-09-25 2004-10-05 Yeda Research And Development Co., Ltd. Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use
US7022663B2 (en) 2000-02-18 2006-04-04 Yeda Research And Development Co., Ltd. Oral, nasal and pulmonary dosage formulations of copolymer 1
HUP0302333A3 (en) * 2000-06-05 2005-07-28 Teva Pharma The use of glatiramer acetate (copolymer 1) for the preparation of pharmaceutical compositions available in the treatment of central nervous system disorders
US20020077278A1 (en) 2000-06-05 2002-06-20 Yong V. Wee Use of glatiramer acetate (copolymer 1) in the treatment of central nervous system disorders
WO2002076503A1 (en) * 2000-06-20 2002-10-03 Mayo Foundation For Medical Education And Research Treatment of central nervous system diseases by antibodies against glatiramer acetate
ES2349033T3 (es) 2001-12-04 2010-12-22 Teva Pharmaceutical Industries, Ltd. Procedimientos para la medida de la actividad del acetato de glatiramer.
DK1429800T3 (da) * 2001-12-06 2009-04-27 Yeda Res & Dev Vaccine og anvendelse deraf til behandling af amyotrofisk lateral sklerose
US20070248569A1 (en) * 2003-01-07 2007-10-25 Michal Eisenbach-Schwartz Eye-Drop Vaccine Containing Copolymer 1 for Therapeutic Immunization
CN1886506B (zh) * 2003-09-29 2012-05-30 中外制药株式会社 在nk细胞中表达的蛋白质
WO2005032482A2 (en) * 2003-10-03 2005-04-14 Bayhill Therapeutics, Inc. Treatment of demyelinating autoimmune disease with modified ordered peptides
JP5456235B2 (ja) * 2003-11-12 2014-03-26 イエダ リサーチ アンド デベロップメント カンパニー リミテッド 神経変性疾患を治療するためのワクチン及び方法
PL1701730T3 (pl) * 2003-12-09 2014-04-30 Yeda Res & Dev Sposób i szczepionka zawierająca kopolimer 1 do leczenia zaburzeń psychicznych
WO2005120542A2 (en) 2004-05-07 2005-12-22 Peptimmune, Inc. Methods of treating disease with random copolymers
ATE536363T1 (de) 2004-09-09 2011-12-15 Teva Pharma Verfahren zur herstellung von mischungen von trifluoroacetyl-glatirameracetat bei verwendung von hydrobromsäure
AU2005308396B2 (en) * 2004-11-29 2011-06-09 Yeda Research And Development Co. Ltd. Induction of neurogenesis and stem cell therapy in combination with Copolymer 1
CA2649296A1 (en) 2006-04-13 2007-10-25 Peptimmune, Inc. Methods for designing and synthesizing directed sequence polymer compositions via the directed expansion of epitope permeability
US8193147B2 (en) 2007-09-24 2012-06-05 Hadasit Medical Research Services & Development Ltd. Use of copolymer 1 for treatment of muscular dystrophy
BRPI0817682A2 (pt) 2007-10-16 2015-04-07 Peptimmune Inc Métodos para projetar e preparar vacinas compreendendo composições de polímero de sequência direcionada via a expansão direta de epítopos
WO2009063459A2 (en) * 2007-11-13 2009-05-22 Yeda Research And Development Co. Ltd Synthetic peptide copolymers for treatment of neurodevelopmental disorders
ES2612001T4 (es) 2009-08-20 2018-02-07 Yeda Research & Development Company, Ltd. Terapia de baja frecuencia con acetato de glatirámero
US8377885B2 (en) 2010-01-04 2013-02-19 Mapi Pharma Ltd. Depot systems comprising glatiramer or pharmacologically acceptable salt thereof
DK3536333T3 (da) * 2010-01-04 2022-10-24 Mapi Pharma Ltd Depotsystem der omfatter glatirameracetat
USRE49251E1 (en) 2010-01-04 2022-10-18 Mapi Pharma Ltd. Depot systems comprising glatiramer or pharmacologically acceptable salt thereof
US8759302B2 (en) * 2010-03-16 2014-06-24 Teva Pharmaceutical Industries, Ltd. Methods of treating a subject afflicted with an autoimmune disease using predictive biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis
NZ609938A (en) 2010-10-11 2015-11-27 Teva Pharma Cytokine biomarkers as predictive biomarkers of clinical response for glatiramer acetate
EP2699317B1 (de) 2011-04-21 2016-08-10 Mapi Pharma Limited Zufallspentapolymer zur behandlung von autoimmunkrankheiten
JP2014530819A (ja) 2011-10-10 2014-11-20 テバ ファーマシューティカル インダストリーズ リミティド 酢酸グラチラマーに対する臨床的応答性を予測するために有用な一塩基多形
EP3320914B1 (de) 2012-09-10 2020-12-30 Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science Th1-typ adjuvans zur behandlung von amyotropher lateralsklerose
CA3050086A1 (en) 2017-03-26 2018-10-04 Mapi Pharma Ltd. Glatiramer depot systems for treating progressive forms of multiple sclerosis
KR20230128606A (ko) * 2022-02-28 2023-09-05 경상국립대학교산학협력단 티로신을 유효성분으로 함유하는 알츠하이머병의 예방, 개선 또는 치료용 조성물

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL36670A (en) * 1971-04-21 1974-09-10 Sela M Therapeutic basic copolymers of amino acids
IL113812A (en) * 1994-05-24 2000-06-29 Yeda Res & Dev Copolymer-1 pharmaceutical compositions containing it and its use
AU2868699A (en) * 1998-02-13 1999-08-30 Autoimmune, Inc. Treatment of multiple sclerosis using cop-1 and th2-enhancing cytokines

Also Published As

Publication number Publication date
EP1294390B1 (de) 2006-01-04
WO2001093893A3 (en) 2002-04-04
AU3451801A (en) 2001-12-17
AU783031B2 (en) 2005-09-15
DE60116467D1 (de) 2006-03-30
CA2398277A1 (en) 2001-12-13
CA2398277C (en) 2013-09-03
ES2256200T3 (es) 2006-07-16
NZ520282A (en) 2004-09-24
JP2004507460A (ja) 2004-03-11
CY1105263T1 (el) 2010-03-03
HK1058892A1 (en) 2004-06-11
CN1462190A (zh) 2003-12-17
DE60116467T2 (de) 2006-11-02
US20020037848A1 (en) 2002-03-28
MXPA02007109A (es) 2002-12-13
CN100438906C (zh) 2008-12-03
KR20030007397A (ko) 2003-01-23
IL150801A (en) 2007-10-31
WO2001093893A2 (en) 2001-12-13
JP4328090B2 (ja) 2009-09-09
IL150801A0 (en) 2003-02-12
DK1294390T3 (da) 2006-04-03
EP1294390A2 (de) 2003-03-26

Similar Documents

Publication Publication Date Title
ATE314860T1 (de) Verwendung des copolymer-1 peptids sowie von damit verwandten peptiden und polypeptiden und von damit behandelten t-zellen zur neuroprotektion vor glutamattoxizitaet
DE60112718D1 (de) Verwendung von copolymer 1- und verwandten peptiden sowie von polypeptiden und damit behandelten t-zellen zur neuroprotektiven therapie
DE69835279D1 (de) Zusammensetzungen und verfahren zur behandlung von infektionen unter verwendung von kationischen peptiden allein oder in kombination mit antibiotika
CY1111120T1 (el) Πεπτιδια που παραγονται απο πρωτεϊνες νευρικων ινων και η ιατρικη τους χρηση
IL161591A0 (en) Peptides effective in the treatment of tumors and other conditions requiring the removal or destruction of cells
NZ504026A (en) Methods for treating hypercoagulable states or acquired protein C deficiency using human-activated protein C
ATE186219T1 (de) Kombination von antihormonale und bindende moleküle zur krebsbehandlung
DE69630890D1 (de) Peptid-immitierende substanzen in der krebstherapie
DE69703689T2 (de) Therapeutische anwendungen von bpi-protein-produkten zur behandlung von humaner meningococcämia
ATE451929T1 (de) Von casein abgeleitete peptide und deren anwendung für die therapie
WO1999060021A3 (en) Use of activated t cells, nervous system-specific antigens for treating disorders of the nevrous system
DE60230807D1 (de) Behandlung von sarkom bei menschen mit adenovirus-vektor tnf-alpha
MXPA05008704A (es) Proteinas de fusion de muteinas de interferon alfa con propiedades mejoradas.
DE69837265D1 (de) Polypeptide zur regenerierung des nervensystems
ATE490972T1 (de) Biologisch aktive peptide und deren verwendung zur reparatur verletzter nerven
WO2024040030A3 (en) Treating protein misfolding disorders
EP1714979A3 (de) Peptide für die Behandlung von Tumoren und anderen Zuständen, die das entfernen oder zerstören von Zellen erfordern
DE50201092D1 (de) Verwendung eines Fibroblastenwachstumsfaktor-Bindeproteins zur Behandlung und Diagnose von diabetischen Wundheilugnsstörungen

Legal Events

Date Code Title Description
UEP Publication of translation of european patent specification

Ref document number: 1294390

Country of ref document: EP