AR031436A1 - Vectores recombinantes virales y no-virales conteniendo el gen humano del activador de plasminogeno derivado de urocinasa y su utilidad en el tratamiento de diversos tipos de fibrosis hepatica, renal, pulmonar, pancreatica, cardiaca y cicatrices hipertroficas - Google Patents

Vectores recombinantes virales y no-virales conteniendo el gen humano del activador de plasminogeno derivado de urocinasa y su utilidad en el tratamiento de diversos tipos de fibrosis hepatica, renal, pulmonar, pancreatica, cardiaca y cicatrices hipertroficas

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Publication number
AR031436A1
AR031436A1 ARP010105552A ARP010105552A AR031436A1 AR 031436 A1 AR031436 A1 AR 031436A1 AR P010105552 A ARP010105552 A AR P010105552A AR P010105552 A ARP010105552 A AR P010105552A AR 031436 A1 AR031436 A1 AR 031436A1
Authority
AR
Argentina
Prior art keywords
liver
viral
hupa
human gene
vector
Prior art date
Application number
ARP010105552A
Other languages
English (en)
Original Assignee
Tgt Lab S A De C V
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 Tgt Lab S A De C V filed Critical Tgt Lab S A De C V
Publication of AR031436A1 publication Critical patent/AR031436A1/es

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    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • 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
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1833—Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6456—Plasminogen activators
    • C12N9/6462—Plasminogen activators u-Plasminogen activator (3.4.21.73), i.e. urokinase
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21073—Serine endopeptidases (3.4.21) u-Plasminogen activator (3.4.21.73), i.e. urokinase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/10011—Adenoviridae
    • C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
    • C12N2710/10341—Use of virus, viral particle or viral elements as a vector
    • C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Abstract

En el presente se utilizo el gen humano de uPA modificado e insertado en el vector adenoviral (pAd-deltahuPA), que no se secreta y no produce hipocoagulacion ni sangrados espontáneos internos. Así mismo, datos del estudio de bio-distribucion con un vector adenoviral con el gen reportero beta-gal, nos demostro la especificidad del hígado como organo blanco del vector. Se detecto la proteína de huPA por ELISA en homogenados de hígado (4500 pg/ml) en animales inyectados con PAd-deltahuPA y también fue detectada intracelularmente por inmunohistoquímica en cortes de hígado (80% de células positivas). HuPA indujo una dramática reduccion de las fibrosis (85%) al día 10 de la administracion del vector, comparado con ratas cirroticas control y una proliferacion de hepatocitos de 55%. Las pruebas funcionales hepáticas (ALT, AST, fosfatasa alcalina y bilirrubina) disminuyeron casi a niveles normales y se verifico la proliferacion de hepatocitos. debido a las dos cascadas de eventos benéficos, la terapía génica con el huPA modificado puede ser desarrollado como un tratamiento potencial definitivo en pacientes con cirrosis hepática.
ARP010105552A 2000-11-28 2001-11-28 Vectores recombinantes virales y no-virales conteniendo el gen humano del activador de plasminogeno derivado de urocinasa y su utilidad en el tratamiento de diversos tipos de fibrosis hepatica, renal, pulmonar, pancreatica, cardiaca y cicatrices hipertroficas AR031436A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
MXPA00011713A MXPA00011713A (es) 2000-11-28 2000-11-28 Vectores recombinantes virales y no virales conteniendo el gen humano del activador de plasminogeno derivado de urocinasa y su utilidad en el tratamiento de diversos tipos de fibrosis hepatica, renal, pulmonar, pancreatica, cardiaca y cicatrices hipe

Publications (1)

Publication Number Publication Date
AR031436A1 true AR031436A1 (es) 2003-09-24

Family

ID=32294070

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP010105552A AR031436A1 (es) 2000-11-28 2001-11-28 Vectores recombinantes virales y no-virales conteniendo el gen humano del activador de plasminogeno derivado de urocinasa y su utilidad en el tratamiento de diversos tipos de fibrosis hepatica, renal, pulmonar, pancreatica, cardiaca y cicatrices hipertroficas

Country Status (16)

Country Link
US (1) US7807457B2 (es)
EP (1) EP1411128B1 (es)
JP (1) JP4733337B2 (es)
AR (1) AR031436A1 (es)
AT (1) ATE409234T1 (es)
AU (1) AU2001217374A1 (es)
CA (1) CA2430367C (es)
CY (1) CY1108667T1 (es)
DE (2) DE60040352D1 (es)
DK (1) DK1411128T3 (es)
ES (1) ES2226597T3 (es)
HK (1) HK1062454A1 (es)
MX (1) MXPA00011713A (es)
PT (1) PT1411128E (es)
TR (1) TR200403256T3 (es)
WO (1) WO2002044393A1 (es)

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EP1391214A4 (en) 2001-05-09 2006-05-17 Anges Mg Inc GM TRANSFER OF ANGIOGENIC FACTOR IN SKIN DISEASES
WO2007094071A1 (ja) * 2006-02-17 2007-08-23 Tokyo University Of Agriculture And Technology Tlo Co., Ltd. 肝機能改善剤
JP6484444B2 (ja) 2011-08-26 2019-03-13 イエキュリス コーポレーションＹｅｃｕｒｉｓ Ｃｏｒｐｏｒａｔｉｏｎ フマリルアセト酢酸ヒドロラーゼ（ｆａｈ）欠損及び免疫不全ラット、並びにそれらの使用
ES2783879T3 (es) * 2016-01-28 2020-09-18 Accendatech Dimetilaminomiqueliolida para su uso en el tratamiento de fibrosis pulmonar
CN114807152A (zh) * 2016-06-08 2022-07-29 哈佛学院院长及董事 工程化病毒载体减少了炎症和免疫反应的诱导
TWI734798B (zh) 2016-12-15 2021-08-01 大陸商深圳瑞健生命科學研究院有限公司 一種預防和治療肺纖維化的方法
CN108210905A (zh) * 2016-12-15 2018-06-29 深圳瑞健生命科学研究院有限公司 预防和治疗皮肤纤维化的药物及其用途
CN111344004A (zh) 2017-06-19 2020-06-26 泰伦基国际有限公司 一种调控glp-1/glp-1r 的方法和药物
US11613744B2 (en) 2018-12-28 2023-03-28 Vertex Pharmaceuticals Incorporated Modified urokinase-type plasminogen activator polypeptides and methods of use
CN113661239A (zh) 2018-12-28 2021-11-16 催化剂生物科学公司 经修饰的尿激酶型纤溶酶原激活物多肽和使用方法

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Also Published As

Publication number Publication date
MXPA00011713A (es) 2002-05-31
AU2001217374A1 (en) 2002-06-11
DE00980071T1 (de) 2005-03-31
US7807457B2 (en) 2010-10-05
ES2226597T1 (es) 2005-04-01
CA2430367C (en) 2012-10-30
JP4733337B2 (ja) 2011-07-27
HK1062454A1 (en) 2004-11-05
DK1411128T3 (da) 2009-02-02
CA2430367A1 (en) 2002-06-06
WO2002044393A1 (es) 2002-06-06
EP1411128A1 (en) 2004-04-21
CY1108667T1 (el) 2014-04-09
US20040097455A1 (en) 2004-05-20
EP1411128B1 (en) 2008-09-24
ATE409234T1 (de) 2008-10-15
TR200403256T3 (tr) 2005-02-21
PT1411128E (pt) 2008-12-30
JP2004527224A (ja) 2004-09-09
DE60040352D1 (de) 2008-11-06
ES2226597T3 (es) 2009-03-16

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