Nothing Special   »   [go: up one dir, main page]

BR112012027282A2 - meio de cultura de células aperfeiçoado - Google Patents

meio de cultura de células aperfeiçoado

Info

Publication number
BR112012027282A2
BR112012027282A2 BR112012027282A BR112012027282A BR112012027282A2 BR 112012027282 A2 BR112012027282 A2 BR 112012027282A2 BR 112012027282 A BR112012027282 A BR 112012027282A BR 112012027282 A BR112012027282 A BR 112012027282A BR 112012027282 A2 BR112012027282 A2 BR 112012027282A2
Authority
BR
Brazil
Prior art keywords
cell culture
culture medium
improved cell
producing polypeptides
shift
Prior art date
Application number
BR112012027282A
Other languages
English (en)
Other versions
BR112012027282B1 (pt
Inventor
Christian Leist
Jörg Schmidt
Petra Meissner
Original Assignee
Novartis Ag
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=44074260&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BR112012027282(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of BR112012027282A2 publication Critical patent/BR112012027282A2/pt
Publication of BR112012027282B1 publication Critical patent/BR112012027282B1/pt

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018Culture media for cell or tissue culture
    • C12N5/0031Serum-free culture media
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018Culture media for cell or tissue culture
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018Culture media for cell or tissue culture
    • C12N5/005Protein-free medium
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00Specific components of cell culture medium
    • C12N2500/05Inorganic components
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00Specific components of cell culture medium
    • C12N2500/05Inorganic components
    • C12N2500/10Metals; Metal chelators
    • C12N2500/12Light metals, i.e. alkali, alkaline earth, Be, Al, Mg

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

meio de cultura de células aperfeiçoado. a presente invenção refere-se a um meio otimizado para o crescimento de células de mamíferos, bem como a produção de polipeptídeos. o meio de cultura de células é distiguido por uma razão sow de íons de sódio para potássio, e ele refere-se ainda ao método para produzir polipeptídeos usando tais meios de cultura de células. em outro aspecto, o método para produzir polipeptídeos usando pode compreender também um deslocamento de temperatura e/ou um deslocamento de ph para otimizar ainda mais o crescimento e o rendimento do produto.
BR112012027282-9A 2010-04-26 2011-04-25 Meio de cultura de células aperfeiçoado e processo para a produção de um polipeptídeo recombinante BR112012027282B1 (pt)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US32783610P 2010-04-26 2010-04-26
US61/327,836 2010-04-26
PCT/EP2011/056508 WO2011134920A1 (en) 2010-04-26 2011-04-25 Improved cell culture medium

Publications (2)

Publication Number Publication Date
BR112012027282A2 true BR112012027282A2 (pt) 2015-09-22
BR112012027282B1 BR112012027282B1 (pt) 2020-09-29

Family

ID=44074260

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112012027282-9A BR112012027282B1 (pt) 2010-04-26 2011-04-25 Meio de cultura de células aperfeiçoado e processo para a produção de um polipeptídeo recombinante

Country Status (17)

Country Link
US (2) USRE48864E1 (pt)
EP (1) EP2563904B1 (pt)
JP (3) JP6347949B2 (pt)
KR (1) KR101828623B1 (pt)
CN (1) CN102858952B (pt)
AU (1) AU2011246503B2 (pt)
BR (1) BR112012027282B1 (pt)
CA (1) CA2797356C (pt)
DK (1) DK2563904T3 (pt)
ES (1) ES2533074T3 (pt)
IL (1) IL222452B (pt)
MX (1) MX2012012526A (pt)
PL (1) PL2563904T3 (pt)
PT (1) PT2563904E (pt)
RU (1) RU2644651C2 (pt)
SG (1) SG185038A1 (pt)
WO (1) WO2011134920A1 (pt)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2663442A1 (en) 2006-09-13 2008-03-20 Abbott Laboratories Cell culture improvements
US8911964B2 (en) 2006-09-13 2014-12-16 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
EP2346897A2 (en) 2008-10-20 2011-07-27 Abbott Laboratories Viral inactivation during purification of antibodies
SG10201702922VA (en) 2008-10-20 2017-06-29 Abbvie Inc Isolation and purification of antibodies using protein a affinity chromatography
RU2644651C2 (ru) * 2010-04-26 2018-02-13 Новартис Аг Среда для культивирования клеток
KR101848945B1 (ko) 2010-04-26 2018-04-16 노파르티스 아게 개선된 세포 배양 배지
BR112013009934A2 (pt) 2010-12-07 2016-07-05 Hoffmann La Roche dispositivo para adicionar pelo menos duas soluções de alimentação, aparelho de cultivo celular, uso de um dispositivo e método para obter um polipeptídeo
WO2012149197A2 (en) 2011-04-27 2012-11-01 Abbott Laboratories Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US10485869B2 (en) 2011-10-18 2019-11-26 Coherus Biosciences, Inc. Etanercept formulations stabilized with meglumine
SI2768525T1 (sl) 2011-10-18 2019-10-30 Coherus Biosciences Inc Formulacije etanercepta, stabilizirane z magnezijevimi ioni
US9505833B2 (en) 2012-04-20 2016-11-29 Abbvie Inc. Human antibodies that bind human TNF-alpha and methods of preparing the same
WO2013158279A1 (en) 2012-04-20 2013-10-24 Abbvie Inc. Protein purification methods to reduce acidic species
US9181572B2 (en) 2012-04-20 2015-11-10 Abbvie, Inc. Methods to modulate lysine variant distribution
US9067990B2 (en) 2013-03-14 2015-06-30 Abbvie, Inc. Protein purification using displacement chromatography
US20130281355A1 (en) 2012-04-24 2013-10-24 Genentech, Inc. Cell culture compositions and methods for polypeptide production
US9249182B2 (en) 2012-05-24 2016-02-02 Abbvie, Inc. Purification of antibodies using hydrophobic interaction chromatography
MX2015000337A (es) 2012-07-09 2015-09-25 Coherus Biosciences Inc Formulaciones de etanercept que exhiben reduccion notable en particulas subvisibles.
BR112015004467A2 (pt) 2012-09-02 2017-03-21 Abbvie Inc método para controlar a heterogeneidade de proteínas
US9512214B2 (en) 2012-09-02 2016-12-06 Abbvie, Inc. Methods to control protein heterogeneity
BR112015005161A2 (pt) 2012-09-11 2017-07-04 Coherus Biosciences Inc etanercepte corretamente dobrado em alta pureza e excelente rendimento
US8921526B2 (en) 2013-03-14 2014-12-30 Abbvie, Inc. Mutated anti-TNFα antibodies and methods of their use
AU2013384204B2 (en) 2013-03-14 2017-03-16 Abbvie Inc. Low acidic species compositions and methods for producing and using the same
US9017687B1 (en) 2013-10-18 2015-04-28 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same using displacement chromatography
BR112016002622B1 (pt) 2013-08-20 2023-04-11 Lek Pharmaceuticals D.D Meio de cultura celular e uso de selênio
WO2015051293A2 (en) 2013-10-04 2015-04-09 Abbvie, Inc. Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins
US11390663B2 (en) 2013-10-11 2022-07-19 Regeneron Pharmaceuticals, Inc. Metabolically optimized cell culture
PL3351620T3 (pl) * 2013-10-11 2021-03-08 Regeneron Pharmaceuticals, Inc. Hodowla komórek zoptymalizowana metabolicznie
US9085618B2 (en) 2013-10-18 2015-07-21 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9181337B2 (en) 2013-10-18 2015-11-10 Abbvie, Inc. Modulated lysine variant species compositions and methods for producing and using the same
US8946395B1 (en) 2013-10-18 2015-02-03 Abbvie Inc. Purification of proteins using hydrophobic interaction chromatography
US20150139988A1 (en) 2013-11-15 2015-05-21 Abbvie, Inc. Glycoengineered binding protein compositions
EP3099324B1 (en) * 2014-01-30 2020-04-01 Coherus Biosciences, Inc. Perfusion media
MX368664B (es) 2014-04-29 2019-10-10 Novartis Ag Células novedosas de vertebrados y métodos para la expresión recombinante de un polipéptido de interés.
ES2733298T3 (es) 2014-07-18 2019-11-28 Sandoz Ag Cuantificación de TNFR2:Fc plegado erróneamente
US10822584B2 (en) * 2015-12-17 2020-11-03 Life Technologies Corporation Pellets used in cell culture and methods of making thereof
BR112018070063A2 (pt) * 2016-04-05 2019-02-12 Pfizer Inc. processo de cultivo de células
US20200377918A1 (en) * 2017-03-31 2020-12-03 Boehringer Ingelheim International Gmbh Perfusion medium
CA3054593A1 (en) * 2017-03-31 2018-10-04 Boehringer Ingelheim International Gmbh Perfusion medium
KR20220097421A (ko) * 2019-11-05 2022-07-07 아지노모토 가부시키가이샤 단백질의 제조 방법
US20230313259A1 (en) * 2020-08-14 2023-10-05 Bristol-Myers Squibb Company Manufacturing process for protein
UY39484A (es) 2020-11-02 2022-06-30 Novartis Ag Inhibidores de interleucina-17

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5672502A (en) 1985-06-28 1997-09-30 Celltech Therapeutics Limited Animal cell culture
EP0283942B1 (en) 1987-03-24 1992-05-20 W.R. Grace & Co.-Conn. Basal nutrient medium for cell culture
US6048728A (en) * 1988-09-23 2000-04-11 Chiron Corporation Cell culture medium for enhanced cell growth, culture longevity, and product expression
CA2001550A1 (en) 1989-03-03 1990-09-03 Aaron H. Heifetz Very low protein nutrient medium for cell culture
US5135866A (en) 1989-03-03 1992-08-04 W. R. Grace & Co.-Conn. Very low protein nutrient medium for cell culture
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
GB9022545D0 (en) 1990-10-17 1990-11-28 Wellcome Found Culture medium
JPH0789908B2 (ja) 1991-02-28 1995-10-04 倉敷紡績株式会社 動物細胞培養用無血清培地
GB9118664D0 (en) 1991-08-30 1991-10-16 Celltech Ltd Cell culture
US5856179A (en) * 1994-03-10 1999-01-05 Genentech, Inc. Polypeptide production in animal cell culture
US5830761A (en) 1995-06-07 1998-11-03 Genetics Institute, Inc. Medium and methods for culturing mammalian cho cells
EP0953041A4 (en) * 1996-08-30 2003-01-29 Life Technologies Inc SERUM-FREE CULTURAL MEDIUM FOR MAMMAL CELLS AND THEIR USE
US5804420A (en) 1997-04-18 1998-09-08 Bayer Corporation Preparation of recombinant Factor VIII in a protein free medium
US6406909B1 (en) 1998-07-10 2002-06-18 Chugai Seiyaku Kabushiki Kaisha Serum-free medium for culturing animal cells
US7294481B1 (en) 1999-01-05 2007-11-13 Immunex Corporation Method for producing recombinant proteins
EP1757700A3 (en) 1999-04-26 2009-03-11 Genentech, Inc. Cell culture process for glycoproteins
EP1180142A2 (en) 1999-05-27 2002-02-20 PHARMACIA & UPJOHN COMPANY Methods and compositions for measuring ion channel conductance
AT409379B (de) * 1999-06-02 2002-07-25 Baxter Ag Medium zur protein- und serumfreien kultivierung von zellen
JP2003518378A (ja) 1999-12-28 2003-06-10 イソティス エヌ.ブイ. 成長因子及びl−グルタミンを含む細胞培養培地
WO2002066603A2 (en) 2001-02-15 2002-08-29 Centocor, Inc. Chemically defined medium for cultured mammalian cells
WO2002101019A2 (en) 2001-06-13 2002-12-19 Genentech, Inc. Methods of culturing animal cells and polypeptide production in animal cells
AU2003249055B2 (en) 2002-07-15 2008-06-26 Immunex Corporation Methods and media for controlling sialylation of proteins produced by mammalian cells
US7541164B2 (en) 2002-12-23 2009-06-02 Bristol-Myers Squibb Company Mammalian cell culture processes for protein production
GB0304799D0 (en) * 2003-03-03 2003-04-09 Glaxosmithkline Biolog Sa Novel method
DE10338536A1 (de) 2003-08-19 2005-04-07 Bircher Reglomat Ag Verfahren zum Betreiben eines Radarsensors
TWI374935B (en) 2004-08-27 2012-10-21 Pfizer Ireland Pharmaceuticals Production of α-abeta
US7294484B2 (en) 2004-08-27 2007-11-13 Wyeth Research Ireland Limited Production of polypeptides
EP1707634A1 (en) 2005-03-29 2006-10-04 Octapharma AG Method for isolation of recombinantly produced proteins
WO2006113629A1 (en) * 2005-04-15 2006-10-26 The Trustees Of Columbia University In The City Of New York Chemically defined culture media for expansion and differentiation of epidermal cells and uses thereof for in vitro growth of hair follicles
US20070231895A1 (en) 2005-11-02 2007-10-04 Lee Gene W Methods for adapting mammalian cells
US20070190057A1 (en) 2006-01-23 2007-08-16 Jian Wu Methods for modulating mannose content of recombinant proteins
DK2078071T3 (en) * 2006-11-08 2015-04-20 Wyeth Llc Rationally crafted cell culture media
RU2644651C2 (ru) 2010-04-26 2018-02-13 Новартис Аг Среда для культивирования клеток

Also Published As

Publication number Publication date
RU2018101201A3 (pt) 2021-05-27
RU2012150346A (ru) 2014-06-10
BR112012027282B1 (pt) 2020-09-29
RU2018101201A (ru) 2019-02-21
AU2011246503B2 (en) 2013-09-26
JP2019216728A (ja) 2019-12-26
MX2012012526A (es) 2012-11-23
ES2533074T3 (es) 2015-04-07
KR101828623B1 (ko) 2018-02-12
EP2563904B1 (en) 2015-01-21
JP2017012180A (ja) 2017-01-19
JP2013524825A (ja) 2013-06-20
IL222452A0 (en) 2012-12-31
CA2797356C (en) 2020-12-29
US9428727B2 (en) 2016-08-30
RU2644651C2 (ru) 2018-02-13
JP6603628B2 (ja) 2019-11-06
IL222452B (en) 2019-03-31
JP7034991B2 (ja) 2022-03-14
KR20130058699A (ko) 2013-06-04
EP2563904A1 (en) 2013-03-06
USRE48864E1 (en) 2021-12-28
WO2011134920A1 (en) 2011-11-03
SG185038A1 (en) 2012-11-29
PT2563904E (pt) 2015-05-12
CA2797356A1 (en) 2011-11-03
US20130122543A1 (en) 2013-05-16
JP6347949B2 (ja) 2018-06-27
DK2563904T3 (en) 2015-04-07
AU2011246503A1 (en) 2012-11-22
CN102858952A (zh) 2013-01-02
CN102858952B (zh) 2015-10-14
PL2563904T3 (pl) 2015-06-30

Similar Documents

Publication Publication Date Title
BR112012027282A2 (pt) meio de cultura de células aperfeiçoado
BR112012027430A2 (pt) processo de cultivo de células aprimorado
EP4148121A3 (en) Cell-controlled perfusion in continuous culture
MY156588A (en) Systems using cell culture for production of isoprene
BR112012009828B8 (pt) Método para a produção de uma imunoglobulina glicosilada e seu uso
EA201171018A1 (ru) Биореактор для культивирования клеток млекопитающих
MY182355A (en) Hmo synthesis
WO2008153180A1 (ja) 脂肪組織由来細胞から肝小葉様細胞塊を得る方法
AR069956A1 (es) Procesos para cultivar celulas mamiferas secretoras de proteinas sanguineas heterologas
MX2013014937A (es) Cultivo de celulas de mamifero.
MX2013007650A (es) Metodo de cultivo de celulas animales.
WO2010096588A3 (en) Cell culture media containing combinations of proteins
BR112017021255A2 (pt) microrganismo modificado para a produção otimizada de 2,4-di-hidroxibutirato
BRPI0813359A2 (pt) Ácidos nucleicos isolados, vetor, células, métodos para produzir um hidrocarboneto, para produzir uma cetona alifática, para produzir um polipeptídeo purificado, para produzir um hidrocarboneto, para produzir biocombustíveis, hidrocarboneto, biocombustível, polipeptídeo isolado, ácido nucleico isolado, organismos geneticamente engenheirados, método para identificar uma enzima útil para a produção de hidrocarbonetos
BR112014013152A2 (pt) sistema automatizado para a produção de células-tronco pluripotentes induzidas ou células diferenciadas
BR112013010278A2 (pt) método para produzir uma planta, me´todo para modular a composição de biomassa em uma planta, célula vegetal, planta transgênica, produto de semente, acido nucléico isolado, método para identificar um polimorfimo está associado a uma variação de uma característica, método para fazer uma linhagem vegetal, método para alterar a composição de biomassa em uma planta
NO20064379L (no) Anvendelse av et serumfritt cellekulturmedium for produsjonen av IL-18BP i pattedyrceller
EA201390444A1 (ru) Производство бутанола из монооксида углерода рекомбинантным микроорганизмом
WO2008090770A1 (ja) L-アミノ酸を生産する微生物及びl-アミノ酸の製造法
AR086790A1 (es) Un microorganismo para la produccion de metionina con importacion de glucosa mejorada
EA201390602A1 (ru) Способ и система для производства углеводородных продуктов
WO2012129962A8 (zh) 一种联合制碱大循环工艺
MY163228A (en) Process for Producing 3-Hydroxybutyric Acid or Salt Thereof
IN2014DN07980A (pt)
BR112015032515A8 (pt) método para a produção de um açúcar líquido, método para a produção de um açúcar sólido, açúcar líquido, açúcar sólido e métodos para a produção de uma substância química

Legal Events

Date Code Title Description
B06F Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]
B07A Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]
B06A Patent application procedure suspended [chapter 6.1 patent gazette]
B09A Decision: intention to grant [chapter 9.1 patent gazette]
B16A Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]

Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 25/04/2011, OBSERVADAS AS CONDICOES LEGAIS.