CY1120980T1 - Μεθοδοι παρασκευης για τον ελεγχο της περιεκτικοτητας σε c-τελικη λυσινη, γαλακτοζη και σιαλικο οξυ σε ανασυνδυασμενες πρωτεϊνες - Google Patents

Μεθοδοι παρασκευης για τον ελεγχο της περιεκτικοτητας σε c-τελικη λυσινη, γαλακτοζη και σιαλικο οξυ σε ανασυνδυασμενες πρωτεϊνες

Info

Publication number
CY1120980T1
CY1120980T1 CY181101150T CY181101150T CY1120980T1 CY 1120980 T1 CY1120980 T1 CY 1120980T1 CY 181101150 T CY181101150 T CY 181101150T CY 181101150 T CY181101150 T CY 181101150T CY 1120980 T1 CY1120980 T1 CY 1120980T1
Authority
CY
Cyprus
Prior art keywords
sialic acid
galactose
control
preparation methods
acid contents
Prior art date
Application number
CY181101150T
Other languages
English (en)
Inventor
Marcel Flikweert
Charles Goochee
Francis Maslanka
Francisus Johannes Ignatius Nagel
James Ryland
Eugene Schafer
Original Assignee
Janssen Biotech Inc
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=51528780&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CY1120980(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Janssen Biotech Inc filed Critical Janssen Biotech Inc
Publication of CY1120980T1 publication Critical patent/CY1120980T1/el

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/54—F(ab')2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)

Abstract

Στο παρόν παρέχεται μία μέθοδος για την παραγωγή ενός αντισώματος, όπως ενός αντισώματος αντι-TNFα (π.χ., ινφλιξιμάμπη) που έχει μία περιεκτικότητα σε C-τελική λυσίνη περίπου 20% έως περίπου 70%, και μία περιεκτικότητα σε σιαλικό οξύ περίπου 1% έως περίπου 20%, η οποία περιλαμβάνει καλλιέργεια ενός αποκρινόμενου σε ψευδάργυρο κυττάρου ξενιστή επιμολυσμένου με DNA που κωδικοποιεί το αντίσωμα σε ένα μέσο καλλιέργειας το οποίον περιλαμβάνει τουλάχιστον 0,5Μ ψευδάργυρο• και έλεγχο της συγκέντρωσης του ψευδαργύρου στο μέσο καλλιέργειας, και με αυτό τον τρόπο παραγωγή του αντισώματος.
CY181101150T 2013-03-15 2018-11-02 Μεθοδοι παρασκευης για τον ελεγχο της περιεκτικοτητας σε c-τελικη λυσινη, γαλακτοζη και σιαλικο οξυ σε ανασυνδυασμενες πρωτεϊνες CY1120980T1 (el)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361791094P 2013-03-15 2013-03-15
PCT/US2014/021574 WO2014149935A1 (en) 2013-03-15 2014-03-07 Manufacturing methods to control c-terminal lysine, galactose and sialic acid content in recombinant proteins

Publications (1)

Publication Number Publication Date
CY1120980T1 true CY1120980T1 (el) 2019-12-11

Family

ID=51528780

Family Applications (1)

Application Number Title Priority Date Filing Date
CY181101150T CY1120980T1 (el) 2013-03-15 2018-11-02 Μεθοδοι παρασκευης για τον ελεγχο της περιεκτικοτητας σε c-τελικη λυσινη, γαλακτοζη και σιαλικο οξυ σε ανασυνδυασμενες πρωτεϊνες

Country Status (26)

Country Link
US (3) US20140273092A1 (el)
EP (1) EP2970980B2 (el)
JP (1) JP2016512029A (el)
KR (1) KR102216003B1 (el)
CN (1) CN105378086B (el)
AR (2) AR095660A1 (el)
AU (2) AU2014237635B2 (el)
BR (1) BR112015022971B1 (el)
CA (1) CA2907140A1 (el)
CY (1) CY1120980T1 (el)
DK (1) DK2970980T3 (el)
EA (1) EA201591807A1 (el)
ES (1) ES2690047T3 (el)
HR (1) HRP20181741T1 (el)
IL (1) IL240689B (el)
LT (1) LT2970980T (el)
MX (1) MX366910B (el)
PH (1) PH12015501837A1 (el)
PL (1) PL2970980T3 (el)
PT (1) PT2970980T (el)
RS (1) RS57791B1 (el)
SG (1) SG11201507577RA (el)
SI (1) SI2970980T1 (el)
TW (1) TWI630216B (el)
WO (1) WO2014149935A1 (el)
ZA (1) ZA201507671B (el)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012149197A2 (en) 2011-04-27 2012-11-01 Abbott Laboratories Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US9067990B2 (en) 2013-03-14 2015-06-30 Abbvie, Inc. Protein purification using displacement chromatography
US9181572B2 (en) 2012-04-20 2015-11-10 Abbvie, Inc. Methods to modulate lysine variant distribution
US9150645B2 (en) 2012-04-20 2015-10-06 Abbvie, Inc. Cell culture methods to reduce acidic species
US9512214B2 (en) 2012-09-02 2016-12-06 Abbvie, Inc. Methods to control protein heterogeneity
AU2013381687A1 (en) 2013-03-12 2015-09-24 Abbvie Inc. Human antibodies that bind human TNF-alpha and methods of preparing the same
WO2014151878A2 (en) 2013-03-14 2014-09-25 Abbvie Inc. Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosacharides
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
PT2970980T (pt) * 2013-03-15 2018-11-19 Janssen Biotech Inc Métodos de produção para controlor o teor de lisina c-terminal, galactose e ácido siálico em proteínas recombinantes
SG11201601262QA (en) 2013-08-20 2016-03-30 Lek Pharmaceuticals CELL CULTURE MEDIUM AND PROCESS FOR CONTROLLING α-AMIDATION AND/OR C-TERMINAL AMINO ACID CLEAVAGE OF POLYPEPTIDES
EP3052640A2 (en) 2013-10-04 2016-08-10 AbbVie Inc. Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins
US9181337B2 (en) 2013-10-18 2015-11-10 Abbvie, Inc. Modulated lysine variant species compositions and methods for producing and using the same
US9085618B2 (en) 2013-10-18 2015-07-21 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
WO2015073884A2 (en) 2013-11-15 2015-05-21 Abbvie, Inc. Glycoengineered binding protein compositions
AU2016348388B2 (en) 2015-11-03 2023-11-30 Janssen Biotech, Inc. Antibodies specifically binding PD-1 and their uses
CN108350416A (zh) * 2015-11-09 2018-07-31 百时美施贵宝公司 操纵在cho细胞中产生的多肽的品质属性的方法
EP3390453A2 (en) 2015-12-17 2018-10-24 Janssen Biotech, Inc. Antibodies specifically binding hla-dr and their uses
KR102587941B1 (ko) 2016-08-12 2023-10-11 얀센 바이오테크 인코포레이티드 향상된 효능작용 및 이펙터 기능을 갖는 조작된 항체 및 다른 Fc-도메인 함유 분자
WO2018031400A1 (en) 2016-08-12 2018-02-15 Janssen Biotech, Inc. Fc engineered anti-tnfr superfamily member antibodies having enhanced agonistic activity and methods of using them
EP3634486A4 (en) 2017-06-05 2021-03-31 Janssen Biotech, Inc. GENETICALLY PRODUCED MULTISPECIFIC ANTIBODIES AND OTHER MULTIMERIC PROTEINS WITH ASYMMETRIC MUTATIONS OF THE CH2-CH3 REGION
PE20200294A1 (es) 2017-06-05 2020-02-05 Janssen Biotech Inc Anticuerpos que se unen especificamente a pd-1 y metodos de uso
WO2019077628A1 (en) * 2017-10-16 2019-04-25 Council Of Scientific & Industrial Research ZINC SUPPLEMENTATION TO DECREASE GALACTOSYLATION OF RECOMBINANT GLYCOPROTEINS
MA52772A (fr) 2018-05-24 2021-04-14 Janssen Biotech Inc Anticorps anti-tmeff2 monospécifiques et multispécifiques et leurs utilisations
US20220081479A1 (en) * 2018-12-31 2022-03-17 Momenta Pharmaceuticals, Inc. Methods of producing ustekinumab
CR20220025A (es) 2019-07-26 2022-05-04 Janssen Biotech Inc Proteínas que comprenden dominios de unión al antígeno de la peptidasa 2 relacionada con la calicreína y sus usos
MX2022001799A (es) 2019-08-15 2022-03-11 Janssen Biotech Inc Materiales y metodos para fragmentos variables de cadena unica mejorados.
KR20230051616A (ko) 2020-03-13 2023-04-18 얀센 바이오테크 인코포레이티드 Siglec-3/cd33을 결합시키기 위한 물질 및 방법
US20220411504A1 (en) 2020-05-27 2022-12-29 Janssen Biotech, Inc. Proteins comprising cd3 antigen binding domains and uses thereof
US11827708B2 (en) 2020-07-29 2023-11-28 Janssen Biotech, Inc. Proteins comprising HLA-G antigen binding domains and their uses
TW202231292A (zh) 2020-10-13 2022-08-16 美商健生生物科技公司 用於調節分化簇ｉｖ及／或ｖｉｉｉ的經生物工程改造之ｔ細胞介導之免疫力、材料、及其他方法
CA3199319A1 (en) 2020-10-22 2022-04-28 Janssen Biotech, Inc. Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses
PE20240761A1 (es) 2021-01-28 2024-04-17 Janssen Biotech Inc Proteinas de union a psma y usos de estas
KR20230160314A (ko) 2021-03-24 2023-11-23 얀센 바이오테크 인코포레이티드 Cd22 및 cd79b를 표적화하는 항체
MX2023011266A (es) 2021-03-24 2023-12-07 Janssen Biotech Inc Proteínas que comprenden dominios de unión al antígeno de cd3 y usos de estas.
WO2023037333A1 (en) 2021-09-13 2023-03-16 Janssen Biotech, Inc CD33 X Vδ2 MULTISPECIFIC ANTIBODIES FOR THE TREATMENT OF CANCER
WO2023046322A1 (en) 2021-09-24 2023-03-30 Janssen Pharmaceutica Nv Proteins comprising cd20 binding domains, and uses thereof
IL312968A (en) 2021-11-22 2024-07-01 Janssen Biotech Inc The compositions containing multispecific binding agents enhance an immune response
WO2024089551A1 (en) 2022-10-25 2024-05-02 Janssen Biotech, Inc. Msln and cd3 binding agents and methods of use thereof

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4376110A (en) 1980-08-04 1983-03-08 Hybritech, Incorporated Immunometric assays using monoclonal antibodies
US4870163A (en) 1985-08-29 1989-09-26 New York Blood Center, Inc. Preparation of pure human tumor necrosis factor and hybridomas producing monoclonal antibodies to human tumor necrosis factor
DE3631229A1 (de) 1986-09-13 1988-03-24 Basf Ag Monoklonale antikoerper gegen humanen tumornekrosefaktor (tnf) und deren verwendung
US5075236A (en) 1987-04-24 1991-12-24 Teijin Limited Method of detecting kawasaki disease using anti-tumor necrosis antibody
DE10399036I1 (de) 1989-08-07 2004-04-01 Peptide Technology Ltd Bindeligande für Tumornekrosisfaktor.
US5919452A (en) 1991-03-18 1999-07-06 New York University Methods of treating TNFα-mediated disease using chimeric anti-TNF antibodies
DE06001779T1 (de) * 1991-03-18 2010-01-14 New York University Monoklonale und chimäre Antikörper gegen humanen Tumornekrosefaktor
US6277969B1 (en) 1991-03-18 2001-08-21 New York University Anti-TNF antibodies and peptides of human tumor necrosis factor
US7192584B2 (en) 1991-03-18 2007-03-20 Centocor, Inc. Methods of treating psoriasis with anti-TNF antibodies
FR2807767B1 (fr) 2000-04-12 2005-01-14 Lab Francais Du Fractionnement Anticorps monoclonaux anti-d
UA81743C2 (uk) 2000-08-07 2008-02-11 Центокор, Инк. МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ
CA2450289A1 (en) 2003-03-20 2005-05-19 Imclone Systems Incorporated Method of producing an antibody to epidermal growth factor receptor
US20040185047A1 (en) 2003-03-21 2004-09-23 Jill Giles-Komar Anti- TNF antibodies, compositions, methods and uses
DK1807504T3 (da) 2004-11-02 2011-03-21 Ares Trading Sa Serumfrit cellekulturmedium til celler fra pattedyr
CA2720610C (en) * 2008-04-07 2016-08-23 Bayer Healthcare Llc Methods of recombinant production of glycoproteins
PL2702164T3 (pl) * 2011-04-29 2016-06-30 Biocon Res Limited Sposób obniżania heterogeniczności przeciwciał i sposób ich wytwarzania
US9475858B2 (en) 2011-07-08 2016-10-25 Momenta Pharmaceuticals, Inc. Cell culture process
US9181572B2 (en) 2012-04-20 2015-11-10 Abbvie, Inc. Methods to modulate lysine variant distribution
PT2970980T (pt) * 2013-03-15 2018-11-19 Janssen Biotech Inc Métodos de produção para controlor o teor de lisina c-terminal, galactose e ácido siálico em proteínas recombinantes

Also Published As

Publication number Publication date
PH12015501837B1 (en) 2015-11-09
WO2014149935A1 (en) 2014-09-25
AU2020203864B2 (en) 2022-05-26
EP2970980B1 (en) 2018-08-15
US20160237149A1 (en) 2016-08-18
AR095660A1 (es) 2015-11-04
AU2014237635B2 (en) 2020-03-12
US20140273092A1 (en) 2014-09-18
CN105378086B (zh) 2019-05-28
PL2970980T3 (pl) 2019-01-31
AU2020203864A1 (en) 2020-07-02
KR102216003B1 (ko) 2021-02-16
IL240689A0 (en) 2015-10-29
AU2014237635A1 (en) 2015-09-03
MX2015012361A (es) 2016-04-28
TW201441263A (zh) 2014-11-01
EP2970980A1 (en) 2016-01-20
AR124871A2 (es) 2023-05-17
BR112015022971B1 (pt) 2022-05-17
ES2690047T3 (es) 2018-11-19
EA201591807A1 (ru) 2016-02-29
ZA201507671B (en) 2017-11-29
TWI630216B (zh) 2018-07-21
BR112015022971A2 (pt) 2017-11-14
HRP20181741T1 (hr) 2018-12-28
EP2970980B2 (en) 2022-07-27
DK2970980T3 (en) 2018-10-22
PT2970980T (pt) 2018-11-19
CA2907140A1 (en) 2014-09-25
US20220089712A1 (en) 2022-03-24
JP2016512029A (ja) 2016-04-25
KR20150129025A (ko) 2015-11-18
SG11201507577RA (en) 2015-10-29
US11149085B2 (en) 2021-10-19
LT2970980T (lt) 2018-10-25
SI2970980T1 (sl) 2018-11-30
CN105378086A (zh) 2016-03-02
PH12015501837A1 (en) 2015-11-09
RS57791B1 (sr) 2018-12-31
EP2970980A4 (en) 2016-09-07
IL240689B (en) 2021-12-01
MX366910B (es) 2019-07-30

Similar Documents

Publication Publication Date Title
CY1120980T1 (el) Μεθοδοι παρασκευης για τον ελεγχο της περιεκτικοτητας σε c-τελικη λυσινη, γαλακτοζη και σιαλικο οξυ σε ανασυνδυασμενες πρωτεϊνες
PH12017501114A1 (en) Anti-c5 antibodies and methods of use
HRP20211882T1 (hr) Protutijela protiv cd40 i njihova upotreba
MX2020011334A (es) Cultivo celular metabolicamente optimizado.
BR112018003214A2 (pt) fabricação de fosfatases alcalinas
AR080942A1 (es) Produccion de proteinas heteromultimericas
BR112012017896A2 (pt) Excisão de transgenes em organismos geneticamente modificados
EA201290168A1 (ru) Растения, обладающие повышенными урожайностными свойствами, и способ создания таких растений
BR112018011896A2 (pt) promotor, ácido nucleico, célula hospedeira procariótica, método de fermentação, e, método para aumentar a expressão ou atividade de catalase em uma célula hospedeira procariótica
BR112016008830A2 (pt) Método para produzir uma substância alvo
AR095418A1 (es) Métodos para aumentar el contenido de manosa en proteínas recombinantes
BR112014027264A2 (pt) processo para purificar ácido succínico a partir de um caldo de fermentação, e método para produzir um sal succinato
MX2019009045A (es) Nuevas luciferasas y metodos para su uso.
BR112013021836A2 (pt) plantas que possuem características relativas a rendimento aprimoradas e métodos de sua produção
Baković et al. Redox regulation of the quorum-sensing transcription factor AgrA by coenzyme A
MY184387A (en) Improved surface display of functional proteins in a broad range of gram negative bacteria
BR112016015812A2 (pt) Método para aumentar a biomassa e o conteúdo lipídico em um microrganismo e um microrganismo geneticamente modificado exibindo autofagia reforçada
BR112017020401A2 (pt) processo de produção com íons de cobre controlados
EA201390667A1 (ru) Ферменты и их применения
BR112015028050A2 (pt) plantas que possuem uma ou mais características relativas a rendimento aprimoradas e método de sua elaboração
EA201591558A1 (ru) Составы и способы увеличения производства рекомбинантного белка
Yoon et al. Enhanced production of the Mical redox domain for enzymology and F-actin disassembly assays
MX2013013063A (es) Plantas que tienen rasgos mejorados relacionados con el rendimiento y metodo para elaborar las mismas.
Wojciechowski et al. A Novel Flow Cytometry-Based Assay for the Identification of HCN4 CNBD Ligands
MX2017008633A (es) Procedimiento para preparar una proteina de fusion tnfr-fc que contiene un contenido objetivo de impurezas.