ATE402260T1 - Rekombinante lactoferrin, verfahren zu ihrer herstellung mittels pflanzen und ihre verwendung - Google Patents

Rekombinante lactoferrin, verfahren zu ihrer herstellung mittels pflanzen und ihre verwendung

Info

Publication number: ATE402260T1
Authority: AT; Austria
Prior art keywords: lactoferrin; derived proteins; plants; production; plant cell
Prior art date: 1997-05-02

Application number

AT98924373T

Other languages

English (en)

Inventor

Dominique Legrand

Valerie Salmon

Genevieve Spik

Veronique Gruber

Philippe Bournat

Bertrand Merot

Original Assignee

Meristem Therapeutics S A

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.)

1997-05-02

Filing date

1998-05-04

Publication date

2008-08-15

1998-05-04 Application filed by Meristem Therapeutics S A filed Critical Meristem Therapeutics S A

2008-08-15 Application granted granted Critical

2008-08-15 Publication of ATE402260T1 publication Critical patent/ATE402260T1/de

Links

102000010445 Lactoferrin Human genes 0.000 title abstract 4
108010063045 Lactoferrin Proteins 0.000 title abstract 4
CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 title abstract 4
229940078795 lactoferrin Drugs 0.000 title abstract 4
235000021242 lactoferrin Nutrition 0.000 title abstract 4
235000018102 proteins Nutrition 0.000 abstract 3
102000004169 proteins and genes Human genes 0.000 abstract 3
108090000623 proteins and genes Proteins 0.000 abstract 3
239000002299 complementary DNA Substances 0.000 abstract 2
230000035897 transcription Effects 0.000 abstract 2
238000013518 transcription Methods 0.000 abstract 2
101000798114 Homo sapiens Lactotransferrin Proteins 0.000 abstract 1
102000050459 human LTF Human genes 0.000 abstract 1
239000002773 nucleotide Substances 0.000 abstract 1
125000003729 nucleotide group Chemical group 0.000 abstract 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/79—Transferrins, e.g. lactoferrins, ovotransferrins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
- C12N15/8257—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon
- 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
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8261—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield
- C12N15/8271—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance
- C12N15/8279—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for biotic stress resistance, pathogen resistance, disease resistance
- C12N15/8281—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for biotic stress resistance, pathogen resistance, disease resistance for bacterial resistance
- 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
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8261—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield
- C12N15/8271—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance
- C12N15/8279—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for biotic stress resistance, pathogen resistance, disease resistance
- C12N15/8282—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for biotic stress resistance, pathogen resistance, disease resistance for fungal resistance

Landscapes

Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Molecular Biology (AREA)
Zoology (AREA)
Wood Science & Technology (AREA)
Biomedical Technology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Medicinal Chemistry (AREA)
Plant Pathology (AREA)
Cell Biology (AREA)
Physics & Mathematics (AREA)
Microbiology (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Toxicology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Gastroenterology & Hepatology (AREA)
Pain & Pain Management (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Rheumatology (AREA)
Peptides Or Proteins (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Fertilizers (AREA)

AT98924373T 1997-05-02 1998-05-04 Rekombinante lactoferrin, verfahren zu ihrer herstellung mittels pflanzen und ihre verwendung ATE402260T1 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR9705699A FR2762850B1 (fr)	1997-05-02	1997-05-02	Lactoferrines recombinantes, leurs procedes de production par les plantes ainsi que leurs utilisations

Publications (1)

Publication Number	Publication Date
ATE402260T1 true ATE402260T1 (de)	2008-08-15

Family

ID=9506722

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AT98924373T ATE402260T1 (de)	1997-05-02	1998-05-04	Rekombinante lactoferrin, verfahren zu ihrer herstellung mittels pflanzen und ihre verwendung

Country Status (9)

Country	Link
US (3)	US6569831B1 (de)
EP (1)	EP0981617B1 (de)
JP (1)	JP2001527406A (de)
AT (1)	ATE402260T1 (de)
AU (1)	AU7659298A (de)
CA (1)	CA2288435A1 (de)
DE (1)	DE69839768D1 (de)
FR (1)	FR2762850B1 (de)
WO (1)	WO1998050543A1 (de)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2762850B1 (fr) *	1997-05-02	2000-02-11	Biocem	Lactoferrines recombinantes, leurs procedes de production par les plantes ainsi que leurs utilisations
IT1299565B1 (it) *	1998-07-17	2000-03-16	Plantechno S R L	Polinucleotide sintetico codificante per la lattoferrina umana, vettori, cellule e piante transgeniche che lo contengono.
US6399570B1 (en) *	1999-02-05	2002-06-04	Agennix, Inc.	Antimicrobial/endotoxin neutralizing polypeptide
CN1351667A (zh) *	1999-03-17	2002-05-29	维多利亚大学创新和发展公司	抗广谱病原体的转基因植物
US6835868B1 (en)	1999-03-17	2004-12-28	University Of Victoria Innovation And Development Corporation	Transgenic plants expressing dermaseptin peptides providing broad spectrum resistance to pathogens
US7304208B2 (en)	2000-05-02	2007-12-04	Ventria Bioscience	Expression of human serum albumin (HSA) in monocot seeds
US7138150B2 (en) *	2000-05-02	2006-11-21	Ventria Bioscience	Method of making an anti-infective composition for treating oral infections
US6991824B2 (en) *	2000-05-02	2006-01-31	Ventria Bioscience	Expression of human milk proteins in transgenic plants
US20080050503A1 (en) *	2000-05-02	2008-02-28	Ning Huang	Expression of human milk proteins in transgenic plants
US7417178B2 (en) *	2000-05-02	2008-08-26	Ventria Bioscience	Expression of human milk proteins in transgenic plants
US20030172403A1 (en) *	2000-05-02	2003-09-11	Ning Huang	Plant transcription factors and enhanced gene expression
CA2437819A1 (en) *	2001-02-14	2002-08-22	Ventria Bioscience	Feed additive compositions and methods
AU2012202697B2 (en) *	2001-02-14	2015-05-07	Ventria Bioscience	Expression of human milk proteins in transgenic plants
EP2294930A3 (de) *	2001-02-14	2011-08-03	Ventria Bioscience	Expression von humanen Milchproteinen in transgenen Pflanzen
ES2467155T3 (es) *	2001-02-14	2014-06-12	Ventria Bioscience	Expresión de proteínas de leche humana en plantas transgénicas
SE0200598D0 (sv) *	2002-02-27	2002-02-27	A & Science Invest Ab	Pharmaceutical composition and method for treatment or prevention of vascular disease or states of tissue hypoperfusion with hypoxic and/or ischemic consequences
AU2002360677A1 (en) *	2002-12-20	2004-07-29	Ventria Bioscience	Lactoferrin protein with iron for treating iron deficiency and anemia
JP2007517504A (ja) *	2003-12-09	2007-07-05	ベントリアバイオサイエンス	融合担体として種子貯蔵蛋白を利用する植物種子中の融合ポリペプチドの高水準発現
US20080010697A1 (en) *	2003-12-23	2008-01-10	Daichang Yang	Methods of Expressing Heterologous Protein in Plant Seeds Using Monocot Non Seed-Storage Protein Promoters
US20100015713A1 (en) *	2005-06-28	2010-01-21	Scott Deeter	Components of cell culture media produced from plant cells
JP2009501784A (ja)	2005-07-18	2009-01-22	プロタリクスリミテッド	生物学的に活性な高分子の粘膜投与または経腸投与
CN102847141A (zh) *	2005-09-28	2013-01-02	文特里亚生物科学公司	用于肠道病症和/或补水的口服制剂
EP1808491A1 (de) *	2006-01-13	2007-07-18	Meristem Therapeutics S.A.	Genetisch modifizierte Pflanze mit verändertem Gehalt an Reserveproteinen
NZ555163A (en)	2007-05-14	2010-05-28	Fonterra Co Operative Group	Methods of immune or hematological enhancement, inhibiting tumour formation or growth, and treating or preventing cancer, cancer symptoms, or the symptoms of cancer treatments
WO2010096588A2 (en)	2009-02-20	2010-08-26	Ventria Bioscience	Cell culture media containing combinations of proteins
US12295990B2 (en)	2018-11-09	2025-05-13	The Wistar Institute Of Anatomy And Biology	Use of lactoferrin for generating myeloid-derived suppressor cells
US10947552B1 (en)	2020-09-30	2021-03-16	Alpine Roads, Inc.	Recombinant fusion proteins for producing milk proteins in plants
IL301396A (en)	2020-09-30	2023-05-01	Nobell Foods Inc	Recombinant milk proteins and food compositions comprising the same
US10894812B1 (en)	2020-09-30	2021-01-19	Alpine Roads, Inc.	Recombinant milk proteins
CN118324930B (zh) *	2024-06-13	2024-08-20	广州暨南大学医药生物技术研究开发中心有限公司	重组人源化乳铁蛋白及其制备方法
CN120271696B (zh) *	2025-06-11	2025-08-19	杭州纽龙生物科技有限公司	一种基于大肠杆菌载体的重组人乳铁蛋白的制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1995030339A1 (en) *	1994-05-05	1995-11-16	Ferrodynamics, Inc.	Cloning, expression, and uses of human lactoferrin
KR0154495B1 (ko) *	1995-05-22	1998-10-15	김은영	인체 락토페린 유전자로 형질전환된 항바이러스성 식물체의 제조방법
FR2736930B1 (fr)	1995-07-17	1997-09-19	Biocem	Procede de production, par des cellules vegetales, de proteines heminiques, proteines ainsi obtenues et produits contenant ces proteines
TR199900312T2 (xx) *	1996-08-14	1999-04-21	Novartis Ag	Bitki patojenik mantar�na kar�� menedici tesirli peptid.
FR2762850B1 (fr) *	1997-05-02	2000-02-11	Biocem	Lactoferrines recombinantes, leurs procedes de production par les plantes ainsi que leurs utilisations

1997
- 1997-05-02 FR FR9705699A patent/FR2762850B1/fr not_active Expired - Lifetime
1998
- 1998-05-04 US US09/423,097 patent/US6569831B1/en not_active Expired - Lifetime
- 1998-05-04 AT AT98924373T patent/ATE402260T1/de not_active IP Right Cessation
- 1998-05-04 DE DE69839768T patent/DE69839768D1/de not_active Expired - Fee Related
- 1998-05-04 WO PCT/FR1998/000895 patent/WO1998050543A1/fr not_active Ceased
- 1998-05-04 JP JP54778398A patent/JP2001527406A/ja active Pending
- 1998-05-04 CA CA002288435A patent/CA2288435A1/fr not_active Abandoned
- 1998-05-04 EP EP98924373A patent/EP0981617B1/de not_active Expired - Lifetime
- 1998-05-04 AU AU76592/98A patent/AU7659298A/en not_active Abandoned
2003
- 2003-05-27 US US10/446,234 patent/US7354902B2/en not_active Expired - Fee Related
2008
- 2008-04-08 US US12/099,462 patent/US8334254B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US8334254B2 (en)	2012-12-18
EP0981617B1 (de)	2008-07-23
US6569831B1 (en)	2003-05-27
FR2762850A1 (fr)	1998-11-06
US20110092411A1 (en)	2011-04-21
FR2762850B1 (fr)	2000-02-11
US20030229925A1 (en)	2003-12-11
US7354902B2 (en)	2008-04-08
JP2001527406A (ja)	2001-12-25
AU7659298A (en)	1998-11-27
WO1998050543A1 (fr)	1998-11-12
EP0981617A1 (de)	2000-03-01
DE69839768D1 (de)	2008-09-04
CA2288435A1 (fr)	1998-11-12

Legal Events

Date	Code	Title	Description
2009-01-15	RER	Ceased as to paragraph 5 lit. 3 law introducing patent treaties

Publication	Publication Date	Title
DE69839768D1 (de)	2008-09-04	Rekombinante lactoferrin, verfahren zu ihrer herstellung mittels pflanzen und ihre verwendung
ATE308614T1 (de)	2005-11-15	Durch pflanzen hergestelltes rekombinantes kollagen, verfahren zu ihrer herstellung und verwendung
ATE339509T1 (de)	2006-10-15	Stress-gekoppelter transkriptionsfaktor und dessen verwendung in pflanzen
ATE286126T1 (de)	2005-01-15	Glialmitogene faktoren, ihre herstellung und verwendung
ATE252157T1 (de)	2003-11-15	Nucleinsäuremoleküle aus pflanzen codierend enzyme, die an der stärkesynthese beteiligt sind
DE69737507D1 (de)	2007-05-03	Neue nukleinsäuremoleküle aus mais und deren verwendung zur herstellung modifizierter stärke
ATE447855T1 (de)	2009-11-15	Verfahren zur herstellung einer modifizierten stärke
ATE248872T1 (de)	2003-09-15	Alkoxysilan-endgruppen aufweisende polyurethanprepolymere, ein verfahren zu ihrer herstellung sowie ihre verwendung zur herstellung von dichtstoffen
DE69030539D1 (de)	1997-05-28	Wachstumsfaktor aus parenchymalen Lebenszellen, dafür kodierendes Gen, Verfahren zur Herstellung dieses Faktors und Transformanten
DE59003144D1 (de)	1993-11-25	Destillationsanlage zur Herstellung von Wasserstoff-Peroxid.
DE3787998D1 (de)	1993-12-09	ART-Nukleotidsegmente, -Vektoren, -Zellinien, Verfahren zur Herstellung und Verwendung.
DE68907608D1 (de)	1993-08-19	Verfahren zur herstellung von lignin-peroxidase durch verwendung von nichtproliferierenden phanerochaete chryosporium-zellen.
DE69332148D1 (de)	2002-08-29	Verwendung einer dna sequenz, kodierende für ein protein mit der fäligkeit oxalsäure abzubauen, zur genselektion
DE59404358D1 (de)	1997-11-20	Verfahren zur herstellung von 1,4-butandiol
DE69634753D1 (de)	2005-06-23	"targeting" polypeptide der inneren plastidenhüllmembran; ihre herstellung und verwendung
DE50010015D1 (de)	2005-05-12	Tetrahydropyrimidin-dioxygenase-gen, dadurch kodierte polypeptide und verfahren zur deren herstellung
ATE77621T1 (de)	1992-07-15	3-perfluoroalkyl-isoxazol-5-yl-oxycarbonsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als herbizide.
ATE364082T1 (de)	2007-06-15	Verfahren zur herstellung von pflanzen mit erhöhter resistenz gegen wasserstress
DE3768985D1 (de)	1991-05-08	Verwendung eines feststoffkatalysators zur herstellung von chlorfluorkohlenwasserstoffen.
ATE359364T1 (de)	2007-05-15	Verfahren zur mutagenese von nukleotidsequenzen aus pflanzen, algen, oder pilzen
ATE91502T1 (de)	1993-07-15	Verfahren zur herstellung von lignin-peroxidase durch verwendung von nichtproliferierenden phanerochaete chryosporium-zellen.