EP1888620A1 - Procede pour produire des particules de type viral contenant un principe actif - Google Patents

Procede pour produire des particules de type viral contenant un principe actif

Info

Publication number
EP1888620A1
EP1888620A1 EP06707650A EP06707650A EP1888620A1 EP 1888620 A1 EP1888620 A1 EP 1888620A1 EP 06707650 A EP06707650 A EP 06707650A EP 06707650 A EP06707650 A EP 06707650A EP 1888620 A1 EP1888620 A1 EP 1888620A1
Authority
EP
European Patent Office
Prior art keywords
antigen
virus
amino acid
acid sequence
protein
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP06707650A
Other languages
German (de)
English (en)
Inventor
Christoph Reichel
Claus RÜHLAND
Jürgen Hess
Christian Reiser
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
responsif GmbH
Original Assignee
responsif GmbH
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 responsif GmbH filed Critical responsif GmbH
Publication of EP1888620A1 publication Critical patent/EP1888620A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5256—Virus expressing foreign proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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
    • C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
    • C12N2710/22022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
    • C12N2710/22023—Virus like particles [VLP]
    • 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
    • C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
    • C12N2710/22051—Methods of production or purification of viral material
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to a process for the preparation of virus-containing particles containing an active substance and to the virus-like particles produced by the process.
  • WO 00/61616 A1 discloses a synthetic biologically active molecule for anchoring an active substance to pentamers of virus protein 1 (VP1) of the polyoma virus.
  • VP1 virus protein 1
  • an amino acid sequence which binds to VPl-pentamers and is derived from the C-terminal end of virus protein 2 (VP2) or 3 (VP3) of the polyoma virus is connected at one end to the active substance.
  • VLPs virus-like particles
  • VP1 polyoma virus
  • the proteins to be assembled are introduced in solution in an increased concentration and incubated until VLPs are formed.
  • E. coli already precipitates in low concentration. Such a hydrophobic domain of VP2 produced in E. coli is often unable to specifically bind to VP1 pentamers.
  • expression of recombinant VP2-binding VP2 in E. coli can be promoted by having the amino acid sequence of VP2 together with a hydrophilic amino acid sequence as described in Abbing et al. the amino acid sequence of GFP expressed as a fusion protein.
  • a recombinant fusion protein which, besides the VPl-pentamer interacting domain of VP2, reverses a predominantly hydrophobic amino acid sequence.
  • the problem of proper protein folding exists. Since the VPl-pentamerically interacting domain of VP2 is also hydrophobic, it can interact with the predominantly hydrophobic amino acid sequence and thereby adversely affect protein folding so that the resulting fusion protein can not bind specifically to VPl-pentamers.
  • the expression of such fusion proteins in E. coli often results in the formation of inclusion bodies, which are also referred to as "inclusion bodies". Proteins contained in the inclusion bodies are denatured and non-functional.
  • a solution of the tumor antigens or peptides in DMSO often also does not lead to a structure as it is present in the native tumor antigens.
  • One against the native Tumor antigens effective immunization can not be ensured.
  • the disadvantage here is that the process is complicated and additional purification is required for in vivo administration in order to remove the reagents required for the covalent coupling.
  • the object of the present invention is to eliminate the disadvantages of the prior art.
  • a method is to be provided which allows the preparation of a drug-containing virus-like particles, wherein the drug is to be presented so that it can induce formation of specific cytotoxic T cells in a mammal or human.
  • the virus-like particles and a use of the particles are to be specified.
  • a method for producing virus-like particles containing an active ingredient, wherein proteins which each have a first amino acid sequence derived from a first viral protein and fusion proteins assemble into the virus-like particles.
  • the first amino acid sequence is an amino acid sequence which is sufficient for the formation of capsid-forming and a second viral protein-specific binding capsomeres.
  • the fusion proteins each have a second amino acid sequence which specifically binds to one of the capsomers and is derived from the second virus protein, and a third amino acid sequence which forms the active substance.
  • the proteins and the fusion proteins are coexpressed in yeast cells.
  • the coexpression of the fusion proteins in the yeast cells ensures that the second amino acid sequence is folded so that it can specifically bind to the capsomeres, even if the third amino acid sequence forming the active substance is predominantly hydrophobic.
  • virus-like particles which contain the active ingredient can form from the fusion proteins and the capsules formed from the proteins.
  • the active ingredient is arranged so that it often repeats itself at a small distance.
  • the specific binding of the region of the fusion protein formed by the second amino acid sequence to the capsomers ensures good association of the active ingredient with the virus-like particles.
  • VLPs Process located on the inside of the VLPs and is thus protected from degradation, for example by proteases.
  • capsules are first formed in the yeast cells from the proteins, each of which has the first amino acid sequence. From the capsomeres and the fusion proteins, VLPs form in the yeast cells, which can then be isolated from the hepatic cells.
  • a further advantage of the method according to the invention is that all proteins contained in the VLPs are produced and assembled in an organism. As a result, it is not necessary in the production of a drug to provide a separate proof of production for all components according to GMP practice. All it takes is one
  • VLPs produced in yeasts. Since the VLPs are hydrophilic as a whole, they can easily be precipitated in aqueous solution. ger solution be administered. The use of DMSO for administration is not required.
  • the first virus protein and / or the second virus protein originate from a virus or can be obtained, wherein the virus is selected from the group of non-enveloped viruses comprising Papovaviridae, in particular polyoma and papillomaviruses, Iridoviridae, Adenoviridae, Parvoviridae, Picornaviridae, in particular polioviruses, Caliciviridae, Reoviridae and Birnaviridae.
  • the first virus protein is virus protein 1 of the polyoma virus (VP1) and the second virus protein is virus protein 2 (VP2) or virus protein 3 (VP3) of the polyoma virus.
  • the capsomers are preferably in the form of pentamers, hexamers or heptamers.
  • the process according to the invention is particularly advantageous if the third amino acid sequence is, at least predominantly, hydrophobic.
  • the hydrophobicity of the amino acid sequence can be determined, for example, by the method known from Kyte, J. and Russell, F.D., Journal of Molecular Biology (1982), Vol. 157, Issue 1, pages 105 to 132. The hydrophilic and hydrophobic properties of each of the 20 amino acid side chains are taken into account.
  • An amino acid sequence is predominantly hydrophobic if the majority of the amino acids forming the sequence are hydrophobic or if a peptide / protein having the amino acid sequence would be sparingly soluble or insoluble in water.
  • Fusion proteins the respective extent of the expression of the proteins and the fusion proteins coordinated so that a maximum in the process of the amount of the active substance-containing virus-like particles is formed. This can be achieved by introducing expression plasmids which code for the proteins and the fusion proteins into the yeast cells in a matched copy number. There may also be nucleic acid sequences which coding for the proteins and the fusion proteins are stably integrated into the genome of the yeast cells in a coordinated copy number.
  • the expression of the proteins takes place under the control of a first promoter, which is contained in a coding for the first plasmid, and the expression of the fusion proteins under the control of a second promoter, which in a coding for the fusion proteins second plasmid is included.
  • the respective extent of the expression of the proteins and the fusion proteins is coordinated by a suitable choice of the first and the second promoter.
  • the first and / or the second promoter are selected from the group consisting of the promoters of the genes of alcohol dehydrogenase 1 (ADHI), alcohol dehydrogenase 2 (ADH2), orthophosphoric monoester phosphohydrolase (Apase) , Format Dehydrogenase (FOD), Galactokinase (GALl), UDP-Glucose-4-Epimerase (GALlO), Glyceraldehyde-3-Phosphate (GAP), Glyceraldehyde-Phosphate-Dehydrogenase (GAPDH), Alcohol-Oxides (AOX) , Methanol oxidase (MOX), no message in thiamine 1 (NMTl), 3-phosphoglycerate kinase (PGK) and pyruvate kinase (PYKl) and the hybrid promoters GAL10 / PYK1 and ADH2 / GAPDH.
  • ADHI alcohol dehydr
  • the third amino acid sequence preferably comprises a sequence of at least one antigen, of at least one epitope of this antigen or of different epitopes of this antigen. If the third amino acid sequence comprises different epitopes of the antigen, the fusion protein is a so-called multi-epitope construct.
  • the antigen may be a tumor-associated antigen.
  • An antigen is any protein or peptide which can induce an immune reaction in a mammal or human, in particular the formation of cytotoxic T cells. To trigger the immune response, it may be necessary to appropriately present the antigen to the immune system.
  • a tumor-associated antigen an antigen which is expressed by tumor cells in a different way than by the corresponding non-degenerated cells of the same type or an antigen which has a specific influence on the growth or multiplication of tumor cells.
  • the tumor-associated antigen is selected from the group comprising NY-ESO-I, telomerase reverse transcriptase (TERT), p53, MDM2, CYPlB1, HER-2 / neu, CEACAM (Carcinoembryonic antigen-related cell adhesion molecule 5 ) and the apoptosis-inhibiting protein survivin.
  • the antigen is an antigen of an agent of a viral disease or infectious disease.
  • An antigen of a pathogen is an antigen which the pathogen itself has or for which the pathogen has a coding nucleotide sequence.
  • the viral disease or infectious disease can be a chronic viral disease or infectious disease.
  • the antigen may be selected from a group comprising: HIV-associated antigen, HCV-associated antigen antigen, tuberculosis-associated antigen, in particular Ag85A, Ag85B, Rv3407, Esat-6 and Hsp65, malaria-associated antigen, in particular CSP-I, LSA-I, LSA-3 and EXP-1, with a merozoite stage of the malaria pathogen, in particular MSP-I, and bilharzia-associated antigen.
  • the antigen is associated with one of the pathogens if the pathogen expresses the antigen itself or triggers its expression in the affected organism.
  • the third amino acid sequence forms an MHC class I-specific antigen.
  • the first amino acid sequence derived from the virus protein 1 of the polyomavirus (VP1) does not contain the DNA-binding domain contained in the VP1 and / or the nuclear localization sequence (NLS) contained in the VP1.
  • the DNA-binding domain is contained in the NLS or overlaps with the NLS.
  • the function of NLS is usually to translocate the VPI into the nucleus.
  • the DNA-binding domain can bind any DNA. By omitting the DNA-binding domain or the NLS can be achieved that little or no unwanted DNA from the host organism is packaged in the VLPs. As a result, a higher quality of the VLPs can be achieved. Undesirable side effects of DNA from the host organism are avoided. Tolerability of VLPs when administered to a mammal is improved.
  • yeast cells used for coexpression are preferably yeast cells of the species Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pichia pastoris, Hansenula polyraorpha, Kluyveromyces lactis or Kluyveromyces marxianus.
  • the invention further relates to virus-like particles, comprising proteins which each have a first amino acid sequence derived from a first virus protein, and fusion proteins.
  • the first amino acid sequence is an amino acid sequence which is sufficient for the formation of capsid-forming and a second viral protein specific binding capsomeres.
  • the fusion proteins each have a second amino acid sequence which specifically binds to one of the capsomers and is derived from the second virus protein, and a predominantly hydrophobic third amino acid sequence which forms an active substance.
  • Such particles with a predominantly hydrophobic third amino acid sequence could not be produced so far. However, their production succeeds when the proteins and the fusion proteins are coexpressed in yeast cells and the particles are formed in the yeast cells. Another way to make them is unknown.
  • Advantageous embodiments of the particles according to the invention result from the preceding embodiments relating to the method according to the invention.
  • the invention furthermore relates to the particles according to the invention for use as a medicament.
  • virus-like particles by coexpression of the virus protein VP1 of the polyoma virus and of a fusion protein from the virus protein VP3 of the polyoma virus and the tumor antigen Her2 / neu
  • the yeast expression plasmid pGCH-VP1 contains the yeast-specific GAL1 promoter, a yeast-specific CYCl transcription termination sequence, a CEN / ARS DNA fragment (origin of replication), a HIS3 selection marker and the coding DNA for the polyomavirus protein VP1.
  • the extracellular domain and the transmembrane domain of Her2 / neu (amino acids 1-683) are translationally fused with VP3.
  • the yeast expression plasmid pGCL-Her2 / neu (1-683) -VP3 contains - the yeast-specific GAL1 promoter, a yeast-specific CYCl transcription termination sequence,
  • the yeast expression plasmid pGCL-VP3-Her2 / neu contains the yeast-specific GAL1 promoter, a yeast-specific CYCl transcription termination sequence,
  • yeast cells are then centrifuged off at 1,000 ⁇ g for 2 minutes and the cell pellets are incubated with SG medium (6.7 g / l YNB (Becton Dickinson GmbH, Heidelberg, Germany).
  • SG medium 6. g / l YNB (Becton Dickinson GmbH, Heidelberg, Germany).
  • the virus-like particles For further purification of the virus-like particles to be 6 ml each of the supernatant carefully to 32 ml of a sucrose cushion (45% sucrose, in cell disruption buffer) layered and centrifuged for 4 hours at 4 0 C and 100,000. The pellets formed thereby contain the virus-like particles.
  • Pellets are taken up in cell disruption buffer (without PMSF) and insoluble material is removed by centrifugation at 5,000 xg for 10 minutes. The supernatant is on one Cesium chloride step gradient applied.
  • the cesium chloride step gradient is prepared from 4 ml fractions of increasing density (1.23 g / cm 3 , 1.26 g / cm 3 , 1.29 g / cm 3 , 1.32 g / cm 3 , 1.35 g / cm 3 , 1.38 g / cm 3 in 20 mM Tris-HCl, pH 7.6). Subsequent centrifugation is carried out at 100,000 xg and 4 ° C for 36 hours.
  • the yeast expression plasmid pmSurv-VP2 contains - a yeast-specific MET25 promoter that encodes
  • Cultivation of the hEP cells transformed with both plasmids is carried out as described in Example 1. Subsequently, the yeasts are centrifuged for 10 minutes at 1,000 xg and the yeast pellet in 0.5 ml cell disruption buffer (20 mM Tris-HCl, pH 7.6, 100 mM NaCl, 1 mM EDTA, 0.01% Triton X-100 , 1 mM PMSF) per gram fresh weight of the yeasts.
  • Fig. 3 shows a Western blot analysis of fractions 1 to 38 of the cesium chloride gradient.
  • the upper panel shows a Western blot analysis performed with VPI-specific antibodies and the lower panel a Western blot analysis performed with survivin-specific antibodies.
  • Fractions 18 to 27 show both VP1 and survivin-VP2 fusion protein.
  • FIG. 4 shows an electron micrograph of the VLPS contained in the fractions 24 to 27 of the cesium chloride gradient.
  • the VLPs are purified after culturing the yeast using classical biochemical methods.
  • the cell pellets in buffer QSA (20 mM ethanolamine, 2 mM EDTA, 6 mM DTT, 50 mM NaCl, 5% glycerol, pH 9.0, 10 ml buffer per gram cell pellet + protease inhibitor + benzonase, final concentration 1 U / ml) resuspended.
  • the cells are disrupted with a French press (3 cycles at 2000 bar). Subsequently, by centrifugation at 75,000 xg for 45 min and 4 ° C cell debris removed.

Abstract

L'invention concerne un procédé pour produire des particules de type viral contenant un principe actif, procédé selon lequel des protéines, qui présentent chacune une première séquence d'acides aminés dérivée d'une première protéine virale, ainsi que des protéines hybrides sont assemblées pour former les particules de type viral, lesdites protéines et lesdites protéines hybrides étant coexprimées dans des cellules de levure.
EP06707650A 2005-05-24 2006-03-28 Procede pour produire des particules de type viral contenant un principe actif Withdrawn EP1888620A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005024421 2005-05-24
PCT/EP2006/002809 WO2006125490A1 (fr) 2005-05-24 2006-03-28 Procede pour produire des particules de type viral contenant un principe actif

Publications (1)

Publication Number Publication Date
EP1888620A1 true EP1888620A1 (fr) 2008-02-20

Family

ID=36593032

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06707650A Withdrawn EP1888620A1 (fr) 2005-05-24 2006-03-28 Procede pour produire des particules de type viral contenant un principe actif

Country Status (5)

Country Link
US (1) US20090215146A1 (fr)
EP (1) EP1888620A1 (fr)
AU (1) AU2006251454A1 (fr)
CA (1) CA2615415A1 (fr)
WO (1) WO2006125490A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2008279584A1 (en) * 2007-04-27 2009-01-29 Dow Global Technologies Inc. Improved production and in vivo assembly of soluble recombinant icosahedral virus-like particles
EP2742139A4 (fr) * 2011-08-11 2015-04-15 Univ Queensland Compositions immunogènes et procédés associés

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4844076A (en) * 1988-08-26 1989-07-04 The Johns Hopkins University Ingestible size continuously transmitting temperature monitoring pill
US5167626A (en) * 1990-10-02 1992-12-01 Glaxo Inc. Medical capsule device actuated by radio-frequency (RF) signal
US6374670B1 (en) * 1995-03-13 2002-04-23 University Of Washington Non-invasive gut motility monitor
US8092224B2 (en) * 1995-11-22 2012-01-10 James A. Jorasch Systems and methods for improved health care compliance
US5984875A (en) * 1997-08-22 1999-11-16 Innotek Pet Products, Inc. Ingestible animal temperature sensor
DE69909327T2 (de) * 1998-12-21 2004-04-22 Sequella, Inc. Verwendungsmethoden und zusammenstellungen enthaltend überwachungsystem
US7039453B2 (en) * 2000-02-08 2006-05-02 Tarun Mullick Miniature ingestible capsule
JP2004516863A (ja) * 2000-07-24 2004-06-10 モトローラ・インコーポレイテッド 摂取可能な電子カプセル
US7160258B2 (en) * 2001-06-26 2007-01-09 Entrack, Inc. Capsule and method for treating or diagnosing the intestinal tract
US6951536B2 (en) * 2001-07-30 2005-10-04 Olympus Corporation Capsule-type medical device and medical system
JP3962250B2 (ja) * 2001-08-29 2007-08-22 株式会社レアメタル 生体内情報検出システム及びこれに用いるタグ装置、中継装置
US7102508B2 (en) * 2002-09-09 2006-09-05 Persephone, Inc. Method and apparatus for locating and tracking persons
US7118531B2 (en) * 2002-09-24 2006-10-10 The Johns Hopkins University Ingestible medical payload carrying capsule with wireless communication
US7554452B2 (en) * 2003-07-18 2009-06-30 Cary Cole Ingestible tracking and locating device
JP4332152B2 (ja) * 2003-09-02 2009-09-16 富士通株式会社 薬服用状況管理方法及び薬剤
US20050062644A1 (en) * 2003-09-08 2005-03-24 Leci Jonathan Ilan Capsule device to identify the location of an individual
US8306592B2 (en) * 2003-12-19 2012-11-06 Olympus Corporation Capsule medical device
JP4198045B2 (ja) * 2003-12-25 2008-12-17 オリンパス株式会社 被検体内位置検出システム
CN1284505C (zh) * 2004-02-28 2006-11-15 重庆金山科技（集团）有限公司 医用无线电胶囊式内窥系统
JP4520198B2 (ja) * 2004-04-07 2010-08-04 オリンパス株式会社 被検体内位置表示システム
US20050285746A1 (en) * 2004-06-25 2005-12-29 Sengupta Uttam K Radio frequency identification based system to track consumption of medication
US7414534B1 (en) * 2004-11-09 2008-08-19 Pacesetter, Inc. Method and apparatus for monitoring ingestion of medications using an implantable medical device
US7504954B2 (en) * 2005-03-17 2009-03-17 Spaeder Jeffrey A Radio frequency identification pharmaceutical tracking system and method
US20060262180A1 (en) * 2005-05-17 2006-11-23 Robbins Gene A Object processing assembly operable to form dynamically variable images in objects in single shot events
JP4933538B2 (ja) * 2005-05-20 2012-05-16 ダウ グローバル テクノロジーズ エルエルシー 無線周波識別標識を用いた経口薬服薬履行監視
US7616111B2 (en) * 2005-06-20 2009-11-10 Carestream Health, Inc. System to monitor the ingestion of medicines
US7796043B2 (en) * 2005-07-20 2010-09-14 Neil R. Euliano Medication compliance system and associated methods
US20090124871A1 (en) * 2005-08-22 2009-05-14 Khalil Arshak Tracking system
US20070156016A1 (en) * 2005-12-29 2007-07-05 Ido Betesh Method and system for communication with an ingestible imaging device
US7678043B2 (en) * 2005-12-29 2010-03-16 Given Imaging, Ltd. Device, system and method for in-vivo sensing of a body lumen
JP2009532119A (ja) * 2006-03-30 2009-09-10 ダウ グローバル テクノロジーズ インコーポレイティド 内服投薬レジメンの服薬遵守を監視し分析する方法とシステム
WO2008018076A2 (fr) * 2006-08-10 2008-02-14 Given Imaging Ltd. Système et procédé pour une imagerie in vivo
US20080303638A1 (en) * 2007-03-24 2008-12-11 Hap Nguyen Portable patient devices, systems, and methods for providing patient aid and preventing medical errors, for monitoring patient use of ingestible medications, and for preventing distribution of counterfeit drugs
US8115618B2 (en) * 2007-05-24 2012-02-14 Proteus Biomedical, Inc. RFID antenna for in-body device
US20090048498A1 (en) * 2007-08-17 2009-02-19 Frank Riskey System and method of monitoring an animal
US20090088618A1 (en) * 2007-10-01 2009-04-02 Arneson Michael R System and Method for Manufacturing a Swallowable Sensor Device
JP5132335B2 (ja) * 2008-01-29 2013-01-30 富士フイルム株式会社 カプセル内視鏡及びカプセル内視鏡システム
SG188839A1 (en) * 2008-03-05 2013-04-30 Proteus Digital Health Inc Multi-mode communication ingestible event markers and systems, and methods of using the same
US9538937B2 (en) * 2008-06-18 2017-01-10 Covidien Lp System and method of evaluating a subject with an ingestible capsule

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2006125490A1 *

Also Published As

Publication number Publication date
AU2006251454A1 (en) 2006-11-30
US20090215146A1 (en) 2009-08-27
WO2006125490A1 (fr) 2006-11-30
CA2615415A1 (fr) 2006-11-30

Similar Documents

Publication Publication Date Title
EP0809700B1 (fr) Particules semblables au virus du papillome, proteines de fusion et leur procede de production
DE19543553B4 (de) VP-Antigene des JC-Virus
DE60122300T2 (de) Hepatitis b kernprotein fusionsproteine
DE69532532T2 (de) Chimerische papillomavirus-ahnliche partikel
DE69929232T2 (de) Virusähnliche partikel zur induktion von autoantikörpern
DE69535018T2 (de) Papillomavirus vakzine
DE69535519T2 (de) Auf hefe basierte vehikel zur abgabe
EP1159405B1 (fr) Particules virales liberees apres infection par le virus cytomegalique humain et leur utilisation comme vaccin
DE60132770T2 (de) Chimäre humane papillomavirus (hpv) l1 moleküle und deren verwendungen
DE60126737T2 (de) Modifizierte HPV E6- und E7-Gene und -Proteine als Impfstoff
DE19618797C2 (de) Vehikel zum Transport molekularer Substanz
DE69531308T2 (de) Verfahren zur Herstellung von gereinigten papillomavirus Proteinen
DE69631586T9 (de) Für menschliches papillomavirus stamm 18 kodierende dns
DE69933875T2 (de) Protein-verabreichungssystem, das dem menschlichen papillomavirus ähnliche partikel benützt.
EP1888620A1 (fr) Procede pour produire des particules de type viral contenant un principe actif
DE4435907C2 (de) Papillomavirusähnliche Partikel und deren Anwendung
WO2002043757A2 (fr) Medicament pour la prophylaxie ou le traitement de tumeurs induites par le virus du papillome humain de type 18
EP1140987B1 (fr) Peptide pour l'inhibition des proteines e6 du virus de l'hepatite b
DE19925199A1 (de) Zytotoxische T-Zellepitope des Papillomavirus L1-Proteins und ihre Verwendung in Diagnostik und Therapie
DE69924262T3 (de) Verfahren zur herstellung von durch hefe exprimierte hpv typs 6 und 16 kapsid-proteinen
EP1064014B1 (fr) Medicament permettant de prevenir ou de traiter les tumeurs a papillomavirus
EP1183367B1 (fr) Epitope cytotoxiques des lymphocytes t, de proteine l1 du papillomavirus, et utilisation dans les domaines du diagnostic et de la therapie
DE19526752C2 (de) Hocheffiziente Bildung von Papillomavirusähnlichen Partikeln
EP1030923B1 (fr) Procede d'obtention de particules semblables a des virus a base de virus de polyome
DE19812940A1 (de) Formulierung mit Papillomavirus-spezifischem Protein, seine Herstellung und Verwendung

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20071218

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

RIN1 Information on inventor provided before grant (corrected)

Inventor name: REISER, CHRISTIAN

Inventor name: REICHEL, CHRISTOPH

Inventor name: HESS, JUERGEN

Inventor name: RUEHLAND, CLAUS

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20090707

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20101005