Abstract: Described are vaccines against malarial infections, which are based on recombinant viral vectors, such as alpha viruses, adenoviruses, or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Codon-optimized circumsporozoite genes are disclosed. Replication-defective adenoviruses may be used, derived from serotypes that encounter low titers of neutralizing antibodies. Also described is the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.
Type:
Grant
Filed:
December 1, 2010
Date of Patent:
January 17, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Maria G. Pau, Lennart Holterman, Jorn Kaspers, Antonius J. H. Stegmann
Abstract: The present invention provides new uses of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, the invention provides new assays to determine the best regimen for applying the most suitable recombinant viral vector in a vaccination or gene therapy setting.
Type:
Grant
Filed:
August 24, 2009
Date of Patent:
December 13, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Ronald Vogels, Maria Grazia Pau, Lennart Holterman, Stefan Kostense, Menzo Jans Emco Havenga, Mieke Caroline Sprangers
Abstract: The present invention provides human binding molecules specifically binding to a host cell protein and having virus neutralizing activity, nucleic acid molecules encoding the human binding molecules, compositions comprising the human binding molecules and methods of identifying or producing the human binding molecules. The human binding molecules can be used in the diagnosis, prophylaxis and/or treatment of viral infections.
Type:
Grant
Filed:
May 11, 2006
Date of Patent:
November 8, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Mark Throsby, Cornelis Adriaan De Kruif
Abstract: Provided are methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B-55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.
Type:
Grant
Filed:
September 5, 2007
Date of Patent:
November 8, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Ronald Vogels, Menzo Jans Emco Havenga, David Adrianus Theodorus Maria Zuijdgeest
Abstract: The invention relates to vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding for at least two antigens from one or more tuberculosis-causing bacilli. The invention also relates to the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. The invention furthermore relates to the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.
Type:
Grant
Filed:
November 15, 2005
Date of Patent:
September 6, 2011
Assignees:
Crucell Holland B.V., Aeras Global TB Vaccine Foundation
Inventors:
Menzo J. E. Havenga, Ronald Vogels, Jerald Sadoff, David Hone, Yasir A. W. Skeiky, Katarina Radosevic
Abstract: Provided are processes for culturing cells derived from embryonic retinoblast cells immortalized by adenovirus E1 sequences, such as PER.C6® cells, to improve product yields from such cells. Feed strategies for such cells and cultures with very high cell densities are provided, resulting in high yields of products, such as recombinant antibodies.
Abstract: A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and/or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprise a tissue tropism-determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing these gene delivery vehicles are provided.
Type:
Grant
Filed:
May 28, 2009
Date of Patent:
June 28, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Ronald Vogels, Menzo J. E. Havenga, Abraham Bout
Abstract: The present invention provides human binding molecules that specifically bind to CD1a, nucleic acid molecules encoding the human binding molecules, compositions comprising the human binding molecules and methods of identifying or producing the human binding molecules. The human binding molecules can be used in the diagnosis, prevention and treatment of neoplastic disorders and diseases.
Type:
Grant
Filed:
March 23, 2006
Date of Patent:
June 28, 2011
Assignees:
Crucell Holland B.V., The Johns Hopkins University
Inventors:
Mark Throsby, Marja van Meijer, Wilfred T. V. Germeraad, Robert J. Arceci, Ada M. Kruisbeek
Abstract: Described are of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, described are assays to determine the best regimen for applying the most suitable recombinant viral vector in a vaccination or gene therapy setting.
Abstract: Described are vaccines against malarial infections, which are based on recombinant viral vectors, such as alpha viruses, adenoviruses, or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Codon-optimized circumsporozoite genes are disclosed. Replication-defective adenoviruses may be used, derived from serotypes that encounter low titers of neutralizing antibodies. Also described is the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.
Type:
Application
Filed:
December 1, 2010
Publication date:
June 23, 2011
Applicant:
Crucell Holland B.V.
Inventors:
Maria G. Pau, Lennart Holterman, Jorn Kaspers, Antonius J. H. Stegmann
Abstract: Means and methods for producing mammalian viruses, the method comprising infecting a culture of immortalized human cells with a virus, incubating the culture infected with virus to propagate the virus under conditions that permit growth of the virus, and to form a virus-containing medium, and removing the virus-containing medium. The viruses can be harvested and be used for the production of vaccines. Advantages include that human cells of the present invention can be cultured under defined serum-free conditions and the cells show improved capability for propagating virus. Methods are provided for producing, in cultured human cells, influenza virus and vaccines derived thereof. This method eliminates the necessity of using whole chicken embryos for the production of Influenza vaccines. The method also provides for the continuous or batch-wise removal of culture media. As such, the present invention allows the large-scale continuous production of viruses to a high titer.
Type:
Grant
Filed:
February 24, 2009
Date of Patent:
June 21, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Maria G. Pau, Alphonsus G. C. M. UytdeHaag, Govert J. Schouten
Abstract: The present invention provides pharmaceutical antibody formulations, in particular liquid pharmaceutical formulations comprising anti-rabies virus antibodies. The formulations can be used in the post exposure prophylaxis of rabies.
Type:
Grant
Filed:
December 4, 2007
Date of Patent:
June 14, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Alexander B. H. Bakker, Willem E. Marissen
Abstract: The present invention provides human binding molecules specifically binding to enterococci and having killing activity against enterococci, nucleic acid molecules encoding the human binding molecules, compositions comprising the human binding molecules and methods of identifying or producing the human binding molecules. The human binding molecules can be used in the diagnosis, prophylaxis and/or treatment of a condition resulting from Enterococcus.
Type:
Grant
Filed:
June 5, 2007
Date of Patent:
June 14, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Mark Throsby, Robert Arjen Kramer, Cornelis Adriaan De Kruif
Abstract: Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.
Type:
Grant
Filed:
October 25, 2006
Date of Patent:
March 15, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Abraham Bout, Menzo Havenga, Ronald Vogels
Abstract: The invention relates to the field of generating helper phages and phage display libraries for the identification of binding molecules. The invention provide chimaeric phages having a coat comprising a protein mixture. The protein mixture comprises a fusion protein having a proteinaceous molecule fused to a functional form of a phage coat protein and a mutant form of the phage coat protein, wherein the mutant form is impaired in binding to a host cell receptor. The invention further provides new phage collections, novel helper phages and methods and means for producing chimaeric phages, infectious phages and helper phages.
Type:
Grant
Filed:
October 26, 2007
Date of Patent:
March 8, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Erwin Houtzager, Ton Logtenberg, Cornelis Adriaan De Kruif
Abstract: The present invention addresses the need to improve the long-term storage stability (i.e. infectivity) of vector formulations. In particular, it has been demonstrated that for adenovirus, the use of bulking agents, cryoprotectants and lyoprotectants imparts desired properties that allow both lyophilized and liquid adenovirus formulations to be stored at 4° C. for up to 6 months and retain an infectivity between 60-100% of the starting infectivity.
Abstract: The present invention addresses the need to improve the long-term storage stability (i.e. infectivity) of vector formulations. In particular, it has been demonstrated that for adenovirus, the use of bulking agents, cryoprotectants and lyoprotectants imparts desired properties that allow both lyophilized and liquid adenovirus formulations to be stored at 4° C. for up to 6 months and retain an infectivity between 60-100% of the starting infectivity.
Abstract: The invention relates to the production of coronaviruses. In particular, the invention relates to methods for producing SARS-CoV by using cells expressing a functional SARS-CoV receptor.
Type:
Grant
Filed:
July 21, 2006
Date of Patent:
February 15, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Edward Norbert Van Den Brink, Jan Henrik Ter Meulen
Abstract: The present invention relates to novel vaccines against malaria infections, based on recombinant viral vectors, such as alpha viruses, adenoviruses or vaccinia viruses. The recombinant viral-based vaccines can be used to immunize against different Plasmodium infections, such as infections by P. falciparum or P. yoelii. Novel codon-optimized circumsporozoite genes are disclosed. Preferably, replication-defective adenoviruses are used, derived from serotypes that encounter low titers of neutralizing antibodies. The invention, therefore, also relates to the use of different adenoviral serotypes that are administered to elicit a strong immune response, either in single vaccination set-ups or in prime-boost set-ups in which compositions based on different serotypes can be applied.
Type:
Grant
Filed:
October 18, 2007
Date of Patent:
January 11, 2011
Assignee:
Crucell Holland B.V.
Inventors:
Maria G. Pau, Lennart Holterman, Jorn Kaspers, Antonius J. H. Stegmann
Abstract: The present invention provides new tumor-associated antigens, binding molecules that specifically bind to the antigens, nucleic acid molecules encoding the binding molecules, compositions comprising the binding molecules and methods of identifying or producing the binding molecules. The new tumor-associated antigen are expressed on cancer cells and binding molecules capable of specifically binding to the antigens can be used in the diagnosis, prevention and/or treatment of cancer.
Type:
Grant
Filed:
October 11, 2005
Date of Patent:
December 28, 2010
Assignee:
Crucell Holland B.V.
Inventors:
Cecilia Anna Wilhelmina Geuijen, Cornelis Adriaan De Kruif