Abstract: The present invention relates recombinant human ?1-antitrypsin (rhAAT) comprising N-linked glycans, wherein at least 10% of said N-linked glycans are tetra-antennary glycans; and the degree of capping with sialic acid on said N-linked glycans (Z/A) is at least 50%. The invention further relates to rhAAT for use as a medicament, in particular for use in the prevention and/or treatment of a disease associated with AAT deficiency, and/or a disease involving neutrophil-mediated tissue damage.
Type:
Grant
Filed:
April 20, 2010
Date of Patent:
January 22, 2013
Assignee:
Crucell Holland B.V.
Inventors:
Elisabeth C. M. Brinkman, Ingrid Van Den Nieuwenhof
Abstract: Described are methods for separating hemagglutinin (HA) antigens, comprising the steps of applying a reduced and derivatized antigen preparation comprising solubilized HA antigens and a detergent in a pH controlled solution, on a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) column; and eluting the HA antigens from the column with an ion pairing agent in an organic mobile phase. The invention further relates to quantifying methods using the methods for separating the antigens with the further step of measuring the peak area of the eluted antigen in a chromatogram resulting from the elution step.
Abstract: Provided is a human C-type lectin, binding molecules that specifically bind to the human C-type lectin, nucleic acid molecules encoding the binding molecules or the human C-type lectin, compositions comprising the binding molecules or the human C-type lectin and methods of identifying or producing the binding molecules. The human C-type lectin is specifically expressed on myeloid cells and binding molecules capable of specifically binding to the human C-type lectin can be used in the diagnosis, prevention and/or treatment of neoplastic disorders and diseases.
Type:
Grant
Filed:
December 18, 2009
Date of Patent:
September 18, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Sonja van den Oudenrijn, Marja van Meijer, Adrianus Q. Bakker, Alexander Berthold Hendrik Bakker
Abstract: Described are 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:
May 19, 2011
Date of Patent:
August 14, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Mark Throsby, Robert Arjen Kramer, Cornelis Adriaan De Kruif
Abstract: The invention provides methods for large-scale adenovirus purification from high cell density suspensions, using host cell DNA fragmentation and/or precipitation followed by a clarification step with tangential flow filtration.
Abstract: The invention provides an immortalized human retina cell expressing E1A and E1B proteins of an adenovirus, wherein the cell has recombinant nucleic acid encoding an IgA molecule in expressible format. Also provided is a method for recombinant production of an IgA molecule, the method involving culturing a cell of the invention and expressing the recombinant nucleic acid encoding an IgA.
Abstract: Cells capable of at least, in part, complementing adenovirus an adenovirus defective in E2A function. Such cells include a nucleic acid-encoding adenovirus E2A or a functional part, derivative, temperature-sensitive mutation and/or analogue thereof, integrated into the cell's genome. Methods for producing an adenovirus particle/vector with a functional deletion of E2A are also disclosed. Such methods involve providing a cell with the functionally deleted adenovirus vector, culturing the cell, and harvesting viral particles. The functional deletion may comprise a deletion in E2A. The nucleic acid-encoding E2A in the cell's genome may lack sequence overlap with the vector, preventing formation of a replication-competent adenovirus or restoration of E2A function. The adenovirus vector may further include a functional deletion in the E1-region.
Type:
Grant
Filed:
May 19, 2005
Date of Patent:
August 7, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Frits J. Fallaux, Robert C. Hoeben, Abraham Bout, Domenico Valerio, Alex J. van der Eb, Govert Schoutten
Abstract: Described are new uses of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, also described are 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 23, 2011
Date of Patent:
July 24, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Ronald Vogels, Maria Grazia Pau, Lennart Holterman, Stefan Kostense, Menzo Jans Emco Havenga, Mieke Caroline Sprangers
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 29, 2007
Date of Patent:
July 17, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Abraham Bout, Menzo Jans Emco Havenga, Ronald Vogels
Abstract: The present invention provides human binding molecules specifically binding to staphylococci and having killing activity against staphylococci, 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 Staphylococcus.
Type:
Grant
Filed:
June 5, 2007
Date of Patent:
July 3, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Mark Throsby, Cecilia A. W. Geuijen, Cornelis Adriaan De Kruif
Abstract: Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is 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. Also described is 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:
May 31, 2011
Date of Patent:
June 19, 2012
Assignees:
Crucell Holland B.V., Aeras Global TB Vaccine Foundation
Inventors:
Menzo Jans Emco Havenga, Ronald Vogels, Jerald C. Sadoff, David Hone, Yasir Abdul Wahid Skeiky, Katarina Rado{hacek over (s)}evic
Abstract: Described are human binding molecules specifically binding to staphylococci and having killing activity against staphylococci, 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 Staphylococcus.
Type:
Application
Filed:
February 15, 2012
Publication date:
June 7, 2012
Applicant:
Crucell Holland B.V.
Inventors:
Mark Throsby, Cecilia A.W. Geuijen, Cornelis Adriaan De Kruif
Abstract: The present invention relates to binding molecules such as human monoclonal antibodies that bind to influenza virus H5N1 and have neutralizing activity against influenza virus H5N1. The disclosure provides nucleic acid molecules encoding the antibodies, their sequences and compositions comprising the antibodies and methods of identifying or producing the antibodies. The antibodies can be used in the diagnosis, prophylaxis and/or treatment of an influenza virus H5N1 infection. In a preferred embodiment, the antibodies provide cross-subtype protection in vivo, such that infections with H5, H2, H6, H9 and H1-based influenza subtypes can be prevented and/or treated.
Type:
Grant
Filed:
September 6, 2007
Date of Patent:
June 5, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Edward Norbert Van Den Brink, Cornelis Adriaan De Kruif, Mark Throsby
Abstract: The invention provides binding molecules that specifically bind to rabies virus and are capable of neutralizing the virus. The invention further provides nucleic acid molecules encoding the binding molecules, compositions comprising the binding molecules and methods of identifying or producing the binding molecules. The binding molecules can be used in the diagnosis, prophylaxis and/or treatment of a condition resulting from rabies virus. Preferably, they can be used in the post-exposure prophylaxis of rabies.
Type:
Grant
Filed:
July 6, 2009
Date of Patent:
April 3, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Alexander Berthold Hendrik Bakker, Willem Egbert Marissen, Robert Arjen Kramer, Cornelis Adriaan de Kruif
Abstract: Provided are human binding molecules that specifically bind to a host cell protein and have virus neutralizing activity, nucleic acid molecules encoding such 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:
Application
Filed:
August 25, 2011
Publication date:
March 29, 2012
Applicant:
Crucell Holland B.V.
Inventors:
Mark Throsby, Cornelis Adriaan de Kruif
Abstract: The present invention provides binding molecules, such as human binding molecules, that bind to and stimulate the human OX40-receptor. The invention also provides nucleic acids encoding such binding molecules. Methods for producing such binding molecules are also provided by the present invention. The binding molecules and nucleic acids are useful in the stimulation of human T-cells and can be used to enhance antigen-specific immune responses.
Type:
Grant
Filed:
March 23, 2009
Date of Patent:
March 13, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Alexander Berthold Hendrik Bakker, Pauline Marie Louise Meester-Rood, Adrianus Quirinus Bakker
Abstract: Provided is a method for purifying a virus from a host cell, the method comprising: a) culturing host cells, b) infecting the host cells with a virus, c) treating the cell culture with nuclease, and d) lysing the host cells to provide a lysate comprising the virus. The virus may be recombinant adenovirus. Further provided are methods for purifying a recombinant virus expressing a heterologous protein capable of binding nucleic acid, comprising: a) culturing host cells, b) infecting the host cells with recombinant virus, c) lysing the host cells to provide a lysate comprising the recombinant virus, d) subjecting the recombinant virus to anion exchange chromatography and size exclusion chromatography, wherein the virus-containing mixture is buffer exchanged at least once with a solution comprising at least 2 M NaCl, or another salt providing an equivalent ionic strength.
Type:
Grant
Filed:
July 28, 2008
Date of Patent:
February 28, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Miranda Weggeman, Emile J. J. M. van Corven
Abstract: In the absence of substantial sequence overlap between a recombinant adenoviral vector and the genome of a packaging cell, helper-dependent E1-containing particles (HDEP) can be formed at low frequency. Provided are means and methods for reducing or preventing the generation of HDEP. To this purpose, novel packaging cells and methods of making these are provided.
Type:
Grant
Filed:
July 14, 2010
Date of Patent:
February 14, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Ronald Vogels, Menzo Jans Emco Havenga, David Adrianus Theodorus Maria Zuijdgeest
Abstract: The present invention provides compositions of binding molecules specifically binding to a coronavirus such as SARS-CoV and capable of neutralizing an infection caused by the virus. The compositions are suitable for diagnosing, preventing and/or treating a condition resulting from a coronavirus such as SARS-CoV.
Type:
Grant
Filed:
November 10, 2005
Date of Patent:
January 31, 2012
Assignee:
Crucell Holland B.V.
Inventors:
Jan Henrik Ter Meulen, Edward Norbert Van Den Brink, Cornelis Adriaan De Kruif, Jaap Goudsmit
Abstract: Described are vaccine regimens in which specific prime/boost regimens are applied using low-neutralized recombinant adenoviral vectors harboring nucleic acids encoding antigens from Plasmodium falciparum and purified recombinant protein vaccines such as RTS,S, in the context of appropriate adjuvants.
Type:
Application
Filed:
August 23, 2011
Publication date:
January 19, 2012
Applicants:
Crucell Holland B. V., behalf of the Walter Reed Army Institute of Research, GlaxoSmithKline Biologicals S. A.
Inventors:
Maria-Grazia Pau, Jaap Goudsmit, Joseph D. Cohen, Patrice M. Dubois, V. Ann Stewart, Donald Gray Heppner, JR.