Crucell Holland B.v.

Introgene B.v.

Merus B.v.

Other

Merus N.v.

Mallinckrodt Pharma IP Trading D.a.c.

Galapagos Genomics N.v.

Octoplus B.v.

Galapagos Geonomics N.v.

Universiteit Utrecht Introgene B.v.

Mallinckrodt Oharma IP Trading D.a.c.

Profibrix B.v.

Abraham Bout

Ronald Vogels

Robert Cornelis Hoeben

Domenico Valerio

Alex Jan Van Der Eb

Frits Jacobus Fallaux

Govert Johan Schouten

Ton Logtenberg

Menzo Jans Emco Havenga

Menzo Havenga

Ronald Hendrik Peter Brus

Guus Hateboer

Karina Cornelia Verhulst

Alphonsus Gerardus Uytdehaag

Jacob Koopman

Johan Christiaan Kapteyn

Dirk Jan Elbertus Opstelten

Joseph Grimbergen

Patrick H C Van Berkel

Ronald Hendrik Brus

Wilhelmus Everhardus Hennink

Menzo J E Havenga

Helmuth Van Es

Patricius H C Van Berkel

Petrus Christianus Johannes Josephus Passier

Alphonsus Gerardus Cornelis Maria Uytdehaag

Ronald H P Brus

Dirk Willem Van Bekkum

Marie Elisabeth Draijer-van Der Kaaden

Helmuth H G Van Es

Govert Shouten

Petrus Christianius Johannes Josephus Passier

Dirk W Van Bekkum

David Halford Ashton Jones

Govert Schoutten

Govert John Schouten

Patricius Hendrikus Van Berkel

Patrick Hendrikus Cornelis Van Berkel

David H A Jones

Ronald Hendrik Pieter Brus

Petrus Passier

Menzo Jans Emko Havenga

Provided is methods for producing mixtures of antibodies from a single host cell clone, wherein, a nucleic acid sequence encoding a light chain and nucleic acid sequences encoding different heavy chains are expressed in a recombinant host cell. The recombinantly produced antibodies in the mixtures according to the invention suitably comprise identical light chains paired to different heavy chains capable of pairing to the light chain, thereby forming functional antigen-binding domains. Mixtures of the recombinantly produced antibodies are also provided by the invention. Such mixtures can be used in a variety of fields.

Recombinant production of mixtures of antibodies

The present invention relates to nucleotide sequences encoding a fibrinogen alpha, beta or gamma chain. The sequences are optimized for expression in a eukaryotic cell culture system. Such optimized nucleotide sequences allow for the efficient expression of recombinant fibrinogen and variants thereof in intact form in a eukaryotic cell culture system.

Recombinant fibrinogen

The present invention relates to fibrinogen preparations enriched in &#x3b1;-extended fibrinogen. Compositions comprising such preparations show improved clotting properties compared to preparations based on HMW Fib which typically contain no or only low amounts of &#x3b1;-extended fibrinogen. In particular, clot formation time and the clot strength of a clot made by &#x3b1;-extended fibrinogen are improved. In addition, plasmin-mediated degradation of &#x3b1;-extended fibrinogen is reduced as compared to plasma derived fibrinogen.

Fibrinogen preparations enriched in fibrinogen with an extended alpha chain

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.

Efficient production of IgA in recombinant mammalian cells

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. Methods are disclosed for providing cells of an individual with a nucleic acid of interest, without risk of administering simultaneously a replication-competent adenovirus vector, comprising administering the individual an adenovirus vector described herein.

Means and methods for nucleic acid delivery vehicle design and nucleic acid transfer

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.

Serotype of adenovirus and uses thereof

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. Further, a method is disclosed for delivering nucleic acid to cells such as smooth muscle cells and/or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism-determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular constructs are also disclosed.

Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells

The invention provides methods for producing mixtures of antibodies from a single host cell clone, wherein, a nucleic acid sequence encoding a light chain and nucleic acid sequences encoding different heavy chains are expressed in a recombinant host cell. The recombinantly produced antibodies in the mixtures according to the invention suitably comprise identical light chains paired to different heavy chains capable of pairing to the light chain, thereby forming functional antigen-binding domains. Mixtures of the recombinantly produced antibodies are also provided by the invention. Such mixtures can be used in a variety of fields.

The invention relates to methods and means for producing adenoviral vectors on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenoviral vector and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products provided by the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.

Means and methods for producing adenovirus vectors

Described are methods for identifying, selecting, and obtaining mammalian cells capable of producing proteinaceous molecules having predetermined post-translational modifications, wherein the post-translational modifications are brought about by the mammalian cell in which the proteinaceous molecule is expressed. Preferably, the predetermined post-translational modifications include glycosylation. Also described are methods for obtaining and producing proteinaceous molecules, using mammalian cells obtainable by a method of the present invention. Preferably, the proteinaceous molecules include erythropoietin (EPO), since EPO's effect depends heavily on its glycosylation pattern. Mammalian cells that have been obtained on the basis of their ability to produce proteins and/or post-translational modifications that are indicative for a predetermined post-translational modification that is desired are also provided. Preferably, the mammalian cells have neural characteristics and properties such that significant amounts of recombinant proteins can be produced that harbor 'neural- or brain-type' properties.

Methods and means for producing proteins with predetermined post-translational modifications

Growing community of inventors

Moerkapelle, Netherlands

Abraham Bout