National Research Council of Canada

Yves Durocher

Traian Sulea

Danica Stanimirovic

Amine A Kamen

Anne Marcil

Balu Chakravarthy

Martin Loignon

Phuong Lan Pham

Sylvie Perret

Michel Gilbert

Maria L Jaramillo

Mehdi Arbabi-Ghahroudi

Anne E G Lenferink

Kristin Kemmerich

Maria Moreno

Maureen D O'Connor

Maurizio Acchione

Simon Joubert

Marzia Martina

Umberto Banderali

Anne Eg Lenferink

The present document describes an alpha-(1,6)-fucosyltransferase (FUT8) antibody, antigen binding domain thereof, or a fusion protein thereof, operable to inhibit FUT8 activity in a cell, and methods of producing recombinant proteins, in particular antibodies, having reduced fucosylation. The present document also describes methods of inhibiting expression and/or activity of a protein in a cell by expressing an antibody and/or a fusion protein operable to inhibit expression and/or activity of the protein. The antibody, antigen binding domain thereof, or fusion protein thereof may comprise a transmembrane domain of a protein resident in an endoplasmic reticulum (ER), a cis Golgi apparatus, a trans Golgi apparatus, or a combination thereof.

Intrabodies for reducing FUT8 activity

The present disclosure concerns antibodies specific for the Na v.7 polypeptides which are capable of antagonizing the biological activity of the Na v.7 polypeptide. The anti-Na v.7 antibodies can be used for alleviating the symptoms of pain and/or for treating or alleviating the symptoms of an hyperproliferative disease. The presence disclosure also concerns immunogens and methods for making antibodies, such as the anti-Na v.7 antibodies, comprising a single-domain antibody.

Antibodies and antibody fragments against HNAV1.7 channel and their use in pain and cancer indications

A brain-penetrating composition of amyloid-&#xdf; binding peptide is disclosed. This may be useful in the treatment of Alzheimer's disease, for example as a bifunctional molecule, comprising a blood-brain barrier crossing antibody and an amyloid-&#xdf; targeting peptide linked via an Fc fragment that is able to transmigrate across the blood-brain barrier into the brain, and compositions comprising same. Methods of using this composition for treating Alzheimer's disease are disclosed.

Fusion protein comprising a blood-brain barrier (BBB)-crossing single domain antibody Fc5, an immunoglobulin Fc fragment and a beta-amyloid binding polypeptide (ABP)

The present invention relates to compounds, compositions, and methods are provided for covalently linking a cargo molecule, such as a therapeutic or a diagnostic agent, to a glycan in the Fab region of an antibody. Also provided are methods of modeling and producing antibodies having de novo Fab glycosylation sites. Also provided are antibody carrier conjugates, methods of using the conjugates.

Antibody glycoconjugates and methods of production and use

Disclosed is a new process for the production of recombinant proteins, by transient transfection of suspension-grown human embryonic kidney cells (293 cell line and its genetic variants) with an expression vector, using polyethylenimine (PEI) as a transfection reagent. In a preferred embodiment, the process uses 293E cells expressing the Epstein-Barr virus (EBV) EBNA 1 protein, in combination with an oriP-based episomal expression vector having an improved cytomegalovirus expression cassette comprising the CMV5 promoter. The process combines in a single step the cell growth, transfection and protein expression, is carried out without changing the culture medium, and allows to achieve high expression levels in a short period of time. The process may be carried out in a serum-free, low-protein culture medium, is easily scalable, compatible with continuous production processes, and fully adapted to high-throughput production of milligram quantities of recombinant proteins.

Enhanced production of recombinant proteins by transient transfection of suspension-growing mammalian cells

The present invention relates to antibodies and fragments thereof derived by humanization of an existing antibody, and methods of making them. The humanized antibodies of the present invention show enhanced binding to the brain endothelial antigen, improved transmigration across the blood-brain barrier, and increased thermal stability relative to the parent non-humanized antibody.

Humanized antibodies transmigrating the blood-brain barrier and uses thereof

The present invention relates to isolated or purified antibodies or fragments thereof specific for Carbohydrate Anhydrase IX (CA-IX) and their use as therapeutic tools. Specifically, the present invention is directed to high-affinity Carbohydrate Anhydrase IX-specific antibodies and fragments thereof and their use as antibody-drug conjugates. Compositions for use in therapy as well as therapeutic methods are also described.

Carbonic anhydrase IX-specific antibodies and uses thereof

Processes, vectors and engineered cell lines for large-scale transfection and protein production in mammalian cells, especially Chinese Hamster Ovary (CHO) cells are described in which transfection efficiencies are realized through the use of a single vector system, the use of functional oriP sequences in all plasmids, the use of codon-optimized Epstein-Barr virus nuclear antigen-1 (EBNA1) constructs, the use of a fusion protein between a truncated Epstein-Barr virus nuclear antigen-1c (EBNA1c) protein and a herpes simplex virus protein VP16, the use of a 40 kDa fully deacetylated poly(ethylenimine) as a transfection reagent, the use of co-expression of a fibroblast growth factor (FGF) and/or the use of protein kinase B to potentiate heterologous gene expression enhancement by valproic acid (VPA).

Process, vectors and engineered cell lines for enhanced large-scale transfection

A short human genomic nucleotide sequence from the SAR3 region of the human interferon &#x3b1;2 gene permits enhances expression stability in the absence of drug selection and permits generation of stable clones or stable pools of cells for producing recombinant proteins. Although stable clones may be generated, the ability to generate stable pools reduces the burden of generating stable clones.

Expression system with SAR element from IFN&#x3b1;2

Processes vectors and engineered cell lines for large-scale transfection and protein production in mammalian cells, especially Chinese Hamster Ovary (CHO) cells are described in which transfection efficiencies are realized through the use of a single vector system, the use of functional oriP sequences in all plasmids, the use of codon-optimized Epstein-Barr virus nuclear antigen-1 (EBNA1) constructs the use of a fusion protein between a truncated Epstein-Barr virus nuclear antigenen-1c (EBNA1c) protein and a herpes simplex virus protein VP16, the use of a 40 kDa fully deacetylated poly(ethylenimine) as a transfection reagent, the use of co-expression of a fibroblast growth factor (FGF) and/or the use of protein kinase B to potentiate heterologous gene expression enhancement by valproic acid (VPA).

This invention relates to the unexpected discovery that nucleotide coding sequences coding for a truncated Epstein Barr Nuclear Antigen 1 (EBNA1t) protein (lacking the Gly-Gly-Ala domain), when in cells of mammalian origin, are associated with improved growth and increased transient gene expression when compared with cells expressing a complete EBNA1 coding sequence. The expression of EBNA1t also appear to be more stable over time.

Expression vectors containing a truncated epstein barr nuclear antigen 1 lacking the Gly-Gly-Ala domain for enhanced transient gene expression

The present invention relates to an expression system for the expression of desired gene. The expression system of the present invention comprises a cyclic AMP sensitive promoter operably linked to a DNA sequence comprising the coding region of the desired gene. The expression system of the present invention has the advantage of having a low basal level and an high induced level.

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Montreal, Canada

Yves Durocher