Gtc Biotherapeutics, Inc.

Genzyme Transgenics Corporation

Biogen, Incorporated

Laboratoire Francais Du Fractionnement Et Des Biotechnologies

Genzyme Corporation

Pharming B.v.

Genzyme Transgenic Corporation

Genzyme Transgenics Corporatiion

Lfb Usa, Inc.

Harry M Meade

Paul Ditullio

Edward S Cole

Li-How Chen

Daniel Pollock

Li How Chen

Jeffrey L Garwin

Paul DiTullio

Ian Krane

Michael Young

Nils Lonberg

Seng H Cheng

Alan E Smith

Karl M Ebert

Geoffrey F Cox

Timothy Edmunds

John Mcpherson

In one aspect, the disclosure relates to highly galactosylated anti-TNF-alpha antibodies and compositions thereof. In one aspect, the disclosure relates to populations of anti-TNF-alpha antibodies with a high level of galactosylation, and compositions thereof. In one aspect, the disclosure relates to methods of production and use of highly galactosylated anti-TNF-alpha antibodies and populations of anti-TNF-alpha antibodies with a high level of galactosylation. In some embodiments, the anti-TNF-alpha antibody is adalimumab.

Highly galactosylated anti-TNF-&#x3b1; antibodies and uses thereof

In one aspect, the disclosure provides proteins with modified glycosylation and methods of their production. In aspect, the disclosure provides transgenic animals and cells for the production of proteins with modified glycosylation. In some embodiment, the modified glycosylation is increased sialylation.

Proteins with modified glycosylation and methods of production thereof

The invention provides, in part, methods for the production of proteins in a transgenic non-human mammal, wherein the proteins are transported from the blood to the mammary gland for secretion in milk. The transport of the protein to the mammary gland and/or milk is facilitated by binding to a transport receptor in the mammary gland.

Non-human transgenic mammal expressing a human FcRn on its mammary gland cells and expressing a transgenic protein-human Fc-domain fusion

This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GalNAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.

Transgenically produced antithrombin III

The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of proteins which are known to be, or are likely to be, difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred 'difficult' protein candidates for expression using the recombinant techniques of the invention are those proteins derived from heterologous cells preferably those of lower organisms such as parasites, bacteria, and virus, having DNA coding sequences comprising high overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the recombinant expression system to be used.

Modified nucleic acid sequences and methods for increasing mRNA levels and protein expression in cell systems

Desirable fusion proteins can be produced in and purified from the milk of transgenic animals. The peptides are made as fusion proteins with a suitable fusion partner such as human alpha-fetoprotein. The fusion partner protein acts to promote and increase the half-life of the overall molecule as well as having therapeutic effects on its own. The fusion protein is typically produced through the use of transgenic animals and can be purified away from the now the milk or other bodily fluid of such an animal by an affinity purification method. A particular advantage of producing peptides via this route, in addition to the obvious advantages of high yield and biocompatibility, is that specific post-translational modifications, such as carboxy terminal amidation, can be performed in the mammary gland. Biologically active polypeptides comprising a therapeutically active polypeptide fused to human alpha-fetoprotein fragment or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Method for the production of fusion proteins in transgenic mammal milk

The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of malarial surface protein MSP-1 which is known to be difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred protein candidates for expression using the recombinant techniques of the invention are MSP-1 proteins expressed from DNA coding sequences comprising reduced overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the native MSP-1 gene.

Non-human transgenic mammal comprising a modified MSP-1 nucleic acid

Merozoite surface protein 1 lacking glycosylation sites

Erythropoietin analog-human serum albumin (EPOa-hSA) fusion protein and methods of making and using the fusion protein.

Erythropoietin analog-human serum albumin fusion

Treatments using transgenic goat produced antithrombin III

Modified MSP-1 nucleic acid sequences and methods for increasing MRNA levels and protein expression in cell systems

The invention provides a method of making and secreting a non-secreted protein. The method includes expressing the protein from a nucleic acid construct which includes: (a) a mammary epithelial specific promoter; (b) a milk protein specific signal sequence which can direct the secretion of a protein; (c) optionally, a sequence which encodes a sufficient portion of the amino terminal coding region of a secreted protein to allow secretion in the milk of a transgenic mammal, of the non-secreted protein; and (d) a sequence which encodes a non-secreted protein, wherein elements (a), (b), optionally (c), and (d) are preferably operatively linked in the order recited. Both glutamic acid decarboxylase (GAD) and myelin basic protein (MBP), which are cytoplasmic proteins, have been produced by the methods of the present invention. The invention also provides methods for treating diabetes and multiple sclerosis using proteins produced by the methods of the present invention.

Transgenically produced non-secreted proteins

This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GaINAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.

Transgenically produced Antithrombin III

A method for the production of monoclonal antibodies in mammal's milk through the creation of transgenic animals that selectively express foreign antibody genes in mammary epithelial cells.

Growing community of inventors

Newton, MA, United States of America

Harry M Meade