Abbott Laboratories Corporation

University of Georgia Research Foundation, Inc.

Amgen Inc.

James Michael Pierce

Kelley Wilson Moremen

Richard D Cummings

John J Kopchick

Pedro A Prieto

David Fletcher Smith

Pradip Mukerji

Maria Kamar

Jin-Kyu Lee

Mika Kaneko

Beverly S Adler

Stephen Dalton

Ronald Carl Orlando

Nevis L Fregien

Mohamed G Shoreibah

Robert Lance Wells

James A Atwood, Iii

Karen L Abbott

Michael Tiemeyer

William S York

The present invention relates to a method of isotopically labeling glycans and in facilitating high throughput quantitative/comparative analysis of glycomic compositions of biological cells. The method is applicable inter alia for identifying differentiated cells and their glycomic characteristics, differentiation conditions, disease and/or therapeutic progression, diagnosing disease states, determining drug activity, establishing manufacturing efficiencies and for determining the half-life of glycans in cells.

Vivo isotopic labeling method for quantitative glycomics

The invention relates to glycoproteins having a cancer-specific glycoform. Cancer-specific glycoforms are useful in diagnostics and therapeutics.

Glycoprotein cancer biomarker

A previously unknown mammalian UDP-N-acetylglucosamine:&#x3b1;-6-D-mannoside &#x3b2;-1,6-N-acetylglucosaminyl-transferase (termed GlcNAc T-Vb herein) coding sequence, protein, recombinant host cells and antibodies which specifically bind GlcNAc T-Vb are described. In particular, GlcNAc T-Vb of mouse is disclosed.

N-acetylglucosaminyltransferase Vb coding sequences, recombinant cells and methods

A previously unknown mammalian UDP-N-acetylglucosamine:&#x3b1;-6-D-mannoside &#x3b2;-1,6-N-acetylglucosaminyl-transferase (termed GlcNAc T-Vb herein) coding sequence, protein, recombinant host cells and antibodies which specifically bind GlcNAc T-Vb are described. GlcNAc T-Vb is encoded on human chromosome 17, whereas the prior GlcNAc T-V is encoded on human chromosome 2.

The subject invention relates to methods of producing non-human transgenic mammals which produce various oligosaccharides and glycoconjugates in their milk. Additionally, the subject invention relates to the mammals themselves, the milk which they produce, compositions comprising the milk, fractions of the milk, and the purified oligosaccharides, as well as glyconjugates, present in the milk.

Transgenic non-human mammals expressing heterologous glycosyltransferase DNA sequences produce oligosaccharides and glycoproteins in their milk

The present invention provides substantially purified UDP-N-acetylglucosamine: .alpha.-6-D-mannoside .beta.-1,6-N-acetylglucosaminyl transferase (GlcNAc T-V; EC 2.4.1.155) proteins and antibodies which specifically bind GlcNAc T-V. The present invention also provides polynucleotide sequences and oligonucleotide probes capable of specifically hybridizing to nucleic acid sequences which encode GlcNAc T-V, and cDNA and genomic clones encoding GlcNAc T-V, as well as nucleotide sequences encoding GlcNAc T-V, as specifically exemplified by GlcNAc T-V coding sequences from rat, hamster, mouse and human.

N-acetylglucosaminyltransferase V proteins and coding sequences

The invention relates to humanized milk. The milk is produced by a non-human transgenic mammal wherein the genome of said transgenic non-human mammal contains at least one heterologous gene encoding for a human catalytic entity and wherein the catalytic entity produces oligosaccharides and glycoconjugates that are present in the milk of said transgenic non-human mammal. An especially useful catalytic entity is human glycosyltransferases which produce oligosaccharides and glyconjugates. Specifically exemplified, is the production of 2'-fucosyl-lactose in the milk of transgenic mice which contain and express a transgene encoding .alpha.-1,2-fucosyltransferase operatively linked to a mammary gland specific promoter. A method of obtaining humanized milk is disclosed. The method comprises the steps of (a) inserting into the genome of a non-human mammal a heterologous gene encoding the production of a human catalytic entity wherein said catalytic entity produces a secondary gene product in the milk of said non-human mammal; and (b) milking said non-human mammal. The humanized milk may be used in the preparation of an enteral nutritional product useful in the nutritive maintenance of an animal.

Oligosaccharides and glycoproteins produced in milk of transgenic

The invention relates to transgenic non-human mammals characterized in that the genome of said mammals contain at least one heterologous gene encoding for the production of heterologous catalytic entity selected from the group consisting of enzymes and antibodies, and wherein said catalytic entity produces a second heterologous product in the milk of said mammal. Especially useful in the practice of the invention are human glycosyltransferases and transgenic sheep, goats and cows. The heterologous product includes oligosaccharides and glycoconjugates. Specifically exemplified, is the production of 2'-fucosyl-lactose in the milk of transgenic mice which contain and express a transgene encoding .alpha.-1,2-fucosyltransferase operatively linked to a mammary gland specific promoter.

Transgenic non-human mammals producing oligosaccharides and

The invention relates to the milk of a transgenic non-human mammal. The milk is characterized in that it contains heterologous components produced as the secondary gene products of a heterologous gene contained in the genome of the transgenic non-human mammal. The heterologous gene encodes a heterologous catalytic entity such as a human enzyme selected from the group consisting of glycosyltransferases, phosphorylases, hydroxylases, peptidases and sulfotransferases. Especially useful in the practice of the invention are human glycosyltransferases. The desired heterologous components include oligosaccahrides, glycoconjugates. Specifically exemplified, is the production of 2'-fucosyl-lactose in the milk of transgenic mice which contain and express a transgene encoding .alpha.-1,2-fucosyltransferase operatively linked to a mammary gland specific promoter. The oligosaccahrides and glycoconjugates may be isolated from the milk of the transgenic mammals and used in the preparation of pharmaceuticals, diagnostic kits, nutritional products and the like. The whole transgenic milk may also be used to formulate nutritional products that provide special advantages. The transgenic milk may also be used in the production of specialized enteral nutritional products.

Transgenic non-human mammal milk comprising 2'-fucosyl-lactose

The invention relates to transgenic non-human mammals characterized in that the genome of said mammals contain at least one heterologous gene encoding for the production of heterologous catalytic entity selected from the group consisting of enzymes and antibodies, and wherein said catalytic entity produces a second heterologous product in the milk of said mammal. Especially useful in the practice of the invention are human glycosyltransferases and transgenic sheep, goats and cows. The heterologous product includes oligosaccharides and glycoconjugates.

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Athens, GA, United States of America

James Michael Pierce