Transgenically produced antithrombin III

• US 20030096974A1
• Filed: 07/02/2002
• Published: 05/22/2003
• Est. Priority Date: 02/21/1995
• Status: Active Grant

• Current Assignee: rEVO Biologics, Inc. (Agence des Participations de l’Etat)
• Original Assignee: Genzyme Transgenics Corporation
• Inventors: Cole, Edward S., Meade, Harry M., Ditullio, Paul
• Granted Patent: US 7,019,193 B2
• Time in Patent Office: Days
• US Class Current: 530/381
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C07K 14/8128 Antithrombin III
• CPC Class Codes: Y10S 530/832 Milk; colostrum

Abstract

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.

Claims

1. Transgenically produced antithrombin III comprising a monosaccharide composition which includes GalNAc.

9. The transgenically produced antithrombin III of claims 1, 2, 3, 4, 5, 6, 7 or 8 wherein the antithrombin III is transgenically produced in a mammal.

10. The transgenically produced antithrombin III of claim 1, 2, 3, 4, 5, 6, 7 or 8 wherein the antithrombin III is transgenically produced in a goat.

2. Transgenically produced antithrombin III comprising a monosaccharide composition which includes GalNAc and which lacks O-linked glycosylation.

3. Transgenically produced antithrombin III comprising a monosaccharide composition of Fuc, GalNAc, GlcNAc, Gal, Man, and NANA/NGNA.

4. Transgenically produced antithrombin III having one of its glycosylation sites comprising oligomannose and/or hybrid oligosaccharide structures.

5. Transgenically produced antithrombin III comprising a monosaccharide composition which is primarily an oligomannose or hybrid type structure on one site and complex oligosaccharide on the remaining 3 sites.

6. Transgenically produced antithrombin III comprising a monosaccharide composition which is partially sialylated.

7. Transgenically produced antithrombin III comprising a monosaccharide composition including sialic acid which includes NGNA.

8. Transgenically produced antithrombin III comprising a monosaccharide composition which includes a fucose on its proximal GlcNAc on each of the sites having complex oligosaccharides.

11. A transgenic method for producing antithrombin III in mammalian milk, comprising:

a. producing a transgenic mammal that expresses a transgene which encodes a human antithrombin III with a monosaccharide composition which includes GalNAc;

b. collecting milk from the transgenic animal which contains the human antithrombin III; and

c isolating the human antithrombin III from milk.