Materials and methods for improved immunoglycoproteins
View Patent ↗Immunoglycoproteins, including antibodies, with improved ADCC and altered glycosylation patterns are provided. Also provided are cell culturing methods and media for producing such immunoglycoproteins, and therapeutic uses of such immunoglycoproteins.
1. A composition comprising recombinant immunoglycoprotein molecules, wherein the recombinant immunoglycoprotein molecules each comprise an N-linked glycosylation site for linkage of oligosaccharide, and wherein at least 60% of the N-linked oligosaccharides of the N-linked glycosylation site have a hexose content of at least ten hexose molecules.
2. The composition of claim 1 , wherein the immunoglycoprotein molecules exhibit at least 5-fold higher ADCC compared to control immunoglycoprotein molecules of the same encoded amino acid sequence produced in CHO-K1 cells in the absence of a carbohydrate modifier.
3. The composition of claim 1 , wherein at least 60% of the N-linked oligosaccharides of the N-linked glycosylation site contain no fucose.
4. The composition of claim 1 formulated in a pharmaceutically acceptable carrier or diluent.
5. The composition of claim 4 , wherein the composition is sterile.
6. The composition of claim 1 comprising at least 100 g of immunoglycoprotein molecules and a pharmaceutically acceptable carrier or diluent.
7. The composition of claim 1 comprising at least 100 liters of culture medium.
8. The composition of any one of claims 1 - 3 , wherein the recombinant immunoglycoprotein molecules are bispecific in antigen-binding.
9. The composition of any one of claims 1 - 3 , wherein the recombinant immunoglycoprotein molecules are trispecific in antigen-binding.
10. The composition of any one of claims 1 - 3 , wherein the recombinant immunoglycoprotein molecule is an antibody or a small modular immunopharmaceutical.
11. The composition of claim 10 , wherein the small modular immunopharmaceutical comprises amino acids 24-496 of SEQ ID NO:2.