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Glycoengineered binding protein compositions

a technology of glycoengineered binding proteins and compositions, which is applied in the field of compositions of recombinant fc binding proteins, can solve the problems of utility of therapeutic binding proteins, reducing the serum drug levels, and reducing the overall efficacy of treatment, so as to reduce the anti-drug antibody response of subjects, increase the g/m ratio of the population, and increase the serum half-life

Inactive Publication Date: 2015-05-21
ABBVIE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a way to make protein-based drugs that have a longer half-life in the body, which means they need to be taken less frequently. This is done by adding a specific sugar molecule to the protein molecule. The text also describes a method to reduce the body's response to the drug by reducing the amount of certain antibodies that are formed when the body encounters the drug. This is done by also adding a specific sugar molecule to the protein molecule.

Problems solved by technology

The development of ADA results in progressively lower serum drug levels and a diminished treatment efficacy.
Such ADA immune responses, therefore, decrease the overall efficacy and utility of therapeutic binding proteins.

Method used

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  • Glycoengineered binding protein compositions
  • Glycoengineered binding protein compositions
  • Glycoengineered binding protein compositions

Examples

Experimental program
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Effect test

example 1

Generation of Monoclonal Antibody-Producing Cho Cells Overexpressing β 1, 4 Galactosyl-Transferase

[0211]A mouse galactosyltransferase β 1, 4 (Genbank accession number: D00314) was amplified by PCR and cloned downstream of CMV promoter of the pcDNA™3.3 TOPO® Mammalian Expression Vector (Invitrogen Life Sciences, Catalog Number: K8300-01) as shown in FIG. 2A. The nucleic acid and corresponding amino acid sequence of mouse galactosyltransferase β 1, 4 is shown in FIG. 2B.

[0212]Adalimumab-producing CHO cells were electroporated with the mouse galactosyltransferase β 1, 4 expression vector. After 48 hours of culture, G418 (Geneticin®, Life Technologies Catalog Number 10131035) was added to the cell media at a final concentration of 500 μg / ml and the cells were cultured an additional 2-3 weeks. Media was changed once every other day. Stable neomycin resistant transformants were isolated and expanded in culture for 1-3 passages prior to cryopreservation. Two exemplary cell lines, designate...

example 2

Generation of Monoclonal Antibody-Producing Cho Cells Having a Beta-Galactosidase Knock Down

[0213]A knock out in one of the alleles of the beta galactosidase gene (Cricetulus griseus Glb1 (Gene ID: 100767446); mRNA sequence: NCBI Reference Sequence: XM—007630176.1; genomic sequence NW—003613697.1 from 2278553 to 2336708) of the adalimumab-producing DHFR-deficient CHO cell line was generated using zinc finger nuclease following procedures that are well known in the art (Santiago et al., Proc. Natl. Acad. Sci. USA. 2008; 105(15):5809-14; Remy et al., Transgenic Res. 2010; 19(3): 363-71; Zhang et al., Advances in Biochemical Engineering / Biotechnology Volume 131, 2013, pp 63-87; U.S. Pat. No. 8,313,925). One exemplary cell line, designated ZFN-B1 was analyzed further.

example 3

Generation of DVD-Ig-Producing CHO Cells Overexpressing β 1, 4 Galactosyltransferase

[0214]IL17xTNF DVD-Ig-producing CHO cells are electroporated with the mouse galactosyltransferase β1, 4 expression vector and G418 (Geneticin®, Life Technologies Catalog Number 10131035) is added to the cell media 48 hours after the transfection at a final concentration of 500 μg / ml for 2-3 weeks. Media is changed once every other day. Stable neomycin resistant transformants are isolated and cultured for 1-3 passages prior to cryopreservation.

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Abstract

Provided are glycoengineered populations of Fc domain-containing binding proteins with a reduced anti-drug immune response (ADA). Also provided are methods of treating disease using such compositions, and methods and host for making such compositions.

Description

RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 61 / 904,487, filed Nov. 15, 2013 and U.S. Provisional Application No. 62 / 051,669, filed Sep. 17, 2014, the contents of which are hereby incorporated by reference herein in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to compositions of recombinant Fc binding proteins, e.g., recombinant antibodies, which exhibit improved properties (e.g., a reduced anti-drug immune response) as a result of their optimized glycosylation profile.BACKGROUND[0003]The use of therapeutic binding proteins has revolutionized the treatment of many diseases, including cancer, inflammatory bowel disease (IBD), ankylosing spondylitis, multiple sclerosis, psoriasis and rheumatoid arthritis (RA). Despite their success in improving the quality of life of patients, long-term treatment with therapeutic binding proteins is often associated with the emergence of anti-drug antibodies (ADA) against ...

Claims

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Application Information

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IPC IPC(8): C07K16/24
CPCC07K16/241C07K2317/41C07K2317/77C07K2317/52C07K2317/56C07K2317/30A61K2039/505C07K16/00Y02A50/30C07K2317/14C07K2317/21
Inventor LABKOVSKY, BORISGHAYUR, TARIQGAZA-BULSECO, GEORGEENMISHRA, PRATIBHAHEDGE, SUBRAMANYAKRISHNAN, SUDHA
Owner ABBVIE INC