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Improved safety and efficacy with CHO cell glycosylated chimeric antibody to TNF

A glycosylation, antibody technology, applied in the direction of antibodies, chemical instruments and methods, anti-inflammatory agents, etc., can solve problems such as adverse reactions of patients

Inactive Publication Date: 2018-11-09
SORRENTO THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some commercially available therapeutic glycoproteins have caused serious adverse reactions in patients due to their presence of NGNA residues

Method used

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  • Improved safety and efficacy with CHO cell glycosylated chimeric antibody to TNF
  • Improved safety and efficacy with CHO cell glycosylated chimeric antibody to TNF
  • Improved safety and efficacy with CHO cell glycosylated chimeric antibody to TNF

Examples

Experimental program
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Effect test

Embodiment Construction

[0013] The present invention is based at least in part on the therapeutic advantages of producing anti-TNF antibodies in Chinese Hamster Ovary (CHO) cells. STI002 is an anti-TNF antibody that is produced in CHO cells and has the amino acid sequence of infliximab. Structurally, infliximab has a light chain comprising the amino acid sequence shown in SEQ ID NO:1, and a heavy chain comprising the amino acid sequence shown in SEQ ID NO:2. The amino acid sequences of the light and heavy chains of Infliximab are described below:

[0014] Asp Ile Leu Leu Thr Gln Ser Pro Ala Ile Leu Ser Val Ser Pro Gly GluArg Val Ser Phe Ser Cys Arg Ala Ser Gln Phe Val Gly Ser Ser Ile His Trp TyrGln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile Lys Tyr Ala Ser Glu Ser MetSer Gly Ile Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu SerIle Asn Thr Val Glu Ser Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Ser His SerTrp Pro Phe Thr Phe Gly Ser Gly Thr Asn Leu Glu Val Lys (SEQ ID NO: 1)

[0015] Glu...

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Abstract

There is disclosed a chimeric infliximab-like monoclonal antibody having at least 80% NANA glycosylation terminal sialic acid and a glycosylation pattern of Gal-alpha(2,3 / 6)-Gal that binds to tumor necrosis factor alpha (TNF). The disclosed infliximab-like monoclonal antibody is a chimeric antibody having the same amino acid sequence (light chain / heavy chain of SEQ ID NO. 1 / SEQ ID NO. 2) as infliximab which has at least 80% NGNA terminal sialic acid and a glycosylation pattern of Gal-alpha(1,3)-Gal.

Description

technical field [0001] The present disclosure provides an infliximab-like chimeric monoclonal antibody having at least 80% NANA glycosylated terminal sialic acid and a glycosylation pattern of Gal-α(2,3 / 6)-Gal. An infliximab-like chimeric monoclonal antibody binds to a tumor necrosis factor (TNF) alpha target. The disclosed infliximab-like monoclonal antibody is a Chimeric antibody with identical amino acid sequence (light chain / heavy chain of SEQ ID NO.1 / SEQ ID NO.2). However, the present invention is improved in that it has at least 80% glycosylation of NGNA terminal sialic acid and a Gal-α(1,3)-Gal glycosylation pattern. Background technique [0002] Glycosylation is a post-translational modification. Sugar chains on the surface of protein molecules can affect the structure and function of protein molecules. The glycosylation and glycan structure of monoclonal antibodies are related to their functions, and regulate antibody-dependent cellular cytotoxicity (ADCC), com...

Claims

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Application Information

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IPC IPC(8): A61K39/395A61P35/00
CPCA61P19/02A61P29/00A61P35/00C07K16/241C07K2317/41C07K2317/51C07K2317/515
Inventor 杰弗里·苏曹剑
Owner SORRENTO THERAPEUTICS INC
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