| Literature DB >> 14499710 |
Carl K Edwards1, Steven W Martin, James Seely, Olaf Kinstler, Scott Buckel, Alison M Bendele, Mary Ellen Cosenza, Ulrich Feige, Tadahiko Kohno.
Abstract
A recombinant C-terminal truncated form of the human soluble tumor necrosis factor receptor type I (sTNF-RI) was produced in E. coli. This soluble receptor contains the first 2.6 of the 4 domains of the intact sTNF-RI molecule. A monoPEGylated form of this molecule was produced using a 30 kD methoxyPEG aldehyde with approximately 85% selectivity for the N-terminal amino group. This molecule was shown to be less immunogenic in primates than the full length (4.0 domain) molecule or other versions of sTNF-RI which were either PEGylated at different sites or with different molecular weight PEGs. The 30 kD PEG also has a longer serum half-life to the molecule than lower molecular weight PEGs. This molecule markedly blunts the inflammatory response in a number of rheumatoid arthritis animal models. In addition, phase I/II and early phase II data in humans indicate that PEG sTNF-RI is non-immunogenic and that weekly dosing with this drug can reduce the number of tender and swollen joints in rheumatoid arthritis patients. PEG sTNF-RI has comparable American College of Rheumatology (ACR) efficacy scores as other anti-TNF molecules currently used to treat rheumatoid arthritic patients.Entities:
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Year: 2003 PMID： 14499710 DOI： 10.1016/s0169-409x(03)00112-1
Source DB: PubMed Journal: Adv Drug Deliv Rev ISSN： 0169-409X Impact factor: 15.470