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.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Edwards CK 3rd,Martin SW,Seely J,Kinstler O,Buckel S,Bendele AM,Ellen Cosenza M,Feige U,Kohno Tdoi
10.1016/s0169-409x(03)00112-1subject
Has Abstractpub_date
2003-09-26 00:00:00pages
1315-36issue
10eissn
0169-409Xissn
1872-8294pii
S0169409X03001121journal_volume
55pub_type
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