Modified HIL-6

DETAILED DESCRIPTION OF THE INVENTION Described below is the chemical modification with PEG of at least one amino group of polypeptides possessing IL-6 activities.
This modification results in an increase in in vivo half-life in blood and an increase of in vivo platelet producing activity as compared to that of unmodified IL-6.
Thus, in one aspect of the present invention, modified glycosylated and unglycosylated proteins or polypeptides (preferably polypeptides) possessing improved interleukin-6 activities, particularly platelet producing activity, in primates, and especially in humans, are provided where the modification comprises the attachment of PEG to the polypeptides.
The attachment of PEG (hereafter referred to as PEGylation) to the molecules possessing IL-6 activities may be done via the amino or carboxyl groups present in the polypeptides, and is preferably via the amino groups.
For PEGylation via amino groups, at least one hydrogen atom of an amino group of the protein or protein fragment to be PEGylated is substituted with a group as shown in formula 1 or 2: FORMULA 1 ##STR1## n: a positive integer between 7 and 600.
R.
sub.
1 : an alkyl group with one to three carbons.
FORMULA 2 ##STR2## n, m: a positive integer between 7 and 600, and may be equal or different.
R.
sub.
1, R.
sub.
2 : an alkyl group with one to three carbons, and may be the same or different.
In the present invention, hIL-6 polypeptides having substantially the following amino acid sequence are preferred as either the glycosylated or unglycosylated proteins or polypeptides possessing IL-6 activities: SEQUENCE ID NO.
: 1 ##STR3## As used herein "substantially" means that the polypeptides may have one or more amino acid modification(s) (deletions, additions, insertions, or substitutions) of the above amino acid sequence as long as the modification(s) does not have any adverse affect on the function and biological activity of the polypeptides.
Examples of such modifications are described in published patent applications EP 257406, WO 88/00206 and EP 363083 as well as in Brakenhoff, J