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Home Gene Therapy Azlactone-activated-polyalkylene-oxides-conjugated-to-biologically-active-nucleophiles

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 Azlactone activated polyalkylene oxides conjugated to biologically active nucleophiles

Details
Inventors: Greenwald, Richard B.;
Assignee: Enzon, Inc. (Piscataway, NJ)
Primary Examiner: Webman; Edward J.
Assistant Examiner:
Attorney, Agent or Firm: Mercanti; Michael N.

Water-soluble azlactone activated polyalkylene oxides having improved hydrolytic stability and conjugates of the azlactone activated polyalkylene oxides with biologically active nucleophiles are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The azlactone activated polyalkylene oxides of the present invention are preferably prepared from polyalkylene oxides that are soluble in water at room temperature.
Polyalkylene oxides meeting this requirement are polyethylene glycol (PEG) and copolymers thereof.
Block copolymers of PEG with polypropylene glycol or polypropylene oxide are also suitable for use with the present invention, provided that the degree of block copolymerization is not so great as to render the polymer insoluble in water at room temperature.
Other polymers suitable for use with the present invention include polyacrylates, polymethacrylates and polyvinyl alcohols.
The molecular weight of the polyalkylene oxide will depend mainly upon the end use of a particular polymer conjugate.
Those of ordinary skill in the art are capable of determining molecular weight ranges suitable for their end-use applications.
In general, the useful range of molecular weight is a number average molecular weight between about 600 and about 100,000 daltons, and preferably between about 2,000 and about 20,000 daltons.
A molecular weight of 5,000 daltons is most preferred.
Preferred azlactone activated polyalkylene oxides are represented by the structures of Formula IA and IB, wherein R is a water-soluble polyalkylene oxide, L is selected from --O--, --CH.
sub.
2 --, amino acid and peptide residues; R.
sub.
1 is a moiety selected from hydrogen, alkyl, phenyl, phenylalkyl and cycloalkyl moieties, and X is a terminal moiety of the polyalkylene oxide.
X can be a group into which a terminal hydroxyl group may be converted, including the reactive derivatives of the prior art disclosed in U.
S.
Pat.
Nos.
4,179,337, 4,847,325, 5,122,614 and in copending and commonly owned U.
S.
patent application Ser.
No.
626,696, filed Mar.
18, 1991, the disclosures of all of which are hereby incorporated herein by reference thereto.
The heterobifunctional polymers can be prepared by methods known to those skilled in the art without undue experimentation



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