Merck Sharp + Dohme Corp.

Schering Corporation

Nektar Therapeutics

Enzon, Inc.

Seoju Lee

Susan V Cannon-Carlson

David C Wylie

Brian Bray

Bhalchandra V Joshi

Patrick Spence

Anthony O Chong

Shaoyong Nie

Patrick L Spence

Samuel Mcmanus

David Swallow

Antoni Kozlowski

Samuel P McManus

Mary J Bossard

Harold Zappe

Anthony G Schaefer

Charles W McNemar

John R Handley

Marcio Voloch

Sachin Tipnis

Greg Lavaty

Andres Frei

Roland Mengisen

Lal A Fernando

Lal A R Fernando

Andres c/o Schering-Plough Corporation Frei

Interleukin-10 (IL-10) conjugated via a linker to one or more polyethylene glycol (PEG) molecules at a single amino acid residue of the IL-10, and a method for preparing the same, are provided. The method produces a stable mono-pegylated IL-10, which retains IL-10 activity, where pegylation is selective for the N-terminus on one subunit of IL-10 with little or no formation of monomeric IL-10. The method also provides a substantially homogenous population of mono-PEG-IL-10.

Pegylated interleukin-10

Among other aspects, provided herein is a mixed-acid salt of a water-soluble polymer-drug conjugate, along with related methods of making and using the same. The mixed-salt acid salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding predominantly pure acid salt or free base forms of the polymer-drug conjugate. The mixed acid salt is reproducibly prepared and recovered, and provides surprising advantages over non-mixed acid salt forms of the water-soluble polymer drug conjugate.

Acid salt forms of polymer-drug conjugates and alkoxylation methods

Among other aspects, provided herein is a hydrohalide salt of a multi-arm water-soluble polyethylene glycol-drug conjugate, along with related methods of making and using the same. The hydrohalide salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding free base form of the conjugate.

Salt form of a multi-arm polymer-drug conjugate

The present invention provides methods for isolating adjunct isoforms of proteins and converting them to the desired protein. In preferred embodiments, the present invention contemplates the use of acid solutions or zinc solutions to cleave a chemical group from a desired protein. In further preferred embodiments, the present invention contemplates the oxidation of reduced sulfhydryl groups with cleavage of chemical groups to form a functional desired protein.

Methods for conversion of protein isoforms

Substantially pure histidine-linked protein-polymer conjugates and processes for their preparation are disclosed. The processes include contacting a protein with an activated polymer under conditions sufficient to facilitate covalent attachment of at least a portion of the polymer strands on histidine residues of the protein and thereafter substantially separating the histidine-linked conjugates from the remaining reactants.

Substantially pure histidine-linked protein polymer conjugates

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Madison, AL, United States of America

Seoju Lee