Mountain View Pharmaceuticals, Inc.

Alexa L Martinez

L David Williams

Mark G P Saifer

Merry R Sherman

Shyam S Bhaskaran

John A French

Mark G Saifer

David L Williams

Methods are provided for the synthesis of polymer conjugates of cytokines and receptor-binding antagonists thereof, especially a non-glycosylated interferon-beta, which conjugates retain unusually high biological potency. Preparation of polymer conjugates according to the methods of the present invention diminishes or avoids steric inhibition of receptor-ligand interactions that commonly results from the attachment of polymers to receptor-binding regions of cytokines, as well as to agonistic and antagonistic analogs thereof. The invention also provides conjugates and compositions produced by such methods. The conjugates of the present invention retain a high level of biological potency compared to those produced by traditional polymer coupling methods that are not targeted to avoid receptor-binding domains of cytokines. In assays in vitro, the biological potency of the conjugates of non-glycosylated interferon-beta of the present invention is substantially higher than that of unconjugated interferon-beta and is similar to that of interferon-beta-1a that is glycosylated. The conjugates of the present invention also exhibit an extended half-life in vivo compared to the corresponding unconjugated cytokine. The present invention also provides kits comprising such conjugates and/or compositions, and methods of use of such conjugates and compositions in a variety of diagnostic, prophylactic and therapeutic applications, including treatment of multiple sclerosis.

Polymer conjugates of interferon-beta with enhanced biological potency

Methods are provided for the preparation of conjugates of a variety of bioactive components, especially proteins, with water-soluble polymers (e.g., poly(ethylene glycol) and derivatives thereof), which conjugates have reduced antigenicity and immunogenicity compared to similar conjugates prepared using poly(ethylene glycol) containing a methoxyl or another alkoxyl group. The invention also provides conjugates prepared by such methods, compositions comprising such conjugates, kits containing such conjugates or compositions and methods of use of the conjugates and compositions in diagnostic and therapeutic protocols.

Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof

Methods are provided for the stabilization of proteinases by the covalent attachment of or admixture with water-soluble polymers. The resultant stabilized proteinases have increased stability under the harsh conditions used in industrial genomics, which permits their use in the extraction and isolation of nucleic acids and the identification of disease-related prion proteins at elevated temperatures in solutions containing chaotropic agents, such as sodium dodecyl sulfate, urea or guanidinium salts, conferring advantages for robotic applications.

Polymer conjugates of proteinases

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San Jose, CA, United States of America

Alexa L Martinez