Polymer-modified bioactive synthetic chemokines, and methods for their manufacture and use
OwnerJames Bradburne, Gerd Kochendoerfer +1inventors
InventorsJames Bradburne, Gerd Kochendoerfer, Jill Wilken
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Abstract
The invention relates to polymer-modified bioactive synthetic chemokines and to methods for their production and use. The bioactive synthetic chemokines of the invention comprises a polymer modified polypeptide chemokine backbone. The compounds and methods or the invention are useful for the treatment of disorders involving naturally occurring chemokines, such as for the treatment of HIV and AIDS related disorders and for the treatment of asthma, allergic rhinitis, atopic dermatitis, atheroma/atherosclerosis, organ transplant rejection, and rheumatoid arthritis.
Claims47
A synthetic chemokine having a water-soluble polymer attached thereto and having in vitro bioactivity characterized by downmodulation of a chemokine receptor to which it binds.
A bioactive synthetic chemokine comprising a water-soluble polymer attached thereto, and having an in vitro EC50 that is equivalent to or less than that of a corresponding wild type chemokine for a biological response comprising inhibition of viral infection, said EC50 being measured in an in vitro cell-based assay characterized by binding of said bioactive synthetic chemokine to one or more of its corresponding chemokine receptors, where one or more of said receptors is a co-receptor for viral infection.
A bioactive synthetic chemokine comprising a water-soluble polymer attached thereto and having:
- (1) an EC50 that is equivalent to or less than that of a corresponding wild type chemokine, said EC50 being measured in an in vitro viral infection assay characterized by binding of said bioactive synthetic chemokine to one or more of its corresponding chemokine receptors, where one or more of said receptors is a viral coreceptor, and
- (2) a serum circulating half-life of greater than 10-fold compared to said synthetic chemokine that is devoid of said water-soluble polymer.
Dependencies are inferred from the claim text.