CONJUGATES COMPRISED OF POLYMER AND HIV gp-41-DERIVED PEPTIDES AND THEIR USE IN THERAPY

Abstract

Provided are conjugates comprising a polymer having operably bound thereto no less than two molecules of synthetic peptide derived from HIV gp41; methods of using these conjugates to inhibit transmission of HIV to a target cell by adding an amount of effective to inhibit infection of the cell by the virus; and methods of producing the conjugates by operably binding each molecule of synthetic peptide, via a reactive functionality, to the polymer.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to application Ser. No. 10 / 671,282, filed Sep. 24, 2003, which claims the benefit of Provisional Application No. 60 / 414,439, filed Sep. 27, 2002, both of which are incorporated by reference herein in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to conjugates comprised of polymer and synthetic peptides derived from Human Immunodeficiency Virus (HIV) gp41. More particularly, the present invention comprises a conjugate formed by operably binding to a polymer no less than two molecules of synthetic peptide comprising an amino acid sequence derived from either the HR1 region or the HR2 region of HIV-1 gp41.BACKGROUND OF THE INVENTION[0003]It is now well known that cells can be infected by HIV through a process by which fusion occurs between the cellular membrane and the viral membrane. The generally accepted model of this process is that the viral envelope glycoprotein complex (gp1...

AI Technical Summary

Benefits of technology

[0007]There is provided, in accordance with the present invention, a conjugate comprising a polymer to which is attached two or more synthetic peptides derived from the HR region of gp41 (HR1 region, HR2 region, or a combination thereof), and which offers the advantages of retaining substantial biological activity (i.e., antiviral activity against HIV), and exhibiting durability (as compared to the synthetic peptide alone (e.g., without being part of a conjugate)). Other features, such as increasing the biological half-life of synthetic peptide which is part of the conjugate (e.g., enabling the synthetic peptide to survive longer in vivo before being degraded in and / or removed from the bloodstream as compared to synthetic peptide alone), will be apparent to one skilled in the art from the descriptions herein. The conjugate according to the present invention may further comprise a pharmaceutically acceptable carrier.

Problems solved by technology

However, as known to those skilled in the art (see, e.g., U.S. Pat. Nos. 6,258,774 and 6,113,906), such modifications to the therapeutic agent have inherent limitations, i.e. such modifications typically limit the bioavailability of the therapeutic agent.

More particularly, attaching a water-soluble polymer to a therapeutic agent, particularly a small peptide, frequently modulates the biological activity of the therapeutic agent in a deleterious manner.

While the prior art may teach conjugating therapeutic agents to a water-soluble polymer, the prior art fails to teach a conjugate comprising a polymer attached to two or more molecules of synthetic peptide, wherein the conjugate retains substantial bioactivity (e.g., retains substantial biological activity as compared to synthetic peptide alone), and durability (substantial biological activity against a strain of HIV-1 resistant to a synthetic peptide not in the form of a conjugate, as compared to that of the synthetic peptide).

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