Title:  Method for preventing HIV-1 infection of CD4+ cells

United States Patent:  6,344,545

Inventors:  Allaway; Graham P. (Mohegan Lake, NY); Litwin; Virginia M. (Fayetteville, NY); Maddon; Paul J. (Elmsford, NY); Olson; William C. (Ossining, NY)

Appl. No.:  831823

This invention provides methods for inhibiting fusion of HIV-1 to CD4⁺cells which comprise contacting CD4⁺ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4⁺ cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4⁺cells which comprise contacting CD4⁺ cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4⁺cells is inhibited, thereby inhibiting the HIV-1 infection. This invention provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4⁺cells. This invention also provides pharmaceutical compositions comprising an amount of the non-chemokine agent capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4⁺cells effective to prevent fusion of HIV-1 to CD4⁺cells and a pharmaceutically acceptable carrier.

SUMMARY OF THE INVENTION

This invention provides a method for inhibiting fusion of HIV-1 to CD4⁺cells which comprises contacting CD4⁺cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4⁺cells is inhibited.

This invention also provides a method for inhibiting HIV-1 infection of CD4⁺cells which comprises contacting CD4⁺cells with a non-chemokine agent capable of binding to a chemokine receptor in an amount and under conditions such that fusion of HIV-1 to the CD4⁺cells is inhibited, thereby inhibiting the HIV-1 infection.

This invention further provides non-chemokine agents capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4⁺cells.

This invention provides an agent which is capable of binding to fusin and inhibiting infection. In an embodiment, the agent is an oligopeptide. In another embodiment, the agent is an polypeptide. In still another embodiment, the agent is an antibody or a portion of an antibody. In a separate embodiment, the agent is a nonypeptidyl agent.

In addition, this invention provides pharmaceutical compositions comprising an amount of the above non-chemokine agents or agents capable of binding to fusin effective to inhibit fusion of HIV-1 to CD4⁺ cells and a pharmaceutically acceptable carrier.

This invention provides a composition of matter capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4⁺cells comprising a non-chemokine agent linked to a ligand capable of binding to a cell surface receptor of the CD4⁺cells other than the chemokine receptor such that the binding of the non-chemokine agent to the chemokine receptor does not prevent the binding of the ligand to the other receptor.

This invention also provides a pharmaceutical composition comprising an amount of the above-described composition of matter effective to inhibit fusion of HIV-1 to CD4⁺cells and a pharmaceutically acceptable carrier.

This invention provides a composition of matter capable of binding to the chemokine receptor and inhibiting fusion of HIV-1 to CD4⁺cells comprising a non-chemokine agent linked to a compound capable of increasing the in vivo half-life of the non-chemokine agent.

This invention also provides a pharmaceutical composition comprising an amount of a composition of matter comprising a non-chemokine agent linked to a compound capable of increasing the in vivo half-life of the non-chemokine agent effective to inhibit fusion of HIV-1 to CD4⁺cells and a pharmaceutically acceptable carrier.

This invention provide methods for reducing the likelihood of HIV-1 infection in a subject comprising administering an above-described pharmaceutical composition to the subject. This invention also provides methods for treating HIV-1 infection in a subject comprising administering an above-described pharmaceutical composition to the subject.

This invention also provides methods for determining whether a non-chemokine agent is capable of inhibiting the fusion of HIV-1 to a CD4⁺cell which comprise: (a) contacting (i) a CD4⁺cell which is labeled with a first dye and (ii) a cell expressing the HIV-1 envelope glycoprotein on its surface which is labeled with a second dye, in the presence of an excess of the agent under conditions permitting the fusion of the CD4⁺cell to the cell expressing the HIV-1 envelope glycoprotein on its surface in the absence of the agent, the first and second dyes being selected so as to allow resonance energy transfer between the dyes; (b) exposing the product of step (a) to conditions which would result in resonance energy transfer if fusion has occurred; and (c) determining whether there is a reduction of resonance energy transfer, when compared with the resonance energy transfer in the absence of the agent, a decrease in transfer indicating that the agent is capable of inhibiting fusion of HIV-1 to CD4⁺cells.

Claim 1 of 6 Claims

What is claimed is:

1. A method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with an antibody or portion of an antibody capable of binding to a chemokine receptor on the surface of the CD4+ cell in an amount and under conditions such that fusion of HIV-1 or an HIV-1 infected cell to the CD4+ cell is inhibited, thereby inhibiting HIV-1 infection of the CD4+ cell.

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