US2004062767A1PendingUtilityA1

Compositions and methods for inhibition of HIV-1 infection

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Assignee: PROGENICS PHARM INCPriority: Jan 28, 2000Filed: Oct 9, 2003Published: Apr 1, 2004
Est. expiryJan 28, 2020(expired)· nominal 20-yr term from priority
Inventors:William OlsonPaul J. Maddon
A61K 38/00C07K 14/70514C07K 2319/30C07K 2319/00
60
PatentIndex Score
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Cited by
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Claims

Abstract

This invention provides a composition which comprises an admixture of two compounds, wherein one compound retards attachment of HIV-1 to a CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell and the other compound retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate, wherein the relative mass ratio of the compounds in the admixture ranges from about 100:1 to about 1:100, the composition being effective to inhibit HIV-1 infection of the CD4+ cell. This invention also provides a method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with an amount of the above composition effective to inhibit HIV-1 infection of the CD4+ cell so as to thereby inhibit HIV-1 infection of the CD4+ cell.

Claims

exact text as granted — not AI-modified
What is claimed:  
     
         1 . A composition which comprises an admixture of two compounds, wherein one compound retards attachment of HIV-1 to a CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell and the other compound retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate, wherein the relative mass ratio of the compounds in the admixture ranges from about 100:1 to about 1:100, the composition being effective to inhibit HIV-1 infection of the CD4+ cell.  
     
     
         2 . The composition of  claim 1 , wherein the compound which retards attachment of HIV-1 to the CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell is a CD4-based protein.  
     
     
         3 . The composition of  claim 2 , wherein the CD4-based protein is a CD4-immunoglobulin fusion protein.  
     
     
         4 . The composition of  claim 3 , wherein the CD4-immunoglobulin fusion protein is CD4-IgG2, wherein the CD4-IgG2 comprises two heavy chains and two lights chains, wherein the heavy chains are encoded by an expression vector designated CD4-IgG2HC-pRcCMV (ATCC Accession No. 75193) and the light chains are encoded by an expression vector designated CD4-kLC-pRcCMV (ATCC Accession No. 75194).  
     
     
         5 . The composition of  claim 1 , wherein the compound which retards attachment of HIV-1 to the CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell is a protein, the amino acid sequence of which comprises that of a protein found in HIV-1 as an-envelope glycoprotein.  
     
     
         6 . The composition of  claim 5 , wherein the protein binds to an epitope of CD4 on the surface of the CD4+ cell.  
     
     
         7 . The composition of  claim 6 , wherein the envelope glycoprotein is selected from the group consisting of gp120, gp160, and gp140.  
     
     
         8 . The composition of  claim 1 , wherein the compound which retards the attachment of HIV-1 to the CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell is an antibody or portion of an antibody.  
     
     
         9 . The composition of  claim 8 , wherein the antibody is a monoclonal antibody.  
     
     
         10 . The composition of  claim 9 , wherein the monoclonal antibody is a human, humanized or chimeric antibody.  
     
     
         11 . The composition of  claim 8 , wherein the portion of the antibody is a Fab fragment of the antibody.  
     
     
         12 . The composition of  claim 8 , wherein the portion of the antibody comprises the variable domain of the antibody.  
     
     
         13 . The composition of  claim 8 , wherein the portion of the antibody comprises a CDR portion of the antibody.  
     
     
         14 . The composition of  claim 9 , wherein the monoclonal antibody is an IgG, IgM, IgD, IgA, or IgE monoclonal antibody.  
     
     
         15 . The composition of  claim 9 , wherein the monoclonal antibody binds to an HIV-1 envelope glycoprotein.  
     
     
         16 . The composition of  claim 15 , wherein the HIV-1 envelope glycoprotein is selected from the group consisting of gp120 and gp160.  
     
     
         17 . The composition of  claim 16 , wherein HIV-1 envelope glycoprotein is gp120 and the monoclonal antibody which binds to gp120 is IgG1b12 or F105.  
     
     
         18 . The composition of  claim 8 , wherein the antibody binds to an epitope of CD4 on the surface of the CD4+ cell.  
     
     
         19 . The composition of  claim 1 , wherein the compound which retards attachment of HIV-1 to the CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell is a peptide.  
     
     
         20 . The composition of  claim 1 , wherein the compound which retards attachment of HIV-1 to the CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell is a nonpeptidyl agent.  
     
     
         21 . The composition of  claim 1 , wherein the compound which retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate is an antibody.  
     
     
         22 . The composition of  claim 21 , wherein the antibody is a monoclonal antibody.  
     
     
         23 . The composition of  claim 1 , wherein the compound which retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate is a peptide.  
     
     
         24 . The composition of  claim 1 , wherein the compound which retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate is a fusion protein which comprises a peptide selected from the group consisting of T-20 (SEQ ID NO: 1), DP107 (SEQ ID NO: 2), N34 (SEQ ID NO: 3), C28 (SEQ ID NO: 4), and N34(L6)C28 (SEQ ID NO: 5).  
     
     
         25 . The composition of  claim 23 , wherein the peptide is selected from the group consisting of T-20 (SEQ ID NO: 1), DP107 (SEQ ID NO: 2), N34 (SEQ ID NO: 3), C28 (SEQ ID NO: 4), and N34(L6)C28 (SEQ ID NO: 5).  
     
     
         26 . The composition of  claim 23 , wherein the peptide is T-20 (SEQ ID NO: 1).  
     
     
         27 . The composition of  claim 1 , wherein the compound which retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate is a non-peptidyl agent.  
     
     
         28 . The composition of  claim 1 , wherein the relative mass ratio of each such compound in the admixture ranges from about 25:1 to about 1:1.  
     
     
         29 . The composition of  claim 28 , wherein the mass ratio is about 25:1.  
     
     
         30 . The composition of  claim 28 , wherein the mass ratio is about 5:1.  
     
     
         31 . The composition of  claim 28 , wherein the mass ratio is about 1:1.  
     
     
         32 . The composition of  claim 1 , wherein the composition is admixed with a carrier.  
     
     
         33 . The composition of  claim 32 , wherein the carrier is an aerosol, intravenous, oral or topical carrier.  
     
     
         34 . A method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with an amount of the composition of  claim 1  effective to inhibit HIV-1 infection of the CD4+ cell so as to thereby inhibit HIV-1 infection of the CD4+ cell.  
     
     
         35 . The method of  claim 34 , wherein the CD4+ cell is present in a subject and the contacting is effected by administering the composition to the subject.  
     
     
         36 . The method of  claim 33 , wherein the effective amount of the composition comprises from about 0.000001 mg/kg body weight to about 100 mg/kg body weight of the subject.  
     
     
         37 . A method of inhibiting HIV-1 infection of a CD4+ cell which comprises contacting the CD4+ cell with an amount of a compound which retards attachment of HIV-1 to the CD4+ cell by retarding binding of HIV-1 gp120 envelope glycoprotein to CD4 on the surface of the CD4+ cell effective to inhibit HIV-1 infection of the CD4+ cell and an amount of a compound which retards gp41 from adopting a conformation capable of mediating fusion of HIV-1 to a CD4+ cell by binding noncovalently to an epitope on a gp41 fusion intermediate so as to thereby inhibit HIV-1 infection of the CD4+ cell.  
     
     
         38 . The method of  claim 37 , wherein the CD4+ cell is present in a subject and the contacting is effected by administering the compounds to the subject.  
     
     
         39 . The method of  claim 38 , wherein the compounds are administered to the subject simultaneously.  
     
     
         40 . The method of  claim 38 , wherein the compounds are administered to the subject at different times.  
     
     
         41 . The method of  claim 38 , wherein the compounds are administered to the subject by different routes of administration.

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