Progenics Pharmaceuticals, Inc.

Columbia University

Psma Development Company, LLC

Smithkline Beckman Corporation

Amgen Fremont Inc.

Facet Biotech Corporation

Cytodyn Inc.

Aaron Diamond Aids Research Centre (adarc)

Other

Pdl Biopharma, Inc.

Arogenics Pharmaceuticals, Inc.

Cornell Research Foundation Inc.

Abbott Biotherapeutics Corp.

Paul J Maddon

William C Olson

Graham P Allaway

Virginia M Litwin

Richard Axel

Norbert Schuelke

Leonard Chess

Robin Weiss

Dan R Littman

John S Moore

Dangshe Ma

Gerald P Donovan

Jason Gardner

James M Binley

J Steven McDougal

Naoya Tsurushita

Paul Robert Hinton

Gary A Beaudry

Larry L Green

Jaspal Singh Kang

Daniel C Pevear

Raymond W Sweet

Robert J Israel

Maximillano Vasquez

Jose D Murga

James Arthos

Karl W Hasel

Maximiliano Vasquez

Peter Senter

Brian E Toki

Min Lu

Svetlana O Doronina

Peter D Senter

Norbert Schulke

Donovan Gerald

John P Moore

Rogier Sanders

This invention provides a method of reducing viral load in an HIV-1-infected human subject which comprises administering to the subject an effective HIV-1 viral load reducing dose of a CCR5 receptor antagonist, such as a humanized antibody designated PRO 140 or an anti-CCR5 receptor monoclonal antibody, wherein the viral load reducing dose achieves an average maximum decrease of viral load in the subject of at least 1.83 logto 2.5 logat about ten days following administration of the CCR5 receptor antagonist and wherein the viral load reducing dose further achieves a mean viral load reduction of 1.7 logat about nine days following administration of the CCR5 receptor antagonist.

Methods for reducing viral load in HIV-1 infected patients

The invention includes stable multimeric, particularly dimeric, forms of PSMA protein, compositions and kits containing dimeric PSMA protein as well as methods of producing, purifying and using these compositions. Such methods include methods for eliciting or enhancing an immune response to cells expressing PSMA, including methods of producing antibodies to dimeric PSMA, as well as methods of treating cancer, such as prostate cancer.

PSMA antibodies and uses thereof

This method provides a method for reducing HIV-1 viral load in an HIV-1-infected human subject which comprises administering to the subject at a predefined interval effective HIV-1 viral load-reducing doses of (a) a humanized antibody designated PRO 140, or of (b) an anti-CCR5 receptor monoclonal antibody. This invention also provides a method for inhibiting in a human subject the onset or progression of an HIV-1-associated disorder, the inhibition of which is effected by inhibiting fusion of HIV-1 to CCR5CD4target cells in the subject. This invention also provides a method for treating a subject infected with HIV-1 comprising administering to the subject (a) a monoclonal antibody which (i) binds to a CCR5 receptor on the surface of the subject's CD4cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Methods for inhibiting HIV-1 replication involving the administration of an anti-CCR5 receptor monoclonal antibody and small molecule CCR5 receptor antagonist

The invention includes antibodies or antigen-binding fragments thereof which bind specifically to conformational epitopes on the extracellular domain of PSMA, compositions containing one or a combination of such antibodies or antigen-binding fragments thereof, hybridoma cell lines that produce the antibodies, and methods of using the antibodies or antigen-binding fragments thereof for cancer diagnosis and treatment. The invention also includes oligomeric forms of PSMA proteins, compositions comprising the multimers, and antibodies that selectively bind to the multimers.

Compositions of PSMA antibodies

This invention provides methods for inhibiting fusion of HIV-1 to CD4cells which comprise contacting CD4cells 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 CD4cells is inhibited. This invention also provides methods for inhibiting HIV-1 infection of CD4cells which comprise contacting CD4cells 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 CD4cells 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 CD4cells. 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 CD4cells effective to prevent fusion of HIV-1 to CD4cells and a pharmaceutically acceptable carrier.

CCR5 chemokine receptor-specific monoclonal antibodies capable of inhibiting HIV-1 cell fusion

This invention provides: agents determined to be capable of specifically inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4cell, but not a T cell-tropic isolate of HIV-1 to a CD4cell; and agents determined to be capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4cell, but not a macrophage-tropic primary isolate of HIV-1 to a CD4+ cell. This invention also provides: agents capable of specifically inhibiting the fusion of a macrophage tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1; and agents capable of specifically inhibiting the fusion of a T cell-tropic isolate of HIV-1 with a CD4cell susceptible to infection by a T cell-tropic isolate of HIV-1. The agents include but are not limited to antibodies. This invention further provides: methods of inhibiting fusion of a macrophage-tropic primary isolate of HIV-1 with a CD+ cell susceptible to infection by a macrophage-tropic primary isolate of HIV-1 which comprises contacting the CD4cell with an amount of an agent capable of specifically inhibiting such fusion so as to thereby inhibit such fusion; and methods of inhibiting fusion of a T cell-tropic isolate of HIV-1 with a CD4cell susceptible to infection by a T cell-tropic isolate of HIV-1 which comprises contacting the CD4cell with an amount of an agent capable of specifically inhibiting such fusion so as to thereby inhibit such fusion.

Methods for assaying inhibition of HIV-1 envelope glycoprotein-mediated membrane fusion

This invention provides agents determined to be capable of inhibiting the fusion of a macrophage-tropic primary isolate of HIV-1 to a CD4cell and agents determined to be capable of inhibiting the fusion of a T cell-tropic isolate of HIV-1 to a CD4cell. This invention also provides methods to identify such agents. This invention further provides methods of inhibiting fusion of a macrophage-tropic primary isolate of HIV-1 with a CD+ cell and methods of inhibiting fusion of a T cell-tropic isolate of HIV-1 with a CD4cell susceptible to infection by a T cell-tropic isolate of HIV-1.

Methods for inhibiting HIV-1 envelope glycoprotein-medicated membrane fusion

Methods of inhibiting human immunodeficiency virus type 1 (HIV-1) infection through the administration of CCR5 chemokine receptor antagonists

The invention is directed an anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO140-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising an expression product of either a plasmid designated pVg1:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmid designated pVg1:HuPRO140 (mutB+D+I)-VH (ATCC Deposit Designation PTA-4099) or a fragment thereof which binds to CCR5 on the surface of a human cell.

Anti-CCR5 antibody

PSMA antibodies and protein multimers

This invention provides a composition which comprises an admixture of three compounds, wherein: (a) one compound is an antibody which binds to a CCR5 receptor; (b) 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 (c) one 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 any two 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 composition of the subject invention effective to inhibit HIV-1 infection of the CD4+ cell so as to thereby inhibit HIV-1 infection of the CD4+ cell.

Methods of inhibiting human immunodeficiency virus infection through the administration of synergistic combinations of anti-CCR5 monoclonal antibodies, fusion inhibitors, and CD4-GP120 binding inhibitors

The invention is directed an anti-CCR5 antibody which comprises (i) two light chains, each light chain comprising the expression product of a plasmid designated pVK:HuPRO14O-VK (ATCC Deposit Designation PTA-4097), and (ii) two heavy chains, each heavy chain comprising an expression product of either a plasmid designated pVgl:HuPRO140 HG2-VH (ATCC Deposit Designation PTA-4098) or a plasmic designated pVgl:HuPRO140 (mutB+D+I)-VH (ATCC Deposit Designation PTA-4099) or a fragment thereof which binds to CCR5 on the surface of a human cell.

This invention provides an isolated nucleic acid which comprises a nucleotide segment having a sequence encoding a viral envelope protein comprising a viral surface protein and a corresponding viral transmembrane protein wherein the viral envelope protein contains one or more mutations in amino acid sequence that enhance the stability of the complex formed between the viral surface protein and transmembrane protein. This invention also provides a viral envelope protein comprising a viral surface protein and a corresponding viral transmembrane protein wherein the viral envelope protein contains one or more mutations in amino acid sequence that enhance the stability of the complex formed between the viral surface protein and transmembrane protein. This invention further provides methods of treating HIV-1 infection.

Stabilized viral envelope proteins and uses thereof

This invention provides a DNA which upon transcription produces an RNA encoding a modified HIV-1 gp140 polypeptide, which polypeptide upon cleavage produces a modified gp120 and a modified ectodomain of gp41 which together form a complex exhibiting enhanced binding to HIV-1 neutralizing antibodies and reduced binding to HIV-1 non-neutralizing antibodies, wherein the modifications comprise an A492C mutation in gp120 and a T596C mutation in gp41, said mutations being numbered by reference to the HIV-1 isolate JR-FL, and resulting in a disulfide bond between gp120 and ectodomain gp41 which stabilizes the otherwise non-covalent gp120-gp41 interaction.

Nucleic acids encoding mutant disulfide bond-stabilized human immunodeficiency virus type 1 (HIV-1) gp140 envelope glycoproteins

Growing community of inventors

Scarsdale, NY, United States of America

Paul J Maddon