Abstract: This invention provides humanized IgG4 monoclonal antibodies having the light and heavy chain variable region amino acid sequences of PRO 140, wherein the antibody comprises (i) a heavy chain modification that inhibits half antibody formation, (ii) a heavy chain modification that increases the antibody's terminal half-life, and, optionally, (iii) a heavy chain modification that lowers the antibody's effector function. This invention also provides a related humanized IgG2/IgG4 monoclonal fusion antibody. This invention further provides related nucleic acid molecules; recombinant vectors; recombinant AAV particles; pharmaceutical compositions; prophylactic and therapeutic methods for addressing HIV-1 infection, SARS-CoV-2 infection, and CCR5-mediated disorders; and kits for performing these methods.

Abstract: This invention provides a monoclonal antibody that (i) specifically binds to the extracellular portion of human angiotensin converting enzyme 2 (hACE2); (ii) specifically inhibits binding of SARS-CoV-2 to the extracellular portion of hACE2; and (iii) does not significantly inhibit the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide. This invention also provides related recombinant AAV vectors, recombinant AAV particles, compositions, prophylactic and therapeutic methods, and kits.

Abstract: This invention provides a composition comprising (a) a first monoclonal antibody that (i) specifically binds to the extracellular portion of human angiotensin converting enzyme 2 (hACE2), (ii) specifically inhibits binding of SARS-CoV-2 to the extracellular portion of hACE2, and (iii) does not significantly inhibit the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide; and (b) a second monoclonal antibody that (i) specifically binds to the extracellular portion of human TMPRSS2 (hTMPRSS2), and (ii) specifically inhibits the entry into hACE2+/hTMPRSS2+ human cells of a pseudovirus bearing SARS-CoV-2 S protein. This invention also provides related recombinant AAV vectors, recombinant AAV particles, compositions, prophylactic and therapeutic methods, and kits.

Abstract: This invention provides a bispecific antibody that (i) specifically binds to the extracellular portion of human angiotensin converting enzyme 2 (hACE2); (ii) specifically binds to the extracellular portion of human TMPRSS2 (hTMPRSS2); (iii) does not significantly inhibit the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide; and (iv) specifically inhibits the entry into hACE2+/hTMPRSS2+ human cells of a pseudovirus bearing SARS-CoV-2 S protein. This invention also provides related pharmaceutical compositions, recombinant nucleic acid molecules, vectors, AAV particles, therapeutic and prophylactic methods, and kits.

Abstract: This invention provides a monoclonal antibody that (i) specifically binds to the extracellular portion of human angiotensin converting enzyme 2 (hACE2); (ii) specifically inhibits binding of SARS-CoV-2 to the extracellular portion of hACE2; and (iii) does not significantly inhibit the ability of hACE2 to cleave angiotensin II and/or a synthetic MCA-based peptide. This invention also provides related recombinant AAV vectors, recombinant AAV particles, compositions, prophylactic and therapeutic methods, and kits.

Abstract: This invention relates generally to antibody-drug conjugates (ADCs). In particular, the invention relates to ADCs which comprise an antibody or antigen-binding fragment thereof which binds to prostate-specific membrane antigen (PSMA) and is conjugated to monomethylauristatin norephedrine or monomethylauristatin phenylalanine. The antibody-drug conjugate has a PC-3™ cell to C4-2 or LNCaP™ cell selectivity of at least 250. The invention also relates, in part, to compositions of and methods of using the ADCs. The methods provided include, for example, methods for treating a PSMA-mediated disease.

Abstract: 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 log10 to 2.5 log10 at 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 log10 at about nine days following administration of the CCR5 receptor antagonist. The viral load reducing dose results in a suppression of mean viral load by 1.0 log10 within about four days following administration of the CCR5 receptor antagonist, and suppression of viral load in the subject persists at or below a level of reduction of 1.0 log10 for about two to three weeks.

Abstract: 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 log10 to 2.5 log10 at 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 log10 at about nine days following administration of the CCR5 receptor antagonist.

Abstract: Certain R5 virus tropic HIV-1 subjects with viral load effectively conventionally controlled using HAART, i.e., subject having less than 50 viral copies/mL (<50 cp/mL), may be substantially more susceptible than others to effective monotherapy treatment using anti-CCR5 agents, e.g, PRO 140 mAbs. Certain HIV-1 subjects using PRO 140 monotherapy treatment may experience prolonged or unlimited time periods with actual undetectable viral loads, extremely low viral load counts ?1 cp/mL, very low, or low levels, or at conventionally undetectable levels, during monotherapy. Increasing dose amounts of anti-CCR5 agents, e.g., PRO 140, from 350 mg to 525 mg or 700 mg, may beneficially suppress a subject's viral load count before, during, and/or maintain effective prolonged monotherapy and may shorten the period of time necessary to determine if a subject will respond positively to PRO 140 monotherapy to less than eight (8) weeks. This invention includes protocols, methods, and kits.

Abstract: 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.

Abstract: 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.

Abstract: 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 CCR5+CD4+ target 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 CD4+ cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5+CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Abstract: 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.

Abstract: 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 CCR5+CD4+ target 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 CD4+ cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5+CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Abstract: This invention provides methods for inhibiting fusion of HIV-1 to CD4+ cells, comprising 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 CD4+ cells is inhibited. Also provided are methods for inhibiting HIV-1 infection of CD4+ cells, comprising 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 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 and 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.

Abstract: 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.

Abstract: 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.

Abstract: 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 CCR5+CD4+ target 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 CD4+ cells and (ii) inhibits fusion of HIV-1 to the subject's CCR5+CD4+ cells, and (b) a non-antibody CCR5 receptor antagonist, in amounts effective to treat the subject.

Abstract: 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.

Abstract: 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.