Ortho Pharmaceutical Corporation

Thymon, LLC

Sloan-kettering Institute for Cancer Research

Immunobiology Research Institute, Inc.

Other

Gideon Goldstein

Patrick C Kung

George Heavner

Tapan Audhya

Daniel J Kroon

David H Schlesinger

Michael D Culler

Foe-Siong Tjoeng

Ponniah Shenbagamurthi

Mary A Talle

Roland Carlsson

John J Siekierka

Leif Strandberg

Crafford A Harris

James I Koenig

Elisabeth Sonesson

Krishnamurthy Venkatasubramanian

Patric C Kung

Patricia E Rao

Yvonne Stenberg

Mohmed K Anwer

Walter Newman

Diane R Setcavage

An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF. These methods and compositions disrupt or reduce the in vivo assembly or reassembly of dissociated monomers of TNF into bioactive trimeric human sTNF.

Compositions for selective reduction of circulating bioactive soluble TNF and methods for treating TNF-mediated disease

A self-adjuvanting immunogenic composition comprising multiple immunogens, each immunogen comprising a lipopeptide cap, a universal T helper sequence and an immunodominant HIV-1 Tat B cell epitope. The immunogen also comprises one or more linker sequences and/or polar charged amino acid sequences. The HIV-1 Tat B cell epitope of each immunogen has an amino acid sequence of V-D-P-Xaa7-L-Xaa9-P-W-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-amide SEQ ID NO: 1, in which the amino acid positions at Xaa7, Xaa9 and Xaa12 are selected from specific amino acid residues choices and in which the amino acid positions at Xaa13-Xaa16 may be absent or specific amino acid residue choices. The lipopeptide is a dipalmitoyl-S-glyceryl-cysteine or a tripalmitoyl-S-glyceryl cysteine or N-acetyl (dipalmitoyl-S-glyceryl cysteine), each with an optional neutral amino acid linker. Optional polar sequences of at least four charged polar amino acids enhance solubility of the immunogen and are located at the carboxy terminal end of the lipopeptide cap, optionally flanked by neutral linker amino acids, or elsewhere in the immunogen. In the composition, each immunogen differs from another immunogen by an amino acid variation at amino acid position Xaa7, Xaa9 or Xaa12 of the immunodominant HIV-1 Tat epitope. Such compositions can induce anti-HIV-1 Tat antibodies with geometric mean titers of greater than 1,000,000 on multiple HIV-1 Tat variants, when employed to immunize a subject, without any extrinsic adjuvant.

Compositions and methods for the treatment and prophylaxis of multiple strains and subtypes of HIV-1

A single isolated antibody or antibody fragment thereof binds to multiple variant sequences within an epitope of HIV-1 Tat protein displayed in multiple strains and subtypes of HIV-1. This 'pan-epitope' antibody is useful in therapeutic and prophylactic compositions and treatments of HIV-1 infection, regardless of strain. This pan-epitope antibody is useful in assays for the detection of levels of HIV-1 based on a measurement of the amount of Tat protein in a biological sample.

Methods and compositions for impairing multiplication of HIV-1

A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-terminal Pro). Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y -Leu-X -Pro-Trp-Z -R2 (SEQ ID NO: 8). In this composition, at least one of the two variants contains Arg at Y and Lys at Z , and in at least a second of the two variants Y is Asn and Z is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-termninal Pro). Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, in multiple antigenic peptides or as part of recombinant proteins. Various combinations of the Epitope I through IV peptides can provide other compositions useful in eliciting anti-Tat antibodies which cross-react with multiple strains and variants of HIV-1 Tat protein. Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y -Leu-Glu-Pro-Trp-Z -R2 SEQ ID NO: 8. In this composition, at least one of the two variants contains Arg at Y and Lys at Z , and in at least a second of the two variants Y is Asn and Z is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides, or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-terminal Pro). Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, in multiple antigenic peptides or as part of recombinant proteins. Various combinations of the Epitope I through IV peptides can provide other compositions useful in eliciting anti-Tat antibodies which cross-react with multiple strains and variants of HIV-1 Tat protein. Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

A composition is provided which contains a non-naturally occurring peptide or polypeptide comprising at least two or more, and preferably all four amino acid sequences -Asp-Pro-Arg-Leu-Glu-Pro- SEQ ID NO: 6; -Asp-Pro-Lys-Leu-Glu-Pro- SEQ ID NO: 7; -Asp-Pro-Ser-Leu-Glu-Pro- SEQ ID NO: 8; and -Asp-Pro-Asn-Leu-Glu-Pro- SEQ ID NO: 9. This composition, including a number of additional optional peptides or polypeptides, and in a variety of forms, demonstrates a biological activity of inducing antibodies that react with most HIV-1 Tat proteins and impairing the multiplication of HIV-1. Also provided are synthetic genes encoding these peptides, recombinant viruses and commensal bacterium carrying these genes, transfected host cells, and polyclonal or other types of antibodies produced by immunizing other mammals with these aforementioned compositions. Methods for making and using such compositions to lower the viral level of HIV-1 are described.

Tripeptides capable of regulating the function of cells of the mammalian immune and/or central nervous system, pharmaceutical compositions containing the peptides and methods of use thereof are provided.

Tripeptides useful in immune and CNS therapy

Method for accurately measuring thymopoietin (TP) in human serum or plasma by dissociating TP from protein complexes, releasing bound TP in a unbound form, extracting TP, preparing it for assay, and measuring TP levels in a suitable assay.

Method of measuring thymopoietin proteins in plasma and serum including

The invention provides a novel means of diagnosing, or confirming a diagnosis of, affective disorders, such as depression, based on the blood levels of arginine vasopressin and thymopoietin, either alone or in combination.

Method for the diagnosis of depression based on monitoring blood levels

The present invention provides novel nucleotide and amino acid sequences for human thymopoietin .alpha., .beta., and .gamma., methods of recombinantly expressing same, and diagnostic and therapeutic uses thereof.

Recombinant human thymopoietin proteins and uses therefor

Tetrapeptides and pentapeptides are disclosed which are capable of regulating the function of cells of the mammalian immune system. Also provided are pharmaceutical compositions containing the peptides and methods of use thereof.

Growing community of inventors

Short Hills, NJ, United States of America

Gideon Goldstein