Autoimmune Technologies, LLC

The Administrators of the Tulane Educational Fund

The Administration of the Tulane Educational Fund

The Administrators of the Tulane

Educational Fund and Autoimmune Technologies, LLC

The Administrators of the Tulane Educational Fund and Autoimmune Technologies, LLC

Russell B Wilson

Robert F Garry

Bruce Alan Bunnell

Samuel E Hopkins

Luis Manuel Branco

Kevin David Simpson

Luis M Branco

Immunoprotective primary mesenchymal stems cells (IP-MSC) which episomally express immunoreactive polypeptides that specifically target a pathogen (e.g., an infectious species of virus, bacterium, or parasite) or toxin are described herein. The immunoreactive polypeptides can be, e.g., full antibodies, single-chain antibodies (ScFV), Fab or F(ab)antibody fragments, diabodies, tribodies, and the like). Optionally IP-MSC are transfected to express one or more other immunomodulating polypeptides, e.g., a cytokine such as an interleukin (e.g., IL-2, IL-4, IL-6, IL-7, IL-9, and IL-12), an interferon (e.g., IFN&#x3b1;, IFN&#x3b2;, or IFN&#x3c9;), and the like, which can enhance the effectiveness of the immunoreactive polypeptides.

Immunoprotective primary mesenchymal stem cells and methods

Immunogenic influenza hemagglutinin-derived peptide compositions described herein induce a specific therapeutic antibody response against influenza virus. The immunogenic peptide compositions comprise a segment from the fusion initiation region (FIR) domain of an influenza hemagglutinin protein bound to an immunogenic carrier protein, such as an influenza hemagglutinin (HA) protein (i.e., full length HA), and the like. The immunogenic peptide compositions described herein can be utilized to treat or prevent influenza infection and to prepare influenza-specific therapeutic antibodies that interfere with influenza virus-host cell membrane fusion. The peptide conjugates can be formulated in pharmaceutical compositions useful for broad spectrum treatment or prevention of influenza infections.

Immunogenic peptide composition and method

Immunoprotective primary mesenchymal stems cells (IP-MSC) which episomally express multiple immunoreactive polypeptides that specifically target a pathogen (e.g., an infectious species of virus, bacterium, or parasite) or toxin are described herein. The IP-MSC express two or more (e.g., 2 to about 100) immunoreactive polypeptides (e.g., full antibodies, single-chain antibodies (ScFV), Fab or F(ab)antibody fragments, diabodies, tribodies, and the like), and optionally one or more other immunomodulating polypeptides, e.g., a cytokine such as an interleukin (e.g., IL-2, IL-4, IL-6, IL-7, IL-9, and IL-12), an interferon (e.g., IFN&#x3b1;, IFN&#x3b2;, or IFN&#x3c9;), and the like, which can enhance the effectiveness of the immunoreactive polypeptides.

An assay method for detecting antipolyvinyl alcohol (anti-PVAL) antibodies in test samples, such as serum, is described. The method comprises combining a sample to be tested for an anti-PVAL antibody with polyvinyl alcohol (PVAL) to form a binary complex of the PVAL with an anti-PVAL antibody in the sample, followed by reacting an indicator reagent with the binary complex to form a labeled ternary complex, and then detecting the presence or absence of the ternary complex in the sample. Kits for performing the test are also described.

Assay for anti-polyvinyl alcohol antibodies

Immunogenic influenza hemagglutinin-derived peptide conjugates described herein induce a specific therapeutic antibody response against influenza virus. The immunogenic peptide conjugates comprise a segment from the fusion initiation region (FIR) domain of an influenza hemagglutinin protein conjugated to an immunogenic carrier protein, such asbovine serum albumin (BSA), an influenza hemagglutinin (HA) protein (i.e., full length HA), and the like. The immunogenic peptide conjugates described herein can be utilized to treat or prevent influenza infection and to prepare influenza-specific therapeutic antibodies that interfere with influenza virus-host cell membrane fusion. The peptide conjugates can be formulated in pharmaceutical compositions useful for broad spectrum treatment or prevention of influenza infections.

Immunogenic peptide conjugate and method for inducing an anti-influenza therapeutic antibody response therewith

The present invention provides compositions and methods for treating a measles virus infection. A pharmaceutical composition comprises a polypeptide in a biocompatible pharmaceutical carrier, in which the polypeptide consists of at least a portion of SEQ ID NO: 5 or SEQ ID NO: 6. A method embodiment comprises administering the polypeptide (preferably in a biocompatible pharmaceutical carrier) to a subject suffering from a measles infection.

Compositions and methods for measles virus inhibition

Immunogenic influenza hemagglutinin-derived peptide conjugates described herein induce a specific therapeutic antibody response against influenza virus. The immunogenic peptide conjugates comprise a segment from the fusion initiation region (FIR) domain of an influenza hemagglutinin protein conjugated to an immunogenic carrier protein, such as keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), an influenza hemagglutinin (HA) protein (i.e., full length HA), and the like. The immunogenic peptide conjugates described herein can be utilized to treat or prevent influenza infection and to prepare influenza-specific therapeutic antibodies that interfere with influenza virus-host cell membrane fusion. The peptide conjugates can be formulated in pharmaceutical compositions useful for broad spectrum treatment or prevention of influenza infections.

The present invention provides peptides, peptide analogs, peptide derivatives and pharmaceutical compositions useful for treating or preventing influenza infections or preventing the person-to-person transmission of an influenza infection. A peptide of the invention comprises an influenza virus-cell fusion inhibiting portion of the fusion initiation region (FIR) of a wild-type influenza hemagglutinin 2 protein or a variant thereof. In a preferred embodiment, a peptide of the invention consists of 8 to 40 consecutive amino acid residues a portion of a wild-type influenza hemagglutinin 2 protein or a variant thereof, the portion of the protein comprising the FIR of the protein and up to five amino acid residues on the amino-terminal and carboxy-terminal sides of the FIR.

Influenza inhibiting compositions and methods

The present invention provides compositions and methods for treating a coronavirus infection. A method embodiment comprises administering a polypeptide (preferably in a biocompatible pharmaceutical carrier) to a subject suffering from a coronavirus infection. The polypeptide comprises or consists of at least a portion of the fusion initiation region (FIR) of a coronavirus fusion protein. In some embodiments, the polypeptide comprises or consists of a sequence selected from SEQ ID NO: 2, 22, 23, 24, and 25 or an 8 to 40 contiguous amino acid residue portion thereof.

Compositions and methods for coronavirus inhibition

The present invention provides methods for the treatment of an ongoing influenza infection by administering a polypeptide to a subject suffering from an influenza infection. The polypeptide consists of SEQ ID NO: 4. The present invention also provides a method of interfering with fusion of an influenza virus envelope with a host cell membrane by contacting the host cell with a polypeptide consisting of SEQ ID NO: 4.

Treatment of influenza virus infection

The present invention provides compositions useful for treating or preventing influenza infections. The composition comprises an isolated polypeptide including a sequence of at least 8 contiguous amino acid residues of the fusion initiation region (FIR) of an influenza hemagglutinin 2 protein or a peptide analog of the sequence. The FIR is a segment of the full length hemagglutinin 2 protein which is bounded by an amino-terminal region within the amino-terminal alpha-helix thereof and a carboxy terminus within the carboxy-terminal alpha-helix thereof, with a cysteine loop therebetween. The amino-terminal region of the FIR comprises a portion of the final 10 to 20 amino acid residues of the amino-terminal alpha-helix of the hemagglutinin 2 protein, and includes 3 or 4 hydrophobic amino acid residues, a positively-charged amino acid residue, a negatively-charged amino acid residue, and an aromatic amino acid residue. The carboxy terminus of the FIR is the carboxy terminus of the first peptide sequence of the hemagglutinin 2 protein beyond the amino terminal helix, which exhibits a positive Wimley-White interfacial hydrophobicity.

The present invention relates to a method of preventing or inhibiting viral infection of a cell and/or fusion between the envelope of a virus and the membranes of a cell targeted by the virus (thereby preventing delivery of the viral genome into the cell cytoplasm, a step required for. viral infection). The present invention particularly relates to the families of RNA viruses, including the arenaviruses, coronaviruses, filoviruses, orthomyxoviruses, paramyxoviruses, and retroviruses, having Class I membrane fusion proteins as the fusion proteins that mediate this fusion process. The present invention provides for a method of identifying a conserved motif or domain called the fusion initiation region (FIR) in these viruses. The present invention further provides for methods of preventing infection by such viruses, by interfering with their FIR. The present invention further provides for methods of treatment and prophylaxis of diseases induced by such viruses.

Growing community of inventors

Mandeville, LA, United States of America

Russell B Wilson