Trimeris, Inc.

Other

Duke University

Dennis Michael Lambert

Stephen Robert Petteway

Shawn O'Lin Barney

Gene Merutka

Shawn Barney

Kelly I Guthrie

Mohmed K Anwer

Carl Thomas Wild

Dani Paul Bolognesi

Thomas James Matthews

Alphonse J Langlois

M Ross Johnson

Thomas J Matthews

Shawn O'lin Barney

Stephen R Petteway

Joel Burton Erickson

Mary Katherine Delmedico

James B Antczak

Prakash Sista

Cart T Wild

Ross M Johnson

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID NO:1) peptide corresponding to amino acids 638 to 673 of the HIV-1gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Isolated peptides derived from human immunodeficiency virus types 1 and 2 containing fusion inhibitory domains

The present invention relates to peptides which exhibit potent anti-viral activity. In particular, the invention relates to methods of using such peptides as inhibitory of hepatitis B virus ('HepB') transmission to uninfected cells. The peptides used in the methods of the invention are homologs of the DP-178 and DP-107 peptides, peptides corresponding to amino acid residues 638 to 673, and to amino acid residues 558 to 595, respectively, of the HIV-1transmembrane protein (TM) gp41.

Methods for inhibition of membrane-fusion-associated events, including Hepatitis B virus transmission

The present invention relates to enhancer peptide sequences originally derived from various retroviral envelope (gp41) protein sequences that enhance the pharmacokinetic properties of any core polypeptide to which they are linked. The invention is based on the discovery that hybrid polypeptides comprising the enhancer peptide sequences linked to a core polypeptide possess enhanced pharmacokinetic properties such as increased half life. The invention further relates to methods for enhancing the pharmacokinetic properties of any core polypeptide through linkage of the enhancer peptide sequences to the core polypeptide. The core polypeptides to be used in the practice of the invention can include any pharmacologically useful peptide that can be used, for example, as a therapeutic or prophylactic reagent.

DNA encoding T-1249 and other viral fusion inhibitor peptides useful for treating aids

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Fusion proteins comprising DP-178 and other viral fusion inhibitor peptides useful for treating aids

Parainfluenza virus types 1 to 4 (PIV1 to PIV4) are important human pathogens that cause upper and lower respiratory tract infections, particularly in infants and children. The claimed invention is directed toward novel methods for the inhibition of parainfluenza virus transmission to a cell involving the administration of synthetic peptide fusion inhibitors. These inhibitors are derived from the parainfluenza virus and vary in length between 16 to 39 amino acids. The peptides were identified by screening for the presence of fusion inhibitory motifs (e.g., ALLMOTI5, 107x178x4, and PLZIP) within the parainfluenza virus genome. A number of peptides were identified and their fusion inhibitory activities ascertained. These peptides should provide useful antiviral agents.

Methods and compositions for inhibition of membrane fusion-associated events, including HIV transmission

Novel antiviral combinations for the treatment or prevention of viral infections, in particular, HIV, are disclosed. This new antiviral therapy employs either DP-178 or DP-107, viral fusion inhibitors, in combination with at least one other antiviral therapeutic agent. The combinations of the invention are better than single therapies alone, and in certain cases are synergistic. The use of DP-178 or DP-107 is an ideal therapy to combine with another antiviral, given both the novel mechanism which this therapeutic blocks HIV transmission and the non-toxicity of the therapeutic.

Methods and compositions for treatment of HIV-1 infection using antiviral compounds in simultaneous or sequential combinations

An traction apparatus for use in manipulating a patient's arm and wrist bones comprises a traction assembly having a plurality of finger traps, a plurality of springs with each spring capable of releasably associating with at least one trap, and a swivel base secured to each of the springs. Also, included are a traction force scale coupled to the traction assembly, a first traction force generating mechanism linked to the traction force scale, a second traction force generating mechanism coupled to the patient's upper arm, and a support attachment system for securing the subject apparatus components to a support. Additionally, a spacer for separating and positioning the patient's fingers is included.

Traction device

Hybrid polypeptides with enhanced pharmacokinetic properties

The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention are derived from regions of viral fusion proteins referred to as HR1 and HR2. In particular, the invention relates to peptides referred to herein as DP107 and DP178 which comprise amino acid sequences corresponding to sequences found in the HR1 and HR2 regions, respectively of the HIV-1 gp41 protein. The invention further relates to &ldquo;DP107-like&rdquo; and &ldquo;DP178-like&rdquo; peptides that are derived from HR1 and HR2 regions, respectively, of other proteins, including DP107-like and DP178-like peptides derived from the HR1 and HR2 regions of the F1 subunit of the respiratory syncytial virus fusion protein.

Methods and compositions for inhibition of membrane fusion-associated events including RSV transmission

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1(HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI 5, 107&times;178&times;4, and PLZIP) in other viral proteins was employed to identify similar regions in the Epstein-Barr virus (EBV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the EBV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of EBV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of EBV infections.

Methods for the inhibition of epstein-barr virus transmission employing anti-viral peptides capable of abrogating viral fusion and transmission

The present invention relates to peptides which exhibit potent anti-viral activity. In particular, the invention relates to methods of using such peptides as inhibitory of respiratory syncytial virus (&ldquo;RSV&rdquo;) transmission to uninfected cells. The peptides used in the methods of the invention are homologs of the DP-178 and DP-107 peptides, peptides corresponding to amino acid residues 638 to 673, and to amino acid residues 558 to 595, respectively, of the HIV-1 transmembrane protein (TM) gp41.

Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission

Treatment of HIV and other viral infections using combinatorial therapy

Fusion of the viral envelope, or infected cell membranes with uninfected cell membranes, is an essential step in the viral life cycle. Recent studies involving the human immunodeficiency virus type 1 (HIV-1) demonstrated that synthetic peptides (designated DP-107 and DP-178) derived from potential helical regions of the transmembrane (TM) protein, gp41, were potent inhibitors of viral fusion and infection. A computerized antiviral searching technology (C.A.S.T.) that detects related structural motifs (e.g., ALLMOTI5, 107&times;178&times;4, and PLZIP) in other viral proteins was employed to identify similar regions in the respiratory syncytial virus (RSV). Several conserved heptad repeat domains that are predicted to form coiled-coil structures with antiviral activity were identified in the RSV genome. Synthetic peptides of 16 to 39 amino acids derived from these regions were prepared and their antiviral activities assessed in a suitable in vitro screening assay. These peptides proved to be potent inhibitors of RSV fusion. Based upon their structural and functional equivalence to the known HIV-1 inhibitors DP-107 and DP-178, these peptides should provide a novel approach to the development of targeted therapies for the treatment of RSV infections.

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Cary, NC, United States of America

Dennis Michael Lambert