Los Angeles Biomedical Research Institute at Harbor-Ucla Medical Center

University of Rochester

University of California

Other

University of Guelph

The Lundquist Institute for Biomedical Innovation at Harbor-Ucla Medical Center

Harbor-Ucla Research and Education Institute

Lindquist Institute for Biomedical Innovation at Harbor-Ucla Medical Center

Alan J Waring

Larry M Gordon

Frans J Walther

Robert I Lehrer

Robert H Notter

Teresa B Hong

Zhengdong Wang

Alexander M Cole

Joseph A Zasadzinski

Jason A Davy

Adrian L Schwan

Zhongyi Wang

Virender Rehan

John S Torday

Brian F Tack

Virender K Rehan

Sherry M Haynes

Kenneth J Longmuir

The present disclosure provides compositions and therapies that can address both the symptoms and disorders associated with insufficient surfactant production and hyperoxia. In one embodiment, the composition can be formulated for aerosol delivery during ventilation therapy. The composition can comprise one or more of the following: a PPAR gamma agonist, a surfactant peptide, and one or more phospholipids. The compositions are formulated to provide the complementary benefits of reducing the likelihood of developing or the severity of RDS in infants, as well as protecting and promoting lung maturation in a hyperoxic environment.

Compositions and methods for administering PPARγ agonists, surfactant peptides and phospholipids

Compositions and method for administering PPARgamma agonists, surfactant peptides and phosopholipids

Peptides suitable for preparation of lung surfactants are described. Examples include one that include a first fragment comprising the amino acid sequence of XWLXRALIKRIQAZI (SEQ ID NO: 1) or a first amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and a second fragment comprising the amino acid sequence of RZLPQLVXRLVLRXS (SEQ ID NO: 2) or a second amino acid sequence having at least 90% sequence identity to SEQ ID NO: 2, wherein X is any amino acid but at least one amino acid at the X positions is not cysteine, or Z is any amino acid but at least one amino acid at the Z positions is not methionine. Surfactants that contain such peptides, and related compositions, methods of preparing and using the compositions are also described.

Synthetic lung surfactant with enhanced stability and effectiveness

The present invention relates to synthetic lung surfactant compositions that include a novel surface active peptide and a phospholipid, including phospholipase-resistant phospho-glycerol derivatives, phospholipase-resistant phospho-choline derivatives, naturally occurring phospholipids, or a combination thereof. Uses of the surfactant compositions of the present invention to treat endogenous surfactant dysfunctional or deficient lung tissue and to deliver therapeutic agents are also disclosed.

SP-B and SP-C peptides, synthetic lung surfactants, and use thereof

The present invention relates to synthetic lung surfactant compositions that contain one or more of phospholipase-resistant phospho-glycerol derivatives, phospholipase-resistant phospho-choline derivatives, and surface active proteins or peptides, more preferably a combination of at least two or all three of these materials. Novel phospholipase-resistant phospho-glycerol derivatives, phospholipase-resistant phospho-choline derivatives, and surface active peptides are also disclosed herein. Uses of the surfactant compositions of the present invention to treat endogenous surfactant dysfunctional or deficient lung tissue, to prepare synthetic peptides for use in the surfactant compositions, and to deliver therapeutic agents are also disclosed.

Synthetic lung surfactant and use thereof

Retrocyclin peptides are small antimicrobial agents with potent activity against bacteria and viruses. The peptides are nonhemolytic, and exhibit minimal in vitro cytotoxicity. A pharmaceutical composition comprising retrocyclin as an active agent is administered therapeutically to a patient suffering from a bacterial and/or viral infection, or to an individual facing exposure to a bacterial and/or viral infection, especially one caused by the HIV-1 retrovirus or other sexually-transmitted pathogens.

Retrocyclins: antiviral and antimicrobial peptides

A composition including a C terminal region having residues corresponding to a peptide identified by PDB ID: 1RG3; an N terminal region having residues corresponding to a peptide identified by PDB ID: 1RG4; and a disulfide linkage between the residues near the C terminal region and the N terminal region. A composition including an exogenous peptide comprising amino acid residues comprising a C terminal region; amino acid residues comprising an N terminal region; a helix-loop-helix conformation between the residues comprising the C terminal region and the residues including the N terminal region; and at least one disulfide linkage between the residues comprising the C terminal region and the residues including N terminal region, wherein the residues including the C terminal region and the residues comprising the N terminal region have an amphiphatic property, and wherein the peptide has an a biological activity comparable to native surfactant protein SP-B. A method including delivering to a body a composition comprising an exogenous peptide having a biological activity comparable to native surfactant protein SP-B. A kit including an exogenous peptide having a biological activity comparable to native surfactant protein SP-B; and a treatment agent different from the peptide.

Exogenous surfactant protein B mimic

A therapeutic pharmaceutical composition for the treatment of respiratory disease is disclosed, including particularly Respiratory Distress Syndrome (RDS). The composition is comprised of a synthetic dimer of an N-terminal fragment of Surfactant Protein B (SP-B) that advantageously mimics the functional activity of native human Surfactant Protein B, and to therapeutic methods of administration of such pharmaceutical compositions.

Respiratory distress syndrome therapy with peptide analogs of human SP-B

Novispirin peptides are antimicrobial agents with potent activity against Gram-negative bacteria. The peptides are nonhemolytic, exhibit reduced in vitro cytotoxicity relative to other antimicrobial peptides, and were well-tolerated in vivo after intravenous injection. Novispirins also bind lipopolysaccharide (LPS), a property that may mitigate symptoms associated with Gram-negative bacterial infection. A pharmaceutical composition comprising novispirin as an active agent is administered to a patient suffering from or predisposed to a microbial infection, particularly Gram-negative bacterial infections.

Novispirins: antimicrobial peptides

Described herein are liposome complexes and the individual components thereof for intracellular and/or intranuclear delivery of substances. Methods of use of the provided liposome complexes and components are also described. Generally, the liposome complexes described herein include a non-cationic lipid, a fusogenic peptide and a substance to be delivered to the cell and/or nucleus. In some of the liposome complexes described herein, the fusogenic peptide does not contain multiple positive charges at neutral pH and above. In these liposome complexes, two additional components are used in assembling the liposome complex with DNA.

Liposome fusion and delivery vehicle

Growing community of inventors

Irvine, CA, United States of America

Alan J Waring