Los Angeles Biomedical Research Institute at Harbor-ucla Medical Center

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

Novadigm Therapeutics, Inc.

Harbor-ucla Research and Education Institute

The Lundquist Institute for Biomedical Innovation

La Biomedical Research Institute at Harbor-ucla Medical Center

Michael R Yeaman

Nannette Y Yount

John E Edwards, Jr

Ashraf S Ibrahim

Eric P Brass

Alexander J Shen

Yue Fu

Scott G Filler

Arnold S Bayer

John P Hennessey, Jr

Brad J Spellberg

Bradley J Spellberg

Guanpingsheng Luo

Nannette I Yount

Liana Chan

John E Edwards

Cell populations, compositions, and methods are provided relating to target priming of macrophage cells. The macrophages, once primed or activated with a microorganism, can be used to prevent or treat infection by the microorganism. Likewise, once primed or activated by a tumor cell or tumor antigen, the macrophage cell can be used to prevent or treat tumor of the same kind. The priming can be carried out in vitro or ex vivo. The macrophages can be isolated from the subject of disease prevention or treatment.

Target-primed macrophages and therapeutic uses thereof

Computational systems and methods are described for identifying new type-II bacteriocins using a systemic consensus formula and other related criteria. Newly identified type-II bacteriocin peptides are tested experimentally and show potent microbiocidal activities.

Antimicrobial type-II bacteriocins

Computational systems and methods are described for identifying new α-helical antimicrobial peptides using a systemic consensus formula. Newly identified α-helical antimicrobial peptides are tested experimentally and show potent microbiocidal activities.

Antimicrobial peptides with alpha-core helices

Computational systems and methods are described for identifying new type-ll bacteriocins using a systemic consensus formula and other related criteria. Newly identified type-ll bacteriocin peptides are tested experimentally and show potent microbicidal activities. Further provided are the sequences of Newly identified type-ll bacteriocin peptides, and a method of treating an infection in a patient in need thereof, comprising administering to the patient an effective amount of a peptide comprising an amino acid sequence disclosed.

The invention features a method of vaccinating a mammal againstwhich includes the steps of: a) identifying a mammal at risk for the development of askin or soft tissue infection; and b) administering to said mammal an immunogenic amount of a vaccine that includes a polypeptide including an isolated agglutinin-like sequence (Als) 3 protein (Als3p), or an immunogenic fragment thereof, in a pharmaceutically acceptable medium.

Methods and compositions for vaccinating against

Antimicrobial peptides, compositions and methods are described that are useful for treating infectious diseases, including those caused by drug resistant Gram-negative bacteria (e.g.,and) and parasite-caused diseases such as malaria. The peptides include a modular kinocidin gamma-core connected directly, or through a short spacer, to a kinocidin C-terminal alpha-helix.

Antimicrobial fusion peptides

The present invention provides novel kinocidin peptides comprising a C-terminal portion of a kinocidin, wherein the C-terminal portion encompasses an &#x3b1;-helical secondary structure and further displays antimicrobial activity. The kinocidin peptides of the invention are derived from and correspond to a C-terminal portion of a kinocidin that includes a &#x3b3;core and that can be a CXC, CC, or C class chemokine. Structural, physicochemical and functional properties of this novel class of antimicrobial peptides and amino acid sequences of particular kinocidin peptides are also disclosed. The invention also provides related antimicrobial methods.

Antimicrobial kinocidin compositions and methods of use

The invention provides a vaccine including an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, with an adjuvant in a pharmaceutically acceptable medium. The invention also provides a method of treating or preventing hematogenously disseminated or mucocutaneous candidiasis. The method includes administering an immunogenic amount of a vaccine an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, in a pharmaceutically acceptable medium. A method of treating or preventing disseminated candidiasis also is provided that includes administering an effective amount of an isolated Als protein family member having cell adhesion activity, or an functional fragment thereof, to inhibit the binding or invasion ofto a host cell or tissue. The Als protein family member can be derived from astrain selected from the group consisting ofandand the Als protein family member includes Als1p, Als3p, Als5p, Als6p, Als7p or Als9p. Also provided is a method of treating or preventinginfections. The method includes administering an immunogenic amount of a vaccine an isolated Als protein family member having cell adhesion activity, or an immunogenic fragment thereof, in a pharmaceutically acceptable medium.

Pharmaceutical compositions and methods to vaccinate against disseminated candidiasis and other infectious agents

The disclosure features isolated polypeptides of Hyr1. The disclosure further features vaccines and antibodies useful in treating or preventing candidiasis orinfections or both. Further disclosed are isolated polypeptides consisting of between 14 and 20 amino acids for vaccine preparation. The specific amino acid sequences of isolated polypeptides of Hyr1 are also disclosed.

HYR1-derived compositions and methods of treatment using same

The invention features fragments of thecell surface proteins Als3 and Hyr1 and combinations thereof useful in immunizing a subject against fungal or bacterial infections or both.

Compositions and methods for treating fungal and bacterial pathogens

The invention provides a method for preventing or treating a disease caused by an extracellular microorganism, said method comprising systemically administering to a subject in need thereof a prophylactically or therapeutically effective amount of a salicylic acid (SAL) or a SAL analog. The extracellular microorganism can be of the bacterial genus, for example,. The extracellular microorganism can be a strain that is resistant to at least one antibiotic. The strain can be selected from the group consisting of methycillin-resistant(MRSA), vancomycin-intermediate(VISA) and vancomycin-resistant(VRSA). The invention also provides a method for preventing or treating an infectious disease caused by of methycillin-resistant(MRSA), vancomycin-intermediate(VISA) or vancomycin-resistant(VRSA), comprising systemically co-administering in a synergistic combination to a subject in need thereof prophylactically or therapeutically effective amounts, individually or collectively, of a salicylic acid (SAL) or a SAL analog and at least one additional antimicrobial agent, for example, vancomycin and/or linezolid.

Anti-infective hydroxy-phenyl-benzoates and methods of use

The invention provide isolated peptides, protides and conjugates having novel peptide sequences which are able to induce antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. The invention also provides a method of inducing programmed cell death in a cell by contacting the cell with an isolated peptide, protide or conjugate described herein. In some aspects, the method can be used in the diagnosis, prevention, or treatment of a disease, such as an infection, cancer, autoimmune disease, or inflammatory disease.

Peptides and methods for inducing cell death

The present invention provides novel kinocidin peptides comprising a C-terminal portion of a kinocidin, wherein the C-terminal portion encompasses an &#x3b1;-helical secondary structure and further displays antimicrobial activity. The kinocidin peptides of the invention are derived from and correspond to a C-terminal portion of a kinocidin that includes a &#x3b3;&#x3ba;o core and that can be a CXC, CC, or C class chemokine. Structural, physicochemical and functional properties of this novel class of antimicrobial peptides and amino acid sequences of particular kinocidin peptides are also disclosed. The invention also provides related antimicrobial methods.

The peptides and derivative metapeptides based upon natural antimicrobial peptides have potent and broad spectrum activity against pathogens exhibiting multiple antibiotic resistance. Specific peptides can also potentiate the antimicrobial functions of leukocytes, such as neutrophils. In addition, they exhibit lower inherent mammalian cell toxicities than conventional antimicrobial peptides, and overcome problems of toxicity, immunogenicity, and shortness of duration of effectiveness due to biodegradation, retaining activity in plasma and serum. The peptides and derivative metapeptides exhibit rapid microbicidal activities in vitro, can be used to potentiate conventional antimicrobial agents, to potentiate other antimicrobial peptides and are active against many organisms that exhibit resistance to multiple antibiotics currently in existence.

Growing community of inventors

Redondo Beach, CA, United States of America

Michael R Yeaman