The Brigham and Women's Hospital, Inc.

Ugp Therapeutics, Inc.

Resother Pharma Aps

Jesmond P Dalli

Charles Nicholas Serhan

Nozer M Mehta

Angelo P Consalvo

Mauro Perretti

Nan Chiang

Lucy V Norling

Matthew Spite

New host-protective molecules containing conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5) were produced in neutrophil-endothelial co-cultures, and they are present in human and mouse tissues after sterile inflammation or infection. These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival duringinfections. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. Atorvastatin and RvT were additive ininfections in mice where they accelerated resolution of inflammation and increased survival &#x3e;60%. Results documented novel host protective molecules in bacterial infections, namely RvT, derived from n-3 DPA via transcellular biosynthesis and increased by atorvastatin. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components to regulate key innate protective responses in the resolution of infectious-inflammation.

Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections

A family of bioactive compounds identified in self-resolving inflammatory exudates is disclosed. The compounds give UV chromophores characteristics of a conjugated triene double bond system coupled to an auxochrome allylic to the triene. Further elucidation of the compounds reveals that they have an oxylipin backbone conjugated to a peptide or amino acid moiety via an auxochrome. In some embodiments the auxochrome is sulfur. However, the auxochrome may be NH, CH2 or O. The compounds have potent bioactivity, in vitro, and, in vivo, including promoting resolution of infection, stimulating macrophage phagocytosis of bacteria; protecting tissues from neutrophil mediated damage, promoting tissue repair and regeneration and preventing or limiting second organ reflow/reperfusion damage.

Cysteinyl-proresolving mediators that promote resolution of infection and organ protection

Described herein are compositions and methods relating to particles comprising at least one component of a cellular-derived microparticle. Aspects of technology described herein relate to compositions and methods for treating inflammation, wounds, and pain.

Anti-inflammatory particles

Polypeptides having homology to regions of the N-terminal 50 residues of human Annexin 1 are provided for medical use as anti-inflammatory agents. Some of the polypeptides have homology to the N-terminal 48 residues of human Annexin 1, especially to residues 2-48 and 11-48 thereof. In some embodiments, properties of these compounds are improved by at least one modification at residues corresponding to residues 11, 22, 25 and/or 36 of human Annexin 1, and/or by C-terminal amidation of the polypeptide. Analogs of amino acids 2-26 of human Annexin 1, especially acetylated at the N-terminus and/or amidated at the C-terminus and having modifications at 11 and/or 22 are also disclosed for medical use as anti-inflammatory agents.

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Brookline, MA, United States of America

Jesmond P Dalli