Apg Therapeutics, Inc.

Anthera Pharmaceuticals, Inc.

Joaquim Trias

Jaume Pons

David L Shelton

Patrick Irving Eacho

Debra Odink

Scott Chadwick

Kenneth Gould

Colin Hislop

Marian Mosior

Paul Truex

Antoni Planas

Bernadine Fraser

The present application provides PEI compounds comprising a linker, PEI-polypeptide conjugates (e.g., PEI-antibody conjugates), and complexes thereof comprising a biologically active molecule. Methods of preparing and using the compounds, conjugates and complexes are further provided. The PEI-polypeptide conjugates and complexes are useful for delivering biologically active molecules to the cytoplasm of cells and promoting release of the biologically active molecules from the endo-lysosomal pathway.

Polyethylenimine (PEI)-polypeptide conjugates and methods of use thereof

Administration of sPLAinhibitors has been found to decrease cholesterol levels, atherosclerotic plaque formation and aortic aneurysm in mice, and to decrease cholesterol and triglyceride levels in humans. Interestingly, administration of sPLAinhibitors was found to decrease cholesterol levels even when the inhibitors were administered only once per day. Therefore, provided herein are methods of treating dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome, by administering one or more sPLAinhibitors. Significantly, administration of sPLAinhibitors and various compounds used in the treatment of CVD, such as for example statins, resulted in greater decreases in LDL and LDL particle levels in a synergistic manner. In addition, administration of sPLAinhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more sPLAinhibitors and one or more compounds used in the treatment of CVD, such as for example statins, and methods of using these compositions to treat dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome.

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Millbrae, CA, United States of America

Joaquim Trias