The present invention relates to a vaccine capable to induce production of antibodies directed to PCSK9 in vivo.

The present invention relates to a vaccine capable to induce the formation of antibodies directed to PCSK9 in vivo.

Neutralizing PCSK9 variants that interact with low density lipoprotein receptor (LDLR) are described. Methods and compositions for treating disorders by administering a pharmaceutically effective amount of a neutralizing PCSK9 variant are described.

Methods and compositions for modulating blood-neural barrier (BNB) for the treatment of CNS conditions such as edema, and for increased drug delivery efficacy across the BNB. The present invention further relates to improved tPA treatment of ischemic cerebrovascular and related diseases in combination with antagonism of the PDGF signaling pathway. The inventive method and composition is particularly suitable for conjunctive therapy of ischemic stroke using tPA and an anti-PDGF-C antagonist or an anti-PDGFR- antagonist.

The present invention provides compositions comprising an isolated or purified therapeutically effective hPCSK9 polypeptide derived from the hPCSK9 catalytic domain, and their use in methods of treating hypercholesterolemia.

Disclosed herein are methods for production of fully-processed mature Factor X in an expression system producing a controlled amount of furin between 50 U/mL and 300 U/mL of culture supernatant. Also disclosed are transformed cells, expression systems, and expression vectors for the expression of furin and Factor X.

Provided in some aspects are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA (gRNA) systems for the transcriptional repression of genes to promote a cellular phenotype that leads to reduction of low-density lipoprotein (LDL). In some embodiments, the epigenetic-modifying DNA-targeting systems bind to or target a target site of at least one gene or regulatory element thereof that regulate LDL. In some embodiments, the systems are multiplexed systems that bind to or target a target site in at least two genes or regulatory elements thereof. Also provided herein are methods and uses related to the provided epigenetic-modifying DNA targeting systems in connection with treatments for cardiovascular disease and familial hypercholesterolemia.

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies.

Provided herein are multifunctional heteromer proteins. In specific embodiments is a heteromultimer that comprises: at least two monomeric proteins, wherein each monomeric protein comprises at least one cargo polypeptide, attached to a transporter polypeptide, such that said monomeric proteins associate to form the heteromultimer. These therapeutically novel molecules comprise monomers that function as scaffolds for the conjugation or fusion of therapeutic molecular entities resulting in the creation of bispecific or multivalent molecular species.

The present invention relates to a immunogen comprising at least two fragments of Proprotein convertase subtilisin/kexin type 9 (PCSK9), wherein at least two fragments comprise at least 8 consecutive amino acid residues of amino acid residues 150 to 170 and/or 205 to 225 of PCSK9 (SEQ ID NO:9).