Pfizer Corporation

Rinat Neuroscience Corporation

Other

Bruce Charles Gomes

Jaume Pons

Javier Fernando Chaparro Riggers

Hong Liang

Yasmina Noubia Abdiche

Julie Jia Li Hawkins

Yuli Wang

David L Shelton

Arvind Rajpal

Pavel Strop

Jeffrey Raymond Chabot

Xiayang Qiu

Kapil Mayawala

Jerome Thomas Mettetal, Ii

Garrett M Kasof

Judith C Prosser

Julie Jia Hawkins

The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

PCSK9 antagonists

The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the Kor kratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent Ks at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present at high levels (e.g., IgE, DKK1, C5 and SOST). In addition, such antibodies can increase antigen half life when the antigen is a receptor and the receptor has increased clearance when bound to antibody (e.g., GMCSF receptor).

Anti-PCSK9 antibodies with pH dependent antigen binding

Method for reducing a level of LDL-cholesterol by an antibody that specifically binds to PCSK9

Isolated nucleic acid encoding an antibody which specifically binds to PCSK9 and a host cell that produces the antibody

Isolated antibody which specifically binds to PCSK9

A novel isolated and purified human protein inhibitor of apoptosis, termed livin, is described. A cDNA sequence which encodes the native inhibitor of apoptosis (livin) is disclosed as well as the structural coding region and the amino acid residue sequence. Molecular sequences are provided for the design and synthesis of entities that modulate biological and/or pharmacological activity of the native biomolecule. Methods are provided which employ the sequences to identify compounds that modulate biological and/or pharmacological activity of the native biomolecule. Biologically-effective antisense molecules as well as dominant negative mutant versions of the livin protein which are suitable for therapeutic are also provided. The invention is also drawn toward the study, prevention, diagnosis, and treatment of pathophysiological disorders related to apoptosis.

Linvin, a novel inhibitor of apoptosis protein

Growing community of inventors

Ashburnham, MA, United States of America

Bruce Charles Gomes