Merck Sharp + Dohme Corp.

Other

Merck + Co., Inc.

Merck Sharpe & Dohme Corp.

The Wellcome Trust Limited as Trustee for the Wellcome Trust

Holly A Hammond

Jon H Condra

Ayesha Sitlani

Shilpa Pandit

Yan Li

Pingyu Zhong

Feng Dong

Rose M Cubbon

Kevin Caili Wang

Jeffrey T Blue

Laurence B Peterson

Denise K Nawrocki

Joseph C Santoro

Sonia M Gregory

Dana D Wood

Henryk Mach

Michael L Metzker

John W Hess

David L Gerhold

Charles T Caskey

Michael S Phillips

Yusuke Nakagawa

Patricia Hey

Yoshihiko Kawaguchi

John A Todd

Roger D Cox

Tony R Merriman

Peter Peizhi Luo

Timothy McCabe

Heidi Pixley

Peizhi (Peter) Luo

Rebecca C J Twells

Heidi Yoder

Laura Orsatti

Rebecca Cj Twells

Carl P Sparrow

Timothy Mccabe

Antagonists of human proprotein convertase subtilisin-kexin type 9 ('PCSK9') are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

1B20 PCSK9 antagonists

1D05 PCSK9 antagonists

Antagonists of human proprotein convertase subtilisin-kexin type 9 ('PCSK9') are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Antagonists of PCSK9

A novel receptor, 'LDL-receptor-related protein-5' ('LRP-5'), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.

Method of screening for modulator of LRP5 activity

A novel receptor, &ldquo;LDL-receptor related protein-3&rdquo; (&ldquo;LRP-3&rdquo;), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.

LDL-receptor

Receptor

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Telford, PA, United States of America

Holly A Hammond