Denali Therapeutics Inc.

Washington University

Adam P Silverman

Mark S Dennis

Joy Yu Zuchero

Mihalis S Kariolis

Ryan Jefferson Watts

Ankita Srivastava

Xiaocheng Chen

Yin Sheng Zhang

Robert C Wells

Cathal S Mahon

David Michael Holtzman

Hong Jiang

Anastasia Henry

Thu Nga Bien-Ly

Jing Guo

Rinkan Shukla

Rachel Prorok

Bettina Van Lengerich

Kathryn M Monroe

Joshua I Park

Suresh Poda

Fan Liao

Do Jin Kim

Rishi Rakhit

Zhenyu Gu

Lesley Ann Kane

Joseph W Lewcock

Jennifer A Getz

Julie Ullman

Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.

Methods of engineering transferrin receptor binding polypeptides

The present disclosure encompasses compositions and methods for effectively treating at least one symptom or sign of Aß plaque or cerebral amyloid angiopathy (CAA) associated symptoms, or for decreasing amyloid plaque load or CAA load. The method comprises administering an effective amount of an anti-ApoE antibody to a mammalian subject, such as to a human.

Anti-ApoE antibodies

Provided herein are fusion proteins that comprise an enzyme replacement therapy enzyme and an Fc region, as well as methods of using such proteins to treat a lysosomal storage disorder. Methods for transporting agents across the blood-brain barrier are also provided herein.

Fusion proteins comprising enzyme replacement therapy enzymes

Engineered transferrin receptor binding polypeptides

In one aspect, antibodies that specifically bind to a human BACE1 protein are provided herein. In some embodiments, the antibodies contain modifications that reduce effector function, extend serum stability or serum half-life, or promote heterodimerization. In other aspects, bispecific antibodies and pharmaceutical compositions comprising antibodies that bind to human BACE1 protein are provided herein. Methods for inhibiting amyloid-&#x3b2; formation and/or aggregation, inhibiting amyloid plaque formation, and treating neurodegenerative diseases are also provided herein.

Anti-BACE1 antibodies and methods of use thereof

In some aspects, the present invention provides chimeric transferrin receptor (TfR) polynucleotides and polypeptides. In other aspects, this invention provides chimeric TfR transgenic animal models and methods of using the animal models to identify therapeutics that can cross the blood-brain barrier.

Transferrin receptor transgenic models

In one aspect, antibodies that specifically bind to a human Tau protein are provided. In some embodiments, an anti-Tau antibody recognizes an epitope within residues 111-125 of full-length human Tau, an epitope within residues 251-270 and/or residues 346-360 of full-length human Tau, or an epitope within residues 186-205 of full-length human Tau. In some embodiments, an anti-Tau antibody specifically binds to phosphorylated human Tau, unphosphorylated human Tau, and/or multiple splice isoforms of human Tau. An anti-Tau antibody disclosed herein may also include one or two modified Fc polypeptides.

Anti-Tau antibodies and methods of use thereof

The present disclosure encompasses compositions and methods for effectively treating at least one symptom or sign of A plaque or cerebral amyloid angiopathy (CAA) associated symptoms, or for decreasing amyloid plaque load or CAA load. The method comprises administering an effective amount of an anti-ApoE antibody to a mammalian subject, such as to a human.

In one aspect, antibodies that specifically bind to a human triggering receptor expressed on myeloid cells 2 (TREM2) protein are provided. In some embodiments, the antibody decreases levels of soluble TREM2 (sTREM2). In some embodiments, the antibody enhances TREM2 activity.

Anti-TREM2 antibodies and methods of use thereof

Growing community of inventors

South San Francisco, CA, United States of America

Adam P Silverman