Leland Stanford Junior University

Aravive Biologics, Inc.

Akso Biopharmaceutical, Inc.

Mihalis S Kariolis

Jennifer R Cochran

Amato J Giaccia

Douglas Scott Jones

Yu Rebecca Miao

Katherine Cynthia Fuh

Erinn Bruno Rankin

Ping-Chuan Tsai

Todd A Aguilera

Raymond Tabibiazar

Susan Hershenson

Adam Silverman

Patrick O'Connor

Kaushik Thakkar

Xin Eric Zhang

The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Fusion proteins comprising an engineered knottin peptide and uses thereof

The invention is directed to novel sPD-1 variant&#x2014;Fc fusion proteins.

SPD-1 variant# FC fusion proteins

Provided herein are compositions and methods for alleviating cancer or infection in a subject by administering a therapeutically effective amount of a pharmaceutical composition comprising an isolated PD-1 variant polypeptide. The PD-1 variant polypeptide can inhibit the activity of PD-1 by, for example, competitive or non-competitive inhibition of the interaction between wild-type PD-1 and one or more of its ligands, PD-L1 and PD-L2.

Receptor-based antagonists of the programmed cell death 1 (PD-1) pathway

Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL, MER or Tyro3 protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.

Modified AXL peptides and their use in inhibition of AXL signaling in anti-metastatic therapy

Compositions and methods are provided for treating fibrosis in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits AXL, MER or Tyro3 protein activity, for example by inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.

Antifibrotic activity of GAS6 inhibitor

The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform for increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.

Compositions and methods are provided for alleviating endometriosis, kidney disease, inflammatory disease and/or transplant rejection in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits AXL, MER or Tyro3 protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.

Inhibition of AXL/GAS6 signaling in the treatment of liver fibrosis

Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.

Inhibition of AXL signaling in anti-metastatic therapy

Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against &#x3b1;&#x3b2;integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to &#x3b1;&#x3b2;integrin or to both &#x3b1;&#x3b2;and &#x3b1;&#x3b2;integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for &#x3b1;&#x3b2;integrin.

Growing community of inventors

Stanford, CA, United States of America

Mihalis S Kariolis