Ap Biosciences Inc.

Kalobios Pharmaceuticals, Inc.

Multispan, Inc.

Kalobios, Inc.

Leland Stanford Junior University

Allgenesis Biotherapeutics Inc.

Innovent Biologics, Inc.

Innovent Biologis, Inc.

Jeng-Horng Her

Ching-Hsuan Hsu

Robert F Balint

Jhong-Jhe You

Po-Lin Huang

Huang-Tsu Chen

Samuel X Li

Helena S Mancebo

Hsin-Ta Hsieh

Hung-Tsai Kan

Ting-Yi Chang

Jianfu L Wang

Christopher Robert Bebbington

Geoffrey T Yarranton

Helen M Blau

Kenneth Luehrsen

Thomas S Wehrman

Peter Flynn

Pei-Tzu Wu

Jiun-Shyang Leou

Kevin Zen

Antibodies that include an antigen binding region that binds to CD137 are provided herein. Also provided herein are bispecific antibodies that include a first antigen binding region that binds to CD137 and a second antigen binding region that binds to an immune checkpoint molecule, an immune stimulatory molecule, or a tumor antigen. Pharmaceutical compositions that include the antibodies and methods of treating cancer are provided.

Bispecific CD137-binding antibodies for T-cell activation

Provided are monospecific and bispecific proteins that bind specifically to OX40 and/or PD-L1. Exemplary proteins release the inhibition through PD-L1 and stimulate T cell through OX40. Exemplary polyvalent proteins comprise at least one OX40 binding site and at least one PD-L1 binding site. In certain embodiments, the binding sites may be linked through an immunoglobulin constant region. Anti-OX40 and anti-PD-L1 antibodies are also provided.

PD-L1 and OX40 binding proteins for cancer regulation

Provided are bispecific proteins that comprise a binding domain binding cell surface protein and a vascular endothelial growth factor (VEGF) inhibiting domain. Provided also is an antibody-drug conjugate that comprises a therapeutic agent and an antibody or an antigen-binding fragment binding PD-L1 and/or a VEGF inhibiting domain, wherein the therapeutic agent is covalently conjugated to the antibody or the antigen-binding fragment by a linker.

Bifunctional proteins combining checkpoint blockade for targeted therapy

CD137 antibodies for T-cell activation

PD-L1 and OX40 binding proteins for cancer Regulation

The invention provides bispecific fusion proteins that inhibit activation of complement pathway and vascular endothelial growth factor (VEGF) pathway and methods for using these fusion proteins.

Protein inhibitors to complement and VEGF pathways and methods of use thereof

Fusion proteins containing a PDGF binding portion, a VEGF binding portion, and an Fc antibody region are described. Also described are nucleic acids encoding the fusion proteins, compositions comprising the fusion proteins, and methods of using the fusion proteins for treating or preventing clinical conditions characterized by abnormal angiogenesis, such as vascular permeability, edema or inflammation.

Fusion protein comprising a ligand binding domain of VEGF and PDGF

The present invention provides expression vectors that facilitate high levels of expression of GPCR proteins. Encompassed by the invention are methods and compositions for recombinant cell lines expressing GPCR proteins with the aid of the expression vectors of the instant invention. The recombinant cell lines of the instant invention express GPCR proteins at levels of at least about 150,000 copies of the protein per cell. The present invention also provides methods and compositions for raising antibodies against GPCR proteins using the high expressing recombinant cells of the instant invention.

GPCR expression vector

Methods and compositions for detecting molecular interactions, particularly protein-protein interactions, using at least two inactive, weakly-complementing &#x3b2;-lactamase fragments are provided. The invention allows detection of such interactions in eukaryotic and mammalian cells, in situ or in vitro. Detection of molecular interactions in mammalian cells is not limited to the nuclear compartment, but can be accomplished in the cytoplasm, cell surface, organelles, or between these entities. Methods provided utilize novel compositions comprising fusion proteins between molecules of interest and inactive, weakly-complementing &#x3b2;-lactamase fragments. Association of the molecules of interest brings the corresponding complementary &#x3b2;-lactamase fragments into close enough proximity for complementation to occur and &#x3b2;-lactamase activity to be observed. The invention is useful in the study of protein-protein interactions, functional genomics, agonist and antagonist screening and drug discovery.

Detection of molecular interactions by &#x3b2;-lactamase reporter fragment complementation

The present invention provides methods of making antibodies having the binding specificity of a reference antibody. Antibodies generated by the methods of the inventions have at least one minimal essential binding specificity determinant from a heavy chain or light chain CDR3 from the reference antibody. The method can be used, e.g., in humanization procedures. The invention also provides libraries and antibodies made in accordance with the methods.

Antibody specificity transfer using minimal essential binding determinants

GPCR-expressing cell lines

Interaction-activated circularly permutated proteins are disclosed that depend for their functional reassembly into the parent protein on the interaction of heterologous polypeptides or other molecules which have been genetically or chemically conjugated to the break-point termini of engineered enzymes. In addition, methods are provided for identifying circularly permutated marker proteins that will optimally reassemble into a functional parent protein, and which are dependent on the association of heterologous interactor domains. The invention is exemplified by circular permutations of a Class A &#x3b2;-lactamase (TEM-1 of). Circularly permutated marker proteins that comprise molecular interaction-dependent enzymes particularly find use in (1) cell-based sensors for activation or inhibition of metabolic or signal transduction pathways for high-efficiency, (2) high-throughput screening for agonists/antagonists of the target pathway and in high-throughput mapping of pair-wise protein-protein interactions within and between the proteomes of cells, tissues, and pathogenic organisms, and in (3) cell-based screens for high-throughput selection of inhibitors of any protein-protein interaction.

Circularly permutated, interaction-activated proteins

This invention provides methods of obtaining a binding molecule, e.g., an antibody, that has enhanced affinity for a binding partner relative to a reference binding molecule.

Methods for affinity maturation

This invention provides methods and systems for linking the functional activation of a responder molecule to the interaction of two or more binding ensemble members of interest either in vitro or in vivo, and thereby producing a signal, phenotype, or other functional output in response to the interaction of the binding ensemble members. The systems comprise a responder, an inhibitor of the responder, and an inhibitor of the inhibitor, or 'reactivator' of the responder, and interacting components. Two binding ensemble members are complexed to the other components of the system in such a way that interaction of the binding ensemble members, either directly or via additional ensemble members, causes a shift in the equilibrium of inhibitor binding from the responder to the reactivator, thereby functionally activating the responder.

Growing community of inventors

San Jose, CA, United States of America

Jeng-Horng Her