Genentech, Inc.

Genencor International, Inc.

University of California

Genencor, Inc.

Other

Genetech, Inc.

James A Wells

Brian C Cunningham

Henry Bernard Lowman

David Aaron Estell

Richard Ray Bott

Scott Douglas Power

Marcus D Ballinger

Robert Mark Caldwell

Manuel Baca

Leonard G Presta

Germaine G Fuh

David J Matthews

Yvonne Man-Yee Chen

Paul J Carter

John P Burnier

Ross G Clark

Wayne J Fairbrother

Lars B Abrahmsen

Dennis J Henner

Kenneth C Olson

Steven H Bass

Ronald Greene

Jennifer T Jones

Mark X Sliwkowski

Adam Renslo

Melissa A Starovasnik

Erica M W Lauterwasser

Lisa J Garrard

Shaun D Fontaine

Andrew C Braisted

Benjamin B Spangler

Mark Zoller

Daniel G Yansura

Robin M Adams

Juan E Diaz

Alexander J Martinko

Sami Mahrus

David Brian Powers

Napoleone Ferrara

Robert S McDowell

Sachdev Singh Sidhu

J Kevin Judice

Eugenio Ferrari

David Y Jackson

Bruce A Keyt

Bing Li

Gregory A Weiss

Mark Ultsch

Michael George Mulkerrin

Francis Hung Nguyen

Gregg Weinschreider

Joseph H Hallock

Michael J Hornsby

Yun Mou

Mark S Sliwkowski

J Christopher Phelan

Abraham M DeVos

David T Jackson

Zachary B Hill

Leonard G Lowman

Chemically induced dimerizers (AbCIDs) have emerged as one of the most powerful tools to artificially regulate signaling pathways in cells; however, no facile method to identify or design these systems currently exists. The present invention provides a methodology to rapidly generate antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule-protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. Success of this strategy is demonstrated by generating ten chemically-inducible antibodies against the BCL-xL/ABT-737 complex. Three of the antibodies are highly selective for the BCL-xL/ABT-737 complex over BCL-xL alone. Two exemplary important cellular applications of AbCIDs are demonstrated by applying them intracellularly to induce CRISPRa-mediated gene expression and extracellularly to regulate CAR T-cell activation with the small molecule, ABT-737. ABT-737 is not toxic at the concentrations used to activate AbCIDs in cells. AbCIDs provided by this invention are new and orthogonal AbCIDs, expanding the limited toolbox of available CIDs.

Antibody chemically induced dimerizer (AbCID) as molecular switches for regulating cellular therapies

The disclosure is related to antibodies and antibody fragments that specifically bind the CUB domain-containing protein 1 (CDCP1) and their methods and uses in treating and detecting cancers.

Antibodies against CDCP1 for the treatment and detection of cancer

Presented herein are novel phosphotyrosine binding compositions, including antibodies and antibody fragments. The inventors of the present disclosure have resolved the crystal structures of two widely utilized pan-specific pY antibodies, PY20 and 4G10. These two known antibodies, although developed independently from animal immunizations, have surprisingly similar modes of recognition of the phosphate group, and revealed a generic binding structure among pan-specific pY antibodies. Based on this newly discovered convergent structure, engineered CDR-L3 loops were developed that impart greatly improved affinity to pY binding antibodies and other pY binding compositions. The inventions disclosed herein include antibodies and antibody fragments bearing these novel CDR-L3 sequences and methods of using such pY binding compositions for the detection of phosphotyrosine-bearing proteins.

Engineered antibodies for the detection of phosphorylated tyrosine

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5] decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier. 

Cyclic peroxides as prodrugs for selective delivery of agents

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5]decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier. 

The invention described herein features methods of isolating monoclonal antibodies or polypeptides that bind to a cell surface expressed antigen. The method of catch and release utilizes engineered protease site for cleavage antigen-antibody or antigen-polypeptide complexes. In some embodiments the protease cleavage site to cleave the complexes is an exogenous protease to mammalian cell. In various embodiments the protease cleavage site to cleave the complexes is an endogenous protease to mammalian cell.

Proteolytic release of cell surface antigens for phage biopanning

The present invention relates to the discovery of novel biomarkers of in vivo apoptosis based on a large number of caspase-like cleavage sites. These biomarkers are useful for detection and quantification of apoptosis in a biological sample. The invention also provides synthetic peptides and proteins corresponding to neo-epitopes created by proteolytic processing of these cleavage sites. The synthetic peptides can be used as standards to enable identification and quantitation of these biomarkers using mass spectrometry. The synthetic proteins can be used to generate antibodies and other binding reagents specific for these biomarkers. Methods for detecting apoptosis as well as for diagnosing or for providing a prognosis for a disease or disease state characterized by apoptosis are also provided herein. Finally, the invention provides compositions and kits for performing the methods of the invention.

Discovery of candidate biomarkers of in vivo apoptosis by global profiling of  caspase cleavage sites

The transformation yield of electroporation is increased by using higher DNA concentrations and DNA affinity purification. Fusion proteins of a viral coat protein variant and a heterologous polypeptide are useful in phage display systems.

Phage display

This invention provides general methods for selective labeling of proteins on their N-termini with synthetic peptides. The methods of this invention can be applied to the global proteomic profiling of complex mixtures of proteins and polypeptides.

Specific N-terminal labeling of peptides and proteins in complex mixtures

The invention provides variants of human growth hormone having an amino acid substitution at amino acid residue R77, numbered from the N-terminus of 191-amino add human growth hormone as well as nucleic acid molecules encoding these variants.

Growth hormone variants

The present invention provides heregulin variants that are capable of binding an ErbB receptor. Included in the invention are variants of human heregulins, and, in particular, variants of human heregulin-&#x3b2;1 having enhanced affinity for the ErbB-3 and ErbB-4 receptors. These variants include at least one amino acid substitution and can include further modifications. The invention also provides nucleic acid molecules encoding heregulin variants and related vectors, host cells, pharmaceutical compositions, and methods.

Heregulin variants

A crash worthy vehicle partition for securely separating the front of a vehicle from the rear of vehicle. The vehicle partition includes upper mounting brackets and lower mounting brackets that allow for limited, rearward motion of the vehicle parrition in the event of a rear-end collision to reduce the crash impact forces on front seat occupants. The vehicle partition further includes pivotable wings that are disposed on each side of the vehicle partition in a vehicle's side curtain airbag deployment zones. These pivota+e wings are mechanically retracted out of the side curtain airbag; deployment zones in the event of an airbag deployment event.

Crash appropriate vehicle partition

Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.

Anti-VEGF antibodies

Growing community of inventors

Burlingame, CA, United States of America

James A Wells