The Scripps Research Institute

Scripps Clinic and Research Foundation

Other

Medical Research Council

Stratagene

Hesperix Sa

Palo Alto Research Center Inc.

Johnson & Johnson Gmbh

Medical Research Institute

Catalyst Assets LLC

Zebra Biologics, Inc.

Zebra Biologies, Inc.

Richard A. Lerner

Angray Kang

Carlos Barbas

Richard A Lerner

Carlos F Barbas, Iii

Kim D Janda

Carlos F Barbas

Joseph A Sorge

Gregory Paul Winter

Dennis R Burton

Lutz Riechmann

Angray Singh Kang

Dale L Boger

Henry L Niman

Guofu Zhong

Alfonso Tramontano

Jia Xie

William D Huse

Stephen J Benkovic

D Elliot Parks

Hongkai Zhang

Benjamin List

Sydney Brenner

Benjamin F Cravatt

Christoph Rader

Ian A Wilson

Richard S Smith

Joakim Dillner

Steven J Henriksen

Juergen Wagner

Andrew D Napper

Chi-Huey Wong

Dmitry Dmitrievich Genkin

Ann M Moriarty

Peter Wirsching

Norton B Gilula

Hannah Alexander

Doron Shabat

Jean-Louis Reymond

Alexander Gabibovich Gabibov

Hicham Fenniri

Subhash C Sinha

James L Bittle

Alexey Anatolievich Belogurov

Changshou Gao

Ronald M Lindsay

Alexey Vyacheslavovich Stepanov

Peter G Schultz

Samuel J Danishefsky

Richard H Bruce

Douglas N Curry

Robert Thomas Krivacic

Huangpin Ben Hsieh

James P Light, Ii

Philip E Dawson

Vaughn V Smider

Jan Grunewald

Meng-Lin Tsao

Elizabeth D Getzoff

Gary E Siuzdak

Frank J Dixon

Argyrios N Theofilopoulos

Yuanwei Chen

Andreas Koch

Jonathan Rosenblum

Erling C Norrby

Victoria A Roberts

John A Tainer

Roshan Perera

Ben Cravatt

Amnon Altman

Patricia McDonald

Emmanuel Sturchler

Rajesh Grover

Xueyong Zhu

Diane Schloeder

Brent L Iverson

Yingjie Peng

Jon A Ashley

Ii Light James Paul

Iii Barbas Carlos F

Described are methods for providing personalized medicine for the treatment of B cell malignancies including lymphoma. The methods make use of Chimeric Antigen Receptor (CAR) technology.

Articles and methods directed to personalized therapy of cancer

The invention provides TrkB agonist antibodies or antigen-binding fragments that specifically enhance TrkB signaling activities. The invention also provides therapeutic methods of using such antibodies for promoting survival and regeneration of retinal ganglion cells, and for treating or preventing subjects suffering from or at risk of developing various neurodegenerative conditions such as glaucoma.

TrkB agonist antibodies and methods for treating an ocular degenerative disorder characterized by degeneration of retinal ganglion cells (RGCs)

The present invention provides methods for generating functional derivatives of effector polypeptides (e.g., hormones and receptor ligands) embedded in a different protein scaffold (e.g., antibody scaffolds). The methods involve modifying the effector polypeptide with a combinatorial library of terminal linker sequences, inserting the modified sequences into the host scaffold, and then selecting functional derivatives from the library of modified polypeptide sequences embedded in the host scaffold. As exemplifications, the invention also provides specific functional derivatives of leptin, scFSH and scRelaxin embedded in an antibody scaffold, as well as therapeutic applications of such functional fusion molecules.

Methods and compositions related to functional polypeptides embedded in heterologous protein scaffolds

The invention provides combinatorial peptide or polypeptide libraries that can become membrane tethered once expressed in cells. The invention additionally provides methods for selecting peptide modulators (e.g., agonists) of GPCRs from the combinatorial libraries of the invention. The invention also provides novel GPCR polypeptide modulators, e.g., biased polypeptide agonists of the glucagon-like peptide 1 receptor (GLP-1R). The invention further provides methods of promoting insulin sensitivity, lowering blood glucose, and reducing body weight as well as methods for treating various diseases such as diabetes and obesity.

Methods and compositions related to GPCR agonist polypeptides

The invention provides methods for identifying binding partners (e.g., peptide ligands) that binds to a target protein (e.g., a cellular receptor). The methods entail co-localized expression of the target protein and candidate binding partners, and selection of binding partners based on their proximity in the plasma membrane.

Proximity based methods for selection of binding partners

The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist of a target molecule (e.g., a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

Methods and compositions related to modulators of eukaryotic cells

Methods for Identifying protein modulators of eukaryotic cells by expressing a combinatorial library of potential agonists inside a eukaryotic cell and then directly selecting for an agonist of a target molecule. Some methods involve co-culturing a cell expressing a combinatorial library of potential agonists and a second cell, and then selecting agents that modulate a phenotype of or a desired cellular response in the second cell. Preferably, the agonists are antibodies introduced into and expressed in the starting cells, such as agonist anti-EpoR, anti-TpoR, or G-CSFR antibodies. Also disclosed are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

Provided herein methods of alleviating the symptoms of multiple myeloma in a patient or subject in need thereof, methods of treating multiple myeloma in a patient or subject, and methods of preventing development of multiple myeloma in a patient at risk thereof, such as a patient with monoclonal gammopathy of undetermined significance (MGUS), which methods include administering an agent effective to treat ainfection. The invention also relates to a new class of antigen, MG281 protein {also referenced as Protein M), that binds to various immunoglobulins with high affinity, and their uses in purifying immunoglobulins. The invention additionally relates to using MG281 protein and analog or derivative molecules for treating autoimmune diseases. Further provided are antigens and antibodies for use in the disclosed methods, and the identification of molecules that bind to MG281 protein.

Immunoglobulin-binding human mycoplasma antigens and methods of use thereof

The present invention relates to a method for isolating from the immunological gene repertoire a gene coding for a receptor having the ability to bind a preselected ligand. Receptors produced by the gene isolated by the method, particularly catalytic receptors, are also contemplated.

Method for producing polymers having a preselected activity

The present invention comprises methods and compositions for producing and/or enhancing an immunological response in a subject against a target moiety such as a disease-related moiety by administration of an antigenic version of the target moiety having one or more unnatural amino acid and/or by administration of an antibody against a version of a target moiety having one or more unnatural amino acid which antibody is cross reactive with the natural target moiety.

Breaking immunological tolerance with a genetically encoded unnatural amino acid

The present invention provides antibody targeting compounds in which the specificity of the antibody has been reprogrammed by covalently or noncovalently linking a targeting agent to the combining site of an antibody. By this approach, the covalently modified antibody takes on the binding specificity of the targeting agent. The compound may have biological activity provided by the targeting agent or by a separate biological agent. Various uses of the invention compounds are provided.

Antibody targeting compounds

Filamentous phage comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a filamentous phage coat protein membrane anchor domain fused to at least one of the polypeptides.

Heterodimeric receptor libraries using phagemids

Method for tapping the immunological repertoire

Nine efficient aldolase antibodies were generated using hapten 2. This hapten combines, in a single molecule, structural components employed for reactive immunization with structural components employed for forming a transition state analog of the aldol reaction. Characterization of two of these antibodies reveals that they are highly proficient (up to 1000-fold better than any other antibody catalyst) and enantioselective catalysts for aldol and retro-aldol reactions and exhibit enantio- and diastereo-selectivities opposite that of antibody 38C2.

Antibody catalysis of enantio- and diastereo-selective aldol reactions

Growing community of inventors

La Jolla, CA, United States of America

Richard A Lerner