Medimmune Limited

The University of Texas System

Ludwig Institute for Cancer Research Limited

Medimmine, LLC

William Dall'Acqua

Herren Wu

Leslie Sydnor Johnson

Melissa Marie Damschroder

Elizabeth Sally Ward

Peter Kiener

Anthony Coyle

Ronald Herbst

Elizabeth Sally Ward Ober

Ralph Raymond Minter

Vahe Bedian

Andrew Grier Buchanan

Michael A Bowen

Ping Tsui

Martin Borrok, Iii

Jeffrey Brown

Jean-Christophe Renauld

Jacques Van Snick

Christian B Allan

Catherine Uyttenhove

Jeffrey S Swers

Jose Casas-Finet

Vaheh Oganesyan

Yanli Wu

Jennifer Lynne Reed

Chris Stannard

Jose Casa-Finet

Olga Lubman

Francoise Cormont

Nurten Beyaz-Kavuncu

The present invention provides molecules, including proteins, more particularly, immunoglobulins whose in vivo half-lives are altered (increased or decreased) by the presence of an IgG constant domain, or FcRn binding fragment thereof (e.g., an Fc region or hinge-Fc region) (e.g., from a human IgG, e.g., human IgG1), that have modifications of one or more of amino acid residues in at least the CH3 domain.

Molecules with altered neonate Fc receptor binding having enhanced therapeutic and diagnostic properties

Stabilized antibodies directed to Angiopoeitin-2 and uses of such antibodies are described. Nucleic acid and amino acid sequences, hybridomas or other cell lines for expressing such antibodies are also provided.

Stabilized angiopoietin-2 antibodies and uses thereof

Provided are polypeptides comprising a variant IgG Fc domain, wherein the polypeptides exhibit reduced or ablated effector functions (e.g., ADCC and/or CDC) and increased stability and plasma half-life compared to a parent polypeptide. Also provided are compositions, methods of treatment, and methods to diminish Fc-induced effector function in a parent polypeptide.

Molecules with reduced effector function and extended half-lives, compositions, and uses thereof

The present invention provides chimeric and humanized versions of anti-CD19 mouse monoclonal antibodies. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD19 antigen and that may mediate ADCC, CDC, and/or apoptosis for the treatment of B cell diseases and disorders, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft-versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.

Humanized anti-CD19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease

The present invention provides molecules, including IgGs, non-IgG immunoglobulins, proteins and non-protein agents, that have increased in vivo half-lives due to the presence of an IgG constant domain, or a portion thereof that binds the FcRn, having one or more amino acid modifications that increase the affinity of the constant domain or fragment for FcRn. Such proteins and molecules with increased half-lives have the advantage that smaller amounts and or less frequent dosing is required in the therapeutic, prophylactic or diagnostic use of such molecules.

Molecules with extended half-lives, compositions and uses thereof

Isolated nucleic acids encoding anti-CD19 mouse monoclonal antibodies are described herein. Also described are expression vectors, host cells and a method of producing anti-CD19 antibodies.

Humanized anti-CD19 antibodies

Provided herein are crystalline forms of a human IgG Fc variant comprising triple-mutation M252Y/S254T/T256E that provides for increased binding affinity to human neonatal Fc receptor, methods of obtaining such crystals and high-resolution X-ray diffraction structures and atomic structure coordinates. Also provided are machine readable media embedded with the three-dimensional atomic structure coordinates of the human IgG Fc variant and methods of using them.

Crystals and structure of a human IgG Fc variant with enhanced FcRn binding

The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., Fc&#x3b3;Rs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more Fc&#x3b3;R and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

Modulation of antibody effector function by hinge domain engineering

The invention provides method for therapeutic protein drug development that incorporates therapeutic and/or formulation and/or manufacturing considerations in the early screening process. The approach involves screening a plurality of different variants of a domain that have been determined to have the desired therapeutic property to identify one or more variants that have desired therapeutic and/or formulation characteristics, and constructing the full multidomain proteins using the identified domain variants. The present invention also provides a method for determining the shelf life of multidomain proteins in formulations. The method comprises determining a thermal denaturation and/or renaturation curve of a domain of the protein whose unfolding leads to aggregation of the protein in a solution. The method evaluates the shelf life of the multidomain protein based on the denaturation/renaturation curve. The invention also provides methods for engineering multidomain proteins to improve their therapeutic and/or formulation characteristics.

Integrated approach for generating multidomain protein therapeutics

Growing community of inventors

Gaithersburg, MD, United States of America

William Dall'Acqua