Merck Patent Gmbh

Emd Lexigen Research Center Corp.

Fuji Immunopharmaceuticals Corp.

Emd Serono Research Center, Inc.

Antisoma Research Limited

Abbott Biotech, Inc.

Merk Patent Gmbh

Merck Patent Gesellschaft MIT Beschraenkter Haftung

Stephen D. Gillies

Kin-Ming Lo

Yan Lan

Stephen D Gillies

Susan Xiuqi Qian

Pascal Andre Stein

Christa Burger

Suzanne P McKenzie

Gordon D Webster

Matthew Baker

Pascal André Stein

John S Wesolowski, Jr

Yukio Sudo

Yue Li

Nigel John Watkins

Mitsunori Ono

Hiroshi Kitaguchi

Jeffrey Charles Way

Simon Lawrence Goodman

Yumiko Wada

Yaming Wu

Ryoichi Nemori

Yuan Liu

Yaping Sun

Francesc Mitjans

Jaume Adan

Diane Hahn

Rakesh Verma

Steven C Degon

Aroop Sircar

Yumiko Jimbo

Nora Zizlsperger

Xiuqi Qian

Suzanne P Mckenzie

This invention relates generally to bifunctional molecules including (a) a TGF&#x3b2;RII or fragment thereof capable of binding TGF&#x3b2; and (b) an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1), uses of such molecules (e.g., for treating cancer), and methods of making such molecules.

Targeted TGF&#x3b2; inhibition

The invention discloses immunoglobulin fusion proteins designed to bind both CD47 and a tumor cell antigen. The immunoglobulin fusion proteins include a SIRP&#x3b1; moiety that binds CD47 and an antigen binding site for a tumor cell antigen.

SIRP-&#x3b1; immunoglobulin fusion proteins

Targeted TGF&#x3b2; inhibitors

Modified interleukin-12 (IL-12) p40 polypeptides are disclosed. The modified polypeptides have alterations in the IL-12p40 subunit to eliminate the protease site between positions Lys260 and Arg261. The modified IL-12p40 polypeptides according to the invention have improved stability compared to wild-type mature human IL-12p40 polypeptides.

Methods of treating cancer using interleukin-12p40 variants having improved stability

Disclosed are antibody fusion proteins with a modified FcRn binding site and nucleic acid molecules encoding them. The antibody fusion protein include two polypeptide chains, wherein the first polypeptide chain includes a biologically active molecule linked to at least a portion of an immunoglobulin constant region. The second polypeptide chain includes at least a portion of an immunoglobulin constant region. One of the polypeptide chains includes a mutation in the FcRn binding site that reduces binding to FcRn. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins for treating diseases and conditions alleviated by the administration of the fusion proteins.

Antibody fusion proteins with a modified FcRn binding site

A fusion protein of the invention comprises an immunoglobulin Fc region and a first target protein linked to the immunoglobulin Fc region. The first target protein comprises a collagen XVIII fragment, preferably endostatin. The immunoglobulin Fc region preferably comprises a hinge region, a Cregion, and a Cregion.

Expression and export of angiogenesis inhibitors as immunofusins

The invention relates to engineered antibodies which specifically bind to integrin receptors, especially the alpha V integrin receptor subunit. The antibodies comprise the antigen binding sites (CDRs) of a known mouse anti-integrin antibody, as well as hybrid light chain variable sequences, mutated heavy chain variable sequences (Frs) and modified heavy chain constant sequences. The novel antibodies have improved immunogenic and expression properties and elicit excellent anti-angiogenic as well as anti-tumor activities in humans in monotherapy but also and above all in combination with other angiogenesis and tumor inhibiting agents.

Engineered anti-alpha V-integrin hybrid antibodies

Disclosed are Fc-interferon-beta (Fc-IFN-&#x3b2;) fusion proteins and nucleic acid molecules encoding them. The Fc-IFN-&#x3b2; fusion proteins include variants of the interferon-beta (IFN-&#x3b2;) protein that are altered to achieve enhanced biological activity, prolonged circulating half-life and greater solubility. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins and/or nucleic acid molecules for treating diseases and conditions alleviated by the administration of interferon-beta.

Stabilization of Fc-interferon-beta fusion proteins

The invention provides a family of antibodies that specifically bind the human cell surface glycosphingolipid GD2. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies may be coupled to a therapeutic agent and used in the treatment of cancer.

Immunocytokine sequences and uses thereof

The invention provides a compound comprising a target specific portion and an effector portion wherein the target specific portion comprises or consists of a monoclonal antibody having specificity for oncofoetal fibronectin, or a fragment or variant thereof which retains the antigen binding specificity of the parent monoclonal antibody and the effector portion comprises or consists of interleukin-12, or a functional fragment or variant thereof, characterized in the monoclonal antibody having specificity for oncofoetal fibronectin binds to a region of oncofoetal fibronectin other than the ED-B region. The invention further provides nucleic acids encoding the compounds of the invention, and the use of such compounds in medicine, e.g. in the treatment of cancer.

Interleukin-12 targeted to oncofoetal fibronectin

A homodimeric protein of the invention has angiogenesis inhibiting activity. The homodimeric protein consists of two identical fusion proteins bound together as a homodimer. Each fusion protein comprises an immunoglobulin Fc region and a first target protein linked to the immunoglobulin Fc region. The first target protein has an angiogenesis inhibiting activity of angiostatin or endostatin, and is selected from the group consisting of a plasminogen fragment and a collagen XVIII fragment. The immunoglobulin Fc region comprises a hinge region, a CH2 region, and a CH3 region.

Nucleic acids encoding interleukin-12P40 variants with improved stability

Disclosed are methods and compositions for efficiently expressing antibody fusion proteins. Antibody fusion proteins of the invention include a hybrid antibody moiety containing sequences from more than one type of antibody and/or mutant antibody sequences. Hybrid antibody fusion proteins of the invention may be produced at high levels and may combine functional properties characteristic of different antibody types in addition to functional properties of a non-antibody moiety.

Proteins comprising an IgG2 domain

Disclosed herein are methods and compositions for enhancing the immunogenicity of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusion proteins bind Fc receptors on the surface of antigen presenting cells, thereby targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins to enhance or modulate a particular immune response against the preselected antigen.

Methods of using Fc-cytokine fusion proteins

Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens

Growing community of inventors

Lexington, MA, United States of America

Kin-Ming Lo