Genzyme Corporation

Sanofi

Xilio Development, Inc.

Genzyme Coporation

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Huawei Qiu

Clark Qun Pan

James E Stefano

Sunghae Park

Pradeep K Dhal

Qun Zhou

Bo Chen

Raphael Rozenfeld

Parker Johnson

Julie Bird

Margaret Karow

Ronnie Rong Wei

Cendrine Lemoine

Ronan O'Hagan

Robert J Miller

Gary J Nabel

Ercole Rao

Kurt Jenkins

Peter D Kwong

Joerg Thomas Regula

John R Mascola

Luis Z Avila

Tongqing Zhou

Andreas Menrad

Christian Lange

Magali Mathieu

William Harold Brondyk

Jochen Kruip

Mark Connors

Dheeraj Singh Tomar

Patrick Finn

Kevin Brower

Christopher Winter

Béatrice Cameron

Young Do Kwon

Diego A Gianolio

Feng Song Liu

Tarik Dabdoubi

Christian Beil

Catherine Prades

Ling Xu

Zhi-Yong Yang

Gloria Matthews

Jochen Beninga

Lan Wu

Edward Seung

Joerg Birkenfeld

Ugur Eskiocak

Wulf Dirk Leuschner

Jinghe Huang

Deborah Moore Lai

Rao Koduri

Joachim Theilhaber

Marcella Yu

Richard C Gregory

Natalia Malkova

Parminder Mankoo

Jack R Pollard

Gary Shapiro

Srinivas Shankara

Daniel Snell

Gina Lacorcia

Marie Mandron

Jonathan Rothblatt

Zhen Xing

Benjamin Kebble

Aaron Moulin

Kara Carter

Michael O'Callaghan

Pradeep Dhal

Yangde Chen

Francis Duffieux

Mangaiarkarasi Asokan

Amarendra Pegu

Diego Gianolio

Clark Pan

Marie-Priscille Brun

Rebecca Sendak

Scott M Van Patten

Kenneth P Karey

Yves Sabbagh

Yu Qiu

Yanfeng Zhou

HyunSuk Cho

James Stefano

Richard A Koup

Ronnie Wei

Magali Pederzoli-Ribeil

Rebekah Kay O'donnell

Robert Miller

Feng Liu

Nicole A Doria-rose

The present disclosure is related to improved compositions and methods for treating T-cell-mediated diseases and disorders (e.g., autoimmune disorders, graft-versus-host-disease, and graft rejection). Provided are anti-apβTCR binding polypeptides, including antibodies, which comprise at least one amino acid substitution or modification that increases the stability of the binding polypeptide by reducing fragmentation of the light chain variable region. The methods provided herein generally involve administering to a subject in need thereof an effective amount of a stabilized, humanized binding polypeptide that is specific to the alpha beta T-cell receptor (apβTCR).

Anti-alpha beta TCR binding polypeptides with reduced fragmentation

The present disclosure provides tumor-specific cleavable linkers and their use in drugs and prodrugs for delivering therapeutics to a tumor cell environment. The present disclosure also provides cleavage products of said drugs and prodrugs, and methods related to the use of the same.

Tumor-specific cleavable linkers

The present invention concerns antibodies and antigen-binding fragments of antibodies which specifically bind to and neutralize Chikungunya virus (CHIKV) and which are engineered to develop therapeutics in order to treat CHIKV disease or prevent CHIKV infection. The invention also relates to pharmaceutical compositions comprising antibodies of the invention and the use of the antibodies for the prevention and treatment of CHIKV disease.

Anti-CHIKV antibodies and uses thereof

Provided herein are trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation, and wherein and a second pair of polypeptides possess a single variable domain forming a single antigen binding site. In some embodiments, the binding proteins comprise a binding site that binds a CD28 polypeptide, a binding site that binds a CD3 polypeptide, and a binding site that binds a third polypeptide, such as a tumor target protein. In some embodiments, the binding proteins comprise four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins. The disclosure also relates to methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins.

Trispecific binding proteins, methods, and uses thereof

A modified IgG antibody binds and neutralizes TGFβ1 selectively and with high affinity and avidity. The modified IgG antibody comprises four polypeptide chains and may comprise modifications to the elbow regions of the polypeptide chains. The modified IgG antibody may comprise the same VH and VL domains or CDR regions as metelimumab. The modified IgG anti-body is useful in therapeutic and diagnostic applications.

Modified-IgG antibodies that bind transforming growth factor-β1 with high affinity, avidity and specificity

The current disclosure provides binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof (e.g., antibody-drug conjugates or ADCs), comprising a site-specifically engineered drug-glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

Site-specific antibody-drug conjugation through glycoengineering

Provided are recombinant and chemically-conjugated antibodies and fragments thereof modified with one or more poly-aspartate (poly-D) peptides (e.g., a D10 sequence) to improve localization of the antibodies or fragments to bone. Methods of making and using of these antibodies and fragments also are disclosed.

Bone-targeting antibodies

The invention provides an improved pan-TGF-β antibody for treatment of conditions that are mediated by TGF-β, including autoimmune diseases, fibrotic conditions, and cancers. Also provided are methods and uses of the antibody in conjunction with other immunomodulatory agents such as an anti-PD-1 antibody.

Anti-TGF-beta antibodies and their use

An scFv-Fc dimer binds and neutralizes TGFβ1 selectively and with high affinity and avidity. The scFv region may comprise the same VH and VL domains or CDR regions as metelimumab. The unique combination of their smaller size, high selectivity, potency against TGFβ1, and long in vivo half-life makes the scFv-Fc dimers ideal candidates for therapeutic applications.

scFv-Fc dimers that bind transforming growth factor-β1 with high affinity, avidity and specificity

Engineered antibodies that are stable and can be conjugated to a ligand or drug at a ligand/drug to antibody ratio of above 3, making these conjugates suitable for treatment of a variety of indications, are provided. Methods of producing these engineered antibodies are also provided.

Modified binding polypeptides for optimized drug conjugation

Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Masked IL-2-Fc fusion polypeptides

A modified IgG antibody binds and neutralizes TGF&#x3b2;1 selectively and with high affinity and avidity. The modified IgG antibody comprises four polypeptide chains and may comprise modifications to the elbow regions of the polypeptide chains. The modified IgG antibody may comprise the same VH and VL domains or CDR regions as metelimumab. The modified IgG anti-body is useful in therapeutic and diagnostic applications.

Modified-IgG antibodies that bind transforming growth factor-BETA1 with high affinity, avidity and specificity

Masked cytokine polypeptides

Provided are binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof, comprising a CH1 domain (e.g., a human IgG1 CH1 domain), wherein the CH1 domain has an engineered N-linked glycosylation site at amino acid position 114, according to Kabat numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

Hyperglycosylated binding polypeptides

Growing community of inventors

Westborough, MA, United States of America

Huawei Qiu