Sanofi

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

Dana-Farber-Cancer Institute Inc.

Genvec, Inc.

Ling Xu

Gary J Nabel

Zhi-Yong Yang

Lan Wu

Ercole Rao

Béatrice Cameron

Christian Beil

Tarik Dabdoubi

Catherine Prades

Cendrine Lemoine

Jochen Beninga

Edward Seung

Peter D Kwong

John R Mascola

Joseph G Sodroski

Tongqing Zhou

Richard Wyatt

Ronnie Rong Wei

Barna Dey

Wen Yuan

Shi-Hua Xiang

Joerg Thomas Regula

Huawei Qiu

Christian Lange

Jochen Kruip

Joerg Birkenfeld

Zhen Xing

Zhi-yong Yang

C Richter King

Jason G D Gall

Mark Connors

Young Do Kwon

Wulf Dirk Leuschner

Bimal Chakrabarti

Yue Huang

Jinghe Huang

Mangaiarkarasi Asokan

Amarendra Pegu

Chih-Chin Huang

Richard A Koup

Ronnie Wei

Nicole A Doria-rose

Lan VRC/NIAID/NIH Wu

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

Provided herein are bivalent, bispecific binding proteins that specifically bind to two different HIV-1 Env protein epitopes.

Bivalent, bispecific binding proteins for prevention or treatment of HIV infection

The disclosure provides methods of treating viral infection using trispecific binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind a CD38 polypeptide (e.g., human and/or cynomolgus monkey CD38 polypeptides), a CD28 polypeptide, and a CD3 polypeptide.

Trispecific anti-CD38, anti-CD28, and anti-CD3 binding proteins and methods of use for treating viral infection

The disclosure provides binding proteins that bind CD38 polypeptides, e.g., human and cynomolgus monkey CD38 polypeptides. For example, the binding proteins can be monospecific, bispecific, or trispecific binding proteins with at least one antigen binding domain that binds a CD38 polypeptide. The disclosure also provides methods for making binding proteins that bind CD38 polypeptides and uses of such binding proteins.

Anti-CD38 antibodies and methods of use

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a subject.

Conformationally stabilized HIV envelope immunogens

The present disclosure provides compositions for eliciting an immune response, including a prophylactic immune response, against human immunodeficiency virus. The composition includes nucleic acid constructs encoding HIV antigenic polypeptides of multiple clades or strains. Methods for eliciting an immune response by administering the composition to a subject are also provided.

Method for inducing a multiclade immune response against HIV utilizing a multigene and multiclade immunogen

Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.

Conformationally stabilized HIV envelope immunogens and triggering HIV-I envelope to reveal cryptic V3-loop epitopes

Growing community of inventors

Bridgewater, NJ, United States of America

Ling Xu