Harpoon Therapeutics, Inc.

Werewolf Therapeutics, Inc.

Amphivena Therapeutics, Inc.

Other

Takeda Pharmaceutical Company Limited

Anji Bruno, LLC

Luke Evnin

Jeanmarie Guenot

Patrick A Baeuerle

Vinay Bhaskar

William Winston

Cynthia Seidel-Dugan

Heather R Brodkin

Jose Andres Salmeron Garcia

Robert B Dubridge

Daniel Hicklin

Richard J Austin

Bryan D Lemon

Lori Kunkel

Holger Wesche

Melvyn Little

Vanitha Ramakrishnan

Uwe Reusch

Stefan Knackmuss

Ivica Fucek

Kristina Ellwanger

Erich Rajkovic

Judith A Fox

Michael Weichel

Pui Seto

Vera Molkenthin

Eugene Zhukovsky

Claudia Wall

Anand Panchal

Maia Vinogradova

Giselle Knudsen

Daniel J Hicklin

Jeanmarie Dean Guenot

The disclosure features fusion proteins that are conditionally active variants of IL-12. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g., a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling.

Activatable interleukin 12 polypeptides and methods of use thereof

The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment.

Constrained conditionally activated binding proteins

Provided herein are trispecific antigen-binding proteins comprising a domain binding to CD3, a half-life extension domain, and a domain binding to a target antigen. Also provided are pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such trispecific antigen-binding proteins. Also disclosed are methods of using the disclosed trispecific antigen-binding proteins in the prevention, and/or treatment diseases, conditions and disorders.

Trispecific binding proteins and methods of use

The disclosure features fusion proteins that are conditionally active variants of IL-2. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g., a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling.

Activatable interleukin-2 polypeptides and methods of use thereof

Described herein are binding proteins that specifically bind to human CD33, and in particular to bispecific binding proteins that specifically bind to human CD33 and human CD3. Also described herein are bispecific tandem diabodies that bind to CD33 and CD33, and their uses for immunotherapy of CD33cancers, diseases and conditions such as acute myeloid leukemia (AML).

Methods of using bispecific CD33 and CD3 binding proteins

Provided herein are separation moieties that are suitable for use in conjunction with a variety of therapeutic payloads. The separation moieties serve to generate conditionally active macromolecules whereby the macromolecules have reduced or minimal biological activity until the separation moieties are modified under specific conditions.

Separation moieties and methods of use thereof

Disclosed herein are single chain variable fragment CD3 binding proteins with improved binding affinities, and robust aggregation profiles. Also described are multispecific binding proteins comprising a single chain variable fragment CD3 binding protein according to the instant disclosure. Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations are provided.

Single chain variable fragment CD3 binding proteins

Disclosed herein are single domain serum albumins binding proteins with improved thermal stability, binding affinities, and robust aggregation profiles. Also described are multispecific binding proteins comprising a single domain serum albumin binding protein according to the instant disclosure. Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations are provided.

Single domain serum albumin binding protein

Described herein are binding proteins that specifically bind to human CD33, and in particular to bispecific binding proteins that specifically bind to human CD33 and human CD3. Also described herein are bispecific tandem diabodies that bind to CD33 and CD33, and their uses for immunotherapy of CD33+ cancers, diseases and conditions such as acute myeloid leukemia (AML).

Activatable interleukin 12 polypeptides

Activatable interleukin-2 polypeptides

Growing community of inventors

San Francisco, CA, United States of America

Luke Evnin