University of California

Cytomx Therapeutics, Inc.

Immungene Inc

Amgen Inc.

Sanjay Khare

James William West

Jason Gary Sagert

Nancy E Stagliano

Patrick Sean Daugherty

Kathryn Kamath

Jerry Thomas

Iqbal Grewal

Michael Gresser

Rashid Syed

Ulrich Feige

The present disclosure provides activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM). The present disclosure provides activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM. Furthermore the present disclosure also provides ABPs which contain a first TBM, a second TBM and a CM. The ABPs exhibit an 'activatable' conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. The disclosure further provides libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. The disclosure further provides ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

Activatable anti-VEGF scFv

Activatable binding polypeptides (ABPs), which contain a target binding moiety (TBM), a masking moiety (MM), and a cleavable moiety (CM) are provided. Activatable antibody compositions, which contain a TBM containing an antigen binding domain (ABD), a MM and a CM are provided. Furthermore, ABPs which contain a first TBM, a second TBM and a CM are provided. The ABPs exhibit an 'activatable' conformation such that at least one of the TBMs is less accessible to target when uncleaved than after cleavage of the CM in the presence of a cleaving agent capable of cleaving the CM. Further provided are libraries of candidate ABPs, methods of screening to identify such ABPs, and methods of use. Further provided are ABPs having TBMs that bind VEGF, CTLA-4, or VCAM, ABPs having a first TBM that binds VEGF and a second TBM that binds FGF, as well as compositions and methods of use.

Methods for manufacturing activatable binding polypeptides comprising matrix metalloprotease cleavable moieties

The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to fusion molecule constructs wherein a tumor associated antigen (TAA) antibody (Ab) serves as a targeting moiety to selectively deliver a cytokine to a tumor cell for purposes of killing or inhibiting the growth or proliferation of said tumor cell. In various embodiments, the engineered fusion molecules comprise a TAA Ab fused to an interferon-alpha (IFN-&#x3b1;) mutant molecule. The engineered Ab-IFN-&#x3b1; mutant fusion molecules of the present invention demonstrate improved therapeutic index and preserved or increased efficacy as compared to Ab-wildtype IFN-&#x3b1; fusion molecules, and/or demonstrate improved PK properties as compared to Ab-wildtype IFN-&#x3b1; fusion molecules.

Engineered antibody-interferon mutant fusion molecules

Activatable binding polypeptides and methods of identification and use thereof

The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof for treatment of autoimmune diseases. More specifically, the present invention provides novel genetically engineered fusion molecules comprising an interferon (IFN) molecule attached to an antibody (Ab) which targets an antigen which is differentially expressed or up-regulated on activated T cells as compared to resting T cells, wherein the fusion molecule when contacted to an activated T cell results in induced apoptosis and programmed cell death or impairment of functions of said activated T cell.

Engineered antibody-interferon fusion molecules for treatment of autoimmune diseases

The field of the present invention relates to genetically engineered fusion molecules, methods of making said fusion molecules, and uses thereof in anti-tumor immunotherapies. More specifically, the present invention relates to engineered fusion molecules comprising an antibody (Ab) which can target tumor cells (e.g., RITUXIN&#xae;), fused to one or more biologic moieties capable of inducing apoptosis in tumor cells, e.g., tumor necrosis factor super family (TNFSF) member ligands such as TNF-&#x3b1;, CD40L, CD95L (also 'FasL/Apo-1L') and TRAIL/Apo-2L. Importantly, the engineered fusion molecules of the present invention retain the death-inducing properties of the biologic moiety at optimum concentrations and with reduced systemic toxicities.

Engineered TAA antibody-TNFSF member ligand fusion molecules

Methods of treating tumors with engineered antibody-interferon mutant fusion molecules

Methods for treating an inflammatory or an immune condition are described. Methods for treating an inflammatory or an immune condition with IL-1 inhibitors and an inhibitor of B cell or T cell activation are described. Methods for treating an inflammatory or an immune condition with TNF inhibitors and an inhibitor of B cell or T cell activation are described.

Combination therapy with co-stimulatory factors

Methods and compositions for modulating an immune response to an immunogenic therapeutic agent are disclosed. One of the disclosed methods comprises administering an effective amount of CTLA-4 to decrease the incidence of an immune reaction in conjunction with the administration of a potentially immunogenic substance. Another method contemplates tolerizing a subject to a therapeutic molecule that is or is capable of being immunogenic by the administration of CTLA-4. Various embodiments of CTLA-4 are also disclosed.

Growing community of inventors

Newbury Park, CA, United States of America

Sanjay Khare