Gilead Biologics, Inc.

Synthekine, Inc.

Gilead Sciences, Inc.

Armo Biosciences, Inc.

Scott Alan McCauley

Victoria Smith

Hector Rodriguez

Carlos Aurelio Garcia

Peter Van Vlasselaer

Derek Marshall

Alison Kay Holzer

Scott Ogg

Donna Hiroko Tokuoka Biermann

Vivian E Barry

Miho Oyasu

Maria Vaysberg

Martin Oft

Steve Kauder

Paul-Joseph Penaflor-Aspuria

Jan Emmerich

The present disclosure relates to hIL2 orthogonal ligands ('IL2 orthologs') that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.

IL-2 orthologs and methods of use

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

Antibodies to matrix metalloproteinase 9

The present disclosures related to human interleukin-2 (hIL2) muteins, pharmaceutical formulations thereof, methods for preparing interleukin-2 muteins, recombinant vectors and cells comprising nucleic acids encoding IL2 muteins and methods for the treatment of human disease.

Biased IL2 muteins methods and compositions

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an l=g light chain (or functional fragment thereof).

The present application relates to anti-LOX and anti-LOXL2 antibodies and their use in purification, diagnostic and therapeutic methods. Antibodies include monoclonal antibodies, humanized antibodies and functional fragments thereof. Anti-LOX and anti-LOXL2 antibodies can be used to identify and treat conditions such as a fibrotic condition, angiogenesis, or to prevent a transition from an epithelial cell state to a mesenchymal cell state.

LOX and LOXL2 inhibitors and uses thereof

Interleukin-15 muteins and other interleukin-15-related molecules are described, as well as methods of identifying interleukin-15 muteins and other interleukin-15-related molecules. Also described herein are modifications of the foregoing, which modifications may enhance a property (e.g., half-life) of the muteins or other molecules compared to human interleukin-15. Pharmaceutical compositions and methods of use are also described herein.

Interleukin-15 compositions and uses thereof

Method of detecting human matrix metalloproteinase 9 using antibodies

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), wherein the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

Nucleic acids encoding antibodies to matrix metalloproteinase 9

Disclosed herein are amino acid sequences, and encoding nucleotide sequences, of isolated catalytic domains of the LOX and LOXL2 proteins from human and mouse. Methods for the preparation and use of these isolated catalytic domains are also provided.

Catalytic domains from lysyl oxidase and LOXL2

The present disclosure provides lysyl oxidase-like-2 (LOXL2) polypeptide binding agents, including, for example, antibodies that specifically bind a LOXL2 polypeptide; and further provides compositions comprising same. The binding agents can be used in various treatment and diagnostic methods, which are also provided.

Antibodies that bind to lysyl oxidase-like 2 (LOXL2)

The present disclosure provides methodology and compositions for preventing and treating various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using an inhibitor of processed forms of lysyl oxidase or lysyl oxidase-like proteins, an inhibitor of LOX or LOXL, or a synergistic combination thereof combined with other therapeutic agents. Methods and compositions for diagnosing or monitoring various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, are also provided. Also provided herein are methods and related compositions, medical devices, systems and kits for preventing or treating various diseases and conditions associated with fibrosis with compositions comprising inhibitors of LOX or LOXL.

Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis

Provided are methodology, compositions and kits to prevent and treat diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using processed lysyl oxidase or lysyl oxidase-like protein inhibitors, LOX inhibitors and LOXL inhibitors, or synergistic combinations of such inhibitors with therapeutic agents. Provided are methods for selecting tumor invasion, angiogenesis and metastasis inhibiting agents, by contacting cells in EMT states with candidate agents and detecting changes in such states; and methods, compositions, and kits for diagnosing or monitoring diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, using molecules or agents specifically recognizing processed LOX or LOXL. Provided are methods, compositions, medical devices, systems and kits for preventing or treating diseases and conditions associated with fibrosis, including pathological cardiovascular conditions and diseases, e.g., hypertension, hypertensive heart disease, myocardial infarction, atherosclerosis, restenosis, liver fibrosis, kidney fibrosis, lung fibrosis, dermal scaring, keloid formation, and Alzheimer's disease, with LOX or LOXL inhibitors.

Growing community of inventors

San Francisco, CA, United States of America

Scott Alan McCauley