The invention relates generally to polypeptides that include at least a first cleavable moiety (CM1) that is a substrate for at least one matrix metalloprotease (MMP) and at least a second cleavable moiety (CM2) that is a substrate for at least one serine protease (SP), to activatable antibodies and other larger molecules that include these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease, and to methods of making and using these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease in a variety of therapeutic, diagnostic and prophylactic indications.

Antibodies and antibody fragments that inhibit the activity of vascular cell adhesion molecule 1 (VCAM1) and/or macrophage erythroblast attacher (MAEA) are provided, along with formulations and kits comprising these antibodies and antibody fragments and the use of the disclosed compositions, formulations, and kits to treat cancers, sickle cell disease, and Polycythemia Vera.

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof pharmaceutical compositions containing them, and to their use in therapy for the prevention treatment of cancer.

Provided herein are cross-reactive antibodies (or antigen binding fragments thereof) that bind to human CTLA4, activatable antibodies that bind to human CTLA4, nucleic acid molecules encoding the same, pharmaceutical compositions thereof, and methods of their therapeutic use (e.g., for treatment of cancer).

The invention provides humanized mouse anti-human IL-31 antibodies and antibody fragments that are capable of binding IL-31 and thereby neutralizing, inhibiting, limiting, or reducing the proinflammatory or pro-pruritic effects of IL-31.

A transgenic chicken comprising an inactivated heavy immunoglobulin gene and/or inactivated light chain immunoglobulin gene is provided, as well as cells and targeting vectors for making the same.

The present invention provides antibodies that bind to human interleukin-25 (IL-25) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human IL-25 with high affinity. In certain embodiments, the invention includes antibodies that bind human IL-25 and block IL-25-mediated cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies. The antibodies of the invention are useful for the treatment of various disorders associated with IL-25 activity or expression, including asthma, allergy, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, atopic dermatitis (AD), and Eosinophilic Granulomatosis with Polyangiitis (EGPA), also know as Churg-Strauss Syndrome.

In certain embodiments, the disclosure provides an IgG4 antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises: (a) a modified IgG4 CH1 region having a substitution of the lysine residue at position 196; or (b) a modified IgG4 hinge region having a substitution of the serine residue at position 217, the glycine residue at position 220, the proline residue at position 224 or the proline residue at position 225. Preferably, the IgG4 antibody further comprises a substitution of the serine residue at position 228 in the heavy chain hinge region.

The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma.

The present invention relates to improved pharmaceutical compositions and dosage unit forms of bispecific CD3×CD20 antibodies and to routes of administration.