Provided herein are conjugated immunoglobulins and methods for generating conjugated immunoglobulins using a microbial transglutaminase.

Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection and diagnosis of early stage pancreatic cancer. In preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay can detect a marker for early stage pancreatic cancer in serum. More preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay.

Compounds, e.g., radioimmunoconjugates, including a chelating moiety or a metal complex thereof, a linker, and an antibody or antigen-binding fragment thereof targeting both EGFR and cMET. Pharmaceutical compositions of such compounds and methods of treatment for conditions, e.g., cancer, using such compounds or pharmaceutical compositions.

The disclosure provides radiolabeled and/or cytotoxin labelled antibodies and methods and uses of these antibodies. In one embodiment, provided is a cytotoxic agent comprising an antibody that specifically binds a target disease cell surface receptor, a cytotoxin, and a radiolabel, wherein the cytotoxin is linked directly or indirectly to the antibody, and wherein the radiolabel comprises a radionuclide and optionally a scaffold, wherein the scaffold is directly or indirectly coupled to the antibody. Also provided are methods of preparing the cytotoxic agent and methods of treating disease using the cytotoxic agent.

The present application discloses compositions and methods of use of .sup.68Ga labeled molecules. Preferably, the .sup.68Ga is attached to a peptide targetable construct and is used in a pretargeting technique with a bispecific antibody (bsAb). The bsAb comprises at least one binding site for a disease-associated antigen, such as a tumor-associated antigen, and at least one binding site for a hapten on the targetable construct. Exemplary haptens include In-DTPA and HSG. More preferably, the bsAb is administered about 24-30 hours before the targetable construct, and detection by PET imaging occurs about 1-2 hours after the targetable construct is administered. The methods and compositions are suitable for detection, diagnosis and/or imaging of various diseases, such as cancer or infectious disease.

The present invention relates to dimers comprising a first polypeptide and a second polypeptide, wherein each of said first and second polypeptide comprises at least one immunoglobulin single variable domain (ISVD) and a C-terminal extension comprising a cysteine moiety (preferably at the C-terminus), wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety of said first polypeptide and the cysteine moiety of said second polypeptide, in which the dimer outperformed the benchmark constructs, e.g. cognate multivalent and multispecific constructs, in various assays. The present invention provides methods for making the dimers of the invention.

The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

A non-naturally occurring peptide linker, comprising a site-specific conjugation motif of GGX.sub.1X.sub.2Q, which allows for site-specific conjugation mediated by a transglutaminase; wherein each of X.sub.1 and X.sub.2 independently represents any naturally-occurring amino acid or one of X.sub.1 and X.sub.2 is absent; and wherein the non-naturally occurring peptide has a length of 9-20 amino acids. Also provided herein are fusion polypeptides such as tandem single-domain multi-specific antibodies containing such peptide linkers.