This invention provides, and in certain specific but non-limiting aspects relates to: —assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay). Such predictive assays could for example be used to test whether a given ISV could have a tendency to give rise to such protein interference and/or such a signal; to select ISV's that are not or less prone to such protein interference or to giving such a signal; as an assay or test that can be used to test whether certain modification(s) to an ISV will (fully or partially) reduce its tendency to give rise to such interference or such a signal; and/or as an assay or test that can be used to guide modification or improvement of an ISV so as to reduce its tendency to give rise to such protein interference or signal; —methods for modifying and/or improving ISV's to as to remove or reduce their tendency to give rise to such protein interference or such a signal; —modifications that can be introduced into an ISV that remove or reduce its tendency to give rise to such protein interference or such a signal; —ISV's that have been specifically selected (for example, using the assay(s) described herein) to have no or low(er)/reduced tendency to give rise to such protein interference or such a signal; —modified and/or improved ISV's that have no or a low(er)/reduced tendency to give rise to such protein interference or such a signal.

Provided herein are engineered antibodies that comprise a modified IgA heavy chain constant region, pharmaceutical compositions, and methods of use. The engineered antibodies described herein comprise one or more amino acid substitution or deletion in a constant region of an IgA domain. Further provided herein are methods of treating disorders, including cancer, by administering an engineered IgA antibody described herein.

The present invention relates to compositions and methods involving diagnostic tests with multiple test antigens. The present invention involves the expanded use of test antigens as cross-reactive control antigens (CCAs). The invention advantageously provides for enhanced test results analysis by simultaneously providing both test antigen and CCA signal results. These results, in turn, allow useful sample comparison and cross-reference between samples to more accurately identify and verify the fidelity of test results obtained for multiple infective agents at once. The present invention may include compositions and methods for detecting infection by Zika virus or another flavivirus, and may distinguish between infections caused by genetically similar agents.

Provided herein are engineered antibodies that comprise a modified IgA heavy chain constant region, pharmaceutical compositions, and methods of use. The engineered antibodies described herein comprise one or more amino acid substitution or deletion in a constant region of an IgA domain. Further provided herein are methods of treating disorders, including cancer, by administering an engineered IgA antibody described herein.

Disclosed is a calibrator comprising IgA having a biotin group and a biotin-binding site, the calibrator being used to obtain a concentration of an IgA aggregate in a sample.

An objective of the present invention is to provide target tissue-specific antigen-binding molecules, antigen-binding molecules whose antigen-binding activity varies depending on the concentration of an unnatural compound, libraries comprising a plurality of the antigen-binding molecules which are different from one another, pharmaceutical compositions comprising the antigen-binding molecules, methods of screening for the antigen-binding molecules, and methods for producing the antigen-binding molecules. The present inventors created antigen-binding domains whose antigen-binding activity varies depending on the concentration of a small molecule compound or antigen-binding molecules containing an antigen-binding domain, and libraries comprising a plurality of the antigen-binding domains which are different from one another or antigen-binding domains, and demonstrated that the above-noted objective could be achieved by using the libraries. Various diseases originating from target tissues can be treated in a target tissue-specific manner by using the antigen-binding molecules of the present invention.

Using protein structural probes one can identify tumor-induced or -produced (TIPS) factors that bind to therapeutic antibodies and change their dynamic structure, thereby negatively affecting their humoral immune functions as well as their pharmacologic activity. Using such protein structural probes and TIPS factors one can screen and identify inhibitors that can counter the binding of TIPS factors to affected therapeutic antibodies. These inhibitors can be used in the presence of a TIPS factor-susceptible antibody (TSA) for treating cancer. An inhibitor can be used alone or in combination with chemotherapy for treating cancer. Patients can be screened to identify those with low or no TIPS factor production as candidates for antibody therapy even in the case in which the antibody is a TSA. Conversely, those with high TIPS factor production are candidates for inhibitor therapy.

The present inventors discovered that incorporating an Fc region and an antigen-binding domain whose antigen-binding activity varies depending on ion concentration into an antigen-binding molecule that binds to an aggregate-forming antigen produces an antigen-binding molecule that can preferentially clear protein aggregates in comparison to protein monomers from plasma. Use of antigen-binding molecules of the present invention allows various diseases stemming from target tissues to be treated target-tissue-specifically. Use of antigen-binding molecules of the present invention enables treatment of diseases caused by protein aggregates.

The present invention relates to monoclonal antibodies that specifically bind to human pituitary adenylate cyclase activating polypeptide (PACAP) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the monoclonal antibodies are also described.

An improved method for the preparation of tetrameric antibody complexes directly on the surface of target entities in a sample is described. In particular, this method involves linking, in the sample, a first target entity with a second target entity in a sample using antibodies with specificity for the first and second target entities.