The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.

The present application is directed to compounds of Formula (I)-(VIII): ##STR00001## compositions comprising these compounds and their uses, for example as medicaments and/or diagnostics.

The present invention relates to antibodies having specificity to HER4 and uses thereof, which are able to induce biased 4ICD routing/signaling. The inventors have isolated by antibody phage display three fully human anti-HER4 single-chain variable antibody fragment (scFv), selected on human HER4 extracellular domain, referred as C6 mAb, D5 mAb and F4 mAb and one fully human anti-HER4 scFv named H2 mAb, selected on NRG 1β1-stimulated EGFR/HER4 JMaCYT1-transfected NIH3T3 cells. In particular, the present invention relates to an isolated anti-HER4 antibody, wherein said antibody binds to an epitope of the HER4 protein.

The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives, and fragments thereof as well as compositions and kits comprising them. Further provided are methods of using glycan-interacting antibodies to target cells and treat disease.

Antibodies are engineered by replacing one or more amino acids of a parent antibody with non cross-linked, highly reactive cysteine amino acids. Antibody fragments may also be engineered with one or more cysteine amino acids to form cysteine engineered antibody fragments (ThioFab). Methods of design, preparation, screening, and selection of the cysteine engineered antibodies are provided. Cysteine engineered antibodies (Ab), optionally with an albumin-binding peptide (ABP) sequence, are conjugated with one or more drug moieties (D) through a linker (L) to form cysteine engineered antibody-drug conjugates having Formula I:

Ab-(L-D).sub.p  I

where p is 1 to 4. Diagnostic and therapeutic uses for cysteine engineered antibody drug compounds and compositions are disclosed.

Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.

The invention provides anti-CLL-1 antibodies and immunoconjugates and methods of using the same.

The invention relates to antibodies, and in particular, to antibodies exhibiting specificity for Receptor tyrosine kinase-like Orphan Receptors (ROR), and to uses thereof, for example in the treatment of cancer. The invention extends to polynucleotide and polypeptide sequences encoding the antibodies, and therapeutic uses thereof, and to diagnostic kits comprising these molecules. The invention also extends to antibody-drug conjugates and to uses thereof in therapy.

The present invention pertains to humanized anti-Lewis Y antibodies which specifically bind to Lewis Y and do not show any cross-reactivity. Especially, the humanized anti-Lewis Y antibodies do not bind to Lewis b or any other blood group carbohydrate antigen. In particular, the present invention is directed to humanized anti-Lewis Y antibodies which are useful in the treatment of cancer.

Methods of treating cancer are provided that include administering glycan-interacting antibodies. Included are anti-sialyl Tn antigen antibodies and related compositions and formulations suitable to achieve desirable bioactivity, bioavailability, and toxicity levels.