The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.

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.

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

Described herein are Siglec ligand-antibody conjugates and compositions thereof that are useful for suppressing unwanted immune responses such as allergies and anaphylaxis.

The present invention provides modified catalytic antibody 38C2 with arylation of the reactive lysine residue (Lys99). The Lys99 residue is arylated with a heteroaryl methyl sulfonyl compound such as methylsulfone phenyl oxadiazole (MS-PODA). The invention also provides antibody conjugated agents (e.g., antibody drug conjugates) that contain an agent moiety that is site-specifically conjugated to 38C2 via a methyl sulfonyl compound. Further provided in the invention are methods of making the antibody conjugated agents and therapeutic applications of the antibody conjugated agents.

The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.

Isolated polypeptides having a heavy chain variable region and/or light chain variable region that specifically binds to Nectin-4 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to Nectin-4 protein. Pharmaceutical compositions and kits comprising the polypeptide and antibodies and antibody fragments containing the polypeptide are also provided.

Provided are a bispecific antibody and use thereof. The bispecific antibody comprises a B7-H4-targeting antigen-binding domain and a 4-1BB-targeting antigen-binding domain. The bispecific antibody has one or two or three sites for binding to 4-1BB, along with a novel fully human B7-H4 antibody. The bispecific antibody specifically binds to tumor cells by targeting B7-H4, reducing toxicity induced by 4-1BB activation. In addition, the bispecific antibody of the present invention comprises a human Fc fragment, and thus retains the binding of Fc to FcRn and has a longer half-life.

The present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel DOTA-haptens that may be complexed with a radioisotope (e.g., .sup.225Ac). Also disclosed herein are methods of the using the DOTA-haptens of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

This invention relates to anti-ROR1 antibodies and methods of using them in treating diseases and conditions related to ROR1 activity, e.g., cancer.