Provided herein are methods for the treatment of cancers with antibody drug conjugates (ADC) that bind to 191P4D12 proteins. Also provided herein are methods for the treatment of urothelial cancer using an antibody drug conjugate (ADC) that binds 191P4D12. Additionally provided herein are methods for the treatment of solid tumors using an antibody drug conjugate (ADC) that binds 191P4DI2.

The present invention relates generally to glycoconjugates comprising a saccharide covalently conjugated to a carrier protein through a spacer containing ((2-oxoethyl)thio)). In an aspect the invention provides oxo-eT linked glycoconjugates comprising a saccharide covalently conjugated to a carrier protein through a ((2-oxoethyl)thio) spacer having the formula (I): ##STR00001## wherein: A is a group (C═X).sub.m wherein X is S or O and m is 0 or 1; B is a bond, O, or CH.sub.2; and when m is 0, B can also be (C═O); R is a C.sub.2-C.sub.16 alkylene, C.sub.2-C.sub.16 heteroakylene, NH—C(═O)—C.sub.2-C.sub.16 alkylene, or NH—C(═O)—C.sub.2-C.sub.16 heteroakylene, wherein said alkylene and heteroalkylene are optionally substituted by 1, 2 or 3 groups independently selected from COOR′ where R′ is selected from H, methyl, ethyl or propyl. The invention further relates to immunogenic compositions comprising such glycoconjugates, and to methods for the preparation and use of such glycoconjugates and immunogenic compositions.

The present invention provides compositions for the production of an antibody or functional fragment thereof directed against Tn antigen or sTn antigen. The compositions disclosed herein include isolated antibody or functional fragments thereof that binds to Tn antigen or sTn antigen and polynucleotides encoding the heavy chain and/or a light chain variable domains of such antibody or functional fragment. The invention also provides methods of treating or preventing a disease, such as cancer or tumor formation, wherein the antibody or functional fragment includes a variable heavy chain domain and a variable light chain domain that has an amino acid sequence provided herein. The invention further provides a conjugate of an antibody or functional fragment thereof conjugated or recombinantly fused to a localizing agent, detectable agent or therapeutic agent, and methods of treating, preventing or diagnosing a disease in a subject in need thereof.

Degradation compounds include a cyclic cell penetrating peptide (cCPP) and a degradation construct. The degradation construct includes a degradation moiety and a targeting moiety. The targeting moiety binds a target protein. When the targeting moiety is bound to the target protein, the degradation moiety mediates degradation of the target protein. The cCPP facilitates transfer of the degradation construct into a cell. The degradation compound may further include an exocyclic peptide to enhance endosomal escape of the compound or degradation construct once inside the cell.

A fusion peptide comprising a GLP1 variant, and at least one adiponectin agonist peptide which is chemically attached to the GLP1 variant via by a spacer. The GLP1 variant portion can include one or more substitutions relative to the native GLP1. The adiponectin agonist peptide can be attached to the GLP1 variant at different attachment sites. A method of treating a metabolic disorder or condition using the fusion peptide is also provided.

A fusion peptide comprising a GLP1 variant, and at least one adiponectin agonist peptide which is chemically attached to the GLP1 variant via by a spacer. The GLP1 variant portion can include one or more substitutions relative to the native GLP1. The adiponectin agonist peptide can be attached to the GLP1 variant at different attachment sites. A method of treating a metabolic disorder or condition using the fusion peptide is also provided.

Combination therapy of a cancer with a multi-specific binding protein that bind a tumor associated antigen, the NKG2D receptor, and CD16, in combination with a second anti-cancer agent are described. Also described are pharmaceutical compositions of the multi-specific binding protein, and therapeutic methods useful for the treatment of cancer in combination with a second anti-cancer agent.

The present invention provides a covalent conjugate. The conjugate includes an antibody or antibody derivative, at least two LL37-derived polypeptides, and a payload. The antibody or antibody derivative targets a cell that has phosphatidylserine in its outer leaflet. The payload includes: a small molecule cytotoxic drug of less than 3 kDa, or a plurality thereof; or a peptide or protein of less than 100 kDa. Uses and methods of using these covalent conjugates are also provided, related to enhancing delivery of the antibody/derivative or the payload, e.g. to enhance therapeutic or diagnostic effectiveness.

The present invention provides a covalent conjugate. The conjugate includes an antibody or antibody derivative, at least two LL37-derived polypeptides, and a payload. The antibody or antibody derivative targets a cell that has phosphatidylserine in its outer leaflet. The payload includes: a small molecule cytotoxic drug of less than 3 kDa, or a plurality thereof; or a peptide or protein of less than 100 kDa. Uses and methods of using these covalent conjugates are also provided, related to enhancing delivery of the antibody/derivative or the payload, e.g. to enhance therapeutic or diagnostic effectiveness.

The present invention relates to a unit drug conjugate wherein a binding group capable of binding to another unit drug conjugate is additionally linked to a unit drug conjugate in which a targeting substance, which binds specifically to target cells, and a drug, are linked together. When the unit drug conjugates according to the present invention are sequentially administered in vivo, complexes form a cluster by in vivo crosslinking, and the cluster promotes endocytosis of the drug conjugate, thereby significantly enhancing cellular internalization of the drug included in the drug conjugate.