Patent classifications
A61K51/1045
ANTI-TROP-2 ANTIBODY-DRUG CONJUGATES AND USES THEREOF
Described herein are compositions and methods of use of antibody-drug conjugates (ADCs) comprising an anti-Trop-2 antibody or antigen-binding fragment thereof, conjugated to one or more cytotoxic drugs. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. More preferably, the antibody is humanized. Preferably the drug is SN-38, pro-2-pyrrolinodoxorubicin, paclitaxel, calichemicin, DM1, DM3, DM4, MMAE, MMAD or MMAF. The compositions and methods are of use to treat Trop-2 expressing cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer. Preferably, the cancer is one that is resistant to one or more standard cancer therapies. More preferably, the anti-Trop-2 antibody binds to Trop-2 expressed on normal cells, but administration of the anti-Trop-2 ADC to human cancer patients at a therapeutically effective dosage produces only limited toxicity.
RS7 Antibodies
This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.
Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseases
Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKKα/β and IκBα, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC.sub.50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.
Antibodies to TIP-1
The present invention is directed towards isolated antibodies that bind to GRP78 and TIP-1.
Cysteine linked nanobody dimers
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 (1ISVD) 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.
Anti-CD146 antibodies and uses thereof
The present invention relates to the field of diagnostic and treatment of cancer, particularly melanoma, pancreatic cancer, kidney cancer and colon cancer. In particular, the invention relates to an antibody directed specifically to CD146-positive tumors and its applications, particularly for use as a medicament for the prevention and/or treatment of cancer, for use in a method of diagnostic or prognostic of a cancer, or for use as a radiotracer when labelled with a radioactive element.
NOVEL THERANOSTIC AGENTS FOR PSMA POSITIVE CANCERS
The present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel radiohalogenated (e.g., radioiodinated) PSMA targeting agents and methods of using the same in diagnostic imaging as well as radiation therapy.
ADENOCARCINOMA ANTIGENIC DETERMINANTS AND METHODS
Adenocarcinoma antigenic determinants, methods for their production and use, and broadly-specific human monoclonal antibodies reactive to the epitopes. These epitopes, which can be physically recapitulated, are conserved across a range of adenocarcinomas and are capable of eliciting an immune response in humans.
Alpha-emitting complexes
The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.
Antibody against transporter and use thereof
The present invention provides a prophylactic or therapeutic agent for various malignant tumors, including currently intractable solid tumors, which contains an antibody having the ability to bind to human LAT1/CD98 and inducing antibody-dependent cellular cytotoxicity specifically against cancer cells as an active ingredient.