The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.

The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.

The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6′-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.

The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6′ of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6′ of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

Provided herein are methods of depleting T cells for therapeutic uses, including administration of anti-CD2 or anti-CD5 antibody drugs conjugates (ADCs) for treatment. Provided are anti-CD2 ADCs or anti-CD5 ADCs for use as agents to treat a stem cell disorder, cancer, or autoimmune disease, among other hematological and proliferative diseases. The compositions and methods described can be used to deplete populations of CD2+ or CD5+ cells, such as CD2+ or CD5+ cancer cells or CD2+ or CD5+ immune cells, and can also be used to prepare a patient for hematopoietic stem cell transplantation or solid organ transplantation.

The present disclosure provides antibody-drug conjugate structures, which include a cleavable linker that links the antibody to the drug and has a first enzymatically cleavable moiety and a second enzymatically cleavable moiety which includes a glycoside selected from a galactoside, a glucoside, a mannoside, a fucoside, O-GlcNAc, and O-GalNAc. The disclosure also encompasses compounds and methods for production of such conjugates, as well as methods of using the conjugates.

Disclosed are methods and compositions relating to the treatment of autoimmune diseases using anti-CD45 antibody drug conjugates (ADCs).

The invention provides methods of depleting CD45+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD45 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.

The present invention relates to bi-specific antigen binding molecules and associated fusion proteins and conjugates. In particular, the present invention relates to bi-specific antigen binding molecules with specificity for both receptor tyrosine kinase-like orphan receptor 1 (ROR1) and epidermal growth factor receptor (EGFR) and associated fusion proteins and conjugates. In a further aspect, the present invention relates to conjugated immunoglobulin-like shark variable novel antigen receptors (VNARs).

The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.