The present disclosure provides conjugate structures and hydrazinyl-pyrrolo compound structures used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same.

The invention provides antibodies, antibody drug conjugates, antibody-based fragments or antibody fragments (antigen-binding fragments), as well as antibody drug conjugates (ADCs) and chimeric antigen receptors (CARs), that specifically recognize human ROR1 and related compositions. Also provided in the invention are methods of using such antibodies in various diagnostic and therapeutic applications.

The present invention provides improved processes for the preparation of drug-linkers with a β-glucuronide cleavable unit, as well as intermediates thereof.

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

Methods to improve the success of cancer therapies that target the human folate receptor 1 are provided. Kits comprising reagent useful in the methods are further provided.

The invention provides a one-step process for preparing a cell-binding agent cytotoxic agent conjugate comprising contacting a cell-binding agent with a cytotoxic agent to form a first mixture comprising the cell-binding agent and the cytotoxic agent and contacting the first mixture comprising the cell-binding agent and the cytotoxic agent with a bifunctional crosslinking reagent, which provides a linker, in a solution having a pH of about 4 to about 9 to provide a second mixture comprising the cell-binding agent cytotoxic agent conjugate, wherein the cell-binding agent is chemically coupled through the linker to the cytotoxic agent, free cytotoxic agent, and reaction by-products. The second mixture is then optionally subjected to purification to provide a purified cell-binding agent cytotoxic agent conjugate.

The invention relates to a pharmaceutical combination comprising: a first conjugate comprising at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule; and comprising a saponin, a derivative thereof, or a second conjugate comprising a binding molecule for binding to a second cell-surface molecule on the same cell surface as the first cell-surface molecule and the saponin and/or the derivative thereof, wherein the saponin or the derivative thereof is a monodesmosidic or bidesmosidic triterpene glycoside. The invention also relates to a composition comprising the first conjugate and the saponin (derivative) or the second conjugate comprising the saponin (derivative). In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, and for use in the treatment or the prophylaxis of a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease relating to a gene defect, an amyloidosis, a disease related to an enzyme deficiency, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis. Furthermore, the invention relates to an in vitro or ex vivo method for transferring the first conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

The invention relates to a therapeutic combination comprising: (a) a first pharmaceutical composition comprising a conjugate comprising a first binding molecule for binding to a first binding site of a cell-surface molecule and the conjugate comprising a saponin bound to said first binding molecule, wherein the saponin is a triterpene glycoside; and (b) a second pharmaceutical composition comprising a conjugate comprising a second binding molecule different from the first binding molecule, the second binding molecule comprising a second binding region different from the first binding region, for binding to a second binding site of said cell-surface molecule different from the first binding site of said cell-surface molecule, and the conjugate comprising an effector molecule covalently bound to said second binding molecule. The invention also relates to a pharmaceutical composition comprising said two conjugates. In addition, the invention relates to the pharmaceutical combination or the pharmaceutical composition of the invention for use as a medicament. Furthermore, the invention relates to the pharmaceutical combination or the pharmaceutical composition of the invention, for use in the treatment or prevention of a cancer, an autoimmune disease, a disease relating to (over)expression of a protein, a disease relating to an aberrant cell such as a tumor cell or a diseased liver cell, a disease relating to a mutant gene, a disease relating to a gene defect, a disease relating to a mutant protein, a disease relating to absence of a (functional) protein, a disease relating to a (functional) protein deficiency.

The present invention relates to a novel compound comprising a galactose trigger moiety and cyclopropabenzindole (CBI), and an antibody-drug conjugate prepared by using same.

The present invention relates to a “one-pot process” for preparing intermediate of antibody-drug conjugate. The preparation process provided by the present invention is simple in operation, and needs no such steps like concentration, washing and filtration of the intermediate reaction liquid, disposal of the organic waste liquid, and packaging and storage of the intermediate. The entire reaction system comprises only one separation and purification treatment, saving costs for labor, equipment, venues, raw materials, etc., and greatly reducing the pollution to the environment. In addition, the “one-pot process” for preparing intermediate of antibody-drug conjugate of the present invention produces the intermediate of antibody-drug conjugate with higher yield. The “one-pot process” for preparing intermediate of antibody-drug conjugate provided by the present invention is more suitable for scale-up production.