The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one binding site for Trop-2 (EGP-1) and at least one binding site for CD3. The bispecific antibodies are of use for inducing an immune response against a Trop-2 expressing tumor, such as carcinoma of the esophagus, pancreas, lung, stomach, colon, rectum, urinary bladder, breast, ovary, uterus, kidney or prostate. The methods may comprising administering the bispecific antibody alone, or with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-?), and/or checkpoint inhibitor antibodies. The bispecific antibody is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of Trop-2.sup.+ cancer cells. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC.

The present invention relates to combination therapy with ADCs against a tumor-associated antigen, such as Trop-2, and drugs, such as microtubule inhibitors and/or PARP inhibitors. Where ADCs are used, they preferably incorporate SN-38 or another drug that induces DNA strand breaks. Preferably, the combination of ADC and PARPi or microtubule inhibitor exhibits synergistic effects against the cancer. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.

The present invention relates to novel anti-TPBG antibody comprising Fc silencing mutations such as leucine (L) to alanine (A) substitution at the position 234 and 235 (LALA mutations), antibody-drug-conjugates (ADCs) based thereon as well as to therapeutic methods and uses thereof, particularly in relation to cancer treatment.

The present application relates to a method for preparing an antibody drug conjugate and an application thereof. Specifically, the present application relates to a compound, or a tautomer, mesomer, racemate, enantiomer, and diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, as well as a method for preparing the compound and related antibody drug conjugates and use thereof in the preparation of drugs for the treatment of cancers.

The present application relates to a preparation method for an antibody-drug conjugate and an application, and in particular, to a compound, or a tautomer, mesomer, racemate, enantiomer, and diastereomer, or mixture thereof, or a pharmaceutically acceptable salt, prodrug or solvate thereof, a preparation method for the compound and related antibody-drug conjugates, and a use of the same in the preparation of drugs for the treating cancer.

The present invention provides Polar units, Linker intermediates, Linkers, Drug-Linkers and Conjugates thereof.

The present application relates to a preparation method for and an application of an antibody conjugated drug, in particular to a compound, or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or a pharmaceutically acceptable salt, prodrug, or solvate thereof, preparation methods of the compound and related antibody conjugated drug, and uses thereof in the preparation of drugs for treating cancers.

The present invention relates to the use of a medicament in treatment of a tumor disease. In particular, the present invention provides the use of a biologically active conjugate represented by formula (I) in treatment of a tumor disease. The tumor disease particularly and preferably refers to an unresectable locally advanced or metastatic solid tumor that is refractory according to existing treatment standards, including but not limited to breast cancer, gastric cancer, lung cancer, ovarian cancer, urinary tract epithelial cancer, esophageal cancer, liver cancer, colorectal cancer, cervical cancer, endometrial cancer, pancreatic cancer, and brain tumor.