The present invention relates to novel anti-NaPi2b antibodies, antibody-drug-conjugates (ADCs) based thereon as well as to therapeutic methods and uses thereof, particularly in relation to cancer treatment.

Enzyme-triggered self-reacting arm compounds and chemical intermediates used for preparing such compounds and uses thereof, specifically in prodrug design and conjugation technologies. A Ligand-Drug-Conjugate (LDC) includes such enzyme-triggered self-reacting arms.

Provided are a dual-drug link assembly unit represented by formula III, or a stereoisomer thereof, or an optical isomer thereof. The dual-drug link assembly unit can be linked to a targeting linker to obtain a dual-drug targeting linker-drug conjugate represented by formula I. The specific structure can effectively reduce the aggregation of the dual-drug targeting linker-drug conjugate, which facilitates process scale-up, thereby improving the efficiency of the targeting effect on tumor cells, reducing the toxic and side effects on normal cells, and at the same time, effectively overcoming drug resistance and achieving a synergistic anti-tumor effect. Compared with DS-8201 which is already on the market, the ADC provided by the present invention significantly improves the inhibition effect on HER2 positive cell strains N87 and SKBR-3d.

##STR00001##

The present disclosure provides an immunoconjugate includes an antibody comprising an antigen-binding fragment that specifically binds to an epitope in mesothelin, N-glycan binding domain and an N-glycan; a linker linking to the N-glycan; and a payload A and a payload B conjugated to the linker, respectively; wherein the payload A and the payload B are the same or different. A pharmaceutical composition comprises the immunoconjugate and a method for treating cancer are also provided in the disclosure.

The present disclosure relates to the biopharmaceutical field, in particular, Exatecan derivatives, linker-payloads, and conjugates and thereof antibody-drug conjugates, and the corresponding preparing process and use thereof.

To provide an antitumor drug having excellent therapeutic effect, which is excellent in terms of antitumor effect and safety. Provided is an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-HER3 antibody via a linker having a structure represented by the formula: -L.sup.1-L.sup.2-L.sup.P-NH(CH.sub.2)n.sup.1-L.sup.a-(CH.sub.2)n.sup.2-C(?O) or -L.sup.1-L.sup.2-L.sup.P- (the anti-HER3 antibody is connected to the terminal of L.sup.1, the antitumor compound is connected to the carbonyl group of (CH.sub.2)n.sup.2-C(?O) moiety or the C terminal of L.sup.P, with the nitrogen atom of the amino group at position 1 as a connecting position).

##STR00001##

It is intended to provide an antitumor drug having an excellent therapeutic effect, which is excellent in terms of antitumor effect and safety. There is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-TROP2 antibody via a linker having a structure represented by the following formula: -L.sup.1-L.sup.2-L.sup.P-NH(CH.sub.2)n.sup.1-L.sup.a-(CH.sub.2)n.sup.2-C(?O) wherein the anti-TROP2 antibody is connected to the terminal of L.sup.1, and the antitumor compound is connected to the carbonyl group of the (CH.sub.2)n.sup.2-C(?O) moiety with the nitrogen atom of the amino group at position 1 as a connecting position.

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 invention relates to therapeutic conjugates with improved ability to target various cancer cells containing a targeting moiety and a therapeutic moiety. The targeting and therapeutic moieties are linked via an acid cleavable linkage that increases therapeutic efficacy of the immunoconjugate.

A PEG linker as represented by formula (I), wherein n and m are respectively an integer from 1 to 7, providing the PEG linker with 1 to 49 linking sites. A ligand drug conjugate as represented by formula (II). The conjugate uses the PEG linker to increase a drug loading capacity and drug loading diversity, thereby improving pharmaceutical efficacy.

Y1-PEG1-{R.sup.1-PEG2-{Y4}.sub.n}.sub.m(I)

TM-{R.sup.2-PEG1-{R.sup.1-PEG2-{R.sup.3-A-drug}.sub.n}.sub.m}.sub.l(II)