The present disclosure relates to the field of biotechnology. In particular, provided are a ligase fusion protein and an immobilized ligase comprising the same. Also provided is use of the ligase fusion protein or the immobilized ligase in the preparation of conjugates. Further provided is a process for the preparation of conjugates using a ligase or a ligase unit.

Metastatic triple negative breast cancer (TNBC) still carries a dismal prognosis with the current treatment paradigms. The effectiveness of drug treatment for many solid tumors such as TNBC is limited by tumor heterogeneity, lack of tumor specificity, off-target toxicities, and transient therapeutic action(s). Strategies that provide tumor-specific, sustained concentrations of drugs to the tumors and tumor receptor-specific binding, while reducing off-target effects are needed to ensure sufficient tumor cell uptake within the primary and metastatic tumor microenvironment. The decreased non-specific adhesivity, receptor-targeted nanoparticle formulations (“DART” nanoparticles) of the invention were assessed for clinical potential in directing biological agents to the cell surface receptor Fn14, which is expressed in many solid cancer types, including TNBC primary tumors and metastatic lesions. They are contemplated for use against solid tumors, particularly brain tumors such as glioblastoma and breast cancer, including metastatic breast cancer.

The invention provides a method for producing an immunoconjugate, the method comprising combining one or more compounds of Formula I and an antibody construct of Formula II to provide the immunoconjugate of Formula III, wherein TA is a therapeutic agent, L is a linker, r is an integer from 1 to 50, Ar is an aromatic moiety comprising a substituent selected from PEG, —SO.sub.2CX.sub.3, —NR.sub.3.sup.+, —NO.sub.2, —SO.sub.3R, —SO.sub.2R, —CN, —CX.sub.3, —PO.sub.3R.sub.2, —OPO.sub.3R.sub.2, and salts thereof, each R independently is H, CX.sub.3, or C.sub.1-C.sub.4 alkyl, each X independently is hydrogen or a halogen, Y is CH.sub.2, PEG, or a bond, n is an integer from 1 to 4, and PEG has the formula: —(CH.sub.2CH.sub.2O)m-(CH.sub.2).sub.p—, where p is an integer from 1 to 5 and m is an integer from 2 to 50. The invention also provides an immunoconjugate and a composition of immunoconjugates formed from said method.

##STR00001##

The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more 8-amido-2-aminobenzazepine derivatives. The invention also provides 8-amido-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Provided herein are linkers, linker-drug groups and anti-body-drug conjugates comprising hydrophilic groups.

The present application relates to an anti-tumor compound and a preparation method and use thereof, and in particular to a compound or a tautomer, a mesomer, a racemate, an enantiomer or a diastereoisomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof, and a preparation method and use thereof.

The present invention provides a novel antibody-pyrrolodiazepine derivative and a novel antibody-pyrrolodiazepine derivative conjugate using the same, and a novel CLDN6 and/or CLDN9 antibody.

A hetero-targeted, dual-responsive nanogel to deliver chemotherapeutic agents to a metastatic cancer is provided. The nanogel includes a first chemotherapeutic agent, a second chemotherapeutic agent, a first targeting ligand, and a second targeting ligand. A method of treating cancer in a mammal with the nanogel are also provided.

Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.

Objects of the present invention are to provide a novel phthalocyanine dye for use in photoimmunotherapy, and a method for producing the same, and to provide a conjugate of the above-described phthalocyanine dye and an antibody or a peptide. According to the present invention, a compound represented by the following formula (1) or a salt thereof is provided:

##STR00001## wherein X represents a substituent having a hydrophilic group at the terminus thereof; L.sub.3, L.sub.4, L.sub.5, and L.sub.6 each independently represent a divalent linking group; Y represents a group capable of binding to an antibody or a peptide; R.sub.3 represents a substituent, such as an alkyl group containing 1 to 6 carbon atoms, an alkoxy group containing 1 to 6 carbon atoms, a halogen atom, —SR.sub.11, —SOR.sub.12, an aryl group containing 6 to 10 carbon atoms, —N(R.sub.13)(R.sub.14), or —NO.sub.2, wherein when a plurality of R.sub.3s are present, the plurality of R.sub.3s may be identical to or different from one another; and s represents an integer of 0 to 4.