The present invention relates to an anti-tumor/anti-tumor-associated fibroblast (TAF)/anti-hapten trispecific antibody (TsAb). The anti-hapten domain enables TsAb to arm various hapten-conjugated anti-cancer drugs (nanocarrier drugs, small molecule drugs, protein drugs, and radioactive drugs). The anti-tumor domain enables TsAb-armed drugs to target tumor cells, while the anti-TAF domain enables the TsAb-armed drugs to target TAFs. The present invention allows the simultaneous killing of tumor cells and TAFs by various drugs through arming with TsAb.

The present invention provides a hybrid biocompatible carrier (hybridosome) which comprises structural and bioactive elements originating from at least one biocompatible delivery module (BDM) and at least one engineered drug encapsulation module (EDEM) comprising at least one tunable fusogenic moiety. The invention further provides pharmaceutical compositions comprising said hybridosomes, processes for their manufacture, as well as pharmaceutical uses and pharmaceutical methods based thereon.

The present disclosure features compositions and methods for the treatment of bacterial infections, such as bacterial infections caused by bacterial cells residing within a host cell (e.g., a mammalian cell, e.g., immune cell, e.g., macrophage or dendritic cell). The compositions and methods include delivering antimicrobial agents to specifically target the intracellular compartment (endosome, phagosome, lysosome, or cytosol) in which the bacterial cell resides.

Antibodies which bind selectively to cardiac conduction system (CCS) cells, imaging and/or diagnostic reagents and compositions visualizing the CCS cells and therapeutic products and compositions comprising one or more of the antibodies. Methods for delivering therapeutic agents to the CCS cells. The disclosure further provides methods for visualizing the CCS cells in vivo in real time, including in a subject undergoing a cardiothoracic surgery or other cardiac intervention. Compositions and methods for isolation, purification, analyses and/or transplantation of the CCS cells, including pluripotent stem cell (hiPSC)-derived or human embryonic stem cell (hESC)-derived CCS cells.

Disclosed herein are methods of treating a tumor in a subject, including administering to the subject one or more miRNA nucleic acids or variants (such as mimics or mimetics) thereof with altered expression in the tumor. Also disclosed herein are compositions including one or more miRNA nucleic acids. In some examples, the miRNA nucleic acids are modified miRNAs, for example, and miRNA nucleic acid including one or more modified nucleotides and/or a 5′-end and/or 3′-end modification. In particular examples, the modified miRNA nucleic acid is an miR-30a nucleic acid. Further disclosed herein are methods of diagnosing a subject as having a tumor with altered expression of one or more miRNA nucleic acids. In some embodiments, the methods include detecting expression of one or more miRNAs in a sample from the subject and comparing the expression in the sample from the subject to a control.

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with alpha or D-gamma polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

The present application relates to ligands targeted to epidermal growth factor receptor (EGFR) and compositions for use in treating tumors. Specifically, a ligand targeted to EGFR is disclosed. The ligand comprises a heavy chain variable domain and a light chain variable domain. The ligand may be selected from the group consisting of a single chain variable fragment, a fusion protein, a monoclonal antibody, and an antigen-binding fragment thereof. The ligand may be conjugated to a liposome or a nanoparticle that encapsulates at least one chemotherapeutic agent to form a ligand-targeted liposomal or nanoparticle drug. Also disclosed are conjugates and formulations for use in treating tumors such as squamous cell carcinoma of head and neck. A method for making a ligand-targeted liposomal drug is also disclosed. The drug may be a chemotherapeutic agent selected from the group consisting of doxorubicine and vinorelbine.

This disclosure relates to novel ligand-drug particles comprising at least one ligand specific for one or more cell surface receptor molecules for targeting the ligand-drug particles to a target cell. This disclosure also relates to pharmaceutical compositions comprising the particles herein and systems and methods for determining the ligand valency of the particles.

Disclosed is a solid phase method of synthesising biomolecule-effector-conjugates and biomolecule-reporter-conjugates. In particular, this invention relates to a solid phase method of synthesising antibody-effector-conjugates and antibody-reporter conjugates. This invention also relates to intermediate methods of producing immobilised, chemically modified biomolecules, e.g., antibodies.

The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provide methods of making the liposome compositions provided by the present invention.