A camptothecin drug having a highly stable hydrophilic connecting unit and its conjugate, or its pharmaceutically acceptable salt thereof, including methods for preparation thereof, and its applications in preventing and/or treating cancer. The conjugate can specifically bind to receptors highly expressed in tumor cells. The conjugates have excellent water solubility, stability, and homogeneity, and can be used for preventing and/or treating tumors and/or other diseases.

The invention provides compositions comprising a single protein having one or more molecules of a pharmaceutical agent tightly bound therein. The compositions are useful to decrease the toxicity and/or to widen the therapeutic window of the pharmaceutical agent. The invention also provides methods for preparing such a composition.

The invention relates generally to polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator (uPA), to activatable antibodies and other larger molecules that include the cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator, and to methods of making and using these polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator in a variety of therapeutic, diagnostic and prophylactic indications.

The present disclosure relates to dosage forms for extended release of an antibody or large protein. The extended release dosage forms comprise a biodegradable multi-block copolymer matrix and provide for extended release of antibody or large protein over a desired time period.

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

New aminooxylipids of general formula I, wherein n.sub.1=5-30 and X is polymethylene linker of the general formula II where n.sub.2=2-10, or X is polyethylene glycol linker of the general formula III, wherein n.sub.3=1-14 are provided. A method of preparation of the aminooxylipids of general formula I characterized in that the acylation of N-tert-butoxycarbonyl-polymethylenediamine {(CH.sub.3).sub.3C—O—(C═O)—HN—(CH.sub.2).sub.n—NH.sub.2, n=2-13}, or N-tert-butoxycarbonyl-polyethyleglycoldiamine {(CH.sub.3).sub.3C—O—(C═O)—HN—(CH.sub.2).sub.2—[O—(CH.sub.2)].sub.n—O—(CH.sub.2).sub.2NH.sub.2, n=1-14} with in position C(2) symmetrically branched fatty acids of general formula IV, wherein n.sub.1=5-30, in the presence of condensation reagent, or from acid of general formula IV derived acylchloride of general formula V wherein n.sub.1=5-30, produces N-Boc-aminolipids of general formula VI, wherein n.sub.1=5-30 a X is polymethylene linker of the general formula II or X is polyethylene glycol linker of the general formula III.

The present invention relates to the conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

An immunotoxin for use in the treatment of leishmaniasis A wherein the immunotoxin comprises a portion which is specifically binding to the cellular surface receptor CD64 as a component A and a cell killing portion as a component B, wherein the cell killing portion alters the function, gene expression, or viability of a cell thereby killing Leishmania-infected macrophages and by this eliminates Leishmania.

This application relates to nanoparticles, including nanoparticles derived from a plasma, and their use in the formation of conjugates. The nanoparticles can be stably conjugated to a wide variety of second species, forming conjugates which can be used, for example, in therapeutic, diagnostic and experimental methods.