Abstract: The invention provides methods of increasing the production of polypeptides, optionally recombinant polypeptides, from mammalian cells using an aromatic carboxylic acid, an acetamide, and/or a hydroxamic acid compound, and cultures containing the same.

Abstract: Compounds and methods are disclosed that are useful in inhibiting the TNF-.alpha. converting enzyme (TACE) responsible for cleavage of TNF-.alpha. precursor to provide biologically active TNF-.alpha.. The compounds employed in the invention are peptidyl derivatives having active groups capable of inhibiting TACE such as, hydroxamates, thiols, phosphoryls and carboxyls.

Abstract: Compounds and methods are disclosed that are useful in inhibiting the TNF-.alpha. converting enzyme (TACE) responsible for cleavage of TNF-.alpha. precursor to provide biologically active TNF-.alpha.. The compounds employed in the invention are peptidyl derivatives having active groups capable of inhibiting TACE such as, hydroxamates, thiols, phosphoryls and carboxyls.

Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier.

Abstract: The present invention provides conjugates formed from calcified tissues targeting agents and radiolabeled compounds. One such conjugate comprises a chelate and a targeting agent that is capable of associating with calcified tissue, wherein the chelate contains at least one nitrogen atom or at least one sulfur atom or combinations thereof as the donor atoms.Another aspect of the invention provides method for using the conjugates for diagnostic and therapeutic purposes, including those related to bone cancer.

Abstract: Chelating compounds of specified N.sub.2 S.sub.2 N.sub.3 S derived structure are useful for radiolabeling targeting molecules such as antibodies. Cleavable ester orthioester linkers connect the radionuclide metal chelates to the antibodies. The radiolabeled antibodies have improved biodistribution properties, including reduced localization within the intestines and kidneys.

Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier.

Abstract: Chelating compounds of specified structure are useful for radiolabeling targeting molecules such as antibodies. Cleavable linkers connect the radionuclide metal chelates to the antibodies. The radiolabeled antibodies have improved biodistribution properties, including reduced localization within the intestines and kidneys.

Abstract: The present invention provides conjugates formed from calcified tissues targeting agents and radiolabeled compounds. One such conjugate comprises a chelate and a targeting agent that is capable of associating with calcified tissue, wherein the chelate contains at least one nitrogen atom or at least one sulfur atom or combinations thereof as the donor atoms.Another aspect of the invention provides methods for using the conjugates for diagnostic and therapeutic purposes, including those related to bone cancer.

Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier.