Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the effector function of monoclonal antibodies and monoclonal antibodies with increased effector function.

Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the effector function of monoclonal antibodies and monoclonal antibodies with increased effector function.

Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the effector function of monoclonal antibodies and monoclonal antibodies with increased effector function.

Abstract: Methods are provided for using paclitaxel for treating diseases associated with abnormal cell proliferation and angiogenesis. In particular, methods are provided for administration of paclitaxel formulated with vitamin E derivatives such as d-&agr;-tocopherol polyethylene glycol succinate to a cancer patient. By administering to a patient paclitaxel in a vehicle containing a solubilizer other than Cremophor, acute hypersensitivity caused by Cremophor can be avoided and therapeutic index of paclitaxel may also be increased through potentiation of anti-neoplastic effects by the vitamin E derivatives.

Abstract: Oral formulations of pharmaceuticals are provided with enhanced bioavailability by targeting specific regions of the gastrointestinal tract. Particularly, water soluble and acid-labile drugs such as cytidine analogs (e.g., decitabine) and 2′-deoxyadenosine analogs (e.g., pentostatin) are formulated with pH-sensitive polymers so that these drugs are preferably absorbed in the upper regions of the small intestine, such as the jejunum. In addition, drugs with poor oral bioavailability such as camptothecin compounds (e.g., 9-nitro-camptothecin) can also be formulated using similar strategies in order to significantly improve their oral bioavailability. These formulations can be used to treat a wide variety of diseases or conditions, such hematological disorders, benign tumors, cancer, restenosis, inflammatory diseases, and autoimmune diseases.

Abstract: Methods are provided for using paclitaxel for treating diseases associated with abnormal cell proliferation and angiogenesis. In particular, methods are provided for administration of paclitaxel formulated with vitamin E derivatives such as d-&agr;-tocopherol polyethylene glycol succinate to a cancer patient. By administering to a patient paclitaxel in a vehicle containing a solubilizer other than Cremophor, acute hypersensitivity caused by Cremophor can be avoided and therapeutic index of paclitaxel may also be increased through potentiation of anti-neoplastic effects by the vitamin E derivatives.

Abstract: A method for administering a camptothecin to a patient comprising: injecting into a patient a pharmaceutical composition comprising an aqueous suspension of solid particles suitable for intravenous delivery, the solid particles comprising a camptothecin, and a 0.3 nm to 3.0 &mgr;m thick layer of a membrane-forming amphipathic lipid wherein the solid particles have mean diameters between about 0.05 &mgr;m and 10 &mgr;m. The method is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.

Abstract: A pharmaceutical composition is provided which comprises an aqueous suspension of solid particles, the solid particles comprising a camptothecin, the solid particles having mean diameters between about 0.05 um and 10 um, the particles coated with a 0.3 nm to 3.0 um thick layer of a membrane-forming amphipathic lipid. The pharmaceutical composition is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.

Abstract: A method for administering a camptothecin to a patient comprising: injecting into a patient a pharmaceutical composition comprising an aqueous suspension of microdroplets suitable for intravenous delivery, the microdroplets having a mean diameter between 200 Angstroms and one micron, the microdroplets comprising a substantially water-insoluble, pharmacologically acceptable liquid, a camptothecin dissolved in the water-insoluble, pharmacologically acceptable liquid, and an outer layer comprising a phospholipid. The pharmaceutical composition is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.

Abstract: An injectable pharmaceutical composition comprising: an aqueous suspension of microdroplets suitable for intravenous delivery, the microdroplets having a mean diameter between 200 Angstroms and one micron, the microdroplets comprising a substantially water-insoluble, pharmacologically acceptable liquid, a camptothecin dissolved in the water-insoluble, pharmacologically acceptable liquid, and an outer layer comprising a phospholipid. The pharmaceutical composition is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.

Abstract: A method for administering a camptothecin to a patient comprising: injecting into a patient a pharmaceutical composition comprising an aqueous suspension of solid particles suitable for intravenous delivery, the solid particles comprising a camptothecin, and a 0.3 nm to 3.0 &mgr;m thick layer of a membrane-forming amphipathic lipid wherein the solid particles have mean diameters between about 0.05 &mgr;m and 10 &mgr;m. The method is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.

Abstract: A method for administering a camptothecin to a patient comprising: injecting into a patient a pharmaceutical composition comprising an aqueous suspension of microdroplets suitable for intravenous delivery, the microdroplets having a mean diameter between 200 Angstroms and one micron, the microdroplets comprising a substantially water-insoluble, pharmacologically acceptable liquid, a camptothecin dissolved in the water-insoluble, pharmacologically acceptable liquid, and an outer layer comprising a phospholipid. The pharmaceutical composition is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.

Abstract: A pharmaceutical composition is provided which comprises an aqueous suspension of solid particles, the solid particles comprising a camptothecin, the solid particles having mean diameters between about 0.05 um and 10 um, the particles coated with a 0.3 nm to 3.0 um thick layer of a membrane-forming amphipathic lipid. The pharmaceutical composition is particularly well suited for delivering camptothecins, particularly 9-nitro-camptothecin intravenously.