Supergen, Inc

Chiron Corporation

Astex Pharmaceuticals, Inc.

Joseph Rubinfeld

Ashok Y Gore

Rajesh Shrotriya

Rajashree Joshi-Hangal

Rajashree Joshi

Maninder Singh Hora

John F Lyons

Gregory J Wong

Warren Stern

Elliott L Fineman

Sanjeev Redkar

Howard Sands

Jorge F DiMartino

Simeon M Wrenn, Jr

Lawrence A Romel

Lucy Chang

Julius A Vida

Karl L Mettinger

H Leon Bradlow

Jorge Dimartino

Methods are provided for treating diseases associated with abnormal activity of kinases. The method comprises: administering a DNA methylation inhibitor to the patient in therapeutically effective amount; and administering a kinase inhibitor to the patient in therapeutically effective amount, such that the in vivo activity of the kinase is reduced relative to that prior to the treatment. The method can be used to treat cancer associated with abnormal activity of kinases such as phosphatidylinositol 3'-kinase (PI3K), protein kinases including serine/threonine kinases such as Raf kinases, protein kinase kinases such as MEK, and tyrosine kinases such as those in the epidermal growth factor receptor family (EGFR), platelet-derived growth factor receptor family (PDGFR), vascular endothelial growth factor receptor (VEGFR) family, nerve growth factor receptor family (NGFR), fibroblast growth factor receptor family (FGFR) insulin receptor family, ephrin receptor family, Met family, Ror family, c-kit family, Src family, Fes family, JAK family, Fak family, Btk family, Syk/ZAP-70 family, and Ab1 family.

Method for treating diseases associated with abnormal kinase activity

A method is provided for treating a patient having a disease associated with undesirable or uncontrolled cell proliferation, the method comprising: administering to the patient a 20(S)-camptothecin for a period of time during which a pyrimidine base analog is not being administered to the patient; and administering a pyrimidine base analog to the patient.

Sequential therapy comprising a 20(S)-camptothecin and a pyrimidine base analog

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.

Methods for administration of paclitaxel

A method is provided for preparing a pharmaceutical composition comprising: taking polyoxyethylated castor oil which if diluted 1:10 in water has a pH greater than 5 and aging the polyoxyethylated castor oil by exposing the polyoxyethylated castor oil to a gas comprising oxygen for a period of time, the exposure to the gas over the period of time causing an acidity of the polyoxyethylated castor oil to increase; and forming a pharmaceutical composition comprising the aged polyoxyethylated castor oil and a pharmaceutically active agent such as paclitaxel; wherein at least 80% of the potency of the pharmaceutically active agent is retained by the pharmaceutical composition after the pharmaceutical composition is stored for at least 7 days at 40&deg; C.

Method for preparing and using polyoxyethylated castor oil in pharmaceutical compositions

A method for treating a patient having a disease associated with undesirable or uncontrolled cell proliferation such as cancer and restenosis is provided. The method comprises: delivering to the patient a therapeutically effective amount of 9-nitro-20(S)-camptothecin in combination with an effective amount of an antibiotic agent such as bleomycin.

Combination therapy including 9-nitro-20(S)-camptothecin and bleomycin

Disclosed is a compound that includes a camptothecin conjugated to a lactone ring protecting moiety. Also disclosed are compositions and kits including the compound, and methods of making and using the compound.

Camptothecin conjugates

A method is provided for treating a patient having a disease associated with undesirable or uncontrolled cell proliferation. The method comprises: administering to the patient an anthracycline for a period of time during which a 20(S)-camptothecin is not present in a pharmacologically active form in patient's blood; and administering a 20(S)-camptothecin to the patient.

Sequential therapy comprising a 20(S)-camptothecin and an anthracycline

Compositions and methods are provided for treating diseases associated with abnormal cell proliferation such as cancer by storing inherent tumor-suppressing functions of neoplastic cells through DNA hypomethylation. The method comprises: delivering to a patient suffering from cancer a therapeutically effective amount of a DNA methylation inhibitor such as decitabine, in combination with an effective amount of an anti-neoplastic agent whose activity as an anti-neoplastic agent in vivo is adversely affected by aberrant DNA methylation. The anti-neoplastic agent can be an alkylating agent, an antibiotic agent, an antimetabolic agent, a retinoid, a hormonal agent, a plant-derived agent, an anti-angiogenesis agent and a biologic agent such as monoclonal antibody and interferon.

Restore cancer-suppressing functions to neoplastic cells through DNA hypomethylation

Compositions of matter comprising a substituted cyclodextrin and cytotoxic compound, especially cytotoxic drugs such as antibiotic, anti-fungal and anti-neoplastic, drugs are claimed. The compositions cause significantly less ulceration compared to the same formulation of cytotoxic compound without cyclodextrin compound when extravasated. The compositions may also cause less vascular irritation compared to the same formulation of cytotoxic compound without cyclodextrin when administered intravenously without extravasation. Compositions of matter comprising watersoluble cytotoxic agents, especially anticancer drugs and anti-ulceration effective or anti-irritatioin effective amounts of cyclodextrin compounds are also claimed. Methods for reducing the likelihood of ulceration and or irritation when administering the compositions according to the invention are also disclosed and claimed.

Formulation of nitrogen mustard

Paclitaxel formulation

Liposome preparations which comprise a lipid, or lipid like compound and a 5&bgr; steroid, DHEA or an organic acid derivative of the 5&bgr; steroid or DHEA are described. The lipsome may also include an entraped aqueous portion which comprises dissolved therein the expression product of the ob gene. Methods for treating conditions including obesity,hypercorticoidism and diabetes using the liposome preparations are also claimed.

Liposome formulation of 5 &bgr; steroids

A method for treating diseases associated with abnormal cell proliferation comprises delivering to a patient in need of treatment a compound selected from the group consisting of 20(S)-camptothecin, analog of 20(S)-camptothecin, derivative of 20(S)-camptothecin, prodrug of 20(S)-camptothecin, and pharmaceutically active metabolite of 20(S)-camptothecin, in combination with an effective amount of one or more agents selected from the group consisting of alkylating agent, antibiotic agent, an alkylating agent, antibiotic agent, antimetabolic agent, hormonal agent, plant-derived agent, anti-angiogenesis agent and biologic agent. The method can be used to treat benign tumors, malignant or metastatic tumors, leukemia and diseases associated with abnormal angiogenesis.

Inhibition of abnormal cell proliferation with camptothecin and combinations including the same

Oral formulation for paclitaxel

Compositions of matter comprising a substituted cyclodextrin and cytotoxic compound, especially cytotoxic drugs such as antibiotic, anti-fungal and anti-neoplastic, drugs are claimed. The compositions cause significantly less ulceration compared to the same formulation of cytotoxic compound without cyclodextrin compound when extravasated. The compositions may also cause less vascular irritation compared to the same formulation of cytotoxic compound without cyclodextrin when administered intravenously without extravasation. Compositions of matter comprising watersoluble cytotoxic agents, especially anticancer drugs and anti-ulceration effective or anti-irritation effective amounts of cyclodextrin compounds are also claimed. Methods for reducing the likelihood of ulceration and or irritation when administering the compositions according to the invention are also disclosed and claimed.

Growing community of inventors

Danville, CA, United States of America

Joseph Rubinfeld