NEAL L ROSEN, MD
Osteopathic Medicine at York Ave, New York, NY

7211562, May 1, 2007

Nov 1, 2001

10/415878

Neal Rosen - New York NY, US
Pamela Nathalie Munster - Tampa FL, US

Sloan-Kettering Institute for Cancer Research - New York NY

A61K 35/00, A61K 41/00, A61K 38/00

514 12, 424114, 4241741

The administration of cytotoxic agents followed by the administration of heat shock protein 90 inhibitors, such as ansamycins, has a synergistic effect on the growth inhibition of cells. This synergy occurs at doses of each cytotoxic agent that normally only causes minimal growth inhibition of cells. Such combination therapy thus allows one to use lower doses of cytotoxic agents to avoid or reduce their respective toxicity to patients without compromising their growth inhibitory effects. Thus, these combinations can be used for the treatment of an animal, preferably a mammal, that has a cell proliferative disorder, whether the cells have wild-type Rb or are Rb deficient or Rb negative. One such method, directed to treating cell proliferative disorders includes the step of administering a therapeutic effective amount of a cytotoxic agent followed by administering a therapeutic effective amount of a heat shock protein 90 inhibitor. The cytotoxic agent may be a microtubule-affecting agent, topoisomerase II inhibitor, a platinum complex, paclitaxel, or a paclitaxel derivative. The HSP90 inhibitor may be an ansamycin, radicicol or a synthetic compound that binds to the ATP-binding site of HSP90.

7439359, Oct 21, 2008

Nov 1, 2001

10/415868

Gabriela Chiosis - New York NY, US
Neal Rosen - New York NY, US

Sloan-Kettering Institute for Cancer Research - New York NY

C07D 473/40, C07D 473/30, C07D 473/34, A61K 31/52, A61K 31/522, A61P 35/00

544277, 544264, 544265, 544276

Structural differences in binding pockets of members of the HSP90 family can be exploited to achieve differential degradation of kinases and other signaling proteins through the use of designed small molecules which interact with the N-terminal binding pocket with an affinity which is greater than ADP and different from the ansamycin antibiotics for at least one species of the HSP90 family. Moreover, these small molecules can be designed to be soluble in aqueous media, thus providing a further advantage over the use of ansamycin antibiotics. Pharmaceutical compositions can be formulated containing a pharmaceutically acceptable carrier and a molecule that includes a binding moiety which binds to the N-terminal pocket of at least one member of the HSP90 family of proteins. Such binding moieties were found to have antiproliferative activity against tumor cells which are dependent on proteins requiring chaperones of the HSP90 family for their function. Different chemical species have different activity, however, allowing the selection of, for example Her2 degradation without degradation of Raf kinase.

2007017, Aug 2, 2007

Jun 30, 2004

10/595029

Gabriela Chiosis - New York NY, US
Neal Rosen - New York NY, US
Henri Huezo - New York NY, US

Sloan-Kettering Institute for Cancer Research - New York NY

G01N 33/574, C07K 16/46

435007230, 530391100

A method for evaluation of molecules to identify those that can act as therapeutic inhibitors of Hsp90 makes use of a fluorescence polarization (FP) assay and a cell based assay, either individually or in combination. The FP assay uses a fluorescently-labeled Hsp90 binding agent and measure the degree of fluorescence polarization relative to the standard. A decrease in the degree of polarization indicates that fluorescently-labeled Hsp90 binding agent has been wholly or partially displaced by a candidate molecule, and identifies the molecule as having activity as an inhibitor of Hsp90. The cell based assay tests for decrease is an Hsp90-dependent activity of normal or tumor cells.

7812143, Oct 12, 2010

Apr 2, 2007

11/732362

Christine Pratilas - New York NY, US
Neal Rosen - New York NY, US

Memorial Sloan-Kettering Cancer Center - New York NY

C07H 21/04

536 231, 530350, 422 61, 435 6

The present invention provides identification of a thirty-five gene set that predicts the anticancer activity of inhibitors of the RAF/MEK/MAPK pathway, methods of qualifying cancer status in a subject, methods of identifying an anti-tumor response in a subject, methods of monitoring the efficacy of a therapeutic drug in a subject, and methods of identifying an agent useful in the treatment of a cancer based on expression of the thirty-five gene set.