Mamoru J Shoji

6664272, Dec 16, 2003

Dec 4, 2000

09/729662

James P. Snyder - Atlanta GA
Matthew C. Davis - Decatur GA
Brian Adams - Decatur GA
Mamoru Shoji - Atlanta GA
Dennis C. Liotta - McDonough GA
Eva M. Ferstl - Chamblee GA
Ustun B. Sunay - Tucker GA

Emory University - Atlanta GA

C07D21174

514327, 514432, 514460, 5142102, 51425214, 51425218, 514256, 514253, 514151, 514304, 514332, 514333, 514318, 544295, 544296, 546216, 549 28, 549416, 552 1, 568327

The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

7371766, May 13, 2008

Oct 21, 2003

10/690462

James P. Snyder - Atlanta GA, US
Matthew C. Davis - Decatur GA, US
Brian Adams - Decatur GA, US
Mamoru Shoji - Atlanta GA, US
Dennis C. Liotta - McDonough GA, US
Eva M. Ferstl - Chamblee GA, US
Ustun B. Sunay - Tucker GA, US

Emory University - Atlanta GA

C07D 401/14
C07D 407/14
C07D 409/14
A61K 31/4427
A61K 31/445
A61K 31/35
A61K 31/38
A61P 35/00

514332, 514333, 544255, 544256

The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

7842705, Nov 30, 2010

Mar 25, 2008

12/055068

James P. Snyder - Atlanta GA, US
Matthew C. Davis - Decatur GA, US
Brian Adams - Decatur GA, US
Mamoru Shoji - Atlanta GA, US
Dennis C. Liotta - McDonough GA, US
Eva M. Ferstl - Chamblee GA, US
Ustun B. Sunay - Tucker GA, US

Emory University - Atlanta GA

C07D 211/74
C07D 309/30
C07D 335/02
A61K 31/4412
A61K 31/351
A61K 31/382
A61P 35/00

514335, 514432, 514451, 546242, 549 28, 549416

The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

20040009914, Jan 15, 2004

Mar 7, 2003

10/383898

Mamoru Shoji - Conyers GA, US
James Snyder - Atlanta GA, US
Dennis Liotta - Atlanta GA, US
Aiming Sun - Atlanta GA, US

A61K038/17

514/012000

The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. The present invention provides methods to deliver a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors. The method involves tethering the drug to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The present invention further provides for the synthesis of novel curcuminoid-tether-linker-factor VIIa compositions and for methods of delivery of effective doses of the novel compositions to target tumor or endothelial cells in a patient

20050069551, Mar 31, 2005

Jul 28, 2004

10/900490

Mamoru Shoji - Conyers GA, US
James Snyder - Atlanta GA, US
Dennis Liotta - Atlanta GA, US
Aiming Sun - Atlanta GA, US

A61K039/395
C07K016/46

424178100, 530391100

Compositions and methods are provided for delivering cytotoxic compounds, such as natural curcumoids and synthetic curcumin analogs, specifically to cancer cells and to blood vessels that nourish solid tumors. The compositions include a cytotoxic drug tethered to a protein, such as factor VIIa, which can bind with high affinity to a receptor, such as tissue factor, expressed on the surface of cancer cells and vascular endothelial cells within the tumor microenvironment. Upon binding, the drug-protein-receptor complex is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The compositions and methods may increase the efficacy of the cytotoxic agets and decrease their side effects by delivering the agents to specific target cells, such as cancer cells, vascular endothelial cells in a tumor, and metastatic foci anywhere in the body, providing the target cells express surface bound tissue factor. Additionally, methods of synthesis of cytotoxic compound-protein conjugates are provided, for example, curcuminoid-tether-linker-factor VIIa composition, as well as pharmaceutically acceptable compositions and methods for delivering a therapeutically-effective amount of a cytotoxic compound-protein conjugate together with one or more pharmaceutically acceptable carriers (additives) and/or diluents to an animal or human patient.

20070270464, Nov 22, 2007

Feb 23, 2007

11/678156

Dennis Liotta - Atlanta GA, US
James Snyder - Atlanta GA, US
Mamoru Shoji - Conyers GA, US
Yang Lu - Lilbura GA, US
Aiming Sun - Atlanta GA, US

A61K 38/10
A61K 31/4433
A61K 31/4436
A61K 31/4545
A61P 3/10
C07D 211/44
C07D 211/82
C07D 401/12
C07D 405/06
C07D 409/06
A61K 38/08
A61K 38/06
A61K 38/05

514318000, 514327000, 514336000, 546193000, 546208000, 546216000, 546280100, 546282100, 514018000, 514012000, 514015000, 514016000, 514017000, 514019000, 530328000, 530329000, 530330000, 530331000

The invention provides sulfur-linked and nitrogen-linked peptidic conjugates of curcumin analogs that can provide increased water solubility and photostability as compared to the corresponding unmodified curcumin analogs without sacrificing therapeutic efficacy. The conjugates, which are believed to act as prodrugs, can be used therapeutically in the same manner as the unmodified curcumin analogs, such as in the treatment or prevention of cancer, diabetes, or inflammatory diseases. One conjugate comprises 3,5-Bis-(2-fluorobenzylidene)-piperidin-4-one, or a salt thereof, covalently attached through a sulfur linkage to a thiol-containing peptide such as glutathione.

20090011991, Jan 8, 2009

Feb 22, 2008

12/035995

Mamoru Shoji - Conyers GA, US
James Synder - Atlanta GA, US
Dennis Liotta - Atlanta GA, US
Aiming Sun - Atlanta GA, US

A61K 38/36
A61P 35/00

514 12

The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. Conjugates for delivering a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors, and methods of making and using thereof are described herein. The conjugate contains a cytotoxic compound bound to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. The cytotoxic compound is bound to the protein via a linker and a hydrolyzable bond. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage.