DR. JOHN W WARREN, M.D.
Osteopathic Medicine at Greene St, Baltimore, MD

6376197, Apr 23, 2002

May 22, 2000

09/576396

Susan K. Keay - Ellicott City MD
John W. Warren - Baltimore MD
Michael K. Hise - Columbia MD

University of Maryland, Baltimore - Baltimore MD

G01N 3353

435 71, 435 12, 436501, 530350, 530399

Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known that the bladder epithelium is often abnormal in IC. We discovered that normal, adult, human bladder epithelial cells are inhibited from proliferating by an anti-proliferative factor (APF) present in IC urine specimens. Inhibited proliferation may cause epithelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that levels of heparin binding—epidermal growth factor-like growth factor (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis. The invention herein is directed to the use of urine levels of HB-EGF as a diagnostic marker for IC.

6232289, May 15, 2001

Apr 16, 1999

9/293037

Susan Keay - Ellicott City MD
John Warren - Baltimore MD
Michael Hise - Columbia MD

University of Maryland, Baltimore - Baltimore MD

C07K 1400

514 2

Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known that the bladder epithelium is often abnormal in IC. We discovered that human bladder epithelial cells from both normal controls and IC patients are inhibited from proliferating by an anti-proliferative factor (APF) present in IC urine specimens. Inhibited proliferation may cause epithelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that 1) levels of heparin binding-epidermal growth factor-like growth factor (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis; 2) the APF found in IC urine specimens inhibits HB-EGF production by bladder epithelial cells; and 3) that the administration of rHB-EGF blocks the effects of APF on bladder epithelial cells from either IC patients or controls. The invention herein is directed to the administration of HB-EGF, or a functional derivative or agonist thereof, to bladder epithelial cells to inhibit the effects of APF on bladder cell proliferation, thereby reducing or eliminating the chronic damage to the bladder epithelium. HB-EGF or a functional derivative may be used as a therapy for patients suffering from IC or other diseases characterized by inhibited epithelial cell proliferation.

2001000, May 3, 2001

Dec 20, 2000

09/742140

Susan Keay - Ellicott City MD, US
John Warren - Baltimore MD, US
Michael Hise - Columbia MD, US

A61K031/70, A01N043/04

514/002000, 514/044000, 435/007100

Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known that the bladder epithelium is often abnormal in IC. We discovered that human bladder epithelial cells from both normal controls and IC patients are inhibited from proliferating by an anti-proliferative factor (APF) present in IC urine specimens. Inhibited proliferation may cause epithelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that 1) levels of heparin binding—epidermal growth factor-like growth factor (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis; 2) the APF found in IC urine specimens inhibits HB-EGF production by bladder epithelial cells; and 3) that the administration of rHB-EGF blocks the effects of APF on bladder epithelial cells from either IC patients or controls. The invention herein is directed to the administration of HB-EGF, or a functional derivative or agonist thereof, to bladder epithelial cells to inhibit the effects of APF on bladder cell proliferation, thereby reducing or eliminating the chronic damage to the bladder epithelium. HB-EGF or a functional derivative may be used as a therapy for patients suffering from IC or other diseases characterized by inhibited epithelial cell proliferation.

6156522, Dec 5, 2000

Jul 2, 1998

9/109548

Susan K. Keay - Ellicott City MD
John W. Warren - Baltimore MD
Michael K. Hise - Columbia MD

University of Maryland Baltimore - Baltimore MD

G01N 3353

435 71

Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known that the bladder epithelium is often abnormal in IC. We discovered that normal, adult, human bladder epithelial cells are inhibited from proliferating by an anti-proliferative fact (APF) present in IC urine specimens. Inhibited proliferation may cause epthelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that levels of heparin binding--epidermal growth factor-like growth fact (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis. The invention herein is directed to the use of urine levels of HB-EGF as a diagnostic marker for IC.

5962645, Oct 5, 1999

Oct 3, 1997

8/944202

Susan Keay - Ellicott City MD
John W. Warren - Baltimore MD
Michael Kleinberg - Baltimore MD
Michael K. Hise - Ellicott City MD

University of Maryland - Baltimore MD

C07K 100, C12G 100, G01N 33574

530350

A novel antiproliferative factor (APF) present in urine of patients with interstitial cystitis (IC) is described. This urine antiproliferative factor can serve as a marker for disease activity and its antagonists as therapeutic medicaments for IC. In addition, APF and its agonists can be used for treating diseases associated with cell proliferation.

2002003, Mar 21, 2002

May 22, 2001

09/862810

Harry Mobley - Baltimore MD, US
Xin Li - Elicott City MD, US
John Warren - Baltimore MD, US

A61K039/02, C07H021/04, C12N001/21, C07K014/195, C12N015/74

424/190100, 530/350000, 435/252300, 435/069300, 435/320100, 536/023700

The present invention is directed to a gene encoding an adhesin polypeptide of , the MrpH gene, its gene product, antigenic fragments of the adhesin polypeptide and antibodies directed against the MrpH gene product and fragments thereof. The present invention is also directed to a vaccine against and treatment of infection with anti-adhesin antibodies.

2002001, Feb 7, 2002

Apr 21, 2001

09/839859

Susan Keay - Ellicott City MD, US
John Warren - Baltimore MD, US
Michael Kleinberg - Baltimore MD, US
Michael Hise - Columbia MD, US

G01N033/53, G01N033/567, A61K039/395, C12N015/12, C12P021/00

530/350000, 424/130100, 435/007200, 514/002000, 536/023500

The invention relates to a novel antiproliferative factor (APF) present in urine of patients with interstitial cystitis (IC). APF is useful as a marker for disease activity and its antagonists are useful as therapeutic medicaments for IC and other conditions associated with elevated APF. APF and its agonists are useful in the treatment of diseases associated with cell proliferation, such as bladder cancer.