PATRICK A MCKEE, MD
Osteopathic Medicine at Everett Dr, Oklahoma City, OK

2004020, Oct 14, 2004

Feb 6, 2004

10/774242

Patrick McKee - Oklahoma City OK, US
Kyung Lee - Oklahoma City OK, US
Kenneth Jackson - Edmond OK, US
Victoria Christiansen - Oklahoma City OK, US

C12Q001/37, C07H021/04, C12N009/64

435/069100, 435/226000, 435/320100, 435/325000, 435/023000, 536/023200

Human -antiplasmin (AP) is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. Two forms of AP circulate in human plasma: a 464-residue protein, which we have termed “pro”-form, or AP, and an N-terminally-shortened 452-residue “activated”-form, or AP. The latter becomes crosslinked to fibrin by activated factor XIII about 5-fold more rapidly than APand makes fibrin resistant to digestion by plasmin. A new human plasma proteinase has been identified herein that cleaves the Pro12-Asn13 bond of APto yield AP. This enzyme is identified herein as Antiplasmin Cleaving Enzyme (APCE). Novel inhibitors of circulating APCE can diminish AP inhibitory capacity within forming fibrin or blood clots thereby making fibrin deposits or blood clots more susceptible to removal by plasmin. Patients who are susceptible to atherosclerotic plaque formation or are susceptible to developing thrombi that compromise organ function will benefit by therapies providing such inhibitors on a long term basis.

2008011, May 22, 2008

Nov 20, 2007

11/986058

Patrick McKee - Oklahoma City OK, US
Kyung Lee - Oklahoma City OK, US
Kenneth Jackson - Edmond OK, US
Victoria Christiansen - Oklahoma City OK, US

G01N 33/53, C12N 9/68

435007100, 435217000

Human α-antiplasmin (αAP) is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. Two forms of αAP circulate in human plasma: a 464-residue protein, which we have termed “pro”-form, or αAPand an N-terminally-shortened 452-residue “activated”-form, or αAP. The latter becomes crosslinked to fibrin by activated factor XIII about 5-fold more rapidly than αAPand makes fibrin resistant to digestion by plasmin. A new human plasma proteinase has been identified herein that cleaves the Pro12-Asn13 bond of αAPto yield αAP. This enzyme is identified herein as Antiplasmin Cleaving Enzyme (APCE). Novel inhibitors of circulating APCE can diminish αAP inhibitory capacity within forming fibrin or blood clots thereby making fibrin deposits or blood clots more susceptible to removal by plasmin. Patients who are susceptible to atherosclerotic plaque formation or are susceptible to developing thrombi that compromise organ function will benefit by therapies providing such inhibitors on a long term basis.

2011014, Jun 16, 2011

Dec 15, 2010

12/969161

Patrick A. McKee - Oklahoma City OK, US
Kenneth W. Jackson - Edmond OK, US
Kyung N. Lee - Oklahoma City OK, US
Victoria J. Christiansen - Oklahoma City OK, US

A61K 38/07, C07K 5/083, C07D 233/54, C07D 209/52, C07C 229/04, C07C 229/26, C07K 5/097, C07K 5/10, C07K 5/103, C07K 5/117, C07K 7/06, A61K 38/06, A61K 38/08, A61K 31/195, A61K 31/198, A61K 31/4172, A61K 31/4035, C12N 5/071, A61P 9/10, A61P 35/00

514 216, 530331, 5483391, 548516, 562553, 562561, 562562, 562563, 530330, 530329, 530328, 514 219, 514 218, 514 217, 514561, 514564, 514568, 514399, 514416, 435325

The presently disclosed and claimed inventive concepts include inhibitors of antiplasmin cleaving enzyme (APCE) and fibroblast activation protein alpha (FAP) which can be used in various therapies related to disorders of fibrin and α-antiplasmin and abnormal cell proliferation. The presently disclosed and claimed inventive concepts also include substrates of APCE and FAP, which may be used, for example, in screening methods for identifying such inhibitors. The presently disclosed and claimed inventive concepts further include, but are not limited to, methods of treating or inhibiting atherosclerosis and thrombus disorders by altering the ratios of types of plasma α-antiplasmin and to methods of treating conditions involving abnormal cell proliferation such as cancers.

2008005, Mar 6, 2008

Jun 6, 2007

11/811002

Patrick McKee - Oklahoma City OK, US
Kyung Lee - Oklahoma City OK, US
Kenneth Jackson - Edmond OK, US
Victoria Christiansen - Oklahoma City OK, US

C12Q 1/00, C07K 14/00, C07K 5/00, C07K 7/06, C07K 7/08

435004000, 530324000, 530325000, 530326000, 530327000, 530328000, 530330000

The present invention is directed toward inhibitors of antiplasmin cleaving enzyme for use in various therapies related to fibrin and α-antiplasmin, and to substrates of APCE, which may be used, for example, in screening methods for identifying such inhibitors. The present invention is further directed to methods of treating or inhibiting atherosclerosis and thrombus disorders by altering the rations of types of plasma α-antiplasmin.