PROF. WILLIAM G STETLER-STEVENSON, M.D., PH.D.
Medical Practice in Gaithersburg, MD

5585356, Dec 17, 1996

Aug 12, 1994

8/289825

Lance A. Liotta - Potomac MD
William G. Stetler-Stevenson - Gaithersburg MD
Henry C. Krutsch - Bethesda MD

A61K 3800

514 17

A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity.

5270447, Dec 14, 1993

Mar 1, 1989

7/317407

Lance A. Liotta - Potomac MD
William Stetler-Stevenson - Gaithersburg MD
Henry Krutzsch - Bethesda MD

The United States of America as represented by the Department of Health
& Human Services - Washington DC

A61K 3702, C12N 1108

530326

A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV Procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence PRCG. The cysteine residue is required for activity.

5595885, Jan 21, 1997

Mar 29, 1993

8/039525

William G. Stetler-Stevenson - Gaithersburg MD
Lance A. Liotta - Potomac MD
Henry C. Krutzsch - Bethesda MD

The United States of America as represented by the Department of Health
and Human Services - Washington DC

C12N 1500

435 692

The present invention is an isolated protein of 21,600 Da which binds to both latent and activated type IV collagenase with high affinity at 1:1 molar stoichiometry, thereby abolishing enzyme activity. The protein is purified by affinity chromatography on solid phase metalloproteinase, or solid phase metalloproteinase substrates which bind the enzyme-inhibitor complex. The complete primary structure of this protein (initially called CSC-21K), as determined by sequencing overlapping peptides spanning the entire protein, reveals homology with a protein called TIMP, Tissue Inhibitor of Metalloproteinases. In addition, a cDNA for this novel inhibitor, now designated TIMP-2, was cloned from a melanoma cell and its sequence was compared with that of human TIMP-1. Northern blots of melanoma cell mRNA showed two distinct transcripts of 0. 9 kb and 3.

5698671, Dec 16, 1997

Aug 2, 1994

8/284721

William G. Stetler-Stevenson - Gaithersburg MD
Lance A. Liotta - Potomac MD
Henry C. Krutzsch - Bethesda MD

The United States of America as represented by the Secretary of the
Department of Health and Human Services - Washington DC

C07K 700

530324

Inappropriate degradation of extracellular matrix molecules by metalloproteinases plays an important role in a wide variety of pathologic conditions including neoplasia and arthritis. The present invention is an isolated protein of approximately 23,000 daltons in size which binds to metalloproteinases with high affinity, can be purified using affinity chromatography on solid phase metalloproteinases, and is potentially useful for therapy of pathologic conditions involving the inappropriate production of metalloproteinases. This protein is characterized by the presence of the following amino acid sequences: CSCSPVHPQQAFCNADVVIRAKAVSEKEVDSGNPIYGNNI KDIEFIYTAPSEAVCGVELDVEGK KRHITLCDFIVPWDTLSTTQKKSLNHRYQQGCEECKITRCPMIPCYISSPDECLWTDTVV KFFACIKRHITLCDFIVPWSQIADXLSS With the positions of the cysteine residues and associated disulfide bridges required for biologic activity.

5869277, Feb 9, 1999

Nov 8, 1991

7/789652

William G. Stetler-Stevenson - Gaithersburg MD
Lance Liotta - Potomac MD

C12Q 128, C12Q 137, G01N 3353

435 28

The present invention relates to the development of a modified substrate capture immunoassay useful in the detection of a neutral metalloproteinase enzyme, type IV collagenase. Capture and immobilization of this enzyme can be achieved by coating the microtiter plate with gelatin, an alternative substrate for this enzyme. The captured enzyme can then be detected by affinity purified rabbit anti-type IV collagenase antibodies prepared against synthetic peptides from the amino terminus of the enzyme. Soluble type IV collagenase can readily be detected in samples known to contain this enzyme. Using purified enzyme this assay method can detect less than 50 ng of latent type IV collagenase. Using EDTA, an inhibitor of this metalloproteinase, gelatin binding can be shown to be independent of catalytic activity.

7462593, Dec 9, 2008

Nov 7, 2003

10/529116

Frank Cuttitta - Adamstown MD, US
Alfredo Martinez - 26144 Galilea, La Rioja, ES
William G. Stetler-Stevenson - Kensington MD, US

A61K 38/00

514 2, 514 13

The present disclosure concerns the use of peptides and compositions, such as pharmaceutical compositions, to influence angiogenesis. Particular methods are useful for promoting angiogenesis, while others are particularly useful for inhibiting angiogenesis.

7862815, Jan 4, 2011

Sep 29, 2008

12/240656

Frank Cuttitta - Adamstown MD, US
Alfredo Martinez - La Rioja, ES
William G. Stetler-Stevenson - Kensington MD, US

The United States of America as represented by the Department of Health and Human Services - Washington DC

A61K 39/395, A61K 38/08, C07K 4/12, C07K 7/06, C07K 16/18

4241391, 514 15, 530328, 5303879

The present disclosure concerns the use of peptides and compositions, such as pharmaceutical compositions, to influence angiogenesis. Particular methods are useful for promoting angiogenesis, while others are particularly useful for inhibiting angiogenesis.

7364719, Apr 29, 2008

Oct 3, 2003

10/529118

Frank Cuttitta - Adamstown MD, US
Alfredo Martinez - Bethesda MD, US
William G. Stetler-Stevenson - Kensington MD, US
Edward J. Unsworth - Kensington MD, US
Juan M. Saavedra - Bethesda MD, US

The United States of America as represented by the Department of Health and Human Services - Washington DC

A61K 49/00

424 91, 424 111, 424 165, 424 169, 424 92

Methods and compounds are described for regulating blood pressure in a subject. Specific embodiments are methods for reversing vasodilation of blood vessels, by administering to a subject a therapeutically effective amount peptide AM(11-22). The vasoconstrictor can be used for a variety of purposes, including hemostasis or the treatment of shock, for example vasodilatory shock syndromes such as septic shock. Other specific embodiments are methods for reversing vasoconstriction of blood vessels, by administering to a subject a therapeutically effect amount of an inhibitor of AM(11-22), sufficient to reduce hypertension in the subject. Compounds and pharmaceutical compositions are also provided, as are kits.