Patents Represented by Attorney, Agent or Law Firm David A. Muthard
-
Patent number: 6391305Abstract: Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA), hydrophilic oligopeptide blocking groups and known cytotoxic agents are disclosed. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).Type: GrantFiled: June 28, 1999Date of Patent: May 21, 2002Assignee: Merck & Co., Inc.Inventors: Dong-Mei Feng, Victor M. Garsky, Raymond E. Jones, Allen I. Oliff, Jenny M. Wai
-
Patent number: 6380228Abstract: The present invention is directed to peptidomimetic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: April 6, 2001Date of Patent: April 30, 2002Assignee: Merck & Co., Inc.Inventors: Craig A. Stump, Theresa M. Williams
-
Patent number: 6376496Abstract: The present invention comprises piperazine-containing compounds which inhibit prenyl-protein transferases, including farnesyl-protein transferase and geranylgeranyl-protein transferase type I. Such therapeutic compounds are useful in the treatment of cancer.Type: GrantFiled: March 1, 2000Date of Patent: April 23, 2002Assignee: Merck & Co., Inc.Inventors: George D. Hartman, William C. Lumma, Jr., John T. Sisko, Anthony M. Smith, Thomas J. Tucker, Jeffrey M. Bergman
-
Patent number: 6358956Abstract: The present invention comprises piperazine-containing compounds which inhibit prenyl-protein transferases, including-farnesyl-protein transferase and geranylgeranyl-protein transferase type I. Such therapeutic compounds are useful in the treatment of cancer.Type: GrantFiled: March 1, 2000Date of Patent: March 19, 2002Assignee: Merck & Co., Inc.Inventors: George D. Hartman, William C. Lumma, Jr., John T. Sisko, Anthony M. Smith, Thomas J. Tucker, Gerald E. Stokker
-
Patent number: 6358985Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: June 29, 1999Date of Patent: March 19, 2002Assignee: Merck & Co., Inc.Inventors: Neville J. Anthony, Ian M. Bell, Douglas C. Beshore, Terrence M. Ciccarone, S. Jane de Solms, Christopher J. Dinsmore, Gerald E. Stokker
-
Patent number: 6355611Abstract: The present invention is directed to the sodium salt of formula 5: which may be useful in the treatment of prostate cancer and benign prostatic hyperplasia. Also described are lyophilized formulations that comprise the sodium salt 5 or the corresponding free acid.Type: GrantFiled: October 27, 2000Date of Patent: March 12, 2002Assignee: Merck & Co., Inc.Inventors: Shyam B. Karki, Mark Cameron, David R. Lieberman, Joseph E. Lynch, Michael A. Robbins, Yao-Jun Shi, Örn Almarsson, Michael J. Kaufman, Maneesh J. Nerurkar
-
Patent number: 6355643Abstract: The present invention comprises unsubstituted and substituted piperazine-containing compounds having alkanoyl, alkylsulfonyl, alkylamido or alkoxycarbonyl substituents, and having the formula A, which inhibit prenyl-protein transferases. In particular, the invention relates to prenyl-protein transferase inhibitors which are efficacious in vivo as inhibitors of geranylgeranyl-protein transferase type I (GGTase-I) and that inhibit the cellular processing of both the H-Ras protein and the K4B-Ras protein. Such therapeutic compounds are useful in the treatment of cancer.Type: GrantFiled: March 1, 2000Date of Patent: March 12, 2002Assignee: Merck & Co., Inc.Inventors: William C. Lumma, John T. Sisko, Anthony M. Smith, Thomas J. Tucker, Christopher J. Dinsmore, Jeffrey M. Bergman
-
Patent number: 6350755Abstract: The present invention is directed to peptidomimetic macrocyclic compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: January 9, 2001Date of Patent: February 26, 2002Assignee: Merck & Co., Inc.Inventors: S. Jane deSolms, Anthony W. Shaw
-
Patent number: 6335343Abstract: The present invention comprises piperazine/piperazinone-containing compounds having multicyclic ring system substituents on one of the piperazine/piperazinone nitrogens, which inhibit prenyl-protein transferases, including farnesyl-protein transferase and geranylgeranyl-protein transferase type I. Such therapeutic compounds are useful in the treatment of cancer.Type: GrantFiled: March 1, 2000Date of Patent: January 1, 2002Assignee: Merck & Co., Inc.Inventors: William C. Lumma, Jr., Anthony M. Smith, John T. Sisko
-
Patent number: 6333335Abstract: The present invention is directed to tetrahydro-imidazopyridinyl compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: June 30, 2000Date of Patent: December 25, 2001Assignee: Merck & Co., Inc.Inventors: Christopher J. Dinsmore, Samuel L. Graham, Theresa M. Williams
-
Patent number: 6329376Abstract: The present invention is directed to peptidomimetic piperazine-containing macrocyclic compounds which inhibit a prenyl-protein transferase (FTase) and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: October 26, 1999Date of Patent: December 11, 2001Assignee: Merck & Co., Inc.Inventor: Jeffrey M. Bergman
-
Patent number: 6239280Abstract: The present invention is directed to a process for synthesizing 1,5 disubstituted imidazoles with biaryl components of the formula (I): which are usefull as Farnesyl-Protein Transferase inhibitors.Type: GrantFiled: June 30, 1999Date of Patent: May 29, 2001Assignee: Merck & Co., Inc.Inventors: David Askin, Jennifer A. Cowen, Peter E. Maligres, J. Christopher McWilliams, Marjorie S. Waters
-
Patent number: 6207798Abstract: We have modified PE40 toxin by removing at least two of its four cysteine amino acid residues and have formed hybrid molecules containing modified PE40 linked to a cell recognition protein that can be an antibody, a growth factor, a hormone, a lymphokine, or another polypeptide cell recognition protein for which a specific cellular receptor exists whereby the modified PE40 toxin is directed to cell types having receptors for the cell recognition protein linked to the modified PE40.Type: GrantFiled: February 10, 1997Date of Patent: March 27, 2001Assignee: Merck & Co., Inc.Inventors: Allen I. Oliff, Gwynneth M. Edwards, Deborah D. Jones
-
Patent number: 6177404Abstract: Novel pharmaceutical compositions useful for the treatment of benign prostatic hyperplasia which comprises novel oligopeptides, which are selectively cleaved by enzymatically active PSA, in conjugation with a cytotoxic agent are described. Methods of treating benign prostate hypertrophy are also disclosed.Type: GrantFiled: August 3, 1998Date of Patent: January 23, 2001Assignee: Merck & Co., Inc.Inventors: Deborah DeFeo-Jones, Raymond E. Jones, Allen I. Oliff, Edward M. Scolnick, Victor M. Garsky
-
Patent number: 6160015Abstract: The present invention relates to compositions useful in the treatment of benign proliferative disorder neurofibromatosis comprising a farnesyl protein transferase inhibitor. Further contained in this invention are methods of treating benign proliferative disorder neurofibromatosis in a mammal, which methods comprise administering to said mammal, a farnesyl protein transferase inhibitor.Type: GrantFiled: July 27, 1999Date of Patent: December 12, 2000Assignee: University of CincinnatiInventor: Nancy Ratner
-
Patent number: 6143864Abstract: Oligopeptides which comprise amino acid sequences that are recognized and proteolytically cleaved by free prostate specific antigen (PSA) are described. Also described are assays which comprise such oligopeptides useful for determining free PSA protease activity in vitro and in vivo. Therapeutic agents which comprise conjugates of such oligopeptides and known cytotoxic agents are also described.Type: GrantFiled: June 6, 1995Date of Patent: November 7, 2000Assignee: Merck & Co., Inc.Inventors: Deborah DeFeo-Jones, Dong-Mei Feng, Victor M. Garsky, Raymond E. Jones, Allen I. Oliff
-
Patent number: 6130204Abstract: Oligopeptides which comprise amino acid sequences that are recognized and proteolytically cleaved by free prostate specific antigen (PSA) are described. Also described are assays which comprise such oligopeptides useful for determining free PSA protease activity in vitro and in vivo. Therapeutic agents which comprise conjugates of such oligopeptides and known cytotoxic agents are also described.Type: GrantFiled: April 6, 1998Date of Patent: October 10, 2000Assignee: Merck & Co., Inc.Inventors: Deborah DeFeo-Jones, Dong-Mei Feng, Victor M. Garsky, Raymond E. Jones, Allen I. Oliff
-
Patent number: 6127390Abstract: The present invention is directed to compounds which inhibit prenyl-protein transferase (FTase) and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.Type: GrantFiled: October 1, 1998Date of Patent: October 3, 2000Assignee: Merck & Co., Inc.Inventors: S. Jane deSolms, William C. Lumma, Jr., Anthony W. Shaw, John T. Sisko, Thomas J. Tucker
-
Patent number: 6127333Abstract: Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. The conjugates of the invention are characterized by a diamine linker between the oligopeptide and vinblastine. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).Type: GrantFiled: July 9, 1998Date of Patent: October 3, 2000Assignee: Merck & Co., Inc.Inventors: Stephen F. Brady, Victor M. Garsky, Joseph M. Pawluczyk
-
Patent number: 6103487Abstract: The instant invention provides for a method of inhibiting prenyl-protein transferases and treating cancer which comprises administering to a mammal a prenyl-protein transferase inhibitor which is efficacious in vivo as an inhibitor of geranylgeranyl-protein transferase type I (GGTase-I). The invention also provides for a method of inhibiting farnesyl-protein transferase and geranylgeranyl-protein transferase type I by administering a compound that is a dual inhibitor of both of those prenyl-protein transferases. The invention also provides for a method of identifying such a compound, the method comprising a modified inhibitory assay that incorporates a modulator anion that alters the in vitro potency of prenyl-protein transferase inhibitors in a way that predicts their potency in vivo, thus providing convenient identification of compounds that possess such in vivo activity.Type: GrantFiled: August 26, 1998Date of Patent: August 15, 2000Assignee: Merck & Co., Inc.Inventors: Stanley F. Barnett, David C. Heimbrook, Hans E. Huber, Denis R. Patrick