Abstract: This invention relates to a method for the selective treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type 2 (HER2). More specifically, this invention relates to the use of substituted or unsubstituted mono- or bi-cyclic aryl, heteroaryl, cycloalkyl or heterocycloalkyl compounds in selectively regulating cell growth. Pharmaceutical compositions useful for the selective treatment of cell growth and differentiation are also described.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
February 24, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Michael R. Myers, Alfred P. Spada, Martin P. Maguire, Paul E. Persons
Abstract: This invention relates to the treatment of intimation in a patient suffering from such disorder. More specifically, the invention relates to mono- and/or bicyclic aryl or heteroaryl quinazoline compounds in the treatment of inflammation.
Type:
Grant
Filed:
June 4, 1996
Date of Patent:
February 3, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
Michael R. Myers, Alfred P. Spada, Martin P. Maguire, Paul E. Persons, Asher Zilberstein, Chin-Yi Jenny Hsu, Susan E. Johnson
Abstract: This invention relates to the modulation and/or inhibition of cell signaling, cell proliferation, cell inflammatory response, the control of abnormal cell growth and cell reproduction. More specifically, this invention relates to the use of mono- and/or bicyclic aryl or heteroaryl quinazoline compounds in inhibiting cell proliferation, including compounds which are useful protein tyrosine kinase (PTK) inhibitors. The method of treating cell proliferation using said quinazoline compounds and their use in pharmaceutical compositions is described.
Type:
Grant
Filed:
April 19, 1994
Date of Patent:
January 20, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Michael R. Myers, Alfred P. Spada, Martin P. Maguire, Paul E. Persons
Abstract: A method of improving the therapeutic activity of von Willebrand Factor obtained from materials comprising on Willebrand Factor comprising incubating said Factor at a temperature of about 20.degree. C. to about 55.degree. C. for about 1 to about 30 hours, most preferably at from about 45.degree. C. to about 55.degree. C. for about 1 to about 5 hours.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
January 20, 1998
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Abstract: Methods of inhibiting cell proliferation in a patient suffering from such disorder comprising the use of a styryl-substituted heteroaryl compound wherein the heteroaryl group is a monocyclic ring with 1 or 2 heteroatoms, or a bicyclic ring with 1 to about 4 heteroatoms, said compound optionally substituted or polysubstituted, with the proviso that when said ring is polysubstituted, the substituents do not have a common point of attachment to said ring, and those compounds wherein no substituent on the heteroaryl group is a carboxy group or an ester group, and pharmaceutical compositions comprising such compounds.
Type:
Grant
Filed:
May 19, 1995
Date of Patent:
October 14, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
Alfred P. Spada, Paul E. Persons, Alexander Levitzki, Chaim Gilon, Aviv Gazit
Abstract: A biologically active polymeric compound comprising an alkylaryl or heteroalkylaryl backbone having about 5 to about 50 repeating aromatic ring-containing units and which, according to the computer program marketed as SYBYL.RTM. version 5.2 running on a DEC VAX.RTM. 11/750 computer, is capable of forming a linear backbone having a helical secondary structure, and wherein the maximum diameter of the helical structure, as measured by the alkylaryl or heteroalkylaryl backbone, is less than 3 times greater than the maximum diameter of the aryl group of the alkylaryl or heteroalkylaryl backbone.
Type:
Grant
Filed:
August 9, 1991
Date of Patent:
October 7, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
John R. Regan, Michael N. Chang, Jack Newman, Schmuel Ben-Sasson
Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.
Type:
Grant
Filed:
February 8, 1995
Date of Patent:
August 12, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Martin P. Maguire, Paul E. Persons, Michael R. Myers
Abstract: The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of such treatment.
Type:
Grant
Filed:
May 31, 1995
Date of Patent:
August 12, 1997
Assignees:
Rhone-Poulenc Rorer Pharmaceuticals Inc., Osteosa Inc.
Inventors:
Colin R. Dunstan, Elzbieta Izbicka, Gregory R. Mundy, Wilson Burgess, Michael C. Jaye
Abstract: A method of inhibiting cell proliferation in a patient suffering from such disorder comprising the administration to the patient of a pharmaceutically effective amount of a pharmaceutical composition containing, in admixture with a pharmaceutically acceptable carrier, a compound, or a pharmaceutically acceptable salt thereof, of the formula ##STR1## wherein the radicals are defined in the specification.
Type:
Grant
Filed:
May 19, 1995
Date of Patent:
August 12, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
Alfred P. Spada, Paul E. Persons, Alexander Levitzki, Chaim Gilon, Aviv Gazit
Abstract: This invention relates to di[(1 R)-(-)-camphosulfonic acid) salt of [1S-[1.alpha.,2.beta.,3.beta.,4.alpha.,(S*)]]-4-[7-[[2-(3-chloro-2-thienyl )-1-ethylethyl]amino]3 H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,3-dihydroxycyclopentanecarboxamide , and a process for preparing the compound, comprising reacting a reaction mixture of (-)-1.beta.-N-ethyl-2.alpha.,3.alpha.-isopropylidenedioxy-4.beta.-[3-amino -4-[2-(5-chloro-2-thienyl)-(1R)-1-ethylethyl]amino-2-pyridyl]aminocyclopent anecarboxamide and formamidine acetate, and then treating the reaction mixture with (1 R)-(-)-10-camphorsulfonic acid.The salt is useful in purifying [1 S-[1.alpha.,2.beta.,3.beta.,4.alpha.,(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)- 1-ethylethyl]amino]-3 H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,3-dihydroxycyclopentanecarboxamide which possesses adenosine agonist activity and is useful as an anti-hypertensive, cardioprotective, anti-ischemic, and antilipolytic agent.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
July 29, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Cynthia A. Fink, Michael R. Myers, Laurence W. Reilly, Benoit J. Vanasse
Abstract: The present invention provides DNA constructs comprising a promoter DNA sequence and a DNA sequence coding for human serum albumin. In one embodiment the human serum albumin sequence comprises at least one, but not all, of the introns in the naturally occurring gene encoding for the HSA protein. In another embodiment the DNA constructs comprise a 5' regulatory sequence which directs the expression and secretion of HSA protein in the milk of a transgenic animal. Preferably, the promoter gene is a milk protein promoter sequence such as .beta.-lactoglobulin. The present invention also provides transgenic animals which secrete HSA in the milk of lactating females. The present invention also provides vectors comprising the constructs of the present invention.
Type:
Grant
Filed:
September 21, 1994
Date of Patent:
July 15, 1997
Assignees:
Rhone-Poulenc Rorer Pharmaceuticals, Inc., Peri Development Applications (1985) Ltd.
Inventors:
David R. Hurwitz, Margret Nathan, Moshe Shani
Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.
Type:
Grant
Filed:
May 11, 1995
Date of Patent:
July 8, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Alfred P. Spada, Michael R. Myers, Martin P. Maguire, Paul E. Persons
Abstract: The present invention provides therapeutic compositions for the prevention and treatment of pathological conditions involving bone and dental tissue. The present invention also provides a method to promote bone repair and/or growth for the treatment of pathological conditions involving bone tissue, for example, osteoporosis, Paget's disease, osteopetrosis, and periodontal disease and fracture repair, and healing of bone defects by administering FGF-1 to an animal or human in need of treatment.
Type:
Grant
Filed:
June 2, 1995
Date of Patent:
March 25, 1997
Assignees:
OsteoSA Inc., Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Colin R. Dunstan, Elzbieta Izbicka, Gregory R. Mundy, Wilson Burgess, Michael C. Jaye
Abstract: The compounds of formula I exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are Factor Xa inhibitors. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, which are for treating a patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of Factor Xa.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
March 18, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
William R. Ewing, Michael R. Becker, Henry W. Pauls, Daniel L. Cheney, Jonathan S. Mason, Alfred P. Spada
Abstract: Stable, highly purified Factor VIII protein formulations are provided in high ionic strength media which comprises: sodium chloride, potassium chloride or mixtures thereof; calcium chloride; and histidine as the buffering agent.
Type:
Grant
Filed:
December 27, 1994
Date of Patent:
February 25, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Abstract: This invention relates to a class of novel amino bi- and tri-carbocyclic alkane compounds having bis-aryl substitution which exhibit squalene synthase inhibition properties. The bi- and tri-carbocyclic alkane ring contains an amino group and the ring is further linked or bridged to two mono- and/or bicyclic rings. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
December 7, 1994
Date of Patent:
January 21, 1997
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Robert L. Morris, Kent W. Neuenschwander, Keith S. Learn, Anthony C. Scotese
Abstract: Simplified methods to produce recombinant adeno-associated virus (rAAV) vectors are described. The AAV rep and cap genes are combined in a single recombinant adenovirus vector, i.e., a rep/cap adenovirus vector which combines in a single vector all complementing functions required for rAAV production. The rep/cap vectors of the present invention comprise: genes encoding helper functions, preferably from adenovirus, sufficient to permit AAV replication; and AAV cap and rep genes. In adenovirus rep/cap vectors the rep and cap genes may, for example, replace the adenovirus E3 gene or the adenovirus E1a and E1b genes.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
December 31, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
Jane S. Lebkowski, Maureen A. McNally, Thomas B. Okarma
Abstract: Endothelial cell growth factor is achieved through the application of recombinant DNA technology to prepare cloning vehicles encoding the ECGF protein and procedures are disclosed for recovering ECGF protein essentially free of other proteins of human origin. The product is useful for, among other purposes, diagnostic applications and as potential in the treatment of damaged blood vessels or other endothelial cell-lined structures.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
November 5, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals, Inc.
Inventors:
Michael Jaye, Wilson Burgess, Thomas Maciag, William N. Drohan
Abstract: This invention relates to aromatic oligomeric compounds useful in the treatment of cardiovascular, bone metabolic, hypolipidaemic, neuronal, gastrointestinal and elastase-mediated connective tissue degradation disorders and disorders which may be treated by agents effective in binding DNA, to processes for preparation of such oligomeric compounds, to pharmaceutical compositions including such oligomeric compounds, and to their use in the treatment of such disorders.
Type:
Grant
Filed:
September 10, 1993
Date of Patent:
November 5, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
John R. Regan, Daniel G. McGarry, Michael N. Chang, Jeffrey N. Barton, Jack Newman, Schmuel Ben-Sasson
Abstract: This invention relates to a class of novel phosphonate derivatives of lipophilic amines which exhibit squalene synthase inhibition properties. More specifically the compounds are bis aryl cycloalkylamino and azacycloalkyl phosphonates. Compounds of this invention reduce levels of serum cholesterol in the body without significantly reducing mevalonic metabolite synthesis. This invention relates also to pharmacological compositions and method of treatment for lowering serum cholesterol levels using the compounds of this invention.
Type:
Grant
Filed:
May 4, 1995
Date of Patent:
October 8, 1996
Assignee:
Rhone-Poulenc Rorer Pharmaceuticals Inc.
Inventors:
Henry W. Pauls, Yong-Mi Choi, Dilip V. Amin