DAVID J RILEY, MD
Osteopathic Medicine in New Brunswick, NJ

6517824, Feb 11, 2003

May 20, 1996

08/650324

Joachim Kohn - Highland Park NJ
George J. Poiani - Jamesburg NJ
David J. Riley - New Brunswick NJ

University of Medicine Denistry of New Jersey - New Brunswick NJ
Rutgers University - New Brunswick NJ

A61K 3174

424 7806, 424 7817, 424 7808, 424 7827

A method for treating pulmonary hypertension and other diseases involving a defect in collagen metabolism, by administration of an effective amount of a liposome encapsulated copolymer conjugate antifibrotic composition, is disclosed. The antifibrotic agent is preferably a proline analog, such as cis-4-hydroxy-L-proline (cHyp). Consistent, high loadings ( 98%) of the antifibrotic agent are achieved by first forming a dipeptide with L-lysine, after which the dipeptide is copolymerized with the polymer component to form the copolymer conjugate. The polymer is preferably poly(ethylene glycol) having a weight average molecular weight of from about 500 to about 15,000. There is thus provided the efficient delivery and rateable release of the antifibrotic agent to inhibit collagen accumulation and thereby treat the diseases involved. Accordingly, there is a substantial reduction in the quantity of antifibrotic agent necessary, and thus a corresponding reduction in the potential for toxicity that would otherwise result from its prolonged administration.

5372807, Dec 13, 1994

Aug 24, 1992

7/934818

George J. Poiani - Jamesburg NJ
David J. Riley - New Brunswick NJ
Wei-Chi Liao - Princeton Junction NJ
Joachim Kahn - Highland Park NJ
Keria F. Gean - Highland Park NJ

University of Medicine and Dentistry of New Jersey - Newark NJ
Rutgers University - Piscataway NJ

A61K 3174, C07D20700

424 7836

The present invention concerns a method for treating fibrotic conditions by administration of an effective amount of an antifibrotic agent. The antifibrotic agent is preferably a proline analog, such as cis-4-hydroxy-L-proline (cHyp). The antifibrotic agent is operatively linked to a monomer or a polymer, with or without a linking compound, e. g. , lysine. Intravenous administration is preferred. The present method facilitates the delivery and release of the antifibrotic agent to inhibit collagen accumulation and thereby to treat fibrosis where collegen metabolism is implicated. A reduced quantity of the antifibrotic agent and a corresponding reduction in the potential for toxicity resulting from prolonged administration thereof may be realized.

2003018, Oct 2, 2003

Oct 30, 2002

10/285270

George Poiani - Mount Crawford VA, US
David Riley - New Brunswick NJ, US
Joachim Kohn - South Plainfield NJ, US
John Kemnitzer - San Diego CA, US

A61K038/16, A61K038/08, A61K038/06, A61K038/10

514/012000, 514/013000, 514/014000, 514/015000, 514/016000, 514/017000, 514/018000, 514/019000

A method for treating pulmonary hypertension and other diseases involving a defect in collagen metabolism, by administration of an effective amount of a liposome encapsulated copolymer conjugate antifibrotic composition, is disclosed. The antifibrotic agent is preferably proline analogs, such as cis-4-hydroxy-L-proline (CHOP), 3,4-dehydro-DL-proline (DHP), (R)-(-)-2-thiazolidine-4-carboxylic acid (THP), and (S)-(-)-2-azetidinecarboxylic acid (ACA). Consistent, high loadings ( 90%) of the antifibrotic agent are achieved by first forming a dipeptide with L-lysine, after which the dipeptide is copolymerized with the polymer component to form the copolymer conjugate. The polymer is preferably poly(ethylene glycol) having a weight average molecular weight of from about 500 to about 15,000. Efficient delivery and consistent release of the antifibrotic agent inhibits collagen accumulation and treats the diseases involved. Accordingly, there is a substantial reduction in the quantity of antifibrotic agent necessary, and thus a corresponding reduction in the potential for toxicity that would otherwise result from its prolonged administration.

5660822, Aug 26, 1997

Jun 7, 1995

8/479150

George J. Poiani - Jamesburg NJ
David J. Riley - New Brunswick NJ
Wei-Chi Liao - Princeton Junction NJ
Joachim Kahn - Highland Park NJ
Keria Fiorella Gean - Highland Park NJ

University of Medicine & Dentistry of N.J. - Piscataway NJ
Rutgers University - Piscataway NJ

A61K 31765, A61K 31785

424 7817

The present invention concerns a method for treating fibrotic conditions by administration of an effective amount of an antifibrotic agent. The antifibrotic agent is preferably a proline analog, such as cis-4-hydroxy-L-proline (cHyp). The antifibrotic agent is operatively linked to a monomer or a polymer, with or without a linking compound, e. g. , lysine. Intravenous administration is preferred. The present method facilitates the delivery and release of the antifibrotic agent to inhibit collagen accumulation and thereby to treat fibrosis where collegen metabolism is implicated. A reduced quantity of the antifibrotic agent and a corresponding reduction in the potential for toxicity resulting from prolonged administration thereof may be realized.

5720950, Feb 24, 1998

Jun 15, 1994

8/260080

George J. Poiani - Jamesburg NJ
David J. Riley - New Brunswick NJ
Wei-Chi Liao - Princeton Junction NJ
Joachim Kahn - Highland Park NJ
Keria Fiorella Gean - Highland Park NJ

University of Medicine & Dentistry of New Jersey - Piscataway NJ

A61K 31765, A61K 9127

424 7829

The present invention concerns a method for treating fibrotic conditions by administration of an effective amount of an antifibrotic agent. The antifibrotic agent is preferably a proline analog, such as cis-4-hydroxy-L-proline (cHyp). The antifibrotic agent is operatively linked to a monomer or a polymer, with or without a linking compound, e. g. , lysine. Intravenous administration is preferred. The present method facilitates the delivery and release of the antifibrotic agent to inhibit collagen accumulation and thereby to treat fibrosis where collagen metabolism is implicated. A reduced quantity of the antifibrotic agent and a corresponding reduction in the potential for toxicity resulting from prolonged administration thereof may be realized.