Title of Invention	N-(9-OXA-n-DECYL)-1,5--DIDEOXY-1,5-IMINO-D-GLUCITOL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
Abstract	A salt of a) an Msubstituted-l,5-dideoxy-1.5-D-glwcitol compound of Formula I: Of a nucleotide having an acidic moiety and a nucleotide. Wherein R is selected from the group consisting of straight chain alkyl having a chain length of * branched chain alkyl having a chain length of in the main chain, alkoxy acyl, aerially and cydoalkylalkyK and Wherein W, X, Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aryl, and trifluoroalkanoyl; and a compound selected from the group consisting of a nucleoside having an acidic moiety and a nucleotide.

Title of Invention

N-(9-OXA-n-DECYL)-1,5--DIDEOXY-1,5-IMINO-D-GLUCITOL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Abstract

A salt of a) an Msubstituted-l,5-dideoxy-1.5-D-glwcitol compound of Formula I: Of a nucleotide having an acidic moiety and a nucleotide. Wherein R is selected from the group consisting of straight chain alkyl having a chain length of * branched chain alkyl having a chain length of in the main chain, alkoxy acyl, aerially and cydoalkylalkyK and Wherein W, X, Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aryl, and trifluoroalkanoyl; and a compound selected from the group consisting of a nucleoside having an acidic moiety and a nucleotide.

Full Text	The present invention relates to a salt of N-Substituted-1, 5-Dideoxy-l, 5-D-Glucitol for Hepatitis virus infections. Field pr the Invention The present invention relates to methods and compositions for treating hepatitis virus infections, especially hepatitis B virus infections, in mammals, especially humans. The methods comprise (1) administer Msubstimted-l,5-didcoxy-l ,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral a gems, nucleotide antiviral agents, mixtures thereof, or immunomodulatingZ-immunostimulating agents, or (2) administering A'-substituted-l,5-dideoxy'l,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and iinmunoroodulating/'unmunosiimulating agents. Such combinations of -hepatitis viral agents show unexpected efficacy in neighing replication and secretion of hepatitis viruses in cells of mammals infected with these viruses. Description of Related Art Hepatitis Viruses Hepatitis B Virus (HBV. HcpB) is a causative agent of acute and chronic liver disease including liver fibrosis, cirrhosis inflammatory liver disease, and hepatic cancer that can lead to death in some patients (Jokily, Wolfgang K., Virology, Third Edition, Appleton & Lange. Norwalk, Connecticut, 1988 (ISBN 0-8385-9462.X)). Although effective vaccines are available, there arc still more than 300 million people worldwide, i.e., 5% of the world's population, chronically infected with the virus (Ocarina, S. A., ct. ah, Antiviral Chemistry & Chemotherapy {«1996) 7(2):53-64). Such vaccines have no therapeutic value for those already infected with the virus. In Europe and North America, between 0.1% to 1% of he population is infected. Estimates arc that 15% to 20% of individuals who acquire the infection develop cirrhosis or another chronic disability from IIBV infection. Once liver cirrhosis is established, morbidity and mortality are substantial, with about a 5-year patient survival period (Bloc, H., E., etal., Advanced Drug Delivery Reviews (1995) 17:321 -331). It is therefore necessary and of high priority to find improved and effective anti-HBV anti-hepatitis therapies (Learning, S. A., et. al.. Antiviral Chemistry & Chemotherapy (1996) 7(2): 53-64). Other localities viruses significant as agents of Hinnen disease include Hepatic A, Hepatitis B, Hepatitis C, Hepatitis Delta, Hepatitis E, Hepatitis F, and Hepatitis G (Coates, J. A. V., etal., Exp. Open, Ther. Patents (1995) 5(8):747-756). In addition, there arc animal hepatitis viruses that are species-specific. These include, for example, those infecting ducks, woodchucks, and mice. Glycosidase inhibitors such as N-alkyl ,5-dideoxy-l ,5-iniino-D-glucilDl compounds wherein the alkyl group contains between three and six carbon anions have been shown lo be effective in the treatment of Hepatitis B infection (PCT International Publication WO 95/19172). For example, A' (n-butyl)-dcoxynojxnmycin (N-butyl-DNJ; M(n-buty 1)-1 -5-didcoxy-1,5-imino-D-giucitol) is effective for this purpose (Block, T. M.. Proc. Nat CaClz Csl USA (1994) 91:2235-2239; Ganem, B. Chemiracis: Organic Chemistry (1994) 7(2), 106-l(r7). N-butyl-DNJ has also been tested as an anti-HTV-1 same in HIV infected patients, and is known to be well tolerated. Avoider alpha glycosidase inhibitor, dcoxynojirinnycin (DNJ), has been suggested as an antiviral agent for use in combination with //-(phosphonoaceiyl)-L-asp artic acid (PALA) (WO 93/18763). However, combinations of A -substituted-imino-D-glucitol derivatives and other antiviral agents for the treatment of hepatitis virus infections have not been previously disclosed or suggested. From results obtained in a woodchuck animal model of hepatitis vim’s infection, Block et al. ((1998) Nature Medicine 4(5):610-614) suggested that glucosidase inhibitors such as /V-only DNJ, which interfere with specific steps in the N-linked glycosylation pathway of hepatitis virus lipoproteins, may be tactful in targeting glycosylation processing as a therapeutic intervention for chapatti; B vim’s. Nucleoside and Nndeotide Antiviral Agents Reverse transcripts inhibitors, including the class of nucleoside and nucleotide analogs, were first developed as drags for the treatment of retroviruses such as human immunodeficiency virus (HIV), the causative agent of AIDS. Increasingly, these compounds have footed use against other vises, including both RNA and DNA viruses, via viral screening and chemical modification strategies. Nucleoside and nucleotide analogs exert their antiviral activities by inhibiting the corresponding DNA and RNA polymerases responsible for synthesis of viral DNA and RNA, respectively. Because viruses contain different forms of polymerases, the same nucleoside/nucleotide compound can have a dramatically different effect against different viruses. For example. lamivudinc (3TC7' ) to be useful against HBV infection, whereas zidovudine (AZT™) appears 10 have little use against the same vim’s (Gash. R.G., etal,, Exp. Open. Invest, Drugs (1995) 4(2):95-115). Toxicity has been significant wit some nucleoside analog antiviral. For example, clinical tests on the use of the nucleoside analog fialuridine (FIAU) treatment of chronic liepatitis B were suspended recently due to drug-related liver failure leading to death in some patients. Consequently, there is still a need for safer drug regimens for the tegument of hepatitis B infections and hqjatitis (Mechanic, M. G., et. al., Am viral Research (1994) 24:245-257). Immunomoduiaiors/immunostimulators such as interferon Alfa and other cytokines have been used for the treatment of H6V infection with promising results. Unfortunately. the response rates are lower than dashed. interferon treatment is currently approved by the FDA for the tegument of Hepatitis B. Other immune system-affecting drug candidates are presently being investigated. These include thematic peptides for use in the trcatixKrnt of chronic hesitates B (CHB), isoprinosint, steroids, Sniff base-forming salicylaldehydc derivatives such as Tucarcsol, levamisoU and the like (Gash. R. G., etal., Exp, Open. Invest, Drugs (1995) 4(2):95-115; Coates, J.A.Y,, etal.. Exp. Open. Ther. Patents (1995) 5(8):747-765). SUMMARY OF THE INVENTION As noted above, the use of the iV-substituted-imino-D-gluchol coxnpoimds and derivatives thereof disclosed herein alone, or in combination with other aim-hepatitis virus compounds has, to the present inventor's knowledge, neither been suggested nor disclosed. The use of two or more anti-viral agents to provide improved then for the treatment of hepatitis B virus infections is disable due to the morbidity and mortality of (he disease. Commotion they is also desirable since h should reduce toxicity m patients as it enables the physician to administer lower doses of one or more of the drugs being given to a patient can also help to prevent the development of drug resistance inpatients (Wiling, E. H. H., Pharmacia’s Weekblads Scientific Edition (1992) 14(4A):268-274) The result of an improved efficacy configuration combined with a relative lack of toxicity and development of resistance would provide a much improved drug treatment profile. The present inventors have surprisingly discovered that the use of the A^-substituted-l,5-dideoxy-l,5-imino-D-glucitol compounds disclosed herein are effective in treating hepatitis virus infections. Furthermore, the use of these compounds in combination with nucleoside or nucleotide antiviral compounds. or combinations thereof, and/or immunomodulators/iinmunostiraulanls, results in unexpectedly greater anti-hepatitis virus effectiveness of the compounds canard to the combined antiviral activities expected of the individual compounds alone. Whether this is due to different mechanisms of action of the different classes of drugs employed or some other biological phenomenon is presently unclear. Accordingly, in a first aspect, the present invention provides a method for treating a hepatitis virus infection in a mammal, comprising administering to said mammal an anti-hepatitis virus effective amount of at least one /V-substituted-l,5-didcoxy-l,5-imino-D-glucitol compound of formula I or a pharmaceutically acceptable salt thereof; (I) wherein R is selected from the group consisting of straight chain alkyl having a chain length of C7 to C20. branched chain alkyl having a chain length of C3 to C10 in the main chain, alkoxyalkyl, aryl alkyl, and cycloalkylalkyl, and wherein W, X, Y and Z are each Woodchucks can be anesthetized (Smog/kg ketonic, Smog/kg zylazine), weighed, and blood obtained prior lo initial irearaieni, at weekly intervals during the six week period of treatment, and at 1, 2, and 4 weeks following treatment. Serum can be harvested and divided into aliquots. One aliquot can be used for analysis of WHV DNA by dot blot hybrid/ on and for What by ELISA. Cobs and clinical biochemical profiles can be obtained prior to treatment and at the end of treatment. A second aliquot can be maintained as an archive sample. Other aliquots of serum can be used for drug analysis and special WHV DNA analyses. The invention being thus described, it will be obvious that the same can be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications and equivalents as would be obvious to one skilled in the art are intended to be included within the scope of the following claims WE CLAIM: 1 . A salt of a) an Msubstituted-l,5-dideoxy-1.5-D-gluci lO compound of Formula I: and b) a compound selected from the group consisting of a nucleoside having an acidic moiety and a nucleotide. wherein R is selected from the group consisting of straight chain alkyl having a chain length of . branched chain alkyl having a chain length of C1 to C20 in the main chain, alkoxyaUcyl, aryl alkyl. and cycloalkylalkyl, and wherein W. X, Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aryl, and trifluoroalkanoyl; and a compound selected from the group consisting of a nucleoside bashing an acidic moiety and a nucleotide. S. The salt as claimed in claim 1, wherein said nucleoside having an acidic moiety is selected from the group consisting of compounds of Formula JI, III, IV, V, and VL 9. The salt as claimed in claim 1, wherein said nucleotide is selected from tick group consisting of compounds of Formula II. Ill, IV, V, and VL 10 . The salt as claimed in claim 9,wherein said nucleotide is selected from the group consisting of: (-)-2 * -deoxy-3 * -thiocytidine-5' -triphosphate (3TC); l-C?'-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine triphosphate (FIACTP); cycloid triphosphate (ACVTP); E-5-(2-bromovtnyl).2'-deoxyuridine triphosphate; and 9-beta-D-arabinofuranosyI-9H-purinc-6-amine-5 '-monophosphate monohydratc (Aral-AMP). U . The salt as claimed in claim 1, wherein: said A^-substituted-l,5-dideoxy-l,5'immo-D-glucitol compound is selected from the group consisting of Aft-(n-only)-l,5-dideoxy-l,5-imino-D-glucitol and Ar-(n-only)- l,5-didcoxy-l,5-imino-D-glucitol, tetra butyrate; and said nucleotide is (•)-2'-dcoxy-3'-thiocytidinc-5'•triphosphate. 12. A method, comprising reacting N-(n-only)-l,5-dideoxy-1.5-imino-D-glucitol and (-)-2-deoxy-3'-thiocytidme-5'-iriphosphatc under salt-forming conditions. 13 . A salt formed by the method as claimed in claim 12.

Full Text

The present invention relates to a salt of N-Substituted-1, 5-Dideoxy-l, 5-D-Glucitol for Hepatitis virus infections.
Field pr the Invention
The present invention relates to methods and compositions for treating hepatitis virus infections, especially hepatitis B virus infections, in mammals, especially humans. The methods comprise (1) administer Msubstimted-l,5-didcoxy-l ,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral a gems, nucleotide antiviral agents, mixtures thereof, or immunomodulatingZ-immunostimulating agents, or (2) administering A'-substituted-l,5-dideoxy'l,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and iinmunoroodulating/'unmunosiimulating agents. Such combinations of -hepatitis viral agents show unexpected efficacy in neighing replication and secretion of hepatitis viruses in cells of mammals infected with these viruses.
Description of Related Art Hepatitis Viruses
Hepatitis B Virus (HBV. HcpB) is a causative agent of acute and chronic liver disease including liver fibrosis, cirrhosis inflammatory liver disease, and hepatic cancer that can lead to death in some patients (Jokily, Wolfgang K., Virology, Third Edition, Appleton & Lange. Norwalk, Connecticut, 1988 (ISBN 0-8385-9462.X)). Although effective vaccines are available, there arc still more than 300 million people worldwide,

i.e., 5% of the world's population, chronically infected with the virus (Ocarina, S. A., ct. ah, Antiviral Chemistry & Chemotherapy {«1996) 7(2):53-64). Such vaccines have no therapeutic value for those already infected with the virus. In Europe and North America, between 0.1% to 1% of he population is infected. Estimates arc that 15% to 20% of individuals who acquire the infection develop cirrhosis or another chronic disability from IIBV infection. Once liver cirrhosis is established, morbidity and mortality are substantial, with about a 5-year patient survival period (Bloc, H., E., etal., Advanced Drug Delivery Reviews (1995) 17:321 -331). It is therefore necessary and of high priority to find improved and effective anti-HBV anti-hepatitis therapies (Learning, S. A., et. al.. Antiviral Chemistry & Chemotherapy (1996) 7(2): 53-64).
Other localities viruses significant as agents of Hinnen disease include Hepatic A, Hepatitis B, Hepatitis C, Hepatitis Delta, Hepatitis E, Hepatitis F, and Hepatitis G (Coates, J. A. V., etal., Exp. Open, Ther. Patents (1995) 5(8):747-756). In addition, there arc animal hepatitis viruses that are species-specific. These include, for example, those infecting ducks, woodchucks, and mice.

Glycosidase inhibitors such as N-alkyl ,5-dideoxy-l ,5-iniino-D-glucilDl compounds wherein the alkyl group contains between three and six carbon anions have been shown lo be effective in the treatment of Hepatitis B infection (PCT International Publication WO 95/19172). For example, A' (n-butyl)-dcoxynojxnmycin (N-butyl-DNJ; M(n-buty 1)-1 -5-didcoxy-1,5-imino-D-giucitol) is effective for this purpose (Block, T. M.. Proc. Nat CaClz Csl USA (1994) 91:2235-2239; Ganem, B. Chemiracis: Organic Chemistry (1994) 7(2), 106-l(r7). N-butyl-DNJ has also been tested as an anti-HTV-1 same in HIV infected patients, and is known to be well tolerated. Avoider alpha glycosidase inhibitor, dcoxynojirinnycin (DNJ), has been suggested as an antiviral agent for use in combination with //-(phosphonoaceiyl)-L-asp artic acid (PALA) (WO 93/18763). However, combinations of A -substituted-imino-D-glucitol derivatives and other antiviral agents for the treatment of hepatitis virus infections have not been previously disclosed or suggested. From results obtained in a woodchuck animal model of hepatitis vim’s

infection, Block et al. ((1998) Nature Medicine 4(5):610-614) suggested that glucosidase inhibitors such as /V-only DNJ, which interfere with specific steps in the N-linked glycosylation pathway of hepatitis virus lipoproteins, may be tactful in targeting glycosylation processing as a therapeutic intervention for chapatti; B vim’s.
Nucleoside and Nndeotide Antiviral Agents
Reverse transcripts inhibitors, including the class of nucleoside and nucleotide analogs, were first developed as drags for the treatment of retroviruses such as human immunodeficiency virus (HIV), the causative agent of AIDS. Increasingly, these compounds have footed use against other vises, including both RNA and DNA viruses, via viral screening and chemical modification strategies. Nucleoside and nucleotide analogs exert their antiviral activities by inhibiting the corresponding DNA and RNA polymerases responsible for synthesis of viral DNA and RNA, respectively. Because viruses contain different forms of polymerases, the same nucleoside/nucleotide compound can have a dramatically different effect against different viruses. For example. lamivudinc (3TC7' ) to be useful against HBV infection, whereas zidovudine

(AZT™) appears 10 have little use against the same vim’s (Gash. R.G., etal,, Exp. Open. Invest, Drugs (1995) 4(2):95-115).
Toxicity has been significant wit some nucleoside analog antiviral. For example, clinical tests on the use of the nucleoside analog fialuridine (FIAU) treatment of chronic liepatitis B were suspended recently due to drug-related liver failure leading to death in some patients. Consequently, there is still a need for safer drug regimens for the tegument of hepatitis B infections and hqjatitis (Mechanic, M. G., et. al., Am viral Research (1994) 24:245-257).

Immunomoduiaiors/immunostimulators such as interferon Alfa and other cytokines have been used for the treatment of H6V infection with promising results. Unfortunately. the response rates are lower than dashed. interferon treatment is currently approved by the FDA for the tegument of Hepatitis B. Other immune system-affecting drug candidates are presently being investigated. These include thematic peptides for use in the trcatixKrnt of chronic hesitates B (CHB), isoprinosint, steroids, Sniff base-forming salicylaldehydc derivatives such as Tucarcsol, levamisoU and the like (Gash. R. G., etal., Exp, Open. Invest, Drugs (1995) 4(2):95-115; Coates, J.A.Y,, etal.. Exp. Open. Ther. Patents (1995) 5(8):747-765).
SUMMARY OF THE INVENTION As noted above, the use of the iV-substituted-imino-D-gluchol coxnpoimds and derivatives thereof disclosed herein alone, or in combination with other aim-hepatitis virus compounds has, to the present inventor's knowledge, neither been suggested nor disclosed. The use of two or more anti-viral agents to provide improved then for the treatment of hepatitis B virus infections is disable due to the morbidity and mortality of (he disease. Commotion they is also desirable since h should reduce toxicity m patients as it enables the physician to administer lower doses of one or more of the drugs being given to a patient can also help to prevent the development

of drug resistance inpatients (Wiling, E. H. H., Pharmacia’s Weekblads Scientific Edition (1992) 14(4A):268-274) The result of an improved efficacy configuration combined with a relative lack of toxicity and development of resistance would provide a much improved drug treatment profile.
The present inventors have surprisingly discovered that the use of the A^-substituted-l,5-dideoxy-l,5-imino-D-glucitol compounds disclosed herein are effective in treating hepatitis virus infections. Furthermore, the use of these compounds in combination with nucleoside or nucleotide antiviral compounds. or combinations thereof, and/or immunomodulators/iinmunostiraulanls, results in unexpectedly greater anti-hepatitis virus effectiveness of the compounds canard to the combined antiviral activities expected of the individual compounds alone. Whether this is due to different mechanisms of action of the different classes of drugs employed or some other biological phenomenon is presently unclear.
Accordingly, in a first aspect, the present invention provides a method for treating a hepatitis virus infection in a mammal, comprising administering to said mammal an anti-hepatitis virus effective amount of at least one /V-substituted-l,5-didcoxy-l,5-imino-D-glucitol compound of formula I or a pharmaceutically acceptable salt thereof;

(I) wherein R is selected from the group consisting of straight chain alkyl having a chain length of C7 to C20. branched chain alkyl having a chain length of C3 to C10 in the main chain, alkoxyalkyl, aryl alkyl, and cycloalkylalkyl, and wherein W, X, Y and Z are each

Woodchucks can be anesthetized (Smog/kg ketonic, Smog/kg zylazine), weighed, and blood obtained prior lo initial irearaieni, at weekly intervals during the six week period of treatment, and at 1, 2, and 4 weeks following treatment. Serum can be harvested and divided into aliquots. One aliquot can be used for analysis of WHV DNA by dot blot hybrid/ on and for What by ELISA. Cobs and clinical biochemical profiles can be obtained prior to treatment and at the end of treatment. A second aliquot can be maintained as an archive sample. Other aliquots of serum can be used for drug analysis and special WHV DNA analyses.
The invention being thus described, it will be obvious that the same can be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the present invention, and all such modifications and equivalents as would be obvious to one skilled in the art are intended to be included within the scope of the following claims

WE CLAIM:
1 . A salt of a) an Msubstituted-l,5-dideoxy-1.5-D-gluci lO compound of Formula I: and b) a compound selected from the group consisting of a nucleoside having an acidic moiety and a nucleotide.

wherein R is selected from the group consisting of straight chain alkyl having a chain length of . branched chain alkyl having a chain length of C1 to C20 in the main chain, alkoxyaUcyl, aryl alkyl. and cycloalkylalkyl, and
wherein W. X, Y and Z are each independently selected from the group consisting of hydrogen, alkanoyl, aryl, and trifluoroalkanoyl; and
a compound selected from the group consisting of a nucleoside bashing an acidic moiety and a nucleotide.

S. The salt as claimed in claim 1, wherein said nucleoside having an acidic moiety is selected from the group consisting of compounds of Formula JI, III, IV, V, and VL
9. The salt as claimed in claim 1, wherein said nucleotide is selected from tick group consisting of compounds of Formula II. Ill, IV, V, and VL
10 . The salt as claimed in claim 9,wherein said nucleotide is selected from the group consisting of:
(-)-2 * -deoxy-3 * -thiocytidine-5' -triphosphate (3TC);
l-C?'-deoxy-2*-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine triphosphate (FIACTP);
cycloid triphosphate (ACVTP);
E-5-(2-bromovtnyl).2'-deoxyuridine triphosphate; and
9-beta-D-arabinofuranosyI-9H-purinc-6-amine-5 '-monophosphate monohydratc
(Aral-AMP).
U . The salt as claimed in claim 1, wherein:
said A^-substituted-l,5-dideoxy-l,5'immo-D-glucitol compound is selected from
the group consisting of Aft-(n-only)-l,5-dideoxy-l,5-imino-D-glucitol and Ar-(n-only)-
l,5-didcoxy-l,5-imino-D-glucitol, tetra butyrate; and
said nucleotide is (•)-2'-dcoxy-3'-thiocytidinc-5'•triphosphate.

12. A method, comprising reacting N-(n-only)-l,5-dideoxy-1.5-imino-D-glucitol and (-)-2*-deoxy-3'-thiocytidme-5'-iriphosphatc under salt-forming conditions.
13 . A salt formed by the method as claimed in claim 12.

Documents:

5290-CHENP-2007 EXAMINATION REPORT REPLY RECEIVED 17-10-2012.pdf

5290-CHENP-2007 AMENDED PAGES OF SPECIFICATION 11-06-2013.pdf

5290-CHENP-2007 AMENDED CLAIMS 11-06-2013.pdf

5290-CHENP-2007 AMENDED PAGES OF SPECIFICATION 30-09-2013.pdf

5290-CHENP-2007 ASSIGNMENT 02-07-2013.pdf

5290-CHENP-2007 ASSIGNMENT 11-06-2013.pdf

5290-CHENP-2007 CORRESPONDECE OTHERS. 30-09-2013.pdf

5290-CHENP-2007 CORRESPONDENCE OTHERS 26-07-2013.pdf

5290-CHENP-2007 CORRESPONDENCE OTHERS 20-09-2013.pdf

5290-CHENP-2007 CORRESPONDENCE OTHERS 02-07-2013.pdf

5290-CHENP-2007 CORRESPONDENCE OTHERS 12-08-2013.pdf

5290-CHENP-2007 EXAMINATION REPORT REPLY RECEIVED 11-06-2013.pdf

5290-CHENP-2007 FORM-1 30-09-2013.pdf

5290-CHENP-2007 FORM-13 02-07-2013.pdf

5290-CHENP-2007 FORM-3 11-06-2013.pdf

5290-CHENP-2007 FORM-6 02-07-2013.pdf

5290-CHENP-2007 OTHER PATENT DOUCMENT 11-06-2013.pdf

5290-CHENP-2007 OTHER PATENT DOUCMENT 1 11-06-2013.pdf

5290-CHENP-2007 OTHERS. 02-07-2013.pdf

5290-CHENP-2007 DECLARATION 30-09-2013.pdf

5290-chenp-2007-abstract.pdf

5290-chenp-2007-claims.pdf

5290-chenp-2007-correspondnece-others.pdf

5290-chenp-2007-description(complete).pdf

5290-chenp-2007-drawings.pdf

5290-chenp-2007-form 1.pdf

5290-chenp-2007-form 26.pdf

5290-chenp-2007-form 3.pdf

5290-chenp-2007-form 5.pdf

5290-chenp-2007-pct.pdf

abs-5290-chenp-2007.jpg

« Previous Patent

Next Patent »

Patent Number

259080

Indian Patent Application Number

5290/CHENP/2007

PG Journal Number

09/2014

Publication Date

28-Feb-2014

Grant Date

25-Feb-2014

Date of Filing

21-Nov-2007

Name of Patentee

UNITED THERAPEUTICS CORPORATION

Applicant Address

1735 CONNECTICUT AVENUE, N.W. THIRD FLOOR, WASHINTON, D.C. 2009, USA

Inventors:

#	Inventor's Name	Inventor's Address
1	MUELLER, RICHARD, A	GLENCOE, IL, USA.
2	PARTIS, RICHARD, A	EVANSTON, IL, USA.
3	BRYANT, MARTIN, L	LOS ALTOS, CA USA.

PCT International Classification Number

A61K31/445

PCT International Application Number

PCT/US99/01874

PCT International Filing date

1999-02-12

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	09/023,401	1998-02-12	U.S.A.