Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Acyclic nitrogen double bonded to acyclic nitrogen – acyclic...
Reexamination Certificate
2001-08-29
2003-06-24
Powers, Fiona T. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Acyclic nitrogen double bonded to acyclic nitrogen, acyclic...
C534S660000, C534S852000, C534S853000
Reexamination Certificate
active
06583128
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to immunoregulatory compounds and methods of treating diseases therewith.
BACKGROUND OF THE INVENTION
Many people suffer from inflammatory bowel disease (IBD). IBD is a generic term used to refer to two inflammatory diseases, ulcerative colitis and Crohn's disease. Ulcerative colitis is a chronic inflammatory disease of unknown etiology that affects various portions of the gastrointestinal (GI) tract, particularly the lower GI tract, and more particularly the colon and/or rectum. Crohn's disease is a serious inflammatory disease of the GI tract. It predominates in the small intestine (ileum) and the large intestine (colon). Various medications are being used to treat inflammatory bowel disease.
It is known to use mesalamine, 5-aminosalicylic acid (5-ASA) to treat ulcerative colitis. While mesalamine may be active in treating ulcerative colitis, it may be absorbed as it passes through the GI tract. This absorption may adversely affect the amount of mesalamine that reaches the lower GI tract, particularly the colon and rectum.
Various mesalamine formulations have been introduced in an attempt to protect mesalamine as it passes through the gut and the upper GI tract. One such formulation is a delayed-release formulation that relies on a pH-sensitive coating surrounding the mesalamine. The coating allows the mesalamine to pass through the gut and upper GI tract without being absorbed so that the mesalamine reaches the target (i.e. the lower GI tract, particularly the colon and/or rectum) intact. In another formulation, mesalamine microspheres surround a mesalamine core. This formulation releases mesalamine throughout the GI tract, rather than targeting the colon specifically. It may be difficult to predict the bioavailability of the various mesalamine formulations when administered to a wide variety of individuals. As a result, it may be difficult to determine the proper dosage for a given individual.
It is also known to use sulfasalazine having the following formula to treat ulcerative colitis.
However, sulfasalazine is metabolized in the body to form mesalamine (5-aminosalicylic acid (5-ASA)) and sulfapyridine. Several adverse side affects have been noted from the use of sulfasalazine including nausea, vomiting, abdominal discomfort, and headache to name just a few. These adverse side effects are usually attributed to the activity of sulfapyridine in the GI tract, as well as that absorbed into the system.
U.S. Pat. No. 4,412,992 to Chan proposes mesalamine derivatives. Unlike sulfalazine, the breakdown of these compounds in the intestinal tract may not give rise to undesirable metabolic products. In fact, the non-mesalamine metabolic products may be innocuous.
Olsalazine having the following formula has been used to treat ulcerative colitis.
In addition to being relatively expensive to make, olsalazine may have adverse side effects including diarrhea.
It is known to use azathioprine (6-(1-methyl-4-nitoimidazol-5-ylthio)purine) in the treatment of inflammatory bowel disease. Azathioprine has the following chemical structure:
It is also known to use 6-mercaptopurine, a metabolite of azathioprine, to treat inflammatory bowel disease. 6-mercaptopurine has the following chemical structure:
Methotrexate (L-4-amino-N
10
-methylpteroyl-glutamic acid) has also been used to treat inflammatory bowel disease. Methotrexate has the following chemical structure:
The polypeptide cyclosporine, which has traditionally been given to transplant patients to prevent organ rejection, has also been used to treat inflammatory bowel disease. The use of cyclosporine to treat IBD may be limited, however, by the various side effects associated with this medication. These side effects include high blood pressure, kidney damage, tremors, headaches, seizures, excessive hair growth, excessive gum growth, confusion, coma, and gout.
SUMMARY OF THE INVENTION
According to embodiments of the present invention, compounds are provided having the following formula:
where R
1
, R
3
, and R
4
are independently hydrogen or C
1
to C
4
alkyl, and R
2
is:
where R
5
is selected from the group consisting of hydrogen and C
1
to C
4
alkyl, or
where R
6
, R
7
and R
8
are independently hydrogen or C
1
to C
4
alkyl, as well as the esters or pharmaceutically acceptable salts of such compounds. Pharmaceutical compositions including compounds according to embodiments of the present invention are also provided, as are methods of treating inflammatory conditions with such compounds.
According to other embodiments of the present invention, methods of treating an inflammatory condition of the GI tract in a subject in need of such treatment include administering to the subject an effective amount of an active pharmaceutical ingredient that includes a compound of Formula II:
where R
9
, R
10
and R
11
are independently selected from the group consisting of hydrogen and C
1
to C
4
alkyl; and R
12
is selected from the group consisting of hydrogen and —C(O)R
13
, where R
13
is a C
1
to C
6
alkyl or an aryl group, or an ester or a pharmaceutically acceptable salt of such compound, in admixture with a solid or liquid pharmaceutical diluent or carrer. The active pharmaceutical ingredient may further comprise a compound of Formula III:
REFERENCES:
patent: 2270676 (1942-01-01), Behnisch et al.
patent: 2314023 (1943-03-01), Straub et al.
patent: 2336275 (1943-12-01), McNally et al.
patent: 2396019 (1946-03-01), Murray
patent: 3244694 (1966-04-01), May et al.
patent: 3641040 (1972-02-01), Carney et al.
patent: 3915951 (1975-10-01), Agback et al.
patent: 4298595 (1981-11-01), Parkinson et al.
patent: 4348399 (1982-09-01), Shepherd
patent: 4374932 (1983-02-01), Pitzele et al.
patent: 4412992 (1983-11-01), Chan
patent: 4455305 (1984-06-01), Rokos
patent: 4472433 (1984-09-01), Ueda et al.
patent: 4496553 (1985-01-01), Halskov
patent: 4528367 (1985-07-01), Agback et al.
patent: 4539198 (1985-09-01), Powell et al.
patent: 4540685 (1985-09-01), Bauer
patent: 4559330 (1985-12-01), Agback et al.
patent: 4591584 (1986-05-01), Agback
patent: 4595699 (1986-06-01), Terada et al.
patent: 4628083 (1986-12-01), Agback
patent: 4632921 (1986-12-01), Bauer
patent: 4657900 (1987-04-01), Powell et al.
patent: 4663308 (1987-05-01), Saffran et al.
patent: 4664256 (1987-05-01), Halskov
patent: 4670112 (1987-06-01), Lund
patent: 4699902 (1987-10-01), Bauer
patent: 4720506 (1988-01-01), Munakata et al.
patent: 4725676 (1988-02-01), Agback et al.
patent: 4780318 (1988-10-01), Appelgren et al.
patent: 4788331 (1988-11-01), Sjöstrand
patent: 4837229 (1989-06-01), Rokos et al.
patent: 4849416 (1989-07-01), Pendleton et al.
patent: 4880794 (1989-11-01), Halskov
patent: 4889846 (1989-12-01), Crossley
patent: 4911922 (1990-03-01), Masuhara et al.
patent: RE33239 (1990-06-01), Halskov
patent: 4933330 (1990-06-01), Jorgensen et al.
patent: 4960765 (1990-10-01), Halskov
patent: 5010069 (1991-04-01), Bottom et al.
patent: 5013727 (1991-05-01), Halskov
patent: 5026560 (1991-06-01), Makino et al.
patent: 5041431 (1991-08-01), Halskov
patent: 5082651 (1992-01-01), Healey et al.
patent: 5254587 (1993-10-01), Burzynski
patent: 5274002 (1993-12-01), Hawkins
patent: 5352681 (1994-10-01), Wittebrood et al.
patent: 5378470 (1995-01-01), Lahr
patent: 5393779 (1995-02-01), Holloway et al.
patent: 5409711 (1995-04-01), Mapelli et al.
patent: 5434184 (1995-07-01), Holloway et al.
patent: 5476849 (1995-12-01), Ulrich et al.
patent: 5480910 (1996-01-01), Holloway et al.
patent: 5484605 (1996-01-01), Scheiffele et al.
patent: 5498608 (1996-03-01), Johnson et al.
patent: 5502078 (1996-03-01), Holloway et al.
patent: 5514676 (1996-05-01), Ulrich et al.
patent: 5541170 (1996-07-01), Rhodes et al.
patent: 5541171 (1996-07-01), Rhodes et al.
patent: 5602183 (1997-02-01), Martin et al.
patent: 5629012 (1997-05-01), Halskov
patent: 5629020 (1997-05-01), Leone-Bay et al.
patent: 5637618 (1997-06-01), Kurtz et al.
patent: 5648380 (1997-07-01), Martin
patent: 5663208 (1997-09-01), Martin
patent: 5668123 (1997-09-01
Ekwuribe Nnochiri Nkem
Riggs-Sauthier Jennifer A.
Barrett, Esq. William A.
Myers Bigel Sibley & Sajovec P.A.
Nobex Corporation
Powers Fiona T.
LandOfFree
Immunoregulatory compounds and derivatives and methods of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Immunoregulatory compounds and derivatives and methods of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Immunoregulatory compounds and derivatives and methods of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3155979