Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1998-09-04
2001-05-08
Arthur, Lisa B. (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091200
Reexamination Certificate
active
06228585
ABSTRACT:
BACKGROUND OF THE INVENTION
Clinical assessment of disease activity in ulcerative colitis or Crohn's disease is very difficult. Patient symptoms do not necessarily correlate with the inflammatory (disease) activity in the small intestine and colon, leading to educated guesses being used to direct anti-inflammatory therapy. Similar difficulty exists in measuring or testing the efficacy of new therapeutic compounds. Currently the gold standard in diagnosing ulcerative colitis or Crohn's disease is the use of fiberoptic endoscopy coupled with multiple biopsies and pathologic analysis. This very expensive approach requires a skilled specialist and has associated risks, such as risk of sedation, bleeding, and colon perforation. The patient is also subjected to discomfort from the procedure and preparation.
A less invasive and less risky assessment of mucosal disease activity is needed to accurately guide treatment and to provide an objective measure of mucosal injury, both for patients and for use in clinical studies. There is also a need for a simple test to aid in the differentiation of chronic inflammatory disease (UC or CD) from common acute inflammatory disorders or common non-inflammatory benign disorders. There is a further need for a simple method for the differentiation of ulcerative colitis and Crohn's disease because the surgical and medical management for these two diseases is profoundly different.
SUMMARY OF THE INVERSION
It is an object of the invention to provide a method for identifying chronic mucosal injury in a human.
It is another object of the invention to provide a method of determining the degree of injury to the small intestine or colon of a human with chronic mucosal injury.
It is yet another object of the invention to provide a method for monitoring the efficacy of therapy for chronic mucosal injury.
It is a further object of the invention to provide a method of screening compounds for anti-chronic mucosal injury or anti-ulcerative colitis activity.
These and other objects of the invention are provided by one or more of the embodiments described below.
One embodiment of the invention provides a method of diagnosing chronic inflammatory bowel disease. At least one gene expression product of the regenerating (REG) gene family is detected in a body sample of a human who is suspected of having chronic inflammatory bowel disease. The human is identified as having chronic inflammatory bowel disease if the gene expression product is detected.
A further embodiment of the invention provides a method to aid in the differentiation of chronic mucosal injury from common acute inflammatory colon disorder and common non-inflammatory benign colon disorder in a human with symptoms of bowel disease. The amount of at least one gene expression product of the REG gene family in a body sample of a first human who is suspected of having bowel disease, is compared with the amount of the gene expression product in a body sample of a second human who is healthy. The first human is identified as having chronic mucosal injury if the body sample of the first human contains more of the gene expression product than the body sample of the second human.
Another embodiment of the invention provides a method to determine degree of injury to small intestine or colon tissue of a human with chronic mucosal injury. A quantity of a gene expression product of the REG gene family in a body sample of a human having chronic mucosal injury is determined. The amount is correlated with the degree of injury to the small intestine or colon.
Still another embodiment of the invention provides a method of monitoring the efficacy of therapy for chronic mucosal injury in a human body sample. At least one gene expression product of the REG gene family is quantitated in a body sample of a human who has been subjected to therapy for chronic mucosal injury. The quantity of the expression product in the sample is compared to the quantity of the gene expression product in a matched body sample of the human at an earlier time. A reduction in the quantity of the gene expression product after therapy is an index of efficacy of the therapy.
Another embodiment of the invention provides a method of screening compounds for anti-chronic mucosal injury activity. A colonic cell expressing a gene which is a member of the REG gene family is contacted with a test compound. The expression of the REG gene is quantitated. A test compound which decreases expression of the gene is identified as a potential compound for treating chronic mucosal injury.
A further embodiment of the invention provides a method of diagnosing ulcerative colitis. An mRNA which is expressed by a gene represented by a Hs.111244 polynucleotide is detected in a body sample of a first human who is suspected of having ulcerative colitis. The human is identified as having ulcerative colitis if the mRNA is detected.
Still another embodiment of the invention provides a method to aid in the differentiation of ulcerative colitis from common acute inflammatory colon disorder, common non-inflammatory benign colon disorder, and Crohn's disease in a human with symptoms of bowel disease. The amount of mRNA which is expressed by a gene represented by a Hs.111244 polynucleotide in a body sample of a first human suspected of having bowel disease is compared with the amount of the mRNA in a comparable body sample of a second human who is healthy. A body sample of the first human which contains more of the mRNA than the body sample of the second human identifies the first human as having ulcerative colitis.
Another embodiment of the invention provides a method to determine the degree of injury to small intestine or colon tissue of a human with ulcerative colitis. A quantity of an mRNA which is expressed by a gene represented by a Hs.111244 polynucleotide in a body sample of a first human having ulcerative colitis is determined. The quantity of the mRNA is correlated with the degree of injury to the small intestine or colon.
Even another embodiment of the invention provides a method of monitoring the efficacy of therapy for ulcerative colitis in a human body sample. An mRNA which is expressed by a gene represented by a Hs.111244 polynucleotide is quantitated in a body sample of a human who has been subjected to therapy for ulcerative colitis. The quantity of the mRNA in the sample is compared to the quantity of the mRNA in a matched body sample of the human at an earlier time. A reduction in the quantity of the mRNA after therapy is an index of efficacy of the therapy.
Still another embodiment of the invention provides a method of screening compounds for anti-ulcerative colitis activity. A colonic cell expressing an mRNA which is expressed by a gene represented by a Hs.111244 polynucleotide is contacted with a test compound. The expression of the mRNA by the cell is quantitated. A test compound which decreases expression of the mRNA is identified as a potential compound for treating ulcerative colitis.
REFERENCES:
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Arthur Lisa B.
Banner & Witcoff Ltd
Washington University
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