# US 6,297,214 B1 · Methods of enhancing functioning of the large intestine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,297,214 B1 - Document ID: US6297214B1 - Status: Granted - Kind: B1 - Application number: 09/149,831 - Filed: 1998-09-08 - Granted: 2001-10-02 - Earliest claimed: 1997-05-02 - Assignees: 1149336 Ontario Inc. - Inventors: Daniel J. Drucker - Web page: https://patentgrep.com/patent/US6297214B1 ## CPC - A61K 38/26: Glucagons - A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure} - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - C07K 14/605: Glucagons - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The invention relates to glucagon-related peptides and their use for the prevention or treatment of disorders involving the large intestine. In particular, it has now been demonstrated that GLP-2 and peptidic agonists of GLP-2 can cause proliferation of the tissue of large intestine. Thus, the invention provides methods of proliferating the large intestine in a subject in need thereof. Further, the methods of the invention are useful to treat or prevent inflammatory conditions of the large intestine, including inflammatory bowel diseases. ## Claims ### Claim 1 A method for treating a subject having, or at risk of developing, a condition in which functioning of the large intestine is impaired to enhance functioning of the large intestine, comprising the step of delivering to the large intestine of the subject a GLP-2 receptor agonist in an amount effective to ameliorate said condition or the onset thereof. ### Claim 2 A method of treating a subject having, or at risk of developing, a condition ameliorated by enhanced growth of the large intestine to proliferate the tissue of the large intestine, comprising the step of delivering to the large intestine of the subject GLP-2 or a peptidic analog of GLP-2, in an amount effective to proliferate the tissue of the large intestine. ### Claim 3 (depends on 2) A method according to claim 2, wherein the subject is suffering from an inflammatory condition involving the large intestine. ### Claim 4 (depends on 3) A method according to claim 3, wherein the inflammatory condition involving the large intestine is selected from the group comprising Crohn's disease, ulcerative colitis, infectious colitis, drug or chemical-induced colitis, diverticulitis, and ischemic colitis. ### Claim 5 (depends on 2) A method according to claim 2, wherein the subject has undergone partial or subtotal resection of the large intestine. ### Claim 6 (depends on 2) A method according to claim 2, wherein the subject is a human. ### Claim 7 (depends on 6) A method according to claim 6, wherein the analog of GLP-2 has enhanced large intestine cell proliferating activity relative to native rat GLP-2. ### Claim 8 (depends on 7) A method according to claim 7, wherein the analog of GLP-2 is resistant to cleavage by DPP-IV. ### Claim 9 (depends on 8) A method according to claim 8, wherein the analog of GLP-2 is selected from the group consisting of [D-Ala2]rGLP-2, [Gly2]rGLP-2, [Val2]rGLP-2, and [Gly2]hGLP-2. ### Claim 10 (depends on 8) A method according to claim 8, wherein the analog of GLP-2 is [Gly2]hGLP-2. ### Claim 11 (depends on 8) A method according to claim 8, wherein the analog of GLP-2 is delivered to the large intestine by oral, subcutaneous, or rectal administration. ### Claim 12 A method to identify peptides useful to treat inflammatory conditions involving the large intestine, comprising the steps of: a) obtaining an analog of a vertebrate GLP-2 peptide, the analog having at least one amino acid substitution, deletion, addition, or an amino acid with a blocking group; b) inducing an inflammatory condition of the intestine involving the large intestine in a test animal; c) treating the test animal having an induced inflammatory condition of the large intestine, with the analog using a regimen capable of eliciting an amelioration of the inflammatory condition of the large intestine when utilized for native GLP-2; and d) determining the effect of the analog on the health status or mortality of the test animal compared with control animals not receiving the peptide or determining the effect of the analog on the weight of the large intestine of test animals compared to control animals not receiving peptide. ### Claim 13 A method useful to identify peptides capable of proliferating tissue of the large intestine, comprising the steps of a) obtaining an analog of a vertebrate GLP-2 peptide, the analog having at least one amino acid substitution, deletion, addition, or an amino acid with a blocking group; b) delivering the analog to the large intestine of the test animal using a regimen capable of eliciting proliferation of the large intestine when utilized for native GLP-2; and c) assessing the increase in the mass or length of the large intestine after completion of the treatment regimen. ### Claim 14 A method of prophylactically treating a subject at risk of developing an inflammatory condition of the intestine involving inflammation of the large intestine, the method comprising administering to the subject an amount of GLP-2 or a GLP-2 analog demonstrated to inhibit onset of the inflammatory condition. ### Claim 15 A method for treating a subject suffering from colitis, comprising the step of delivering to said subject an amount of a GLP-2 receptor agonist effective to ameliorate said disease. ### Claim 16 (depends on 15) A method according to claim 15, wherein the GLP-2 receptor agonist is GLP-2 or an analog thereof. ### Claim 17 (depends on 16) A method according to claim 16, wherein the GLP-2 receptor agonist is [Gly2]hGLP-2. ### Claim 18 A method for treating a subject to enhance large intestine mucosal function, comprising the step of delivering to a subject in need of such treatment an effective amount of a GLP-2 receptor agonist. ### Claim 19 (depends on 18) A method according to claim 18, wherein the GLP-2 receptor agonist is GLP-2 or an analog thereof. ### Claim 20 (depends on 19) A method according to claim 19, wherein the GLP-2 receptor agonist is [Gly2]hGLP-2.