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(12) United States Patent (10) Patent No.: US 7459,155 B2 Margolin Et Al US007459 155B2 (12) United States Patent (10) Patent No.: US 7459,155 B2 Margolin et al. (45) Date of Patent: Dec. 2, 2008 (54) TREATING ABDOMINAL PAINDUE TO “American Gastroenterological Association Medical Position State PANCREATITIS WITH SEAPROSE ment: Treatment of Pain in Chronic Pancreatitis.” Gastroenterology, 115,763-764 (1998). (75) Inventors: Alexey L. Margolin, Newton, MA (US); Andren-Sandberg, A., “Enzyme Substitution in Pancreatic Disease.” Bhami C. Shenoy, South Grafton, MA Digestion, 37(1), 35-46 (1987). (US); Margaret McGrath, Brighton, Andren-Sandberg, A., “Theory and Practice in the Individualization MA (US) of Oral Pancreatic Enzyme Administration for Chronic Pancreatitis.” (73) Assignee: Altus Pharmaceuticals Inc., International Journal of Pancreatology, 5, 51-62 (1989). Cambridge, MA (US) Apte, M.V., et al. "Chronic Pancreatitis: Complications and Manage ment.” J. Clin. Gastroenterol, 29(3), 225-240 (1999). (*) Notice: Subject to any disclaimer, the term of this Bracale G. et al., “Clinical Study of the Efficacy of and Tolerance to patent is extended or adjusted under 35 Seaprose S in Inflammatory Venous Disease. Controlled Study Ver U.S.C. 154(b) by 123 days. sus Serratio-Peptidase'. Minerva Cardioangiol. 44 (10), 515-524 (1996)—English abstract only from PubMed, www.ncbi.nlm.gov. (21) Appl. No.: 10/977,737 Braga, P.C., et al., “Effects of Seaprose on the Rheology of Bronchial Mucus in Patients with Chronic Bronchitis. A Double-Blind Study (22) Filed: Oct. 29, 2004 vs. Placebo.” Int. J. Clin. Pharm. Res., 13(3), 179-185 (1993). (65) Prior Publication Data Braga, P.C., et al., “The Influence of Seaprose on Erythromycin Penetration into Bronchial Mucus in Bronchopulmonary Infections.” US 2005/O158299 A1 Jul. 21, 2005 Drugs Exptl. Clin. Res., 18(3), 105-111 (1992). Braga, P.C., et al., “In Vitro Rheological Assessment of Mucolytic Related U.S. Application Data Activity Induced by Seaprose.” Pharmacological Research, 22(5), (60) Provisional application No. 60/515,552, filed on Oct. 611-617 (1990). 29, 2003, provisional application No. 60/527,490, Brown, A., et al., “Does Pancreatic Enzyme Supplementation Reduce filed on Dec. 5, 2003. Pain in Patients with Chronic Pancreatitis: A Meta-Analysis.” Am. J. Gastroenterology, 92(11), 2032-2035 (1997). (51) Int. Cl. Buscher, H.C.J.L., et al., “Bilateral Thoracoscopic A6 IK 38/48 (2006.01) Splanchnicectomy in Patients with Chronic Pancreatitis.” Scand.J. (52) U.S. Cl. ................................................... 424/94.64 Gastroenterol. Supp. 230, 29-34 (1999). (58) Field of Classification Search ........... ... None Copenhagen Pancreatitis Study Group, "Copenhagen Pancreatitis See application file for complete search history. Study. An Interim Report from a Prospective Epidemiological (56) References Cited Multicentre Study.” Scand. J. Gastroent. 16, 305-312 (1981). Dindelli, M., et al., “Efficacia clinicae tolerabilitadel Seaprose Snel U.S. PATENT DOCUMENTS trattamento delle complicanze delle ferite chirurgiche in puerperio”. 4.485,095 A 1 1/1984 Fujisaki et al. ................ 424.94 Minerva Ginecologica, 42, (7-8), 313-315 (1990)—English abstract 4,755,383 A 7/1988 Fujii et al. .................... 424.94 only. 5,514,373 A 5/1996 Harris, Jr. ................ 424/94.65 DiMagno, E. P. et al., “Impaired Cholecystokinin-Pancreozymin 6,413.512 B1 7/2002 Houston et al. .......... 424/94.63 Secretion, Intraluminal Dilution, and Maldigestion of Fat in Sprue.” 2001 OOO6617 A1 7/2001 Liversidge et al. ......... 424,129 Gastroenterology, 63(1), 25-32 (1972). 2003/0026794 A1 2/2003 Fein .......................... 424.942 2003.0143292 A1 T/2003 424/756 (Continued) 2004/0038874 A1 2/2004 Omoigui...................... 514/12 2004/0057944 A1 3f2004 Galle et al. ................... 424.94 Primary Examiner Sheridan Swope 2004/0092449 A1 5/2004 Ekwuribe .................... 514/12 (74) Attorney, Agent, or Firm—Lowrie, Lando & Anastasi, LLP FOREIGN PATENT DOCUMENTS DE 3941324 11, 1990 (57) ABSTRACT FR 2.129.947 11, 1972 JP HEI 11-49699 2, 1999 WO WO 98.36734 8, 1998 This invention relates to methods for maintaining the basal OTHER PUBLICATIONS level or reducing the level of cholecystokinin (CCK) in blood plasma of a mammal. Additionally, the invention provides van Esch et al., Pharmacological management of pain in chronic methods for treating pain in a mammal and more particularly, pancreatitis. Dig Liver Dis. Jul. 2006;38(7):518-26. Epub Apr. 14. 2006. Review. methods for treating abdominal pain in a mammal. The meth Shiratori et al., Clinical evaluation of oral administration of a ods include administering to the mammal a non-pancreatic cholecystokinin-A receptor antagonist (loxiglumide) to patients with protease or a composition comprising a non-pancreatic pro acute, painful attacks of chronic pancreatitis: a multicenter dose tease. The methods of this invention are particularly useful for response study in Japan. Pancreas. Jul. 2002:25(1): e1-5.* treating abdominal pain in a mammal Suffering from acute or Ochietal, Clinical evaluation of cholecystokinin-A-receptor antago chronic pancreatitis and related conditions. nist (loxiglumide) for the treatment of acute pancreatitis. A prelimi nary clinical trial. Study Group of Loxiglumide in Japan. Digestion. 1999:60 Suppl 1:81-5.* 58 Claims, 5 Drawing Sheets US 7459,155 B2 Page 2 OTHER PUBLICATIONS Radun, D., et al., “Chronische Pankreatitis: Konservative Therapie.” Therapeutische Umschau, 53, 359-364 (1996)—Summary at end of Dobrilla, G., “Management of Chronic Pancreatitis.” International article in English. Journal of Pancreatology, 5, 17-29 (1989). Rosewicz, S., et al., “Pancreatic Digestive Enzyme Gene Expression: Food and Drug Administration, "75-day Premarket Notification for Effects of CCK and Soybean Trypsin Inhibitor.” Am. J. Physiol. New Dietary Ingredient.” (1998). Gastrointest. Liver Physiol., 256, G733-G738, (1989). Greenberger, N.J., “Enzymatic Therapy in Patients with Chronic Rydzewska, Grazyna, et al., “Assessment of the Effectiveness of the Pancreatitis.” Gastroenterology Clinics of North America, 28(3), Preparation Panzytrat(R) 20 000 U in the substitutive Treatment of 687-692 (1999). Chronic Pancreatitis.” Wiadomosci Lekarskie, XLVII, 19-20, pp. Halgreen, H., et al., “Symptomatic Effect of Pancreatic Enzyme 738-744 (1994). Therapy in Patients with Chronic Pancreatitis.” Scand. J. Gastroent. Sidhu, S., et al., "Chronic Pancreatitis: Diagnosis and Treatment.” 21, 104-108 (1986). Postgrad. Med. Journal, 72,327-333 (1996). Isaksson, G., et al., “Pain Reduction by an Oral Pancreatic Enzyme Preparation in Chronic Pancreatitis.” Digestive Diseases and Sci Simek, M., et al., “Substitution Treatment of Insufficient External ences, 28 (2), 97-102 (1983). Pancreatic Secretion.” Vinitini lék., 39, No. 3, pp. 250-252 (1993). Lankisch, P.G., “Conservative Treatment of Chronic Pancreatitis.” Schneider, M.U., et al., “Prancreatic Enzyme Replacement Therapy: Digestion, 37(1), 47-55 (1987). Comparative Effects of Conventional and Enteric-Coated Layer, P.H., et al., “Klinik und Klassifikation der akuten microspheric pancreatin and acid-stable fungal Enzyme Preparations Pankreatitis.” Praxis, 392-396—English abstract only. on Steatorrhoea in Chronic Pancreatitis.” Hepatogastroenterology, Lebenthal, E., et al., “Enzyme Therapy for Pancreatic Insufficiency: 32(2) 97-102 (1985)—abstract only. Present Status and Future Needs.” Pancreas, 9(1), 1-12 (1994). Scolapio, J. S., et al., “Nutrition Supplementation in Patients with Liddle, R. A., et al., “Proteins but not Amino Acids, Carbohydrates, or Acute and Chronic Pancreatitis.” Pancreas Update, 28(3), 695-707 Fats Stimulate Cholecystokinin Secretion in the Rat.” Am. J. Physiol. (1999). Gastrointest. Liver Physiol., 251, G243-G248 (1986). Sharara, A. I., et al., “Evidence for Indirect Dietary Regulation of Liddle, R. A., “Regulation of Cholecystokinin Secretion by Cholecystokinin Release in Rats.” Am. J. Physiol. Gastrointest. Liver Intraluminal Releasing Factors.” Am. J. Physiol. Gastrointest. Liver Physiol., 265, G 107-G112, (1993). Physiol., 269, G319-G327 (1995). Shea, J. C., et al., “An Enteral Therapy Containing Medium-Chain Liddle, R. A., “Regulation of Cholecystokinin Secretion in Humans.” Triglycerides and Hydrolyzed Peptides Reduces Postprandial Pain J. Gastroenterology, 35, 181-187 (2000). Associated with Chronic Pancreatitis.” Pancreatology, 3, 36-40 Liddle, R. A., “Cholecystokinin Cells.” Annu. Rev. Physiol. 59,221 (2003). 242 (1997). Singh, V. V., “Medical Therapy for Chronic Pancreatitis Pain.” Cur Liddle, R. A., “On the Measurement of Cholecystokinin.” Clinical rent Gastroenterology Reports, 5, 110-116 (2003). Chemistry, 44(5), 903-904 (1998). Slaff, J., et al., “Protease-Specific Suppression of Pancreatic Exo Liddle, R. A., “Regulation of Cholecystokinin Synthesis and Secre crine Secretion.” Gastroenterology, 87. 44-52 (1984). tion in Rat Intestine.” American Institute of Nutrition, 1308S-1314S Somogyi, L., et al., “Can a meta-Analysis That Mixes Apples With (1994). Oranges Be Used to Demonstrate That Pancreatic Enzymes Do Not Luisetti, M., et al., “Some Properties of the Alkaline Proteinase from Decrease Abdominal Pain in Patients With chronic Pancreatitis?' Aspergillus Melleus.” Int. J. Tiss. Reac. 13(4), 187-192 (1991). Am. J. Gastroenterology, 93, 8, 1396-1398 (1998). Malfertheiner, P. et al., “Effect of Exogenous Pancreatic Enzymes on Spannagel, A. W., et al., “Purification and Characterization of a Gastrointestinal and Pancreatic Hormone Release and Luminal
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