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United States Patent (19) 11 Patent Number: 6,020,310 Beck Et Al US00602031 OA United States Patent (19) 11 Patent Number: 6,020,310 Beck et al. (45) Date of Patent: Feb. 1, 2000 54 METHOD FOR ASSISTING IN Fara, Madden, “Effect of secretin and cholecystokinin on DIFFERENTIAL DIAGNOSIS AND small intestinal blood flow distribution,” Am. J. Physiology, TREATMENT OF AUTISTC SYNDROMES 1975; 229(5):1365–70. Dollinger, Berz, Raptis, von Uexkill, Goebell, “Effects of 75 Inventors: Victoria Beck, Bedford, N.H.; Karoly Secretin and Cholecystokinin on Motor Activity of Human Horvath, Baltimore, Md. Jejunum, Digestion 12:1975, pp. 9-16. Horvath, Stefanatos,Sokolski, Wachtel, Nabors, Tildon, 73 Assignee: Repligen Corporation, Needham, “Improved Social and language skills after Secretin admin Mass. istration in patients with autistic Spectrum disorders”, J. ASSOc. for Academic Minority Physicians 9(1):1998, pp. 21 Appl. No.: 09/080,631 9-15. Raymond, Bauman, Kemper, “Hippocampus in autism: a 22 Filed: May 19, 1998 Golgi analysis”, Acta Neuropathologica, 1996; 91(1): 117-9. Charlton, O'Donohue, Miller, Jacobowitz, "Secretin immu Related U.S. Application Data noreactivity in rat and pig brain', Peptides, 1981; 2 Suppl 60 Provisional application No. 60/047,049, May 19, 1997. 1:45-9. Fremeau, Korman, Moody, “Secretin stimulates cyclic AMP (51) Int. Cl." ..................................................... A61K 38/00 formation in the rat brain”, Journal of Neurochemistry, 52 U.S. Cl. ................................... 514/12; 514/2; 436/63; 1986; 46(6):1947–55. 436/86; 436/87; 424/198.1 Fremeau, Jensen, Charlton, Miller, O'Donohue, Moody, 58 Field of Search .................................. 436/63, 86, 87, “Secretin: specific binding to rat brain membranes”,Journal 436/501; 424/1841, 198.1, 514/2-21, 254 of Neuroscience, 1983; 3(8):162-05. 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Schopler, Reichler, DeVellis, Daly, “Toward Objective Clas (List continued on next page.) sification of Childhood Austism: Childhood Autism Rating Scale (CARS)”, J. of Autism & Dev. Disorders 10(1):1980, Primary Examiner Maureen M. Wallenhorst pp. 91–103. Attorney, Agent, or Firm Fish & Richardson P.C. Karelson, Laasik, Sillard, "Regulation of Adenylate Cyclase 57 ABSTRACT by Galanin, Neuropeitide Y, Secretin and Vasoactive Intes tinal Polypeptide in Rat Frontal Cortex.Hippocampus and A novel relationship between pancreatico-biliary Secretion Hypothalamus', Neuropeptides 28;1995, pp. 21-28. and autistic Syndrome is disclosed. This relationship enables van Calker, Miller, Hamprecht, “Regulation by secretin, a novel therapy for the treatment of the Symptoms of autistic vasoactive intestinal peptide, and Somatostatin of cyclic Syndromes, comprising the administration of a therapeuti AMP accumulation in cultured brain cells', Proc. Natl. cally effective, preferably intravenous, dose of Secretin to an Acad. Sci. USA 77(11):1980, pp. 6907–6911. individual with autistic syndrome. The relationship further McGill, Basavappa, Gettys, Fitz, “Secretin activates enables a differential diagnosis for autistic Syndrome, com C1 channels in bile duct epithelial cells through a cAMP dependent mechanism”, Am. J. Physiology, 1994; prising an analysis of an individual’s blood and/or intestinal 266:C731-6. tissue for the presence of Secretin and comparison of the Leiter, Chey, Kopin, “Secretin”, Gut peptides. Biochemistry level of Secretin to known norms. and Physiology edited by Walsh and Dockray, Raven Press, Ltd., New York, 1994: 147-93. 28 Claims, 8 Drawing Sheets 6,020,310 Page 2 OTHER PUBLICATIONS Horvath et al., “Improved Social and Language Skills After Secretin Administration in Patients with Autistic Spectrum Dawson, Klinger, Panagiotides, Lewy, Castelloe, "Sub Disorders”, J. ASSOc. Acad. 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(Aug. 23, 1996). Westland, Secretin, email to newsgroup bit...listserv.autism McDougle, Price, Volkmar, “Recent advances in the phar (Aug. 24, 1996). macotherapy of autism and related conditions”, Child & Timpson, Secretin, email to newsgroup bit...listserv.autism Adolescent Psych. Clinics of N. Am., 1994; 3(1):71-89. (Aug. 24, 1996). Patel, Kong, Sreedharan, “Molecular cloning and expression Conaty, Secretin, email to newsgroup bit...listserv.autism of a human secretin receptor, Molecular Pharmacology, (Aug. 25, 1996). 1995; 47(3):467–73. Conaty, Pancreatic Lipase deficiency, email to newsgroup Lenzen, Alpini, Tavoloni, “Secretin Stimulates bile ductular bit...listserv.autism (Aug. 26, 1996). secretory activity through the cAMP system”, American Mayberry, Secretin, email to newsgroup bit...listserV.autism Journal of Physiology, 1992; 263(4 pt 1):G527–32. (Sep. 10, 1996). Pollack, Wood, Solomon, “Effect of secretin on growth of Mayberry, Canadian listmates, email to newsgroup bit...list Stomach, Small intestine, and pancreas of developing rats', serv.autism (Sep. 20, 1996). Digestive Diseases & Sciences, 1990; 35(6):749–58. Binstock, Secretin, email to newsgroup bit...listserV.autism Lebenthal, Clark, “Immunoglobin concentrations in the (Sep. 26, 1996). duodenal
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