Source: https://patents.justia.com/patent/8637451
Timestamp: 2019-07-22 07:57:38
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Matched Legal Cases: ['Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 02721604', 'Application No. 02721604', 'Application No. 02721604', 'Application No. 02721604', 'Application No. 02721604', 'Application No. 02721604', 'Application No. 02721604', 'Application No. 02721604']

US Patent for Guanylate cyclase receptor agonists for the treatment of tissue inflammation and carcinogenesis Patent (Patent # 8,637,451 issued January 28, 2014) - Justia Patents Search
Justia Patents Transporter Affecting Or UtilizingUS Patent for Guanylate cyclase receptor agonists for the treatment of tissue inflammation and carcinogenesis Patent (Patent # 8,637,451)
Dec 29, 2011 - Synergy Pharmaceuticals Inc.
The present application is a continuation of U.S. patent application Ser. No. 12/763,707, filed Apr. 20, 2010, now U.S. Pat. No. 8,114,831, which is a continuation of U.S. patent application Ser. No. 11/347,115, filed Feb. 2, 2006, now U.S. Pat. No. 7,799,897, which is a continuation of U.S. patent application Ser. No. 10/107,814, filed Mar. 28, 2002, now U.S. Pat. No. 7,041,786 and claims the benefit of U.S. Patent Application No. 60/279,438, filed on Mar. 29, 2001; U.S. Patent Application No. 60/279,437, filed on Mar. 29, 2001; U.S. Patent Application No. 60/300,850, filed on Jun. 27, 2001; U.S. Patent Application No. 60/303,806, filed on Jul. 10, 2001; U.S. Patent Application No. 60/307,358, filed on Jul. 25, 2001; and U.S. Patent Application No. 60/348,646, filed on Jan. 17, 2002. The contents of these applications are incorporated by reference in their entireties.
The contents of the text file named “40737-501C03US_ST25.txt”, which was created on Dec. 29, 2011 and is 19 KB in size, are hereby incorporated by reference in their entirety.
Asn1 Asp2 Glu3 Cys4 Glu5 Leu6 Cys7 Val8 Asn9 Val10 Ala11 Cys12 Thr13 Gly14 Cysl5 Leu16 * ** * **
Molecular modeling was applied to the design of novel guanylate cyclase receptor agonists using methods detailed in (30). It consisted of energy calculations for three compounds known to interact with guanylate cyclase receptors, namely for human uroguanylin, bicyclo[4,12; 7,15]Asn1-Asp2-Asp3-Cys4-Glu5-Leu6-Cys7-Val8-Asn9-Val10-Ala11-Cys12-Thr13-Gly14-Cys15-Leu16 (UG, SEQ ID NO:1); human guanylin, bicyclo [4,12; 7,15] Pro1-Gly2-Thr3-Cys4-Glu5-Ile6-Cys7-Ala8-Tyr9-Ala10-Ala11-Cys12-Thr13-Gly14-15Cys (GU, SEQ ID NO:22); and E. coli small heat-stable enterotoxin, tricyclo [6,10; 7,15; 11-18] Asn1-Ser2-Ser3-Asn4-Tyr5-Cys6-Cys7-Glu8-Leu9-Cys10-Cys11-Asn12-Pro13-Ala14-Cys15-Thr16-Gly17-Cys18-Tyr19 (ST, SEQ ID NO:23). Geometrical comparisons of all possible low-energy conformations for these three compounds were used to reveal the common 3D structures that served as the “templates” for the bioactive conformation, i.e., for the conformation presumably adopted by GU, UG and ST during interaction with receptor. It allowed designing novel analogs with significantly increased conformational population of the bioactive conformation at the expense of other low-energy conformations by selecting individual substitutions for various amino acid residues.
where N is the number of the Cα-atom pairs chosen for superposition, and x, y and z are the Cartesian coordinates. By the criterion of geometrical similarity of rms<2.0 Å, low-energy conformations of the rigid conformational fragment UG 4-15 fell into seven conformational families. One of them consists of the same six conformers that are similar both to 1UYA and 1ETN; this family contains also the lowest-energy conformer of UG. (1UYA and 1ETN are the experimentally defined 3D structures of UG and ST, respectively, which are known to possess high biological activity (36,37); the 3D structures were available in the Protein Data Bank.)
Parent compound, uroguanylin SEQ ID NO: 1 Asn1-Asp2-Asp3-Cys4-Glu5-Leu6-Cys7-Val8-Asn9-Val10-Ala11-Cys12-Thr13-Gly14-Cys15- Leu16 Compounds without modifications of cysteines: Common sequence (SEQ ID NO: 2): Asn1-Xaa2-Xaa3-Cys4-Glu5-Leu6-Cys7-Val8-Asn9-Xaa10-Xaa11-Cys12-Thr13-Xaa14-Cys15- Leu16 where Xaa2 = Asp, Glu; Xaa3 = Asp, Glu with the exception that Xaa2 and Xaa3 are not both Asp in same molecule And where Xaa10 = Val, Pro; Xaa11 = Ala, Aib; Xaa14 = Gly, Ala Compounds with mercaptoproline (Mpt) substituted for cysteine in position 7: Common sequence (SEQ ID NO: 3): Asn1-Xaa2-Xaa3-Cys4-Glu5-Leu6-Xaa7-Val8-Asn9-Xaa10-Xaa11-Cys12-Thr13-Xaa14-Cys15- Leu16 where Xaa2 = Asp, Glu; Xaa3 = Asp, Glu where Xaa10 = Val, Pro; Xaa11 = Ala, Aib; Xaa14 = Gly, Ala Compounds with penicillamines (β,β-dimethylcysteines, Pen) substituted for cysteines: Common sequence (SEQ ID NO: 4): Asn1-Xaa2-Xaa3-Xaa4-Glu5-Leu6-Xaa7-Val8-Asn9-Xaa10-Xaa11-Xaa12-Thr13-Xaa14-Xaa15- Leu16 where Xaa2 = Asp, Glu; Xaa3 = Asp, Glu where Xaa10 = Val, Pro; Xaa11 = Ala, Aib; Xaa14 = Gly, Ala and Xaa4, Xaa7, Xaa12, Xaa15 are either Cys or Pen (except not all are Cys in the same conformer) Compounds with lactam bridges substituted for disulfide bridges: Common sequence (SEQ ID NO: 5): Asn1-Xaa2-Xaa3-Xaa4-Glu5-Leu6-Xaa7-Val8-Asn9-Xaa10-Xaa11-Xaa12-Thr13-Xaa14-Xaa15- Leu16 where Xaa2 = Asp, Glu; Xaa3 = Asp, Glu where Xaa10 = Val, Pro; Xaa11 = Ala, Aib; Xaa14 = Gly, Ala and all combinations of the following (Dpr is diaminopropionic acid): Xaa4 is either Asp or Glu, and Xaa12 is Dpr; Xaa7 is either Cys or Pen; Xaa15 is either Cys or Pen; or: Xaa7 is Dpr and Xaa15 is either Asp or Glu; Xaa7 is either Asp or Glu, and Xaa15 is Dpr; Xaa4 is either Cys or Pen; Xaa12 is either Cys or Pen;
SEQ ID NO: 6 X1 Glu Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 7 X1 Glu Asp Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 8 X1 Asp Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 9 X1 Asp Asp Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 10 X1 Glu Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 11 X1 Asp Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 12 X1 Glu Asp Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 13 X1 Asp Asp Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 14 X1 Glu Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 15 X1 Asp Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 16 X1 Glu Asp Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 17 Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 SEQ ID NO: 18 Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys SEQ ID NO: 19 X1 Glu Cys X2 X3 Cys X4 Asn X5 X6 Cys X7 X8 Cys X9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 SEQ ID NO: 20 Asn Asp Glu Cys Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu SEQ ID NO: 21 Glu Cys Glu Leu Cys Val Asn Val Ala Cys Thr Gly Cys Leu
cGMP SEQ Compound Level** ID NO.* Code (pmol/well)
1. A method for stimulating water transport in the gastrointestinal tract in a patient comprising administering to said patient a guanylate cyclase receptor agonist peptide consisting of SEQ ID NO:20, wherein said peptide is administered in an amount sufficient to induce cGMP production in a gastrointestinal epithelial cell and wherein said peptide is (4,12; 7,15) bicycle.
2. The method of claim 1, further comprising administering to said patient an effective dose of an inhibitor of cGMP-dependent phosphodiesterase either concurrently or sequentially with said guanylate cyclase receptor agonist peptide, wherein said inhibitor of cGMP-dependent phosphodiesterase is selected from the group consisting of sulindac sulfone, zaprinast, and motapizone.
3. The method of claim 1, wherein said peptide is formulated as a powder.
20120196797 August 2, 2012 Currie et al.
19744027 April 1999 DK
WO-8805306 July 1988 WO
WO-9926567 June 1999 WO
WO-2004069165 August 2004 WO
WO-2005087797 September 2005 WO
WO-2008106429 September 2008 WO
WO-2010009319 January 2010 WO
WO-2010065751 June 2010 WO
Shailubhai et al. (Inflammatory Bowel Diseases. Feb. 2008; 14: S5; 2007 IBD Abstracts: Oral Presentation).
Roberts et al., “Chemistry of Peptide and Protein PEGylation”, Adv. Drug. Deliv. Rev., 54:459-476 (2002).
Reddy and Rao, “Lipid Metabolism and Liver Inflammation II Fatty Liver Disease and Fatty Acid Oxidation”, Am. J. Physiol. Gastrointest. Liver Physiol., 290:G852-G858 (2006).
http://www.merckmanuals.com/home/childrens—health—issues/hereditary—metabolic—disorders/disorders—of—lipid—metabolism.html; last updated 2009; last visited Sep. 25, 2012.
http://www.nlm.nih.gov/medlineplus/obesity.html; 1999-2011; last visited Sep. 25, 2012.
St. John's Providence Health Center; Preventing Obesity, http://www.stjohnprovidence.org/HealthInfoLib/swArticle.aspx?85,P07863; last visited Sep. 25, 2012.
Advisory Committee Briefing Document for Merida [sibutramine hydrochloride monohydrate], Abbott, Aug. 13, 2010.
Askling et al., “Colorectal Cancer Rates Among First Degree Relatives of Patients with Inflammatory Bowel Disease: A Population-Based Cohort Study”, Lancet, 357:262-266 (2001).
Beltowski, J., “Guanylin and Related Peptides”, J. Physiol. Pharmacol., 52(3):351-375 (2001).
Cermak et al., “Natriuretic peptides increase a K+ conductance in rat mesangial cells”, Pflügers Arch.—Eur. J. Physiol., 431:571-577 (1996).
Cui et al., “The Permissive Effect of Zinc Deficiency on Uroguanylin and Inducible Nitric Oxide Synthase Gene Upregulation in Rat Intestine Induced by Interleukin 1a is Rapidly Reversed by Zinc Repletion”, J. Nutri.,133(1): 51-56 (2003).
Eastwood, G. “Epithelial Renewal in Premalignant Conditions of the Gastrointestinal Tract: A Review ”, J. Clin. Gastroenterol., 14(1):S29-S33 (1992).
Evan et al., “Proliferation, cell cycle and apoptosis in cancer ”, Nature (London), 411:342-348 (2001).
Gali et al., “In Vivo Evaluation of an 111In -labeled ST-peptide Analog for Specific-Targeting of Human Colon Cancers”, Nucl. Med. Bio., 28(8):903-909 (2001).
Garcia et al., “Processing and characterization of human proguanylin expressed in Escherichia coli ”, J. Biol. Chem., 268(30):22397-22401 (1993).
Guba et al., “Guanylin strongly stimulates rat duodenal HCO3- secretion: proposed mechanism and comparison with other secretagogues ”, Gastroenterol., 111(6):1558-1568 (1996).
Gülcan et al., “Increased Frequency of Pre-diabetes in Patients With Irritable Bowel Syndrome”, Am. J. Med. Sci., 338:116-119 (2009).
Gura, T., “Systems for identifying new drugs are often faulty”, Sci., 278:1041-1042 (1997).
Hamra et al., “Uroguanylin: structure and activity of a second endogenous peptide that stimulates intestinal guanylate cyclase ”, Proc. Natl. Acad. Sci. USA, 90:10464-10468 (1993).
Hughes et al., “Intracellular K+Suppresses the Activation of Apoptosis in Lymphocytes”, J. Biol. Chem., 272(48):30567-30576 (1997).
Joo et al., “Regulation of intestinal Cl− and HCO3− secretion by uroguanylin ”, Am. J. Physiol., 274:G633-G644 (1998).
Klodt et al., “Synthesis, biological activity and isomerism of guanylate cyclase C-activating peptides guanylin and uroguanylin”, J. Pep. Res., 50(2):77-152(1997).
Lorenz et al., “Uroguanylin knockout mice have increased blood pressure and impaired natriuretic response to enteral NaCI load”, J. Clin. Invest.,112(8):1244-1254 (2003).
Nyburg et al., “Some uses of best molecular fit routine Acta”, Crystallographica B30. (Part I):251-253 (1974).
Pitari et al., “Guanylyl cydase C agonists regulate progression through the cell cycle of human colon carcinoma cells ”, Proc. Natl. Acad. Sci. USA, 98(14):7846-7851 (2001).
Provenzale et al., “Surveillance Issues in Inflammatory Bowel Disease: Ulcerative Colitis”, J. Clin. Gastroenterol, 32:99-105 (2001).
Samuel et al., “Absorption of bile acids from the large bowel in man”, J. Clin. Invest., 47:2070-2078 (1968).
Schulz, et al., “Side Chain Contributions to the Interconversion of the Topological Isomers of Guanylin-like Peptides”, J. Pep. Sci., 11(6):319-330 (2005).
Sciaky et al., “-Mapping of guanylin to murine chromosome 4 and human chromosome 1p34p35 <http://www.sciencedirect.com.ezp-prod1.hul.harvard.edu/science?—ob=ArticleURL&—udi=B6WG1-471W7HX-8G&—user=209690&—coverDate=03%2F20%2F1995&—rdoc=41&—fmt=high&—orig=browse&—srch=doc-info(%23toc%236809%231995%23999739997%23350519%23FLP%23display%23Volume)&—cdi=6809&—sort=d&—docanchor=&—ct=44&—acct=C000014438&—version=1&—urlVersion=0&—userid=209690&md5=8e6a2fa157ff2c774f28040cf2e7ae30>”, Genomics, 26:427-429 (1995).
Shailubhai et al., “Guanilib, an agonist of Guanylate C, is a new class of oral drug candidate for GI disorders and colon cancer”, [Abstract]: In GTCbio, 2008.
Shailubhai et al., “Guanilib, an antagonist of Guanylate C, is a new class of oral drug candidate that amerliorates inflammation in models of experimental colitis”, [Abstract]: In Crohn's and Colitis Foundation of America, 2007.
Shailubhai et al., Clin. Cancer Res., (Proc. 1999 AACR NCI EORTC Int. Conf.), [Abstract], 5(Suppl.) (1999).
Shailubhai et al., “Guanylate Cyclase-C Agonists as a New Class of Drug Candidates for GI Motility and Inflammatory Bowel Disease”, [Abstract] (2009).
Shailubhai et al., “Therapeutic Applications of Guanylate Cyclase-C Receptor Agonists” Curr. Opin. Drug Disc. Develop., 5(2):261-268 (2002).
Sindic et al., “Guanylin, Uroguanylin, and Heat-stable Euterotoxin Activate Guanylate Cyclase C and/or a Pertussis Toxin-sensitive G Protein in Human Proximal Tubule Cells”, J. Biol. Chem., 277:17758-17764 (2002).
Takada et al., “Alteration of a Single Amino Acid in Peroxisome Proliferator-Activated Receptor- (PPAR) Generates a PPAR Phenotype”, Mol. Endocrinol., 14(5):733-740 (2000).
Tian et al., “STa Peptide Analogs for Probing Guanylyl Cyclase C”, BIOPOLYMERS (Pept. Sci.), 90(5):713-723 (2008).
Venkatakrishnan et al., “Exaggerated Activation of Nuclear Factor- B and Altered I B—Processing in Cystic Fibrosis Bronchial Epithelial Cells”, Am. J. Resp. Cell Mol. Biol., 23(3):396-403 (2000).
Weber et al., Activation of NF− B in airway epithelial cells is dependent on CFTR trafficking and CI channel function, Am. J. Physiol. Lung Cell Mol. Biol., 281(1):L71-78 (2001).
Welsh et al., “Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis”, Cell, 73:1251-1254 (1993).
Zhang et al., “Gene Expression Profiles in Normal and Cancer Cells ”, Sci. 276:1268-1272 (1997).
Genbank 1UYBA—Chain A, Solution Structure B-Form Uroguanylin, Mar. 15, 2010.
Li et al., “Purification, cDNA Sequence and Tissue Distribution of Rat Uroguanylin”, Reg. Pep., 68:45-56 (1997).
Genbank: PRF: 738946 (opossum, 1993), Mar. 15, 2011.
Whitaker et al., “Uroguanylin and Guanylin: Distint but Overlapping Patterns of Messenger RNA Expression Mouse Intestine”, Gastroenterol., 113(3):1000-6 (1997).
Opposition to European Patent No. 1,379,224 B1 by Christopher Michael Hill dated Apr. 22, 2010.
CombiMab, Inc. Annex to Notice of Opposition against European Patent 1,379,224 B1 dated Apr. 22, 2010.
Summons to Attend Oral Hearing and Preliminary Opinion of the Opposition Division dated Jun. 24, 2011 for European Patent Application No. 02721604.
Response to Communication from Opposition Division relating to European Patent No. 1379224.3 dated Oct. 8, 2010.
Written submission dated Oct. 7, 2011 in response to the Jun. 24, 2011 preliminary opinion of the Opposition Division regarding European Patent Application No. 02721604.3.
Written submission dated Oct. 14, 2011 by Ironwood regarding European Patent Application No. 02721604.3.
Written submission dated Oct. 14, 2011 regarding European Patent Application No. 02721604.3.
Written submission dated Oct. 25, 2011 regarding European Patent Application No. 02721604.3.
Written submission by Ironwood dated Nov. 18, 2011 regarding European Patent Application No. 02721604.3.
Written submission dated Nov. 22, 2011 regarding European Patent Application No. 02721604.3.
Written submission dated Dec. 7, 2011 regarding European Patent Application No. 02721604.3.
Veronese et al., “PEGylation, successful approach to drug delivery”, Drug Disc. Today, 10(21):1451-1458 (2005).
Howard et al., “Obesity and Dyslipidemia”, Endocrinol. Metab. Clin. N. Am., 32:855-867 (2003).
Shailubhai et al., “Inflammatory Bowel Disease”, Feb. 2008: S5 2007 IBD Abstract: Oral Presentation.
Patent Publication Number: 20120142614
Current U.S. Class: Transporter Affecting Or Utilizing (514/1.2); Peptide (e.g., Protein, Etc.) Containing Doai (514/1.1); Cyclopeptide Utilizing (514/2.9); Cyclopeptide Utilizing (514/3.6); 16 To 24 Amino Acid Residues In The Peptide Chain (514/21.4); Peptides Of 3 To 100 Amino Acid Residues (530/300); Cyclic Peptides (530/317); 15 To 23 Amino Acid Residues In Defined Sequence (530/326)