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(12) United States Patent (10) Patent No.: US 9,051,349 B2 Callens Et Al

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(12) United States Patent (10) Patent No.: US 9,051,349 B2 Callens Et Al US009051349B2 (12) United States Patent (10) Patent No.: US 9,051,349 B2 Callens et al. (45) Date of Patent: Jun. 9, 2015 (54) LARAZOTIDEACETATE COMPOSITIONS FOREIGN PATENT DOCUMENTS EP O184243 6, 1986 (71) Applicant: Alba Therapeutics Corp., Baltimore, JP 61-268.700 11, 1986 MD (US) JP 2003034653 2, 2003 WO WO96,37196 11, 1996 (72) Inventors: Roland Callens, Grimbergen (BE): WO WOOOO7609 2, 2000 WO WOO1,895.51 11, 2001 Georges Blondeel, Aalst (BE); Thierry WO WOO3,055900 T 2003 Delplanche, Mont-St-Guibert (BE) WO WO 2005/063800 7/2005 WO WO 2005/121164 12/2005 (73) Assignee: Alba Therapeutics Corporation, WO WO 2006/034056 3, 2006 WO WO 2006/041945 4/2006 Baltimore, MD (US) WO WO 2006/119388 11, 2006 WO WO 2006,135811 12/2006 (*) Notice: Subject to any disclaimer, the term of this WO WO 2007/095092 8, 2007 patent is extended or adjusted under 35 WO WO 2009/065836 5, 2009 U.S.C. 154(b) by 0 days. WO WO 2009/065949 5, 2009 (21) Appl. No.: 13/832,820 OTHER PUBLICATIONS Kolpuru et al., “Analysis of binding affinity of the Zonulin agonist (22) Filed: Mar 15, 2013 (AT1002) and antagonist (AT1001) to the Zonulin intestinal recep tor.' North American Society for pediatric gastroenterology, hepatol (65) Prior Publication Data ogy, and nutritional annual meeting, J. Ped. Gastroent. Nutr., 43(4): US 2013/0281384 A1 Oct. 24, 2013 E14-E76, p. E52, poster #121; Oct. 21, 2006).* DiPierro et al., "Zonula occludens toxin structure-function analysis: identification of the fragment biologically active on tight junctions and of the Zonulin receptor binding domain.” J. Biol. Chem. Related U.S. Application Data 276:19160-165 (2001)).* (63) Continuation-in-part of application No. 12/743,411, Singhal et al. "Drug polymorphism and dosage form design: a prac filed as application No. PCT/EP2008/066037 on Nov. tical perspective” Advanced Drug Delivery Reviews, 2004, 56,335 21, 2008. 347.* Brittain et al. “Physical Characterization of Pharmaceutical Solids.” (60) Provisional application No. 61/014,938, filed on Dec. Pharmaceutical Research, vol. 8, No. 8, 1991, pp.963-973.* 19, 2007, provisional application No. 61/073,843, Raw et al. “Regulatory considerations of pharmaceutical Solid filed on Jun. 19, 2008, provisional application No. polymorphism in Abbreviated New Drug Applications (ANDAs).” 61/103,289, filed on Oct. 7, 2008. Advanced Drug Delivery Reviews 56 (2004)397-414.* Shah et al. "Analytical Techniques for Quantification of Amorphous/ Crystalline Phases in Pharmaceutical Solids,” Journal of Pharmaceu (30) Foreign Application Priority Data tical Sciences, vol. 95, No. 8, Aug. 2006, pp. 1641-1665.* Newman et al. “Solid-state analysis of the active pharmaceutical Nov. 21, 2007 (EP) ..................................... O7121207 ingredient in drug products.” Drug Discovery Today vol. 8, No. 19 Oct. 2003, pp. 898-905.* (51) Int. Cl. Bis et al. “Defining & Addressing Solid-State Risks. After the Proof C07K 7/06 (2006.01) of-Concept Stage of Pharmaceutical Development.” Drug Develop C07C 53/10 (2006.01) ment & Delivery, Apr. 2011, pp. 32-34.* A6 IK38/08 (2006.01) Andersson, L. et al., "Large-scale synthesis of peptides.” (52) U.S. Cl. Biopolymers, 55(3):227-250 (2000). CPC. C07K 7/06 (2013.01); C07C 53/10 (2013.01); (Continued) A6 IK38/08 (2013.01) (58) Field of Classification Search None Primary Examiner — Christina Bradley See application file for complete search history. (74) Attorney, Agent, or Firm — Morgan, Lewis & Bockius LLP (56) References Cited U.S. PATENT DOCUMENTS (57) ABSTRACT 3,960,830 A 6/1976 Bayer et al. The invention provides crystalline forms of the peptide Gly 4,725,645 A 2, 1988 Anteunis et al. Gly-Val-Leu-Val-Gln-Pro-Gly (SEQ ID NO 1), and salts of 6,884,345 B1 4/2005 Irgum et al. the peptide, which may further have associated water mol 7,026,294 B2 4/2006 Fasano et al. ecules. These salts and hydrated salts of the peptide and 8,546,530 B2 10/2013 Callens et al. 2002/0115825 A1* 8/2002 Fasano .......................... 530/324 compositions comprising these materials have advantageous 2005, OO65074 A1 3/2005 Fasano et al. pharmaceutical properties. 2005/O1652.15 A1 7/2005 Bigelow et al. 2008/O103100 A1* 5/2008 Fasano et al. ................... 514, 16 2010/028O221 A1 11/2010 Callens et al. 8 Claims, 11 Drawing Sheets US 9,051,349 B2 Page 2 (56) References Cited Wisniewski, R., “Principles of the design and operational consider ations of large scale high performance liquid chromatography OTHER PUBLICATIONS (HPLC) systems for proteins and peptides purification. BioSepara tion, 3(2-3):77-143 (1992). von Bahr-Lindstrom, H. et al., “Ion-exchange high-performance liq Di Pierro, M. et al., "Zonula occludens toxin structure-function uid-chromatography steps in peptide purifications. Bioscience analysis. 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International Journal of Peptide & Protein Research, 48(2):200-207 medsafe.govt.nz/profs/datasheet/i/integrilininj.htm>, retrieved on (1996). Sep. 27, 2006), 12 pgs. Najera, C., “From O-amino acids to peptides: All you need for the Ramagopal, U. A. et al., “Crystal structure of Boc-LAla-deltaPhe journey.” Synlett, (9): 1388-1404 (2002). deltaPhe-deltaPhe-deltaPhe-NHMe: a left-handed helical peptide.” Journal of Peptide Research, 52(3):208-215 (1998). Montalbetii, C. A. G. N. et al., “Amide bond formation and peptide Meienhofer, J. et al., “A Solid-phase synthesis of (8-arginine)- coupling.” Tetrahedron, 61 (46): 10827-10852 (2005). vasopressin through a crystalline protected nonapeptide intermediate Guzman, F. et al., “Peptide synthesis: chemical or enzymatic.” Elec and biological properties of the hormone.” Journal of the American tronic Journal of Biotechnology, 10(2):279-314 (2007). Chemical Society, 92(24):7199-7202 (1970). Aimoto, S., "Contemporary methods for peptide and protein synthe Lovejoy, B. et al., “Crystallization of proton channel peptides.” Pro sis.” Current Organic Chemistry, 5(1):45-87 (2001). tein Science, 1 (8): 1073-1077 (1992). Hearn, M. T. et al., “High-performance liquid chromatography of Betz, S. F. et al., “Crystallization of a designed peptide from a molten amino acids, peptides and proteins. LXIX. Evaluation of retention globule ensemble.” Folding & Design, 1(1):57-64 (1996). and bandwidth relationships of myosin-related peptides separated by Wissler, J. H., "Chemistry and biology of the anaphylatoxin related gradient elution reversed-phase high-performance liquid chromatog serum peptide system. I. Purification, crystallization and properties raphy,” Journal of Chromatography, 392:33-49 (1987). of classical anaphylatoxin from rat serum.” European Journal of Hearn, M. T. et al., “High-performance liquid chromatography of Immunology, 2(1):73-83 (1972). amino acids, peptides and proteins. LXXXV. Evaluation of the use of Wissler, J. H., "Chemistry and biology of the anaphylatoxin related hydrophobicity coefficients for the prediction of peptide elution pro serum peptide system. II. Purification, crystallization and properties files,” Journal of Chromatography, 438(2): 197-210 (1988). of cocytotaxin, a basic peptide from rat serum.” European Journal of Pradayrol, L. et al., "Pig duodenal Somatostatin: Extraction and puri Immunology, 2(1):84-89 (1972). fication.” Metabolism. 27(9 Suppl. 1): 1197-1200 (1978). Marinaro, M. et al., "Zonula occludens toxin acts as an adjuvant Lees, M. B. et al., “A study of elastase peptides from bovine white through different mucosal routes and induces protective immune matter proteo lipid.” Neurochemical Research, 6(10): 1091-1 104 responses.” Infection and Immunity, 71(4): 1897-1902 (2003). (1981). International Search Report and Written Opinion for International Duvick, J. P. et al., “Purification and characterization of a novel Application No. PCT/EP2008/066037, mailed Jun. 16, 2009. antimicrobial peptide from maize (Zea may’s L.) kernels.” Journal of Biological Chemistry, 267(26): 18814-18820 (1992). * cited by examiner U.S. Patent Jun. 9, 2015 Sheet 1 of 11 US 9,051,349 B2 FIGURE &y 8ty is: 8. Wi & rt &y 3 As s t y 8 FIGURE 2 U.S. Patent Jun. 9, 2015 Sheet 2 of 11 US 9,051,349 B2 FIGURE 3 &y sy s i.: f 2. r &y 3. s & y 3 X ------- y ------- y X YYYY y - ------------ y X -------------------------------- 'y ------------------------------------ y X --- y - --- y X ----------------------------------------------------------------------------------------- y ----------------------------------------------------------------------------------- y H -i-k-k-k-i-...-- y FIGURE 4 Gly ey Wol et V an P ey 1. 2 3. 4. 5 6 7 8 U.S. Patent Jun. 9, 2015 Sheet 3 of 11 US 9,051,349 B2 FIGURE 5 &y &y f &: f &is SY &y FIGURE 6 s y 8ty i.e. Wa isis re &ly U.S. Patent Jun. 9, 2015 Sheet 4 of 11 US 9,051,349 B2 U.S. Patent Jun. 9, 2015 Sheet 5 of 11 US 9,051,349 B2 * * * * * * * & * * * * * * * * * * * * * ----------------------------------------------------- ------------------------------------------------------------- --------------- -------------------------------- --------------- ---------------- ---------------------------- c N (SS23 g : i83 to eifs U.S. Patent US 9,051,349 B2 U.S. Patent US 9,051,349 B2 U.S. Patent Jun. 9, 2015 Sheet 8 of 11 US 9,051,349 B2 wer o st -.-.-.**************************************- U.S.
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