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Prion-Specific Peptoid Reagents Prionspezifische Peptoidreagentien Reactifs Peptoides Specifiques Des Prions

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Prion-Specific Peptoid Reagents Prionspezifische Peptoidreagentien Reactifs Peptoides Specifiques Des Prions (19) TZZ_¥_5B_T (11) EP 1 931 695 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07K 7/06 (2006.01) C07K 7/08 (2006.01) 10.04.2013 Bulletin 2013/15 A61K 38/08 (2006.01) A61K 38/10 (2006.01) A61K 31/16 (2006.01) G01N 33/68 (2006.01) (2006.01) (2006.01) (21) Application number: 06814415.3 G01N 33/50 A61P 25/28 C07K 14/47 (2006.01) (22) Date of filing: 08.09.2006 (86) International application number: PCT/US2006/035226 (87) International publication number: WO 2007/030804 (15.03.2007 Gazette 2007/11) (54) Prion-specific peptoid reagents Prionspezifische Peptoidreagentien Reactifs peptoides specifiques des prions (84) Designated Contracting States: (74) Representative: Marshall, Cameron John et al AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Carpmaels & Ransford HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI One Southampton Row SK TR London WC1B 5HA (GB) (30) Priority: 09.09.2005 US 715761 P 14.10.2005 US 726686 P (56) References cited: 13.01.2006 US 758934 P WO-A1-94/06451 WO-A2-02/052046 WO-A2-2005/016127 WO-A2-2005/060697 (43) Date of publication of application: US-A- 5 965 695 US-A1- 2003 040 468 18.06.2008 Bulletin 2008/25 • HAYNES, RUSSELL D. ET AL: "Comblike, (60) Divisional application: Monodisperse Polypeptoid Drag-Tags for DNA 11171585.0 / 2 383 281 Separations by End-Labeled Free-Solution Electrophoresis (ELFSE)" BIOCONJUGATE (73) Proprietor: Novartis AG CHEMISTRY, vol. 16, no. 4, 4 July 2005 4002 Basel (CH) (2005-07-04), pages 929-938, XP002416791 • KIRSHENBAUM, KENT ET AL: "Sequence- (72) Inventors: specific polypeptoids: a diverse family of • PERETZ, David heteropolymerswith stable secondary structure" Emeryville, CA 94662-8097 (US) PROCEEDINGS OF THE NATIONAL ACADEMY • CONNOLLY, Michael, D. OF SCIENCES OF THE UNITED STATES OF Emeryville, CA 94662-8097 (US) AMERICA, vol. 95, no. 8, 14 April 1998 • ZUCKERMANN, Ronald (1998-04-14), pages 4303-4308, XP002416792 Emeryville, CA 94662-8097 (US) • GORSKE, BENJAMIN C. ET AL: "Expedient •GAO,Man Synthesis and Design Strategies for New Peptoid Emeryville, CA 94662-8097 (US) Construction" ORGANIC LETTERS, vol. 7, no. 8, • SHIMIZU, Robert, M. 14 April 2005 (2005-04-14), pages 1521-1524, Emeryville, CA 94662-8097 (US) XP002416793 • TIMOTEO, Gulliver Emeryville, CA 94662-8097 (US) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 931 695 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 1 931 695 B1 • HUANG, CHIN-YI ET AL: "Lipitoids - novel • ILARIAPERETTO ET AL: "Cell penetrable peptoid cationic lipids for cellular delivery of plasmid carrier vehicles: synthesis and evaluation", DNA in vitro" CHEMISTRY & BIOLOGY, vol. 5, no. CHEMICAL COMMUNICATIONS - CHEMCOM, 6, June 1998 (1998-06), pages 345-354, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 2003, XP002416794 no. 18, 1 January 2003 (2003-01-01), pages • REDDY, M. MURALIDHAR ET AL: 2312-2313, XP002447845, ISSN: 1359-7345 "Transformation of Low-Affinity Lead • STATZ A R ET AL: "New peptidomimetic Compounds into High-Affinity Protein Capture polymers forantifouling surfaces", JOURNALOF Agents" CHEMISTRY & BIOLOGY , 11(8), THE AMERICAN CHEMICAL SOCIETY, 1127-1137 CODEN: CBOLE2; ISSN: 1074-5521, AMERICAN CHEMICAL SOCIETY, NEW YORK, vol. 11, no. 8, August 2004 (2004-08), pages US LNKD- DOI:10.1021/JA0522534, vol. 127, no. 1127-1137, XP002416795 22,1 January 2005 (2005-01-01), pages 7972-7973, XP002541457, ISSN: 0002-7863 [retrieved on 2005-05-13] 2 EP 1 931 695 B1 Description FIELD OF THE INVENTION 5 [0001] The invention relates to peptoid reagents useful in detecting and isolating prions, and in the treatment and prevention of prion-related diseases. The invention also relates to complexes and compositions, comprising the peptoid reagents. Processes for preparing the peptoid reagents, and kits containing them, are also disclosed. BACKGROUND 10 [0002] Prion protein (PrPC) is a 33-35 kD protein of uncertain function and, in humans, is transcribed by a gene on the short arm of chromosome 20. The 27-30 kD protease-resistant core (prion, scrapie protein, or PrP Sc) is the functional component, with several isoforms responsible for "prion diseases," which are protein conformational diseases. [0003] Protein conformational diseases arise from aberrant conformational transition of a protein (a conformational 15 disease protein such as PrP C), which in turn leads to self-association of the aberrant protein forms (e.g., PrP Sc) resulting in tissue deposition and damage. Prions (PrP Sc) have a substantially pleated sheet conformation rather than the α-helix structure of normal PrP C, lack detectable nucleic acid, and generally do not elicit an immune response. In general, protein conformational diseases share striking similarities in clinical presentations, typically a rapid progression from diagnosis to death following varying lengths of incubation. 20 [0004] In humans, prion diseases, also known as, "transmissible spongiform encephalopathies" (TSEs), include, Creut- zfeldt-Jakob disease (CJD), Gerstmann- Straussler-Scheinker syndrome (GSS), Fatal Familial Insomnia, and Kuru (see, e.g., Isselbacher et al., eds. (1994). Harrison’s Principles of Internal Medicine. New York: McGraw-Hill, Inc.; Medori et al. (1992) N. Engl. J. Med. 326: 444-9). In animals, TSEs include sheep scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy, and chronic wasting disease of captive mule deer and elk (Gajdusek, (1990). 25 Subacute Spongiform Encephalopathies: Transmissible Cerebral Amyloidoses Caused by Unconventional Viruses. In: Virology, Fields, ed., New York: Raven Press, Ltd. (pp. 2289-2324)). Transmissible spongiform encephalopathies are characterized by the same hallmarks: the presence of the abnormal (beta- rich, proteinase K resistant) conformation of the prion protein that transmits disease when experimentally inoculated into laboratory animals including primates, rodents, and transgenic mice. 30 [0005] Recently, the rapid spread of BSE and its correlation with elevated occurrence of TSEs in humans has led to increased interest in the detection of TSEs in non-human mammals. The tragic consequences of accidental transmission of these diseases (see, e.g., Gajdusek, Infectious Amyloids, and Prusiner Prions In Fields Virology. Fields, et al., eds. Philadelphia: Lippincott-Ravin, Pub. (1996); Brown et al. Lancet, 340: 24-27 (1992)), decontamination difficulties (Asher et al. (1986) In: Laboratory Safety: Principles and Practices, Miller ed., (pp. 59-71) Am. Soc. Micro.), and concern about 35 BSE (British Med. J. (1995) 311: 1415-1421) underlie the urgency of having both a diagnostic test that would identify humans and animals with TSEs and therapies for infected subjects. [0006] Prions differ significantly from bacteria, viruses and viroids. The dominating hypothesis is that, unlike all other infectious pathogens, infection is caused by an abnormal conformation of the prion protein, which acts as a template and converts normal prion conformations into abnormal, aberrant conformations. A prion protein was first characterized 40 in the early 1980s. (See, e.g., Bolton, McKinley et al. (1982) Science 218: 1309-1311; Prusiner, Bolton et al. (1982) Biochemistry 21: 6942-6950; McKinley, Bolton et al. (1983) Cell 35: 57-62). Complete prion protein-encoding genes have since been cloned, sequenced and expressed in transgenic animals. (See, e.g., Basler, Oesch et al. (1986) Cell 46: 417-428.) [0007] The key characteristic of prion diseases is the formation of the abnormally shaped protein (PrPSc) from the 45 normal form of prion protein (cellular or nonpathogenic or PrPC). (See, e.g., Zhang et al. (1997) Biochem. 36(12): 3543-3553; Cohen & Prusiner (1998) Ann. Rev. Biochem. 67: 793-819; Pan et al. (1993) Proc. Natl. Acad. Sci. USA 90: 10962-10966; Safar et al. (1993) J Biol. Chem. 268: 20276-20284.) The substantiallyβ- sheet structure of PrPSc as compared to the predominantly α-helical folded non-disease forms of PrPC has been revealed by optical spectroscopy and crystallography studies. (See, e.g., Wille et al. (2001) Proc. Nat’l Acad. Sci. USA 99: 3563-3568; Peretz et al. (1997) 50 J. Mol. Biol. 273: 614-622; Cohen & Prusiner, (1999) 5: Structural Studies of Prion Proteins. In Prion Biology And Diseases, S. Prusiner, ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. (pp: 191-228.) The structural changes appear to be followed by alterations in biochemical properties: PrPC is soluble in non- denaturing detergents, PrPSc is insoluble; PrPC is readily digested by proteases, while PrPSc is partially resistant, resulting in the formation of an amino-terminally truncated fragment known as "PrPres" (Baldwin et al. (1995); Cohen & Prusiner (1995)), "PrP 27-30" 55 (27-30 kDa) or "PK-resistant" (proteinase K resistant) form. Additionally, PrPSc can convert PrPC to the pathogenic conformation. See, e.g., Kaneko et al. (1995) Proc. Nat’l Acad. Sci. USA 92: 11160-11164; Caughey (2003) Br Med Bull. 66: 109-20. [0008] Detection of the pathogenic isoforms of conformational disease proteins in living subjects, and samples obtained 3 EP 1 931 695 B1 from living subjects, has proven difficult. Thus, definitive diagnosis and palliative treatments for these transmissible and amyloid-containing conditions before death of the subject remains a substantially unmet challenge. Histopathological examination of brain biopsies is risky to the subject and lesions and amyloid deposits can be missed depending on where the biopsy sample is taken from. Also, there are still risks involved with biopsies to animals, patients, and health 5 care personnel. Further, the results from brain tests on animals are not usually obtained until the animal has entered the food supply.
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