FI111546B - In vitro-förfarande för övervakning av bearbetning av ett beta-amyloidföregångarprotein i celler, för diagnostisering eller övervakning av ett till beta-amyloid hänförd sjukdom eller för identifieringav inhibitorer av beta-amyloidproduktionen samt lösligt fragment av beta-amyloidföregångarprotein - Google Patents

In vitro-förfarande för övervakning av bearbetning av ett beta-amyloidföregångarprotein i celler, för diagnostisering eller övervakning av ett till beta-amyloid hänförd sjukdom eller för identifieringav inhibitorer av beta-amyloidproduktionen samt lösligt fragment av beta-amyloidföregångarprotein Download PDF

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FI111546B
FI111546B FI944847A FI944847A FI111546B FI 111546 B FI111546 B FI 111546B FI 944847 A FI944847 A FI 944847A FI 944847 A FI944847 A FI 944847A FI 111546 B FI111546 B FI 111546B
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βαρρ
fragment
amyloid
beta
residues
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FI944847A (sv
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Peter A Seubert
Dale B Schenk
Lawrence C Fritz
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Lilly Co Eli
Athena Neurosciences Inc
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Claims (10)

1. In vitro-förfarande för övervakning av bearbet-ning av ett β-amyloidföregängarprotein (βΑΡΡ) i celler, 5 kännetecknat av att förfarandet omfattar spe-cifik detektering av ett lösligt aminoterminalt βΑΡΡ-fragment (ATF-ΑΡΡβ) soin avsöndras frän nämnda celler och detektering av en substans, vilken specifikt binder sig vid nämnda lösliga βΑΡΡ-fragment, varvid aminosyrasekven-10 sen hos nämnda βΑΡΡ-fragment väsentligen sträcker sig frän aminoterminus hos βΑΡΡ-fragmentet tili aminoterminus hos β-amyloidpeptiden (β-ΑΡ) och varvid ATF-βΑΡΡ kan avskiljas frän andra spjälkade former av βΑΡΡ, som kan vara närva-rande i ett biologisk prov. 15
2. Förfarande enligt patentkrav 1, känne tecknat av att detekteringen av AFP-βΑΡΡ-fragmentet omfattar exponering av provet för en substans, vilken spe-cifikt binder sig vid en C-terminal region i det avsöndra-20 de fragmentet, vilket frilagts genom spjälkning av β-amyloidpeptiden (βΑΡ) frän βΑΡΡ, och detektering av bindningen mellan substansen och det avsöndrade fragmentet.
3. Förfarande enligt patentkrav 1 eller 2, 25 kännetecknat av att den C-terminala resten ligger inom ett omräde av fem bredvid varandra liggande rester aminoterminalt i förhällande tili βΑΡ.
4. Förfarande enligt patentkrav 1 eller 2, kännetecknat av att den C-terminala resten är 30 metionin596, lysin595 eller leucin596 .
5. Förfarande enligt patentkrav 1 eller 2, kännetecknat av att provet exponeras för en antikropp, vilken är specifik för den C-terminala resten som frilagts genom spjälkning av β-amyloidpeptiden frän 3 5 βΑΡΡ. 111546 31
6. Förfarande enligt patentkrav 5, kännetecknat av att antikroppen ästadkommits mot en pep-tid som omfattar resterna 591 - 596 av βΑΡΡ och väri res-ten596 frilagts.
7. In vitro-förfarande för diagnostisering eller övervakning av ett tili β-amyloid hänförd sjukdom hos en patient, kännetecknat av att det omfattar mätning av mängden av relationen av ett avsöndrad fragment av β-amyloidföregängarprotein (βΑΡΡ) genom att 10 exponera fragmentet för en substans som binder sig speci-fikt vid nämnda βΑΡΡ-fragment, varvid aminosyrasekvensen hos βΑΡΡ-fragmentet väsentligen sträcker sig frän amino-terminus hos βΑΡΡ till aminoterminus hos β-amyloidreptiden; och 15 jämförande av mängden av nämnda βΑΡΡ-fragment med mängden som karakteriserar normala patientprov, varvid en förhöjd mängd indikerar Alzheimers sjukdom.
8. In vitro-förfarande för identifiering av inhi-bitorer av β-amyloidproduktionen, kännetecknat 20 av att det omfattar: odling av celler under förhällanden som leder tili avsöndringen av ett lösligt aminoterminalt fragment (ATF-βΑΡΡ) av β-amyloidföregängarproteinet (βΑΡΡ), varvid aminosyrasekvensen hos nämnda lösliga βΑΡΡ-fragment väsentli-25 gen sträcker sig frän aminoterminus hos βΑΡΡ till aminoterminus hos β-amyloidpeptiden (βΑΡ), exponering av de odlade cellerna för ett flertal testföreningar; och identifiering av mängden av ATF-βΑΡΡ, varvid sänk-30 ningen av mängden av löslig ATF-βΑΡΡ som inte exponeras • · < visar att föreningen är en inhibitor av β-amyloid-produkt i onen.
9. Lösligt fragment av β-amyloidföregängarprotein (βΑΡΡ) i renad och isolerad form, kännetecknat 35 av att aminosyrasekvensen hos nämnda βΑΡΡ-fragment väsent-. . ligen sträcker sig frän aminoterminus hos βΑΡΡ till amino- 111546 32 terminus hos ,S-amyl oidpept iden (jSAP) , varvid nämnda βΑΡΡ-fragment har ett C-terminalt metionin eller leucin, vilket resulterar frän spjälkningen av en /S-amyloidpeptid f ran intakt /SAPP. 5
10. Lösligt fragment enligt patentkrav 9, k ä n - netecknatav att det väsentligen bestär av rester-na 18 - 596 av /SAPP-isoformen 695, resterna 18 - 612 av /SAPP-isof ormen 751, resterna 18 - 671 av /SAPP-isoformen 770, resterna 18 - 595 av /SAPP-isoformen 695, resterna 18-10 611 av /SAPP-isoformen 751 eller resterna 18 - 670 av /SAPP- isoformen 770.
FI944847A 1992-04-15 1994-10-14 In vitro-förfarande för övervakning av bearbetning av ett beta-amyloidföregångarprotein i celler, för diagnostisering eller övervakning av ett till beta-amyloid hänförd sjukdom eller för identifieringav inhibitorer av beta-amyloidproduktionen samt lösligt fragment av beta-amyloidföregångarprotein FI111546B (sv)

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Application Number Priority Date Filing Date Title
US86894992A 1992-04-15 1992-04-15
US86894992 1992-04-15
US07/965,971 US5441870A (en) 1992-04-15 1992-10-26 Methods for monitoring cellular processing of β-amyloid precursor protein
US96597192 1992-10-26
PCT/US1993/001817 WO1993021526A1 (en) 1992-04-15 1993-03-03 METHODS AND COMPOSITIONS FOR MONITORING CELLULAR PROCESSING OF β-AMYLOID PRECURSOR PROTEIN
US9301817 1993-03-03

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FI944847A FI944847A (sv) 1994-10-14
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FI111546B true FI111546B (sv) 2003-08-15

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US5441870A (en) 1995-08-15
ATE251304T1 (de) 2003-10-15
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AU3782793A (en) 1993-11-18
AU688726B2 (en) 1998-03-19
NO943912L (no) 1994-11-10
FI944847A0 (sv) 1994-10-14
ES2206455T3 (es) 2004-05-16
JP3974168B2 (ja) 2007-09-12
JP2006051029A (ja) 2006-02-23
CA2118243A1 (en) 1993-10-28
DE69333225T2 (de) 2004-05-06
US6018024A (en) 2000-01-25
NO943912D0 (no) 1994-10-14
EP0638172A1 (en) 1995-02-15
WO1993021526A1 (en) 1993-10-28
NZ251053A (en) 1996-11-26
EP0638172B1 (en) 2003-10-01
EP0638172A4 (en) 1997-03-19
CA2118243C (en) 2009-11-03
DK0638172T3 (da) 2004-02-02
NO320067B1 (no) 2005-10-17
US5721130A (en) 1998-02-24
JPH07506967A (ja) 1995-08-03

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