DK2733491T3 - Diagnostisk fremgangsmåde - Google Patents

Diagnostisk fremgangsmåde Download PDF

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DK2733491T3
DK2733491T3 DK13194854.9T DK13194854T DK2733491T3 DK 2733491 T3 DK2733491 T3 DK 2733491T3 DK 13194854 T DK13194854 T DK 13194854T DK 2733491 T3 DK2733491 T3 DK 2733491T3
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nucleic acid
protein
disease
sequence
treatment
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Thangue Nicholas B La
Susan Fotheringham
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Univ Oxford Innovation Ltd
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Claims (10)

1. Fremgangsmåde til diagnosticering af modtageligheden af et individ der lider af en sygdom overfor behandling med en HDAC-inhibitor, hvilken fremgangsmåde omfatter vurdering af ekspressionsniveauet eller aktivitet af et gen eller dets ekspressionsprodukter, eller sekvensen af et gen, i en vævsprøve fra en patient og sammenligne ekspressionsniveauet eller aktivitet eller sekvens med en reference, hvor ekspressionsniveauet eller aktivitet eller sekvens der er forskellig fra referencen er indikativ for en ændret modtagelighed for behandling med HDAC-inhibitoren i forhold til referencetilstanden, og hvor genet er Myd88 (myeloid differentiation primary response gene 88).
2. Fremgangsmåden ifølge krav 1, hvor et niveau der er signifikant højere end referenceniveauet indikerer at individet er mere modtagelig overfor behandling med en HDAC-inhibitor.
3. Fremgangsmåden ifølge krav 1, hvor et niveau der er signifikant lavere end referenceniveauet er indikation for et individs potentielle resistens for behandling med HDAC-inhibitoren.
4. Fremgangsmåden ifølge et hvilket som helst af de foregående krav, hvor ekspressionsproduktet er et protein, og hvor eventuelt fremgangsmåden omfatter trinnene at: (a) af bringe en ligand af proteinet i kontakt med en prøve fra en patient under betingelser der er egnede til dannelsen af et ligand-proteinkompleks; og (b) påvise komplekset.
5. Fremgangsmåden ifølge et hvilket som helst af kravene 1-3, hvor fremgangsmåden omfatter trinnene at: (a) isolere et nukleinsyremolekyle der koder for Myd88 fra en prøve fra en patient der er testet for sygdom; og (b) diagnosticere patienten ved påvisning af tilstedeværelsen afen mutation der er associeret med en ændret modtagelighed for behandling med HDAC-inhibitoren.
6. Anvendelsen af et array til diagnosticering af modtageligheden af et individ der lider af en sygdom for behandling med en HDAC-inhibitor ifølge et hvilket som helst af de foregående krav, hvor arrayet omfatter: (a) mindst to nukleinsyremolekyler, hvor hver af disse nukleinsyremolekyler svarer til sekvensen af; er komplementær med sekvensen af; eller hybridiserer specifikt til et nukleinsyremolekyle, hvor nukleinsyremolekylet: (i) omfatter sekvensen af Myd88 reciteret i accessionsnummer NM 002468; (ii) omfatter komplementet af (i); eller (iii) hybridiserer under højstringente betingelser til et nukleinsyremolekyle ifølge (i); eller (b) mindst to forskellige typer antistofspecier, hvor hver antistofspecie er immunospecifik med et protein hvor proteinet i (b): (iv) har en aminosyresekvens der kodes af en nukleinsyresekvens af (i)- (iii) ; eller (v) er et fragment af et protein ifølge (iv), forudsat at dette fragment bevarer den biologiske aktivitet der besiddes af fuldlængdepolypeptidet af (iv) ; eller har en antigen determinant fælles med polypeptidet af (iv).
7. En HDAC-inhibitor til anvendelse i behandling af en patient med en proliferativ sygdom eller en sygdom eller tilstand der involverer en ændring i celledifferentiering eller væksthastighed, hvor patienten er blevet identificeret som modtagelig for HDAC-inhibitorbehandling under anvendelse af fremgangsmåden ifølge et hvilket som helst af kravene 1 til 5, hvor den proliferative sygdom er cancer.
8. Anvendelsen af et antistof til diagnosticering af modtageligheden af et individ der lider afen sygdom for behandling med en HDAC-inhibitor ifølge fremgangsmåden ifølge et hvilket som helst af kravene 1-5, hvor antistoffet binder specifikt til et protein, hvor proteinet: (a) har en aminosyresekvens der kodes af en nukleinsyresekvens der: (i) omfatter sekvensen af Myd88 reciteret i accessionsnummer NM 002468; (ii) omfatter komplementet af (i); eller (iii) hybridiserer under højstringente betingelser til et nukleinsyremolekyle ifølge (i); eller (b) er et fragment af et protein ifølge (a), forudsat at dette fragment bevarer den biologiske aktivitet der besiddes af fuldlængdepolypeptidet af (a); eller har en antigen determinant fælles med polypeptidet af (a).
9. Anvendelse af et kit til diagnosticering af modtageligheden hos et individ der lider af en sygdom for behandling med en HDAC inhibitor, hvor kittet omfatter: (a) en første beholder indeholdende en nukleinsyreprobe der hybridiserer under stringente betingelser med et nukleinsyremolekyle, hvor nukleinsyremolekylet: (i) omfatter sekvensen af Myd88 reciteret i accessionsnummer NM 002468; (ii) omfatter komplementet af (i); eller (iii) hybridiserer under højstringente betingelser et nukleinsyremolekyle ifølge (i); (b) en anden beholder indeholdende primere der er anvendelige til amplificering af dette nukleinsyremolekyle; og (c) instruktioner til anvendelse af proben og primerne til at facilitere diagnosen; eller omfatter: (i) ét eller flere antistoffer ifølge krav 8; og (ii) et reagens der er anvendelig til påvisning af en bindingsreaktion mellem antistoffet og proteinet.
10. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 5, hvor vævsprøven, er blod, urin, spyt, eller en specifik vævsbiopsi.
DK13194854.9T 2006-03-27 2007-03-27 Diagnostisk fremgangsmåde DK2733491T3 (da)

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