DK3102197T3 - Smoothened-mutant og fremgangsmåder til anvendelse deraf - Google Patents

Smoothened-mutant og fremgangsmåder til anvendelse deraf Download PDF

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DK3102197T3
DK3102197T3 DK15705757.1T DK15705757T DK3102197T3 DK 3102197 T3 DK3102197 T3 DK 3102197T3 DK 15705757 T DK15705757 T DK 15705757T DK 3102197 T3 DK3102197 T3 DK 3102197T3
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antibody
smo
amino acid
protein
cell
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DK15705757.1T
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Sauvage Frederic J De
Robert L Yauch
Gerrit J P Dijkraaf
Hayley Sharpe
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Genentech Inc
Curis Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4703—Regulators; Modulating activity
    • G01N2333/4704—Inhibitors; Supressors

Claims (15)

1. Isoleret nukleinsyremolekyle, der koder for et mutant-SMO-protein, omfattende en aminosyresekvens, der er mindst 95 % identisk med SEQ ID NO: 1, hvor aminosyresekvensen omfatter en aminosyre, som ikke er tryptophan ved aminosyrepositionen svarende til position 281 med SEQ ID NO: 1.
2. Nukleinsyresonde, som er i stand til specifikt at hybridisere til en nukleinsyre, der koder for et muteret SMO-protein eller et fragment deraf, som inkorporerer en mutation i den sekvens, der koder for aminosyrepositionen svarende til 281 af SEQ ID NO: 1, hvor sonden yderligere omfatter et detekterbart mærke.
3. Isoleret mutant-SMO-protein, omfattende en aminosyresekvens, der er mindst 95 % identisk med SEQ ID NO: 1, hvor aminosyresekvensen omfatter en aminosyre, som ikke er tryptophan ved aminosyrepositionen svarende til position 281 med SEQ ID NO: 1.
4. Isoleret mutant-SMO-protein ifølge krav 3, hvor aminosyresekvensen omfatter cystein (C) ved aminosyrepositionen svarende til position 281 med SEQ ID NO: 1.
5. Isoleret antistof, der specifikt binder til mutant-SMO-proteinet ifølge krav 3 eller 4, hvor antistoffet ikke binder et vildtype SMO-protein med en tryptophan ved aminosyrepositionen svarende til 281 med SEQ ID NO: 1.
6. Fremgangsmåde til identificering af mindst én SMO-mutation i en prøve, omfattende at bringe en nukleinsyre fra prøven i kontakt med en nukleinsyresonde, som er i stand til specifikt at hybridisere til en nukleinsyre, der koder for et muteret SMO-protein eller et fragment deraf, som inkorporerer en mutation, som ænder den sekvens, der koder for aminosyrepositionen svarende til 281 med SEQ ID NO: 1 til en aminosyre, som ikke er tryptophan, og at detektere hybridiseringen.
7. Sammensætning til anvendelse i behandling af en tumor i et individ, hvor det er bestemt, at individet har en tumor, der er resistent over for behandling med GDC-0449, omfattende bestemmelsen af tilstedeværelsen af et muteret SMO-gen eller muteret SMO-protein i en prøve med tumoren, hvor det muterede SMO-gen koder for et muteret SMO-protein, omfattende en mutation ved aminosyrepositionen svarende til position 281 med SEQ ID NO: 1, og hvor SMO-proteinet omfatter en mutation ved aminosyrepositionen svarende til position 281 med SEQ ID NO: 1, hvor tilstedeværelsen af det muterede SMO-gen eller muterede SMO-protein indikerer, at tumoren er resistent over for behandling med et GDC-0449; hvor sammensætningen binder til den muterede SMO.
8. Sammensætning til anvendelse ifølge krav 7, hvor tilstedeværelsen eller fraværet af mutationen bestemmes ved at undersøge en nukleinsyreprøve.
9. Sammensætning til anvendelse ifølge krav 7, hvor tilstedeværelsen eller fraværet af mutationen bestemmes ved at undersøge en proteinprøve.
10. Fremgangsmåde til screening for forbindelser, der inhiberer signalering af et mutant-SMO-protein, som inkorporerer en mutation ved aminosyrepositionen svarende til aminosyreposition 281 med SEQ ID NO: 1, hvor fremgangsmåden omfatter at bringe det mutante SMO i kontakt med en testforbindelse og detektere binding af forbindelsen til det mutante SMO, hvor binding af testforbindelsen til mutant SMO indikerer, at testforbindelsen er en inhibitor af mutant SMO.
11. Fremgangsmåde til screening for forbindelser, der inhiberer signalering af et mutant-SMO-protein, som inkorporerer en mutation ved aminosyrepositionen svarende til aminosyreposition 281 of SEQ ID NO: 1; hvor fremgangsmåden omfatter at bringe en celle, som eksprimerer det mutante SMO, i kontakt med en testforbindelse og detektere Gli-aktivitet i cellen, hvor tilstedeværelsen af Gli-aktivitet indikerer, at testforbindelsen ikke er en inhibitor af mutant SMO.
12. Sammensætning til anvendelse ved hæmning af proliferation eller vækst i et individ af en celle, som har aberrerende hedgehog-signalering, hvor sammensætningen er en bromodomaininhibitor, hvor cellen eksprimerer et smoothened-protein med en mutation ved aminosyrepositionen svarende til aminosyrepositionerne 281 med SEQ ID NO: 1.
13. Sammensætning til anvendelse ifølge krav 12, hvor cellen yderligere omfatter en SUFU-mutation.
14. Fremgangsmåde til identificering af en hedgehog-pathway-inhibitor, hvor fremgangsmåden omfatter: at bringe en celle i kontakt med en mængde af et testmiddel, hvor cellen reagerer på hedgehog-protein eller har forøget hedgehog-signalering og/eller aktivering af hedgehog-signalvejen, og hvor cellen eksprimerer mutant-SMO-proteinet ifølge krav 3, og b) at bestemme, sammenlignet med en kontrol, om testmidlet hæmmer hedgehog-signalering i cellen, hvor hvis testmidlet hæmmer hedgehog-signalering i cellen i forhold til kontrollen, så identificeres testmidlet som en hedgehog-pathway-inhibitor.
15. Fremgangsmåde til identificering af en hedgehog-pathway-inhibitor, hvor fremgangsmåden omfatter: at bringe en celle i kontakt med en mængde af et testmiddel, hvor cellen reagerer på hedgehog-protein eller har forøget hedgehog-signalering og/eller aktivering af hedgehog-signalvejen, og hvor cellen eksprimerer mutant-SMO-proteinet ifølge krav 3, og b) og bestemme, sammenlignet med en kontrol, om testmidlet hæmmer vækst og/eller proliferation af cellen, hvor hvis testmidlet hæmmer vækst og/eller proliferation af cellen i forhold til kontrollen, så identificeres testmidlet som en hedgehog-pathway-inhibitor.
DK15705757.1T 2014-02-04 2015-02-04 Smoothened-mutant og fremgangsmåder til anvendelse deraf DK3102197T3 (da)

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US (1) US20170044232A1 (da)
EP (1) EP3102197B1 (da)
JP (1) JP6736467B2 (da)
AU (1) AU2015214264B2 (da)
CA (1) CA2937539A1 (da)
DK (1) DK3102197T3 (da)
ES (1) ES2694857T3 (da)
WO (1) WO2015120075A2 (da)

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WO2017136558A1 (en) 2016-02-04 2017-08-10 Curis, Inc. Mutant smoothened and methods of using the same
CN107176993A (zh) * 2017-06-26 2017-09-19 厦门市妇幼保健院（厦门市计划生育服务中心） 一种mmaf致病基因新突变及其应用
EP3752645A4 (en) * 2018-02-14 2022-04-13 Dermtech, Inc. NEW GENE CLASSIFIERS AND THEIR USES IN NON-MELANOMA SKIN CANCERS

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