DK2625197T3 - Smoothened-mutant og fremgangsmåder til anvendelse af samme - Google Patents
Smoothened-mutant og fremgangsmåder til anvendelse af samme Download PDFInfo
- Publication number
- DK2625197T3 DK2625197T3 DK11770024.5T DK11770024T DK2625197T3 DK 2625197 T3 DK2625197 T3 DK 2625197T3 DK 11770024 T DK11770024 T DK 11770024T DK 2625197 T3 DK2625197 T3 DK 2625197T3
- Authority
- DK
- Denmark
- Prior art keywords
- antibody
- smo
- antibodies
- amino acid
- mutant
- Prior art date
Links
Classifications
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
- C07K14/723—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor
Claims (10)
1. Isoleret mutant SMO-protein, som omfatter en aminosyresekvens, som er mindst 95 % identisk med SEQ ID NO: 2, hvor aminosyresekvensen består af alanin (A) eller lysin (K) i aminosyreposition 518 af SEQ ID NO: 2, hvor mutationen overfører mindst delvis resistens af det muterede SMO-protein til GDC-0449.
2. Isoleret mutant SMO-protein ifølge krav 1, som omfatter aminosyresekvensen af SEQ ID NO: 2, hvor aminosyresekvensen består af alanin (A) eller lysin (K) i aminosyreposition 518 af SEQ ID NO: 2.
3. Isoleret nukleinsyremolekyle, der koder et mutant SMO-protein, som omfatter en aminosyresekvens, som er mindst 95 % identisk med SEQ ID NO: 1, hvor aminosyresekvensen består af alanin (A) eller lysin (K) i aminosyreposition 518, hvor mutationen overfører mindst delvis resistens af det muterede SMO-protein til GDC-0449.
4. Nukleinsyresonde, som omfatter en nukleotidsekvens, som er komplementær til en nukleinsyresekvens, som koder et muteret SMO-protein eller fragment deraf, som inkorporerer en mutation ved aminosyre 518 af SEQ ID NO: 2, hvilken mutation består af alanin (A) eller lysin (K) i aminosyreposition 518 af SEQ ID NO: 2, hvor nukleinsyresonden differentieret binder nukleinsyren, som koder det muterede SMO-protein over en nukleinsyre, der koder et SMO-protein af vildtypen, hvor mutationen overfører mindst delvis resistens af det muterede SMO-protein til GDC-0449; og hvor sonden har en længde på 10 til 50 nukleotider.
5. Antistof, som specifikt binder til det mutante SMO-protein ifølge et af kravene 1 eller 2, hvor epitopen af antistoffet er til stede i et mutant SMO, som har en aminosyre, som er en anden end glutaminsyre i position 518, hvor antistoffet ikke binder SMO af vildtypen som har en glutaminsyre i position 518.
6. Antistof ifølge krav 5, hvor antistoffet er et monoklonalt antistof, et kimæ-risk antistof, et humaniseret antistof, et enkeltkædet antistof eller et antigenbindende fragment deraf.
7. Antistof ifølge krav 5, hvor antistoffet er konjugeret til et cytotoksisk middel.
8. Antistof ifølge krav 5, hvor antistoffet inhiberer SMO-aktivitet.
9. Fremgangsmåde til identificering af en tumor i et menneske, som er mindst delvist resistent over for behandling med GDC-0449, omfattende bestemmelse af tilstedeværelsen af et muteret SMO-gen eller muteret SMO-protein i en prøve med tumoren, hvor mutationen resulterer i alanin (A) eller lysin (K) i aminosyreposition 518 af SEQ ID NO: 2, hvor tilstedeværelsen af det muterede SMO-gen eller muterede SMO-protein indikerer, at tumoren er mindst delvist resistent over for en behandling med et GDC-0449, hvor det muterede SMO-gen koder det muterede SMO-protein.
10. Fremgangsmåde til screening af forbindelser, som inhiberer signalering af det mutante SMO-protein ifølge et af kravene 1-2; omfattende: a) 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, og/eller b) 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.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38999510P | 2010-10-05 | 2010-10-05 | |
PCT/US2011/054877 WO2012047968A2 (en) | 2010-10-05 | 2011-10-05 | Mutant smoothened and methods of using the same |
Publications (1)
Publication Number | Publication Date |
---|---|
DK2625197T3 true DK2625197T3 (da) | 2016-10-03 |
Family
ID=44800285
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK11770024.5T DK2625197T3 (da) | 2010-10-05 | 2011-10-05 | Smoothened-mutant og fremgangsmåder til anvendelse af samme |
Country Status (8)
Country | Link |
---|---|
US (2) | US8481680B2 (da) |
EP (1) | EP2625197B1 (da) |
JP (2) | JP5974012B2 (da) |
AU (1) | AU2011312205B2 (da) |
CA (1) | CA2813738A1 (da) |
DK (1) | DK2625197T3 (da) |
ES (1) | ES2588981T3 (da) |
WO (1) | WO2012047968A2 (da) |
Families Citing this family (12)
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JP5887270B2 (ja) | 2009-09-02 | 2016-03-16 | ジェネンテック, インコーポレイテッド | 突然変異体smoothenedおよびその使用方法 |
EP2625197B1 (en) | 2010-10-05 | 2016-06-29 | Genentech, Inc. | Mutant smoothened and methods of using the same |
US9708299B2 (en) | 2011-01-03 | 2017-07-18 | Genentech, Inc. | Hedgehog antagonists having zinc binding moieties |
US10260089B2 (en) | 2012-10-29 | 2019-04-16 | The Research Foundation Of The State University Of New York | Compositions and methods for recognition of RNA using triple helical peptide nucleic acids |
WO2015116902A1 (en) | 2014-01-31 | 2015-08-06 | Genentech, Inc. | G-protein coupled receptors in hedgehog signaling |
CA2937539A1 (en) * | 2014-02-04 | 2015-08-13 | Genentech, Inc. | Mutant smoothened and methods of using the same |
CA2975875A1 (en) * | 2015-02-04 | 2016-08-11 | Genentech, Inc. | Mutant smoothened and methods of using the same |
JP2019509721A (ja) | 2016-02-04 | 2019-04-11 | キュリス,インコーポレイテッド | 突然変異体スムースンド及びその使用方法 |
US10548908B2 (en) | 2016-09-15 | 2020-02-04 | Nostopharma, LLC | Compositions and methods for preventing and treating heterotopic ossification and pathologic calcification |
CA3106067A1 (en) * | 2018-07-11 | 2020-01-16 | Hedgehog, Inc. | Epitope specific to smo protein, antibody recognizing same, and composition comprising same |
WO2020013644A1 (ko) * | 2018-07-11 | 2020-01-16 | 고려대학교 산학협력단 | Smo 단백질의 특이적 에피토프, 이를 인지하는 항체 및 이를 포함하는 조성물 |
WO2023101438A1 (ko) * | 2021-11-30 | 2023-06-08 | 주식회사 헤지호그 | Smo 인간 항체 |
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2011
- 2011-10-05 EP EP11770024.5A patent/EP2625197B1/en not_active Not-in-force
- 2011-10-05 WO PCT/US2011/054877 patent/WO2012047968A2/en active Application Filing
- 2011-10-05 US US13/253,317 patent/US8481680B2/en active Active
- 2011-10-05 DK DK11770024.5T patent/DK2625197T3/da active
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WO2012047968A3 (en) | 2012-05-31 |
US20120039893A1 (en) | 2012-02-16 |
ES2588981T3 (es) | 2016-11-08 |
WO2012047968A2 (en) | 2012-04-12 |
US8481680B2 (en) | 2013-07-09 |
US9096686B2 (en) | 2015-08-04 |
JP2014503180A (ja) | 2014-02-13 |
EP2625197B1 (en) | 2016-06-29 |
JP2016214249A (ja) | 2016-12-22 |
JP5974012B2 (ja) | 2016-08-23 |
US20140004535A1 (en) | 2014-01-02 |
AU2011312205B2 (en) | 2015-08-13 |
EP2625197A2 (en) | 2013-08-14 |
CA2813738A1 (en) | 2012-04-12 |
AU2011312205A1 (en) | 2013-05-02 |
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