The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Jun. 25, 2019

Filed:

Feb. 04, 2016
Applicants:

Genentech, Inc., South San Francisco, CA (US);

Curis, Inc., Lexington, MA (US);

Assistance Publique-hopitaux DE Paris, Paris, FR;

Universite Paris Diderot—paris 7, Paris, FR;

Inventors:

Frederic J. De Sauvage, Foster City, CA (US);

Robert L. Yauch, Redwood City, CA (US);

Gerrit J. P. Dijkgraaf, South San Francisco, CA (US);

Hayley Sharpe, San Francisco, CA (US);

Nicole Basset-Seguin, Paris, FR;

Assignees:

Genentech, Inc., South San Francisco, CA (US);

Curis, Inc., Lexington, MA (US);

Assistance Publique-Hopitaux de Paris, Paris, FR;

Universite Paris Diderot—Paris 7, Paris, FR;

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
C07K 14/47 (2006.01); C12N 15/12 (2006.01); C12N 15/63 (2006.01); G01N 33/68 (2006.01); C07H 21/04 (2006.01); G01N 33/574 (2006.01); G01N 33/50 (2006.01); C07K 14/705 (2006.01); C12Q 1/6886 (2018.01); A61K 47/68 (2017.01); A61K 31/551 (2006.01); C07K 14/71 (2006.01); C07K 16/28 (2006.01);
U.S. Cl.
CPC ...
G01N 33/57492 (2013.01); A61K 31/551 (2013.01); A61K 47/6849 (2017.08); C07H 21/04 (2013.01); C07K 14/47 (2013.01); C07K 14/705 (2013.01); C07K 14/71 (2013.01); C07K 16/2863 (2013.01); C12N 15/63 (2013.01); C12Q 1/6886 (2013.01); G01N 33/502 (2013.01); G01N 33/5011 (2013.01); G01N 33/5041 (2013.01); G01N 33/6872 (2013.01); C07K 2317/24 (2013.01); C07K 2317/569 (2013.01); C07K 2317/76 (2013.01); C12Q 2600/106 (2013.01); C12Q 2600/156 (2013.01); G01N 2333/4704 (2013.01); G01N 2333/71 (2013.01); G01N 2500/04 (2013.01); G01N 2500/10 (2013.01);
Abstract

The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, mutations in the serpentine receptor, Smoothened (SMO) are described, which result in resistance to a Hedgehog (Hh) pathway inhibitor, such as in medulloblastoma. Amino acid substitutions in conserved residues of SMO maintain Hh signaling, but result in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. In some embodiments, the disclosure provides for novel mutant SMO proteins and nucleic acids and for screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.


Find Patent Forward Citations

Loading…