公开(公告)号：US20210338778A1

公开(公告)日：2021-11-04

申请号：US17162924

申请日：2021-01-29

Applicant: Genentech, Inc.

Inventor： Alexander R. ABBAS ,  Nico P. GHILARDI ,  Zora MODRUSAN ,  Dimitry M. DANILENKO ,  Frederic J. DE SAUVAGE ,  Wenjun OUYANG ,  Patricia A. VALDEZ ,  Yan ZHENG

IPC: A61K38/19 ,  A61K38/20 ,  A61K38/17

Abstract: The present invention relates to compositions and methods for treatment of microbial disorder by modulation of the host immune response. More particularly, the present invention relates to compositions that mediate an anti-microbial immune response, and methods of treating a microbial infection using such compositions.

公开(公告)号：US20180045729A1

公开(公告)日：2018-02-15

申请号：US15548591

申请日：2016-02-04

Applicant: Genentech, Inc. ,  Curis, Inc. ,  Assistance Publique-Hopitaux de Paris ,  Universite Paris Diderot - Paris 7

Inventor： Frederic J. DE SAUVAGE ,  Robert L. YAUCH ,  Gerrit J.P. DIJKGRAAF ,  Hayley SHARPE ,  Nicole BASSET-SEGUIN

IPC: G01N33/574 ,  C07K14/71 ,  G01N33/50 ,  A61K31/551 ,  C07K16/28 ,  A61K47/68 ,  G01N33/68 ,  C12Q1/68

CPC classification number: G01N33/57492 ,  A61K31/551 ,  A61K47/6849 ,  C07H21/04 ,  C07K14/47 ,  C07K14/705 ,  C07K14/71 ,  C07K16/2863 ,  C07K2317/24 ,  C07K2317/569 ,  C07K2317/76 ,  C12N15/63 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/5041 ,  G01N33/6872 ,  G01N2333/4704 ,  G01N2333/71 ,  G01N2500/04 ,  G01N2500/10

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.