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Methods of treating FGFR3 related conditions

A technology for FGFR3 and diseases, applied in the field of treatment of FGFR3-related diseases, can solve problems such as detection and treatment difficulties

Inactive Publication Date: 2015-04-01
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cancer (or malignancy) grows and metastasizes rapidly in an uncontrolled manner, making timely detection and treatment extremely difficult

Method used

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  • Methods of treating FGFR3 related conditions
  • Methods of treating FGFR3 related conditions
  • Methods of treating FGFR3 related conditions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0398] Example 1-Scoring of FGFR3 expression by IHC

[0399] In urothelial carcinoma, neoplastic cells labeled with the FGFR-3 IHC assay were evaluated for percentage positive and DAB signal intensity. Immunohistochemical staining in urothelial carcinoma follows a membrane and / or cytoplasmic pattern. Regardless of subcellular location, the signal is classified as strong, medium, weak, or negative.

[0400] The strong signal intensity is golden to dark brown, often granular cytoplasm and / or membrane staining, and can be detected with 4x and 10x objective lenses. Moderate signal intensity manifests as light brown to brown cytoplasm and / or membrane staining, which can be detected with 10x and 20x objective lenses. The medium signal lacks the strong brown color seen in cells with strong staining intensity; the membrane is also thinner and the overall staining is less granular. The weak signal intensity manifests as light brown to gray cytoplasm and / or membrane staining, just beyond ...

Embodiment 2

[0423] Example 2-FGFR3IHC scoring in the urothelial cancer group

[0424] The Definiens software was used to evaluate the expression intensity of FGFR3IHC in a group of 150 urothelial carcinoma cases. The slides stained as described above were scanned using a Hamamatsu Nanozoomer digital slide scanner running Nanozoomer software, using a 20x objective lens and an 8-position camera. All slides only scan the area where specimen tissue exists. All images were analyzed using Definiens Developer (Munich, AG), using RGB (red, green and blue) spectrum. The image is down-sampled by 2%, and the tissue area is selected by excluding bright areas in the slide that correspond to the background. Within the tissue, the stained area is identified by searching for areas with normalized [red / blue] intensity values ​​greater than 0.99. For each slide in the stained area, and for the unstained tissue area, calculate the average brightness (average of the red, green, and blue spectra). Definiens ...

Embodiment 3

[0426] Example 3-Treatment using FGFR3 antibody R3MAb and scoring of FGFR3 by IHC

[0427] FGFR3 (a receptor tyrosine kinase) is involved in the tumorigenesis of cancer. The anti-FGFR3 antibody R3Mab is a novel human monoclonal IgG1 antibody that inhibits FGFR3-mediated cell proliferation and exerts anti-tumor activity in a xenograft model of urothelial cell carcinoma (UCC). see Picture 10 Clone in 184.6.1’. Preclinical data also supports strategies to target FGFR3 in other solid tumors. This phase I dose expansion study evaluates the safety, pharmacokinetics (PK), and phase II recommended dose (RP2D) of the anti-FGFR3 antibody R3MAb.

[0428] Using the standard 3+3 design, treatment with intravenous anti-FGFR3 antibody R3MAb in 5 dose expansion groups (2-30 mg / kg in a 28-day cycle, and a loading dose on day 8 of cycle 1) Of patients with advanced solid malignancies. Cycle 1 contains a dose-limiting toxicity (DLT) assessment window. Allow the patient to expand the dose. Eval...

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Abstract

Provided herein are biomarkers and therapies for the treatment of pathological conditions, such as cancer, and method of using FGFR3 antagonists. In particular, provided is FGFR3 as a biomarker for patient selection and prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.

Description

[0001] Cross references to related applications [0002] This application requires U.S. Provisional Patent Application No. 61 / 676,857 filed on July 27, 2012, U.S. Provisional Patent Application No. 61 / 695,853 filed on August 31, 2012, and U.S. Provisional Patent Application No. 61 / 695,853 filed on September 21, 2012. The rights and interests of patent application No. 61 / 704,052 are included in its entirety by reference accordingly. [0003] Sequence Listing [0004] This application contains a sequence listing, which has been submitted in ASCII form via EFS-Web and is fully included by reference accordingly. The ASCII copy (created on July 23, 2013) is named P4950R1-US.txt and has a size of 49,775 bytes. Invention field [0005] Provided herein are biomarkers and therapies for the treatment of pathological conditions, such as cancer, and methods of using FGFR3 antagonists. In particular, it provides FGFR3 as a biomarker for patient selection and prognosis in cancer, as well as thera...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/35C07K16/28
CPCC07K16/2863A61K39/395A61K39/3955A61K2039/505C07K16/28C07K2317/21C07K2317/24C07K2317/76C12N15/1138C12N2310/14C12N2310/531G01N33/57484G01N33/57488G01N33/57492G01N2333/71G01N2333/96494
Inventor D·弗伦奇
Owner GENENTECH INC