Methods of treating fibroblast growth factor 19-mediated cancers and tumors

Patent metadata

Field	Value
Publication number	US-11370841-B2
Application number	US-201716327756-A
Country	US
Kind code	B2
Filing date	Aug 25, 2017
Priority date	Aug 26, 2016
Publication date	Jun 28, 2022
Grant date	Jun 28, 2022

Abstract

Provided are methods of treating a FGF19-mediated cancer or tumor in a subject by administering to the subject an anti-IL-6 antibody or an anti-IL-6 receptor antibody or an inhibitor of STAT3/JAK signaling pathway, and pharmaceutical compositions relating thereto.

First claim

What is claimed is:

1. A method of treating the initiation or progression of a fibroblast growth factor 19 (FGF19)-mediated cancer or tumor without impacting FGF19-mediated bile acid metabolism in a subject in need thereof, comprising, administering to the subject a therapeutically effective amount of an anti-interleukin-6 (anti-IL-6) antibody, wherein the FGF19-mediated cancer or tumor is a liver cancer or tumor.

2. The method of claim 1 , wherein the anti-IL-6 antibody is siltuximab, clazakizumab, elsilimomab, or sirukumab.

3. The method of claim 1 , wherein the anti-IL-6 antibody is siltuximab, and wherein the dose of the siltuximab (i) is in the range of about 0.1 to 100 mg/kg per day; (ii) is in the range of about 5 to about 25 mg/kg/day; (iii) is about 5 mg/kg per day; (iv) is about 10 mg/kg per day; (v) is about 11 mg/kg per day; or (vi) is about 15 mg/kg per day.

4. The method of claim 1 , wherein the anti-IL-6 antibody is siltuximab, and wherein the siltuximab is administered once every 3 or 4 weeks by intravenous infusion.

5. The method of claim 1 , wherein the administration treats the cancer or tumor without substantially affecting the metabolic function mediated by FGF19.

6. The method of claim 5 , wherein the metabolic function is the ability to regulate bile acid synthesis, glucose metabolism or energy homeostasis.

7. The method of claim 1 , wherein the liver cancer or tumor is a hepatocellular carcinoma (HCC).

8. The method of claim 1 , wherein the expression level of FGF19 or at least one STAT3 target gene is amplified in the cancer or tumor as compared to a control.

9. The method of claim 8 , wherein the at least one STAT3 target gene is BIRC5, BCL2, HSPA4, BCL2L1, or MCL1.

10. The method of claim 8 , wherein the expression level of the FGF19 or the at least one STAT target gene is determined by Quantitative Polymerase Chain Reaction (qPCR), Real-Time Polymerase Chain Reaction (RT-PCR), RNA-seq, Microarray, Serial Analysis of Gene Expression (SAGE), MassARRAY technique, or Fluorescence In Situ Hybridization (FISH), an immunohistochemistry (IHC) assay, an immunoblotting (IB) assay, flow cytometry (FACS), or Enzyme-Linked Immunosorbent Assay (ELISA).

11. A method of modulating FGF19 signaling in a liver cancer cell or liver tumor cell, the method comprising contacting the cell with an anti-IL-6 antibody, thereby reducing FGF19-mediated oncogenic signaling without impacting FGF19-mediated bile acid metabolism in the liver cancer cell or liver tumor cell.

Assignees

• Ngm Biopharmaceuticals Inc

Inventors

• Ling Lei
• Tian Hui

Classifications

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C07K16/248

  IL-6 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title