Metabolic biomarkers for predicting responsiveness to FGF-18 compound

Patent metadata

Field	Value
Publication number	US-11513128-B2
Application number	US-201816650881-A
Country	US
Kind code	B2
Filing date	Sep 28, 2018
Priority date	Sep 29, 2017
Publication date	Nov 29, 2022
Grant date	Nov 29, 2022

Abstract

The present invention relates to biomarkers associated with the clinical response to an FGF-18 compound before or during treatment of a cartilage disorder. The present invention more particularly relates to specific proteins present in the blood, serum, synovial fluid or in the urine, which can be used for the diagnosis and treatment of cartilage disorders. The invention further discloses specific proteins that are related to cartilage response to an FGF-18 compound treatment as well as diagnostic tools and kits based on their expression profile. Thus, the invention can be used in predicting the response to an FGF-18 compound treatment, before starting the treatment with FGF-18 or during the treatment. It could be used for selecting/identifying subjects to be treated by intra-articular administration of an FGF-18 compound. The use of these biomarkers in diagnostics could result in increased benefit and reduced risk in subjects.

First claim

The invention claimed is:

1. A method for treating a subject having a cartilage disorder characterized by articular cartilage injury or loss of articular cartilage with an FGF-18 compound, comprising the following steps:
a) determining, from a sample from said subject, the quantity of at least one of the biomarkers selected from the group consisting of CTX-II (C-terminal telopeptide of type II collagen) and/or ProC2 (neo-epitope of Collagen type II), wherein said quantities are predictive about the subject's risk for being high or intermediate sensitive to a treatment with said FGF-18 compound;
b) selecting the subject having:
i) lower than 350±2SD ng/mmol of CTX-II, and/or
ii) lower than 4.2±2SD ng/mL of ProC2, and

c) administering intraarticularly said FGF-18 compound to said selected subject, wherein said FGF-18 compound comprises amino acid residues 28-196 of SEQ ID NO: 1, optionally fused to a heterologous protein or chemical compound.

2. The method according to claim 1 , wherein the FGF-18 compound is to be administered in a treatment cycle of once weekly for 3 weeks.

3. The method according to claim 2 , wherein the treatment cycle is repeated.

4. The method according to claim 1 , wherein the FGF-18 compound is sprifermin or sprifermin fused to a heterologous protein or chemical compound.

5. The method according to claim 1 , wherein the cartilage disorder is selected from the group consisting of femorotibial osteoarthritis, articular cartilage injury, fractures affecting joint cartilage, surgical procedures with impact on joint cartilage, or microfracture of articular cartilage.

Assignees

• Merck Patent Gmbh

Inventors

• Ladel Christoph H
• Guehring Hans
• Bay-Jensen Anne-Christine
• Karsdal Morten
• Qvist Per

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C07K14/50

  Fibroblast growth factor [FGF] · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• C07K14/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• G01N33/6887 Primary

  from muscle, cartilage or connective tissue · CPC title