Osteometer Biotech A/s

Merck Patent Gmbh

Nordic Bioscience A/s

Osteometer A/s

Per Qvist

Martin Bonde

Morten A Karsdal

Hans Guehring

Anne-Christine Bay-Jensen

Christoph Hubertus Ladel

Christian Fledelius

Christian Rosenquist

Stephan Christgau

Natasha Barascuk Michaelsen

Natasha Barascuk

Paul Cloos

Inger Byrjalsen

Diana Julie Leeming

The present invention relates to pharmacogenetics, more specifically to strategies involving biomarkers associated with the clinical response to a compound before or during treatment of a cartilage disorder, such as osteoarthritis. The present invention more particularly relates to the combination of JSW measurements and level of specific proteins present in the blood, serum, synovial fluid or in the urine, which can be used in strategies such as patients' enrichment in clinical trials, patients' selection strategy before or during treatment or for adapting the treatment of a patient in the frame of treatments for cartilage disorder, such as osteoarthritis.

Markers useful in enrichment strategies for the treatment of osteoarthritis

The present invention relates to biomarkers associated with the clinical response to an FGF-18 compound before or during treatment of a cartilage disorder. It relates more particularly to specific proteins present in the blood, serum, synovial fluid or in the urine, which can be used as biomarkers for the diagnosis, pre-treatment of patients and during therapy of cartilage disorders. The invention can be used in predicting the response to an FGF-18 compound treatment, before starting the treatment or during the treatment. It could be used for selecting/identifying subjects to be treated according to specific doses and/or dosing regimens by intra-articular administration of an FGF-18 compound. The use of these biomarkers in diagnostics could result in increased benefit and reduced risk-benefit ratio in subjects.

Inflammatory biomarkers for predicting responsiveness to FGF-18 compound

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.

Metabolic biomarkers for predicting responsiveness to FGF-18 compound

Provided is a method of bioassay for the quantification of N- or C-terminal neo-epitope biomarkers formed by cleavage of a CRP, ApoE, lumican, versican, perlecan, decorin, biglycan or elastin by a proteinase. The method includes contacting a biofluid sample with an antibody reactive with the neo-epitope biomarker and determining the level of binding of the antibody to the biomarker in the sample. The assay is predictive of risk of cardiovascular disease events.

Biochemical markers for CVD risk assessment

A method of bioassay for the quantification of peptide fragments comprising a neo-epitope formed by cleavage of a protein of an atherosclerotic plaque such as lumican, versican, perlecan, decorin, biglycan, collagen type III, CRP, ApoE, or elastin, by a proteinase, said comprises contacting a sample such as urine or serum with an antibody reactive with the neo-epitope and determining the level of binding of said immunological binding partner to peptide fragments in said sample. The assay is predictive of risk of cardiovascular disease events.

0Type II collagen degradation is measurable using a sandwich immunoassay in which a single antibody specific for the amino acid sequence EKGPDP is used to form each side of antibody-collagen fragment-antibody sandwich complexes and the amount of said complexes is measured.

Sandwich assays for collagen fragments

Sandwich assays for collagen degradation products are conducted using an antibody of the same specificity on both sides of the sandwich or using a first antibody reactive with an epitope contained in the sequence EKAHDGGR and a second antibody which may be the same or different.

Sandwich assays for collagen type I fragments

This invention relates, in part, to a method of measuring the rate of degradation of collagen is disclosed which comprises determining the amount in a body fluid of one or more fragments of collagen having an amino acid sequence comprising isoaspartic acid. The invention also relates to an immunological binding partner that specifically binds to an amino acid sequence of type II collagen containing an isoaspartic acid residue. The invention further relates to a synthetic peptide having an amino acid sequence of type II collagen that contains an isoaspartic acid residue.

Assaying fragments of collagen in body fluids

Methods of characterizing the degradation of type II collagen in body fluids are disclosed. In a specific method, a sample of body fluid is subjected to at least two distinct immunological assays, each using a different immunological binding partner, and a numerical index is formed representing the difference in the results of the assays.

Method of characterizing the degradation of type II collagen

A method of assaying collagen fragments in body fluids, including bringing a sample of body fluid in contact with at least one immunological binding partner for the collagen fragments, said binding partner being immunoreactive with synthetic peptides, the sequences of which are essentially derived from collagen and containing potential sites for cross-linking. The immunological binding partners are incorporated, either as whole antibodies or as immunologically active fragments thereof, in an assay for quantitative determination of collagen fragments in the sample. In addition to being contacted with the immunological binding partner(s), the sample may be brought into direct contact with the corresponding synthetic peptide. The invention further comprises a test kit and specific means for carrying out the method. The structure of specific peptides is also described.

METHOD OF ASSAYING COLLAGEN FRAGMENTS IN BODY FLUIDS, A TEST KIT AND MEANS FOR CARRYING OUT THE METHOD AND USE OF THE METHOD TO DIAGNOSE THE PRESENCE OF DISORDERS ASSOCIATED WITH THE METABOLISM OF COLLAGEN

A method of assaying type II collagen fragments in body fluids, including bringing a sample of body fluid in contact with at least one immunological binding partner for the collagen fragments, said binding partner being immunoreactive with synthetic peptides, the sequences of which are essentially derived from collagen and containing potential sites for cross-linking. The immunological binding partners are incorporated, either as whole antibodies or as immunologically active fragments thereof, in an assay for quantitative determination of collagen fragments in the sample. In addition to being contacted with the immunological binding partner(s), the sample may be brought into direct contact with the corresponding synthetic peptide. The invention further comprises a test kit and specific means for carrying out the method. The structure of specific peptides is also described.

Method of assaying collagen fragments in body fluids, a test kit and means for carrying out the same

Method of assaying collagen fragments in body fluids, a test KT and means for carrying out the same

The rate of degradation in vivo of a body protein is determined by measuring the amount of a D-amino acid containing fragment of the protein in a body fluid using an antibody capable of discriminating between the D-amino acid containing fragment and its L-amino acid containing analogue.

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Copenhagen, Denmark

Per Qvist