University of California

Bio-Y A/s

Paul A Price

Julia S Johansen

Richard Bonnichsen

Satoru K Nishimoto

The present invention relates to monoclonal anti-human YKL-antibodies which are capable to modulate biological processes in which YKL-40 plays a prominent role, e.g. inhibit the growth and/or inducing apoptosis of cells, in particular cancer cells. The invention also relates to pharmaceutical compositions comprising said antibodies and uses said antibodies and/or pharmaceutical compositions for treatment of a disease wherein inhibition of cell growth, cell differentiation, remodelling of extracellular matrix, metastasis and/or induction of cell death due to apoptosis is a prerequisite for successful curing. An antibody of the invention is capable of inhibiting biological function of YKL-40 in the above mentioned processes by binding to a specific epitope on YKL-40.

YKL-40 monoclonal antibody

YKL-40 monoclonal authority

This invention provides methods for detecting cancers and for evaluating the prognosis of cancer patients. In particular, the methods of this invention utilize YKL-40 as a marker for the presence or absence of a cancer and for the prognosis (e.g. likelihood of recurrence) of a cancer. Elevated levels of YKL-40 are indicative of the presence of a cancer in undiagnosed subjects and indicate likely recurrence of the cancer in subjects diagnosed as having a cancer.

YKL-40 as a marker and prognostic indicator for cancers

The invention is a method of identifying the presence of a disease state in a mammal which is associated with degradation of connective tissue in the mammal which contains the protein known as YKL-40. The method is a competitive immunoassay for YKL-40. It can be used, for example, to identify the presence of inflammatory or degenerative joint disease and tumor metastasis (to the extent it can be correlated to serum YKL-40 levels). Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers.

Assay for YKL-40 as a marker for degradation of mammalian connective tissue matrices

This invention provides methods of inhibiting calcification of a soft tissue (e.g., an artery, a heart valve, an atherosclerotic plaque, a cancer, a kidney, a prostate, skin, muscle, cartilage, viscera, and heart muscle) in a mammal. These methods involve inhibiting osteoclastic bone resorption in said mammal (e.g., a mammal diagnosed as having or at risk for a pathology characterized by calcification of a soft tissue). The inhibition is preferably by administration of a bisphosphonate to the mammal in a concentration sufficient to inhibit bone resorption without inhibiting bone mineralization. The methods of this invention can also be used to mitigate a symptom of atherosclerosis in a mammal. Such methods involve inhibiting osteoclastic bone resorption in the mammal. In preferred embodiment, the inhibiting is by administration of a bisphosphonate to the mammal in a concentration sufficient to inhibit bone resorption without inhibiting bone mineralization

Fetuin-MGP-mineral complex in serum assayed to determine calcification risk

The invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the invention method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers.

This invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory or degenerative joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers. The figure shows the elution position of substantially pure serum YKL-40 on a gel filtration column.

Assay of YKL-40 as a marker for cancer

Assay for YKL-40 as a marker for degradation of mammalian connective

Immunoassay and compositions therefore for detection of human vitamin K-dependent bone protein. Heterologous labeled vitamin K-dependent protein or antigenic fragment thereof is employed with antibodies to the protein in an assay for the protein in various physiological fluids for bone extracts. The assay may be used in the diagnosis of bone diseases, by itself or in conjunction with an alkaline phosphatase assay.

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La Jolla, CA, United States of America

Paul A Price