YKL-40 monoclonal antibody
Inventors
Bonnichsen, Richard • Price, Paul
Assignees
BIO Y AS • University of California San Diego UCSD • University of California Irvine
Publication Number
US-8673301-B2
Publication Date
2014-03-18
Expiration Date
2026-02-16
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Abstract
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.
Core Innovation
The invention relates to monoclonal antibodies, antigen binding fragments, or recombinant proteins that are specific for human YKL-40 and capable of inhibiting biological processes in which YKL-40 plays a prominent role. Specifically, these antibodies can inhibit cell growth, induce apoptosis, and affect cell differentiation, particularly in cancer cells. The antibodies achieve this by binding to specific epitopes on the YKL-40 protein, thereby inhibiting its biological functions tied to cell proliferation, survival, differentiation, angiogenesis, extracellular matrix remodeling, and metastasis.
The background highlights the problem that functional anti-YKL-40 antibodies have not previously been produced or described. Although antibodies against YKL-40 were known for detection and monitoring purposes, none were capable of inhibiting the function of YKL-40 itself. Since YKL-40 is implicated in diseases associated with increased cell growth or tissue remodeling, such as cancer, fibrosis, and rheumatoid arthritis, the lack of function-inhibiting antibodies represented a significant unmet need.
This invention introduces monoclonal antibodies that bind to specific YKL-40 epitopes, such as those comprising or consisting of amino acid residues identified as SEQ ID NOs: 2-7, or key regions like 83-90, 96-105, 137-150, 210-220, 304-314, and 318-329. By targeting these sites, the antibodies inhibit the biological activity of YKL-40, which is essential for various cell processes. As a result, the invention provides a means to interfere therapeutically in conditions where reducing cell proliferation, remodeling, or survival is desired.
Claims Coverage
The patent has two independent claims, covering methods and compositions related to monoclonal antibodies targeting YKL-40.
Method of inhibiting cancer cell growth by monoclonal antibody binding YKL-40
A method comprising contacting a cancer cell with a monoclonal antibody, antigen binding fragment, or recombinant protein specific for human YKL-40 (SEQ ID NO: 1), where the antibody inhibits growth of the cancer cell upon binding to an epitope on YKL-40.
Antibody or fragment specific for YKL-40 that inhibits cancer cell growth by epitope binding
An antibody, antigen binding fragment, or recombinant protein specific for human YKL-40 (SEQ ID NO: 1), capable of inhibiting cancer cell growth upon binding to an epitope consisting of residues 83-90, 96-105, 137-150, 210-220, 304-314, and/or 318-329 of YKL-40, or a combination thereof.
The claims are directed to methods of inhibiting cancer cell growth using antibodies that specifically recognize and bind to particular epitopes on YKL-40, as well as to such antibodies and fragments themselves.
Stated Advantages
Provides monoclonal antibodies capable of inhibiting cell growth, cell differentiation, survival, metastasis, and angiogenesis by targeting YKL-40, which was not achieved by previously known antibodies.
Allows for the treatment of diseases in which inhibition of cell growth, extracellular matrix remodeling, metastasis, or induction of cell death (such as apoptosis) is critical for successful therapy.
Documented Applications
Treatment of cancer, including primary and metastatic carcinomas such as breast, colorectal, pancreas, stomach, hepatocellular, lung, small cell lung, ovarian, uterine, cervix, testis, prostate, bladder, renal, thyroid, head/neck carcinoma, malignant melanoma, osteosarcoma, chondrosarcoma, myosarcoma, glioblastoma, other brain tumors, germ cell tumors, and hematopoietic malignancies.
Treatment of non-malignant diseases characterized by inflammation and fibrosis, such as rheumatoid arthritis, other inflammatory joint diseases, bacterial infection, inflammatory bowel disease, and liver fibrosis (e.g., due to hepatitis B or C virus or alcohol abuse).
Inhibition of proliferation of non-tumor cells, inhibition of angiogenesis, inhibition of extracellular matrix remodeling, and inhibition of tissue, organ, or liver fibrosis, including conditions such as giant cell arteritis, ankylosing spondylitis, tuberculosis, sarcoidosis, scleroderma, Crohn’s disease, ulcerative colitis, alcoholic liver fibrosis, and hepatitis C.
Use in in vitro assays and methods, for example in screening of new anti-cancer compounds.
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