Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Reexamination Certificate
1999-06-07
2001-10-30
Ungar, Susan (Department: 1642)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
C530S387700, C530S387900, C530S388100, C530S388200, C530S388230, C530S388850, C435S326000, C424S130100
Reexamination Certificate
active
06310184
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a monoclonal antibody which specifically binds to fibroblast growth factor-8, has a neutralization activity, namely it inhibits activity of fibroblast growth factor-8, and therefore is useful for the morbid state analysis and treatment of human tumor cells grown through induction by fibroblast growth factor-8.
BACKGROUND OF THE INVENTION
Androgen induced growth factor (AIGF) is a factor isolated in 1992 from a culture supernatant of a mouse mammary tumor cell line SC-3 [(Shionogi Carcinoma-3:
J. Steroid Biochem.,
27, 459 (1987)] which shows sex hormone-dependent growth. AIGF is a growth factor which is induced and produced by androgen stimulation and activates growth of SC-3 cells in an autocrine manner [
Proc. Natl. Acad. Sci.,
89, 8928-8932, (1992)]. The results of gene cloning efforts revealed that it has a homology of 30 to 40% with the FGF family at the amino acid level, and it was named fibroblast growth factor-8 (hereinafter referred to as “FGF-8”). Thereafter, human FGF-8 was cloned from a human placenta genomic library using mouse FGF-8 as a probe, which coincided with the mouse FGF-8 by a factor of 85% at the nucleotide level and 100% at the amino acid level [
FEBS Letters,
363, 226 (1995)]. It has been assumed that sex hormone induced growth factors would exhibit an autocrine role in tumors such as prostatic cancer, and breast cancer which show sex hormone-dependent growth, and the isolation and cloning of FGF-8, though in a mouse system, was the first evidence of such a mechanism. It is probable that FGF-8 also plays a role in carcinogenesis and tumor growth in humans by a similar mechanism, but clear evidence has not yet been obtained. However, since expression of FGF-8 m-RNA can be found in several human tumor cell lines of prostatic cancer and breast cancer and enhancement of cell growth can be observed when FGF-8 expressed in CHO cells is added to the culture system of these cell lines or a cell line of fibroblasts [
FEBS Letters,
363, 226 (1995)], it is highly possible that FGF-8 is one of the growth factors which act on sex hormone-dependent tumors in an autocrine or paracrine manner.
In consequence, an antibody specific for FGF-8 is useful for the analysis of the role and biological function of FGF-8 in the above-mentioned tumor cells, and also for the diagnosis of prostatic cancer, breast cancer and the like by immunological detection. Also, it appears that the antibody having a neutralization activity would be useful in studying biological activities of FGF-8 and effective in treating the cancers.
To date the isolation of a monoclonal antibody specific for FGF-8 has not been reported.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a monoclonal antibody which specifically binds to FGF-8 and inhibits the activity of FGF-8 that has a possibility of being a growth factor of hormone-dependent tumors such as prostatic cancer and breast cancer.
The inventors of the present invention have obtained a monoclonal antibody by preparing hybridomas using a partial peptide of FGF-8 as the immunogen, establishing a hybridoma strain capable of producing a monoclonal antibody which specifically binds to the peptide, culturing the hybridoma in a medium or administering it to an animal to induce an ascites tumor and then collecting the resulting culture supernatant or ascitic fluid. A Western blotting test using the monoclonal antibody confirmed that the antibody can bind to FGF-8 protein, when the monoclonal antibody was added to a culture broth of a mouse mammary tumor cell line SC-3 capable of showing sex hormone-dependent growth, and confirmed that the monoclonal antibody can inhibit the FGF-8 activity, namely it neutralizes FGF-8.
These and other objects of the present invention have been attained by a monoclonal antibody which specifically binds to FGF-8 and inhibits FGF-8 activity.
REFERENCES:
patent: 9503831 (1995-02-01), None
Johnstone and Thorpe (Immunochemistry in Practice, Blackwell Scientific Publications, Oxford), 1987.*
Kimmel et al (J. Neurosurg., 66:161-171), 1987.*
Hird et al (Genes and Cancer, Carney et al., Ed., John Wiley and Sons, Ltd), 1990.*
Freshney (Culture of Animal Cells, A Manual of Basic Technique, Alan R. Liss, Inc., New York), 1983.*
Dermer (Bio/Technology, 12:320), 1994.*
Gura (Science, 278:1041-1042), 1997.*
Jain (Sci. Am., 271:58-65), 1994.*
Curti (Crit. Rev. in Oncology/Hematology, 14:29-39), 1993.*
Hartwell et al (Science, 278:1064-1068), 1997.*
Prac. Natl. Acad. Sci. USA, vol. 89, pp. 8928-8932, Oct. 1992, Biochemistry, “Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells”, Tanaka et al.
Febs Letters 3663 (1995) 226-230, Federation of European Biochemical Societies, “Human androgen-induced growth factor in prostate and breast cancer cells: its molecular cloning and growth properties”, Tanaka et al.
MacArthur et al 1995 Cell Growth and Differentiation, vol. 6 pp. 817-825 FGF-8 Isoforms Differ in NIH3T3.
Roitt Essential Immunology 6thEdition Production of Effectors pp. 107-109 The monoclonal antibody revolution.
Furuya Akiko
Hanai Nobuo
Tanaka Akira
Yamasaki Motoo
Kyowa Hakko Kogyo Co. Ltd.
Nixon & Vanderhye
Ungar Susan
LandOfFree
Anti-fibroblast growth factor-8 monoclonal antibody does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anti-fibroblast growth factor-8 monoclonal antibody, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anti-fibroblast growth factor-8 monoclonal antibody will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2559617