Medicament comprising HGF gene

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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Details

C424S450000

Reexamination Certificate

active

06248722

ABSTRACT:

TECHNICAL FIELD TO WHICH THE INVENTION PERTAINS
The present invention relates to a medicament for use in the gene therapy and the like. More particularly, the present invention relates to a medicament comprising a hepatocyte growth factor (HGF) gene as well as a liposome containing the HGF gene.
PRIOR ARTS
HGF is a physiologically active peptide that exhibit diverse pharmacological activities. The pharmacological activities of HGF are described in, e.g., JIKKEN-IGAKU (Experimental Medicine), Vol. 10, No. 3 (extra issue), 330-339 (1992). In view of its pharmacological activities, HGF is expected to be useful as a drug for the treatment of liver cirrhosis or renal diseases; epithalial cell growth accelerators; anti-cancer agents; agents for the prevention of side effects in cancer therapy; agents for the treatment of lung disorders, gastrointestinal damages or cranial nerve disorders; agents for the prevention of side effects in immunosuppression; collagen degradation accelerators; agents for the treatment of cartilage disorders, arterial diseases, pulmonary fibrosis, hepatic diseases, blood coagulopathy, plasma hypoproteinosis or wounds; agents for the improvement of nervous disorders; hematopoietic stem cell potentiators; and hair growth promoters (Japanese Patent KOKAI (Laid-Open) Nos. 4-18028 and 4-49246, EP 492614, Japanese Patent KOKAI (Laid-Open) No. 6-25010, WO 93/8821, Japanese Patent KOKAI (Laid-Open) Nos. 6-172207, 7-89869 and 6-40934, WO 94/2165, Japanese Patent KOKAI (Laid-Open) Nos. 6-40935, 6-56692 and 7-41429, WO 93/3061, Japanese Patent KOKAI (Laid-Open) No. 5-213721, etc.).
As to gene therapy, extensive studies and investigations have been currently made all over the world for adenosine deaminase deficiency, AIDS, cancer, pustulous fibrosis or hemophilia, etc.
However, gene therapy using the HGF genes is unknown yet. It is even unclear if such gene therapy is effectively applicable.
Problems to be Solved by the Invention
HGF is known to be one of the drugs that have a short half life in blood. As a natural consequence, persistent topical administration has been desired for HGF.
In view of the diverse pharmacological activities of HGF, HGF is expected to be developed as a drug having extended applications to various diseases. On the other hand, when HGF is systemically administered, side effects might be caused due to the diverse pharmacological activities of HGF. In addition, when HGF itself is intravenously administered, HGF encounters such a drawback that a considerable amount of HGF is retained in the liver, resulting in reduction of the amount of HGF to reach the target organ.
Means for Solving the Problems
The present invention has been made to solve the foregoing problems. In summary, the present invention relates to:
(1) a medicament comprising a HGF gene;
(2) a liposome containing the HGF gene;
(3) a liposome according to (2), which is a membrane fusion liposome fused to Sendai virus;
(4) a medicament comprising the liposome according to (2) or (3);
(5) a medicament according to (1) or (4), for use in the treatment for arterial disorders; and,
(6) a medicament according to (1) or (4), for use in the treatment for cartilage injuries.


REFERENCES:
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patent: WO9308821 (1993-05-01), None
patent: WO9406456 (1994-03-01), None
patent: WO 96/40062 (1996-12-01), None
“Scatter Factor (Hepatocyte Growth Factor) is a Potent Angiogenesis Factor In Vivo” by Rosen et al., Society of Experimental Biology 1993, pp. 227-234.
“Scatter Factor Induces Blood Vessel Formation In Vivo” by Grant et al., Proc. Natl. Acad. Sci. USA, vol. 90, Mar. 1993, pp. 1937-1941.
“Hepatocyte Growth Factor/Scatter Factor Modulates Cell Motility, Proliferation, and Proteoglycan Synthesis of Chondrocytes” by Takebayashi et al., Journal of Cell Biology, vol. 129, No. 5, Jun. 1995, pp. 1411-1419 EXS.
“The Interaction of HGF-SF with Other Cytokines in Tumor Invasion and Angiogensis” by Rosen et al., vol. 65, 1993, pp. 301-310.
Gut, Supplement No. 5, vol. 35, s-60, F240 (1994), Selden et al.
Biochem. and Biophys. Res. Comm., 220, 539-545 (1996), Hayashi et al, “Autocrine-Paracrine Effects of Overexpression of Hepatocyte Growth Factor Gene on Growth of Endothelial Cells”.
Verma et al. Sep. (1997) Gene therapy-promises, problems and prospects. Nature 389:239-242.*
Morishita et al. Jun. (1993) Novel in vitro gene transfer method for study of local modulators in vascular smooth muscle cells. Hypertension 21:894-899.*
Nakamura et al., “Molecular Cloning and Expression of Human Hepatocyte Growth Factor”, Nature, Vol. 342, Nov. 23, 1989, Pgs. 440-443, XP000652120.
Miyazawa K. et al., “Molecular Cloning and Sequence Analysis of cDNA for Human Hepatocyte Growth Factor” Biochemical and Biophysical Research Communications, Vol. 163, No. 2, Set. 15, 1989, Pgs. 967-973, XP000651424.
T. Seki et al., “Isolation and Expression of cDNA for Differnt Forms of Hepatocyte Growth Factor” Biochemical and Biophysical Research Communications, Vol. 172, No. 1, Oct. 15, 1990, Pgs. 321-327, XP002084490.

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