Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2002-07-16
2004-11-30
Spector, Lorraine (Department: 1646)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S002600, C435S069100, C435S325000, C435S348000, C435S252300, C435S254110, C536S023500, C536S023100, C530S300000, C530S381000
Reexamination Certificate
active
06825168
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to medical treatments utilizing antithrombin proteins.
BACKGROUND OF THE INVENTION
Thromboembolic diseases are among the most important circulatory diseases. A thrombin is a blood clot that partially or completely blocks blood flow through a blood vessel. An embolus is a thrombus that has formed elsewhere in the body, broken free, and traveled to the site where blockage occurs. Blockage in the brain results in a stroke, i.e., a cerebral infarction, a localized area of dead cells. An embolus in a lung can produce pulmonary embolism, one of the principal lung diseases in bed-ridden patients. Bed ridden and elderly persons are also particularly prone to thrombophlebitis, which is a blockage of circulation in a leg caused by an embolus. An embolus or thrombus lodging in one of the blood vessels serving the heart causes necrosis of part of the heart tissue, a myocardial infarction, commonly called a heart attack.
The initiating event of many myocardial infarctions is the hemorrhage into atherosclerotic plaques. Such hemorrhage often results in the formation of a thrombus (or blood clot) in the coronary artery which supplies the infarct zone. This thrombus is composed of a combination of fibrin and blood platelets. The formation of a fibrin-platelet clot has serious clinical ramifications. The degree and duration of the occlusion caused by the fibrin-platelet clot determines the mass of the infarct zone and the extent of damage.
The formation of fibrin-platelet clots in other parts of the circulatory system may be partially prevented through the use of anticoagulants, such as heparin. Unfortunately, heparin has not been found to be universally effective in preventing re-occlusion in myocardial infarction victims in which the degree of blood vessel occlusion is greater than or equal to 70%, particularly in those patients with severe residual coronary stenosis. Among the more promising of the agents are hirudin and its analogs, which bind to and inactivate thrombin. Hirudin has a theoretical advantage over heparin as an anti-thrombotic agent. Thrombin bound to thrombi or platelets is relatively protected from inhibition by heparin while hirudin, at least in vitro, is still effective. Other promising investigational agents include fibrinogen receptor antagonists, which block platelet aggregation and dense granule release by a mechanism distinct from that of aspirin, and inhibitors of thromboxane production.
There is therefore a need for additional antithrombin agents which exhibit low toxicity, little or no antigenicity, and a very short clearance time from circulation.
SUMMARY OF THE INVENTION
Antithrombin proteins and DNA sequencing coding the proteins are provided. The protein named simulidin is isolated from
Simulium
Spp. The proteins are useful in medical treatments where antithrombin agents are needed.
Methods for preparation and administration of the proteins are additionally provided.
REFERENCES:
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patent: 5356875 (1994-10-01), Sarmientos et al.
patent: 5439820 (1995-08-01), Sarmientos et al.
patent: 5472942 (1995-12-01), Sawyer et al.
Webster's II New Riverside University Dictionary, A. H. Soukhanov, Sr. Ed.(The Riverside Publishing Company:USA), p. 68, 1994.*
Abebe et al., “Anticoagulant Activity In Salivary Gland Extracts of Black Flies (Diptera: Stimuliidae),”J. Med. Entomol, 1994, pp. 908-911, vol. 31, No. 6.
Abebe et al., “Simulidin: A Black Fly (Simulium vittatum) Salivary Gland Protein With Anti-thrombin Activity,”J. Inset Physiol., 1995, pp. 1001-1006, vol. 41, No. 11.
Abebe et al. , “Novel Anticoagulant From Salivary Glands ofSimulium vittatum(Diptera: Simuliidae) Inhibits Activity of Coagulation Factor V,”J. Med. Entomol., 1996, pp. 173-176, vol. 33, No. 1.
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Han et al., “Cloning and Expression of cDNA Encoding Antistasin, a Leech-derived Protein Having Anti-coagulant and Anti-metastatic Properties,”Gene, Jan. 1989, pp. 47-57, vol. 75, No. 1.
Harvey et al., “Cloning and Expression of a cDNA Coding for the Anticoagulant Hirudin from the Bloodsucking Leech,Hirudo medicinalis,” Proc. Natl. Acad. Sci.USA, Feb. 1986, pp. 1084-1088, vol.83, No. 4.
Jacobs et al., “Isolation and Characterization of a Coagulation Factor Xa Inhibitor from Black Fly Salivary Glands,”Thrombosis and Haemostasis, 1990, pp. 235-238, vol. 64, No. 235.
Sun et al., “Purification, Characterization and cDNA Cloning of a Novel Anticoagulant of the Intrinsic Pathway, (Prolixin-S), from Salivary Glands of the Blood Sucking Bug,Rhodnius prolixus,” Thrombosis and Haemostasis, Apr. 1996, pp. 573-577, vol. 75, No. 4.
Cupp Eddie W.
Cupp Mary S.
Alston & Bird LLP
Auburn University
Kaufman Claire M.
Spector Lorraine
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