Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Reexamination Certificate
1998-11-16
2002-05-21
Russel, Jeffrey E. (Department: 1653)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
C424S094640, C424S158100, C435S226000, C514S002600, C514S012200, C530S381000
Reexamination Certificate
active
06391300
ABSTRACT:
BACKGROUND OF THE INVENTION
Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
In cardiopulmonary bypass surgery, one of the critical requirements is the maintenance of blood fluidity and the absence of thrombosis. The cardiopulmonary bypass circuit presents a unique combination of factors favoring the development of a prothrombotic environment. The contact of blood with numerous devices which are associated with this procedure, such as membrane oxygenators and filters, has been implicated in the activation of the intrinsic (contact) pathway of coagulation. Since the bypass circuitry generates a highly-thrombogenic environment, high levels of anticoagulation therapies are required (Edmunds, 1995; Edmunds, 1993; Gravlee et al., 1990; Walenga et al., 1991; DeAnda et al., 1994; Brister et al., 1994; and Chomiak et al., 1993). Traditional intervention to prevent thrombosis in this setting has been the use of heparin. However, the use of heparin causes unacceptable side effects in certain patients. Such side effects may include the development of bleeding, heparin resistance or arterial/venous thrombosis. Despite investigations which have attempted to provide alternatives to the use of heparin, such as thrombin inhibitors (such as hirudin) and dermatan sulfate, no agent has yet been identified to replace or modify its use in clinical cardiac surgery (Walenga et al., 1991; DeAnda et al., 1994; Brister et al., 1994; and Chomiak et al., 1993).
SUMMARY OF THE INVENTION
This invention provides a method for inhibiting thrombosis in a patient whose blood is subjected to extracorporeal blood circulation which comprises contacting the extracorporeal circulating blood with a Factor IXa compound in an amount effective to inhibit thrombosis in the patient. The Factor IXa compound may include an active site-blocked Factor IXa compound or Glu-Gly-Arg chloromethyl ketone-inactivated human factor IXa compound. This invention also provides that the effective amount may be from about 0.1 &mgr;g/ml plasma to about 250 &mgr;g/ml plasma or from about 0.5 &mgr;g/ml plasma to about 25 &mgr;g/ml plasma. The patient may be subjected to extracorporeal blood circulation during transplant surgery or cardiopulmonary bypass surgery. This invention further provides for a pharmaceutical composition which includes an effective amount of a Factor IXa compound and a pharmaceutically acceptable carrier.
REFERENCES:
patent: 4800016 (1989-01-01), Yang
patent: 4885277 (1989-12-01), Nawroth
patent: 5091304 (1992-02-01), La Duca et al.
patent: 5169786 (1992-12-01), Carroll et al.
patent: 5443960 (1995-08-01), Dahlback
patent: 5472850 (1995-12-01), Morrissey
patent: 5498601 (1996-03-01), Sato et al.
patent: 5602233 (1997-02-01), King
patent: 5618788 (1997-04-01), Capon et al.
patent: 5676645 (1997-10-01), Van Waeg et al.
patent: 5801063 (1998-09-01), Grandics et al.
patent: 5839443 (1998-11-01), Rose et al.
patent: 5962266 (1999-10-01), White et al.
patent: 94/22885 (1994-10-01), None
patent: 95/17421 (1995-06-01), None
Wyngaarden et al. Cecil Textbook of Medicine, 19thed. Phil.: W. B. Saunders Company. vol. 2, p. 2376, 1992.*
Benedict et al. Active Site-Blocked Factor IXa Prevents . . . J. Clin. Invest. vol. 88, pp. 1760-1765, 1991.*
Berkowitz et al. Quantification of Contact System Activation . . . Blood. vol. 55, No. 3, pp. 528-531, Mar. 1980.*
Dietrich et al. Influence of High-dose Aprotinin . . . Anesthesiology. vol. 83, No. 4, pp. 679-689, Oct. 1995.*
Kuwabara et al. Calreticulin, an Antithrombotic Agent . . . J. Biol. Chem. vol. 270, No. 14, pp. 8179-8187, Apr. 7, 1995.*
Search Report from European Patent Office regarding European Patent application No. 97926541.0 (Exhibit A) ; Dated Oct. 18, 2000.
U.S. Ser. No. 09/053,871, filed Apr. 07, 1998, (continuation in part) claiming priority of U.S. Ser. No. 08/721,447 and PCT International Application No. PCT/US97/17229; (Exhibit B).
U.S. Ser. No. 09/269,426, national stage of PCT International Application No. PCT/US97/17229 Sep. 25, 1997 (Exhibit C).
Bazan, J.F. (1996) Big rigs in blood coagulation.Nature380:21-23.
Benedict, C.R. et al. (1994) Endothelial-dependent procoagulant and anticoagulant mechanisms, recent advances in understanding.Texas Heart Inst. J. 21:86-90.
Berntop, E. (1993) Biochemical and in vivo properties of high purity factor IX concentrates.Thrombosis and Haemostasis70 (5):768-773.
Freedman, S.J. et al. (1995) Structure of the metal-free &ggr;-carboxyglutamic acid-rich membrane binding region of factor IX by two-dimensional NMR spectroscopy.J. Of Biol. Chem. 270(14):7980-7987.
Furie, B.C. and Furie, B. (1995) Biosynthesis of factor IX: implications for gene therapy.Thrombosis and Haemostasis74(1):274-277.
Iberti, T.J. et al. (1994) Abnormal coagulation profile in brain tumor patients during surgeryNeurosurgery34(3):389-395.
Kirchofer, D., et al. (1995) Active site-blocked factors VIIa and Ixa differently inhibit fibrin formation in a human ex vivo thrombosis modelArterioscler. Thromb. Vasc. Biol. 15:1098-1106.
Miyata, T. et al. (1994) Factor IX Bm Kiryu: a Val-313-to-Asp substitution in the catalytic domain results in loss of function due to a conformational change of the surface loop: evidence obtained by chimeric modeling.Brit. J. Of Haematol. 88:156-165.
Santagostine, E. et al. (1994) Markers of hypercoagulability in patients with hemophilia B given repeated, large doses of factor IX concentrates during and after surgery.Thrombosis and Haemostasis71(6):737-40.
Wacey, A.I. et al. (1994) Determinants of the factor IX mutational spectrum in hemophilia B: an analysis of missense mutations using a multi-domain molecular model of the activated proteinHum. Genet. 94:594-608.
Warrier, I. et al. (1995) Safety of high doses of a monoclonal antibody-purified factor IX concentrateAm. J. of Hematol. 49:92-94.
Wong, A. G. et al. (1995) Relative efficacy of active site-blocked factors IXa Xa in a model of venous thrombosis Supplement I Circulation 98(8) Abstract # 3293 p. I-686.
Rose Eric
Schmidt Ann Marie
Spanier Talia
Stern David
Cooper & Dunham LLP
Russel Jeffrey E.
The Trustees of Columbia University in the City of New York
White John P.
LandOfFree
Method for inhibiting thrombosis in a patient whose blood is... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for inhibiting thrombosis in a patient whose blood is..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for inhibiting thrombosis in a patient whose blood is... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2912759