Treatment of cardiovascular disease and dyslipidemia using...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C514S210020, C514S356000, C514S422000, C514S423000

Reexamination Certificate

active

08048880

ABSTRACT:
Administration of sPLA2inhibitors has been found to decrease cholesterol levels, atherosclerotic plaque formation and aortic aneurysm in mice, and to decrease cholesterol and triglyceride levels in humans. Interestingly, administration of sPLA2inhibitors was found to decrease cholesterol levels even when the inhibitors were administered only once per day. Therefore, provided herein are methods of treating dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome, by administering one or more sPLA2inhibitors. Significantly, administration of sPLA2inhibitors and various compounds used in the treatment of CVD, such as for example statins, resulted in greater decreases in LDL and LDL particle levels in a synergistic manner. In addition, administration of sPLA2inhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more sPLA2inhibitors and one or more compounds used in the treatment of CVD, such as for example statins, and methods of using these compositions to treat dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome.

REFERENCES:
patent: 3485847 (1969-12-01), Bossert et al.
patent: 5273995 (1993-12-01), Roth
patent: 5504073 (1996-04-01), Homan
patent: 5578634 (1996-11-01), Bach et al.
patent: 5641800 (1997-06-01), Bach et al.
patent: 5654326 (1997-08-01), Bach et al.
patent: 5684034 (1997-11-01), Bach et al.
patent: 5767115 (1998-06-01), Rosenblum et al.
patent: 6177440 (2001-01-01), Bach et al.
patent: 6252084 (2001-06-01), Bach et al.
patent: 6274578 (2001-08-01), Denney et al.
patent: 6472389 (2002-10-01), Ohtani et al.
patent: 6713645 (2004-03-01), Bach et al.
patent: 6756376 (2004-06-01), Fuji et al.
patent: 7026318 (2006-04-01), Ogawa et al.
patent: 7098237 (2006-08-01), Todo
patent: 2004/0248898 (2004-12-01), Saiga et al.
patent: 2006/0094693 (2006-05-01), Aziz et al.
patent: 2006/0223865 (2006-10-01), Buch et al.
patent: 2007/0135385 (2007-06-01), Chang et al.
patent: 1378246 (2004-01-01), None
patent: WO 96/03376 (1996-02-01), None
patent: WO 99/56752 (1999-11-01), None
patent: 00/28332 (2000-05-01), None
patent: 01/36420 (2001-05-01), None
patent: WO 01/55108 (2001-08-01), None
patent: 02/08189 (2002-01-01), None
patent: 2004/103960 (2004-12-01), None
patent: 2005/028653 (2005-03-01), None
patent: 2005/058310 (2005-06-01), None
patent: WO 2007/056281 (2007-05-01), None
Clark et al., “Potential therapeutic uses of phospholipase A2 inhibitors”, Expert Opinion on Therapeutic Patents, vol. 14, No. 7, pp. 937-950 (2004).
Aviram, M. et al., “Phospholipase A2-Modified LDL Is Taken Up at Enhanced Rate by Macrophages,” Biochem Biophys Res Commun 185:465-472 (1992).
Boekholdt, S. M., et al., “Serum Levels of Type II Secretory Phospholipase A2 and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study,” Arterioscler. Thromb. Vasc. Biol. 25:839-846 (2005).
Bostrom, M. A., et al., “Group V Secretory Phospholipase A2 Promotes Atherosclerosis: Evidence From Genetically Altered Mice,” Arterioscler. Thromb. Vasc. Bio. 27:600-606 (2007).
Boyanovsky, B., et al., “Group V Secretory Phospholipase A2-modified Low Density Lipoprotein Promotes Foam Cell Formation by a SR-A- and CD36- independent Process That Involves Cellular Proteoglycans,” J Biol Chem 280:32746-32752 (2005).
Camejo, G., et al., “Association of Apo B Lipoproteins with Arterial Proteoglycans: Pathological Significance and Molecular Basis,” Arterioscler. 139:205-222 (1998).
Chait, A., et al., “Lipoprotein-Associated Inflammatory Proteins: Markers or Mediators of Cardiovascular Disease?,” J Lipid Res. 46:389-403 (2005).
Daugherty, A., et al., “Angiotensin II Promotes Atherosclerotic Lesions and Aneurysms in Apolipoprotein E-Deficient Mice,” J Clin. Invest. 105:1605-1612 (2000).
De Beer, F. C., et al., “Secretory Non-Pancreatic Phospholipase A2: Influence on Lipoprotein Metabolism,” J Lipid Res. 38:2232-2239 (1997).
Divchev, D., et al., “The Secretory Phospholipase A2 Group IIA: A Missing Link Between Inflammation, Activated Renin-Angiotensin System, and Atherogenesis,” Vasc Health Risk Manag 4:597-604 (2008).
Draheim, S.E., et al., “Indole Inhibitors of Human Nonpancreatic Secretory Phospholipase A2. 3. Indole-3-Glyoxamides,” J Med Chem 39:5159-5175 (1996).
Eckey, R., et al., “Increased Hepatic Cholesterol Accumulation in Transgenic Mice Overexpressing Human Secretory Phospholipase A2Group IIA,” Inflammation 28:59-65 (2004).
Elinder, L. S., et al., “Expression of Phospholipase A2 Isoforms in Human Normal and Atherosclerotic Arterial Wall,” Arterioscler. Thromb. Vasc. Biol. 17:2257-2263 (1997).
Flood, C., et al., “Molecular Mechanism for Changes in Proteoglycan Binding on Compositional Changes of the Core and the Surface of Low-Density Lipoprotein—Containing Human Apolipoprotein B100,” Arterioscler Thromb Vasc Biol 24:564-570 (2004).
Ghesquiere, S., et al., “Macrophage-Specific Overexpression of Group IIa sPLA2 Increases Atherosclerosis and Enhances Collagen Deposition,” J Lipid Res 46:201-210 (2005).
Hakala, J. K., et al., “Lipolysis of LDL by Human Secretory Phospholipase A2 Induces Particle Fusion and Enhances the Retention of LDL to Human Aortic Proteoglycans,” Arterioscler. Thromb. Vasc. Biol. 21:1053-1058 (2001).
Hanasaki, K., et al., “Potent Modification of Low Density Lipoprotein by Group X Secretory Phospholipase A2 Is Linked to Macrophage Foam Cell Formation,” J Biol Chem 277:29116-29124 (2002).
Hartford, M., et al., “CRP, Interleukin-6, Secretory Phospholipase A2 Group IIA, and Intercellular Adhesion Molecule-1 During the Early Phase of Acute Coronary Syndromes and Long-Term Follow-Up,” J Cardiol. 108:55-62 (2006).
Hurt-Camejo, E., et al., “Localization of Nonpancreatic Secretory Phospholipase A2 in Normal and Atherosclerotic Arteries,” Arterioscler Thromb Vasc Biol 17:300-309 (1997).
Hurt-Camejo, E., et al., “Cellular Consequences of the Association of ApoB Lipoproteins with Proteoglycans,” Arterioscler Thromb Vasc Biol 17:1011-1017 (1997).
Hurt-Camejo, E., et al., “Phospholipase A2 in Vascular Disease,” Circ Res 89:298-304 (2001).
Ivandic, B., et al., “Role of Group II Secretory Phospholipase A2 in Atherosclerosis: 1. Increased Atherogenesis and Altered Lipoproteins in Transgenic Mice Expressing Group IIa Phospholipase A2,” Arterioscler. Thromb. Vasc. Biol. 19:1284-1290 (1999).
Jialal, I., “Evolving Lipoprotein Risk Factors: Lipoprotein(a) and Oxidized Low-Density Lipoprotein,” Clin. Chem. 44:1827-1832 (1998).
Karabina, S.A., et al., “Atherogenic Properties of LDL Particles Modified by Human Group X Secreted Phospholipase A2 on Human Endothelial Cell Function,” FASEB J 20:2547 (2006).
Kimura-Matsumoto, M., et al., “Expression of Secretory Phospholipase A2s in Human Atherosclerosis Development,” Atherosclerosis, doi:10.1016/j.atherosclerosis.2006.08.062 (2007).
Kougias, P., et al., “Lysophosphatidylcholine and Secretory Phospholipase A2 in Vascular Disease: Mediators of Endothelial Dysfunction and Atherosclerosis,” Med Sci Monit 12:RA5-RA16 (2006).
Kovanen, P. T., et al., “Secretory Group II Phospholipase A2: A Newly Recognized Acute-Phase Reactant With a Role in Atherogenesis,” Circ Res 86:610-612 (2000).
Kugiyama, K., et al., “Circulating Levels of Secretory Type II Phospholipase A2 Predict Coronary Events in Patients with Coronary Artery Disease,” Circulation 100:1280-1284 (1999).
Leitinger, N., et al., “Role of Group II Secretory Phospholipase A2 in Atherosclerosis : 2. Potential Involvement of Biologically Active Oxidized Phospholipids,” Arterioscler Thromb Vasc

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