Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1998-12-07
2002-09-03
Davenport, Avis M. (Department: 1654)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S002600, C514S013800, C514S014800, C514S015800, C514S016700, C530S300000, C530S324000, C530S325000, C530S326000, C530S327000, C530S328000, C530S329000, C530S350000, C424S185100
Reexamination Certificate
active
06444644
ABSTRACT:
BACKGROUND TO THE INVENTION
The extrinsic pathway of coagulation is of central importance to the formation of thrombin in major blood vessels. This is initiated by the exposure of tissue factor (thromboplastin) from endothelial cells and monocyte/macrophages in the arterial wall.
Antidotes to tissue factor (TF), such as tissue factor pathway inhibitor, are found in the circulation associated with plasma proteins. However we have also found that plasma lipoproteins, particularly low density lipoproteins, can also exert an inhibitory effect on tissue factor activity (Ettelaie et al, 1995, Biochim. Biophys. Acta. 1257; 25-30).
The inhibition of TF is caused by the apolipoprotein B-100 (apoB-100). Its action is slower, but more long lasting than that of TFPI.
The exposure of thromboplastin, upon injury to endothelium, initiates the extrinsic pathway of coagulation and leads to formation of a blood clot on the injured surface [1, 2]. Following clot formation the procoagulant effect of thromboplastin is restrained by a number of circulating inhibitors within the serum. The ability of low density lipoprotein (LDL) [3-5] to inhibit the procoagulant activity of thromboplatin had been demonstrated previously. We have demonstrated that this inhibition arises from direct interaction of the protein moieties of thromboplastin (apoprotein III) and LDL (apolipoprotein B-100) [5-7]. Furthermore, the binding of the proteins involves the positively charged residues within apolipoprotein B-100 and negatively charged amino acids on thromboplastin [7]. We have previously identified a region within thromboplastin which closely resembled the repeated domains within the LDL-receptor protein, that are responsible for binding to apolipoprotein B-100 [7].
Inhibition of thromboplastin by apo B-100 may be disrupted with poly-L-lysine and to a lesser extent by poly-L-arginine [7]. Furthermore, blocking of lysine residues, e.g. during oxidation also seems to disrupt the inhibition [4,5].
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Bruckdorfer Karl Richard
Ettelaie Camille
Davenport Avis M.
Nixon & Vanderhye P.C.
University College London
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