摘要:
A Ca2+ dependent monoclonal antibody that specifically binds to a specific twelve peptide sequence (E D Q V D P R L I D G K) in the activation region of the protein C. The antibody does not bind to activated protein C and can be used to inhibit activation of protein C by thrombin-thrombomodulin. The antibody can be isolated from cell culture or ascites fluid in large quantities by affinity chromatography with mild conditions using the peptide bound to an immobilized substrate. The antibody has a number of specific uses in isolation and characterization of protein C and as a model for the design of Ca2+ dependent antibodies for the isolation of other proteins, as a diagnostic, and as a therapeutic to prevent activation of protein C. The protein c can be naturally produced or produced by expression of the recombinant gene. Advantages of the antibody in purification of protein C include the specificity for protein C and not activated protein C, and the unique Ca2+-peptide binding specificity which allows the binding site to be protected when it is being immobilized on the chromatographic support. In vivo, the antibody has been demonstrated to inhibit tumor growth. The antibody can also be used to promote clotting in patients having high levels of Factor VIII inhibitors.
摘要:
Hypercoagulable and hyperinflammatory responses can lead to a variety of diseases including but not limited to disseminated intravascular coagulation in sepsis, consumptive coagulopathy in trauma, thrombosis in the postsurgical setting, acute respiratory distress syndrome in lung, and other diseases or conditions. Polyphosphate is accumulated by many infectious microorganisms and may be released by damaged infectious microorganisms. In addition, polyphosphate is found in many organs and is released from activated platelets and mast cells. Polyphosphates activate the intrinsic pathway of coagulation that also induces inflammation. Hypercoagulable and hyperinflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death, which occur in many pathological conditions. As such, polyphosphates can be targeted pharmacologically by inhibitors, such as anti-polyphosphate antibodies, as well as used as biomarkers for diagnosis, prognosis, and treatment response indicators that may be used to provide guidance for alterations in treatment plans.
摘要:
An assay to assess thrombotic risk in which oxidized lipids comprising phospholipids are utilized as a membrane source in a clotting assay and the results compared to an assay in which unoxidized phospholipid is used as a membrane source in the presence and absence of activated protein C ('APC'). The assay can monitor for the presence of antibodies in the patient which interfere specifically with the anticoagulant function of APC in an oxidation dependent or independent manner. This can indicate the propensity of the patient to experience episodes of vein thrombosis or arterial thrombosis.
摘要:
La présente invention se rapporte à un anticorps monoclonal dépendant de la Ca2+, qui se lie spécifiquement à une séquence de 12 peptides spécifiques (EDQVDPRLIDGK) dans la région d'activation de la protéine C. L'anticorps ne se lie pas à la protéine C activée et peut être utilisée pour inhiber l'activation par thrombine-thrombomoduline de la protéine C. L'anticorps peut être isolé d'une culture cellulaire ou d'un fluide ascitique en grandes quantités par chromatographie par affinité dans des conditions douces, grâce à l'utilisation du peptide lié à un substrat immobilisé. L'anticorps trouve un certain nombre d'usages spécifiques comme isolateur et agent de caractérisation de la protéine C et comme modèle pour la mise au point d'anticorps dépendant de la Ca2+ en vue d'isoler d'autres protéines, ainsi que comme agent diagnostique et comme agent thérapeutique pour empêcher l'activation de la protéine C. La protéine C peut être produite naturellement ou par expression du gène recombinant. Parmi les avantages de l'anticorps dans la purification de la protéine C, on trouve sa spécificité pour la protéine C et pour la protéine C non activée et sa spécificité de liaison Ca2+ peptide unique, qui permet de protéger le site de liaison lors de son immobilisation sur le support chromatographique. In vivo, l'anticorps s'est révélé être un inhibiteur de la croissance tumorale. L'anticorps peut également être utilisé pour promouvoir la coagulation chez des patients présentant des hauts niveaux d'inhibiteurs de Facteur VIII.