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US 5,356,781 AGranted
Zymogen activation peptides (ZAP) in the diagnosis of disease
AssigneeBioscience International, Inc.
InventorsJohn Hermon-Taylor, Brian M. Austen
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AssigneeBioscience International, Inc.
InventorsJohn Hermon-Taylor, Brian M. Austen
Estimating the term…
Pancreatic disease can be diagnosed by assaying a patient's body fluid such as serum or urine, for pancreatic activation peptides (PAP) released from zymogens by proteolytic activation. Particularly useful are peptides having C-terminal D.sub.4 K sequences. The method uses polyclonal or monoclonal antibodies generated and selected for C-terminal specificity on PAP so that the tests only report free PAP not parent zymogen. Also described are peptides and antibodies labelled with revealing agents and/or immobilised on solid supports and their use in diagnostic assays and kits. In pancreatic disease the tests distinguish necrotising from oedematous acute pancreatitis and permit severity prediction and monitoring as well as diagnosing chronic pancreatitis in exacerbation. Tests reporting free activation peptides from the zymogens prophospholipase A, procolipase and proelastases are also applicable in non-pancreatic diseases where activation of these zymogens, sharing sequence homology in the activation peptide C-terminal region with pancreatic isoenzymes, forms part of the molecular pathology of the condition.
A immunological method of detecting the activation of pancreatic zymogens in a patient which comprises:
A solid component for a diagnostic test kit comprising the trysinogen activation peptide D.sub.4 K or a hapten conjugate thereof, said D.sub.4 K or hapten conjugate immobilised on an inert solid support having the lysine (K) as a free carboxy terminus, said D.sub.4 K or D.sub.4 K hapten conjugate further bound to a C-terminally directed antibody which specifically binds an activation peptide of a pancreatic zymogen (PAP).
A solid component for a diagnostic test kit comprising an activation peptide of a pancreatic zymogen (PAP) selected from the group consisting of ##STR1## or a hapten conjugate thereof, said activation peptide or hapten conjugate immobilised on a solid support having the arginine (R) as a free carboxy terminus, said peptide or hapten conjugate further bound to a C-terminally directed antibody which specifically binds said activation peptide.
A solid component for a diagnostic test kit comprising a C-terminally directed antibody which specifically binds an activation peptide of a pancreatic zymogen (PAP), immobilised on an inert solid support to which trypsinogen activation peptide D.sub.4 K, or a hapten conjugate thereof, is bound at its specific antigen binding site.
A solid component for a diagnostic test kit comprising a C-terminally directed antibody which specifically binds an activation peptide of a pancreatic zymogen (PAP), immobilised on an inert solid support to the specific antigen binding site of which a peptide selected from the group consisting of DSGISPR, APGPR, GDPTYPPYVTR, and PPYVTR, or a hapten conjugate thereof, is bound.
A diagnostic test kit comprising at least one component selected from the group of activation peptides of a pancreatic zymogen (PAP) consisting of D.sub.4 K, DSGISPR, APGPR, GDPTYPPYVTR, PPYVTR, or a hapten conjugate thereof, and a C-terminally directed antibody which specifically binds said activation peptide, said component carrying a revealing label.
A diagnostic test kit comprising a solid component and a liquid component, said solid component selected from the group of activation peptides of a pancreatic zymogen (PA)P consisting of D.sub.4 K, DSGISPR, APGPR, GDPTYPPYVTR, PPYVTR, or a hapten conjugate thereof, and a C-terminally directed antibody which specifically binds said activation peptide, said solid component immobilised on an inert solid support, and wherein one of said components carries a revealing label.
Dependencies are inferred from the claim text.