New antibodies against pro-brain natriuretic peptide, useful for early diagnosis of congestive heart failure, also new peptides as immunogens

摘要

Antibody (Ab) directed against proBNP(1-108) (A; BNP = brain natriuretic peptide), is new. Antibody (Ab) directed against proBNP(1-108) (A; BNP = brain natriuretic peptide) that: (a) recognizes specifically the sequence Arg-Ala-Pro-Arg76-Ser77-Pro (5) of (A) but does not significantly recognize the BNP peptides 1-76 and 77-108; and (b) recognizes specifically (A) circulating in human serum or plasma. Independent claims are also included for the following: (1) method for preparing Ab by immunization; (2) method for producing a hybridoma that secretes monoclonal Ab (MAb); (3) hybridoma produced by method (2); (4) MAb produced by the hybridoma of (3); (5) in vitro diagnosis of congestive heart failure in humans by using Ab or MAb to detect (A); (6) kit for detecting (A) containing Ab or MAb; (7) peptides of formulae (I)-(III); (8) peptides derived from (II) or (III) by replacing one or more of the amino acids 70, 71, 72, 79-85; (9) method for producing antibodies (Ab1) that recognize specifically sequences (II) and (III) (where X = hydrogen and Y = hydroxy) and/or (5) but not the 1-76 or 77-108 peptides, and can detect (A) in the circulation, by immunization with (I)-(III) or the derivatives of (8); (10) method for preparing hybridomas that produce Ab1; (11) Ab1 produced by method (9) or from the hybridomas of (10); (12) hybridomas of (10); (13) in vitro diagnosis of congestive heart failure in humans by using Ab1 to detect (A); (14) kit for detecting (A) containing Ab1 and/or at least one (II), (III) or the derivatives of (8). a1-X1-Arg-Ala-Pro-Arg-Ser-Pro-a2 (I); X-Tyr70-Thr-Leu-Arg-Ala-Pro-Arg76-Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Z (II); X-Tyr70-Thr-Leu-Arg-Ala-Pro-Arg76-Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Z (III) a1 = hydrogen, thiol, hydroxy, aminoxy, primary or secondary amino, aminocarbonyl, biotinyl or acetyl; X1 = 0-3 peptide amino acids (paa), optionally derived from proBNP; X2 = 0-7 paa, optionally derived from proBNP; a2 = hydroxy, amino or alkoxy; X = hydrogen, acetyl, 1-3 aa that are not part of proBNP; Z = hydroxy or 1-3 aa that are not part of proBNP.