Compositions and methods for the synthesis of natriuretic protein receptor B and methods of use
AssigneeGenentech, Inc.
InventorsMing-Shi Chang, David V. Goeddel, David G. Lowe
Life of this patent
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Abstract
Described are the amino acid sequence of natriuretic peptide receptor B (NPRB) and DNA encoding NPRB. Also disclosed are expression vectors and cells transformed to express the NPRB, DNA encoding NPRB and diagnostic and therapeutic uses for the NPRB and the DNA encoding NPRB.
Claims21
Isolated pure natriuretic protein receptor B (NPRB) selected from the group consisting of NPRB having the amino acid sequence depicted in FIG. 1A-K, NPRB comprising amino acids 1-479 of FIG. 1A-K, NPRB comprising amino acids 1-433 of FIG. 1A-K and porcine atrium NPRB, unaccompanied by associated native glycosylation.
Isolated pure natriuretic protein receptor B (NPRB) selected from the group consisting of NPRB having the amino acid sequence depicted in FIG. 1A-K, NPRB comprising amino acids 1-479 of FIG. 1A-K, NPRB comprising amino acids 1-433 of FIG. 1A-K and porcine atrium NPRB.
A DNA isolate encoding natriuretic protein receptor B (NPRB) selected from the group consisting of NPRB having the amino acid sequence depicted in FIG. 1A-K, NPRB comprising amino acids 1-479 of FIG. 1A-K, NPRB comprising amino acids 1-433 of FIG. 1A-K and porcine atrium NPRB.
A nucleic acid isolate capable of hybridizing under high stringency conditions with nucleic acid encoding natriuretic protein receptor B having the amino acid sequence depicted in FIG. 1 wherein the nucleic acid isolate encodes a polypeptide having the characteristics of i) having a guanylate cyclase domain possessing guanylate cyclase activity, ii) displaying a greater degree of type-C natriuretic peptide (CNP)-dependent activation of the guanylate cyclase domain than atrial natriuretic receptor A (ANP-A receptor) and iii) possessing an immune epitope that is immunologically cross-reactive with an NPRB epitope, other than nucleic acid encoding natriuretic protein receptor C (ANP-C receptor) or nucleic acid encoding atrial natriuretic protein receptor A (ANP-A receptor).
A process for producing natriuretic protein receptor B (NPRB) selected from the group consisting of NPRB having the amino acid sequence depicted in FIG. 1A-K, NPRB comprising amino acids 1-479 of FIG. 1A-K, NPRB comprising amino acids 1-433 of FIG. 1A-K and porcine atrium NPRB, the process comprising constructing a vector which comprises DNA encoding said natriuretic protein receptor B, transforming a host cell with said vector, incubating said transformed cell to express said natriuretic protein receptor B, and recovering said natriuretic protein receptor B from the transformed cell culture.
A pharmaceutical composition comprising a natriuretic protein receptor B (NPRB) selected from the group consisting of NPRB having the amino acid sequence depicted in FIG. 1A-K, NPRB comprising amino acids 1-479 of FIG. 1A-K, NPRB comprising amino acids 1-433 of FIG. 1A-K and porcine atrium NPRB, and a pharmaceutically acceptable carrier.
A natriuretic protein receptor B variant (NPRBDKC) comprising the amino acid sequence 1 to 433 of FIG. 1A-K, and lacking the guanylyl cyclase, protein kinase and transmembrane regions of mature natriuretic protein receptor B.
A natriuretic protein receptor B variant having the amino acid sequence depicted in FIG. 1A-K with the following amino acid substitution:
- Pro.sub.655, Glu.sub.656, Leu.sub.663, Phe.sub.664, and Ala.sub.682.
Dependencies are inferred from the claim text.