# US 5,352,587 A · Compositions and methods for the synthesis of natriuretic protein receptor B and methods of use

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- Number: US 5,352,587 A
- Document ID: US5352587A
- Status: Granted
- Kind: A
- Application number: 07/778,157
- Filed: 1991-12-19
- Granted: 1994-10-04
- Earliest claimed: 1989-06-23
- Assignees: Genentech, Inc.
- Inventors: Ming-Shi Chang; David V. Goeddel; David G. Lowe
- Web page: https://patentgrep.com/patent/US5352587A

## CPC

- C07K 16/2869: {against hormone receptors (for antibodies against neuromediator receptors C07K16/286)}
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/58: Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Cardionatrin; Cardiodilatin
- C07K 14/72: for hormones {(for neuromediators C07K14/70571)}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 1

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.

### Claim 2

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.

### Claim 3

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.

### Claim 4

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).

### Claim 5 (depends on 4)

A recombined expression vector comprising the DNA of claim 4 operably linked to a control sequence recognized by a host transformed with the recombinant expression vector.

### Claim 6 (depends on 5)

A composition of matter comprising a cell transformed with the recombinant expression vector of claim 5.

### Claim 7 (depends on 6)

The cell of claim 6, wherein the cell is a prokaryotic cell.

### Claim 8 (depends on 6)

The cell of claim 6, wherein the cell is a eukaryotic cell.

### Claim 9 (depends on 6)

The cell of claim 6, wherein the cell is a mammalian cell.

### Claim 10 (depends on 6)

The cell of claim 6, wherein the cell is a human embryonic kidney cell.

### Claim 11 (depends on 6)

The cell of claim 6, wherein the cell is a Chinese hamster ovary cell.

### Claim 12

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.

### Claim 13 (depends on 12)

The process of claim 12 wherein said natriuretic protein receptor B is recovered from the cell culture medium.

### Claim 14

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.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14 which additionally comprises one of the following: atrial, brain, or type C natriuretic protein.

### Claim 16 (depends on 15)

The pharmaceutical composition of claim 15 wherein the atrial, brain or type C natriuretic protein is human.

### Claim 17 (depends on 4)

The polypeptide of claim 4 which is human.

### Claim 18 (depends on 14)

A method for the treatment of pathological disorders associated with excess atrial natriuretic peptide, or excess brain natriuretic peptide, or excess type C natriuretic peptide, or excess amounts of any peptide which binds with high affinity to natriuretic protein receptor B in a mammal comprising administering to the mammal the composition of claim 14 in a therapeutically effective amount.

### Claim 19 (depends on 18)

The method of claim 18 wherein the mammal is human.

### Claim 20

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.

### Claim 21

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.