# US 7,745,600 B2 · Isolated nucleic acids for mutant mammalian Nav 1 proteins

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- Number: US 7,745,600 B2
- Document ID: US7745600B2
- Status: Granted
- Kind: B2
- Application number: 11/507,232
- Filed: 2006-08-21
- Published: 2007-06-21
- Granted: 2010-06-29
- Earliest claimed: 2003-06-26
- Assignees: The Research Foundation of State University of New York
- Inventors: Sho-Ya Wang
- Web page: https://patentgrep.com/patent/US7745600B2

## CPC

- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- G01N 33/502: {for testing non-proliferative effects}
- G01N 33/5061: {Muscle cells}
- G01N 2500/10: involving cells
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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)

## Abstract

A method or screen for assessing the potential of a compound to treat a pathological condition, such as arrhythmia, which is manifested by an increased late sodium current in a heart is disclosed. The method employs a mutant sodium channel protein having an amino acid sequence in which one or more amino acids among the ten amino acids occurring at the carboxy end of the S6 segments of D1, D2, D3 or D4 domains of mammalian Nav1 differs from the amino acid in wild-type Nav1 by substitution with tryptophan, phenylalanine, tyrosine or cysteine. Cells transfected with a nucleic acid that encodes a mutant mammalian Nav1 protein, as well as isolated nucleic acid comprising a nucleotide sequence that codes for a mutant mammalian Nav1 protein are disclosed.

## Claims

### Claim 1

An isolated nucleic acid encoding a mutant Nav 1.4 or Nav 1.5 protein, wherein said mutant protein differs from wild-type mammalian human or rat Nav1.4 or Nav1.5 by substitution with tryptophan, phenylalanine, tyrosine or cysteine at from one to five positions selected from the group consisting of positions 19, 21 and 22 of the S6 segment of D1 domain and positions 23 and 24 of the S6 segment of the D4 domain, wherein said mutant protein is fast-inactivation deficient.

### Claim 2

An isolated nucleic acid encoding a rat or human Nav1.4 or Nav1.5 protein that differs from wild-type mammalian human or rat Nav1.4 or Nav1.5 by substitution with tryptophan, phenylalanine, tyrosine or cysteine at from one to five positions selected from the group consisting of positions L435, L437, A438, I1589 and I1590 of rNav1.4, wherein said mutant protein is fast-inactivation deficient.