# US 9,040,046 B2 · Sodium pump antibody agonists and methods of treating heart disease using the same

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- Number: US 9,040,046 B2
- Document ID: US9040046B2
- Status: Granted
- Kind: B2
- Application number: 13/359,723
- Filed: 2012-01-27
- Published: 2012-08-02
- Granted: 2015-05-26
- Earliest claimed: 2011-01-31
- Applicants: Kai Xu
- Inventors: Kai Xu
- Web page: https://patentgrep.com/patent/US9040046B2

## CPC

- C07K 16/18: against material from animals or humans
- A61P 9/00: Drugs for disorders of the cardiovascular system
- C07K 16/40: against enzymes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/75: Agonist effect on antigen
- 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

Antibodies that are agonists of sodium pump (Na+/K+ ATPase; NKA) activity are provided. In particular, antibodies that specifically bind epitopes on the beta-1 (β1) subunit of NKA are disclosed. These antibodies have the ability to increase the activity of the catalytic alpha subunit of NKA upon β1 subunit binding. Due to their activity, the antibodies also have the ability to trigger a positive inotropic effect in cardiac tissues (i.e., increase cardiac contraction). The present invention thus includes, but is not limited to, NKA β1 subunit peptide epitopes, antibodies that specifically bind the epitopes, methods of agonizing NKA activity through administration of the peptides or the antibodies, and methods of treating and/or preventing heart disease through administration of the peptides or the antibodies.

## Claims

### Claim 1

A therapeutically effective composition comprising an isolated and purified antibody which is specifically made against the synthetic amino acid sequence KERGEFNHERGER (SEQ ID NO:1), wherein the binding of said antibody in a therapeutically effective amount to the beta-1subunit of the (Na++K+)-ATPase exerts a positive inotropic effect in cardiac myocytes without inhibiting (Na++K+)-ATPase enzyme activity.

### Claim 2 (depends on 1)

The therapeutically effective composition of claim 1, wherein said antibody is specifically made against the synthetic amino acid sequence KERGEFNHERGER (SEQ ID NO: 1), said synthetic amino acid sequence being a component of an antigen.

### Claim 3 (depends on 1)

The therapeutically effective composition of claim 1, wherein said antibody is a polyclonal antibody, a monoclonal antibody, a humanized antibody or a human antibody.