# US 2018/0022779 A1 · Compositions and methods for regulating arterial tone

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- Number: US 2018/0022779 A1
- Document ID: US20180022779A1
- Status: Published application
- Kind: A1
- Application number: 15/643,633
- Filed: 2017-07-07
- Published: 2018-01-25
- Earliest claimed: 2012-10-22
- Assignees: University of Virginia Patent Foundation
- Applicants: University of Virginia Patent Foundation
- Inventors: Benjamin M. Gaston; Adam C. Straub; Brant E. Isakson; Linda Columbus
- Web page: https://patentgrep.com/patent/US20180022779A1

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/805: Haemoglobins; Myoglobins
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/18: against material from animals or humans
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- 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 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/30: Special therapeutic applications
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

The present invention provides compositions and methods for regulating arterial tone based on the discovery herein of novel expression and regulation of hemoglobin alpha and cytochrome B5 reductase 3 and the effects on NO and NOS.

## Claims

### Claim at position 1

1-32. (canceled)

### Claim 33

A peptide consisting of amino acid sequence LSFPTTKTYFPHFDLSHGSA (SEQ ID NO:1) or a peptide consisting of amino acid sequence LSFPTTKTYF (SEQ ID NO:2), said peptide further comprising a plasma membrane permeability sequence.

### Claim 34 (depends on 33)

The peptide of claim 33, wherein the plasma membrane permeability sequence comprises an HIV-tat tag sequence of YGRKKRRQRRR (SEQ ID NO:3).

### Claim 35

A pharmaceutical composition comprising a peptide consisting of amino acid sequence LSFPTTKTYFPHFDLSHGSA (SEQ ID NO:1) or a peptide consisting of amino acid sequence LSFPTTKTYF (SEQ ID NO:2), and a physiologically acceptable carrier.

### Claim 36

A pharmaceutical composition comprising a peptide consisting of amino acid sequence LSFPTTKTYFPHFDLSHGSA (SEQ ID NO:1) or a peptide consisting of amino acid sequence LSFPTTKTYF (SEQ ID NO:2), and a physiologically acceptable carrier, wherein said amino acid sequence further comprises a plasma membrane permeability sequence.

### Claim 37 (depends on 36)

The pharmaceutical composition of claim 36, wherein the plasma membrane permeability sequence comprises an HIV-tat tag sequence of YGRKKRRQRRR (SEQ ID NO:3).

### Claim 38

A method to prevent or treat a disease or condition comprising administering to a subject in need thereof a pharmaceutical composition comprising a physiologically acceptable carrier and an effective amount of:
a) a peptide having the amino acid sequence LSFPTTKTYFPHFDLSHGSA (SEQ ID NO:1); or
b) a peptide having the amino acid sequence LSFPTTKTYF (SEQ ID NO:2); or
c) an antibody directed against Hb α; or
d) an antibody directed against SEQ ID NO:1; or
e) an antibody directed against SEQ ID NO: 2; or
f) an inhibitor of Hb a; or
g) an inhibitor of CytB5R3 activity or expression,
so as to prevent or treat said condition or disease.

### Claim 39 (depends on 38)

The method of claim 38, wherein the disease or condition is selected from the group consisting of hypertension, stroke, arteriosclerosis, hemoptysis, gastrointestinal bleed, epistaxis, migraine headache, musculoskeletal injuries, trauma, hemangioma repair, intraoperative causes of bleeding, bleeding diatheses, uterine hemorrhage, menorrhagia, septic shock, anaphylactic shock, erectile dysfunction, repair phase sport injuries, and Raynaud's.

### Claim 40 (depends on 38)

The method of claim 38, wherein said method increases nitric oxide, inhibits or reduces vasoconstriction, regulates blood pressure, or relaxes resistance arterioles.

### Claim 41 (depends on 40)

The method of claim 40, wherein the method decreases blood pressure.

### Claim 42 (depends on 38)

The method of claim 38, where said method increases nitric oxide, inhibits or reduces vasoconstriction, regulates blood pressure, and relaxes resistance arterioles.

### Claim 43 (depends on 38)

The method of claim 38, where the administration is intraperitoneal or oral.

### Claim 44 (depends on 38)

The method of claim 38, further comprising administering inhaled oxygen.

### Claim 45 (depends on 38)

The method of claim 38, wherein the inhibitor of Hbα is an Hbα siRNA.

### Claim 46 (depends on 38)

The method of claim 38, wherein the inhibitor of CytB5R3 activity or expression is a CytB5R3 siRNA.

### Claim 47 (depends on 38)

The method of claim 38, wherein the amino acid sequence of a) or b) further comprises a plasma membrane permeability sequence.

### Claim 48 (depends on 47)

The method of claim 47, wherein the plasma membrane permeability sequence comprises an HIV-tat tag sequence of YGRKKRRQRRR (SEQ ID NO:3).