# US 12,005,101 B2 · Modulation of proprotein convertase subtilisin/kexin 9 expression (PCSK9) with HSP 27 and/or HSP25

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- Number: US 12,005,101 B2
- Document ID: US12005101B2
- Status: Granted
- Kind: B2
- Application number: 17/515,001
- Filed: 2021-10-29
- Published: 2022-04-21
- Granted: 2024-06-11
- Earliest claimed: 2015-08-25
- Assignees: Pemi31 Therapeutics Inc.
- Applicants: PEMI31 Therapeutics Inc.
- Inventors: Edward R. M. O'Brien; Chunhua Shi; Yong-Xiang Chen
- Web page: https://patentgrep.com/patent/US12005101B2

## CPC

- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- A61K 38/1709: {from mammals}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 3/06: Antihyperlipidemics
- C07K 14/47: from mammals
- C07K 14/4703: {Inhibitors; Suppressors}
- C07K 16/18: against material from animals or humans
- C12N 9/58: derived from fungi
- G01N 33/54326: {Magnetic particles}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- G01N 2333/4703: Regulators; Modulating activity
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- 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)

## Abstract

This disclosure pertains to compositions and methods for reducing serum cholesterol in mammalian subjects. The exemplary compositions comprise mixtures of HSP27 protein or fragments thereof, a HSP25 protein or fraction thereof, a recombinant rHSP25 peptide, or a recombinant HSP27 peptide in a mixture with an adjuvant. The compositions may optionally comprise anti-HSP27 antibody. The methods for reducing serum cholesterol in mammalian subjects relate to the use of the compositions to increase the subjects' levels of serum HSP27 and/or anti-HSP27 antibodies.

## Claims

### Claim 1

A method for increasing serum levels of HSP27 and/or serum levels of HSP27 antibodies in a human subject comprising administration, to the human subject, of an effective dose of a pharmaceutical composition comprising:
a HSP27 protein that shares at least 85% sequence identity with the amino acid sequence set forth in SEQ.ID NO: 4 wherein the concentration of said HSP27 protein, is in the range of 25 μg/mL to 250 μg/mL; and
an adjuvant wherein the concentration of said adjuvant is in the range of 25 μg/mL to 250 μg/mL;
together with a pharmaceutically acceptable diluent or carrier.

### Claim 2 (depends on 1)

A method according to claim 1, wherein the HSP27 protein shares at least 90% sequence identity with the amino acid sequence set forth in SEQ.ID NO: 4.

### Claim 3 (depends on 1)

A method according to claim 1, wherein the HSP27 protein shares at least 95% sequence identity with the amino acid sequence set forth in SEQ.ID NO: 4.

### Claim 4 (depends on 1)

A method according to claim 1, wherein the HSP27 protein shares at least 99% sequence identity with the amino acid sequence set forth in SEQ.ID NO: 4.

### Claim 5 (depends on 1)

A method according to claim 1, wherein the HSP27 protein consists of the amino acid sequence set forth in SEQ.ID NO: 4.

### Claim 6 (depends on 1)

A method according to claim 1, wherein the pharmaceutical composition additionally comprises an anti-HSP27 antibody.

### Claim 7 (depends on 1)

A method according to claim 1, wherein the adjuvant is an aluminum hydroxide adjuvant.

### Claim 8 (depends on 1)

A method according to claim 1, wherein the ratio of the HSP27 protein, to adjuvant is in the range of 1:1 (v/v) to 1:3 (v/v).

### Claim 9 (depends on 1)

A method according to claim 1, wherein the carrier is sterile water, a buffered saline solution, or a buffered phosphate solution.

### Claim 10 (depends on 1)

A method according to claim 1, wherein the carrier comprises from 0.1% to 95% of the pharmaceutical composition.

### Claim 11 (depends on 1)

A method according to claim 1, wherein the pharmaceutical composition includes at least one of a non-aqueous solvent, an anti-microbial agent, an anti-oxidant, or a chelating agent.

### Claim 12 (depends on 11)

A method according to claim 11, wherein the non-aqueous solvent is propylene glycol, polyethylene glycol, an organic ester, a vegetable oil, or a mixture thereof.

### Claim 13 (depends on 1)

A method according to claim 1, wherein the pharmaceutical composition is administered by injection.

### Claim 14 (depends on 1)

A method according to claim 1, wherein the pharmaceutical composition is administered by oral delivery.

### Claim 15 (depends on 14)

A method according to claim 14, wherein the pharmaceutical composition is administered by oral delivery, and is one of a tablet, a liquid, a powder, a granule, a solution, a syrup, a suspension, or a capsule.

### Claim 16 (depends on 1)

A method of claim 1, wherein the method interferes and/or reduces expression of PCSK9 in the human subject.