# US 2025/0084151 A1 · Recombinant clusterin and use thereof in the treatment and prevention of disease

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- Number: US 2025/0084151 A1
- Document ID: US20250084151A1
- Status: Published application
- Kind: A1
- Application number: 18/891,120
- Filed: 2024-09-20
- Published: 2025-03-13
- Earliest claimed: 2014-12-04
- Assignees: Board of Regents, The University of Texas System
- Applicants: Board of Regents of the University of Texas System
- Inventors: Yong-Jian GENG
- Web page: https://patentgrep.com/patent/US20250084151A1

## CPC

- C07K 14/775: Apolipopeptides
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 25/32: Alcohol-abuse
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- 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 2319/00: Fusion polypeptide
- C07K 2319/21: containing a His-tag
- C07K 2319/50: containing protease site
- 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

Recombinant clusterin polypeptides and compositions comprising the same are provided. In some aspects, recombinant clusterin or nucleic acids encoding the same may be used for treating and preventing an abnormality of morphology and function in a mammal with disease (e.g., cardiovascular diseases or alcoholism).

## Claims

### Claim at position 1

1-33. (canceled)

### Claim 34

A method of providing a cytoprotective effect to vascular cells in a subject having cardiovascular disease comprising administering an effective amount of a composition providing to said subject a polypeptide comprising:
(i) a Clusterin coding sequence, said coding sequence having a deletion of the nuclear localization signal and/or transmembrane domain; or (ii) a Clusterin coding sequence and a heterologous polypeptide sequence fused to said Clusterin coding sequence.

### Claim 35 (depends on 34)

The method of claim 34 comprising administering an effective amount of a Clusterin polypeptide, wherein the Clusterin polypeptide is fused to a heterologous polypeptide sequence.

### Claim 36 (depends on 34)

The method of claim 34 comprising administering an effective amount of nucleic acid expression vector encoding a Clusterin polypeptide, wherein the Clusterin polypeptide is fused to a heterologous polypeptide sequence.

### Claim 37 (depends on 35)

The method of claim 35, wherein the heterologous polypeptide sequence comprises a protease cleavage site.

### Claim 38 (depends on 37)

The method of claim 37, wherein the protease cleavage site is a thrombin cleavage site.

### Claim 39 (depends on 34)

The method of claim 34, wherein the subject has heart disease.

### Claim 40 (depends on 39)

The method of claim 39, wherein the subject further has hypercholesterolemia, hypertension, hyperglycemia and/or thrombogenesis.

### Claim 41 (depends on 34)

The method of claim 34, wherein the cardiovascular disease is hypertension, hyperlipidemia, hypercholesterolemia, hyperglycemia, hypertension, atherosclerosis and atherosclerosis-associated ischemic heart failure, stenosis, calcification of cardiovascular tissues or stroke.

### Claim 42 (depends on 34)

The method of claim 34, wherein the cardiovascular disease is myocardial infarction and cerebral infarction.

### Claim 43 (depends on 41)

The method of claim 41, wherein the cardiovascular disease is hyperlipidemia or hypercholesterolemia.

### Claim 44 (depends on 41)

The method of claim 41, wherein the cardiovascular disease is atherosclerosis, vascular calcification, valve tissue calcification or stenosis.

### Claim 45 (depends on 34)

The method of claim 34, wherein the cardiovascular disease is diabetes, a diabetic vascular complication, vascular inflammation, vascular cell death or destruction of vascular wall.

### Claim 46 (depends on 34)

The method of claim 34, wherein the effective amount is an amount effective to reduce blood cholesterol, blood glucose, blood triglyceride, increase efflux of intracellular cholesterol and/or increase vascular or cardiac cell survival.

### Claim at position 15

47-48. (canceled)

### Claim 49 (depends on 34)

The polypeptide of claim 34, comprising a Clusterin coding sequence having a deletion of the nuclear localization signal and/or transmembrane domain.

### Claim 50 (depends on 34)

The polypeptide of claim 34, comprising a Clusterin coding sequence and a heterologous polypeptide sequence fused to said Clusterin coding sequence.

### Claim 51 (depends on 50)

The polypeptide of claim 50, wherein the heterologous polypeptide sequence comprises a protease cleavage site.

### Claim 52 (depends on 50)

The polypeptide of claim 50, wherein the protease cleavage site is a thrombin cleavage site.

### Claim 53 (depends on 34)

The polypeptide of claim 34, wherein the polypeptide is a fusion protein comprising the Clusterin coding sequence and a heterologous polypeptide sequence.

### Claim 54 (depends on 34)

The polypeptide of claim 34, wherein the polypeptide is aglycosylated.

### Claim 55 (depends on 34)

The polypeptide of claim 34, wherein the Clusterin coding sequence has a deletion of the nuclear localization signal or has a deletion of the transmembrane domain.

### Claim 56 (depends on 55)

The polypeptide of claim 55, wherein the deletion of the transmembrane domain disrupts endoplasmic reticulum (ER)-targeting of the polypeptide.

### Claim 57 (depends on 34)

The polypeptide of claim 34, further comprising a tag sequence, such as a polyhistidine tag.

### Claim 58 (depends on 57)

The polypeptide of claim 57, further comprising a protease cleavage site positioned between the tag sequence and the clusterin coding sequence, such as wherein the protease cleavage site is a thrombin or enteropeptidase cleavage site.

### Claim 59 (depends on 57)

The polypeptide of claim 57, wherein the tag sequence is positioned N-terminally relative to the Clusterin coding sequence or is positioned C-terminally relative to the Clusterin coding sequence.