# US 11,298,402 B2 · Lysosomal degradation of lipids and proteins and method of use thereof

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- Number: US 11,298,402 B2
- Document ID: US11298402B2
- Status: Granted
- Kind: B2
- Application number: 15/743,213
- Filed: 2016-07-08
- Published: 2019-05-02
- Granted: 2022-04-12
- Earliest claimed: 2015-07-10
- Assignees: University of Ottawa
- Applicants: University of Ottawa
- Inventors: Mohsen Amir Alipour; Zemin Yao
- Web page: https://patentgrep.com/patent/US11298402B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557)
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- C07K 14/4702: {Regulators; Modulating activity}
- 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)}
- C12N 2310/14: interfering nucleic acids [NA]
- 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)

## Abstract

Methods for modulating lysosome-mediated microautophagy of a lipid or protein substrate in a cell are provided herein. In certain embodiments, said methods may comprise increasing lysosome-mediated microautophagy by treating the cell with a microautophagy-enhancing agent which increases lysosomal association-dissociation events between lysosomes and the cellular lipid or protein substrate and/or increases lysosomal degradation capacity; or decreasing lysosome-mediated microautophagy by treating the cell with a microautophagy-reducing agent which reduces lysosomal association-dissociation events between lysosomes and the cellular lipid or protein substrate and/or decreases lysosomal degradation capacity; thereby modulating lysosome-mediated microautophagy of the lipid or protein substrate.

## Claims

### Claim 1

A method of increasing lysosome-mediated microautophagy of a lipid or protein substrate in a hepatic cell comprising administering a polypeptide consisting of the amino acid sequence:
(Ar18bT34N; SEQ ID NO: 12)
MLALISRLLDWFRSLFWKEEMELTLVGLQYSGKNTFVNVIASGQFSEDMI
PTVGFNMRKVTKGNVTIKIWDIGGQPRFRSMWERYCRGVNAIVYMIDAAD
REKIEASRNELHNLLDKPQLQGIPVLVLGNKRDLPNALDEKQLIEKMNLS
AIQDREICCYSISCKEKDNIDITLQWLIQHSKSRRS.

### Claim 2

A method for treating hypertriglyceridemia, hepatosteatosis, non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV) infection, hyperglycemia, hepatic insulin insensitivity, or obesity comprising administering to a subject in need thereof a polypeptide comprising the amino acid sequence:
(Ar18bT34N; SEQ ID NO: 12)
MLALISRLLDWFRSLFWKEEMELTLVGLQYSGKTTFVNVIASGQFSEDMI
PTVGFNMRKVTKGNVTIKIWDIGGLPRFRSMWERYCRGVNAIVYMIDAAD
REKIEASRNELHNLLDKPQLQUPVLVLGNKRDLPNALDEKQLIEKMNLSA
IQDREICCYSISCKEKDNIDITLQWLIQHSKSRRS.