# US 2019/0316104 A1 · Methods and compositions for treatment of lafora disease

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- Number: US 2019/0316104 A1
- Document ID: US20190316104A1
- Status: Published application
- Kind: A1
- Application number: 16/332,331
- Filed: 2017-09-08
- Published: 2019-10-17
- Earliest claimed: 2016-09-09
- Assignees: Valerion Therapeutics, LLC
- Applicants: Valerion Therapeutics, LLC
- Inventors: Dustin D. Armstrong
- Web page: https://patentgrep.com/patent/US20190316104A1

## CPC

- C12N 9/2414: {Alpha-amylase (3.2.1.1.)}
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- C12N 9/16: acting on ester bonds (3.1)
- 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 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/55: Fab or Fab'
- C07K 2317/77: Internalization into the cell
- C07K 2319/00: Fusion polypeptide
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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

In certain embodiments, the present disclosure provides compositions and methods for treating Lafora Disease.

## Claims

### Claim 1

A chimeric polypeptide comprising: (i) an alpha-amylase polypeptide, and (ii) an internalizing moiety; wherein the alpha-amylase polypeptide comprises the amino acid sequence of SEQ ID NO: 1; and wherein the internalizing moiety is an antibody or antigen binding fragment, wherein the antibody or antigen binding fragment comprises a heavy chain variable domain and a light chain variable domain; wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 2; and wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 3.

### Claim 2

A chimeric polypeptide comprising: (i) an alpha-amylase polypeptide, and (ii) an internalizing moiety; wherein the alpha-amylase polypeptide comprises the amino acid sequence of SEQ ID NO: 1, but wherein the alpha-amylase polypeptide does not comprise the full-length alpha-amylase polypeptide of SEQ ID NO: 36; and wherein the internalizing moiety is an antibody or antigen binding fragment, wherein the antibody or antigen binding fragment comprises a heavy chain comprising a heavy chain variable domain and a light chain comprising a light chain variable domain; wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 2; and wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 3.

### Claim 3 (depends on 1)

The chimeric polypeptide of claim 1, wherein the alpha-amylase polypeptide consists of the amino acid sequence of SEQ ID NO: 1.

### Claim at position 4

-7. (canceled)

### Claim 8 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide is capable of hydrolyzing alpha-1,4-glucosidic bonds in a cell from a subject having Lafora Disease.

### Claim 9 (depends on 8)

The chimeric polypeptide of claim 8, wherein the subject is a non-human animal.

### Claim 10

(canceled)

### Claim 11 (depends on 8)

The chimeric polypeptide of claim 8, wherein the subject is a human.

### Claim 12

(canceled)

### Claim 13 (depends on 8)

The chimeric polypeptide of claim 8, wherein the cell is selected from the group consisting of a muscle cell, a diaphragm muscle cell, a brain cell, and a neuron.

### Claim at position 11

-16. (canceled)

### Claim 17 (depends on 1)

The chimeric polypeptide of claim 1, wherein the alpha-amylase polypeptide is chemically conjugated to the internalizing moiety.

### Claim 18 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises a fusion protein comprising the alpha-amylase polypeptide and all or a portion of the internalizing moiety.

### Claim 19 (depends on 18)

The chimeric polypeptide of claim 18, wherein the chimeric polypeptide does not include a linker interconnecting the alpha-amylase polypeptide to the internalizing moiety.

### Claim 20 (depends on 18)

The chimeric polypeptide of claim 18, wherein the fusion protein comprises a linker.

### Claim at position 16

-23. (canceled)

### Claim 24 (depends on 1)

The chimeric polypeptide of claim 1, wherein all or a portion of the internalizing moiety is conjugated or joined, directly or via a linker, to the N-terminal amino acid of the alpha-amylase polypeptide; or
wherein all or a portion of the internalizing moiety is conjugated or joined, directly or via a linker, to the C-terminal amino acid of the alpha-amylase polypeptide; or
wherein all or a portion of the internalizing moiety is conjugated or joined, directly or indirectly to an internal amino acid of the alpha-amylase polypeptide.

### Claim at position 18

-32. (canceled)

### Claim 33 (depends on 1)

The chimeric polypeptide of claim 1, wherein the internalizing moiety comprises an antibody.

### Claim 34

(canceled)

### Claim 35 (depends on 1)

The chimeric polypeptide of claim 1, wherein the internalizing moiety comprises an antigen-binding fragment.

### Claim at position 22

-42. (canceled)

### Claim 43 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8.

### Claim 44

(canceled)

### Claim 45 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NOs: 7 and 8.

### Claim 46 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10.

### Claim 47

(canceled)

### Claim 48 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NOs: 9 and 10.

### Claim 49 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 8.

### Claim 50

(canceled)

### Claim 51 (depends on 1)

The chimeric polypeptide of claim 1, wherein the chimeric polypeptide comprises the amino acid sequences of SEQ ID NOs: 8 and 43.

### Claim 52 (depends on 1)

A nucleic acid construct, comprising a nucleotide sequence that encodes the chimeric polypeptide of claim 1 as a chimeric polypeptide comprising a fusion protein.

### Claim at position 33

-70. (canceled)

### Claim 71 (depends on 1)

A method for treating a subject having Lafora disease, comprising administering to the subject a therapeutically effective amount of the chimeric polypeptide of claim 1.

### Claim at position 35

-74. (canceled)