# US 12,215,142 B2 · Antibody fragment degrading and removing abnormal TDP-43

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- Number: US 12,215,142 B2
- Document ID: US12215142B2
- Status: Granted
- Kind: B2
- Application number: 16/980,667
- Filed: 2019-03-15
- Published: 2021-01-28
- Granted: 2025-02-04
- Earliest claimed: 2018-03-16
- Assignees: National University Corporation Shiga University of Medical Science
- Applicants: National University Corporation Shiga University of Medical Science
- Inventors: Makoto Urushitani; Yoshitaka Tamaki
- Web page: https://patentgrep.com/patent/US12215142B2

## CPC

- A61P 25/00: Drugs for disorders of the nervous system
- C07K 16/18: against material from animals or humans
- 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
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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

A modified antibody fragment comprising an antibody fragment capable of binding to misfolded TDP-43, and a chaperone-mediated autophagy localizing signal peptide.

## Claims

### Claim 1

A modified antibody fragment that binds to misfolded TAR DNA-binding protein of 43 kDa, wherein the modified antibody fragment comprises an antibody fragment and a chaperone-mediated autophagy localizing signal peptide comprising KFREQ (SEQ ID NO: 8) and linked to the C-terminus of the antibody fragment;
the antibody fragment comprising:
a heavy-chain variable region comprising a heavy-chain CDR 1 consisting of an amino acid sequence GFNIKDYY (SEQ ID NO: 1), a heavy-chain CDR 2 consisting of an amino acid sequence IDPEDGET (SEQ ID NO: 2), and a heavy-chain CDR 3 consisting of an amino acid sequence TIIYYYGSRYVDY (SEQ ID NO: 3); and
a light-chain variable region comprising a light-chain CDR 1 consisting of an amino acid sequence SSISSSY (SEQ ID NO: 4), a light-chain CDR 2 consisting of an amino acid sequence RTS, and a light-chain CDR 3 consisting of an amino acid sequence QQGSSIPLT (SEQ ID NO: 5); and
wherein the antibody fragment is a scFv; and
wherein the antibody fragment and the chaperone-mediated autophagy localizing signal peptide are directly bonded, or an amino acid sequence exists between them.

### Claim 2 (depends on 1)

The modified antibody fragment according to claim 1, wherein the antibody fragment is a humanized antibody fragment.

### Claim 3 (depends on 1)

A nucleic acid encoding the modified antibody fragment according to claim 1.

### Claim 4 (depends on 3)

An expression vector comprising the nucleic acid according to claim 3.

### Claim 5 (depends on 3)

A method of inducing a heat shock protein in a cell, the method comprising administering the nucleic acid according to claim 3.

### Claim 6 (depends on 5)

The method of claim 5, wherein the heat-shock protein is Hsp70.