# US 10,501,731 B2 · Degradable clostridial toxins

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,501,731 B2
- Document ID: US10501731B2
- Status: Granted
- Kind: B2
- Application number: 15/845,572
- Filed: 2017-12-18
- Published: 2018-05-03
- Granted: 2019-12-10
- Earliest claimed: 2010-05-20
- Assignees: Allergan, Inc.
- Applicants: Allergan, Inc.
- Inventors: Lance E. Steward; Sanjiv Ghanshani; Ester Fernandez-Salas; Marcella A. Gilmore; Joseph Francis; Kei Roger Aoki
- Web page: https://patentgrep.com/patent/US10501731B2

## CPC

- C12N 9/52: derived from bacteria {or Archaea}
- A61K 38/4893: {Botulinum neurotoxin (3.4.24.69)}
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 17/00: Drugs for dermatological disorders
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 35/00: Antineoplastic agents
- C07K 14/33: from Clostridium (G)
- C12Y 304/24069: Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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)
- C12Y: ENZYMES

## Abstract

The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.

## Claims

### Claim 1

A non-naturally occurring Clostridial toxin comprising at least one exogenous protease cleavage site located within an inactivation cleavage site region, wherein the inactivation cleavage site region is located
in the translocation domain and/or the N-terminal subdomain of the binding domain (HCN), wherein the at least one exogenous protease cleavage site comprises a dual Thrombin-Thrombin cleavage site, a Factor Xa cleavage site, a dual Factor Xa-Thrombin cleavage site, and/or a Matrix Metalloproteinase-9 (MMP-9) cleavage site, and
wherein the inactivation cleavage site region comprises a variant of SEQ ID NO:1 comprising the at least one exogenous protease site in amino acids 871-895 of SEQ ID NO: 1.

### Claim 2 (depends on 1)

The Clostridial toxin of claim 1, further comprising a botulinum toxin type A (BoNT/A) enzymatic domain.

### Claim 3 (depends on 1)

The non-naturally occurring Clostridial toxin of claim 1, comprising at least an amino acid sequence selected from the group consisting of the amino acid sequence of SEQ ID: 531, SEQ ID NO: 533, SEQ ID NO: 535 and SEQ ID NO: 537.