# US 2021/0330766 A1 · Albumin-Free Botulinum Toxin Formulations

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- Number: US 2021/0330766 A1
- Document ID: US20210330766A1
- Status: Published application
- Kind: A1
- Application number: 17/322,901
- Filed: 2021-05-18
- Published: 2021-10-28
- Earliest claimed: 2009-06-25
- Assignees: Revance Therapeutics, Inc.
- Applicants: Revance Therapeutics, Inc.
- Inventors: Stewart A. Thompson; Curtis L. Ruegg; Jacob M. Waugh
- Web page: https://patentgrep.com/patent/US20210330766A1

## CPC

- A61K 38/4893: {Botulinum neurotoxin (3.4.24.69)}
- A61K 8/022: {Powders; Compacted Powders}
- A61K 8/4946: {Imidazoles or their condensed derivatives, e.g. benzimidazoles}
- A61K 8/4973: {with oxygen as the only hetero atom}
- A61K 8/4993: {Derivatives containing from 2 to 10 oxyalkylene groups}
- A61K 8/60: Sugars; Derivatives thereof
- A61K 8/602: {Glycosides, e.g. rutin}
- A61K 8/64: Proteins; Peptides; Derivatives or degradation products thereof
- A61K 8/66: Enzymes
- A61K 8/84: obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K 8/90: Block copolymers (A61K8/89 takes precedence)
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- 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 39/08: Clostridium, e.g. Clostridium tetani
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/10: Anti-acne agents
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61Q 19/008: {Preparations for oily skin}
- A61Q 19/08: Anti-ageing preparations
- C07K 14/33: from Clostridium (G)
- C12Y 304/24069: Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

This invention relates to botulinum toxin formulations that are stabilized without the use of any proteinaceous excipients. The invention also relates to methods of preparing and using such botulinum toxin formulations.

## Claims

### Claim 1

A pharmaceutical composition comprising a liquid carrier, wherein the liquid carrier comprises a botulinum toxin,
a non-ionic surfactant, one or more non-reducing sugars selected from non-reducing disaccharides and a non-reducing trisaccharides,
a bulking agent, and a physiologically compatible buffer,
wherein the concentration of the bulking agent is in the range of 1% to 10%, and
wherein the concentration of the non-reducing sugar is in the range of 0.50 to 3.0% (w/v),
wherein the liquid carrier is formulated such that upon vacuum drying or lyophilization an amorphous solid is formed.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein the botulinum toxin is a Type A toxin.

### Claim 3 (depends on 1)

The composition according to claim 1, wherein the botulinum toxin is 150 kD Type A toxin.

### Claim 4 (depends on 1)

The composition according to claim 1, further comprising a gelling agent, a viscosity-modifying agent, or a combination thereof.

### Claim 5 (depends on 1)

The composition according to claim 1, further comprising a gelling agent, wherein the gelling agent is a cellulose-based gelling agent.

### Claim 6 (depends on 1)

The composition according to claim 1, further comprising a viscosity-modifying agent, wherein the viscosity-modifying agent is selected from one or more of polyethylene glycol, a poloxamer, a polyacrylic acid, a polyamide, or a vegetable gum.

### Claim 7 (depends on 1)

The composition according to claim 1, further comprising a viscosity-modifying agent, wherein the viscosity-modifying agent is a poloxamer.

### Claim 8 (depends on 1)

The composition according to claim 1, further comprising a viscosity-modifying agent, wherein the viscosity-modifying agent is a poloxamer selected from poloxamer 181, poloxamer 188, or poloxamer 407.

### Claim 9 (depends on 1)

The composition according to claim 1, wherein the bulking agent is sorbitol, mannitol, glycine, arginine, and histidine.

### Claim 10 (depends on 1)

The composition according to claim 1, wherein the bulking agent is not sodium chloride.

### Claim 11 (depends on 1)

The composition according to claim 1, wherein the non-reducing disaccharide or tri-saccharide used to prepare the composition is selected from the group consisting of trehalose dihydrate, anhydrous trehalose, sucrose, raffinose and combinations thereof.

### Claim 12 (depends on 11)

The composition according to claim 11, wherein the non-reducing disaccharide used to prepare the composition is selected from sucrose, trehalose dihydrate or anhydrous trehalose.

### Claim 13 (depends on 1)

The composition according to claim 1, wherein the non-ionic surfactant used to prepare the composition is selected from the group consisting of polysorbates, sorbitan esters, octylphenol ethylene oxide (TRITON™ X-100), nonylphenol ethoxylate (NP-40), poloxamers and combinations thereof.

### Claim 14 (depends on 13)

The composition according to claim 13, wherein the non-ionic surfactant used to prepare the composition is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, sorbitan monolaurate (SPAN® 20), sorbitan monostearate (SPAN® 60), sorbitan tristearate (SPAN® 65), and sorbitan monooleate (SPAN® 80).

### Claim 15 (depends on 1)

The composition according to claim 1, wherein the physiologically compatible buffer is selected from the group consisting of citric acid, acetic acid, succinic acid, tartaric acid, maleic acid, histidine, citrate/acetate, citrate/histidine, citrate/tartrate, maleate/histidine, succinate/histidine, or salts thereof, and phosphate buffer.

### Claim 16 (depends on 1)

The composition according to claim 1, wherein the concentration of the bulking agent is in the range of 1.5% to 7.5%.

### Claim 17 (depends on 1)

The composition according to claim 1, wherein the concentration of the bulking agent is in the range of 2% to 6%.

### Claim 18 (depends on 1)

The composition according to claim 1, wherein the concentration of the bulking agent is in the range of 3% to 5%.