# US 9,750,808 B2 · Formulation of human antibodies for treating TNF-alpha associated disorders

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- Number: US 9,750,808 B2
- Document ID: US9750808B2
- Status: Granted
- Kind: B2
- Application number: 15/418,460
- Filed: 2017-01-27
- Published: 2017-06-01
- Granted: 2017-09-05
- Earliest claimed: 2002-08-16
- Assignees: AbbVie Biotechnology Ltd.
- Applicants: AbbVie Biotechnology Ltd
- Inventors: Hans-Juergen Krause; Lisa Baust; Michael Dickes
- Web page: https://patentgrep.com/patent/US9750808B2

## CPC

- A61K 39/39591: {Stabilisation, fragmentation}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- 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 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- 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
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 25/02: for peripheral neuropathies
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 31/18: for HIV
- A61P 33/06: Antimalarials
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/241: {Tumor Necrosis Factors}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

## Claims

### Claim 1

A stable liquid aqueous pharmaceutical formulation comprising: a human anti-human Tumor Necrosis Factor alpha (TNFα) IgG1 antibody at a concentration of 45 to 105 mg/ml, wherein the antibody is D2E7, and a buffer system;
wherein the formulation is isotonic, suitable for single-use subcutaneous injection, and has a pH of 4 to 8.

### Claim 2 (depends on 1)

The formulation of claim 1, wherein the buffer system comprises an organic acid.

### Claim 3 (depends on 2)

The formulation of claim 2, wherein the organic acid is selected from the group consisting of succinate, acetate, and histidine.

### Claim 4 (depends on 2)

The formulation of claim 2, wherein the pH is 4.5 to 6.0.

### Claim 5 (depends on 2)

The formulation of claim 2, wherein the formulation comprises a surfactant.

### Claim 6 (depends on 5)

The formulation of claim 5, wherein the surfactant is a polysorbate.

### Claim 7 (depends on 6)

The formulation of claim 6, wherein the polysorbate is polysorbate-80.

### Claim 8 (depends on 2)

The formulation of claim 2, wherein the formulation comprises a tonicity agent.

### Claim 9 (depends on 8)

The formulation of claim 8, wherein the tonicity agent is a polyol.

### Claim 10 (depends on 9)

The formulation of claim 9, wherein the polyol is a sugar, a sugar alcohol or a sugar acid.

### Claim 11 (depends on 10)

The formulation of claim 10, wherein the sugar is trehalose.

### Claim 12 (depends on 10)

The formulation of claim 10, wherein the sugar is sucrose.

### Claim 13 (depends on 10)

The formulation of claim 10, wherein the sugar alcohol is sorbitol.

### Claim 14 (depends on 10)

The formulation of claim 10, wherein the sugar alcohol is mannitol.

### Claim 15 (depends on 10)

The formulation of claim 10, wherein the formulation comprises a surfactant.

### Claim 16 (depends on 15)

The formulation of claim 15, wherein the surfactant is a polysorbate.

### Claim 17 (depends on 16)

The formulation of claim 16, wherein the polysorbate is polysorbate-80.

### Claim 18 (depends on 17)

The formulation of claim 17, wherein the sugar is trehalose.

### Claim 19 (depends on 18)

The formulation of claim 18, wherein the buffer system comprises succinate, acetate, or histidine.

### Claim 20 (depends on 17)

The formulation of claim 17, wherein the sugar is sucrose.

### Claim 21 (depends on 20)

The formulation of claim 20, wherein the buffer system comprises succinate, acetate, or histidine.

### Claim 22 (depends on 17)

The formulation of claim 17, wherein the sugar alcohol is sorbitol.

### Claim 23 (depends on 22)

The formulation of claim 22, wherein the buffer system comprises succinate, acetate, or histidine.

### Claim 24 (depends on 17)

The formulation of claim 17, wherein the sugar alcohol is mannitol.

### Claim 25 (depends on 24)

The formulation of claim 24, wherein the buffer system comprises succinate, acetate, or histidine.

### Claim 26 (depends on 17)

The formulation of claim 17, wherein the buffer system comprises succinate, acetate, or histidine.

### Claim 27 (depends on 17)

The formulation of claim 17, wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.

### Claim 28 (depends on 1)

The formulation of claim 1, wherein the formulation comprises a preservative.

### Claim 29 (depends on 1)

The formulation of claim 1, wherein the formulation comprises a chelating agent.

### Claim 30 (depends on 1)

The formulation of claim 1, wherein the formulation comprises an antioxidant.