# US 2010/0166752 A1 · Anti A Beta Antibody Formulation

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

- Number: US 2010/0166752 A1
- Document ID: US20100166752A1
- Status: Published application
- Kind: A1
- Application number: 12/637,508
- Filed: 2009-12-14
- Published: 2010-07-01
- Earliest claimed: 2005-01-28
- Assignees: Janssen Alzheimer Immunotherapy; Wyeth
- Inventors: Nicholas W. Warne; Donna Luisi; Angela Kantor
- Web page: https://patentgrep.com/patent/US20100166752A1

## CPC

- 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 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 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/4172: Imidazole-alkanecarboxylic acids, e.g. histidine
- A61K 39/39591: {Stabilisation, fragmentation}
- A61K 47/02: Inorganic compounds
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- 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 37/00: Drugs for immunological or allergic disorders
- C07K 16/18: against material from animals or humans
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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)

## Abstract

The present invention provides formulations for maintaining the stability of Aβ binding polypeptides, for example, Aβ antibodies. Exemplary formulations include a tonicity agent such as mannitol and a buffering agent or amino acid such as histidine. Other exemplary formulations include an antioxidant in a sufficient amount as to inhibit by-product formation, for example, the formation of high molecular weight polypeptide aggregates, low molecular weight polypeptide degradation fragments, and mixtures thereof. The formulations of the invention optionally comprise a tonicity agent, such as mannitol, and a buffering agent or amino acid such as histidine. The formulations are suitable for several different routes of administration.

## Claims

### Claim at position 1

1-86. (canceled)

### Claim 87

A stable formulation, comprising:
(a) a humanized 3D6 antibody or antigen binding fragment thereof at a concentration of from about 1 mg/ml to about 100 mg/ml, wherein the humanized antibody or antigen binding fragment comprises a light chain variable region having an amino acid sequence as set forth in residues 1-112 of SEQ ID NO:1 and a heavy chain variable region having an amino acid sequence as set forth in residues 1-119 of SEQ ID NO:2;
(b) histidine at a concentration of from about 5 mM to about 15 mM;
(c) mannitol in an amount of from about 2% w/v to about 6% w/v;
(d) methionine at a concentration of from about 5 mM to about 15 mM; and
(e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v,
wherein the formulation has a pH of from about 5.5 to about 6.5.

### Claim 88 (depends on 87)

The formulation of claim 87, wherein the histidine is present at a concentration of from 8 mM to 12 mM.

### Claim 89 (depends on 88)

The formulation of claim 88, wherein the mannitol is present in an amount of from 3% w/v to 5% w/v.

### Claim 90 (depends on 89)

The formulation of claim 89, wherein the methionine is present at a concentration of from 8 mM to 12 mM.

### Claim 91 (depends on 90)

The formulation of claim 90, wherein the polysorbate is present in an amount of from 0.003% w/v to 0.007% w/v.

### Claim 92 (depends on 91)

The formulation of claim 91, wherein the pH is from 5.8 to 6.2.

### Claim 93 (depends on 92)

The formulation of claim 92, wherein the antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.

### Claim 94 (depends on 92)

The formulation of claim 92, wherein the antibody is present at a concentration of from about 75 mg/ml to about 100 mg/ml.

### Claim 95 (depends on 87)

The formulation of claim 87, further comprising about 2% sucrose.

### Claim 96

A stable unit dosage form, comprising:
(a) a humanized 3D6 antibody or antigen binding fragment thereof in an amount of from about 10 mg to about 250 mg, wherein the humanized antibody or antigen binding fragment comprises a light chain variable region having an amino acid sequence as set forth in residues 1-112 of SEQ ID NO:1 and a heavy chain variable region having an amino acid sequence as set forth in residues 1-119 of SEQ ID NO:2;
(b) histidine at a concentration of from about 5 mM to about 15 mM;
(c) mannitol in an amount of from about 2% w/v to about 6% w/v;
(d) methionine at a concentration of from about 5 mM to about 15 mM; and
(e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v,
at a pH of from about 5.5 to about 6.5.

### Claim 97 (depends on 96)

The unit dosage form of claim 96, wherein the antibody is present in an amount of from 80 mg to 120 mg.

### Claim 98 (depends on 97)

The unit dosage form of claim 97, wherein the histidine is present at a concentration of from 8 mM to 12 mM.

### Claim 99 (depends on 98)

The unit dosage form of claim 98, wherein the mannitol is present in an amount of from 3% w/v to 5% w/v.

### Claim 100 (depends on 99)

The unit dosage form of claim 99, wherein the methionine is present at a concentration of from 8 mM to 12 mM.

### Claim 101 (depends on 100)

The unit dosage form of claim 100, wherein the polysorbate is present in an amount of from 0.003% w/v to 0.007% w/v.

### Claim 102 (depends on 101)

The unit dosage form of claim 101, wherein the pH is from 5.8 to 6.2.

### Claim 103 (depends on 96)

The unit dosage form of claim 96, wherein the antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.

### Claim 104 (depends on 96)

The unit dosage form of claim 96, wherein the antibody is present at a concentration of from about 75 mg/ml to about 100 mg/ml.

### Claim 105 (depends on 96)

The unit dosage form of claim 96, further comprising about 2% sucrose.

### Claim 106

A pharmaceutical product, comprising:
(i) a glass vial comprising a stable humanized 3D6 antibody formulation, the formulation comprising:
(a) a humanized 3D6 antibody or antigen binding fragment thereof in an amount of from about 10 mg to about 250 mg, wherein the humanized antibody or antigen binding fragment comprises a light chain variable region having an amino acid sequence as set forth in residues 1-112 of SEQ ID NO:1 and a heavy chain variable region having an amino acid sequence as set forth in residues 1-119 of SEQ ID NO:2;
(b) histidine at a concentration of from about 5 mM to about 15 mM;
(c) mannitol in an amount of from about 2% w/v to about 6% w/v;
(d) methionine at a concentration of from about 5 mM to about 15 mM; and
(e) polysorbate in an amount of from about 0.001% w/v to about 0.01% w/v,
wherein the formulation has a pH of from about 5.5 to about 6.5; and
(ii) labeling for use comprising instructions to use the appropriate volume of the antibody formulation necessary to achieve a dose of from about 0.01 mg to about 5 mg per kg of patient body weight.

### Claim 107 (depends on 106)

The pharmaceutical product of claim 106, wherein the antibody is present in an amount of from 80 mg to 120 mg.

### Claim 108 (depends on 107)

The pharmaceutical product of claim 107, wherein the histidine is present at a concentration of from 8 mM to 12 mM.

### Claim 109 (depends on 108)

The pharmaceutical product of claim 108, wherein the mannitol is present in an amount of from 3% w/v to 5% w/v.

### Claim 110 (depends on 109)

The pharmaceutical product of claim 109, wherein the methionine is present at a concentration of from 8 mM to 12 mM.

### Claim 111 (depends on 110)

The pharmaceutical product of claim 110, wherein the polysorbate is present in an amount of from 0.003% w/v to 0.007% w/v.

### Claim 112 (depends on 111)

The pharmaceutical product of claim 111, wherein the pH is from 5.8 to 6.2.

### Claim 113 (depends on 112)

The pharmaceutical product of claim 112, wherein the dose is from about 0.15 mg to about 3 mg per kg of patient body weight.

### Claim 114 (depends on 113)

The pharmaceutical product of claim 113, wherein the dose is from about 0.5 mg to about 2 mg per kg of patient body weight.

### Claim 115 (depends on 106)

The pharmaceutical product of claim 106, wherein the antibody is present at a concentration of from about 17 mg/ml to about 23 mg/ml.

### Claim 116 (depends on 106)

The pharmaceutical product of claim 106, wherein the antibody is present at a concentration of from about 75 mg/ml to about 100 mg/ml.

### Claim 117 (depends on 106)

The pharmaceutical product of claim 106, wherein the formulation further comprises about 2% sucrose.