# US 11,299,541 B2 · Biopharmaceutical compositions

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

- Number: US 11,299,541 B2
- Document ID: US11299541B2
- Status: Granted
- Kind: B2
- Application number: 17/373,537
- Filed: 2021-07-12
- Published: 2021-10-28
- Granted: 2022-04-12
- Earliest claimed: 2015-08-24
- Assignees: Glaxosmithkline Intellectual Property (No.2) Limited
- Applicants: Glaxosmithkline Intellectual Property (No. 2) Limited
- Inventors: Myrna A. Monck; Narendra B. Bam; Jennifer Dally; Michelle Spatara
- Web page: https://patentgrep.com/patent/US11299541B2

## CPC

- C07K 16/244: {Interleukins [IL]}
- A61K 39/39591: {Stabilisation, fragmentation}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/40: characterized by post-translational modification
- C07K 2317/90: characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to compositions, for treating interleukin 5 (IL-5) mediated diseases, and related methods.

## Claims

### Claim 1

A composition comprising:
a) an anti-IL-5 antibody having a heavy chain amino acid sequence as shown in SEQ ID NO: 1 and a light chain amino acid sequence as shown in SEQ ID NO: 2, and
b) acidic antibody variants of the anti-IL-5 antibody wherein ≤80% of antibodies in the composition are the acidic antibody variants, wherein the acidic antibody variants comprises:
SEQ ID NO: 1, except that residue N386 of Seq ID NO: 1 is deamidated, or
SEQ ID NO: 2, except that residue N31 of Seq ID NO: 2 is deamidated, or a combination thereof.

### Claim 2 (depends on 1)

The composition of claim 1, wherein ≤75% of the antibodies in the composition are the acidic antibody variants.

### Claim 3 (depends on 1)

The composition of claim 1, wherein 20% to 80% or 20% to 45% of the antibodies in the composition are the acidic antibody variants.

### Claim 4 (depends on 1)

The composition of claim 1, wherein 1% to 15% of the antibodies in the composition are basic antibody variants.

### Claim 5 (depends on 1)

The composition of claim 1, wherein residue N31 of Seq ID NO: 2 is deamidated in ≤25% of the antibodies in the composition.

### Claim 6 (depends on 5)

The composition of claim 5, wherein residue N31 of Seq ID NO: 2 is deamidated in: ≤22.5%, ≤20%, ≤17.5%, ≤15%, ≤12.5, ≤10%, or ≤7.5% of the antibodies in the composition.

### Claim 7 (depends on 1)

The composition of claim 1, wherein residue N386 of Seq ID NO: 1 is deamidated in ≤35% of the antibodies in the composition.

### Claim 8 (depends on 1)

The composition of claim 1, wherein residue M64 of Seq ID NO: 1 is oxidized in ≤50% of the antibodies in the composition and residue W52 of Seq ID NO: 1 is oxidized in ≤3% of the antibodies in the composition.

### Claim 9 (depends on 1)

The composition of claim 1, wherein residue M254 of Seq ID NO: 1 is oxidized in ≤50% of the antibodies in the composition, residue M360 of Seq ID NO: 1 is oxidized in ≤50% of the antibodies in the composition, and residue M430 of Seq ID NO: 1 is oxidized in ≤50% of the antibodies in the composition.

### Claim 10 (depends on 1)

The composition of claim 1, wherein ≥50% of the antibodies in the composition comprises SEQ ID NO: 1 except that C-terminal lysine K449 is deleted.

### Claim 11 (depends on 1)

The composition of claim 1, wherein ≥50% of the antibodies in the composition comprises a pyro-glutamate N-terminal.

### Claim 12 (depends on 1)

The composition of claim 1, wherein ≤20% of the antibodies in the composition are aggregated antibody variants.

### Claim 13 (depends on 1)

The composition of claim 1, wherein an antibody variants is measured using capillary isoelectric focusing of the composition.

### Claim 14 (depends on 1)

The composition of claim 1, wherein the antibodies in the composition is at a concentration of between 75 mg/ml and 100 mg/ml.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the composition further comprises:
a) a buffering agent selected from the group consisting of sodium phosphate dibasic heptahydrate, phosphate, citrate, sodium phosphate, potassium phosphate, sodium citrate, and histidine, providing a pH of between 6.8 and 7.2 or a pH of between 6.2 and 6.6;
b) a sugar;
c) polysorbate 80;
d) EDTA; or
e) a combination thereof.

### Claim 16 (depends on 1)

The composition of claim 1, wherein the composition comprises an aqueous liquid formulation comprising:
a) 100 mg/ml antibody;
b) 15.5 mM sodium phosphate dibasic heptahydrate and 4.5 mM citric acid monohydrate at pH 6.3;
c) 12% weight of sucrose to volume;
d) 0.02% weight of polysorbate 80 to volume; and
e) 0.05 mM EDTA.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the composition is lyophilized and comprises:
a) 100 mg/mL antibody;
b) 20 mM sodium phosphate dibasic heptahydrate at pH 6.8 to 7.2;
c) 12% weight of sucrose to volume; and
d) 0.05% weight of polysorbate 80 to volume.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the composition has at least 0.70 IL-5 specific antigen binding activity or at least 70% FcRn binding activity, compared with a reference standard composition, the reference standard composition comprising:
a) an antibody having a heavy chain amino acid sequence as shown in SEQ ID NO: 1 and a light chain amino acid sequence as shown in SEQ ID NO:2;
b) 98% or more heavy chain C-terminal lysine deleted variant;
c) 95% or more heavy chain N-terminal pyroglutamate variant;
d) 6% or less deamidated variant;
e) 4% or less methionine or cysteine oxidated variant;
f) 0.1% or less tryptophan oxidated variant; and
g) 0.4% or less aggregated antibody variant.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising the composition of claim 1, and a pharmaceutically acceptable carrier.