Granted Patent
B2
US 12,187,789 · App. 18/650,526 · Granted Jan 7, 2025
Biopharmaceutical compositions
Inventors:
Myrna A. Monck (Waltham, MA); Narendra B. Bam (King of Prussia, PA); Jennifer Dally (King of Prussia, PA); Michelle Spatara (King of Prussia, PA)
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Abstract
The present disclosure relates to compositions for treating interleukin 5 (IL-5) mediated diseases, and related methods.
Claims (66)
1. A composition comprising:
(a) mepolizumab comprising 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 mepolizumab wherein the acidic antibody variants comprise 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, except that residue N31 of SEQ ID NO: 2 is deamidated, and wherein said acidic variants are present in the composition in an amount from 3.3% to 17.4%, as determined by peptide mapping LC MS/MS.
2. The composition of claim 1 , wherein said acidic antibody variants are present in an amount from 5.8% to 6.5%, as determined by peptide mapping LC MS/MS.
3. The composition of claim 1 , further comprising (c) oxidized antibody variants of mepolizumab wherein the oxidized antibody variants comprise a heavy chain amino acid sequence as shown in SEQ ID NO: 1, except that residue M64 of SEQ ID NO: 1 is oxidized, and a light chain amino acid sequence as shown in SEQ ID NO: 2, wherein said oxidized variants are present in the composition in an amount from 0.5% to 50%, as determined by peptide mapping LC MS/MS.
4. The composition of claim 3 , wherein said (c) oxidized antibody variants are present in an amount of 50%, as determined by peptide mapping LC MS/MS.
5. The composition of claim 3 , wherein said (c) oxidized antibody variants are present in an amount from 0.7% to 1%, as determined by peptide mapping LC MS/MS.
6. The composition of claim 1 , further comprising (d) oxidized antibody variants of mepolizumab wherein the oxidized antibody variants comprise a heavy chain amino acid sequence as shown in SEQ ID NO: 1, except that residue W52 of SEQ ID NO: 1 is oxidized, and a light chain amino acid sequence as shown in SEQ ID NO: 2, wherein said (d) oxidized antibody variants are present in the composition in an amount from 0.1% to 3%, as determined by peptide mapping LC MS/MS.
7. The composition of claim 6 , wherein said (d) oxidized antibody variants are present in an amount of 3%, as determined by peptide mapping LC MS/MS.
8. The composition of claim 1 , wherein the composition comprises from 20% to 45% total acidic variants of mepolizumab, as measured using capillary isoelectric focusing.
9. The composition of claim 8 , wherein the composition comprises from 33% to 38% total acidic variants of mepolizumab, as measured by capillary isoelectric focusing.
10. The composition of claim 1 , wherein the composition comprises from 1% to 15% total basic variants of mepolizumab, as measured by capillary isoelectric focusing.
11. The composition of claim 10 , wherein the composition comprises from 1.2% to 4.9% total basic variants of mepolizumab, as measured by capillary isoelectric focusing.
12. The composition of claim 1 , wherein the composition comprises from 0.4% to 20% aggregate.
13. The composition of claim 12 , wherein the aggregate is dimer.
14. 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;
(b) a pH of between 6.8 and 7.2;
(c) a sugar;
(d) polysorbate 80; and
(e) EDTA.
15. 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;
(b) a pH of between 6.2 and 6.6;
(c) a sugar;
(d) polysorbate 80; and
(e) EDTA.
16. The composition of claim 1 , wherein the composition is an aqueous liquid formulation comprising:
a. 100 mg/ml mepolizumab and acidic antibody variants thereof;
b. 15.5 mM sodium phosphate dibasic heptahydrate and 4.5 mM citric acid at pH 6.2 to 6.6;
c. 12% sucrose;
d. 0.02% polysorbate 80; and
e. 0.05 mM EDTA.
17. The composition of claim 1 , wherein the composition is a lyophilized formulation comprising:
a. 100 mg/ml mepolizumab acidic and antibody variants thereof;
b. 20 mM sodium phosphate dibasic heptahydrate at pH 6.8 to 7.2;
c. 12% sucrose; and
d. 0.05% polysorbate 80.
18. A composition comprising:
(a) mepolizumab comprising 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) acidic antibody variants of mepolizumab wherein the acidic antibody variants comprise 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, except that residue N31 of SEQ ID NO: 2 is deamidated, and wherein said acidic variants are present in the composition in an amount from 3.3% to 17.4%, as determined by peptide mapping LC MS/MS;
(c) oxidized antibody variants of mepolizumab wherein the oxidized antibody variants comprise a heavy chain amino acid sequence as shown in SEQ ID NO: 1, except that residue M64 of SEQ ID NO: 1 is oxidized, and a light chain amino acid sequence as shown in SEQ ID NO:2, wherein said (c) oxidized variants are present in the composition in an amount from 0.5% to 50%, as determined by peptide mapping LC MS/MS; and
(d) oxidized antibody variants of mepolizumab wherein the oxidized antibody variants comprise a heavy chain amino acid sequence as shown in SEQ ID NO: 1, except that residue W52 of SEQ ID NO: 1 is oxidized, and a light chain amino acid sequence as shown in SEQ ID NO:2, wherein said (d) oxidized variants are present in the composition in an amount from 0.1% to 3%, as determined by peptide mapping LC MS/MS.
19. The composition of claim 18 , wherein the composition further comprises:
i. a buffering agent selected from the group consisting of sodium phosphate dibasic heptahydrate, phosphate, citrate, sodium phosphate, potassium phosphate, sodium citrate, and histidine;
ii. a pH of between 6.8 and 7.2;
iii. a sugar;
iv. polysorbate 80; and
v. EDTA.
20. The composition of claim 18 , 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;
(b) a pH of between 6.2 and 6.6;
(c) a sugar;
(d) polysorbate 80; and
(e) EDTA.
21. The composition of claim 18 , wherein the composition is an aqueous liquid formulation comprising:
a. 100 mg/ml mepolizumab and acidic antibody variants thereof;
b. 15.5 mM sodium phosphate dibasic heptahydrate and 4.5 mM citric acid at pH 6.3;
c. 12% sucrose;
d. 0.02% polysorbate 80; and
e. 0.05 mM EDTA.
22. The composition of claim 18 , wherein the composition is a lyophilized formulation comprising:
a. 100 mg/ml mepolizumab and antibody variants thereof;
b. 20 mM sodium phosphate dibasic heptahydrate at pH 6.8 to 7.2;
c. 12% sucrose; and
d. 0.05% polysorbate 80.
Assignments (5)
CHANGE OF ADDRESS
Recorded Apr 16, 2025
From: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED
Reel/Frame 070854/0469 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 24, 2024
From: MONCK, MYRNA A; BAM, NARENDRA B; DALLY, JENNIFER; SPATARA, MICHELLE
To: GLAXOSMITHKLINE LLC
Reel/Frame 068348/0239 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 24, 2024
From: GLAXOSMITHKLINE LLC
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO. 2) LIMITED
Reel/Frame 068348/0307 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 24, 2024
From: GLAXOSMITHKLINE LLC
To: GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LIMITED
Reel/Frame 068490/0192 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 24, 2024
From: GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LIMITED
To: GLAXOSMITHKLINE LLC
Reel/Frame 068490/0200 →
Continuity (10)
Division
15754768
Provisional Application
62249497
· Nov 2, 2015
Provisional Application
62247906
· Oct 29, 2015
Provisional Application
62240131
· Oct 12, 2015
Provisional Application
62209000
· Aug 24, 2015
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