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US 12,612,465 B2Granted
Formulations comprising PCSK9 specific monoclonal antibodies
AssigneeAmgen Inc.
InventorsChristi L. Clogston, Timothy David Osslund
Life of this patent
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Abstract
The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.
Claims47
A formulation comprising a monoclonal antibody that specifically binds to PCSK9, wherein PCSK9 comprises the amino acids of SEQ ID NO:
- 1, the monoclonal antibody in an amount of about 70 mg/ml to about 200 mg/ml, about 10 mM to about 20 mM sodium acetate buffer, a pharmaceutically acceptable surfactant in an amount that is about 0.004% to about 0.1% w/v, and at least one pharmaceutically acceptable stabilizer selected from the group consisting of:
- proline, arginine, lysine, methionine, benzyl alcohol, and taurine, in an amount of about 1% to about 5%, wherein the formulation has a pH of about 4.8 to about 5.8,
- wherein the monoclonal antibody comprises the light chain complementarity determining region one (CDRL1) sequence in SEQ ID NO:
- 23, the CDRL2 sequence in SEQ ID NO:
- 23, and of the CDRL3 sequence in SEQ ID NO:
- 23, and the heavy chain complementarity determining region one (CDRH1) sequence in SEQ ID NO:
- 49, the CDRH2 sequence in SEQ ID NO:
- 49 and the CDRH3 sequence in SEQ ID NO:
- 49.
6 more elements
A formulation comprising:
- (a) a monoclonal antibody in an amount of about 70 mg/ml to about 200 mg/ml, said monoclonal antibody comprising the light chain complementarity determining region one (CDRL1) sequence in SEQ ID NO:
- 23, the CDRL2 sequence in SEQ ID NO:
- 23, and the CDRL3 sequence in SEQ ID NO:
- 23, and the heavy chain complementarity determining region one (CDRH1) sequence in SEQ ID NO:
- 49, the CDRH2 sequence in SEQ ID NO:
- 49, and a the CDRH3 sequence in SEQ ID NO:49;
- (b) about 10 mM sodium acetate;
- (c) about 2.0% to about 3.0% w/v proline;
- (d) about 0.01% w/v polysorbate 20 or polysorbate 80, and
- (e) a pH of about 5.0.
7 more elements
A formulation comprising:
- (a) a monoclonal antibody in an amount of about 70 mg/ml to about 200 mg/ml, said monoclonal antibody comprising the light chain complementarity determining region one (CDRL1) sequence in SEQ ID NO:
- 23, the CDRL2 sequence in SEQ ID NO:
- 23, and the CDRL3 sequence in SEQ ID NO:
- 23, and the heavy chain complementarity determining region one (CDRH1) of the CDRH1 sequence in SEQ ID NO:
- 49, the CDRH2 sequence in SEQ ID NO:
- 49, and of the CDRH3 sequence in SEQ ID NO:49;
- (b) about 20 mM sodium acetate;
- (c) about 2.0% to about 3.0% w/v proline;
- (d) about 0.01% w/v polysorbate 80, and
- (e) a pH of about 5.0.
7 more elements
A formulation comprising:
- (a) a monoclonal antibody in an amount of about 120 mg/ml to about 140 mg/ml, said monoclonal antibody comprising:
- a light chain variable region comprising an amino acid sequence that is at least 97% identical to that of SEQ ID NO:
- 23, wherein the light chain variable region comprises:
- a complementarity determining region one (CDR1) comprising SEQ ID NO:
- 158;
- a CDR2 comprising SEQ ID NO:
- 162;
- and
- a CDR3 comprising SEQ ID NO:
- 395;
- a heavy chain variable region comprising an amino acid sequence that is at least 97% identical to that of SEQ ID NO:
- 49, wherein the heavy chain variable region comprises:
- a CDR1 comprising SEQ ID NO:
- 308;
- a CDR2 comprising SEQ ID NO:
- 175;
- and
- a CDR3 comprising SEQ ID NO:180;
- (b) about 20 mM sodium acetate;
- (c) about 2.0% to about 3.0% w/v proline;
- (d) about 0.01% w/v polysorbate 80;
- and
- (e) a pH of about 5.0.
20 more elements
A formulation comprising:
- (a) a monoclonal antibody in an amount of about 120 mg/ml to about 140 mg/ml, said monoclonal antibody comprising:
- a light chain comprising:
- a light chain variable region comprising-the amino acid sequence of a light chain variable region in SEQ ID NO:297;
- and
- a light chain constant region comprising the amino acid sequence of SEQ ID NO:
- 156;
- and
- a heavy chain comprising:
- a heavy chain variable region comprising-the amino acid sequence of a heavy chain variable region in SEQ ID NO:298;
- and
- a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:
- 154;
- (b) about 20 mM sodium acetate;
- (c) about 2.0% to about 3.0% w/v proline;
- (d) about 0.01% w/v polysorbate 80;
- and
- (e) a pH of about 5.0.
14 more elements
Dependencies are inferred from the claim text.