US 12,404,344 B2
Low-viscosity, high concentration evolocumab formulations and methods of making the same
Christopher James Sloey, Newbury Park, CA (US); Sekhar Kanapuram, Thousand Oaks, CA (US); Huanchun Cui, Aesch (CH); Chio Mui Chan, Hillsboro, OR (US); and Elaheh Binabaji, Los Angeles, CA (US)
Assigned to AMGEN INC., Thousand Oaks, CA (US)
Filed by AMGEN INC., Thousand Oaks, CA (US)
Filed on Aug. 23, 2022, as Appl. No. 17/893,515.
Application 17/893,515 is a division of application No. 15/902,775, filed on Feb. 22, 2018, granted, now 11,464,857.
Claims priority of provisional application 62/462,266, filed on Feb. 22, 2017.
Prior Publication US 2023/0226177 A1, Jul. 20, 2023
Int. Cl. C07K 16/40 (2006.01); A61K 39/395 (2006.01); A61K 47/18 (2017.01); C07K 1/34 (2006.01); C07K 16/06 (2006.01); A61K 9/00 (2006.01); C07K 1/16 (2006.01); C07K 1/36 (2006.01); C07K 16/22 (2006.01)
CPC C07K 16/40 (2013.01) [C07K 1/34 (2013.01); C07K 16/065 (2013.01); A61K 9/0019 (2013.01); A61K 39/3955 (2013.01); A61K 39/39591 (2013.01); A61K 47/183 (2013.01); C07K 1/16 (2013.01); C07K 1/36 (2013.01); C07K 16/22 (2013.01); C07K 2317/565 (2013.01); C07K 2317/76 (2013.01); C07K 2317/90 (2013.01)] 12 Claims
 
1. A method of formulating a therapeutic polypeptide, comprising
a. a first concentration step, wherein the polypeptide in a first solution is concentrated;
b. a first solution exchange step, wherein the concentrated polypeptide in the first solution is exchanged into a second solution comprising N-acetyl arginine using diafiltration;
c. a second concentration step, wherein the polypeptide in the second solution is concentrated;
d. a second solution exchange step, wherein the polypeptide in the concentrated second solution is exchanged into a third solution comprising N-acetyl arginine using diafiltration; and
e. a third concentration step, wherein the polypeptide in the third solution is concentrated;
wherein the therapeutic polypeptide comprises (A) an antibody:
heavy chain having an amino acid sequence of SEQ ID NO:1 and an antibody light chain having an amino acid sequence of SEQ ID NO:2; or
(B) an antibody heavy chain comprising the following complementarity determining regions (CDRs): a heavy chain CDR1 that is a CDR1 in SEQ ID NOs:14 or 16; a heavy chain CDR2 that is a CDR2 in SEQ ID NOs:14 or 16; a heavy chain CDR3 that is a CDR3 in SEQ ID NOs:14 or 16, and
an antibody light chain comprising the following CDRs: a light chain CDR1 that is a CDR1 in SEQ ID NOs:15 or 17; a light chain CDR2 that a CDR2 in SEQ ID NOs:15 or 17; and a light chain CDR3 that a CDR3 in SEQ ID NOs:15 or 17.