	US 12,226,451 B2
	FGF-21 formulations
Thomas Palm, Helmetta, NJ (US); Mehrnaz Khossravi, West Windsor, NJ (US); and Sanket Patke, Belmont, MA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/257,530
Filed by Bristol-Myers Squibb Company, Princeton, NJ (US)
PCT Filed Jul. 2, 2019, PCT No. PCT/US2019/040356 § 371(c)(1), (2) Date Dec. 31, 2020, PCT Pub. No. WO2020/010117, PCT Pub. Date Jan. 9, 2020.
Claims priority of provisional application 62/693,847, filed on Jul. 3, 2018.
Prior Publication US 2021/0260161 A1, Aug. 26, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/18 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 47/22 (2006.01); A61K 47/26 (2006.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61K 47/64 (2017.01); A61K 47/68 (2017.01)

CPC A61K 38/1825 (2013.01) [A61K 9/0019 (2013.01); A61K 9/08 (2013.01); A61K 47/22 (2013.01); A61K 47/26 (2013.01); A61K 47/542 (2017.08); A61K 47/547 (2017.08); A61K 47/60 (2017.08); A61K 47/64 (2017.08); A61K 47/6811 (2017.08)]

4 Claims

1. A pharmaceutical formulation comprising:

(i) PEGylated FGF-21 polypeptide comprising the sequence set forth in SEQ ID NO: 2 (PEG-FGF-21) at a concentration of 20 mg/mL;

(ii) histidine at a concentration of 20 mM;

(iii) sucrose at a concentration of 600 mM;

(iv) Polysorbate 80 at a concentration of 0.05% (w/v); and

(v) Diethylenetriaminepentaacetic acid (DTPA) at a concentration of 50 μM;

(vi) wherein the pH is 7.1,

wherein DTPA functions as a structural stabilizer and the formulation exhibits:

(a) a lower rate of PEGylated FGF-21 polypeptide deamidation when stored at 40° C. for about a month with respect to a reference formulation without DTPA;

(b) a lower rate of high molecular weight (HMW) PEGylated FGF-21 polypeptide aggregation when stored at 40° C. for about a month with respect to the reference formulation without DTPA; or