US 12,285,468 B2
Liquid neurotoxin formulation stabilized with tryptophan or tyrosine
Anders Jarstad, Uppsala (SE); Anna Friis, Uppsala (SE); Ulf Stahl, Uppsala (SE); Ann Gurell, Stockholm (SE); Barbro Agren, Mattmar (SE); Emilia Edstrom, Uppsala (SE); and Andrew Pickett, Uppsala (SE)
Assigned to IPSEN BIOPHARM LIMITED, Wrexham (GB)
Filed by IPSEN BIOPHARM LIMITED, Wrexham (GB)
Filed on Sep. 28, 2023, as Appl. No. 18/476,731.
Application 18/476,731 is a continuation of application No. 18/173,991, filed on Feb. 24, 2023, abandoned.
Application 18/173,991 is a continuation of application No. 17/304,888, filed on Jun. 28, 2021, abandoned.
Application 17/304,888 is a continuation of application No. 16/304,986, abandoned, previously published as PCT/EP2017/062785, filed on May 26, 2017.
Claims priority of application No. PCT/EP2016/062085 (WO), filed on May 27, 2016.
Prior Publication US 2024/0050539 A1, Feb. 15, 2024
Int. Cl. A61K 38/46 (2006.01); A61K 8/00 (2006.01); A61K 8/19 (2006.01); A61K 8/39 (2006.01); A61K 8/49 (2006.01); A61K 8/66 (2006.01); A61K 9/00 (2006.01); A61K 38/48 (2006.01); A61K 47/02 (2006.01); A61K 47/18 (2017.01); A61K 47/26 (2006.01); A61Q 19/08 (2006.01)
CPC A61K 38/4893 (2013.01) [A61K 8/00 (2013.01); A61K 8/19 (2013.01); A61K 8/39 (2013.01); A61K 8/492 (2013.01); A61K 8/66 (2013.01); A61K 9/0019 (2013.01); A61K 47/02 (2013.01); A61K 47/183 (2013.01); A61K 47/26 (2013.01); A61Q 19/08 (2013.01)] 16 Claims
 
1. A liquid composition comprising:
(i) 4 to 10,000 units/ml of a botulinum neurotoxin;
(ii) 0.01 to 1 vol % of a polysorbate;
(iii) an amino acid selected from tryptophan and tyrosine; and
(iv) a buffer comprising sodium, chloride, and phosphate ions,
wherein:
the liquid composition has a pH between 6.3 and 7.2 and is free of animal derived proteins;
the amino acid is present at a concentration of from about 0.25 mg/ml to about 5 mg/ml and protects the botulinum neurotoxin from degradation, thereby providing a liquid composition that is stable for at least 2 months at 2 to 8° C.; and
the composition does not comprise albumin, and
the composition comprises phosphate ions at 50 mM or greater.