US 12,226,524 B2
Coated implants for long-term controlled release of antibody therapeutics
Steven P. Schwendeman, Superior Township, MI (US); and Rae Sung Chang, Ann Arbor, MI (US)
Assigned to THE REGENTS OF THE UNIVERSITY OF MICHIGAN, Ann Arbor, MI (US)
Appl. No. 16/097,977
Filed by THE REGENTS OF THE UNIVERSITY OF MICHIGAN, Ann Arbor, MI (US)
PCT Filed May 2, 2017, PCT No. PCT/US2017/030642
§ 371(c)(1), (2) Date Oct. 31, 2018,
PCT Pub. No. WO2017/192590, PCT Pub. Date Nov. 9, 2017.
Claims priority of provisional application 62/330,592, filed on May 2, 2016.
Prior Publication US 2019/0151237 A1, May 23, 2019
Int. Cl. A61L 27/34 (2006.01); A61K 9/00 (2006.01); A61K 47/26 (2006.01); A61K 47/34 (2017.01); A61L 27/18 (2006.01); A61L 27/54 (2006.01); A61L 27/58 (2006.01); C07K 16/22 (2006.01)
CPC A61K 9/0051 (2013.01) [A61K 9/0024 (2013.01); A61K 47/26 (2013.01); A61K 47/34 (2013.01); A61L 27/18 (2013.01); A61L 27/34 (2013.01); A61L 27/54 (2013.01); A61L 27/58 (2013.01); C07K 16/22 (2013.01); A61L 2300/252 (2013.01); A61L 2300/256 (2013.01); A61L 2430/16 (2013.01); C07K 2317/24 (2013.01)] 35 Claims
 
1. A method of making an implant to deliver a monoclonal antibody to a tissue, comprising:
a. providing a powder composition comprising the monoclonal antibody;
b. combining the powder composition with a solution comprising a first biodegradable polymer containing lactic acid and/or glycolic acid repeat units in an organic solvent to make a suspension, wherein the suspension comprises the monoclonal antibody, the first biodegradable polymer, the organic solvent, a stabilizer comprising a water soluble saccharide, and a basic material, wherein the basic material has a solubility in water of 2×10−2 M or lower at room temperature,
C. drying the suspension to remove the organic solvent and form a core, wherein the core comprises about 5 to about 10 wt % of the monoclonal antibody, based on the total weight of the core; and
d. applying a coating of a second biodegradable polymer on the core effective to provide an implant having a release profile characterized by:
(i) a release of less than 20% of the total monoclonal antibody in the implant during the first 24 hours, relative to the total amount of monoclonal antibody in step (c), after incubating the implant with 1 mL of phosphate buffered saline with 0.02% polysorbate 80 at 37° C. with no agitation; and
(ii) a continuous release of at least 80% of the total monoclonal antibody in the implant over 42 days, relative to the total amount of the monoclonal antibody in step (c), after incubating the implant with 1 mL of phosphate buffered saline with 0.02% polysorbate 80 at 37° C. with no agitation;
wherein the second biodegradable polymer comprises lactic acid and/or glycolic acid repeat units.