US009724303B2  (IO)  Patent No.:  US 9,724,303 B2  *  Aug. 8, 2017  (45)  Date of Patent:  c12)  United States Patent  Hong et al.  (54)  LIPOSOMES USEFUL FOR DRUG  DELIVERY  (71)  Applicant:  Ipsen Biopharm Ltd.,  Wrexham (GB)  (72)  Inventors:  Keelung Hong,  San Francisco, CA  (US);  Daryl C. Drummond,  Lincoln,  MA (US);  Dmitri Kirpotin,  Revere,  MA (US)  (73)  Assignee:  IPSEN BIOPHARM LTD.,  Wrexham  (GB)  ( *)  Notice:  Subject to any disclaimer, the term ofthis  patent is extended or adjusted under 35  U.S.C. 154(b) by  O  days.  This patent is subject to a terminal dis› claimer.  (21)  Appl. No.:  14/965,140  (22)  Filed:  Dec. 10, 2015  (60)  Continuation of application No. 14/632,422, filed on  Feb. 26, 2015, which is a division of application No.  (51)  Int. Cl.  (52)  U.S. Cl.  CPC ..........  A61K  911271  (2013.01);  A61K 9/0019  (2013.01);  A61K  91127  (2013.01);  (58)  Field of Classification Search  None  See application file for complete search history.  (65)  Prior Publication Data  Related U.S. Application Data  20 Claims, 29 Drawing Sheets  (57)  ABSTRACT  OTHER PUBLICATIONS  FOREIGN PATENT DOCUMENTS  U.S. PATENT DOCUMENTS  (56)  References Cited  (Continued)  US 2016/0095817 Al  Apr. 7, 2016  (Continued)  (Continued)  (Continued)  The present invention provides liposome compositions con› taining substituted ammonium and/or polyanion, and option› ally with a desired therapeutic or imaging entity. The present  invention also provide methods of making the liposome  compositions provided by the present invention.  Primary Examiner  - Isaac Shomer  (Continued)  T-H Chou, S-C Chen, I-M Chu. "Effect of Composition on the  Stability of Liposomal Irinotecan Prepared by a pH Gradient  Method." Journal of Bioscience and Bioengineering, vol. 95 No. 4,  2003, pp. 405-408.*  (74)  Attorney, Agent, or Firm  - Cynthia M. Bott;  Christopher C. Forbes; Honigman Miller Schwartz and  Cohn LLP  (Continued)  A61K  91127  A61K 9/00  (2006.01)  (2006.01)  CN  DE  1351495  4320597  10/2004  1/1995  4,192,869 A  4,321,259 A  3/1980 Nicolau et al.  3/1982 Nicolau et al.  3500  3000  ..,E  2500  E  Qi  E  2000  ::,  g  1500  a  E  1000  ::,  f- 500  0  -0-liposomes TEA-SOS.  50rnglkg  -+-Uposomes TEA-SOS, 25mgik9  .....o- Satine oonlwl  --free lrinolecan, 50 mg/kg  ......... liposomes,  1  EA-Pr>.  50mglkg  -¢---tiposomes. TEA-Pr>, 25m9/kg  10  20  30  40  50  Time posl tumor inoculation, days  60  70 