US009717723B2  c12)  United States Patent  Hong et al.  (IO)  Patent No.:  US 9,717,723 B2  (45)  Date of Patent:  *  Aug. 1, 2017  (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.:  14/632,422  (22)  Filed:  Feb. 26, 2015  (63)  Continuation of application No. 14/175,365, filed on  Feb. 7, 2014, now Pat. No. 8,992,970, which is a  (51)  Int. Cl.  (52)  U.S. Cl.  CPC ........  A61K  3114745  (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  19 Claims, 29 Drawing Sheets  (57)  ABSTRACT  OTHER PUBLICATIONS  FOREIGN PATENT DOCUMENTS  (56)  References Cited  U.S. PATENT DOCUMENTS  (Continued)  (Continued)  US 2015/0182460 Al  Jul. 2, 2015  (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 provides methods of making the liposome  compositions provided by the present invention.  Primary Examiner  - Isaac Shomer  (Continued)  T-H Chou, S-C Shen, 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  A61K  91127  A61K  3114745  (2006.01)  (2006.01)  4,192,869 A  4,321,259 A  3/1980 Nicolau et al.  3/1982 Nicolau et al.  CN  EP  1351495  10/2004  1 121 102 Bl  8/1992  3500  3000  ,.,  2500  E  (U  2000  E  :::i  g  1500  ’"  €  iOOO  :::i  ...  500  0  --0--liposomes  TEA-SOS. 50mglkg  --+--Uposo,11es lEA-$0S, 25mglkg  -o- Saline conuol  ---F,ee lrmolecan, $0 mg/kg  ---Uposvmes, TEA-Pr>, SOmglkg  -¢--Uposomes. lEA-Pn, 2Srnglkg  10  20  30  40  50  Time posl tumor inoculation, days  60  70 