USO09554989B2 (12) United States Patent (10) Patent No.: US 9,554,989 B2 Kaplan et al. (45) Date of Patent: *Jan. 31, 2017 (54) SILK RESERVOIRS FOR DRUG DELIVERY 3,773.919 A 11/1973 Boswell 4,806,355 A 2f1989 Goosen et al. (71) Applicant: RSTEES OF TUF is COLLEGE, 5,093,4895,015,476 A 3/19925/1991 CochrumDiamantoglou et al. edIOrd, (US) 5,263,992 A 11/1993 Guire 5,270,419 A 12, 1993 Domb (72) Inventors: David L. Kaplan, Concord, MA (US); 5,538,735 A 7, 1996 Ahn Tuna Yucel, Medford, MA (US); 5,576,881 A 11/1996 Doerr et al. Michael L. Lovett, Peabody, MA (US); 386 A 58. l al Xiaoqin Wang, Winchester, MA (US) 6,127,143- W4- A 10/2000 Gunasekarana 6,245,537 B1 6/2001 Williams et al. (73) Assignee: Trustees of Tufts College, Medford, 6,267,776 B1 7/2001 O'Connell MA (US) 6,302,848 B1 10/2001 Larson et al. 6,310,188 B1 10/2001 Mukherjee (*)c Notice:- r Subject to any site the still 6,337,1986,325,810 B1 12/20011/2002 LeveneHamilton et etal. al. patent 1s extended or adjusted under 6,372,244 B1 4/2002 Antanavich et al. U.S.C. 154(b) by 0 days. 6,379,690 B2 4/2002 Blanchard et al. 6,395,734 B1 5, 2002 Tang et al. This patent is Subject to a terminal dis- 7,842,780 B2 11/2010 Rii. et al. claimer. 8, 178,656 B2 5/2012 Kaplan et al. 8, 187.616 B2 5/2012 Wang et al. (21) Appl. No.: 14/386,545 2002/0028243 A1 3/2002 Masters 2003/OOOT991 A1 1/2003 Masters 1-1. 2007/0212730 A1 9/2007 Vepari et al. (22) PCT Filed: Mar. 11, 2013 2008/0085272 A1 4/2008 Kaplan et al. 2009, 0232963 A1 9/2009 Kaplan et al. (86). PCT No.: PCT/US2O13/O3O2O6 2009,0263430 A1 10, 2009 Scheibel et al. S 371 (c)(1), 2009,0263460 A1 10, 2009 McDonald (2) Date: Sep. 19, 2014 (Continued) (87) PCT Pub. No.: WO2013/142119 FOREIGN PATENT DOCUMENTS PCT Pub. Date: Sep. 26, 2013 WO WO-93.11161 A1 6, 1993 WO WO-2005/O12606 A2 2, 2005 (65) Prior Publication Data (Continued) US 2015/OO45764 A1 Feb. 12, 2015 OTHER PUBLICATIONS Related U.S. Application Data Acharya, C. et al., Performance evaluation of a silk protein-based (60) Provisional application No. 61/613,185, filed on Mar. matrix for the enzymatic conversion of tyrosine to -DOPA. 20, 2012. Biotechnol. J., 3:226-233 (2008). Bayraktar, O. et al., Silk fibroin as a novel coating material for (51) Int. Cl. controlled release of theophylline, European Journal of A6 IK 9/00 (2006.01) Pharmaceutics and Biopharmaceutics, 60:373-381 (2005). A 6LX 9/50 (2006.01) Beaucage, S. L. and Iyer, R. P. The Functionalization of Oligo A6 IK3I/00 (2006.01) nucleotides Via Phosphoramidite Derivatives, Tetrahedron Report No. 329, 49(10): 1925-1963 (1993). 3. t3. 3. Chothia, C. and Lesk, A. M., Canonical Structures for the ( .01) Hypervariable Regions of Immunoglobulins, J. Mol. Biol. 196:901 A6 IK3I/545 (2006.01) 917 (1987). (52) U.S. Cl. Demura, M and Asakura, T., Immobilization of Glucose Oxidase CPC ........... A61K 9/0024 (2013.01); A61K 9/0019 with Bombyx mori Silk Fibroin by Only Stretching Treatment and (2013.01); A61K 9/0092 (2013.01); A61 K Its Application to Glucose Sensor, 33 Biotech Bioengin., 33:598 9/4825 (2013.01); A61K 9/5052 (2013.01); (1989). A6 IK3I/00 (2013.01); A61K 31/13 (2013.01); (Continued) A61K 3.1/5415 (2013.01) (58) Field of Classification Search Primary Examiner — Robert A Wax CPC ... A61 K9/0024; A61K 9/0092: A61K 31/00; Assistant Examiner — Olga V Tcherkasskaya A61K 31/13; A61K 31/4196; A61 K (74) Attorney, Agent, or Firm — Brenda Herschbach 31/4402: A61K 3.1/5415: A61 K Jarrell; Brian E. Reese; Choate, Hall & Stewart LLP 47/42: A61 K9/0019; A61 K 9/70 See application file for complete search history. 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