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(12) United States Patent (10) Patent No.: US 9,358,282 B2 Cobbold Et Al

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(12) United States Patent (10) Patent No.: US 9,358,282 B2 Cobbold Et Al US009358282B2 (12) United States Patent (10) Patent No.: US 9,358,282 B2 Cobbold et al. (45) Date of Patent: *Jun. 7, 2016 (54) RE-DIRECTED IMMUNOTHERAPY CI2N 7/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/585 (2013.01); A61 K (71) Applicant: The University of Birmingham, 2039/6056 (2013.01); A61K 2039/627 Birmingham (GB) (2013.01); C07K 2317/24 (2013.01); C07K 2317/622 (2013.01); C07K 2319/33 (2013.01); (72) Inventors: Mark Cobbold, Birmingham (GB); C07K 2319/50 (2013.01); C12N 27.10/16134 David Millar, Birmingham (GB) (2013.01) (73) Assignee: As ther of Birmingham, (58) CPCField ....................of Classification A61K Search 47/48276; A61 K47/4833; A61K 47/48415: A61 K47/48584: A61 K (*) Notice: Subject to any disclaimer, the term of this 47/4863; A61 K 2039,505. A61 K 2039,585, patent is extended or adjusted under 35 A61K2037/6056; A61K 38/2026; CO7K U.S.C. 154(b) by 0 days. 16/2887; C07K 16/32: C07K 14/045 USPC .............. 424/178.1, 134.1, 133.1; 530/387.3, This patent is Subject to a terminal dis- 530/3917 claimer. See application file for complete search history. (21) Appl. No.: 14/660,137 (56) References Cited (22) Filed: Mar 17, 2015 U.S. PATENT DOCUMENTS (65) Prior Publication Data 5,585,089 A 12/1996 Queen et al. 5,693,762 A 12/1997 Queen et al. US 2015/O250868A1 Sep. 10, 2015 5,739,116 A 4, 1998 Hamann et al. 5,767.285 A 6/1998 Hamann et al. 5,773,001 A 6/1998 Hamann et al. Related U.S. ApplicationO O Data 6,896,881 B1* 5/2005 Russell ................ CO7K424,192.1 14,485 (63) Continuation of application No. 14/005,452, filed as 7,151,164 B2 * 12/2006 Hansen .............. 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A61K 47,484.84 C07K I4/005 (2006.01) 424,138.1 C07K 6/28 (2006.01) (Continued) A6 IK 45/06 (2006.01) A6 IK38/20 (2006.01) FOREIGN PATENT DOCUMENTS A 6LX39/395 (2006.01) A6 IK 39/245 (2006.01) EP O659438 A1 6, 1995 A6 IK 47/48 (2006.01) EP 19488O2 A1 T 2008 A6 IK 39/2 (2006.01) (Continued) A6C07K IK39/08 16/32 30:2006.O1 8: OTHER PUBLICATIONS A6 IK39/45 (2006.01) Cochran et al., J. Immunol. Meth. 287: 147-158, 2004.* A 6LX39/235 (2006.01) (Continued) CI2N 7/00 (2006.01) A61 K39/00 (2006.01) (52) U.S. Cl. Primary Examiner — Phuong Huynh CPC ............. A61K 39/245 (2013.01); A61K38/204 (74) Attorney, Agent, or Firm — McNeill Baur PLLC (2013.01); A61K38/2013 (2013.01); A61 K 38/2026 (2013.01); A61K 39/08 (2013.01); (57) ABSTRACT A61K 39/12 (2013.01); A61 K39/145 The invention provides an agent for preventing or treating a (2013.01); A61K 39/235 (2013.01); A61 K condition characterized by the presence of unwanted cells, 39/3955 (2013.01); A61K.39/39558 (2013.01); the agent comprising: (i) a targeting moiety that is capable of A61K 45/06 (2013.01); A61 K47/4833 targeting to the unwanted cells; and (ii) a T cell antigen, (2013.01); A61K 47/4863 (2013.01); A61 K wherein the T cell antigen can be released from the targeting 47/48276 (2013.01); A61K 47/48415 (2013.01); moiety by selective cleavage of a cleavage site in the agent in A61K 47/48584 (2013.01); C07K 14/005 the vicinity of the unwanted cells. (2013.01); C07K 16/2863 (2013.01); C07K 16/2887 (2013.01); C07K 16/32 (2013.01); 26 Claims, 20 Drawing Sheets US 9,358,282 B2 Page 2 (56) References Cited Plant, A. et al., “Phospholipid Alkanethiol Bilayers for Cell-Surface Receptor Studies by Surface Plasmon Resonance.” Analytical Bio U.S. PATENT DOCUMENTS chemistry, vol. 226, pp. 342-348 (1995). Ponde, D.E., et al., “Development of Anti-EGF Receptor 2010.0055761 A1* 3, 2010 Seed ................ A61K 47,48561 Peptidomimetics (AERP) as Tumor Imaging Agent. Bioorganic & 435.188 Medicinal Chemistry Letters 21:2550-2553 (2011). 2010, O1897.27 A1* 7, 2010 Rodeck .................. CO7K 14f71 Porcelli, S., et al., “Recognition of Cluster of Differentiation 1 Anti 424,178.1 gens by Human CD4-CD8-Cytolytic T Lymphocytes.” Nature 2011 OOO8840 A1 1/2011 Hoffee et al. 341:447-450 (1989). Rader, C., “DARTs Take Aim at BiTEs, Blood 1 17:4403-4404 FOREIGN PATENT DOCUMENTS (2011). 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