US009315567B2 (12) United States Patent (10) Patent No.: US 9,315,567 B2 Chang et al. (45) Date of Patent: *Apr. 19, 2016 (54) T-CELL REDIRECTING BISPECIFIC I6/2842 (2013.01); C07K 16/2845 (2013.01); ANTIBODES FORTREATMENT OF C07K 16/2851 (2013.01); C07K 16/2863 DISEASE (2013.01); C07K 16/2866 (2013.01); C07K 16/2875 (2013.01); C07K 16/2878 (2013.01); (71) Applicant: IBC Pharmaceuticals, Inc., Morris C07K 16/2884 (2013.01); C07K 16/2887 Plains, NJ (US) (2013.01); C07K 16/2893 (2013.01); C07K (72) Inventors: Chien-Hsing Chang, Downingtown, PA I6/2896 (2013.01); C07K 16/30 (2013.01); (US); David M. Goldenberg, Mendham, C07K 16/3007 (2013.01); C07K 16/32 NJ (US); Edmund A. Rossi, Woodland (2013.01); C07K 16/40 (2013.01); C07K 16/44 Park, NJ (US); Diane Rossi, Woodland (2013.01); A61K 2039/505 (2013.01); C07K Park, NJ (US) 2317/31 (2013.01); C07K 2317/54 (2013.01); C07K 231 7/55 (2013.01); C07K 2317/622 (73) Assignee: IBC Pharmaceuticals, Inc., Morris (2013.01); C07K 2317/73 (2013.01) Plains, NJ (US) (58) Field of Classification Search CPC ........ C07K 16/46; C07K 16/30; C07K 16/28; (*) Notice: Subject to any disclaimer, the term of this C07K 16/2809; C07K 2317/31: C07K patent is extended or adjusted under 35 2317/622; C07K 2317/54; C07K 2317/55; U.S.C. 154(b) by 0 days. C07K 2317/73; A61K 2317/00; A61K38/212: This patent is Subject to a terminal dis A61K2039/505; A61K 39/39958 claimer. See application file for complete search history. (21) Appl. No.: 13/966,450 (56) References Cited (22) Filed: Aug. 14, 2013 U.S. PATENT DOCUMENTS Prior Publication Data 4,046,722 A 9, 1977 Rowland (65) 4,699,784. A 10, 1987 Shih et al. US 2014/0050660 A1 Feb. 20, 2014 (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS (60) Provisional application No. 61/682.965, filed on Aug. WO 99.54440 10, 1999 14, 2012, provisional application No. 61/733,268, WO 00,068248 11, 2000 filed on Dec. 4, 2012, provisional application No. (Continued) 61/807,998, filed on Apr. 3, 2013. OTHER PUBLICATIONS (51) Int. C. Yu et al., Investigative Ophthalmology & Visual Science 49(2): 522 C07K I6/46 (2006.01) 527, Feb. 2008.* C07K 6/28 (2006.01) C07K 6/30 (2006.01) (Continued) A6 IK38/2I (2006.01) A 6LX39/395 (2006.01) Primary Examiner — Phuong Huynh C07K I6/44 (2006.01) (74) Attorney, Agent, or Firm — Richard A. Nakashima C07K 6/8 (2006.01) A6 IK 47/42 (2006.01) (57) ABSTRACT A6 IK 45/06 (2006.01) A6 IK38/9 (2006.01) The present invention concerns compositions and methods of C07K 6/40 (2006.01) use of T-cell redirecting complexes, with at least one binding C07K 16/32 (2006.01) site for a T-cell antigen and at least one binding site for an A61 K39/00 (2006.01) antigen on a diseased cell or pathogen. Preferably, the com (52) U.S. C. plex is a DNLTM complex. More preferably, the complex CPC ............... C07K 16/18 (2013.01); A61K 38/195 comprises a bispecific antibody (bSAb). Most preferably, the (2013.01); A61 K38/21 (2013.01); A61 K bSAb is an anti-CD3xanti-CD19 bispecific antibody, 38/212 (2013.01); A61 K38/215 (2013.01); although antibodies against other T-cell antigens and/or dis A61K38/217 (2013.01); A61K.39/395 ease-associated antigens may be used. The complex is (2013.01); A61 K39/39558 (2013.01); A61 K capable of targeting effector T cells to induce T-cell-mediated 45/06 (2013.01); A61 K47/42 (2013.01); C07K cytotoxicity of cells associated with a disease. Such as cancer, I6/283 (2013.01); C07K 16/2803 (2013.01); autoimmune disease or infectious disease. The cytotoxic C07K 16/2806 (2013.01); C07K 16/2809 immune response is enhanced by co-administration of inter (2013.01); C07K 16/289 (2013.01); C07K feron-based agents that comprise interferon-C. interferon-B, I6/281.2 (2013.01); C07K 16/2815 (2013.01); interferon-W1, interferon-M2 or interferon-M3. C07K 16/2818 (2013.01); C07K 16/2827 (2013.01); C07K 16/2833 (2013.01); C07K 10 Claims, 20 Drawing Sheets US 9,315,567 B2 Page 2 (56) References Cited Golay et al., Archives of Biochemistry and Biophysics 526: 146-153, 2012.* U.S. PATENT DOCUMENTS Davis et al., Clinical Cancer Research 6: 2644-2652, Jul. 2000. 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