United States Patent (10) Patent No.: US 9,624,276 B2 Young Et Al

United States Patent (10) Patent No.: US 9,624,276 B2 Young Et Al

USOO9624276B2 (12) United States Patent (10) Patent No.: US 9,624,276 B2 Young et al. (45) Date of Patent: Apr. 18, 2017 (54) PEPTIDIC CHIMERIC ANTIGEN RECEPTOR 7,258,986 B2 8/2007 Maur et al. T CELL, SWITCHES AND USES THEREOF 7,446,190 B2 11/2008 Sadelain et al. 7,514,537 B2 4/2009 Jensen 8,802.374 B2 8, 2014 Jensen (71) Applicant: The California Institute for 8,916,381 B1 12/2014 June et al. Biomedical Research, La Jolla, CA 2004/0044177 A1 3/2004 Macke et al. (US) 2004f0072299 A1* 4, 2004 Gillies ................. A61K 38, 193 435/695 (72) Inventors: Travis Young, La Jolla, CA (US); 2839; ;: A. 258 at al. Chanhyuk Kim, San Diego, CA (US); ck ooper et al. Peter G. Schultz, La Jolla, CA (US) 2006/0083683 A1* 4/2006 HSei ................... Aikip3. 2007/01725.04 A1 7/2007 Shirwan et al. (73) Assignee: The California Institute for 2008/0260731 A1* 10, 2008 Bernett .............. CO7K 16,2803 Biomedical Research, La Jolla, CA 424,133.1 (US) 2009/0117108 A1 5/2009 Wang et al. 2010/0178276 A1* 7, 2010 Sadelain ............ A61K 39.0011 (*)c Notice:- r Subject to any site- the still 2010/0278830 A1 11/2010 Shoemaker et al. 424,93.7 patent is extended or adjusted under 35 2010, O297076 A1* 11, 2010 Morrison ............. A61K 38,212 U.S.C. 154(b) by 0 days. 424,856 2010/0324008 A1 12/2010 Low et al. (21) Appl. No.: 14/688,894 2012.0034223 A1 2/2012 Hall et al. 2012fO213783 A1 8/2012 Rosenberg et al. 1-1. 2014f0065171 A1 3/2014 Geierstanger et al. (22) Filed: Apr. 16, 2015 2014/0234348 A1 8/2014 Scholler et al. (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2015/0307564 A1 Oct. 29, 2015 DE WO 2008O25558 A2 * 3, 2008 ...... CO7K 14.f4702 WO WO 97.15669 A1 5, 1997 Related U.S. Application Data WO WO 2004/10638O 12, 2004 WO WO 2007/059312 5/2007 (63) Continuation of application No. WO WO 2007/07O659 6, 2007 PCT/US2014/060684, filed on Oct. 15, 2014. WO WO 2007/079 130 7/2007 WO WO 2007/094916 8, 2007 WO WO 2008/O77O79 6, 2008 (60) gril applier Neil S.S. WO WO 2008.083346 T 2008 s provisional application No. 04/u3U,340, WO WO 2010/037062 4/2010 filed on Jul. 29, 2014, provisional application No. (Continued) 62/009,054, filed on Jun. 6, 2014, provisional application No. 61/895,704, filed on Oct. 25, 2013, provisional application No. 61/891.347, filed on Oct. OTHER PUBLICATIONS 15, 2013. Murphy et al., Proc. Amer. Assoc. Cancer Res., 2005, 46, abstract 51) Int. C No. 1495. (51) Int. Cl. U.S. Appl. No. 14/432,065 Restriction Requirement Mailed Nov. 6, C07K I4/395 (2006.01) 2015. C07K I4/00 (2006.01) U.S. Appl. No. 14/432,065, Travis Young. C07K 6/00 (2006.01) AXup, J. et al., Synthesis of site-specific antibody-drug conjugates A6 IK 39/00 (2006.01) using unnatural amino acids. PNAS. 2012, pp. 16101-16106, vol. CI2N 5/10 (2006.01) 109, No. 40. C07K 9/00 (2006.01) Baeuerle, P.A., P. Kufer, and R. Bargou, BiTE: Teaching antibodies CI2N 5/0783 (2010.01) to engage T-cells for cancer therapy. Curr Opin Mol Ther, 2009. pp. 22-30, vol. 11, Issue No. 1. A61 K 38/00 (2006.01) Beers, S.A., et al., Antigenic modulation limits the efficacy of (52) U.S. Cl. anti-CD20 antibodies: implications for antibody selection. Blood, CPC .......... C07K 14/395 (2013.01); C12N5/0636 Jun. 24, 2010. pp. 5191-5201, vol. 115, Issue No. 25. (2013.01); A6 IK 38/00 (2013.01); C07K Bibl. M., et al., Stability of amyloid-beta peptides in plasma and 2319/01 (2013.01); C07K 2319/30 (2013.01) serum. Electrophoresis, 2012. pp. 445-450, vol. 33, Issue No. 3. (58) Field of Classification Search (Continued) NoneSee application file for complete search history. Pririmary ExaminerE iner — Hong9. San9. (57) ABSTRACT (56) References Cited Disclosed herein are chimeric antigen receptor effector cells U.S. PATENT DOCUMENTS (CAR-ECs) and CAR-EC switches. The switchable CAR ECs are generally T cells. The one or more chimeric antigen 5,372,930 A 12/1994 Colton et al. receptors may recognize a peptidic antigen on the CAR-EC 5,861,156 A 1/1999 George et al. switch. The CAR-ECs and switches may be used for the 5,906,936 A 5, 1999 Eshhar et al. treatment of a condition in a Subject in need thereof. 5,912, 172 A 6, 1999 Eshhar et al. 6,083,751 A 7/2000 Feldhaus et al. 25 Claims, 8 Drawing Sheets US 9,624,276 B2 Page 2 (56) References Cited Cole, D.K., et al. The molecular determinants of CD8 co-receptor function. Immunology, Oct. 2012. pp. 139-148, vol. 137, No. 2. Cui et al. Chemically programmed bispecific antibodies that recruit FOREIGN PATENT DOCUMENTS and activate T cells. Journal of Biological Chemistry, 2012, pp. WO WO 2011/028195 3, 2011 28206-28214, vol. 287, No. 34. WO WO 2012/031744 3, 2012 Davila, M.L., et al., CD19 CAR-targeted T cells induce long-term WO WO 2012/079000 6, 2012 remission and B Cell Aplasia in an immunocompetent mouse model WO WO 2012/082841 6, 2012 of B cell acute lymphoblastic leukemia. PLoS One, 2013. p. e61338, WO WO 2012082841 A2 * 6, 2012 ......... CO7K 16,2863 vol. 8 No. 4. WO WO 2012,166.559 12/2012 WO WO 2012, 166560 12/2012 Davis, T.A., et al., Therapy of B-cell lymphoma with anti-CD20 WO WO 2013/O19615 2, 2013 antibodies can result in the loss of CD20 antigen expression. Clin WO WO 2013/044225 3, 2013 Cancer Res, 1999. pp. 611-615, vol. 5, No. 3. WO WO 2013/093809 6, 2013 Dubrovska, A., et al. A chemically induced vaccine strategy for WO WO 2013/123061 8, 2013 prostate cancer. ACS Chem Biol. 2011. pp. 1223-1231, vol. 6, No. WO WO 2014/100615 6, 2014 11. WO WO 2014/1530O2 9, 2014 Gavrilyuk, et al. B-Lactam-based Approach for the Chemical Pro WO WO 2014/153164 9, 2014 gramming of Aldolase Antibody 38C2. Bioorg Med Chem Lett. Mar. 1, 2009, pp. 1421-1424, vol. 19, No. 5, e-pub Jan. 15, 2009. OTHER PUBLICATIONS GenBank Accession No. AB064051: Homo sapiens IGK mRNA for Bluemel, C., et al., Epitope distance to the target cell membrane and immunoglobulin kappa light chain VLJ region, partial cods, clone: antigen size determine the potency of T cell-mediated lysis by BiTE K10. Jul. 2, 2002. antibodies specific for a large melanoma Surface antigen. Cancer Gilham et al., CAR-T cells and solid tumors: tuning T cells to Immunol Immunother, 2010. pp. 1197-1209, vol. 59, Issue No. 8. challenge an inveterate foe, Trends in Molecular Medicine, 2012, Boder, E.T., K.S. Midelfort, and K.D. Wittrup, Directed evolution of pp. 377-384, vol. 18, No. 7. antibody fragments with monovalent femtomolar antigen-binding Grada et al., TanCAR: a novel bispecific chimeric antigen receptor affinity. Proc Natl Acad Sci USA, 2000, pp. 10701-10705, vol. 97. for cancer immunotherapy, Molecular Therapy-Nucleic Acids, No. 20. 2013, pp. 1-11, vol. 2, No. 7. Bonini, C., et al., The Suicide gene therapy challenge: how to Griffioen, M., et al., Retroviral transfer of human CD20 as a suicide improve a Successful gene therapy approach. Mol Ther, 2007. pp. gene for adoptive T-cell therapy. Haematologica, 2009. pp. 1316 1248-1252, vol. 15, No. 7. 1320, vol. 94, No. 9. Boulassel, M.R. and A. Galal, Immunotherapy for B-Cell Neo Gross, G., T. Waks, and Z. Eshhar, Expression of immunoglobulin plasms using T Cells expressing Chimeric Antigen Receptors: From T-cell receptor chimeric molecules as functional receptors with antigen choice to clinical implementation. Sultan Qaboos Univ Med antibody-type specificity. Proc Natl Acad Sci U S A. 1989. 86(24): J, 2012. p. 273-85, vol. 12, No. 3. p. 10024-8. Brentjens, R., et al., Treatment of chronic lymphocytic leukemia Grupp, S.A., et al., Chimeric antigen receptor-modified T cells for with genetically targeted autologous T cells: case report of an acute lymphoid leukemia. NEngl J Med, 2013. pp. 1509-1518, vol. unforeseen adverse event in a phase I clinical trial. Mol Ther, 2010. 68, No. 16. pp. 666-668, vol. 18, No. 4. Hanes, J., et al., Ribosome display efficiently selects and evolves Bridgeman, J.S., et al., Structural and biophysical determinants of high-affinity antibodies in vitro from immune libraries. Proc Natl alphabeta T-cell antigen recognition. Immunology, 2011. pp. 9-18, Acad Sci U S A, 1998. pp. 14130-1435, vol. 95, No. 24. vol. 135, No. 1. Herron, J.N., et al., High resolution structures of the 4-4-20 Fab Cairo, M.S., et al., NCI first International Workshop on the biology, fluorescein complex in two solvent systems: effects of solvent on prevention, and treatment of relapse after allogeneic hematopoietic structure and antigen-binding affinity. Biophys J, 1994. pp. 2167 stem cell transplantation: report from the committee on the biologi cal considerations of hematological relapse following allogeneic 2183, vol. 67, No. 6. stem cell transplantation unrelated to graft-versus-tumor effects: Heslop, H.E., Safer CARS. Mol Ther, Apr. 2010. pp. 661-662, vol. state of the science. Biol Blood Marrow Transplant, 2010. pp. 18, No. 4. 709-728, vol. 16, No. 6. Hollatz, G., et al., T cells for Suicide gene therapy: activation, Cameron, B.J., et al., Identification of a Titin-Derived HLA-Al functionality and clinical relevance.

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