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(15. 11.2018) US C07K 16/28 (2006.01) A61P37/06 (2006.01) 62/767,83 1 15 November 2018 (15 ( 2 (51) International Patent Classification: 62/767,792 15 November 2018 (15. 11.2018) US C07K 16/28 (2006.01) A61P37/06 (2006.01) 62/767,83 1 15 November 2018 (15. 11.2018) US C07K 16/30 (2006.01) A61P 35/00 (2006.01) 62/789,946 08 January 2019 (08.01.2019) US C07K 16/32 (2006.01) A61P 35/02 (2006.01) 62/789,943 08 January 2019 (08.01.2019) US 62/789,947 08 January 2019 (08.01.2019) US (21) International Application Number: 62/817,450 12 March 2019 (12.03.2019) US PCT/US20 19/033255 62/817,442 12 March 2019 (12.03.2019) US (22) International Filing Date: 62/817,467 12 March 2019 (12.03.2019) US 2 1 May 2019 (21.05.2019) 62/822,243 22 March 2019 (22.03.2019) US 62/822,420 22 March 2019 (22.03.2019) US (25) Filing Language: English 62/830,417 06 April 2019 (06.04.2019) US (26) Publication Language: English 62/830,420 06 April 2019 (06.04.2019) US (30) Priority Data: (71) Applicant: COMPASS THERAPEUTICS LLC 62/674,289 2 1 May 2018 (21.05.2018) US [US/US]; 245 First Street, 3rd Floor, Cambridge, Massa¬ 62/674,279 2 1 May 2018 (21.05.2018) US chusetts 02142 (US). 62/674,286 2 1 May 2018 (21.05.2018) US (72) Inventors: WATKINS, Jennifer; 245 First Street, 3rd 62/728,542 07 September 2018 (07.09.2018) US Floor, Cambridge, Massachusetts 02142 (US). SCHMIDT, 62/73 1,030 13 September 2018 (13.09.2018) US Michael March; 245 First Street, 3rd Floor, Cambridge, 62/73 1,045 13 September 2018 (13.09.2018) US Massachusetts 02142 (US). DRAGHI, Monia; 245 First 62/73 1,047 13 September 2018 (13.09.2018) US Street, 3rd Floor, Cambridge, Massachusetts 02142 (US). 62/756,012 05 November 2018 (05. 11.2018) US OLIPHANT, Amanda Frank; 245 First Street, 3rd Floor, 62/760,473 13 November 2018 (13. 11.2018) US Cambridge, Massachusetts 02142 (US). HALMOS, Sara 62/760,670 13 November 2018 (13. 11.2018) US Marie; 245 First Street, 3rd Floor, Cambridge, Massachu¬ 62/760,644 13 November 2018 (13. 11.2018) US setts 02142 (US). SCHUETZ, Thomas Joseph; 245 First 62/767,786 15 November 2018 (15. 11.2018) US Street, 3rd Floor, Cambridge, Massachusetts 02142 (US). (54) Title: COMPOSITIONS AND METHODS FOR ENHANCING THE KILLING OF TARGET CELLS BY NK CELLS (57) Abstract: The present disclosure provides immunotherapeutic compositions and methods for enhancing an immune response and for treating cancer or inflammatory conditions mediated by autoreactive B n¬ n¬ r. d d he e¬ d et or [Continued on nextpage] W O 2019/226617 A1 LAJOIE, Jason Michael; 245 First Street, 3rd Floor, Cam¬ bridge, Massachusetts 02142 (US). NELSON, Allison; 245 First Street, 3rd Floor, Cambridge, Massachusetts 02142 (US). (74) Agent: MCKEON, Tina Williams et al.; Kilpatrick Townsend & Stockton, LLP, 1100 Peachtree Street NE, Suite 2800, Atlanta, Georgia 30309 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a)) COMPOSITIONS AND METHODS FOR ENHANCING THE KILLING OF TARGET CELLS BY NK CELLS CROSS-REFERENCE RELATED APPLICATIONS This application claims benefit under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 62/674,289, filed on May 21, 2018; U.S. Provisional Patent Application No. 62/674,279, filed on May 21, 2018; U.S. Provisional Patent Application No. 62/674,286, filed on May 21, 2018; U.S. Provisional Patent Application No. 62/728,542, filed on September 7, 2018; U.S. Provisional Patent Application No. 62/731,030, filed on September 13, 2018; U.S. Provisional Patent Application No. 62/731,045, filed on September 13, 2018; U.S. Provisional Patent Application No. 62/731,047, filed on September 13, 2018; U.S. Provisional Patent Application No. 62/756,012, filed on November 5, 2018; U.S. Provisional Patent Application No. 62/760,473, filed on November 13, 2018; U.S. Provisional Patent Application No. 62/760,670, filed on November 13, 2018; U.S. Provisional Patent Application No. 62/760,644, filed on November 13, 2018; U.S. Provisional Patent Application No. 62/767,786, filed on November 15, 2018; U.S. Provisional Patent Application No. 62/767,792, filed on November 15, 2018; U.S. Provisional Patent Application No. 62/767,831, filed on November 15, 2018; U.S. Provisional Patent Application No. 62/789,946, filed on January 8, 2019; U.S. Provisional Patent Application No. 62/789,943, filed on January 8, 2019; U.S. Provisional Patent Application No. 62/789,947, filed on January 8, 2019; U.S. Provisional Patent Application No. 62/817,450, filed on March 12, 2019; U.S. Provisional Patent Application No. 62/817,442, filed on March 12, 2019; U.S. Provisional Patent Application No. 62/817,467, filed on March 12, 2019; U.S. Provisional Patent Application No. 62/822,243, filed on March 22, 2019; U.S. Provisional Patent Application No. 62/822,420, filed on March 22, 2019; U.S. Provisional Patent Application No. 62/830,417, filed on April 6, 2019; and U.S. Provisional Patent Application No. 62/830,420, filed on April 6, 2019, the contents of each of which are incorporated herein in their entireties. BACKGROUND Cancer is one of the leading causes of death, accounting for almost one in six deaths worldwide in 2015, according to the American Association for Cancer Research (AACR) Cancer Progress Report of 2017. The molecular mechanisms involved in cancer are highly complex. In some circumstances, immune cells, such as T cells, natural killer cells, and macrophages, exhibit anti-tumor activity and can effectively control the development and/or progression of tumors. The immune cells recognize tumor antigens (tumor-specific or tumor- associated antigens) and eliminate cells expressing the antigens. However, tumors also constitute highly suppressive microenvironments and can downregulate the function of infiltrating immune cells. For example, tumor cells can downregulate the level of tumor- specific or tumor-associated antigens and escape cell death by the infiltrating immune cells. As a result, the patient’s immune system may not recognize cancer cells as foreign or may not be strong enough to destroy the cancer cells. A number of treatments for cancer are currently available, including surgery, radiation, chemotherapy, hormone therapy, immunotherapy, targeted therapy, stem cell transplants, and precision medicine. Immunotherapeutic approaches, in particular, have been developed in recent years to utilize the patient’s endogenous immune system cells (e.g., T cells, natural killer cells, and macrophages) to inhibit tumor formation and progression. CD 16 is a target for certain immunotherapies. For example, margetuximab is an Fc-optimized monoclonal antibody that recognizes human epidermal growth factor receptor 2 (HER2) expressed on a number of tumor cells and targets CDl6a on immune effector cells (e.g., NK cells). In addition, bispecific antibody fragments that recognize CD 16 and CD 19 have been developed to target immunotherapeutic drugs to B cell lymphomas. Another immunotherapy in development involves multispecific binding proteins that bind NKG2D, a tumor antigen, and CD 16. However, certain patients have cancers in which the levels of CD 16 are present at decreased levels on NK cells as compared to control NK cells. The existing immuno-oncology therapies are still somewhat ineffective for the majority of patients and tumors. When tumor cells downregulate expression of tumor antigens, for example, an immunotherapy directed to the tumor antigen can prove ineffective. Monoclonal antibodies targeting tumor-associated antigens have failed to show effectiveness against low antigen-expressing tumors. Therefore, patients with low antigen expression levels are not eligible for certain available immunotherapies. Additionally, inflammatory conditions (e.g, inflammatory conditions mediated in whole or in part by auto-reactive B cells) are common. B cells (including plasma cells) have multiple roles in such conditions, including secretion of autoantibodies, presentation of autoantigen, secretion of inflammatory cytokines, modulation of antigen processing and presentation, and generation of ectopic germinal centers.
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