US 12,065,500 B2
Methods of treating cancers and enhancing efficacy of T cell redirecting therapeutics
Homer Adams, Quakertown, PA (US); Francois Gaudet, Princeton, NJ (US); Niels Van de Donk, De Boelalaan (NL); Kris Frerichs, De Boelelaan (NL); and Christie Verkleij, De Boelelaan (NL)
Assigned to Janssen Biotech, Inc., Horsham, PA (US); and Stichting VUmc, Amsterdam (NL)
Filed by Janssen Biotech, Inc., Horsham, PA (US); and Stichting VUmc, Amsterdam (NL)
Filed on May 15, 2019, as Appl. No. 16/412,701.
Claims priority of provisional application 62/842,080, filed on May 2, 2019.
Claims priority of provisional application 62/736,804, filed on Sep. 26, 2018.
Claims priority of provisional application 62/672,222, filed on May 16, 2018.
Prior Publication US 2019/0352421 A1, Nov. 21, 2019
Int. Cl. C07K 16/28 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); C07K 16/30 (2006.01); C07K 16/46 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2896 (2013.01) [A61K 45/06 (2013.01); A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07K 16/2809 (2013.01); C07K 16/2878 (2013.01); C07K 16/30 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/565 (2013.01); C07K 2317/71 (2013.01)] 28 Claims
 
1. A method of treating a multiple myeloma in a subject, comprising administering a therapeutically effective amount of an anti-CD38 antibody and a T cell redirecting therapeutic to the subject to treat the multiple myeloma,
wherein the anti-CD38 antibody comprises:
(a) a heavy chain complementarity determining region 1 (HCDR1) of SEQ ID NO: 6, an HCDR2 of SEQ ID NO: 7, an HCDR3 of SEQ ID NO: 8, a light chain complementarity determining region 1 (LCDR1) of SEQ ID NO: 9, an LCDR2 of SEQ ID NO: 10 and an LCDR3 of SEQ ID NO: 11, or
(b) a heavy chain variable region (VH) of SEQ ID NO: 4 and a light chain variable region (VL) of SEQ ID NO: 5, and
wherein the T cell redirecting therapeutic comprises:
(c) a CD3 binding domain comprising:
(i) a HCDR1 of SEQ ID NO: 33, an HCDR2 of SEQ ID NO: 34, an HCDR3 of SEQ ID NO: 35, an LCDR1 of SEQ ID NO: 36, an LCDR2 of SEQ ID NO: 37 and an LCDR3 of SEQ ID NO: 38; or
(ii) a VH of SEQ ID NO: 39 and a VL of SEQ ID NO: 40; and
(d) a BCMA binding domain comprising:
(i) a HCDR1 of SEQ ID NO: 23, a HCDR2 of SEQ ID NO: 24, a HCDR3 of SEQ ID NO: 25, a LCDR1 of SEQ ID NO: 26, a LCDR2 of SEQ ID NO: 27 and a LCDR3 of SEQ ID NO: 28; or
(ii) VH of SEQ ID NO: 29 and the VL of SEQ ID NO: 30.