US 12,139,713 B2
Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell
HoWon J. Kim, Lexington, MA (US); In-San Kim, Seoul (KR); Jay S. Kim, Bedford, MA (US); Sun Hwa Kim, Seoul (KR); Ick Chan Kwon, Seoul (KR); Jong Won Lee, Seoul (KR); Yoo Soo Yang, Seoul (KR); and Hong Yeol Yoon, Gyeonggi-do (KR)
Assigned to K2B Therapeutics, Inc., Cambridge, MA (US); and KIST (Korea Institute of Science and Technology), Seoul (KR)
Filed by KIST (Korea Institute of Science and Technology), Seoul (KR); and K2B Therapeutics, Inc., Cambridge, MA (US)
Filed on Jan. 9, 2024, as Appl. No. 18/407,780.
Application 18/407,780 is a continuation of application No. 18/057,050, filed on Nov. 18, 2022.
Claims priority of provisional application 63/392,323, filed on Jul. 26, 2022.
Claims priority of provisional application 63/281,370, filed on Nov. 19, 2021.
Prior Publication US 2024/0191237 A1, Jun. 13, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/113 (2010.01); A61P 35/00 (2006.01); C12Q 1/68 (2018.01)
CPC C12N 15/1138 (2013.01) [A61P 35/00 (2018.01); C12N 2310/11 (2013.01); C12N 2310/531 (2013.01)] 15 Claims
 
1. A therapeutic compound for red blood cell-mediated (RBC-mediated) delivery in a mammalian subject to a cancer cell expressing CD47, the therapeutic compound comprising:
a CD47-binding protein conjugated to an active pharmaceutical ingredient (API) so as to form a conjugate;
wherein:
the CD47-binding protein is selected from the group consisting of wild type thrombospondin-1 (TSP-1) (SEQ ID NO: 7), wild type SIRPγ (SEQ ID NO: 4), vSIRPγ-1 (SEQ ID NO: 5), vSIRPγ-2 (SEQ ID NO: 6), ALX148 (SEQ ID NO: 962), TTI-661 (SEQ ID NO: 963), TTI-662 (SEQ ID NO: 964), a homolog of any of the foregoing, and combinations thereof, and is configured to bind the conjugate to CD47 of a red blood cell of the subject so as to enable transport of the conjugate, through the subject's circulatory system, to the cancer cell, so that (i) the CD47-binding protein, being configured to bind the conjugate to the CD47 of the red blood cell, binds the CD47 of the cancer cell, thus transferring the conjugate from the red blood cell to the cancer cell so as to form a conjugate-CD47 complex on the cancer cell, thereby blocking CD47 and inhibiting CD47 activity as an immune escape mechanism of the cancer cell, and (ii) the conjugate is taken up by the cancer cell via endocytosis of the conjugate-CD47 complex, thereby further inhibiting the immune escape mechanism of the cancer cell and delivering the API into the cancer cell; and
the API is siRNA, the siRNA being a double-stranded RNA molecule including an antisense RNA strand and a sense RNA strand;
wherein:
(a) the antisense RNA strand is 19-29 nucleotides in length and is complementary to contiguous nucleotides in a target mammalian mRNA sequence, the mRNA sequence being selected from the group consisting of SEQ ID NO: 8-747 and 771-824,
(b) the sense RNA strand is 19-29 nucleotides in length and is complementary to 14-29 nucleotides from the antisense RNA strand, and
(c) the double stranded RNA molecule has a double stranded region of 14-29 nucleotides in length and a 3′ overhang region of 0-5 nucleotides in length.