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US 2024/0191237 A1Published application
Therapeutic Compounds for Red Blood Cell-Mediated Delivery of an Active Pharmaceutical Ingredient to a Target Cell
AssigneesKIST (Korea Institute of Science and Technology), K2B Therapeutics, Inc.
InventorsHoWon J. Kim, In-San Kim, Jay S. Kim, Sun Hwa Kim, Ick Chan Kwon, Jong Won Lee, Yoo Soo Yang, Hong Yeol Yoon
Life of this patent
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Abstract
Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell.
Claims15
A therapeutic compound for RBC-mediated delivery in a mammalian subject to a cancer cell expressing CD47, the therapeutic compound comprising:
- a CD47-binding protein conjugated to an 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.
14 more elements
A therapeutic compound for RBC-mediated delivery in a mammalian subject to a cancer cell expressing CD47, the therapeutic compound comprising:
- a CD47-binding protein conjugated to an 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 an miRNA selected from the group consisting of SEQ ID NO:
- 825-844, 849-851, 853, 855, 857, 864, 865, and 867-883.
10 more elements
A therapeutic compound for RBC-mediated delivery in a mammalian subject to a cancer cell expressing CD47, the therapeutic compound comprising:
- a CD47-binding protein conjugated to an 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 an antimiR, the antimiR being a single-stranded nucleic acid molecule of 12-25 nucleotides in length, the antimiR having a sequence of 12-25 contiguous nucleotides that is complementary to contiguous nucleotides in a target mature miRNA product sequence, the mature miRNA product sequence being selected from the group consisting of SEQ ID NO:
- 884-908, wherein the contiguous nucleotides in the mature miRNA product sequence includes, in a 5′ to 3′ direction, nucleotides 2 to 8 of the mature miRNA product sequence.
10 more elements
Dependencies are inferred from the claim text.