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KR-20260065885-A - Lipidoid Compounds, Related Compositions, and Uses

KR20260065885AKR 20260065885 AKR20260065885 AKR 20260065885AKR-20260065885-A

Abstract

The present disclosure provides a composition comprising a lipidoid compound, a method for preparing said composition, and a use of said composition in gene transfer applications.

Inventors

  • 황, 리쥔
  • 데이비스, 알리샤 엠.
  • 하지, 칼리드 에이.

Assignees

  • 포세이다 테라퓨틱스, 인크.

Dates

Publication Date
20260511
Application Date
20240830
Priority Date
20230901

Claims (20)

  1. Compound of chemical formula (I): Chemical formula (I) Or as a salt of this, Here: Z is , , , , , or is a covalent bond; X a , X b and X c are each independently NH or O; Y a , Y b , Y c , Y d , Y e, and Y f are each independently C or O; r, s, and t are each independently integers in the range of 1 to 9; and R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f is each independently a C 1 -C 18 alkyl, C 2 -C 18 alkenyl, -(cyclohexyl)-(C 1 -C 18 alkyl), -(cyclohexyl)-(C 2 -C 18 alkenyl), or -(cyclohexyl)-(CH 2 -O-CO)-(C 1 -C 18 alkyl), wherein the C 1 -C 18 alkyl or C 2 -C 18 alkenyl is optionally substituted with one or more cyclohexyls, a compound or a salt thereof.
  2. In paragraph 1, Z is Phosphorus compound.
  3. In paragraph 1, Z is Phosphorus compound.
  4. In any one of paragraphs 1 through 3, X a , X b , and X c are compounds that are each NH.
  5. In any one of paragraphs 1 through 3, X a , X b , and X c are compounds in which O is each.
  6. In any one of paragraphs 1 through 5, Y a , Y b , Y c , Y d , Y e and Y f are respectively C compound.
  7. In any one of paragraphs 1 through 5, Y a , Y b , Y c , Y d , Y e and Y f are respectively O-compound.
  8. In any one of paragraphs 1 through 7, R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f are respectively C1 - C18 alkyl compounds.
  9. In any one of paragraphs 1 through 8, R 2a , R 2b , R 2c , and R 2d are respectively A C1 - C18 alkyl compound substituted with one or more cyclohexyls.
  10. In any one of paragraphs 1 through 9, R 2a , R 2b , R 2c , and R 2d are respectively Phosphorus compound.
  11. In any one of paragraphs 1 through 9, R 2a , R 2b , R 2c , and R 2d are respectively Phosphorus compound.
  12. In paragraph 1, Z is A compound in which X a and X b are each NH.
  13. In paragraph 1, Z is A compound in which X a and X b are each O.
  14. In paragraph 1, A compound where Z is a covalent bond and X a and X b are each O.
  15. In paragraph 1, Z is A compound in which X a and X b are each NH.
  16. In any one of paragraphs 12 through 15, Y a , Y b , Y c and Y d are respectively C compound.
  17. In any one of paragraphs 12 through 15, Y a , Y b , Y c and Y d are respectively O-compound.
  18. In any one of paragraphs 12 through 17, R 2a , R 2b , R 2c , and R 2d are compounds that are each C 3 -C 18 alkyl.
  19. In any one of paragraphs 12 through 18, R 2a , R 2b , R 2c , and R 2d are compounds that are each C 3 -C 18 alkyls substituted with one or more cyclohexyls.
  20. In any one of paragraphs 12 through 19, R 2a , R 2b , R 2c , and R 2d are respectively Phosphorus compound.

Description

Lipidoid Compounds, Related Compositions, and Uses Related applications This application claims priority to United States Provisional Application No. 63/580,080, filed September 1, 2023 and United States Provisional Application No. 63/610,676, filed December 15, 2023. The contents of each of the above patent applications are incorporated herein in their entirety. Sequence list The sequence list XML related to the present application is provided electronically in XML format and is incorporated herein by reference. The name of the XML file containing the sequence list XML is "POTH-088_001WO_SeqList.xml". This XML file has a size of 25,048 bytes, was created on August 29, 2024, and is submitted electronically through the USPTO Patent Center. The present disclosure generally relates to lipidoid compounds, compositions containing such compounds, methods for preparing such compounds, and the use of such compositions in gene transfer. There has been a long-standing need in the relevant technical field for compositions and methods to deliver nucleic acids to cells and to genetically modify cells in vivo, in vitro, and in vitro, but this need has not yet been met. Widely accepted gene delivery and genetic modification technologies, such as the use of viral vectors including AAV, can cause acute toxicity and harmful side effects in patients. The present disclosure provides novel lipidoid compounds, novel lipid nanoparticle compositions (LNPs) comprising such novel lipidoid compounds, methods for preparing such LNPs, and methods for using the same. In a non-limiting example, the compositions and methods of the limiting disclosure may be used for gene delivery. In a non-limiting example, the compositions and methods of the present disclosure may be widely used to deliver nucleic acids to liver cells in vivo, in vitro, or in vitro for the treatment of certain diseases and disorders, including but not limited to liver disorders. In a non-limiting example, the compositions and methods of the present disclosure may be widely used to deliver nucleic acids to induce the expression of secreted therapeutic proteins. Compounds of the present disclosure In one embodiment, the present disclosure relates to a compound of formula (I): Chemical formula (I) Or as a salt of this, Here: Z is , , , , , or is a covalent bond; X a , X b and X c are each independently NH or O; Y a , Y b , Y c , Y d , Y e, and Y f are each independently C or O; r, s, and t are each independently integers in the range of 1 to 9; and R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f are each independently a C 1 -C 18 alkyl, C 2 -C 18 alkenyl, -(cyclohexyl)-(C 1 -C 18 alkyl), -(cyclohexyl)-(C 2 -C 18 alkenyl), or -(cyclohexyl)-(CH 2 -O-CO)-(C 1 -C 18 alkyl), wherein the C 1 -C 18 alkyl or C 2 -C 18 alkenyl optionally provides a compound or a salt thereof substituted with one or more cyclohexyls. In some embodiments, the novel compound is a compound of formula (I): Chemical formula (I) Or as a salt of this, Here: Z is , , or is a covalent bond; X a and X b are each independently NH or O; Y a , Y b , Y c , and Y d are each independently C or O; r and s are each independently integers in the range of 1 to 9; and R 2a , R 2b , R 2c , and R 2d are each independently a C 1 -C 18 alkyl, C 2 -C 18 alkenyl, -(cyclohexyl)-(C 1 -C 18 alkyl), or -(cyclohexyl)-(C 2 -C 18 alkenyl), where C 1 -C 18 alkyl or C 2 -C 18 alkenyl is optionally a compound substituted with one or more cyclohexyls or a salt thereof. In some modes, Z is am. In some modes, Z is am. In some modes, Z is am. In some modes, Z is am. In some modes, Z is am. In some modes, Z is a covalent bond. In some modalities, X a , X b , and X c are each NH. In some modalities, X a , X b , and X c are each O. In some modes, Y a , Y b , Y c , Y d , Y e , and Y f are, respectively It is C. In some embodiments, Y a , Y b , Y c , Y d , Y e , and Y f are, respectively It is O. In some modalities, r, s, and t are each 3. In some modalities, R 2a , R 2b , R 2c , R 2d , R 2e , and R 2f are each C 1 -C 18 alkyls. In some modalities, X a and X b are each NH. In some modalities, X a and X b are each O. In some embodiments, Y a , Y b , Y c , and Y d are, respectively It is C. In some modalities, Y a , Y b , Y c , and Y d are each O. In some modalities, r and s are each 3. In some modalities, R 2a , R 2b , R 2c and R 2d are each C 1 -C 18 alkyls. In some modes, R 2a , R 2b , R 2c , and R 2d is each a C 1 -C 18 alkyl substituted with one or more cyclohexyls. In some embodiments, R 2a , R 2b , R 2c and R 2d are, respectively am. In some modes, R 2a , R 2b , R 2c and R 2d are each -(cyclohexyl)-(C 1 -C 18 alkyl). In some embodiments, R 2a , R 2b , R2c and R2d are, respectively am. In some modalities, R 2a , R 2b , R 2c , R 2d, R 2e , and R 2f are -(cyclohexyl)-(CH 2 -O-CO)-(C 1 -C 18 alkyl). In some modes, Z is And Xa and Xb are each NH. In some embodiments, Y a , Y b , Y c , and Y d are each C. In some embodiments, Y a , Y b , Y c , and Y