US 6,982,092 B2 | ||
Method of complexing a nucleic acid with a lipid-conjugated polyamide | ||
Ronald N. Zuckermann, Berkeley, Calif. (US); Chin-Yi Huang, Fremont, Calif. (US); John E. Murphy, Oakland, Calif. (US); and Tetsuo Uno, San Francisco, Calif. (US) | ||
Assigned to Chiron Corporation, Emeryville, Calif. (US) | ||
Filed on May 30, 2003, as Appl. No. 10/448,902. | ||
Application 09/620259 is a division of application No. 09/132808, filed on Aug. 12, 1998, granted, now 6,197,332. | ||
Application 10/448902 is a continuation of application No. 09/620259, filed on Jul. 21, 2000, granted, now 6,572,881. | ||
Claims priority of provisional application 60/054743, filed on Aug. 13, 1997. | ||
Prior Publication US 2005/0101525 A1, May 12, 2005 | ||
This patent is subject to a terminal disclaimer. | ||
Int. Cl. A61K 9/127 (2006.01); C07H 21/04 (2006.01); C07J 9/00 (2006.01); C08K 5/21 (2006.01); C11C 3/00 (2006.01) |
U.S. Cl. 424—450 | 4 Claims |
1. A method of preparing a stable preparation of a nucleic acid complexed with a lipid-conjugated polyamide compound, the
method comprising:
combining a solution of said nucleic acid with a solution of a lipid-conjugated polyamide compound comprising a repeating
trimer of monomeric subunits and having the formula: where
![]() m is an integer selected from 2 to about 48,
Ra is selected from the group consisting of —OH, —H, —SH, —COOH, sulfonyl, a C1-C8 aliphatic group and a C3-C12 aryl, arylalkyl,
arylalkenyl, or arylalkynyl group, any of which may include at least one heteroatom selected from the group consisting of
nitrogen, sulfur, oxygen, and phosphorus; and a lipid moiety, wherein said lipid moiety may be conjugated to a linker moiety;
each R1 is independently selected from the group consisting of hydrogen, a C1-C8 aliphatic group and a C3-C12 aryl, arylalkyl, arylalkenyl,
or arylalkynyl group, any of which may include at least one heteroatom selected from the group consisting of nitrogen, sulfur,
oxygen, and phosphorus; and a lipid moiety, wherein said lipid moiety may be conjugated to a linker moiety, wherein at least
one group R1 is not hydrogen;
Rc is selected from the group consisting of —OH, —H, —SH, —NH2, sulfonyl, hydrazine, a C1-C8 aliphatic group and a C3-C12 aryl, arylalkyl, arylalkenyl, or arylalkynyl group, any of which
may include at least one heteroatom selected from the group consisting of nitrogen, sulfur, oxygen, and phosphorus; and a
lipid moiety, wherein said lipid moiety may be conjugated to a linker moiety; and
each group W is selected from the group consisting of —CH2 CH2—, CH2-phenyl-, CH2CH2O—, —CH2CH═CH—, and —CR2R3—, where R2 and R3 are independently selected from the group consisting of hydrogen, a C1-C8 aliphatic group and a C3-C12 aryl, arylalkyl, arylalkenyl,
or arylalkynyl group, any of which may include at least one heteroatom selected from the group consisting of nitrogen, sulfur,
oxygen, and phosphorus; and a lipid moiety, wherein said lipid moiety may be conjugated to a linker moiety;
wherein any said aryl, arylalkyl, arylalkenyl, or arylalkynyl group having fewer than 5 carbon atoms further includes at least
one heteroatom; and wherein at least one of said groups Ra, Rc, R1 for a single monomeric subunit, and W for a single monomeric subunit, comprises a lipid moiety.
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