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:
OG Complex Work Unit Drawing
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.