US 11,530,410 B2Granted

Methods for treating hypercholesterolemia

AssigneeIonis Pharmaceuticals, Inc.

InventorsSusan M. Freier, Rosanne M. Crooke, Mark J. Graham, Kristina M. Lemonidis, Diane Tribble, Sanjay Bhanot, Andrew T. Watt

Life of this patent

Estimating the term…

patentgrep

Loading patent…

Abstract

Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.

Claims12

Dependent claims

A compound comprising a modified oligonucleotide targeting a PCSK9 nucleic acid and consisting of 15 to 30 linked nucleosides and having a nucleobase sequence comprising a portion which consists of at least 8 contiguous nucleobases complementary to an equal-length portion of 294-317, 406-440, 406-526, 410-436, 410-499, 446-526, 545-581, 591-619, 591-704, 591-743, 595-622, 600-626, 600-639, 600-670, 601-628, 602-628, 603-630, 611-636, 620-647, 638-665, 648-674, 657-684, 705-743, 782-810, 821-859, 835-859, 835-917, 835-942, 860-887, 860-899, 860-909, 860-917, 869-895, 878-905, 888-909, 923-952, 960-1034, 960-1173, 960-986, 967-991, 970-1023, 970-1064, 970-1117, 970-996, 977-1004, 985-1011, 989-1016, 992-1019, 997-1024, 997-1024, 998-1025, 999-1026, 1000-1027, 1001-1028, 1002-1029, 1003-1029, 1004-1029, 1005-1029, 1006-1029, 1007-1034, 1036-1061, 1045-1072, 1076-1096, 1088-1115, 1098-1123, 1200-1251, 1210-1237, 1219-1245, 1228-1251, 1273-1444, 1295-1316, 1318-1345, 1328-1354, 1337-1361, 1344-1371, 1354-1377, 1380-1406, 1389-1416, 1400-1426, 1409-1434, 1465-1491, 1465-1602, 1474-1499, 1482-1519, 1513-1540, 1523-1549, 1526-1602, 1526-1624, 1532-1558, 1541-1568, 1552-1579, 1560-1587, 1561-1589, 1564-1591, 1565-1592, 1566-1592, 1567-1592, 1570-1597, 1571-1599, 1605-1706, 1628-1706, 1640-1666, 1672-1698, 1681-1706, 1735-1761, 1735-1765, 1740-1765, 1849-1876, 1849-1879, 1850-1877, 1851-1877, 1852-1878, 1852-1879, 1853-1879, 1854-1879, 1905-1955, 1915-1942, 1916-1943, 1917-1944, 1918-1945, 1919-1946, 1920-1939, 1920-1947, 1921-1948, 1922-1949, 1923-1950, 1924-1951, 1925-1952, 1926-1952, 1927-1952, 1928-1955, 1962-2059, 2040-2126, 2100-2126, 2100-2139, 2100-2206, 2101-2126, 2305-2332, 2305-2354, 2306-2333, 2307-2334, 2308-2334, 2309-2334, 2310-2334, 2410-2434, 2504-2528, 2509-2528, 2582-2625, 2606-2668, 2828-2855, 2832-2851, 2900-2927, 2900-2929, 2902-2927, 2983-3007, 2983-3013, 3227-3252, 3227-3456, 3472-3496, or 3543-3569 of SEQ ID NO:

1, wherein the nucleobase sequence of the modified oligonucleotide is at least 95% complementary to SEQ ID NO:
1 over the entire length of the modified oligonucleotide;
and wherein at least one at least one nucleoside comprises a modified sugar selected from a 2′-F, 2′-OMe and a 2′-O-methoxyethyl;
and at least one internucleoside linkage is a phosphorothioate internucleoside linkage.

1 more element

A compound comprising a modified oligonucleotide targeting a PCSK9 nucleic acid and consisting of 15 to 30 linked nucleosides and having a nucleobase sequence comprising a portion of at least 8 contiguous nucleobases fully complementary to an equal length portion of nucleobases 294-317, 406-440, 406-526, 410-436, 410-499, 446-526, 545-581, 591-619, 591-704, 591-743, 595-622, 600-626, 600-639, 600-670, 601-628, 602-628, 603-630, 611-636, 620-647, 638-665, 648-674, 657-684, 705-743, 782-810, 821-859, 835-859, 835-917, 835-942, 860-887, 860-899, 860-909, 860-917, 869-895, 878-905, 888-909, 923-952, 960-1034, 960-1173, 960-986, 967-991, 970-1023, 970-1064, 970-1117, 970-996, 977-1004, 985-1011, 989-1016, 992-1019, 997-1024, 997-1024, 998-1025, 999-1026, 1000-1027, 1001-1028, 1002-1029, 1003-1029, 1004-1029, 1005-1029, 1006-1029, 1007-1034, 1036-1061, 1045-1072, 1076-1096, 1088-1115, 1098-1123, 1200-1251, 1210-1237, 1219-1245, 1228-1251, 1273-1444, 1295-1316, 1318-1345, 1328-1354, 1337-1361, 1344-1371, 1354-1377, 1380-1406, 1389-1416, 1400-1426, 1409-1434, 1465-1491, 1465-1602, 1474-1499, 1482-1519, 1513-1540, 1523-1549, 1526-1602, 1526-1624, 1532-1558, 1541-1568, 1552-1579, 1560-1587, 1561-1589, 1564-1591, 1565-1592, 1566-1592, 1567-1592, 1570-1597, 1571-1599, 1605-1706, 1628-1706, 1640-1666, 1672-1698, 1681-1706, 1735-1761, 1735-1765, 1740-1765, 1849-1876, 1849-1879, 1850-1877, 1851-1877, 1852-1878, 1852-1879, 1853-1879, 1854-1879, 1905-1955, 1915-1942, 1916-1943, 1917-1944, 1918-1945, 1919-1946, 1920-1939, 1920-1947, 1921-1948, 1922-1949, 1923-1950, 1924-1951, 1925-1952, 1926-1952, 1927-1952, 1928-1955, 1962-2059, 2040-2126, 2100-2126, 2100-2139, 2100-2206, 2101-2126, 2305-2332, 2305-2354, 2306-2333, 2307-2334, 2308-2334, 2309-2334, 2310-2334, 2410-2434, 2504-2528, 2509-2528, 2582-2625, 2606-2668, 2828-2855, 2832-2851, 2900-2927, 2900-2929, 2902-2927, 2983-3007, 2983-3013, 3227-3252, 3227-3456, 3472-3496, or 3543-3569 of SEQ ID NO:

1, wherein the nucleobase sequence of the modified oligonucleotide is at least 95% complementary to SEQ ID NO:
1 over the entire length of the modified oligonucleotide;
and wherein at least one at least one nucleoside comprises a modified sugar selected from a 2′-F, 2′-OMe and a 2′-O-methoxyethyl;
and at least one internucleoside linkage is a phosphorothioate internucleoside linkage.

1 more element

Dependencies are inferred from the claim text.

Facts

Application: 17/032,550Filed 25 Sep 2020 · continuation
Priority: 27 Nov 2006
Published: US 2021/0285003 A116 Sep 2021
Granted: 20 Dec 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C12N 15/1137
Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming…: against enzymes
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…
A61P 3/00
Drugs for disorders of the metabolism

Family

Application60/867,395Us provisional application · filed 27 Nov 2006
Application60/912,892Us provisional application · filed 19 Apr 2007
Application60/986,286Us provisional application · filed 7 Nov 2007
Application60/988,074Us provisional application · filed 14 Nov 2007
PCT/US2007/024369Parent of this continuation-in-part · filed 27 Nov 2007
Application61/058,707Us provisional application · filed 4 Jun 2008
Application61/059,169Us provisional application · filed 5 Jun 2008
Application12/478,488Parent of this continuation · filed 4 Jun 2009
Application13/302,070Parent of this continuation · filed 22 Nov 2011
US 8,084,437 B2Parent of this continuation-in-part · filed 27 Dec 2011
US 8,093,222 B2Parent of this continuation · filed 10 Jan 2012
Application14/152,825Parent of this continuation · filed 10 Jan 2014
US 8,664,190 B2Parent of this continuation · filed 4 Mar 2014
Application14/539,831Parent of this continuation · filed 12 Nov 2014
US 8,912,160 B2Parent of this continuation · filed 16 Dec 2014
Application15/483,992Parent of this continuation · filed 10 Apr 2017
US 9,650,636 B2Parent of this continuation · filed 16 May 2017
Application16/057,471Parent of this continuation · filed 7 Aug 2018
US 2021/0285003 A1Pre-grant publication · published 16 Sep 2021
US 10,858,657 B2Parent of this continuation
Application12/516,457Parent of this continuation-in-part
Application12/478,488Parent of this continuation-in-part
US 2009/0318536 A1Published application
US 2010/0144834 A1Published application
US 2012/0077865 A1Published application
US 2014/0194492 A1Published application
US 2015/0167005 A1Published application
US 2017/0342420 A1Published application
US 2019/0071677 A1Published application
US 11,530,410 B2This patent

From the US filing history. Foreign family members aren’t listed.