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( 12 ) United States Patent ( 10 ) Patent No .: US 10,842,798 B1 Cole Et Al

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( 12 ) United States Patent ( 10 ) Patent No .: US 10,842,798 B1 Cole Et Al US010842798B1 ( 12 ) United States Patent ( 10 ) Patent No .: US 10,842,798 B1 Cole et al . ( 45 ) Date of Patent : Nov. 24 , 2020 ( 54 ) CHARGED ION CHANNEL BLOCKERS AND 4,293,539 A 10/1981 Ludwig et al. METHODS FOR USE 4,360,465 A 11/1982 Buschmann et al . 4,564,629 A 1/1986 Kunz et al . ( 71 ) Applicant: Nocion Therapeutics , Inc. , Cambridge, 4,757,128 A 7/1988 Domb et al . MA ( US ) 4,877,805 A 10/1989 Kligman 4,975,282 A 12/1990 Cullis et al . 4,980,378 A 12/1990 Wong et al. ( 72 ) Inventors: Bridget McCarthy Cole , Quincy, MA 4,994,213 A 2/1991 Aitcheson et al . ( US ) ; James Lamond Ellis , Somerville, 5,000,958 A 3/1991 Fountain et al . MA (US ) 5,023,087 A 6/1991 Yau - Young 5,032,582 A 7/1991 Abra ( 73 ) Assignee : Nocion Therapeutics, Inc. , Cambridge, 5,049,388 A 9/1991 Knight et al . MA ( US ) 5,082,866 A 1/1992 Wong et al . 5,169,637 A 12/1992 Lenk et al . ( * ) Notice: Subject to any disclaimer , the term of this 5,176,907 A 1/1993 Leong patent is extended or adjusted under 35 5,194,266 A 3/1993 Abra et al . U.S.C. 154 ( b ) by 0 days. 5,194,581 A 3/1993 Leong 5,356,633 A 10/1994 Woodle et al . ( 21 ) Appl. No .: 16 /815,325 5,409,704 A 4/1995 Bally et al . 5,409,805 A 4/1995 Haraguchi et al . ( 22 ) Filed : Mar. 11 , 2020 5,480,971 A 1/1996 Houghten et al . 5,552,155 A 6/1996 Jones Related U.S. Application Data 5,591,317 A 1/1997 Pitts , Jr. ( 60 ) Provisional application No. 62 / 931,444 , filed on Nov. (Continued ) 6 , 2019 . FOREIGN PATENT DOCUMENTS ( 51 ) Int . Cl . CA 982148 1/1976 A61K 31/55 ( 2006.01 ) CA 2717042 9/2009 CO7D 409/12 ( 2006.01 ) ( Continued ) A61K 45/06 ( 2006.01 ) A61K 31/4436 ( 2006.01 ) A61K 31/4025 ( 2006.01 ) OTHER PUBLICATIONS ( 52 ) U.S. CI . Sunami, Proc . Natl. Acad . Sci . USA vol . 94 , pp . 14126-14131 , Dec. CPC A61K 31/55 ( 2013.01 ) ; A61K 31/4025 1997. * ( 2013.01 ) ; A61K 31/4436 ( 2013.01 ) ; A61K 45/06 ( 2013.01 ) ; C07D 409/12 ( 2013.01 ) ( Continued ) ( 58 ) Field of Classification Search CPC A61K 31/55 Primary Examiner Nizal S Chandrakumar USPC 546 / 280.4 ( 74 ) Attorney, Agent, or Firm Elmore Patent Law See application file for complete search history . Group , P.C .; Carolyn S. Elmore ; Mahreen Chaudhry Hoda ( 56 ) References Cited U.S. PATENT DOCUMENTS ( 57 ) ABSTRACT 1,889,645 A 11/1932 Otto The invention provides compounds of Formula ( I ) , or phar 2,441,498 A 5/1948 Loefgren et al . maceutically acceptable salts thereof: 2,689,248 A 9/1954 Clinton et al . 2,759,975 A 8/1956 Chiddix et al . 2,774,770 A 12/1956 Kerwin et al . 2,783,230 A 2/1957 Hoffmann 2,799,679 A 7/1957 Thuresson et al . RB 2,955,111 A 10/1960 Thuresson et al . RE Y 3,049,546 A 8/1962 Renner et al . RE 3,080,327 A 3/1963 Hay 3,160,662 A 12/1964 Megnus et al . X1 3,177,252 A 4/1965 Leon -RH 3,264,309 A 8/1966 Zenitz RA RD 3,519,631 A 7/1970 Ost et al . 3,574,216 A 4/1971 Bell 3,773,939 A 11/1973 Janssen 3,812,147 A 5/1974 Adams et al . 3,900,481 A 8/1975 Banitt et al . The compounds , compositions, methods and kits of the 3,931,195 A 1/1976 Dykstra et al . 4,005,038 A 1/1977 Minkoff invention are useful for the treatment of pain , itch , and 4,069,309 A 1/1978 Ciaudelli et al . neurogenic inflammation . 4,070,347 A 1/1978 Schmitt 4,222,766 A 9/1980 Martin 4,233,055 A 11/1980 Martin 13 Claims , No Drawings US 10,842,798 B1 Page 2 ( 56 ) References Cited 2010/0113416 Al 5/2010 Friedman et al. 2010/0120781 A1 5/2010 Neamati U.S. PATENT DOCUMENTS 2011/0086818 Al 4/2011 Bean et al . 2012/0022142 A1 1/2012 Jadhav et al . 5,688,525 A 11/1997 Adler - Moore et al . 2012/0129867 Al 5/2012 Bauer et al . 5,747,470 A 5/1998 Becherer et al . 2012/0172429 Al 7/2012 Woolf et al . 5,783,683 A 7/1998 Morrison 2012/0195902 A1 8/2012 Friedman et al . 5,874,104 A 2/1999 Adler - Moore et al . 2013/0165427 Al 6/2013 Chong 5,883,228 A 3/1999 Darnell, Jr. et al . 2015/0087552 A1 3/2015 Jensen et al . 5,891,919 A 4/1999 Blum et al . 2015/0087714 A1 3/2015 Bean et al . 5,952,451 A 9/1999 Zhao 2016/0258083 Al 9/2016 Weisman et al . 6,008,318 A 12/1999 Zhao 2017/0319517 A1 11/2017 Bean et al . 6,051,576 A 4/2000 Ashton et al . 2018/0133170 A1 5/2018 Weigele et al . 6,083,996 A 7/2000 Buyuktimkin et al . 2018/0237392 Al 8/2018 Bean et al . 6,103,255 A 8/2000 Levene 2018/0303945 A1 10/2018 Adams et al . 6,118,020 A 9/2000 Buyuktimkin et al . 2019/0185416 A1 6/2019 Wyrwa et al . 6,140,351 A 10/2000 Arnaiz et al . 2019/0216747 A1 7/2019 Woolf et al . 6,153,212 A 11/2000 Mao et al . 2019/0374489 Al 12/2019 Lee 6,207,290 B1 3/2001 Blum et al . 6,355,637 B1 3/2002 Axt et al . FOREIGN PATENT DOCUMENTS 6,362,197 B1 3/2002 Page et al . 6,413,961 B1 7/2002 Demopulos et al. CH 311606 11/1955 6,432,937 B1 8/2002 Hallgren CH 311607 11/1955 6,623,040 B1 9/2003 Foley et al. CH 311608 11/1955 6,709,406 B2 3/2004 Laserow CH 311609 11/1955 6,766,319 B1 7/2004 Might CH 311610 11/1955 6,825,190 B2 11/2004 Moon et al. CH 311611 11/1955 6,884,782 B2 4/2005 Huang et al . CH 311612 11/1955 7,166,590 B2 1/2007 Seko et al . CH 311613 11/1955 7,429,673 B2 9/2008 Morazzoni et al . CH 311614 11/1955 7,446,226 B2 11/2008 Helsing et al. CH 311615 11/1955 7,705,004 B2 4/2010 Song et al . CN 101156851 4/2008 8,138,339 B2 3/2012 Bauer et al . CN 101347427 A 1/2009 8,143,412 B2 3/2012 Priebe et al . CN 105566148 A 5/2016 8,258,144 B2 9/2012 Song et al. DE 150423 A1 9/1981 8,273,390 B2 9/2012 Muhammad et al . DE 151036 A1 9/1981 8,652,497 B2 2/2014 Sackler DE 298723 A5 3/1992 8,741,934 B2 6/2014 Marron et al . DE 298726 A5 3/1992 8,822,537 B2 9/2014 Buyuktimkin et al . DE 298727 A5 3/1992 8,841,309 B2 9/2014 Hamprecht et al . DE 100 39 449 7/2003 9,388,137 B2 7/2016 Engel EP 0586106 A1 3/1994 9,511,067 B2 12/2016 Hadida Ruah et al. GB 692332 A 6/1953 9,603,817 B2 3/2017 Bean et al . GB 751522 A 6/1956 10,179,116 B2 1/2019 Bean et al . GB 756538 A 9/1956 10,525,143 B2 1/2020 Wang et al . GB 895601 5/1962 2003/0068276 A1 4/2003 Hughes et al . GB 901377 A 7/1962 2003/0105126 Al 6/2003 Demopulos et al. GB 1221061 A 2/1971 2003/0152637 A1 8/2003 Chasin et al . GB 2212814 A 8/1989 2003/0166629 A1 9/2003 Choi et al . JP 2000-143635 5/2000 2004/0146590 A1 7/2004 Iadarola et al . LV 15002 B 7/2015 2004/0220187 A1 11/2004 Stephenson et al . RU 2105554 C1 2/1998 2004/0266870 A1 12/2004 Allegretti et al . RU 2258700 C1 8/2005 2005/0009016 A1 1/2005 Moskowitz et al . WO 1985/00599 A1 2/1985 2005/0025765 Al 2/2005 DiMauro et al . WO 1996/40061 A1 12/1996 2005/0090557 A1 4/2005 Muhammad et al . WO 98/24428 A1 6/1998 2005/0142596 A1 6/2005 Krolewski et al . WO WO 98/24428 6/1998 A61K 31/34 2005/0152957 Al 7/2005 Cleary et al . WO 1998/37896 A1 9/1998 2005/0233398 Al 10/2005 Chu et al . WO 99/11252 A2 3/1999 2005/0277680 A1 12/2005 Priebe et al . WO 99/63985 A1 12/1999 2006/0036098 Al 2/2006 Kim et al . WO 01/44192 A1 6/2001 2006/0062739 A1 3/2006 Hofmann et al . WO 01/44218 A1 6/2001 2006/0100272 A1 5/2006 Maniar WO 01/45678 A1 6/2001 2006/0106020 A1 5/2006 Rodgers et al . WO 0226712 A2 4/2002 2006/0134008 A1 6/2006 Deaver WO 2004/012757 A2 2/2004 2006/0183906 A1 8/2006 Rodgers et al . WO 2004/110423 A1 12/2004 2007/0135461 A1 6/2007 Rodgers et al . WO 2005/014849 A2 2/2005 2007/0149469 A1 6/2007 Korherr WO 2005/089206 A2 9/2005 2007/0149506 A1 6/2007 Arvanitis et al .
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