IP Library Granted Patent US 12,702,657
Granted Patent B2
US 12,702,657 · App. 17/777,019 · Granted Aug 11, 2026

Treatment and prevention of dengue disease

Inventors: Olivia Gabriella M. Goethals (Bonheiden, BE); Bart Rudolf Romanie Kesteleyn (Berlare, BE); Bart Henri Theresia Stoops (Wechelderzande, BE); Jean-François Bonfanti (Ande, FR); Tim Hugo Maria Jonckers (Heist op den Berg, BE); Marnix Van Loock (Begijnendijk, BE); Suzanne Kaptein (Maastricht, NL); Johan Neyts (Kessel-Lo, BE)
Assignee: Katholieke Universiteit Leuven
A61K31/4045A61P31/14
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Quick Facts
Patent No.
US 12,702,657
App. No.
17/777,019
Filed
May 14, 2022
Granted
Aug 11, 2026
Kind
B2
Art Unit
1625
USPC
514/415
Abstract

The present invention relates to the use of substituted indole derivatives and substituted indoline derivatives in the manufacture of a medicament for the treatment of dengue disease in an individual infected by dengue virus or the prevention of dengue disease in an individual at risk of being infected by Dengue virus. The invention further provides a method for the treatment or the prevention of dengue in an individual at risk of being infected by Dengue virus.

Claims (24)

1 . A method for the prevention of dengue in an individual at risk of being infected by Dengue virus or for the treatment of dengue disease in an individual infected by Dengue virus, comprising the step of administering to said individual a medicament comprising compound of formula I, wherein the first administration of the medicament occurs at least 24 hours prior to viral infection to at most 5 days after being infected, and wherein the formula I corresponds to

a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof; said compound is selected from the group wherein:

R 1 is H, R 2 is F and R 3 is H or CH 3 ,

R 1 is H, CH 3 or F, R 2 is OCH 3 and R 3 is H,

R 1 is H, R 2 is OCH 3 and R 3 is CH 3 ,

R 1 is CH 3 , R 2 is F and R 3 is H,

R 1 is CF 3 or OCF 3 , R 2 is H and R 3 is H,

R 1 is OCF 3 , R 2 is OCH 3 and R 3 is H,

R 1 is OCF 3 , R 2 is H and R 3 is CH 3 .

2 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every 24 hours.

3 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue virus viral load in blood is kept at a level equal to or under 15 log 10 copies/mL.

4 . The method according to claim 1 , wherein the effective amount of the compound is from 0.05 mg/kg to 500 mg/kg body weight.

5 . The method according to claim 1 , wherein the medicament is administered orally, subcutaneously, intramuscularly, or intravenously.

6 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every week.

7 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every two weeks.

8 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every month.

9 . The method according to claim 1 , wherein the medicament is administered intermittently at least once every 6 months.

10 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 10 log 10 copies/mL.

11 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 7 log 10 copies/mL.

12 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 5 log 10 copies/mL.

13 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 3 log 10 copies/mL.

14 . The method according to claim 1 , wherein the medicament comprises an effective amount of compound of formula I, said effective amount is selected such that dengue viral load in blood is kept at a level equal to or under 2 log 10 copies/mL.

15 . The method according to claim 1 , wherein the compound is

16 . The method according to claim 15 , wherein the compound is the (S)-enantiomer of the compound of formula (a).

Assignments (6)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2026
From: JANSSEN PHARMACEUTICALS, INC.
To: KATHOLIEKE UNIVERSITEIT LEUVEN
Reel/Frame 075932/0967 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2023
From: BONFANTI, JEAN-FRANÇOIS
To: JANSSEN-CILAG
Reel/Frame 063184/0945 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2023
From: LOOCK, MARNIX VAN; KESTELEYN, BART RUDOLF ROMANIE; STOOPS, BART HENRI THERESIA; GOETHALS, OLIVIA GABRIELLA M.; JONCKERS, TIM HUGO MARIA
To: JANSSEN PHARMACEUTICA NV
Reel/Frame 063184/0867 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2023
From: NEYTS, JOHAN; KAPTEIN, SUZANNE
To: KATHOLIEKE UNIVERSITEIT LEUVEN
Reel/Frame 063185/0008 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2023
From: JANSSEN PHARMACEUTICA NV
To: JANSSEN PHARMACEUTICALS, INC.
Reel/Frame 063185/0167 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2023
From: JANSSEN-CILAG
To: JANSSEN PHARMACEUTICALS, INC.
Reel/Frame 063185/0068 →
Priority Claims (3)
EP 19209593 · Nov 15, 2019 · regional
EP 19213851 · Dec 5, 2019 · regional
EP 20171172 · Apr 23, 2020 · regional
Continuity (1)
Related Publication 20220409583A1 · Dec 29, 2022
References Cited (218)
US 7601735B2 · Tyms et al. · 2009 [cited by applicant]
US 8143259B2 · Colburn et al. · 2012 [cited by applicant]
US 8299056B2 · Bahmanyar et al. · 2012 [cited by applicant]
US 8324217B2 · Colburn et al. · 2012 [cited by applicant]
US 8524764B2 · Canales et al. · 2013 [cited by applicant]
US 8884030B2 · Canales et al. · 2014 [cited by applicant]
US 8993604B2 · Byrd et al. · 2015 [cited by applicant]
US 9029376B2 · Byrd et al. · 2015 [cited by applicant]
US 9522923B2 · Richards et al. · 2016 [cited by applicant]
US 9944598B2 · Kesteleyn et al. · 2018 [cited by applicant]
US 10029984B2 · Kesteleyn et al. · 2018 [cited by applicant]
US 10064870B2 · Rajagopalan et al. · 2018 [cited by applicant]
US 10071961B2 · Vandyck et al. · 2018 [cited by applicant]
US 10117850B2 · Griffioen et al. · 2018 [cited by applicant]
US 10206902B2 · Kesteleyn et al. · 2019 [cited by applicant]
US 10323026B2 · Ikeda et al. · 2019 [cited by applicant]
US 20050239821A1 · Neyts et al. · 2005 [cited by applicant]
US 20060194835A1 · Dugourd et al. · 2006 [cited by applicant]
US 20060211698A1 · Botyanszki et al. · 2006 [cited by applicant]
US 20080318338A1 · Kamal et al. · 2008 [cited by applicant]
US 20100048589A1 · Colburn et al. · 2010 [cited by applicant]
US 20120136006A1 · Colburn et al. · 2012 [cited by applicant]
US 20130023532A1 · Casillas et al. · 2013 [cited by applicant]
US 20140213586A1 · Bardiot et al. · 2014 [cited by applicant]
US 20160297810A1 · Bardiot et al. · 2016 [cited by applicant]
US 20170002006A1 · Corte et al. · 2017 [cited by applicant]
US 20170096429A1 · Corte et al. · 2017 [cited by applicant]
US 20170281633A1 · Boylan et al. · 2017 [cited by applicant]
US 20170281766A1 · Wiltzius · 2017 [cited by applicant]
US 20170283500A1 · Wiltzius et al. · 2017 [cited by applicant]
US 20170298017A1 · Kesteleyn et al. · 2017 [cited by applicant]
US 20180256544A1 · Kesteleyn et al. · 2018 [cited by applicant]
US 20180256545A1 · Kesteleyn et al. · 2018 [cited by applicant]
US 20180346419A1 · Kesteleyn et al. · 2018 [cited by applicant]
US 20190104738A1 · Narine et al. · 2019 [cited by applicant]
US 20190112266A1 · Kesteleyn et al. · 2019 [cited by applicant]
US 20190183931A1 · Bakker et al. · 2019 [cited by applicant]
CN 102026992A · 2011 [cited by applicant]
CN 102186833A · 2011 [cited by applicant]
CN 104024223A · 2014 [cited by applicant]
JP 2012206959A · 2012 [cited by applicant]
JP 2014527978A · 2014 [cited by applicant]
JP 2017531619A · 2017 [cited by applicant]
JP 2017531638A · 2017 [cited by applicant]
JP 2018503642A · 2018 [cited by applicant]
JP 2018515495A · 2018 [cited by applicant]
WO 1999021559A1 · 1999 [cited by applicant]
WO 2001060826A2 · 2001 [cited by applicant]
WO 2002089780A2 · 2002 [cited by applicant]
WO 2003050295A2 · 2003 [cited by applicant]
WO 2005095403A2 · 2005 [cited by applicant]
WO 2006071618A1 · 2006 [cited by applicant]
WO 2006076529A1 · 2006 [cited by applicant]
WO 2006136305A1 · 2006 [cited by applicant]
WO 2007017093A1 · 2007 [cited by applicant]
WO 2007026920A2 · 2007 [cited by applicant]
WO 2009149054A1 · 2009 [cited by applicant]
WO 2010021878A1 · 2010 [cited by applicant]
WO 2010027500A1 · 2010 [cited by applicant]
WO 2010091413A1 · 2010 [cited by applicant]
WO 2011031669A1 · 2011 [cited by applicant]
WO 2011037643A2 · 2011 [cited by applicant]
WO 2011088303A1 · 2011 [cited by applicant]
WO 2011120025A1 · 2011 [cited by applicant]
WO 2013045516A1 · 2013 [cited by applicant]
WO 2014154682A1 · 2014 [cited by applicant]
WO 2015187815 · 2015 [cited by applicant]
WO 2015188009 · 2015 [cited by applicant]
WO 2016050831A1 · 2016 [cited by applicant]
WO 2016050841A1 · 2016 [cited by applicant]
WO 2016053455A1 · 2016 [cited by applicant]
WO 2016057905 · 2016 [cited by applicant]
WO 2016113371A1 · 2016 [cited by applicant]
WO 2016180696A1 · 2016 [cited by applicant]
WO 2017013265 · 2017 [cited by applicant]
WO 2017046255A1 · 2017 [cited by applicant]
WO 2017046258A1 · 2017 [cited by applicant]
WO 2017079216A1 · 2017 [cited by applicant]
WO 2017165736A1 · 2017 [cited by applicant]
WO 2017167832A1 · 2017 [cited by applicant]
WO 2017167950A1 · 2017 [cited by applicant]
WO 2017167951A1 · 2017 [cited by applicant]
WO 2017167952A1 · 2017 [cited by applicant]
WO 2017167953A1 · 2017 [cited by applicant]
WO 2017171100A1 · 2017 [cited by applicant]
WO 2017173206A1 · 2017 [cited by applicant]
WO 2017173256A1 · 2017 [cited by applicant]
WO 2017173384A1 · 2017 [cited by applicant]
WO 2017173410A1 · 2017 [cited by applicant]
WO 2018178238A1 · 2018 [cited by applicant]
WO 2018178240A1 · 2018 [cited by applicant]
WO 2018215315A1 · 2018 [cited by applicant]
WO 2018215316A1 · 2018 [cited by applicant]
Satoshi Kutsuna, Dengue fever, Infectious Diseases Quick Reference (Kansensyo Quick Reference), 2019 (Well-known art) (Japanese document). [cited by applicant]
Tomohiko Takasaki, What is Dengue Fever? (Dengunetsu to wa), National Institute Of Infectious Disease, Information of Infectious Diseases (Kansensyo Jouhou), 2014 (Wellknown art) (Japanese document). [cited by applicant]
Naziroglu et al., entitled “Synthesis and application of L-proline and R-phenylglycine derived organocatalysts for direct asymmetric Michael addition of cyclohexanone to nitroalkenes,” Turk J Chem, 36 (2012), 659-670. [cited by applicant]
Aripo Office Action dated Feb. 10, 2016 in connection with African Patent Application No. AP/P/2014/007535. [cited by applicant]
Eurasian Office Action dated May 2016 in connection with Eurasian Patent Application No. 201490654, 1 page. [cited by applicant]
Summons to attend oral proceedings pursuant to Rule (115(1) EPC in connection with European Patent Application No. 12775463.8, Jul. 6, 2016. [cited by applicant]
New Zealand First Office Action dated Jul. 19, 2014 in connection with case No. 721700. [cited by applicant]
New Zealand Further Examination Report dated Jul. 19, 2016 in connection with case No. 622588. [cited by applicant]
Singapore Written Opinion dated Jul. 5, 2016 in connection with Singapore Patent Application No. Sep. 26, 2012. [cited by applicant]
Duan et al., entitled “Syntheses and Photochromic Studies of Dithienylethene-Containing Imidazolium Derivatives and Their Reactivity towards Nucleophiles,” Chem. Eur. J. 2010, 16, 13199-13209. [cited by applicant]
STN International, RN 1316109-81-5, 1297049-96-7, 1297011-10-9, 1296377-78-0, 1295540-00-9, 1295460-37-5, 1294813-77-6, 1294288-37-1, 1293697-77-4, 1287503-18-7, 1287040-60-1, 1286579-37-0, 1277962-26-1, 1252467-88-1, 1… [cited by applicant]
Examination Report on Israeli Patent Application No. 231492, 3 pages, with Annex to Report, 1 page, Nov. 30, 2015. [cited by applicant]
Registry No. 1277962-26-1, entered in STN on Apr. 10, 2011. [cited by applicant]
Registry No. 924715-04-8, entered in STN on Mar. 4, 2007. [cited by applicant]
Registry No. 1386766-68-2, entered in STN on Aug. 6, 2012. [cited by applicant]
Registry No. 1388775-15-2, entered in STN on Aug. 9, 2012. [cited by applicant]
Registry No. 1388908-86-8, entered in STN on Aug. 14, 2012. [cited by applicant]
Registry No. 1386200-09-4, entered in STN on Aug. 3, 2012. [cited by applicant]
Registry No. 1388629-42-2, entered in STN on Aug. 9, 2012. [cited by applicant]
Japanese Office Action dated Jun. 2, 2020 from Japanese Patent Appln. No. JP2017-243354 (English language translation). [cited by applicant]
Registry No. 1219356-85-0 entered STN Apr. 15, 2010. [cited by applicant]
Registry No. 1041392-09-9 entered STN Aug. 17, 2008. [cited by applicant]
Registry No. 1036730-78-5 entered STN Jul. 28, 2008. [cited by applicant]
Japanese Office Action dated Apr. 21, 2016 in connection with Japanese Patent Application No. 2014-531279. [cited by applicant]
Prasad L. Polavarapu et al., “Intrinsic Rotation and Molecular Structure,” Chirality 15: S143-S149 (2003). [cited by applicant]
Prevention of Dengue, Centers for Disease Control and Prevention, retrieved from the internet at https://www.cdc.gov/dengue/prevention/index.html, page last updated Sep. 27, 2012, retrieved from the intemet on Jan. 8, 2… [cited by applicant]
Lidia Moreira Lima et al., “Bioisosterism: A Useful Strategy for Molecular Modification and Drug Design,” Current Medicinal Chemistry, Bentham Science Publishers Ltd. (2005), vol. 12, pp. 23-49. [cited by applicant]
Ian Stansfield et al., “Development of carpoxylic acid replacements in indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase,” Bioorganic & Medicinal Chemistry Letters, vol. 17 (2007) 5143-5149, ScienceDire… [cited by applicant]
Boltromeyuk V.V., Obshchaya khimiya (General Chemistry), Minsk, Vysheyshaya shkola, 2012, p. 65 (translation). [cited by applicant]
Wolff et al., Burger's Medicinal Chemistry and Drug Discovery, 5th Ed., vol. 1: Principles and Practice, pp. 975-977 (1995). [cited by applicant]
Banker et al., (1996) Modern Pharmaceuticals, 3rd Edition, Revised and Expanded, p. 596. [cited by applicant]
N.C.B.I.: “qHTS for inhibitors of binding or entry into cells for Marburg Virus,” Pubchem Bioassay Record AID 540276, Jul. 2011, 13 pages, XP55641386, Retreved from the Internet: https://pubchem.ncbi.nlm.nih.gov/bioassa… [cited by applicant]
EP Search Report dated Nov. 19, 2019 from European Patent AppIn No. EP 19183201.3. [cited by applicant]
“Solvation,” Wikipedia, at internet address: https://en.wikipedia.org/wiki/Solvation, web page last edited on Mar. 13, 2019, 6 pages. [cited by applicant]
Examination Report dated Jan. 7, 2020, from Indian Patent Appln. No. 201727014547. [cited by applicant]
ACS on STN Registry No. 931079-09-3, Apr. 20, 2007. [cited by applicant]
ACS on STN Registry No. 931007-71-5, Apr. 19, 2007. [cited by applicant]
ACS on STN Registry No. 930910-25-1, Apr. 19, 2007. [cited by applicant]
ACS on STN Registry No. 930724-99-5, Apr. 18, 2007. [cited by applicant]
ACS on STN Registry No. 930463-83-5, Apr. 17, 2007. [cited by applicant]
ACS on STN Registry No. 925399-60-6, Mar. 7, 2007. [cited by applicant]
ACS on STN Registry No. 920950-24-9, Feb. 14, 2007. [cited by applicant]
ACS on STN Registry No. 920926-40-5, Feb. 14, 2007. [cited by applicant]
ACS on STN Registry No. 920888-80-8, Feb. 14, 2007. [cited by applicant]
ACS on STN Registry No. 920870-55-9, Feb. 14, 2007. [cited by applicant]
ACS on STN Registry No. 920827-69-6, Feb. 14, 2007. [cited by applicant]
ACS on STN Registry No. 920696-97-5, Feb. 13, 2007. [cited by applicant]
ACS on STN Registry No. 920694-81-1, Feb. 13, 2007. [cited by applicant]
ACS on STN Registry No. 920668-38-8, Feb. 13, 2007. [cited by applicant]
ACS on STN Registry No. 879164-92-8, Apr. 4, 2006. [cited by applicant]
ACS on STN Registry No. 878462-38-5, Mar. 29, 2006. [cited by applicant]
ACS on STN Registry No. 853320-15-7, Jun. 30, 2005. [cited by applicant]
International Search Report and Written Opinion dated Aug. 22, 2016, for International Patent Application No. PCT/EP2016/059975. [cited by applicant]
Opposition filed in Ecuadorian Patent Application No. SENADI-2019-83621 (English language translation). [cited by applicant]
Opposition filed in Ecuadorian Patent Application No. SENADI-2019-83640 (English language translation). [cited by applicant]
ACS Registry No. 1295460-37-5, entered STN: May 16, 2011, “Registry Copyright 2015 ACS on STN,” p. 19. [cited by applicant]
ACS Registry 1252467-88-1, entered STN: Nov. 10, 2010, “Registry Copyright 2015 ACS on STN,” p. 20. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2007, Pubchem CID: 16307180, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Dec. 4, 2007, Pubchem CID: 18190680, 11 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 20, 2009, Pubchem CID: 42916879, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377731, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377750, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377765, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377782, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377825, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377845, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377864, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377894, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377913, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377936, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377950, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8377957, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8378071, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 8378972, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 9292530, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2006, Pubchem CID: 9329202, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 31, 2006, Pubchem CID: 9356704, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 31, 2006, Pubchem CID: 9461840, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2007, Pubchem CID: 16267760, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2007, Pubchem CID: 16340406, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2007, Pubchem CID: 16343459, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 30, 2007, Pubchem CID: 16366089, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Dec. 4, 2007, Pubchem CID: 18226977, 10 pages. [cited by applicant]
Database Pubchem [online] NCBI; Feb. 29, 2008, Pubchem CID: 24614828, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Feb. 29, 2008, Pubchem CID: 24614964, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; Feb. 29, 2008, Pubchem CID: 24652310, 11 pages. [cited by applicant]
Database Pubchem [online] NCBI; May 28, 2009, Pubchem CID: 26654475, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; May 29, 2009, Pubchem CID: 31392427, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; May 30, 2009, Pubchem CID: 39912467, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Nov. 25, 2010, Pubchem CID: 47065408, 12 pages. [cited by applicant]
Database Pubchem [online] NCBI; May 20, 2011, Pubchem CID: 52708600, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; May 20, 2011, Pubchem CID: 52764912, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; May 20, 2011, Pubchem CID: 52886897, 9 pages. [cited by applicant]
Database Pubchem [online] NCBI; Sep. 17, 2005, Database accession No. CID 4793342, 4 pages. [cited by applicant]
Database Pubchem [online] NCBI; Sep. 17, 2005, Database accession No. CID 4796066, 4 pages. [cited by applicant]
Database Pubchem [online] NCBI; Sep. 17, 2005, Database accession No. CID 4849237, 4 pages. [cited by applicant]
Database Pubchem [online] NCBI; Sep. 17, 2005, Database accession No. CID 4793878, 4 pages. [cited by applicant]
PubChem [online] 2006.07.30 PubChem CID 8377731, 12 pages. [cited by applicant]
The PCT International Search Report dated Nov. 29, 2012 in connection with PCT International Patent Application No. PCT/EP2012/69007, 4 pages. [cited by applicant]
Columbian Office Action dated Oct. 28, 2015 in connection with Colombian Patent Application No. 14-89597-8. [cited by applicant]
Declaration of Neil Thomas Simpkin Ba regarding certified English-language translation dated Jan. 19, 2015, 1 page. [cited by applicant]
Opposition in connection with patent family member, Costa Rican Patent Application No. 2014-0147 dated Nov. 14, 2014, 23 pages. [cited by applicant]
Invitation to Respond to Written Opinion dated Jan. 8, 2015, from the Intellectual Property Office of Singapore in connection with patent family member Singapore Application No. 11201400927W, 9 pages. [cited by applicant]
Li et al., entitled “Thiazolium-derived N-heterocyclic carbene-catalyzed cross-coupling of aldehydes with unactived imines,” Chem. Commun, 2007, 852-854. [cited by applicant]
Communication European Search Report dated Nov. 19, 2019, in connection with European Patent Application No. 19183201.3. [cited by applicant]
Bergman et al., Synthesis and reactions of some 3-(2-haloacyl)indoles. Tetrahedron 29: 971-976, 1973. [cited by applicant]
PCT Notification Concerning Transmittal of International Preliminary Report on Patentability and Written Opinion of the International Searching Authority dated Apr. 10, 2014 in connection with PCT International Patent A… [cited by applicant]
Office Action dated Jun. 4, 2015 in connection with Columbian Patent Application No. 14-89597-5, 26 pages. [cited by applicant]
Registry No. 1241127-58-1, entered in STN on Sep. 15, 2010. [cited by applicant]
Registry No. 1062257-51-5, entered in STN on Oct. 16, 2008. [cited by applicant]
Registry No. 1062132-16-4, entered in STN on Oct. 16, 2008. [cited by applicant]
Registry No. 1030735-63-7, entered in STN on Jun. 26, 2008. [cited by applicant]
Registry No. 1030232-46-2, entered in STN on Jun. 24, 2008. [cited by applicant]
Registry No. 1014493-63-0, entered in STN on Apr. 14, 2008. [cited by applicant]
Database Pubchem [online] NCBI; Jul. 31, 2006, Pubchem CID: 9356705, 3 page. [cited by applicant]
Database Pubchem [online] NCBI; May 29, 2009, Pubchem CID: 31392243, 1 page. [cited by applicant]
Database Pubchem [online] NCBI; May 29, 2009, Pubcchem CID: 37329396, 2 pages. [cited by applicant]
Office Action dated Jun. 25, 2018 that issued in connection with patent family member Peruvian Patent Application. [cited by applicant]
English translation of an Office Action dated May 4, 2018 that issued in connection with patent family member Eurasian Patent Application No. 201490654. [cited by applicant]
English translation of an Office Action dated Jun. 22, 2018 issued in connection with patent family member Uzbekistan Patent Application. [cited by applicant]
English translation of an Office Action dated Jun. 28, 2018 that issued in connection with patent family member Chilean Divisional Patent Application No. 201601580. [cited by applicant]
Canadian Office Action dated May 2, 2018 that issued in connection with patent family member Canadian Patent App. No. 2,848,604. [cited by applicant]
New Zealand Further Examination Report dated Jan. 19, 2018 in connection with New Zealand Patent Application No. 721700. [cited by applicant]
Wei-Kung Wang et al., High Levels of plasma Dengue Viral Load during Defervescence in Patients with Dengue Hemorrhagic Fever: Implications for Pathogenesis, Virology, 2003, 305, 330-338. [cited by applicant]
Rotem Ben-Shachar et al., Drivers of Inter-individual Variation in Dengue Viral Load Dynamics, PLoS Computational Biology, 2016, 12 (11), e1005194. [cited by applicant]