IP Library › Granted Patent US 50,642
Granted Patent E1
US 50,642 · App. 17/896,658 · Granted Oct 21, 2025

Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer

Inventor: Isan Chen (San Diego, CA)
Assignee: Aragon Pharmaceuticals, Inc.
A61K31/4439A61K31/00A61K31/4166
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 50,642
App. No.
17/896,658
Granted
Oct 21, 2025
Kind
E1
Abstract

Described herein are methods of treating non-metastatic castrate-resistant prostate cancer with anti-androgens.

Claims (86)

1. A method of treating a male human with non-metastatic castration-resistant prostate cancer, the method comprising administering an anti-androgen at a dose of about 30 mg per day to about 480 mg per day to a male human in need of such treatment, wherein the anti-androgen is:

4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2 fluoro-N-methylbenzamide,

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or

4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;

wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.

2. The method of claim 1 , wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer.

3. The method of claim 1 , wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.

4. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered daily to the male human.

5. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5, 7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of about 180 mg per day to about 480 mg per day.

6. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of:

(a) about 30 mg per day;

(b) about 60 mg per day;

(c) about 90 mg per day;

(d) about 120 mg per day; or

(e) about 240 mg per day.

7. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered orally to the male human on a continuous daily dosage schedule.

8. The method of claim 3 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.

9. The method of claim 1 , wherein the anti-androgen is 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide.

10. The method of claim 9 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.

11. The method of claim 1 , wherein the anti-androgen is 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.

12. The method of claim 11 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.

13. The method of claim 1 , wherein the anti-androgen is administered orally to the male human.

14. A method of treating a male human with non-metastatic castration-resistant prostate cancer, the method consisting essentially of administering an anti-androgen at a dose of about 30 mg per day to about 480 mg per day to a male human in need of such treatment, wherein the anti-androgen is:

4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2 fluoro-N-methylbenzamide,

4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or

4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;

wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.

15. The method of claim 14 , wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.

16. The method of claim 15 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.

17. The method of claim 15 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of:

(a) about 30 mg per day;

(b) about 60 mg per day;

(c) about 90 mg per day;

(d) about 120 mg per day; or

(e) about 240 mg per day.

18. The method of claim 9 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 160 mg per day.

19. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 240 mg per day.

20. The method of claim 3 , wherein the GnRH agonist is leuprolide.

21. The method of claim 3 , wherein the GnRH agonist is buserelin.

22. The method of claim 3 , wherein the GnRH agonist is naferelin.

23. The method of claim 3 , wherein the GnRH agonist is histrelin.

24. The method of claim 3 , wherein the GnRH agonist is goserelin.

25. The method of claim 3 , wherein the GnRH agonist is deslorelin.

26. A method of treating non-metastatic castration-resistant prostate cancer in a male human comprising administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer;

wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro [3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;

wherein the anti-androgen is administered in an amount of about 180 mg per day or 120 mg per day;

and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.

27. The method of claim 26 , wherein the anti-androgen is administered in an amount of about 180 mg per day.

28. The method of claim 26 , wherein the anti-androgen is administered in an amount of about 120 mg per day.

29. The method of claim 26 , wherein the male human was previously treated at 240 mg per day and required dose reduction.

30. The method of claim 26 , wherein the male human was previously treated at 240 mg per day and required dose interruption.

31. The method of claim 26 , wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer.

32. The method of claim 31 , wherein the male human with the high risk non-metastatic castration-resistant prostate cancer has a prostate-specific antigen doubling time (PSADT) that is less than or equal to 10 months.

33. The method of claim 28 , wherein the male human has experienced 3 consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with the last PSA>2 ng/ml.

34. The method of claim 26 , wherein the male human is further treated to maintain castrate levels of testosterone of less than 50 ng/dL.

35. The method of claim 26 , wherein the anti-androgen is administered daily to the male human.

36. The method of claim 26 , wherein the anti-androgen is administered orally to the male human.

37. The method of claim 26 , wherein the anti-androgen is administered to the male human orally and on a continuous daily dosing schedule.

38. The method of claim 26 , wherein the male human has previously been treated with either orchiectomy or continuous androgen deprivation therapy (ADT).

39. The method of claim 38 , wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone (GnRH) agonist or antagonist.

40. The method of claim 39 , wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone agonist; and wherein the gonadotropin-releasing hormone is leuprolide, buserelin, nafarelin, histrelin, goserelin, or deslorelin.

41. A method of treating non-metastatic castration-resistant prostate cancer in a male human consisting essentially of administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer;

wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;

wherein the anti-androgen is administered in an amount of about 180 mg per day or 120 mg per day;

and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.

42. The method of claim 41 , wherein the anti-androgen is administered in an amount of about 180 mg per day.

43. The method of claim 41 , wherein the anti-androgen is administered in an amount of about 120 mg per day.

44. The method of claim 41 , wherein the male human was previously treated at 240 mg per day and required dose reduction.

45. The method of claim 41 , wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer.

46. The method of claim 45 , wherein the male human with the high risk non-metastatic castration-resistant prostate cancer has a prostate-specific antigen doubling time (PSADT) that is less than or equal to 10 months.

47. The method of claim 45 , wherein the male human has experienced 3 consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with the last PSA>2 ng/mL.

48. The method of claim 41 , wherein the male human is further treated to maintain castrate levels of testosterone of less than 50 ng/dL.

49. The method of claim 41 , wherein the anti-androgen is administered daily to the male human.

50. The method of claim 41 , wherein the anti-androgen is administered orally to the male human.

51. The method of claim 41 , wherein the anti-androgen is administered to the male human orally and on a continuous daily dosing schedule.

52. The method of claim 41 , wherein the male human has previously been treated with either orchiectomy or continuous androgen deprivation therapy (ADT).

53. The method of claim 52 , wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone (GnRH) agonist or antagonist.

54. The method of claim 53 , wherein the continuous androgen deprivation therapy comprises administration of a gonadotropin-releasing hormone agonist; and wherein the gonadotropin-releasing hormone is leuprolide, buserelin, nafarelin, histrelin, goserelin, or deslorelin.

55. A method of treating non-metastatic castration-resistant prostate cancer in a male human comprising administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer;

wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;

wherein the anti-androgen is administered in an amount of about 180 mg per day;

and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.

56. A method of treating non-metastatic castration-resistant prostate cancer in a male human consisting essentially of administering a therapeutically effective amount of an anti-androgen to a male human with a non-metastatic castration-resistant prostate cancer;

wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;

wherein the anti-androgen is administered in an amount of about 180 mg per day;

and wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.

Continuity (5)
Continuation 16998683 · Aug 20, 2020
Reissue 15851444 · Dec 21, 2017
Continuation 14034460 · Sep 23, 2013
Provisional Application 61705900 · Sep 26, 2012
Reissue 15851444 · Dec 21, 2017
References Cited (400)
US 3798233A · Akiba et al. · 1974 [cited by applicant]
US 3823240A · Sauli · 1974 [cited by applicant]
US 3984430A · Curran · 1976 [cited by applicant]
US 4097578A · Perronnet et al. · 1978 [cited by applicant]
US 4229447A · Porter · 1980 [cited by applicant]
US 4234736A · Bernauer et al. · 1980 [cited by applicant]
US 4304782A · Dumont et al. · 1981 [cited by applicant]
US 4312881A · Wootton · 1982 [cited by applicant]
US 4399216A · Axel et al. · 1983 [cited by applicant]
US 4407814A · Bernauer et al. · 1983 [cited by applicant]
US 4427438A · Nagano et al. · 1984 [cited by applicant]
US 4473393A · Nagpal · 1984 [cited by applicant]
US 4482739A · Bernauer et al. · 1984 [cited by applicant]
US 4559157A · Smith et al. · 1985 [cited by applicant]
US 4596795A · Pitha · 1986 [cited by applicant]
US 4608392A · Jacquet et al. · 1986 [cited by applicant]
US 4749403A · Liebl et al. · 1988 [cited by applicant]
US 4755386A · Hsiao et al. · 1988 [cited by applicant]
US 4820508A · Wortzman · 1989 [cited by applicant]
US 4859228A · Prisbylla · 1989 [cited by applicant]
US 4873256A · Coussediere et al. · 1989 [cited by applicant]
US 4938949A · Borch et al. · 1990 [cited by applicant]
US 4944791A · Schroder et al. · 1990 [cited by applicant]
US 4992478A · Geria · 1991 [cited by applicant]
US 5010182A · Brake et al. · 1991 [cited by applicant]
US 5011692A · Fujioka et al. · 1991 [cited by applicant]
US 5017381A · Maruyama et al. · 1991 [cited by applicant]
US 5033252A · Carter · 1991 [cited by applicant]
US 5052558A · Carter · 1991 [cited by applicant]
US 5069711A · Fischer et al. · 1991 [cited by applicant]
US 5071773A · Evans et al. · 1991 [cited by applicant]
US 5166358A · Seuron et al. · 1992 [cited by applicant]
US 5229135A · Philippon et al. · 1993 [cited by applicant]
US 5323907A · Kalvelage · 1994 [cited by applicant]
US 5355233A · Okamoto · 1994 [cited by applicant]
US 5411981A · Gaillard-Kelly et al. · 1995 [cited by applicant]
US 5434176A · Claussner et al. · 1995 [cited by applicant]
US 5554607A · Elokdah et al. · 1996 [cited by applicant]
US 5556983A · Claussner et al. · 1996 [cited by applicant]
US 5589497A · Claussner et al. · 1996 [cited by applicant]
US 5614620A · Liao et al. · 1997 [cited by applicant]
US 5627201A · Gaillard-Kelly et al. · 1997 [cited by applicant]
US 5631144A · Lemoine et al. · 1997 [cited by applicant]
US 5646172A · Claussner et al. · 1997 [cited by applicant]
US 5656651A · Sovak et al. · 1997 [cited by applicant]
US 5705654A · Claussner et al. · 1998 [cited by applicant]
US 5726061A · Robbins et al. · 1998 [cited by applicant]
US 5738685A · Halm et al. · 1998 [cited by applicant]
US 5739136A · Ellinwood, Jr. et al. · 1998 [cited by applicant]
US 5750553A · Claussner et al. · 1998 [cited by applicant]
US 5780435A · Garnick et al. · 1998 [cited by applicant]
US 5783707A · Elokdah et al. · 1998 [cited by applicant]
US RE35956E · Gaillard-Kelly et al. · 1998 [cited by applicant]
US 5837284A · Mehta et al. · 1998 [cited by applicant]
US 5840329A · Bai · 1998 [cited by applicant]
US 5958936A · Claussner et al. · 1999 [cited by applicant]
US 5968875A · Bis et al. · 1999 [cited by applicant]
US 5985868A · Gray · 1999 [cited by applicant]
US 6004963A · Zimmer et al. · 1999 [cited by applicant]
US 6087509A · Claussner et al. · 2000 [cited by applicant]
US 6107488A · Bouchet et al. · 2000 [cited by applicant]
US 6172076B1 · Embrey et al. · 2001 [cited by applicant]
US 6235910B1 · Beller et al. · 2001 [cited by applicant]
US 6242611B1 · Claussner et al. · 2001 [cited by applicant]
US 6307030B1 · French et al. · 2001 [cited by applicant]
US 6350763B1 · Kelly et al. · 2002 [cited by applicant]
US 6472415B1 · Sovak et al. · 2002 [cited by applicant]
US 6479063B2 · Weisman et al. · 2002 [cited by applicant]
US 6489163B1 · Roy et al. · 2002 [cited by applicant]
US 6506607B1 · Shyjan · 2003 [cited by applicant]
US 6673799B1 · Taniguchi et al. · 2004 [cited by applicant]
US 6710037B2 · Wang et al. · 2004 [cited by applicant]
US 6828471B2 · Sawyers et al. · 2004 [cited by applicant]
US 7166599B2 · Bornemann et al. · 2007 [cited by applicant]
US 7271188B2 · Tachibana et al. · 2007 [cited by applicant]
US 7709517B2 · Sawyers et al. · 2010 [cited by applicant]
US 8110594B2 · Jung et al. · 2012 [cited by applicant]
US 8183274B2 · Sawyers et al. · 2012 [cited by applicant]
US 8445507B2 · Jung et al. · 2013 [cited by applicant]
US 8461343B2 · Ouerfelli et al. · 2013 [cited by applicant]
US 8470829B2 · Tachibana et al. · 2013 [cited by applicant]
US 8648105B2 · Jung et al. · 2014 [cited by applicant]
US 8729082B2 · Koppitz et al. · 2014 [cited by applicant]
US 8802689B2 · Jung et al. · 2014 [cited by applicant]
US 8841081B2 · Persson · 2014 [cited by applicant]
US 8987452B2 · Ouerfelli et al. · 2015 [cited by applicant]
US 9108944B2 · Smith et al. · 2015 [cited by applicant]
US 9126941B2 · Sawyers et al. · 2015 [cited by applicant]
US 9289436B2 · Szmulewitz et al. · 2016 [cited by applicant]
US 9340524B2 · Chen · 2016 [cited by applicant]
US 9388159B2 · Jung et al. · 2016 [cited by applicant]
US 9415085B2 · Van Der Meulen et al. · 2016 [cited by applicant]
US 9481664B2 · Smith et al. · 2016 [cited by applicant]
US 9512103B2 · Ouerfelli et al. · 2016 [cited by applicant]
US 9579359B2 · Olesen et al. · 2017 [cited by applicant]
US 9675586B2 · Chow et al. · 2017 [cited by applicant]
US 9808472B2 · Njar et al. · 2017 [cited by applicant]
US 9877999B2 · Persson · 2018 [cited by applicant]
US 9884054B2 · Chen · 2018 [cited by applicant]
US 9987261B2 · Jung et al. · 2018 [cited by applicant]
US 10052314B2 · Chen · 2018 [cited by applicant]
US 10537586B2 · Altschul et al. · 2020 [cited by applicant]
US 10695398B2 · Van Der Meulen et al. · 2020 [cited by applicant]
US 10702508B2 · Molina · 2020 [cited by applicant]
US 10729739B2 · Olesen et al. · 2020 [cited by applicant]
US 10799488B2 · Chen · 2020 [cited by applicant]
US 10799489B2 · Chen · 2020 [cited by applicant]
US 10849888B2 · Chen · 2020 [cited by applicant]
US 10857139B2 · Jung et al. · 2020 [cited by applicant]
US 10973870B2 · Olesen et al. · 2021 [cited by applicant]
US 11116775B2 · Altschul et al. · 2021 [cited by applicant]
US 11160796B2 · Molina · 2021 [cited by applicant]
US 11491149B2 · Molina · 2022 [cited by applicant]
US RE49353E · Chen · 2023 [cited by examiner]
US 11963952B2 · Yu · 2024 [cited by applicant]
US 20020133833A1 · Sawyers et al. · 2002 [cited by applicant]
US 20030144252A1 · Furr · 2003 [cited by applicant]
US 20030225138A1 · Sircar et al. · 2003 [cited by applicant]
US 20040009969A1 · Jung et al. · 2004 [cited by applicant]
US 20040077605A1 · Salvati et al. · 2004 [cited by applicant]
US 20040116417A1 · Boubia et al. · 2004 [cited by applicant]
US 20050153968A1 · Bi et al. · 2005 [cited by applicant]
US 20060025589A1 · Binet et al. · 2006 [cited by applicant]
US 20060127902A1 · Madden et al. · 2006 [cited by applicant]
US 20070004753A1 · Sawyers et al. · 2007 [cited by applicant]
US 20070027142A1 · Megati et al. · 2007 [cited by applicant]
US 20070249697A1 · Tachibana et al. · 2007 [cited by applicant]
US 20070254933A1 · Jung et al. · 2007 [cited by applicant]
US 20080032935A1 · Engel et al. · 2008 [cited by applicant]
US 20080139634A2 · Jung et al. · 2008 [cited by applicant]
US 20080279865A1 · Gomez-Navarro · 2008 [cited by applicant]
US 20090203622A1 · Persson · 2009 [cited by applicant]
US 20090203623A1 · Olesen et al. · 2009 [cited by applicant]
US 20090312295A1 · Mckearn et al. · 2009 [cited by applicant]
US 20100190991A1 · Ouerfelli et al. · 2010 [cited by applicant]
US 20100267682A1 · Johri et al. · 2010 [cited by applicant]
US 20110003839A1 · Jung et al. · 2011 [cited by applicant]
US 20120190718A1 · Jung et al. · 2012 [cited by applicant]
US 20130029910A1 · Meulen et al. · 2013 [cited by applicant]
US 20130045204A1 · Andersen et al. · 2013 [cited by applicant]
US 20130072511A1 · Jung et al. · 2013 [cited by applicant]
US 20130079241A1 · Luo et al. · 2013 [cited by applicant]
US 20130116258A1 · Smith et al. · 2013 [cited by applicant]
US 20130225821A1 · Ouerfelli et al. · 2013 [cited by applicant]
US 20130253035A1 · McDonnell et al. · 2013 [cited by applicant]
US 20140088129A1 · Chen · 2014 [cited by applicant]
US 20140113870A1 · Olesen et al. · 2014 [cited by applicant]
US 20140187641A1 · Dalton et al. · 2014 [cited by applicant]
US 20140199236A1 · Chen et al. · 2014 [cited by applicant]
US 20140309262A1 · Jung et al. · 2014 [cited by applicant]
US 20140314860A1 · Shah et al. · 2014 [cited by applicant]
US 20140343111A1 · Sawyers et al. · 2014 [cited by applicant]
US 20140349935A1 · Persson · 2014 [cited by applicant]
US 20150133481A1 · Dilhas et al. · 2015 [cited by applicant]
US 20160376252A1 · Bonnefous et al. · 2016 [cited by applicant]
US 20170014399A1 · Jung et al. · 2017 [cited by applicant]
US 20170035833A1 · Van Der Meulen et al. · 2017 [cited by applicant]
US 20170290879A1 · Olesen et al. · 2017 [cited by applicant]
US 20180318276A1 · Jung et al. · 2018 [cited by applicant]
US 20180318277A1 · Chen · 2018 [cited by applicant]
US 20190151335A1 · Altschul et al. · 2019 [cited by applicant]
US 20190167755A1 · Persson · 2019 [cited by applicant]
US 20190269667A1 · Chen · 2019 [cited by applicant]
US 20190269668A1 · Chen · 2019 [cited by applicant]
US 20200237854A1 · Olesen et al. · 2020 [cited by applicant]
US 20210121450A1 · Jung et al. · 2021 [cited by applicant]
US 20210128673A1 · Van Der Meulen et al. · 2021 [cited by applicant]
US 20210177821A1 · Chen et al. · 2021 [cited by applicant]
US 20210361675A1 · Altschul et al. · 2021 [cited by applicant]
US 20220054468A9 · Molina · 2022 [cited by applicant]
AU 217893 · 1958 [cited by applicant]
AU 2013323861A1 · 2015 [cited by applicant]
AU 2018206695C1 · 2020 [cited by applicant]
CA 2579886A1 · 2006 [cited by applicant]
CL 201500715 · 2015 [cited by applicant]
CL 201403331 · 2016 [cited by applicant]
CN 101032483 · 2007 [cited by applicant]
CN 101032483A · 2007 [cited by applicant]
CN 101032486A · 2007 [cited by applicant]
CN 101454002A · 2009 [cited by applicant]
CN 101528308A · 2009 [cited by applicant]
CN 101528309A · 2009 [cited by applicant]
CN 102413831A · 2012 [cited by applicant]
CN 104661658A · 2015 [cited by applicant]
CN 104857157A · 2015 [cited by applicant]
CN 105636594A · 2016 [cited by applicant]
DE 2102605 · 1971 [cited by applicant]
DE 2614831 · 1977 [cited by applicant]
DE 2614831A1 · 1977 [cited by applicant]
EA 030128 · 2018 [cited by applicant]
EP 0017976 · 1980 [cited by applicant]
EP 0017976B1 · 1983 [cited by applicant]
EP 0002259 · 1984 [cited by applicant]
EP 0002259B1 · 1984 [cited by applicant]
EP 0144098 · 1985 [cited by applicant]
EP 0144098A1 · 1985 [cited by applicant]
EP 0331232 · 1989 [cited by applicant]
EP 0331232A2 · 1989 [cited by applicant]
EP 0362179 · 1990 [cited by applicant]
EP 0362179A2 · 1990 [cited by applicant]
EP 0494819 · 1992 [cited by applicant]
EP 0572191 · 1993 [cited by applicant]
EP 0572191A1 · 1993 [cited by applicant]
EP 0578516 · 1994 [cited by applicant]
EP 0578516A1 · 1994 [cited by applicant]
EP 0580459 · 1994 [cited by applicant]
EP 0494819B1 · 1996 [cited by applicant]
EP 0770613 · 1997 [cited by applicant]
EP 0770613A1 · 1997 [cited by applicant]
EP 0721944 · 2001 [cited by applicant]
EP 0721944B1 · 2001 [cited by applicant]
EP 0580459B1 · 2001 [cited by applicant]
EP 1632477 · 2006 [cited by applicant]
EP 1632477A1 · 2006 [cited by applicant]
EP 1007080B1 · 2007 [cited by applicant]
EP 1790640 · 2007 [cited by applicant]
EP 1790640A1 · 2007 [cited by applicant]
EP 1893196B1 · 2012 [cited by applicant]
EP 2439196A1 · 2012 [cited by applicant]
EP 2900224A1 · 2015 [cited by applicant]
EP 2945628A1 · 2015 [cited by applicant]
EP 3305285A1 · 2018 [cited by applicant]
FR 2693461 · 1994 [cited by applicant]
FR 2693461A1 · 1994 [cited by applicant]
FR 2715402 · 1995 [cited by applicant]
FR 2715402A1 · 1995 [cited by applicant]
FR 2845384 · 2004 [cited by applicant]
FR 2845384A1 · 2004 [cited by applicant]
FR 2845385A1 · 2004 [cited by applicant]
GB 0800244A · 1958 [cited by applicant]
HK 1212221A1 · 2016 [cited by applicant]
HU 217893 · 2000 [cited by applicant]
ID 201603647 · 2016 [cited by applicant]
ID 16033432 · 2016 [cited by applicant]
JP 59210083A · 1984 [cited by applicant]
JP 59210083 · 1984 [cited by applicant]
JP 60239737A · 1985 [cited by applicant]
JP 64009978A · 1989 [cited by applicant]
JP 1009978 · 1989 [cited by applicant]
JP 01009978Y2 · 1989 [cited by applicant]
JP 02019363A · 1990 [cited by applicant]
JP 0219363 · 1990 [cited by applicant]
JP 08009997 · 1996 [cited by applicant]
JP 08099977A · 1996 [cited by applicant]
JP 10009978A · 1998 [cited by applicant]
JP 2845384B2 · 1999 [cited by applicant]
JP 2000502053A · 2000 [cited by applicant]
JP 2003530348 · 2003 [cited by applicant]
JP 2004525175 · 2004 [cited by applicant]
JP 2004252175A · 2004 [cited by applicant]
JP 2006022118A · 2006 [cited by applicant]
JP 2006510600 · 2006 [cited by applicant]
JP 2006265244A · 2006 [cited by applicant]
JP 2008512419A · 2008 [cited by applicant]
JP 2008099977A · 2008 [cited by applicant]
JP 2008540523 · 2008 [cited by applicant]
JP 2009502925A · 2009 [cited by applicant]
JP 2009531439 · 2009 [cited by applicant]
JP 2010500975A · 2010 [cited by applicant]
JP 2010504307A · 2010 [cited by applicant]
JP 2011503075A · 2011 [cited by applicant]
JP 4644737B2 · 2011 [cited by applicant]
JP 2011068653A · 2011 [cited by applicant]
JP 2012211190A · 2012 [cited by applicant]
JP 2012236843A · 2012 [cited by applicant]
JP 5133975B2 · 2013 [cited by applicant]
JP 2015531373A · 2015 [cited by applicant]
JP 2015534582A · 2015 [cited by applicant]
JP 2016508991A · 2016 [cited by applicant]
JP 6351597B2 · 2018 [cited by applicant]
JP 2018150365A · 2018 [cited by applicant]
KR 1020150070192A · 2015 [cited by applicant]
MX 2015003909A · 2016 [cited by applicant]
NZ 705815A · 2018 [cited by applicant]
UA 117663 · 2018 [cited by applicant]
WO 9013646A1 · 1990 [cited by applicant]
WO WO9013646 · 1990 [cited by applicant]
WO 9700071A1 · 1997 [cited by applicant]
WO WO9700071 · 1997 [cited by applicant]
WO 9713646A1 · 1997 [cited by applicant]
WO 9719064A1 · 1997 [cited by applicant]
WO WO9719064 · 1997 [cited by applicant]
WO 9719931A1 · 1997 [cited by applicant]
WO WO9719931 · 1997 [cited by applicant]
WO 0017163A1 · 2000 [cited by applicant]
WO WO0017163 · 2000 [cited by applicant]
WO 0026195A1 · 2000 [cited by applicant]
WO WO00026195 · 2000 [cited by applicant]
WO 0044731A1 · 2000 [cited by applicant]
WO WO00044731 · 2000 [cited by applicant]
WO 0107048A1 · 2001 [cited by applicant]
WO WO01007048 · 2001 [cited by applicant]
WO 0192253A2 · 2001 [cited by applicant]
WO 0194346A1 · 2001 [cited by applicant]
WO WO01092253 · 2001 [cited by applicant]
WO WO01094346 · 2001 [cited by applicant]
WO 0253155A1 · 2002 [cited by applicant]
WO WO02053155 · 2002 [cited by applicant]
WO 0281453A1 · 2002 [cited by applicant]
WO WO02081453 · 2002 [cited by applicant]
WO 0329245A1 · 2003 [cited by applicant]
WO 0332994A2 · 2003 [cited by applicant]
WO WO03029245 · 2003 [cited by applicant]
WO WO03032994 · 2003 [cited by applicant]
WO 0357220A1 · 2003 [cited by applicant]
WO WO03057220 · 2003 [cited by applicant]
WO 0393243A1 · 2003 [cited by applicant]
WO 0396980A2 · 2003 [cited by applicant]
WO WO03093243 · 2003 [cited by applicant]
WO WO03096980 · 2003 [cited by applicant]
WO 2004022572A1 · 2004 [cited by applicant]
WO WO2004022572 · 2004 [cited by applicant]
WO 2004031160A2 · 2004 [cited by applicant]
WO WO2004030633A2 · 2004 [cited by applicant]
WO WO2004031160 · 2004 [cited by applicant]
WO 2004041782A1 · 2004 [cited by applicant]
WO 2004030633A3 · 2004 [cited by applicant]
WO 2004070050A2 · 2004 [cited by applicant]
WO WO2004070050 · 2004 [cited by applicant]
WO 2004111031A1 · 2004 [cited by applicant]
WO WO2004111031 · 2004 [cited by applicant]
WO 2005042488A1 · 2005 [cited by applicant]
WO WO2005042488 · 2005 [cited by applicant]
WO WO2005059109 · 2005 [cited by applicant]
WO 2005060661A2 · 2005 [cited by applicant]
WO WO2005060661 · 2005 [cited by applicant]
WO WO2005089752 · 2005 [cited by applicant]
WO 2005099693A2 · 2005 [cited by applicant]
WO WO2005099693 · 2005 [cited by applicant]
WO 2005089752A3 · 2005 [cited by applicant]
WO 2006010641A2 · 2006 [cited by applicant]
WO 2006010642A1 · 2006 [cited by applicant]
WO WO2006010642 · 2006 [cited by applicant]
WO 2006027266A1 · 2006 [cited by applicant]
WO 2006028226A1 · 2006 [cited by applicant]
WO WO2006028226 · 2006 [cited by applicant]
WO 2005059109A3 · 2006 [cited by applicant]
WO 2006124118A1 · 2006 [cited by applicant]
WO WO2006124118 · 2006 [cited by applicant]
WO WO2007012661A1 · 2007 [cited by applicant]
WO 2007045877A1 · 2007 [cited by applicant]
WO WO2007045877 · 2007 [cited by applicant]
WO 2007127010A2 · 2007 [cited by applicant]
WO WO2007126765 · 2007 [cited by applicant]
WO WO2007127010 · 2007 [cited by applicant]
WO 2008024484A1 · 2008 [cited by applicant]
WO 2008024485A2 · 2008 [cited by applicant]
WO 2008034909A2 · 2008 [cited by applicant]
WO 2008119015A2 · 2008 [cited by applicant]
WO WO2008119015 · 2008 [cited by applicant]
WO 2007126765A3 · 2008 [cited by applicant]
WO 2009055053A2 · 2009 [cited by applicant]
WO WO2009055053 · 2009 [cited by applicant]
WO 2009061587A1 · 2009 [cited by applicant]
WO 2009101530A1 · 2009 [cited by applicant]
WO 2010099238A1 · 2010 [cited by applicant]
WO WO2010099238 · 2010 [cited by applicant]
WO WO2011103202A2 · 2011 [cited by applicant]
WO 2011106570A1 · 2011 [cited by applicant]
WO WO2011106570 · 2011 [cited by applicant]
WO WO2012018948A2 · 2012 [cited by applicant]
WO WO2012142208A1 · 2012 [cited by applicant]
WO WO2012145330A1 · 2012 [cited by applicant]
WO 2012158884A1 · 2012 [cited by applicant]
WO WO2012158884 · 2012 [cited by applicant]
WO WO2013066440A1 · 2013 [cited by applicant]
WO 2013079964A1 · 2013 [cited by applicant]
WO WO2013079964 · 2013 [cited by applicant]
WO 2013153342A1 · 2013 [cited by applicant]
WO WO2013152342A1 · 2013 [cited by applicant]
WO WO2013184681A1 · 2013 [cited by applicant]
WO 2014043208A1 · 2014 [cited by applicant]
WO WO2014052237A1 · 2014 [cited by applicant]
WO 2014113260A1 · 2014 [cited by applicant]
WO 2015118015A1 · 2015 [cited by applicant]
WO 2016090098A1 · 2016 [cited by applicant]
WO 2016090101A1 · 2016 [cited by applicant]
WO 2016090105A1 · 2016 [cited by applicant]
Study NCT01171898—Submitted Date: Jan. 27, 2016 (v18). [cited by applicant]
Study NCT01790126—Submitted Date: Sep. 30, 2016 (v31). [cited by applicant]
Study NCT01792687—Submitted Date: Aug. 25, 2016 (v21). [cited by applicant]
Study NCT01946204—Submitted Date: Oct. 14, 2016 (v48). [cited by applicant]
Study NCT02106507—Submitted Date: Jul. 5, 2016 (v6). [cited by applicant]
Study NCT02123758—Submitted Date: Sep. 30, 2016 (v31). [cited by applicant]
Study NCT02257736—Submitted Date: Sep. 26, 2016 (v35). [cited by applicant]
Study NCT02489318—Submitted Date: Sep. 21, 2016 (v20). [cited by applicant]
Study NCT02531516—Submitted Date: Aug. 24, 2016 (v13). [cited by applicant]
Study NCT02578797—Submitted Date: Sep. 21, 2016 (v12). [cited by applicant]
Study NCT02703623—Submitted Date: Sep. 22, 2016 (v6). [cited by applicant]
Study NCT02721979—Submitted Date: Sep. 6, 2016 (v2). [cited by applicant]
Study NCT02770391—Submitted Date: May 10, 2016 (v1). [cited by applicant]
Study NCT02772588—Submitted Date: May 12, 2016 (v1). [cited by applicant]
Study NCT02789878—Submitted Date: Jun. 2, 2016 (v1). [cited by applicant]
Study NCT02811809—Submitted Date: Oct. 10, 2016 (v3). [cited by applicant]
Study NCT02849990—Submitted Date: Sep. 6, 2016 (v2). [cited by applicant]
Study NCT02867020—Submitted Date: Aug. 10, 2016 (v1). [cited by applicant]
Study NCT02903368—Submitted Date: Sep. 12, 2016 (v1). [cited by applicant]
Study NCT02906605—Submitted Date: Sep. 15, 2016 (v1). [cited by applicant]
Study NCT02913196—Submitted Date: Sep. 21, 2016 (v1). [cited by applicant]
Study NCT02924766—Submitted Date: Oct. 4, 2016 (v1). [cited by applicant]