IP Library › Granted Patent US 12,403,146
Granted Patent B2
US 12,403,146 · App. 17/085,824 · Granted Sep 2, 2025

Preferred oral testosterone undecanoate therapy to achieve testosterone replacement treatment

Inventors: Om Dhingra (Morrisville, NC); James S. Bernstein (Raleigh, NC)
Assignee: Marius Pharmaceuticals, Inc.
A61K31/568A61K9/0053A61K47/14A61K47/22A61K47/44
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Quick Facts
Patent No.
US 12,403,146
App. No.
17/085,824
Granted
Sep 2, 2025
Kind
B2
Abstract

The present invention features new testosterone undecanoate (TU) dosing regimens, e.g., for testosterone replacement therapy. The TU may be formulated with phytosterols or phytosterol esters.

Claims (75)

1. A method of treating testosterone deficiency in a subject in need thereof, the method comprising:

a) performing a treatment regimen comprising orally administering to the subject 400 mg of testosterone undecanoate (TU) daily with a meal, wherein the TU is administered in a pharmaceutical composition comprising TU, a non-sterol solubilizing agent effective for solubilization of the TU, and a phytosterol or phytosterol ester;

b) establishing a first steady state serum concentration of testosterone;

c) following step (b), providing a first steady state Serum Value of testosterone in the subject that is measured from about 3 hours to about 6 hours after administration of the pharmaceutical composition; and

d) performing a first titration of the testosterone undecanoate, wherein:

i) if the first Serum Value of testosterone is less than about 460 ng/dl, then orally administering to the subject about 600 mg TU daily to establish a second steady state Serum Value of testosterone that is higher than the first steady state Serum Value of testosterone;

ii) if the first Serum Value of testosterone is from about 460 ng/dl to about 971 ng/dl, then continuing to orally administer to the subject about 400 mg TU daily to maintain the first steady state Serum Value of testosterone; or

iii) if the first Serum Value of testosterone is greater than about 971 ng/dl, then orally administering to the subject about 200 mg TU daily to establish a second steady state Serum Value of testosterone that is lower than the first steady state Serum Value of testosterone.

2. The method of claim 1 , wherein step (a) comprises administering the pharmaceutical composition twice daily.

3. The method of claim 2 , wherein:

a) a first dose is administered in the morning and a second dose is administered in the evening; and/or

b) the first dose comprises about 200 mg TU, and the second dose comprises about 200 mg TU.

4. The method of claim 3 , wherein following the first titration,

i) about 600 mg TU is administered daily to the subject, and the first dose comprises about 300 mg TU, and the second dose comprises about 300 mg TU;

ii) about 400 mg TU is administered daily to the subject, and the first dose comprises about 200 mg TU, and the second dose comprises about 200 mg TU; or

iii) about 200 mg TU is administered daily to the subject, and the first dose comprises about 100 mg TU, and the second dose comprises about 100 mg TU.

5. The method of claim 1 , further comprising:

e) establishing a second steady state serum concentration of testosterone;

f) following step (e), providing a second steady state Serum Value of testosterone in the subject; and

g) performing a second titration of the TU.

6. The method of claim 5 , wherein following the first titration, about 600 mg TU is administered daily to the subject, and

a) if the second Serum Value of testosterone is less than about 460 ng/dL, then orally administering about 800 mg TU daily to the subject to establish a third steady state Serum Value of testosterone that is higher than the second steady state Serum Value of testosterone;

b) if the second Serum Value of testosterone is from about 460 ng/dL to about 971 ng/dL, then continuing to orally administer about 600 mg TU daily to the subject to maintain the second steady state Serum Value of testosterone; or

c) if the second Serum Value of testosterone is greater than about 971 ng/dL, then orally administering about 400 mg TU daily to the subject to establish a third steady state Serum Value of testosterone that is lower than the second steady state Serum Value of testosterone.

7. The method of claim 5 , wherein following the first titration, about 400 mg TU is administered daily to the subject, and

a) if the second Serum Value of testosterone is less than about 460 ng/dL, then orally administering about 600 mg TU daily to the subject to establish a third steady state Serum Value of testosterone that is higher than the second steady state Serum Value of testosterone;

b) if the second Serum Value of testosterone is from about 460 ng/dL to about 971 ng/dL, then continuing to orally administer about 400 mg TU daily to the subject to maintain the second steady state Serum Value of testosterone; or

c) if the second Serum Value of testosterone is greater than about 971 ng/dL, orally administering about 200 mg TU daily to the subject to establish a third steady state Serum Value of testosterone that is lower than the second steady state Serum Value of testosterone.

8. The method of claim 7 , wherein following the first titration, about 200 mg TU is administered daily to the subject, and

a) if the second Serum Value of testosterone is less than about 460 ng/dL, orally administering about 400 mg TU daily to the subject to establish a third steady state Serum Value of testosterone that is higher than the second steady state Serum Value of testosterone;

b) if the second Serum Value of testosterone is from about 460 ng/dL to about 971 ng/dL, then continuing to orally administer about 200 mg TU daily to the subject to maintain the second steady state Serum Value of testosterone; or

c) if the second Serum Value of testosterone is greater than about 971 ng/dL, orally administering about 100 mg TU daily to the subject to establish a third steady state Serum Value of testosterone that is lower than the second steady state Serum Value of testosterone.

9. The method of claim 6 , wherein following the second titration, about 800 mg TU is administered daily to the subject, and the first dose comprises about 400 mg TU, and the second dose comprises about 400 mg TU.

10. The method of claim 7 , wherein following the second titration, about 100 mg TU is administered daily to the subject, and the subject receives a single dose of about 100 mg TU.

11. The method of claim 1 , wherein:

a) the first Serum Value of testosterone is measured prior to day 21 of the treatment regimen; and/or

b) the first titration is performed on from about day 7 to about day 35 of the treatment regimen.

12. The method of claim 11 , wherein:

a) the first Serum Value of testosterone is measured on about day 7 of the treatment regimen; and/or

b) the first titration is performed on about day 28 of the treatment regimen.

13. The method of claim 1 , wherein the pharmaceutical composition comprises:

a) from about 10% to about 25% by weight of solubilized testosterone undecanoate;

b) from about 5% to about 40% by weight of a hydrophilic surfactant;

c) from about 15% to about 65% by weight of a hydrophobic surfactant;

d) from about 2% to about 45% by weight of phytosterol esters; and

e) from about 0% to about 15% by weight of a solubilizer.

14. The method of claim 13 , wherein the pharmaceutical composition comprises:

a) about 18.2% by weight of solubilized testosterone undecanoate;

b) about 15.0% by weight of polyoxyl 40 hydrogenated castor oil;

c) about 39.9% by weight of propylene glycol monolaurate;

d) about 25.0% by weight of one or more phytosterol esters; and

e) about 2.0% by weight of di-alpha-tocopherol and/or an ester or acetate thereof.

15. The method of claim 1 , wherein:

a) the subject is a hypogonadal male;

b) the subject has not previously been administered TU or other testosterone replacement therapy for a period of at least seven days or a period of time sufficient to completely wash exogenous testosterone from the subject; and/or

c) the method is performed on a population of human subjects.

16. The method of claim 15 , wherein:

a) the population comprises at least 10 subjects, at least 50 subjects, at least 100 subjects, at least 200 subjects, at least 500 subjects, or more;

b) the method achieves a Cavg in the serum normal range of about 300 ng/dL to about 1000 ng/dL in at least 75% of the population;

c) the method achieves a Cmax of less than about 1500 ng/dL in at least 85% of the population;

d) the method achieves a Cmax of from about 1800 ng/dL to about 2500 ng/dL in no more than 5% of the population;

e) the method achieves a Cmax of greater than about 2500 ng/dL in no more than 0% of the population;

f) the method reduces an average number of incorrect titrations or the risk of incorrect titrations per subject in the population in order to achieve a steady state testosterone Serum Value of from about 300 ng/dL to about 1000 ng/dl relative to a population receiving a treatment regimen in which an initial dosage is not about 400 mg TU and/or the Serum Value is not measured from about 3 hours to about 6 hours after administration

g) the method achieves a Cavg in the serum normal range of about 300 ng/dl to about 1000 ng/dL in a greater number of subjects in the population as compared to a treatment regimen in which an initial dosage is not about 400 mg TU and/or the Serum Value is not measured from about 3 hours to about 6 hours after administration;

h) the method achieves a Cmax of less than about 1500 ng/dL in a greater number of subjects in the population as compared to the treatment regimen in which the initial dosage is not about 400 mg TU and/or the Serum Value is not measured from about 3 hours to about 6 hours after administration;

i) The method achieves a Cmax of from about 1800 ng/dL to about 2500 ng/dL in a fewer number of subjects in the population as compared to the treatment regimen in which the initial dosage is not about 400 mg TU and/or the Serum Value is not measured from about 3 hours to about 6 hours after administration;

j) the method achieves a Cmax of greater than about 2500 ng/dL in a fewer number of subjects in the population as compared to the treatment regimen in which the initial dosage is not about 400 mg TU and/or the Serum Value is not measured from about 3 hours to about 6 hours after administration; and/or

k) the method decreases the risk of elevated blood pressure of the population of human subjects.

17. The method of claim 16 , wherein the daytime systolic blood pressure, night time systolic blood pressure, and/or 24-hour average systolic blood pressure does not increase by more than 3 mmHg as compared to the blood pressure before onset of treatment in the population of human subjects.

18. The method of claim 1 , wherein the first Serum Value is measured by:

measuring testosterone concentration of serum clotted at room temperature for about 30 minutes prior to centrifugation in a tube.

19. The method of claim 5 , wherein the second Serum Value is measured by:

measuring testosterone concentration of serum clotted at room temperature for about 30 minutes prior to centrifugation in a tube.

20. The method of claim 1 , wherein the first steady state Serum Value of testosterone in the subject is measured from about 3 hours to about 5 hours after administration of the pharmaceutical composition.

21. The method of claim 1 , wherein the second steady state Serum Value of testosterone in the subject is measured from about 3 hours to about 5 hours after administration of the pharmaceutical composition.

Assignments (2)
CHANGE OF NAME Recorded Dec 17, 2024
From: MARIUS PHARMACEUTICALS LLC
To: MARIUS PHARMACEUTICALS, INC.
Reel/Frame 069719/0580 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 21, 2021
From: DHINGRA, OM; BERNSTEIN, JAMES S.; SHAH, SHALIN Y.
To: MARIUS PHARMACEUTICALS LLC
Reel/Frame 056936/0756 →
Continuity (2)
Provisional Application 62928051 · Oct 30, 2019
Related Publication 20220265678A1 · Aug 25, 2022
References Cited (344)
US 4147783A · van der Vies · 1979 [cited by applicant]
US 4797625A · Nakazawa · 1989 [cited by applicant]
US 5376641A · Ammeraal · 1994 [cited by applicant]
US 5567439A · Myers et al. · 1996 [cited by applicant]
US 5645856A · Lacy et al. · 1997 [cited by applicant]
US 6087353A · Stewart et al. · 2000 [cited by applicant]
US 6248363B1 · Patel et al. · 2001 [cited by applicant]
US 6267985B1 · Chen et al. · 2001 [cited by applicant]
US 6284268B1 · Mishra et al. · 2001 [cited by applicant]
US 6294192B1 · Patel et al. · 2001 [cited by applicant]
US 6309663B1 · Patel et al. · 2001 [cited by applicant]
US 6383471B1 · Chen et al. · 2002 [cited by applicant]
US 6451339B2 · Patel et al. · 2002 [cited by applicant]
US 6458383B2 · Chen et al. · 2002 [cited by applicant]
US 6468559B1 · Chen et al. · 2002 [cited by applicant]
US 6569463B2 · Patel et al. · 2003 [cited by applicant]
US 6652880B1 · Aylwin et al. · 2003 [cited by applicant]
US 6696484B2 · Liao et al. · 2004 [cited by applicant]
US 6720001B2 · Chen et al. · 2004 [cited by applicant]
US 6742448B1 · Davis et al. · 2004 [cited by applicant]
US 6742488B2 · Bonde et al. · 2004 [cited by applicant]
US 6743448B2 · Kryger · 2004 [cited by applicant]
US 6761903B2 · Chen et al. · 2004 [cited by applicant]
US 6838484B2 · Steiner et al. · 2005 [cited by applicant]
US 6923988B2 · Patel et al. · 2005 [cited by applicant]
US 6977083B1 · Huebler et al. · 2005 [cited by applicant]
US 6982281B1 · Chen et al. · 2006 [cited by applicant]
US 7138389B2 · Amory et al. · 2006 [cited by applicant]
US 7374779B2 · Chen et al. · 2008 [cited by applicant]
US 8241664B2 · Dudley et al. · 2012 [cited by applicant]
US 8492369B2 · Dudley et al. · 2013 [cited by applicant]
US 8512794B2 · Perlman · 2013 [cited by applicant]
US 8778916B2 · Dudley et al. · 2014 [cited by applicant]
US 8828428B1 · Dudley et al. · 2014 [cited by applicant]
US 9034858B2 · Giliyar et al. · 2015 [cited by applicant]
US 9205057B2 · Giliyar et al. · 2015 [cited by applicant]
US 9480690B2 · Giliyar et al. · 2016 [cited by applicant]
US 9757390B2 · Giliyar et al. · 2017 [cited by applicant]
US 10576089B2 · Dhingra · 2020 [cited by applicant]
US 10576090B2 · Dhingra · 2020 [cited by applicant]
US 10716794B2 · Giliyar et al. · 2020 [cited by applicant]
US 11179402B2 · Dudley et al. · 2021 [cited by applicant]
US 11179403B2 · Dudley et al. · 2021 [cited by applicant]
US 11331325B2 · Dudley et al. · 2022 [cited by applicant]
US 11590146B2 · Dhingra · 2023 [cited by applicant]
US 11617758B2 · Dhingra et al. · 2023 [cited by applicant]
US 20020012680A1 · Patel et al. · 2002 [cited by applicant]
US 20030077297A1 · Chen et al. · 2003 [cited by applicant]
US 20030104048A1 · Patel et al. · 2003 [cited by applicant]
US 20030203043A1 · Yegorova · 2003 [cited by applicant]
US 20030236236A1 · Chen et al. · 2003 [cited by applicant]
US 20040087564A1 · Wright et al. · 2004 [cited by applicant]
US 20040115287A1 · Chen et al. · 2004 [cited by applicant]
US 20040127476A1 · Kershman et al. · 2004 [cited by applicant]
US 20050100608A1 · Ebert · 2005 [cited by applicant]
US 20050101517A1 · De Nijs et al. · 2005 [cited by applicant]
US 20050153948A1 · Spilburg · 2005 [cited by applicant]
US 20050176692A1 · Amory et al. · 2005 [cited by applicant]
US 20050287203A1 · Nijs De et al. · 2005 [cited by applicant]
US 20060003002A1 · Fikstad et al. · 2006 [cited by applicant]
US 20060034937A1 · Patel · 2006 [cited by applicant]
US 20060263397A1 · Li et al. · 2006 [cited by applicant]
US 20070009559A1 · Li et al. · 2007 [cited by applicant]
US 20070022674A1 · Worthington · 2007 [cited by applicant]
US 20070078091A1 · Hubler et al. · 2007 [cited by applicant]
US 20070154533A1 · Dudley · 2007 [cited by applicant]
US 20070190080A1 · Friedman · 2007 [cited by applicant]
US 20070196440A1 · Shulman et al. · 2007 [cited by applicant]
US 20070254026A1 · Stewart · 2007 [cited by applicant]
US 20080124387A1 · Spilburg · 2008 [cited by applicant]
US 20080200533A1 · Krishnan · 2008 [cited by applicant]
US 20080206161A1 · Tamarkin et al. · 2008 [cited by applicant]
US 20080249076A1 · Holm et al. · 2008 [cited by applicant]
US 20080261937A1 · Dudley et al. · 2008 [cited by applicant]
US 20080305177A1 · Kershman et al. · 2008 [cited by applicant]
US 20080317844A1 · Dudley et al. · 2008 [cited by applicant]
US 20090074859A1 · Patel · 2009 [cited by applicant]
US 20090075961A1 · Ebert · 2009 [cited by applicant]
US 20090077961A1 · Baker · 2009 [cited by applicant]
US 20090123564A1 · Jain et al. · 2009 [cited by applicant]
US 20100136105A1 · Chen et al. · 2010 [cited by applicant]
US 20100137271A1 · Chen et al. · 2010 [cited by applicant]
US 20100173882A1 · Giliyar et al. · 2010 [cited by applicant]
US 20110142945A1 · Chen et al. · 2011 [cited by applicant]
US 20110160168A1 · Dhingra · 2011 [cited by applicant]
US 20110251167A1 · Dudley et al. · 2011 [cited by applicant]
US 20110263552A1 · Dhingra et al. · 2011 [cited by applicant]
US 20110312928A1 · Nachaegari et al. · 2011 [cited by applicant]
US 20120135069A1 · Keck et al. · 2012 [cited by applicant]
US 20120135074A1 · Giliyar et al. · 2012 [cited by applicant]
US 20120148675A1 · Chickmath et al. · 2012 [cited by applicant]
US 20120244215A1 · Giliyar · 2012 [cited by examiner]
US 20120309731A1 · Dudley et al. · 2012 [cited by applicant]
US 20120322780A1 · Giliyar et al. · 2012 [cited by applicant]
US 20130022674A1 · Dudley et al. · 2013 [cited by applicant]
US 20130029947A1 · Nachaegari et al. · 2013 [cited by applicant]
US 20130303495A1 · Dhingra et al. · 2013 [cited by applicant]
US 20140011780A1 · Dhingra · 2014 [cited by applicant]
US 20150018324A1 · Chickmath et al. · 2015 [cited by applicant]
US 20150190406A1 · Giliyar et al. · 2015 [cited by applicant]
US 20150273067A1 · Patel · 2015 [cited by applicant]
US 20160166584A1 · Patel et al. · 2016 [cited by applicant]
US 20170106002A1 · Dudley et al. · 2017 [cited by applicant]
US 20180021349A1 · Dhingra et al. · 2018 [cited by applicant]
US 20180153904A1 · Giliyar et al. · 2018 [cited by applicant]
US 20180221387A1 · Patel et al. · 2018 [cited by applicant]
US 20180243319A1 · Dhingra · 2018 [cited by applicant]
US 20180333422A1 · Chidambaram et al. · 2018 [cited by applicant]
US 20190070196A1 · Dudley et al. · 2019 [cited by applicant]
US 20190240236A1 · Chidambaram et al. · 2019 [cited by applicant]
US 20190321374A1 · Patel et al. · 2019 [cited by applicant]
US 20190350942A1 · Patel et al. · 2019 [cited by applicant]
US 20190365780A1 · Giliyar et al. · 2019 [cited by applicant]
US 20200022991A1 · Patel et al. · 2020 [cited by applicant]
US 20200046733A1 · Dudley et al. · 2020 [cited by applicant]
US 20200061191A1 · Patel · 2020 [cited by applicant]
US 20200069805A1 · Fikstad et al. · 2020 [cited by applicant]
US 20200093836A1 · Dudley et al. · 2020 [cited by applicant]
US 20200155570A1 · Patel et al. · 2020 [cited by applicant]
US 20200188304A1 · Chickmath et al. · 2020 [cited by applicant]
US 20200197412A1 · Dudley et al. · 2020 [cited by applicant]
US 20200222425A1 · Patel et al. · 2020 [cited by applicant]
US 20200282061A1 · Chen et al. · 2020 [cited by applicant]
US 20200323880A1 · Dudley et al. · 2020 [cited by applicant]
US 20200383997A1 · Giliyar et al. · 2020 [cited by applicant]
US 20200383998A1 · Patel et al. · 2020 [cited by applicant]
US 20200383999A1 · Giliyar et al. · 2020 [cited by applicant]
US 20200390784A1 · Dhingra · 2020 [cited by applicant]
US 20200390785A1 · Patel et al. · 2020 [cited by applicant]
US 20210007978A1 · Patel et al. · 2021 [cited by applicant]
US 20210008212A1 · Patel · 2021 [cited by applicant]
US 20210038615A1 · Giliyar et al. · 2021 [cited by applicant]
US 20210046087A1 · Dhingra et al. · 2021 [cited by applicant]
US 20210052604A1 · Giliyar et al. · 2021 [cited by applicant]
US 20210169899A1 · Patel et al. · 2021 [cited by applicant]
US 20210177865A1 · Giliyar et al. · 2021 [cited by applicant]
US 20230398128A1 · Dhingra et al. · 2023 [cited by applicant]
US 20240000798A1 · Dhingra · 2024 [cited by applicant]
US 20240342194A1 · Dhingra et al. · 2024 [cited by applicant]
CN 1010538B · 1990 [cited by applicant]
CN 102083420A · 2011 [cited by applicant]
EP 1925294A1 · 2008 [cited by applicant]
EP 2519230A2 · 2012 [cited by examiner]
EP 2682111A1 · 2014 [cited by applicant]
EP 2979699A1 · 2016 [cited by applicant]
EP 2985026A1 · 2016 [cited by applicant]
EP 3078368A1 · 2016 [cited by applicant]
JP 2008133281A · 2008 [cited by applicant]
WO WO9524893A1 · 1995 [cited by applicant]
WO WO9740823A1 · 1997 [cited by applicant]
WO WO9959556A1 · 1999 [cited by applicant]
WO WO03010146A1 · 2003 [cited by applicant]
WO WO03094891A1 · 2003 [cited by applicant]
WO WO2005051290A2 · 2005 [cited by applicant]
WO WO2006084312A1 · 2006 [cited by applicant]
WO WO2006113505A2 · 2006 [cited by applicant]
WO WO2010081032A2 · 2010 [cited by applicant]
WO WO2011082384A2 · 2011 [cited by applicant]
WO WO2011129812A1 · 2011 [cited by examiner]
WO WO2012092202A2 · 2012 [cited by applicant]
WO WO2014096139A1 · 2014 [cited by applicant]
WO WO2014143127A1 · 2014 [cited by applicant]
WO WO2015193224A1 · 2015 [cited by applicant]
WO WO2018098501A1 · 2018 [cited by applicant]
WO WO2020018974A1 · 2020 [cited by applicant]
WO WO2020065401A1 · 2020 [cited by applicant]
WO WO2021168573A1 · 2021 [cited by applicant]
WO WO2022245933A1 · 2022 [cited by applicant]
“Saw palmetto extract,” Wikipedia. < https://en.wikipedia.org/wiki/Saw_palmetto_extract>, retrieved Jun. 27, 2017 (3 pages). [cited by applicant]
“SOV Therapeutics Receives U.S. Orphan Drug Designation for the Use of Oral Testosterone Undecanoate in the Treatment of Constitutional Delay in Growth and Puberty in Adolescent Boys (14-17 Years of Age),” http://biospa… [cited by applicant]
“Technical Data Sheet,” CardioAid XF Plant Sterols ADM, Product Code 040551 (2 pages). [cited by applicant]
Abidi, “Chromatographic analysis of plant sterols in foods and vegetable oils,” J Chromatogr A. 935(1-2):173-201 (2001). [cited by applicant]
Advertisement for Eli Lilly and Company, “Cytellin sitosterols: the cholesterol-lowering agent with an unparalleled record of safety,” Bull NY Acad Med. 39(8) (1963) (2 pages). [cited by applicant]
Advisory Action for U.S. Appl. No. 12/983,216, mailed Apr. 25, 2013 (3 pages). [cited by applicant]
Advisory Action for U.S. Appl. No. 12/983,216, mailed Mar. 21, 2013 (3 pages). [cited by applicant]
Amory et al., “Oral testosterone in oil plus dutasteride in men: a pharmacokinetic study,” J Clin Endocrinol Metab. 90(5):2610-7 (2005). [cited by applicant]
Amory et al., “Oral testosterone in oil: pharmacokinetic effects of 5alpha reduction by finasteride or dutasteride and food intake in men,” J Androl. 27(1):72-8 (2006). [cited by applicant]
Amory et al., “Oral testosterone with and without concomitant inhibition of 5alpha-reductase by dutasteride in hypogonadal men for 28 days,” J Urology. 185:626-32 (2011). [cited by applicant]
Andriole et al., “Effect of dutasteride on the risk of prostate cancer,” Ne J Med. 362(13):1192-202 (2010). [cited by applicant]
Araya et al., “The novel formulation design of O/W microemulsion for improving the gastrointestinal absorption of poorly water soluble compounds,” Int J Pharm. 305(1-2):61-74 (2005). [cited by applicant]
Armand et al., “Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract,” Am J Clin Nutr. 70(6):1096-106 (1999). [cited by applicant]
Awad et al., “Phytosterol feeding induces alteration in testosterone metabolism in rat tissues,” J Nutr Biochem 9(12):712-7 (1998). [cited by applicant]
Bagchus et al., “Important effect of food on the bioavailability of oral testosterone undecanoate,” Pharmacotherapy. 23(3):319-25 (2003). [cited by applicant]
BASF, “DL-alpha-Tocopherol: Technical information human nutrition.” (2009, 2 pages). [cited by applicant]
Bhasin et al., “Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging,” available in PMC Nov. 9, 2007, published in final edited form as: Nat Clin Prac… [cited by applicant]
Bollman et al., “Techniques for the collection of lymph from the liver, small intestine, or thoracic duct of the rat,” J Lab Clin Med. 33(10):1349-52 (1948). [cited by applicant]
Borgström et al., “Studies of intestinal digestion and absorption in the human,” J Clin Invest. 36(10):1521-36 (1957). [cited by applicant]
Borowy-Borowski et al., “Unique technology for solubilization and delivery of highly lipophilic bioactive molecules,” J Drug Target. 12(7):415-24 (2004). [cited by applicant]
Borst et al., “Inhibition of 5alpha-reductase blocks prostate effects of testosterone without blocking anabolic effects,” Am J Physiol Endocrinol Metab. 288:E222-7 (2005). [cited by applicant]
Bramson et al., “Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR,” J Pharmacol Exp Ther. 282(3) 1496-502 (1997). [cited by applicant]
Briefing Document for Bone, Reproductive, and Urologic Drugs Advisory Committee, “Oral Testosterone Undecanoate Capsules (Jatenzo™) for Testosterone Replacement Therapy in Hypogonadal Men,” Clarus Therapeutics, Inc., da… [cited by applicant]
Brown et al., “Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase,” J. Nutr. Bioch. 21(8):736-40 (2010). [cited by applicant]
Cabeza et al., “Effects of beta-sitosterol as Inhibitor of 5alpha-reductase in Hamster Prostate,” Proc West Pharmacol Soc. 46:153-5 (2003). [cited by applicant]
Carey et al., “The characteristics of mixed micellar solutions with particular reference to bile,” Am J Med. 49(5):590-608 (1970). Abstract only. [cited by applicant]
Carlin et al., “Disposition and pharmacokinetics of [14C]finasteride after oral administration in humans,” Drug Metab Dispos. 20(2):148-55 (1992). [cited by applicant]
Charman et al., “Physicochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH,” J Pharm Sci. 86(3):269-282 (1997). [cited by applicant]
Chen et al., “Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays,” Phytother Res. 30(6):1016-20 (2016). [cited by applicant]
Coert et al., “The pharmacology and metabolism of testosterone undecanoate (TU), a new orally active androgen,” Acta Endocrinol (Copenh). 79(4):789-800 (1975). [cited by applicant]
Communication pursuant to Article 94(3) EPC and Form 2906 for European Patent Application No. 13877592.9, dated Jun. 16, 2017 (5 pages). [cited by applicant]
Communication pursuant to Article 94(3) EPC for European Application No. 13170663.2, dated Oct. 7, 2016 (5 pages). [cited by applicant]
Compound Summary for CID 14985: Vitamin E, https://pubchem.ncbi.nlm.nih.gov/compound/alpha-Tocopherol, retrieved May 22, 2018 (106 pages). [cited by applicant]
Connors et al., “Using a Portfolio of Particle Growth Technologies to Enable Delivery of Drugs with Poor Water Solubility,” Drug Deliv Tech. 4(8):1-11 (2004). [cited by applicant]
Corona et al., “Update in testosterone therapy for men,” J Sex Med. 8(3):639-54 (2011). [cited by applicant]
Daggett et al., “Oral testosterone, a reappraisal,” Horm Res. 9(3):121-9 (1978). [cited by applicant]
Debruyne et al., “Efficacy and safety of long-term treatment with the dual 5 alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia,” Eur Urol. 46:488-95 (2004). [cited by applicant]
Decision to refuse a European Patent application for European Patent Application No. 13170663.2, dated May 7, 2018 (10 pages). [cited by applicant]
Delaney et al., “Oral absorption of phytosterols and emulsified phytosterols by Sprague-Dawley rats,” J Nutr Biochem. 15(5):289-95 (2004). [cited by applicant]
Diver et al., “Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men,” Clin Endocrinol. 58(6):710-7 (2003). [cited by applicant]
Eldridge et al., “Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the peyer's patches,” J Control Release. 11(1-3):205-14 (1990) (Abstract only… [cited by applicant]
Extended European Search Report for European Patent Application No. 10841783.3, dated Jun. 7, 2013 (8 pages). [cited by applicant]
Extended European Search Report for European Patent Application No. 13170663.2, dated Dec. 10, 2013 (8 pages). [cited by applicant]
Extended European Search Report for European Patent Application No. 13877592.9, dated Sep. 8, 2016 (6 pages). [cited by applicant]
First Examination Report for Indian Patent Application No. 1959/KOLNP/2012, dated May 31, 2018 (7 pages). [cited by applicant]
First Examination Report for New Zealand Patent Application No. 631833, mailed Nov. 6, 2015 (2 pages). [cited by applicant]
First Office Action for Chinese Patent Application No. 201380074669.9, dated Mar. 22, 2017 (23 pages). [cited by applicant]
Fogh et al., “Serum-testosterone during oral administration of testosterone in hypogonadal men and transsexual women,” Acta Endocrinol (Copenh). 87(3):643-9 (1978). [cited by applicant]
Food and Drug Administration, “Federal Register” 75(235):76526-71 (2010). [cited by applicant]
Gerbino. [cited by applicant]
Giliyar et al., “Challenges & Opportunities in Oral Delivery of Poorly Water-Soluble Drugs,” Drug Deliv Tech. 6(1):57-63 (2006). [cited by applicant]
Grosso et al., “Fatty acid, sterol and proximate compositions of peanut species ( [cited by applicant]
Gursoy et al., “Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs,” Biomed Pharmacother. 58(3):173-82 (2004). [cited by applicant]
Haren et al., “Effect of 12 month oral testosterone on testosterone deficiency symptoms in symptomatic elderly males with low-normal gonadal status,” Age Ageing. 34:125-30 (2005). [cited by applicant]
Hawley et al., “Targeting of colloids to lymph nodes: influence of lymphatic physiology of colloidal characteristics,” Adv Drug Deliv Reviews. 17(1):129-48 (1995). [cited by applicant]
Heinemann et al., “Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia,” Atherosclerosis. 61(3):219-23 (1986) (Abstract only). [cited by applicant]
Horst et al., “Lymphatic absorption and metabolism of orally administered testosterone undecanoate in man,” Klin Wochenschr. 54:875-9 (1976). [cited by applicant]
Houwing et al., “Pharmacokinetic study in women of three different doses of a new formulation of oral testosterone undecanoate, Andriol Testocaps,” Pharmacotherapy. 23(10):1257-65 (2003). [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/US2013/049405, mailed Dec. 12, 2013 (15 pages). [cited by applicant]
Itoh et al., “Sterol composition of 19 vegetable oils,” J Am Oil Chem Soc. 50:122-5 (1973). [cited by applicant]
Johnsen et al., “Therapeutic effectiveness of oral testosterone,” Lancet. 2:1473-5 (1974). [cited by applicant]
Johnsen, “Long-term oral testosterone and liver function,” Lancet. 311(8054):50 (1978). [cited by applicant]
Kaukonen et al., “Drug solubilization behavior during in vitro digestion of simple triglyceride lipid solution formulations,” Pharm Res. 21(2):245-53 (2004). [cited by applicant]
Kincl et al., “Increasing intestinal absorption of drugs by formulation,” Arch Pharm (Weinheim). 319(7):615-24 (1986). [cited by applicant]
Kossena et al., “Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug,” J Pharm Sci. 94(3):481-92 (2005). [cited by applicant]
Kossena et al., “Probing drug solubilization patterns in the gastrointestinal tract after administration of lipid-based delivery systems: a phase diagram approach,” J Pharm Sci. 93(2):332-48 (2004). [cited by applicant]
Kovarik et al., “Reduced inter-and intraindividual variability in cyclosporine pharmacokinetics from a microemulsion formulation,” J Pharm Sci. 83(3):444-6 (1994). [cited by applicant]
Kwei et al., “Lymphatic uptake of MK-386, a sterol 5alpha-reductase inhibitor, from aqueous and lipid formulations,” Int J Pharm. 164(1-2):37-44 (1998). [cited by applicant]
Lea et al., “Safety evaluation of phytosterol-esters. Part 9: Results of a European post-launch monitoring programme,” Food and Chem Toxicol. 44:1213-22 (2006). [cited by applicant]
Lees et al., “Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance,” Atherosclerosis. 28(3):325-338 (1977) (Abstract only). [cited by applicant]
Macgregor et al., “Influence of lipolysis on drug absorption from the gastro-intestinal tract,” Adv Drug Deliv Rev. 25(1):33-46 (1997). [cited by applicant]
Marks et al., “Long-term effects of finasteride on prostate tissue composition,” Urology. 53(3):574-80 (1999). [cited by applicant]
Matsumoto, “Hormonal therapy of male hypogonadism,” Endocrinol Metab Clin North Am. 23(4):857-75 (1994). [cited by applicant]
Mattson et al., “Optimizing the effect of plant sterols on cholesterol absorption in man,” Am J Clin Nutr. 35:697-700 (1982). [cited by applicant]
Mazer et al., “Enhanced transdermal delivery of testosterone: a new physiological approach for androgen replacement in hypogonadal men, ”J Control Release. 19:347-62 (1992). [cited by applicant]
McConnell et al., “The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group,… [cited by applicant]
Melander, “Influence of food and different nutrients on drug bioavailability,” World Rev Nutr Diet. 43:34-44 (1984). [cited by applicant]
Merck Canada Inc. “Andriol Product Monograph: Part III: Consumer Information.” https://pdf.hres.ca/dpd_pm/00033378.PDF (2015) (3 pages). [cited by applicant]
Micallef et al., “The lipid-lowering effects of phytosterols and (n-3) polyunsaturated fatty acids are synergistic and complementary in hyperlipidemic men and women,” J Nutr. 138(6):1086-90 (2008). [cited by applicant]
Miettinen et al., “Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population,” N Engl J Med. 333(20)1308-12 (1995). [cited by applicant]
Miettinen et al., “Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population,” Am J Epidemiol. 131(1):20-31 (1990). Abstract only. [cited by applicant]
Mostaghel et al., “Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer,” Cancer Res. 67(10):5033-41 (… [cited by applicant]
Mueller et al., “Influence of a fat-rich meal on the pharmacokinetics of a new oral formulation of cyclosporine in a crossover comparison with the market formulation,” Pharm Res. 11(1):151-5 (1994). [cited by applicant]
Nieschlag et al., “Influence of sex, testicular development and liver function on the bioavailability of oral testosterone,” Eur J Clin Invest. 7:145-7 (1977). [cited by applicant]
Nieschlag et al., “Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate,” Acta Endocrinol (Copenh). 79:366-74 (1975). [cited by applicant]
Nishiyama et al., “The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer,” Clin Cancer Res. 10:7121-6 (2004). [cited by applicant]
Office Action for Canadian Patent Application No. 2,822,435, mailed Sep. 6, 2016 (4 pages). [cited by applicant]
Office Action for Chinese Patent Application No. 201380074669.9 and English Translation dated Jan. 19, 2018 (17 pages). [cited by applicant]
Office Action for European Patent Application No. 10841783.3, dated Nov. 26, 2015 (5 pages). [cited by applicant]
Office Action for Japanese Patent Application No. 2012-547323, mailed Nov. 18, 2014 (8 pages). [cited by applicant]
Office Action for Japanese Patent Application No. 2012-547323, mailed Sep. 17, 2015 (5 pages). [cited by applicant]
Office Action for Japanese Patent Application No. 2013-124891, mailed Dec. 12, 2014 (9 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Jan. 4, 2013 (20 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/174,756, mailed Mar. 14, 2013 (29 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/843,223, mailed Mar. 31, 2014 (22 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/843,223, mailed Apr. 1, 2016 (25 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/843,223, mailed Aug. 28, 2015 (31 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/843,223, mailed Oct. 14, 2016 (26 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/843,223, mailed Oct. 23, 2014 (24 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Apr. 27, 2016 (25 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Aug. 1, 2012 (14 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Jan. 22, 2015 (31 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Jul. 29, 2013 (37 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Jun. 7, 2012 (12 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Mar. 7, 2014 (43 pages). [cited by applicant]
Office Action for U.S. Appl. No. 12/983,216, mailed Sep. 2, 2015 (22 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/174,756, mailed Oct. 2, 2013 (19 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/936,036, mailed Dec. 5, 2014 (13 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/936,036, mailed Feb. 17, 2016 (13 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/936,036, mailed Jul. 30, 2015 (11 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/936,036, mailed Jun. 5, 2014 (10 pages). [cited by applicant]
Office Action for U.S. Appl. No. 13/936,036, mailed Sep. 6, 2016 (22 pages). [cited by applicant]
Office Action Summary and Notice of References Cited for U.S. Appl. No. 13/936,036, dated Jun. 18, 2018 (21 pages). [cited by applicant]
Office Action Summary and Notice of References Cited for U.S. Appl. No. 15/959,626, dated Jul. 20, 2018 (28 pages). [cited by applicant]
Page et al., “Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial,” J Clin Endocrinol Metab. 96(2):… [cited by applicant]
Page et al., “Persistent intraprostatic androgen concentrations after medical castration in healthy men,” J Clin Endocrinol Metab. 91(10):3850-6 (2006). [cited by applicant]
Pedersen et al., “A comparison of the solubility of danazol in human and simulated gastrointestinal fluids,” Pharm Res. 17(7):891-4 (2000). [cited by applicant]
Perlman et al., “Development of a self-emulsifying formulation that reduces the food effect for torcetrapib,” Int J Pharm. 351(1-2):15-22 (2008). [cited by applicant]
Phillips et al., “Free and Esterified Sterol Composition of Edible Oils and Fats,” J Food Composition and Analysis. 15:123-42 (2002). [cited by applicant]
Porter et al., “Intestinal lymphatic drug transport: an update,” Adv Drug Deliv Reviews. 50:61-80 (2001). [cited by applicant]
Porter et al., “Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs,” Nat Rev Drug Discov. 6(3):231-48 (2007). [cited by applicant]
Porter et al., “Uptake of drugs into the intestinal lymphatics after oral administration,” Adv Drug Deliv Reviews. 25:71-89 (1997). [cited by applicant]
Pouton, “Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system,” Eur J Pharm Sci. 29(3-4):278-87 (2006). [cited by applicant]
Pouton, “Formulation of self-emulsifying drug delivery systems,” Adv Drug Deliv Rev. 25(1):47-58 (1997). [cited by applicant]
Prager et al., “A Randomized, Double-Blind, Placebo-Controlled Trial to Determine the Effectiveness of Botanically Derived Inhibitors of 5-alpha-Reductase in the Treatment of Androgenetic Alopecia,” J Altern Complem Med… [cited by applicant]
PubChem CID 14870. Retrieved on Jun. 28, 2018 (21 pages). [cited by applicant]
Reininger et al., “Effect of digestion on distribution of blood flow in the rat,” Science. 126(3284):1176 (1957). [cited by applicant]
Right fax interview agenda concerning U.S. Appl. No. 13/012,084, dated Aug. 16, 2013 (9 pages). [cited by applicant]
Roehrborn et al., “Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia,” Urology. 60(3):434-41 (2002). [cited by applicant]
Roth et al., “Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5alpha-reductase by finasteride,” Int J Androl. 34(6:1):541-7 (2011). [cited by applicant]
Russell et al., “Steroid 5 alpha-reductase: two genes/two enzymes,” Annu Rev Biochem. 63:25-61 (1994). [cited by applicant]
Schnabel et al., “The effect of food composition on serum testosterone levels after oral administration of Andriol Testocaps,” Clin Endocrinol (Oxf.). 66:579-85 (2007). [cited by applicant]
Search Report for Taiwanese Patent Application No. 103109505, completed Aug. 7, 2017 (2 pages). [cited by applicant]
Shackleford et al., “Contribution of lymphatically transported testosterone undecanoate to the systemic exposure of testosterone after oral administration of two andriol formulations in conscious lymph duct-cannulated d… [cited by applicant]
Shah et al., “Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs,” Int J Pharm. 106:15-23 (1994). [cited by applicant]
Sheen et al., “Bioavailability of a poorly water-soluble drug from tablet and solid dispersion in humans,” J Pharm Sci. 80(7):712-4 (1991). [cited by applicant]
Sikorska et al., “Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble formulation,” BioFactors. 18:173-83 (2003). [cited by applicant]
Steiner, “Clinical pharmacokinetics and pharmacodynamics of finasteride,” Clin Pharmacokinet. 30(1):16-27 (1996). Abstract Only. [cited by applicant]
Täuber et al., “Absolute bioavailability of testosterone after oral administration of testosterone-undecanoate and testosterone,” Eur J Drug Metab Pharmacokinet. 11(2):145-9 (1986). [cited by applicant]
Technical Data Sheet for CardioAid XF—Plant Sterols—040551, Archer Daniels Midland Company, dated Apr. 10, 2019 (1 page). [cited by applicant]
Tilvis et al., “Serum plant sterols and their relation to cholesterol absorption,” Am J Clin Nutr. 43:92-7 (1986). [cited by applicant]
Traish et al., “Adverse side effects of 5alpha-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients,” J Sex Med. 8(3):872-84 (2011). [cited by applicant]
Trevaskis et al., “Bile increases intestinal lymphatic drug transport in the fasted rat,” Pharm Res. 22(11):1863-70 (2005). [cited by applicant]
Trevaskis et al., “Lipid-based delivery systems and intestinal lymphatic drug transport,” Adv Drug Deliv Rev. 60:702-716 (2008). [cited by applicant]
Trevaskis et al., “The lymph lipid precursor pool is a key determinant of intestinal lymphatic drug transport,” J Pharmacol Exp Ther. 316(2):881-91 (2006). [cited by applicant]
Trevaskis et al., “The role of the intestinal lymphatics in the absorption of two highly lipophilic cholesterol ester transfer protein inhibitors (CP524,515 and CP532,623),” Pharm Res. 27(5):878- 93 (2010). [cited by applicant]
U.S. Appl. No. 15/959,626, filed Apr. 23, 2018 (87 pages). [cited by applicant]
Unpublished U.S. Appl. No. 13/843,223, filed Mar. 15, 2013. [cited by applicant]
Unpublished U.S. Appl. No. 61/291,769, filed Dec. 31, 2009. [cited by applicant]
Vahouny et al., “Comparative lymphatic absorption of sitosterol, stigmasterol, and fucosterol and differential inhibition of cholesterol absorption,” Amer J Clin Nutr. 37(5):805-9 (1983). [cited by applicant]
Von Eckardstein et al., “Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: a phase II study,” J Androl. 23(3):419-25 (2002). [cited by applicant]
Wagner, “Drug bioavailability studies,” Hosp Prac. 12:119-27 (1977). [cited by applicant]
Walsh, “Chemoprevention of prostate cancer,” N Engl J Med. 362(13):1237-8 (2010). [cited by applicant]
Welling, “Effects of food on drug absorption,” Pharmacol Ther. 43(3):425-41 (1989). [cited by applicant]
Welling, “How food and fluid affect drug absorption: results of initial studies,” Postgrad Med. 62(1):73-75, 78-82 (1977). [cited by applicant]
Welling, “Interactions affecting drug absorption,” Clin Pharmacokinet. 9:404-34 (1984). [cited by applicant]
Whitten et al., “Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate,” Fertil Steril. 86(6):1664-8 (2006). [cited by applicant]
Yin et al., “Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation,” available in PMC Sep. 19, 2014, published in final edited form as: J Androl. 3… [cited by applicant]
Zmuda et al., “The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity,” Metabolism. 42(4):446-50 (1993). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/029819, mailed Jul. 28, 2022 (10 pages). [cited by applicant]
Lachance et al., “Importance of measuring testosterone in enzyme-inhibited plasma for oral testosterone undecanoate androgen replacement therapy clinical trials,” Future Sci OA. 1(4):FSO55 (Nov. 1, 2015) (10 pages). [cited by applicant]
U.S. Appl. No. 63/378,291, Dhingra et al. [cited by applicant]
Azizi et al., “Phytochemicals With Anti 5-alpha-reductase Activity: A Prospective For Prostate Cancer Treatment,” F1000Res. 10:221 (2021) (21 pages). [cited by applicant]
Quallich, “Determining when men need testosterone,” Clinical Advisor, Jul. 6, 2009 (6 pages). [cited by applicant]
White et al., “Effects of Oral Testosterone Undecanoate (Kyzatrex) Versus Testosterone Gel (Androgel) on Long-Term (to 12 Months) Blood Pressure Levels,” Androgens: Clinical Research and Therapeutics 3.1:233-41 (2022). [cited by applicant]
White et al., “Effects of the oral testosterone undecanoate Kyzatrex™ on ambulatory blood pressure in hypogonadal men,” J Clin Hypertens. 23(7):1420-30 (Jul. 2021). [cited by applicant]
Swerdloff et al., “A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal Men,” J Clin Endocrinol Metab. 105(8):1-17 (Aug. 2020). [cited by applicant]
Broderick, “FDA accepts application for novel testosterone replacement therapy for hypogonadism,” Urology Times. <https://www.urologytimes.com/view/fda-accepts-application-for-novel-trt-for-hypogonadism>, Mar. 11, 2021 … [cited by applicant]
Park, “Kyzatrex Under Review for Primary and Secondary Male Hypogonadism,” Medical Professionals Reference. <https://www.biospace.com/marius-pharmaceuticals-submits-new-drug-application-tou-s-fda-for-next-generation-ora… [cited by applicant]
“Ambulatory Blood Pressure Monitoring (ABPM) Extension Study of Oral Testosterone Undecanoate in Hypogonadal Men,” ClinicalTrials.gov. <https://clinicaltrials.gov/study/NCT04467697?tab=history&a=3#version-content-panel>… [cited by applicant]
Lewington et al., “Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies,” The Lancet 360:1903-13 (Dec. 2002). [cited by applicant]
“FDA issues class-wide labeling changes for testosterone products”, U.S. Food and Drug Administration, <https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-class-wide-labeling-changes-testosterone-products… [cited by applicant]
Bone, Reproductive, And Urologic Drugs Advisory Committee (BRUDAC) Meeting, U.S. Food and Drug Administration, Jan. 9, 2018, Hyattsville, Maryland (363 pages). [cited by applicant]
U.S. Appl. No. 18/201,498, Dhingra et al. [cited by applicant]
U.S. Appl. No. 18/102,136, Dhingra, Om. [cited by applicant]
U.S. Appl. No. 18/176,166, Dhingra et al. [cited by applicant]