IP Library › Granted Patent US 12,435,026
Granted Patent B2
US 12,435,026 · App. 18/199,205 · Granted Oct 7, 2025

Solabegron zwitterion and uses thereof

Inventors: Raymond E. Stevens (West Chester, PA); Dalian Zhao (Fanwood, NJ); Bingidimi Itute Mobele (Altamont, NY)
Assignee: B3AR THERAPEUTICS, INC.
C07C229/52A61K31/196A61K45/06C07C227/16C07D233/26C07D498/04C07B2200/13
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Quick Facts
Patent No.
US 12,435,026
App. No.
18/199,205
Granted
Oct 7, 2025
Kind
B2
Abstract

This application relates to solabegron zwitterion useful for the treatment of lower urinary tract symptoms such as, for example, overactive bladder and prostate disorders. Additionally, this application relates to pharmaceutical compositions and methods of treatment utilizing the solabegron zwitterion for treating lower urinary tract symptoms. This application also relates to methods of preparing solabegron hydrochloride from the solabegron zwitterion.

Claims (26)

1. A solid compound according to Formula II:

wherein the compound is characterized by:

an x-ray powder diffraction pattern having peaks expressed in degrees 2θ at 17.6, 18.7, 19.6, 20.1, 20.5, 23.7, and 25.8; and

a differential scanning calorimetry (DSC) thermograph exhibiting a very broad peak at about 67° C., a broad peak at about 131° C., and a narrow peak at about 180° C.

2. A pharmaceutical composition comprising: a therapeutically effective amount of a solid compound according to Formula II:

wherein the compound is characterized by:

an x-ray powder diffraction pattern having peaks expressed in degrees 2θ at 17.6, 18.7, 19.6, 20.1, 20.5, 23.7, and 25.8; and

a differential scanning calorimetry (DSC) thermograph exhibiting a very broad peak at about 67° C., a broad peak at about 131° C., and a narrow peak at about 180° C.; and

at least one pharmaceutically acceptable carrier or excipient.

3. The solid compound according to claim 1 , wherein the compound is a single polymorph.

4. The solid compound according to claim 1 , wherein the compound is a hydrate of isopropanol solvate.

5. The solid compound according to claim 1 , wherein the compound is at least about 97.0% by weight pure.

6. The solid compound according to claim 1 , wherein the compound is at least about 99.0% by weight pure.

7. The solid compound according to claim 1 , wherein the compound is at least about 99.5% by weight pure.

8. The solid compound according to claim 1 , wherein the compound is at least about 99.9% by weight pure.

9. The solid compound according to claim 1 , wherein no single impurity is present in an amount greater than about 0.5% by weight.

10. The solid compound according to claim 1 , wherein no single impurity is present in an amount greater than about 0.25% by weight.

11. The pharmaceutical composition of claim 2 , wherein the solid compound is a single polymorph.

12. The pharmaceutical composition of claim 2 , wherein the solid compound is a hydrate of isopropanol solvate.

13. The pharmaceutical composition of claim 2 , wherein the solid compound is at least about 97.0% by weight pure.

14. The pharmaceutical composition of claim 2 , wherein the solid compound is at least about 99.0% by weight pure.

15. The pharmaceutical composition of claim 2 , wherein the solid compound is at least about 99.5% by weight pure.

16. The pharmaceutical composition of claim 2 , wherein the solid compound is at least about 99.9% by weight pure.

17. The pharmaceutical composition of claim 2 , wherein no single impurity is present in the solid compound in an amount greater than about 0.5% by weight.

18. The pharmaceutical composition of claim 2 , wherein no single impurity is present in the solid compound in an amount greater than about 0.25% by weight.

19. The pharmaceutical composition of claim 2 , wherein no single impurity is present in the solid compound in an amount greater than about 0.10% by weight.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2023
From: STEVENS, RAYMOND E.
To: VELICEPT THERAPEUTICS, INC.
Reel/Frame 064567/0397 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 12, 2023
From: MOBELE, BINGIDIMI ITUTE; RONDAXE PHARMA, LLC
To: VELICEPT THERAPEUTICS, INC.
Reel/Frame 063926/0193 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 12, 2023
From: VELICEPT THERAPEUTICS, INC.
To: VELICEPT (ASSIGNMENT FOR THE BENEFIT OF CREDITORS), LLC
Reel/Frame 063926/0347 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 12, 2023
From: VELICEPT (ASSIGNMENT FOR THE BENEFIT OF CREDITORS), LLC; VELICEPT THERAPEUTICS, INC.
To: B3AR THERAPEUTICS, INC.
Reel/Frame 063926/0390 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 12, 2023
From: ZHAO, DALIAN; J-STAR RESEARCH, INC.
To: VELICEPT THERAPEUTICS, INC.
Reel/Frame 064559/0900 →
Continuity (10)
Continuation 17077446 · Oct 22, 2020
Continuation 16246114 · Jan 11, 2019
Continuation 16018945 · Jun 26, 2018
Division 15332956 · Oct 24, 2016
Provisional Application 62245656 · Oct 23, 2015
Provisional Application 62245670 · Oct 23, 2015
Provisional Application 62345327 · Jun 3, 2016
Provisional Application 62345357 · Jun 3, 2016
Provisional Application 62345574 · Jun 3, 2016
Related Publication 20240124391A1 · Apr 18, 2024
References Cited (136)
US 4478849A · Ainsworth et al. · 1984 [cited by applicant]
US 4772631A · Holloway et al. · 1988 [cited by applicant]
US 6069176A · Tsuchiya et al. · 2000 [cited by applicant]
US 6123961A · Aberg · 2000 [cited by applicant]
US 6228398B1 · Devane et al. · 2001 [cited by applicant]
US 6251925B1 · Donaldson et al. · 2001 [cited by applicant]
US 6395762B1 · Fobare et al. · 2002 [cited by applicant]
US 6444685B1 · Sum et al. · 2002 [cited by applicant]
US 6451814B1 · Ashwell et al. · 2002 [cited by applicant]
US 6548523B2 · Lawrence et al. · 2003 [cited by applicant]
US 7022716B2 · Hu et al. · 2006 [cited by applicant]
US 7034053B2 · Deaton et al. · 2006 [cited by applicant]
US 7425639B2 · Cooke et al. · 2008 [cited by applicant]
US 7709677B2 · Cooke et al. · 2010 [cited by applicant]
US 8017613B2 · Scilimati et al. · 2011 [cited by applicant]
US 8247415B2 · Berger et al. · 2012 [cited by applicant]
US 8354403B2 · Edmondson et al. · 2013 [cited by applicant]
US 8399408B2 · Austen et al. · 2013 [cited by applicant]
US 8399480B2 · Berger et al. · 2013 [cited by applicant]
US 8642661B2 · Caltabiano et al. · 2014 [cited by applicant]
US 9522129B2 · Caltabiano et al. · 2016 [cited by applicant]
US 9907767B2 · Caltabiano et al. · 2018 [cited by applicant]
US 9956194B2 · Ohlstein et al. · 2018 [cited by applicant]
US 10004747B2 · Klein et al. · 2018 [cited by applicant]
US 10065922B2 · Stevens et al. · 2018 [cited by applicant]
US 10221126B2 · Stevens et al. · 2019 [cited by applicant]
US 10350182B2 · Caltabiano et al. · 2019 [cited by applicant]
US 10668034B2 · Caltabiano et al. · 2020 [cited by applicant]
US 10751311B2 · Ohlstein et al. · 2020 [cited by applicant]
US 10844004B2 · Stevens et al. · 2020 [cited by applicant]
US 11691944B2 · Stevens et al. · 2023 [cited by applicant]
US 20030082230A1 · Baichwal et al. · 2003 [cited by applicant]
US 20040122014A1 · Mammen et al. · 2004 [cited by applicant]
US 20050101607A1 · Michel et al. · 2005 [cited by applicant]
US 20050137236A1 · Hattori et al. · 2005 [cited by applicant]
US 20050154041A1 · Michel et al. · 2005 [cited by applicant]
US 20050181031A1 · Saito et al. · 2005 [cited by applicant]
US 20050261328A1 · Wienrich et al. · 2005 [cited by applicant]
US 20050261369A1 · Mehlburger et al. · 2005 [cited by applicant]
US 20060084700A1 · Michel · 2006 [cited by applicant]
US 20060240105A1 · Devane et al. · 2006 [cited by applicant]
US 20070078181A1 · Michel · 2007 [cited by applicant]
US 20090253705A1 · Berger et al. · 2009 [cited by applicant]
US 20100240697A1 · Suzuki et al. · 2010 [cited by applicant]
US 20100286275A1 · Zhang · 2010 [cited by applicant]
US 20100291209A1 · Vergnault et al. · 2010 [cited by applicant]
US 20110028461A1 · Berger et al. · 2011 [cited by applicant]
US 20110028481A1 · Berger et al. · 2011 [cited by applicant]
US 20110065660A1 · Baron et al. · 2011 [cited by applicant]
US 20110081426A1 · Rao et al. · 2011 [cited by applicant]
US 20120053181A1 · Lin et al. · 2012 [cited by applicant]
US 20120142725A1 · Van Charldorp et al. · 2012 [cited by applicant]
US 20120157432A1 · Edmondson et al. · 2012 [cited by applicant]
US 20120202819A1 · Edmondson et al. · 2012 [cited by applicant]
US 20120225886A1 · Edmondson et al. · 2012 [cited by applicant]
US 20120258963A1 · Berger et al. · 2012 [cited by applicant]
US 20120289565A1 · Paborji et al. · 2012 [cited by applicant]
US 20130053403A1 · Berger et al. · 2013 [cited by applicant]
US 20130150402A1 · Suzuki et al. · 2013 [cited by applicant]
US 20130172277A1 · Caltabiano et al. · 2013 [cited by applicant]
US 20140243544A1 · Wang et al. · 2014 [cited by applicant]
US 20150306170A1 · Ahuja et al. · 2015 [cited by applicant]
US 20150374655A1 · Ibáñez Cabeza et al. · 2015 [cited by applicant]
US 20170035716A1 · Ohlstein · 2017 [cited by applicant]
US 20170348263A1 · Ohlstein et al. · 2017 [cited by applicant]
US 20170348288A1 · Ohlstein et al. · 2017 [cited by applicant]
US 20240197660A1 · Stevens, Jr. et al. · 2024 [cited by applicant]
CA 2507343A1 · 2005 [cited by applicant]
EP 0400519A1 · 1990 [cited by applicant]
EP 0455006A2 · 1991 [cited by applicant]
EP 0543662A2 · 1993 [cited by applicant]
EP 0806948B1 · 2000 [cited by applicant]
EP 1258253A1 · 2002 [cited by applicant]
EP 1967202A1 · 2008 [cited by applicant]
EP 2216021A1 · 2010 [cited by applicant]
GB 940540A · 1963 [cited by applicant]
WO 9533724A1 · 1995 [cited by applicant]
WO 0142195A1 · 2001 [cited by applicant]
WO 0154728A1 · 2001 [cited by applicant]
WO 03024483A1 · 2003 [cited by applicant]
WO 2004041806A2 · 2004 [cited by applicant]
WO 2004047838A2 · 2004 [cited by applicant]
WO 2005065673A1 · 2005 [cited by applicant]
WO 2005067938A1 · 2005 [cited by applicant]
WO 2006113649A1 · 2006 [cited by applicant]
WO 2008107446A1 · 2008 [cited by applicant]
WO 2008121268A1 · 2008 [cited by applicant]
WO 2008122014A1 · 2008 [cited by applicant]
WO 2009057685A1 · 2009 [cited by applicant]
WO 2009124167A1 · 2009 [cited by applicant]
WO 2010118291A2 · 2010 [cited by applicant]
WO 2011025690A1 · 2011 [cited by applicant]
WO 2011043942A1 · 2011 [cited by applicant]
WO 2011075514A1 · 2011 [cited by applicant]
WO 2011084456A1 · 2011 [cited by applicant]
WO 2011084459A1 · 2011 [cited by applicant]
WO 2012018773A1 · 2012 [cited by applicant]
WO 2013119910A1 · 2013 [cited by applicant]
WO 2015120110A2 · 2015 [cited by applicant]
WO 2016004056A1 · 2016 [cited by applicant]
WO 2016090168A1 · 2016 [cited by applicant]
WO 2017070689A2 · 2017 [cited by applicant]
WO 2017210696A1 · 2017 [cited by applicant]
WO 2017210700A1 · 2017 [cited by applicant]
Abrams et al. “Combination Treatment with Mirabegron and Solifenacin in Patients with Overaactive Bladder (Oab) Efficacy Results from a Phase 2 Study (Symphony)” May 4-8, 2013, AUA Annual Meeting, San Diego, CA, 12 page… [cited by applicant]
Arch et al. “Atypical β-adrenoceptor on Brown Adipocytes as Target for Anti-Obesity Drugs” May 10, 1984, Nature 309:163-165. [cited by applicant]
Bianchetti et al. “In Vitro Inhibition Of Intestinal Motiliy by Phenylethanolaminotetralines: Evidence of Atypical SS-adrenoceptors in Rat Colon” Aug. 1990, Br. J. Pharmacol. 100:831-839. [cited by applicant]
Biers et al. “The effects of a new selective β3-adrenoceptor agonist (GW427353) on spontaneous activity and detrusor relaxation in human bladder” Nov. 7, 2006, BJU International 98:1310-1314. [cited by applicant]
Clinical Trial NCT00501267: “A Study to Test the Interaction of Two Medications for the Treatment of Overactive Bladder” Retrieved from the internet: https://clinicaltrials.gov/ct2/show/NCT00501267?term=NCT00501267&… [cited by applicant]
Clinical Trials Gov.: “Alternating Thalidomide and Lenalidomide Plus Rituximab as Initial Treatment for CLL” May 17, 2010, NCT01779167, retrieved from the internet: https://clinicaltrials.jov/archive/NCT0112,5176/2010_0… [cited by applicant]
Definition of “compound” and “composition” from the Grant & Hackh's Chemical Dictionary 1987, McGraw-Hill, Inc. 148 (1 Page). [cited by applicant]
Ellsworth et al. “Solabegron: A Potential Future Addition to the B-3 Adrenoceptor Agonist Armamentarium for the Management of Overactive Bladder” Mar. 2015, Expert Opinion on Investigational Drugs UK 24(3):413-419, doi:… [cited by applicant]
Emorine et al. “Molecular Characterization of the Human Beta 3-Adrenergic Receptor” Sep. 8, 1989, Science 245(4922):1118-1121. [cited by applicant]
Extended European Search Report for EP 15865588.6 dated Apr. 9, 2018, 9 pages. [cited by applicant]
Gillespie et al. “Modulation of non-voiding activity by the muscarinergic antagonist tolterodine and the Beta-3-adrenoceptor agonist mirabegron in conscious rats with partial outflow obstruction” 2012, BJU International… [cited by applicant]
Grudell et al. “Dose-response Effect of a beta3-adrenergic Receptor Agonist, Solabegron, on Gastrointestinal Transit, Bowel Function, and Somatostatin Levels in Health” May 1, 2008, Am. J. Physiol. Gastro. Liver Physiol… [cited by applicant]
Hertzberg et al. “Synthesis of The B 3 -Adrenergic Receptor Agonist Solabegron and Analogous N -(2-Ethylamino)-β-Amino Alcohols From O -Acylated Cyanohydrins—Expanding the Scope of Minor Enantiomer Recycling” Mar. 6, 20… [cited by applicant]
Hicks et al. “GW427353 (Solabegron), a Novel, Selective Beta(3)-Adrenergic Receptor Agonist, Evokes Bladder Relaxation and Increases Micturition Reflex Threshold In the Dog” Oct. 1, 2007, J. of Pharmacology and Experime… [cited by applicant]
Hutchinson et al. “Beta-3-Adrenoceptor Regulation and Relaxation Responses in Mouse Ileum” 2000, Br. J. Pharmacol. 129:1251-1259. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/060264, mailed Feb. 14, 2020, 11 Pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2022/071462, mailed Jun. 21, 2022, 9 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2015/038583 dated Sep. 17, 2015 , 7 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2011/046208 dated Sep. 26, 2011, 9 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2013/025285 dated Mar. 25, 2013, 11 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2015/063795 dated Feb. 11, 2016, 10 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2016/058516 dated Jun. 5, 2017, 18 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2017/036005 dated Aug. 29, 2017, 13 Pages. [cited by applicant]
International Search Report and Written Opinion for PCT/US2017/036016 dated Aug. 28, 2017, 22 Pages. [cited by applicant]
Irwin et al. “Prevalence, Severity, and Symptom Bother of Lower Urinary Tract Symptoms among Men in the EPIC Study: Impact of Overactive Bladder” Mar. 3, 2009, European Urology 56:14-20. [cited by applicant]
Leach et al. “Structure-Function Studies of Muscarinic Acetylcholine Receptors” 2012, Handbook of Experimental Pharmacology 208:29-48. [cited by applicant]
Ma “Gynecological Urology Ed.1” Aug. 2009, Science Press, 323-330. [cited by applicant]
Ohlstein et al. “A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of the Beta3-Adrenoceptor Agonist Solabegron for Overactive Bladder” Jun. 5, 2012, European Urology 62:834-840. [cited by applicant]
Otsuka et al. “Combination Effect of B3-Adrenoceptor Agonist and Muscarinic Receptor Antagonist on Human Detrusor Muscle Relaxation in Vitro” Oct. 2012, International Continence Society Meeting 894-895. [cited by applicant]
Rackley et al. “Nighttime Dosing with Tolterodine Reduces Overactive Bladder-Related Nocturnal Micturitions in Patients with Overactive Bladder and Nocturia” 2006, Urology 67:731-736. [cited by applicant]
Uehling D., et al., “Biarylaniline Phenethanolamines as Potent and Selective [beta] 3 Adrenergic Receptor Agonists,” May 1, 2006, Journal of Medicinal Chemistry, US 49(9):2758-2771, DOI: 10.1021/jm0509445, ISSN 0022-262… [cited by applicant]
Vrydag et al. “Do Gene Polymorphisms Alone or in Combination Affect the Function of Human β3-adrenoceptors?” 2009, Br. J. Pharmacol. 156:127-134. [cited by applicant]