IP Library Granted Patent US 12,714,700
Granted Patent B2
US 12,714,700 · App. 18/615,735 · Granted Aug 25, 2026

Methods of treating RBP4 related diseases with triazolopyridines

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Quick Facts
Patent No.
US 12,714,700
App. No.
18/615,735
Granted
Aug 25, 2026
Kind
B2
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2025
From: PETRUKHIN, KONSTANTIN
To: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
Reel/Frame 073706/0824 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2025
From: LIN, YU-HSIN TOM; WANG, CHENG-CHI IRENE
To: BELITE BIO, INC
Reel/Frame 073032/0613 →
Continuity (5)
Continuation 17228590 · Apr 12, 2021
Division 16272911 · Feb 11, 2019
Division 16008838 · Jun 14, 2018
Provisional Application 62520420 · Jun 15, 2017
Related Publication 20240398780A1 · Dec 5, 2024
References Cited (121)
US 7632837B2 · Sun et al. · 2009 [cited by applicant]
US 8648038B2 · Defossa et al. · 2014 [cited by applicant]
US 8680137B2 · Sun et al. · 2014 [cited by applicant]
US 8980924B2 · Petrukhin et al. · 2015 [cited by applicant]
US 9333202B2 · Petrukhin et al. · 2016 [cited by applicant]
US 9434727B2 · Petrukhin et al. · 2016 [cited by applicant]
US 9487509B2 · Kasai et al. · 2016 [cited by applicant]
US 9637450B2 · Petrukhin et al. · 2017 [cited by applicant]
US 9777010B2 · Petrukhin et al. · 2017 [cited by applicant]
US 9926271B2 · Petrukhin et al. · 2018 [cited by applicant]
US 9938291B2 · Petrukhin et al. · 2018 [cited by applicant]
US 9944644B2 · Petrukhin et al. · 2018 [cited by applicant]
US 10245259B2 · Lin et al. · 2019 [cited by applicant]
US 11007186B2 · Lin et al. · 2021 [cited by applicant]
US 11362225B2 · Kojima et al. · 2022 [cited by applicant]
US 11389444B2 · Lin et al. · 2022 [cited by applicant]
US 12016853B2 · Lin et al. · 2024 [cited by applicant]
US 12364693B2 · Lin et al. · 2025 [cited by applicant]
US 20100022530A1 · Schiemann et al. · 2010 [cited by applicant]
US 20110123521A1 · Monia et al. · 2011 [cited by applicant]
US 20140066420A1 · Kasai et al. · 2014 [cited by applicant]
US 20150315197A1 · Petrukhin et al. · 2015 [cited by applicant]
US 20160004668A1 · Rowles et al. · 2016 [cited by applicant]
US 20160046648A1 · Petrukhin et al. · 2016 [cited by applicant]
US 20160046649A1 · Petrukhin et al. · 2016 [cited by applicant]
US 20170114072A1 · Yang et al. · 2017 [cited by applicant]
US 20210228563A1 · Lin et al. · 2021 [cited by applicant]
US 20220354844A1 · Lin et al. · 2022 [cited by applicant]
US 20220387400A1 · Lin et al. · 2022 [cited by applicant]
US 20230241049A1 · Petrukhin et al. · 2023 [cited by applicant]
US 20230312585A1 · Petrukhin et al. · 2023 [cited by applicant]
US 20250295654A1 · Lin et al. · 2025 [cited by applicant]
AU 2015336480A1 · 2017 [cited by applicant]
AU 2015336480A2 · 2017 [cited by applicant]
CN 101294956A · 2008 [cited by applicant]
EP 2202223A1 · 2010 [cited by applicant]
EP 3210973A1 · 2017 [cited by applicant]
WO WO0174164A1 · 2001 [cited by applicant]
WO WO2009143390A2 · 2009 [cited by applicant]
WO WO2012071369A2 · 2012 [cited by applicant]
WO WO2013166037A1 · 2013 [cited by applicant]
WO WO2014151936A1 · 2014 [cited by applicant]
WO WO2014151959A1 · 2014 [cited by applicant]
WO WO2014152013A1 · 2014 [cited by applicant]
WO WO2014152018A1 · 2014 [cited by applicant]
WO WO2014160409A1 · 2014 [cited by applicant]
WO WO2015168286A1 · 2015 [cited by applicant]
WO WO2016063933A1 · 2016 [cited by applicant]
WO WO2018232150A1 · 2018 [cited by applicant]
WO WO2020028723A1 · 2020 [cited by applicant]
Aguilera CM, et al. Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome. Clin Sci (Lond). Feb. 2008;114(3):183-193. [cited by applicant]
Anon, Diagnosis and Classification of Diabetes Mellitus. 2012 Diabetes care, 35 Suppl 1, pp. S64-S71. [cited by applicant]
Attie AD, et al. Adipocyte metabolism and obesity. J Lipid Res. Apr. 2009;50 Suppl:S395-S399. [cited by applicant]
Balagopal, Prabhakaran. et al. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. The Journal of clinical endocrinology and metabo… [cited by applicant]
Bhat, Pangala V, et al., Serum Retinol-binding Protein, Obesity, and Insulin Resistance. Vitamin-Binding Proteins, 31-47 (2014). [cited by applicant]
Bluher et al.: Does Retinol-Binding Protein 4 Cause or Reflect Fatty Liver Disease. Hepatology. 48(1):4-6 (2008). [cited by applicant]
Cannon, Burger's Medicinal Chemistry and Drug Discovery 1995, Fifth Edition, I: Principles and Practice, Chap. 19, John Wiley & Sons, Inc., 783-802 (1995). [cited by applicant]
Chalasani et al.: The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American… [cited by applicant]
Choe SS, et al. Adipose Tissue Remodeling Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). Apr. 13, 2016;7:30. [cited by applicant]
Cooke DW, et al. Type 1 diabetes mellitus in pediatrics. Pediatr Rev. Nov. 2008;29(11):374-384; quiz 385. [cited by applicant]
EP18816926.2 Examination Report dated Mar. 4, 2024. [cited by applicant]
EP18817386.8 European Examination Report dated Mar. 27, 2024. [cited by applicant]
Esteve, Eduardo. et al. Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes care 32(Suppl 2):S362-S367 (2009). [cited by applicant]
European Patent Application No. EP18817386.8 Extended European Search Report dated Feb. 5, 2021. [cited by applicant]
European Patent Application No. EP19845117.1-1112 Communication Pursuant to Article 94(3) EPC issued Jun. 21, 2022. [cited by applicant]
European Patent Application No. EP19845117.1-1112 Communication Pursuant to Article 94(3) EPC issued Oct. 23, 2023. [cited by applicant]
Fabbrini E, et al. Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology 2008;134:424-431. [cited by applicant]
Find ETDs Home Thesis Resources Find ETDs. Available at https://ndltd.org/thesis-resources/find-etds/ (Retrieved on Jan. 31, 2023). [cited by applicant]
Gavi, Shai. et al. Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. The Journal of clinical endocrinology and metabolism 92(5):1886-… [cited by applicant]
Gong., Research Progress on Role of Serum Retinol-binding Protein 4 in Development of Metabolic Related Diseases. Shandong Yiyao 55(19), 98-100 (2015). [cited by applicant]
Goto T, et al. Farnesol, an isoprenoid, improves metabolic abnormalities in mice via both PPAR-dependent and -independent pathways. Am J Physiol Endocrinol Metab. Nov. 2011;301(5):E1022-1032. [cited by applicant]
Graham et al.: Retinol-Binding Protein 4 and Insulin Resistance in Lean, Obese, and Diabetic Subjects. N. Engl J Med. 354:2552-2563 (2006). [cited by applicant]
International Application No. PCT/US2019/044754 International Search Report and Written Opinion dated Nov. 27, 2019. [cited by applicant]
Irwin, John et al., Zinc—a Free Database of Commercially Available Compounds for Virtual Screening. Journal of Chemical Information and Modeling. 45(1):177-182 (2005). [cited by applicant]
Johansson H, et al. Effect of fenretinide and low-dose tamoxifen on insulin sensitivity in premenopausal women at high risk for breast cancer. Cancer Res. Nov. 15, 2008;68(22):9512-9518. [cited by applicant]
Jung UJ, et al. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease. Int J Mol Sci. A… [cited by applicant]
Kahn SE, et al. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. Dec. 14, 2006;444(7121):840-846. [cited by applicant]
Kim, Sunghwan, et al., Pubchem in 2021: New Data Content and Improved Web Interfaces . Nucleic Acids Research 49(D1):D1388-D1395 (2021). [cited by applicant]
Klöting, Nora. et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell metabolism 6(1):79-87 (2007). [cited by applicant]
Koh IU, et al. Fenretinide ameliorates insulin resistance and fatty liver in obese mice. Biol Pharm Bull. 2012;35(3):369-375. [cited by applicant]
Li et al., Serum retinol-binding protein 4 levels in patients with diabetic retinopathy. The Journal of International Medical Research, 38:95-99, 2010. [cited by applicant]
Moon RC, et al. N-(4-Hydroxyphenyl)retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res. Apr. 1979;39(4):1339-1346. [cited by applicant]
Moraes-Vieira PM, et al. RBP4 Activates Antigen-Presenting Cells, Leading to Adipose Tissue Inflammation and Systemic Insulin Resistance. Cell Metab. Mar. 4, 2014;19(3):512-526. [cited by applicant]
Nair, Anup Kumar. et al. Case-control analysis of SNPs in GLUT4, RBP4 and STRA6: association of SNPs in STRA6 with type 2 diabetes in a South Indian population. PLOS One 5(7):e11444, 1-8 (2010). [cited by applicant]
Okada-Iwabu M, et al. Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity. Diabetes Metab J. Oct. 2015;39(5):363-372. [cited by applicant]
Ost, Anita. et al. Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB journal 21(13):3696-3704 (2007). [cited by applicant]
PCT/US2018/037593 International Search Report and Written Opinion dated Aug. 30, 2018. [cited by applicant]
PCT/US2018/037597 International Search Report and Written Opinion dated Aug. 28, 2018. [cited by applicant]
PCT/US2018/037606 International Preliminary Report on Patentability dated Dec. 17, 2019. [cited by applicant]
PCT/US2018/037606 International Search Report and written Opinion dated Aug. 28, 2018. [cited by applicant]
Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. J Clin Invest 2008;118:829-838. [cited by applicant]
Preitner F, et al. Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis. Am J Physiol Endocrinol Metab. Dec. 2009;297(6):E1420-E1429. [cited by applicant]
Samaras, Katherine. et al. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity 18(5):884-889 (2010). [cited by applicant]
Savage DB, et al. Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance. Physiol Rev. Apr. 2007;87(2):507-520. [cited by applicant]
STN Registry/Zregistry (CAS Registrysm) Sep. 2016 (2 pages.). [cited by applicant]
Taiwan Patent Application No. 107120497 Office Action/Search Report. [cited by applicant]
Taiwan Patent Application No. 107120499 Office Action. [cited by applicant]
Taiwan Patent Application No. 107120499 Office Action/Search Report. [cited by applicant]
Tan et al.: Suppression of retinol-binding protein 4 with RNA oligonucleotide prevents high-fat diet-induced metabolic syndrome and non-alcoholic fatty liver disease in mice. Department of Medical & Molecular BioScience… [cited by applicant]
Tilg H, et al. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. Nov. 2010;52(5):1836-1846. [cited by applicant]
U.S. Appl. No. 16/008,838 Restriction Requirement dated Sep. 21, 2018. [cited by applicant]
U.S. Appl. No. 16/272,911 Restriction Requirement dated Mar. 23, 2020. [cited by applicant]
U.S. Appl. No. 16/622,252 Final Office Action dated Oct. 20, 2021. [cited by applicant]
U.S. Appl. No. 16/622,252 Office Action dated Jun. 29, 2021. [cited by applicant]
U.S. Appl. No. 17/228,590 Office Action dated Jun. 7, 2023. [cited by applicant]
U.S. Appl. No. 17/228,590 Restriction Requirement dated Apr. 7, 2023. [cited by applicant]
U.S. Appl. No. 17/228,590 Notice of Allowance dated Jan. 3, 2024. [cited by applicant]
U.S. Appl. No. 17/228,590 Notice of Allowance dated May 21, 2024. [cited by applicant]
U.S. Appl. No. 17/739,757 Office Action dated Apr. 29, 2024. [cited by applicant]
U.S. Appl. No. 17/739,757 Office Action dated Feb. 1, 2024. [cited by applicant]
U.S. Appl. No. 17/739,757 Office Action dated Oct. 16, 2024. [cited by applicant]
Venkatesh et al. Role of the Development Scientist in Compound Lead Selection and Optimization. J. Pharm. Sci. 89(2):145-154 (Feb. 2000). [cited by applicant]
Wang. Correlation of retinol binding protein 4 with metabolic indexes of glucose and lipid, bile cholesterol saturation index. 40(6):657-665 (2015) DOI:10.11817/j.issn.1672-7347.2015.06.014. [cited by applicant]
West. Solid Solutions. Solid State Chemistry and Its Applications. John Wiley & Sons. Chapter vol. 10: p. 358 (1984). [cited by applicant]
Wolff. Burger's Medicinal Chemistry and Drug Discovery. 5th Ed. Part 1, pp. 975-977 (1995). [cited by applicant]
Yang et al.: Berberine ameliorates non-alcoholic steatohepatitis in ApoE-/- mice. Center for Translational Medicine. 14:4134-4140 (2017). [cited by applicant]
Yang et al.: Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436(7049):356-362 (2005). [cited by applicant]
Zhang et al.: Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus. Chinese Medical Association. 121(21):2124-8 (2022). [cited by applicant]
Chen, Ching-Chu. et al. Levels of retinol-binding protein 4 and uric acid in patients with type 2 diabetes mellitus. Metabolism 58(12):1812-1816 (2009). [cited by applicant]
Co-pending U.S. Appl. No. 19/231,020, inventors Lin; Yu-Hsin Tom et al., filed Jun. 6, 2025. [cited by applicant]
EP19845117.1 Communication dated Oct. 1, 2025. [cited by applicant]