IP Library › Granted Patent US 12,344,606
Granted Patent B2
US 12,344,606 · App. 17/618,007 · Granted Jul 1, 2025

Next-generation modulators of stimulator of interferon genes (STING)

Inventors: Magdalena Izabela Zawadzka (Gdansk, PL); Luigi Piero Stasi (Cracow, PL); Maciej Krzysztof Rogacki (Cracow, PL); Grzegorz Wojciech Cwiertnia (Kamesznica, PL); Lukasz Piotr Dudek (Cracow, PL); Monika Patrycja Dobrzanska (Wroclaw, PL); Grzegorz Witold Topolnicki (Piekary Slaskie, PL); Agnieszka Justyna Gibas (Cracow, PL); Anna Rajda (Gliwice, PL); Sylwia Sudol (Cracow, PL); Karolina Maria Gluza (Wroclaw, PL); Charles-Henry Fabritius (Poznan, PL)
Assignee: Ryvu Therapeutics S.A.
C07D471/04A61P35/00C07D401/14C07D405/14C07D413/14C07D417/14
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 12,344,606
App. No.
17/618,007
Granted
Jul 1, 2025
Kind
B2
Abstract

The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

Claims (40)

1. A compound which is

3-({[(2-methoxypyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1-methyl-1,4-dihydroquinolin-4-one,

1-methyl-3-({[(2-methylpyridin-4-yl)methyl][1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

1-methyl-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

3-({[(2-methoxypyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

1-methyl-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

1-cyclopropyl-6,7-difluoro-3-({[(2-methoxypyridin-4-yl)methyl][(3S)-1-(pyridin-3, yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-bromo-1-methyl-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-chloro-6-fluoro-1-methyl-3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

3-({[(3S,5S)-5-fluoro-1-(pyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-methyl-1,4-dihydroquinolin-4-one,

7-chloro-1-cyclopropyl-6-fluoro-3-({[(2-methoxypyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

1-cyclopropyl-6,7-difluoro-3-({[(2-methoxypyridin-4-yl)methyl][(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-chloro-1-cyclopropyl-6-fluoro-3-({(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl)piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

3-({[(2-methylpyridin-4-yl)methyl][(3S)-1-(pyridin-3-yl) piperidin-3-yl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-bromo-1-methyl-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

1-methyl-3-({[(3S)-1-(pyridin-3-yl) piperidin-3-yl][(pyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-chloro-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-chloro-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydro-1,8-naphthyridin-4-one,

1-cyclopropyl-6-fluoro-7-methoxy-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydro-1,8-naphthyridin-4-one,

1-cyclopropyl-6-fluoro-7-methoxy-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(oxetan-3-yl)-1,4-dihydroquinolin-4-one,

7-chloro-1-cyclopropyl-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydro-1,6-naphthyridin-4-one,

7-(cyclohex-1-en-1-yl)-1-cyclopropyl-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

1-cyclopropyl-6-fluoro-7-hydroxy-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

8-bromo-1-methyl-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one,

7-chloro-6-fluoro-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(propan-2-yl)-1,4-dihydro-1,8-naphthyridin-4-one,

6-fluoro-7-methoxy-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(propan-2-yl)-1,4-dihydro-1,8-naphthyridin-4-one, or

1-cyclopropyl-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-(morpholin-3-yl)-1,4-dihydroquinolin-4-one;

or a salt, stereoisomer, or N-oxide thereof.

2. The compound according to claim 1 , wherein the compound is selected from the group consisting of 3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one, 1-cyclopropyl-6-fluoro-7-hydroxy-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1,4-dihydroquinolin-4-one, 6-fluoro-7-methoxy-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-1-(propan-2-yl)-1,4-dihydro-1,8-naphthyridin-4-one, and 1-cyclopropyl-3-({[(3S)-1-(6-methylpyridin-3-yl) piperidin-3-yl][(2-methylpyridin-4-yl)methyl]amino}methyl)-7-(morpholin-3-yl)-1,4-dihydroquinolin-4-one, or a salt, stereoisomer, tautomer, or N-oxide thereof.

3. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to claim 1 , or a salt, stereoisomer, or N-oxide thereof, and optionally a pharmaceutically acceptable carrier, diluent or excipient.

4. A method of treating a cancerous or pre-cancerous solid tumor or a bacterial or viral infection in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a compound according to claim 1 or a salt, stereoisomer, or N-oxide thereof.

5. The method of claim 4 , wherein the cancerous or pre-cancerous solid tumor is selected from the group consisting of prostate cancer, renal carcinoma, melanoma, pancreatic cancer, cervical cancer, ovarian cancer, colon cancer, head and neck cancer, lung cancer, fibrosarcoma, and breast cancer.

6. A method of treating a disease selected from the group consisting of inflammatory diseases, allergic diseases, and autoimmune diseases in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a compound according to claim 1 or a salt, stereoisomer, or N-oxide thereof.

7. A method of treating a cancerous or pre-cancerous solid tumor or a bacterial or viral infection in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a pharmaceutical composition according to claim 3 .

8. The method of claim 7 , wherein the cancerous or pre-cancerous solid tumor is selected from the group consisting of prostate cancer, renal carcinoma, melanoma, pancreatic cancer, cervical cancer, ovarian cancer, colon cancer, head and neck cancer, lung cancer, fibrosarcoma, and breast cancer.

9. A method of treating a disease selected from the group consisting of inflammatory diseases, allergic diseases, and autoimmune diseases in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a pharmaceutical composition according to claim 3 .

10. A method of enhancing response to an immunogenic composition or vaccine composition in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a compound according to claim 1 or a salt, stereoisomer, or N-oxide thereof, together with said immunogenic composition or vaccine composition.

11. A method of enhancing response to an immunogenic composition or vaccine composition in a patient in need thereof, comprising administering to said patient a pharmaceutically effective amount of a pharmaceutical composition according to claim 3 , together with said immunogenic composition or vaccine composition.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 28, 2022
From: ZAWADZKA, MAGDALENA IZABELA; STASI, LUIGI PIERO; ROGACKI, MACIEJ KRZYSZTOF; CWIERTNIA, GRZEGORZ WOJCIECH; DUDEK, LUKASZ PIOTR; DOBRZANSKA, MONIKA PATRYCJA; TOPOLNICKI, GRZEGORZ WITOLD; GIBAS, AGNIESZKA JUSTYNA; RAJDA, ANNA; SUDOL, SYLWIA; GLUZA, KAROLINA MARIA; FABRITIUS, CHARLES-HENRY
To: RYVU THERAPEUTICS S.A.
Reel/Frame 060337/0179 →
Priority Claims (2)
EP 19460034 · Jun 12, 2019 · regional
EP 19460067 · Dec 11, 2019 · regional
Continuity (1)
Related Publication 20220251082A1 · Aug 11, 2022
References Cited (76)
US 3410851A · Stauffer · 1968 [cited by applicant]
US 20080139558A1 · Smith et al. · 2008 [cited by applicant]
US 20110212946A1 · Barrow et al. · 2011 [cited by applicant]
US 20220402898A1 · Dobrzanska · 2022 [cited by examiner]
US 20230055741A1 · Zawadzka · 2023 [cited by examiner]
US 20230076506A1 · Zawadzka · 2023 [cited by examiner]
GB 2563642A · 2018 [cited by applicant]
WO WO2004042083A2 · 2004 [cited by applicant]
WO WO2007128568A1 · 2007 [cited by applicant]
WO WO2019023635A1 · 2019 [cited by applicant]
WO WO2019182886A1 · 2019 [cited by applicant]
WO WO2019238786A1 · 2019 [cited by applicant]
Wang, T.; et al. “Salts, Cocrystals, and Ionic Cocrystals of a “Simple” Tautomeric Compound” 2018, Crystal Growth and Design, vol. 18, pp. 6973-6983. (Year: 2018). [cited by examiner]
An, X.; et al. “An Analysis of the Expression and Association with Immune Cell Infiltration of the cGAS/STING Pathway in Pan-Cancer” 2019, Molecular Therapy: Nucleic Acids, vol. 14, pp. 80-89 (published with Mar. 2019 i… [cited by examiner]
Bakhoum, S. F.; et al. “Chromosomal instability drives metastasis through a cytosolic DNA response” 2018, Nature, vol. 553, pp. 467-472. (Year: 2018). [cited by examiner]
Aguzzi, A.; et al. “The immunobiology of prion diseases” 2013, Nature Reviews Immunology, vol. 13, p. 888-902. (Year: 2011). [cited by examiner]
Guo, F.; et al. “STING Agonists Induce an Innate Antiviral Immune Response against Hepatitis B Virus” 2015, Antimicrobial Agents and Chemotherapy, vol. 59, pp. 1273-1281. (Year: 2015). [cited by examiner]
Madhun, A. S.; et al. “Intranasal c-di-GMP-adjuvanted plant-derived HS influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice” 2011, Vaccine, vol. 29, pp. 497… [cited by examiner]
Zhang, Z.; et al. “Peptide nanotube loaded with a STING agonist, c-di-GMP, enhance cancer immunotherapy against melanoma” 2023, Nano Research, vol. 16, pp. 5206-5215. (Year: 2023). [cited by examiner]
Demaria, O.; et al. “STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity” 2015, Proceedings of the National Academy of Sciences, vol. 112, pp. 15408-15413. (Year: 2015). [cited by examiner]
Aguirre, S., et al., “DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING,” PloS Pathog, 8(10):e1002934, Plos, United States (2012). [cited by applicant]
Chen, X., et al., “SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex,” Protein Cell 5(5):369-381, Oxford University Press , Unit… [cited by applicant]
Cirulli, E., et al., “Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways,” Science 347(6229):1436-1441, American Association for the Advancement of Science, United States (2015). [cited by applicant]
Collins, A.C., et al., “Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for [cited by applicant]
Corrales, L., and Gajewski, T.F., “Molecular Pathways: Targeting the Stimulator of Interferon Genes (STING) in the Immunotherapy of Cancer,” Clin. Cancer Res. 21(21):4774-4779, American Association for Cancer Research, … [cited by applicant]
Corrales, L., et al., “Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity,” Cell Rep. 11(7):1018-1030, Cell Press, United States (May 2015). [cited by applicant]
Corrales, L., et al., “Extremely potent immunotherapeutic activity of a STING agonist in the B16 melanoma model in vivo,” J. Immunother. Cancer 2013, 1 (Suppl 1):O15, BMJ Publishing Group Ltd, United Kingdom (2013). [cited by applicant]
Crow, Y.J., et al., “Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus,” Nat. Genet. 38(8):917-920, Springer, Germany (2006). [cited by applicant]
Ding, Q., et al., “Hepatitis C virus NS4B blocks the interaction of STING and TBK1 to evade host innate immunity,” J. Hepatol. 59(1):52-58, Elsevier, Netherlands (2013). [cited by applicant]
Dubensky, T.W., et al., “Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants,” Ther. Adv. Vaccines 1(4):131-143, Sage Publications, United States (2013). [cited by applicant]
Freischmidt, A., et al., “Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia,” Nat. Neurosci. 18(5):631-636, Springer, Germany (2015). [cited by applicant]
Fu, J., et al., “STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade,” Sci. Transl. Med. 7(283):283ra52, American Association for the Advancement of Science, United States (20… [cited by applicant]
Gao, D., et al., “Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses,” Science 341(6148):903-906, American Association for the Advancement of Science, United States (2013). [cited by applicant]
Gao, P., et al., “Cyclic [G(2′,5′)pA(3′,5′)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase,” Cell 153:1094-1107, Cell Press, United States (2013). [cited by applicant]
Herzner, A.-M., et al., “Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA,” Nat. Immunol. 16(10):1025-1033, Springer, Germany (2015). [cited by applicant]
Holm, C., et al., “Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses,” Nat Comm. 7:10680, Springer, Netherlands (2016). [cited by applicant]
Huber, J.P., et al., “Cutting Edge: Type I IFN Reverses Human Th2 Commitment and Stability by Suppressing GATA3,” J. Immunol. 185:813-817, American Association of Immunologists, United States (2010). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/EP2020/066370, European Patent Office, Netherlands, mailed on Aug. 28, 2020, 8 pages. [cited by applicant]
Ishikawa, H., and Barber, G.N., “STING is an endoplasmic reticulum adaptor that facilitates innate immune signaling,” Nature 455:674-678, Springer, Netherlands (2008). [cited by applicant]
Ishikawa, H., et al., “STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity,” Nature 461(7265):788-792, Springer, Netherlands (2009). [cited by applicant]
Jin, L., et al., “MPYS Is Required for IFN Response Factor 3 Activation and Type I IFN Production in the Response of Cultured Phagocytes to Bacterial Second Messengers Cyclic-di-AMP and Cyclic-di-GMP,” J. Immunol. 187(5… [cited by applicant]
Lau, L., et al., “DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway,” Science 350(6260):568-571, American Association for the Advancement of Science, Untied States (2015). [cited by applicant]
Lemos, H., et al., “Activation of the Stimulator of Interferon Genes (STING) Adaptor Attenuates Experimental Autoimmune Encephalitis,” J. Immunol. 192(12):5571-5578, American Association of Immunologists, United States … [cited by applicant]
Liu, Y., et al., “RIG-I-Mediated STING Upregulation Restricts Herpes Simplex Virus 1 Infection,” J. Virol. 90(20):9406-9419, American Society for Microbiology, United States (2016). [cited by applicant]
Ma, Z., and Damania, B., “The cGAS-STING Defense Pathway and Its Counteraction by Viruses,” Cell Host & Microbe 19(2):150-158, Cell Press, United States (2016). [cited by applicant]
Ma, Z., et al., “Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses,” PNAS 112(31):E4306-E4315, National Academy of Sciences, Untied States (2015). [cited by applicant]
McNab, F., et al., “Type I interferons in infectious disease,” Nat. Rev. Immunol. 15(2):87-103, Springer, Germany (2015). [cited by applicant]
Moisan, J., et al., “TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway,” Am. J. Physiol. Lung Cell Mol. Physiol. 290:L9… [cited by applicant]
Nitta, S., et al., “Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type I interferon-dependent innate immunity,” Hepatology 57(1):46-58, Wiley, United States (2013). [cited by applicant]
Persing, D.H., et al., “Taking toll: lipid A mimetics as adjuvants and immunomodulators,” Trends Microbiol. 10(10 Suppl):S32-S37, Elsevier, Netherlands (2002). [cited by applicant]
Prantner, D., et al., “Stimulator of IFN gene is critical for induction of IFN-β during [cited by applicant]
Rakoff-Nahoum, S., et al., “Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis,” Cell 118(2):229-241, Cell Press, United States (2004). [cited by applicant]
Sharma, S., et al., “Innate immune recognition of an AT-rich stem-loop DNA motif in the [cited by applicant]
Stetson, D.B., et al., “Trex1 prevents cell-intrinsic initiation of autoimmunity,” Cell 134(4):587-598, Cell Press, United States (2008). [cited by applicant]
Storek, K.M., et al., “cGAS and Ifi204 Cooperate To Produce Type I IFNs in Response to [cited by applicant]
Sun, L., et al., “Coronavirus Papain-like Proteases Negatively Regulate Antiviral Innate Immune Response through Disruption of STING-Mediated Signaling,” PloS One 7(2): e30802, PLOS, United States (2012). [cited by applicant]
Sun, L., et al., “Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway,” Science 339:786-791, American Association for the Advancement of Science, United States (2013). [cited by applicant]
Wasserman, R., et al., “ [cited by applicant]
Watson, R.O., et al., “The Cytosolic Sensor cGAS Detects [cited by applicant]
Woo, S.-R., et al., “The STING pathway and the T cell-inflamed tumor microenvironment,” Trends Immunol. 36(4):250-256, Elsevier, Netherlands (2015). [cited by applicant]
Wu, J., et al., “Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein,” Cell Host Microbe 18(3):333-344, Cell Press, United States (2015). [cited by applicant]
Zitvogel, L., et al., “Type I interferons in anticancer immunity,” Nature Reviews Immunology 15(7):405-414, Springer, Germany (2015). [cited by applicant]
Abdel-Aal, M.A.A., et al., “Towards anticancer fluoroquinolones: A review article,” Arch Pharm Chem Life Sci. 352(7):e1800376, Deutsche Pharmazeutische Gesellschaft, Germany (Jun. 2019), 19 pages. [cited by applicant]
Bargh, J.D., et al., “Cleavable linkers in antibody-drug conjugates,” Chem. Soc. Rev. 10.1039/c8cs00676h, Royal Society of Chemistry, United Kingdom, (Jul. 2019), 14 pages. [cited by applicant]
Beck, A., et al., “Strategies and challenges for the next generation of antibody-drug conjugates,” Nature Reviews Drug Discovery 16(5):315-337, Springer Nature, Germany (May 2017). [cited by applicant]
Database Registry [online], Chemical Abstracts Service, Database Accession No. 1011381-60-4, Columbus, Ohio, United States (Apr. 1, 2008), 11 pages, assessed Aug. 7, 2018. [cited by applicant]
Database Registry [online], Chemical Abstracts Service, Database Accession No. 1244927-19-2, Columbus, Ohio, United States (Oct. 3, 2010), 3 pages, assessed Aug. 7, 2018. [cited by applicant]
File Registry on STN, Document No. 70:77793 (1969), 2 pages. [cited by applicant]
Misra, P.S., et al., “Synthesis of 2-phenyl benzimidazole derivatives and their Schiff bases as possible antimicrobial agents,” Rasayan J. Chem. 3(1):51-54, Rasayan Journal of Chemistry, India (Mar. 2010). [cited by applicant]
Mousavizadeh, A., et al., “Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review,” Colloids Surfaces B. 158:507-517, Elsevier, Netherlands (Oct. 2017). [cited by applicant]
Orava, E.W., et al., “Delivering cargoes into cancer cells using DNA aptamers targeting internalized surface portals,” Biochimica Biophys. Acta 1798:2190-2200, Elsevier, Netherlands (Dec. 2010). [cited by applicant]
Pedley, R.B., et al., “The potential for enhanced tumour localisation by poly(ethylene glycol) modification of anti-CEA antibody,” Br. J. Cancer 70:1126-1130, Macmillan Press Ltd, Great Britain (Dec. 1994). [cited by applicant]
Polakis, P., “Antibody Drug Conjugates for Cancer Therapy,” Pharmacol. Revs. 68(1):3-19, American Society for Pharmacology and Experimental Therapeutics, United States (Jan. 2016). [cited by applicant]
Todorov, A.R., et al., “Tautomeric Switching and Metal-Cation Sensing of Ligand-Equipped 4-Hydroxy-/4-oxo-1,4-dihydroquinolines,” Chemistry: A European Journal 18(23):7269-7277, Wiley-VCH, Germany (Jun. 2012). [cited by applicant]
Turner, A., et al., “Comparative biodistributions of indium-111-labelled macrocycle chimeric B72.3 antibody conjugates in tumour-bearing mice,” Br. J. Cancer 70:35-41, Macmillan Press Ltd, Great Britain (Jul. 1994). [cited by applicant]
Zhang, B., et al., “Molecular Design, Synthesis and Biological Research of Novel Pyridyl Acridones as Potent DNA-binding and Apoptosis-inducing Agents,” European Journal of Medicinal Chemistry 93:214-226, Elsevier Masso… [cited by applicant]
Cited By (2)
US 12,643,879 US 12,655,124