IP Library › Granted Patent US 12,344,626
Granted Patent B2
US 12,344,626 · App. 17/605,795 · Granted Jul 1, 2025

Pharmaceutical compounds and therapeutic methods

Inventors: Spencer David Kimball (New Brunswick, NJ); Darren R. Carpizo (New Brunswick, NJ); John A. Gilleran (New Brunswick, NJ)
Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
C07F3/003A61K45/06C07D213/68C07D401/12C07D405/12
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Quick Facts
Patent No.
US 12,344,626
App. No.
17/605,795
Granted
Jul 1, 2025
Kind
B2
Abstract

The invention provides a complex comprising Zn 2+ and a compound of formula (I): or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt thereof that is useful for treating cancer, as well as compositions and kits comprising such complexes.

Claims (36)

1. A complex comprising Zn 2+ and a compound of formula (I):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex, wherein:

R 1 is (C 1 -C 6 ) alkoxy, (C 3 -C 6 ) cycloalkyoxy, or —OR 5 wherein any (C 1 -C 6 ) alkoxy or (C 3 -C 6 ) cycloalkyoxy is substituted with one or more groups independently selected from —N(R a ) 2 and (C 1 -C 6 ) alkoxy;

R 2 is selected from the group consisting of H, phenyl, heteroaryl, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, and (C 3 -C 6 ) cycloalkyl, wherein any phenyl, heteroaryl, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, and (C 3 -C 6 ) cycloalkyl, is optionally substituted with one or more groups independently selected from halo, —N(R b ) 2 , (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkoxy, (C 2 -C 6 ) alkanoyloxy, (C 2 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino;

R 3 and R 4 are each independently selected from H, (C 1 -C 6 ) alkyl, piperidinyl, or piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl; or R 3 and each R 4 taken together with the nitrogen to which they are attached form a 3, 4, 5, 6, 7, 8, or 9 membered ring that is optionally substituted with one or more groups independently selected from the group consisting of halo;

R 5 is a 4-7 membered heterocyclyl;

Y is S, O, or Se;

each R a is independently selected from the group consisting of H, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, wherein any (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 ) cycloalkyl, and (C 1 -C 6 ) alkoxy; or two R a taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring; and

each R b is independently selected from the group consisting of H, (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, (C 1 -C 6 ) alkylaminocarbonyl and (C 1 -C 6 ) alkoxycarbonyl, wherein any (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, (C 1 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 ) cycloalkyl, and (C 1 -C 6 ) alkoxy; or two R a taken together with the nitrogen to which they are attached form a ring, e.g., azetidino, pyrrolidino, piperidino, or morpholino;

provided the compound of formula (I) is not:

2. The complex of claim 1 comprising Zn 2+ and a compound of formula (I):

or a deuterated analog thereof, or an ion or poly-ion thereof, or a salt of said complex, wherein:

R 1 is (C 1 -C 6 ) alkoxy or (C 3 -C 6 ) cycloalkyoxy, wherein any (C 1 -C 6 ) alkoxy or (C 3 -C 6 ) cycloalkyoxy is substituted with one or more groups independently selected —N(R a ) 2 and (C 1 -C 6 ) alkoxy;

R 2 is selected from the group consisting of H, phenyl, heteroaryl, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, and (C 3 -C 6 ) cycloalkyl, wherein any phenyl, heteroaryl, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, and (C 3 -C 6 ) cycloalkyl and C 4 -C 6 -heterocyclealkyl, is optionally substituted with one or more groups independently selected from halo, —N(R b ) 2 , (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkoxy, (C 2 -C 6 ) alkanoyloxy, (C 2 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino;

R 3 and R 4 are each independently selected from H, (C 1 -C 6 ) alkyl, piperidinyl, or piperazinyl, which piperidinyl or piperazinyl is optionally substituted with pyridyl; or R 3 and each R 4 taken together with the nitrogen to which they are attached form a 3, 4, 5, 6, 7, 8, or 9 membered ring that is optionally substituted with one or more groups independently selected from the group consisting of halo;

Y is S, O, or Se;

each R a is independently selected from the group consisting of H, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, wherein any (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 ) cycloalkyl, and (C 1 -C 6 ) alkoxy; or two R a taken together with the nitrogen to which they are attached form a azetidino, pyrrolidino, piperidino, or morpholino ring; and

each R b is independently selected from the group consisting of H, (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, (C 1 -C 6 ) alkylaminocarbonyl and (C 1 -C 6 ) alkoxycarbonyl, wherein any (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, (C 1 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 ) cycloalkyl, and (C 1 -C 6 ) alkoxy; or two R a taken together with the nitrogen to which they are attached form a ring, e.g., azetidino, pyrrolidino, piperidino, or morpholino;

provided the compound of formula (I) is not:

3. The complex of claim 1 , wherein R 1 is (C 1 -C 6 ) alkoxy that is substituted with one or more groups independently selected —N(R a ) 2 and (C 1 -C 6 ) alkoxy; or wherein R 1 is (C 1 -C 6 ) alkoxy that is substituted with —N(R a ) 2 .

4. The complex of claim 1 , wherein R 1 is (C 1 -C 6 ) alkoxy that is substituted with (C 1 -C 6 ) alkoxy.

5. The complex of claim 1 , wherein R 1 is (C 3 -C 6 ) cycloalkyoxy that is substituted with —N(R a ) 2 or (C 1 -C 6 ) alkoxy.

6. The complex of claim 1 , wherein R 1 is (C 1 -C 6 ) alkoxy or (C 3 -C 6 ) cycloalkyoxy, wherein any (C 1 -C 6 ) alkoxy or (C 3 -C 6 ) cycloalkyoxy is substituted with one or more groups independently selected from —N(R a ) 2 and (C 1 -C 6 ) alkoxy.

7. The complex of claim 1 , which is a complex of formula:

8. The complex of claim 1 , which is a complex of formula:

9. The salt of claim 1 , which is:

bis mesylate salt.

10. The complex of claim 1 , which is a complex of formula:

11. The complex of claim 1 , which is a complex of formula:

12. The complex of claim 1 , wherein each R a is independently selected from the group consisting of H, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, wherein any (C 2 -C 6 ) alkenyl, (C 2 -C 6 ) alkynyl, (C 3 -C 6 ) cycloalkyl, (C 1 -C 6 ) alkanoyl, and (C 1 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkoxycarbonyl, (C 2 -C 6 ) alkylaminocarbonyl, and (C 2 -C 6 ) alkanoylamino is optionally substituted with one or more groups independently selected from halo, (C 3 -C 6 ) cycloalkyl, and (C 1 -C 6 ) alkoxy; and wherein any (C 1 -C 6 ) alkyl is substituted with one or more groups independently selected from halo, (C 3 -C 6 ) cycloalkyl, and (C 1 -C 6 ) alkoxy.

13. The complex of claim 1 , wherein two R a taken together with the nitrogen to which they are attached form a ring, e.g., azetidino, pyrrolidino, piperidino, or morpholino.

14. A pharmaceutical composition, comprising a complex of claim 1 or a solvate thereof, and a pharmaceutically acceptable carrier.

15. The complex of claim 1 , which is a complex of formula:

or the salt of claim 1 , which is:

bis mesylate salt.

16. A pharmaceutical composition, comprising a complex or salt of claim 15 or a solvate thereof, and a pharmaceutically acceptable carrier.

Continuity (2)
Provisional Application 62837707 · Apr 23, 2019
Related Publication 20220185827A1 · Jun 16, 2022
References Cited (82)
US 4657903A · Scovill et al. · 1987 [cited by applicant]
US 4665173A · Klayman et al. · 1987 [cited by applicant]
US 4777166A · Smith et al. · 1988 [cited by applicant]
US 7112680B2 · Hofmann et al. · 2006 [cited by applicant]
US 10221133B2 · Augeri et al. · 2019 [cited by applicant]
US 10604480B2 · Augeri et al. · 2020 [cited by applicant]
US 10604481B2 · Augeri et al. · 2020 [cited by applicant]
US 10729671B2 · Augeri et al. · 2020 [cited by applicant]
US 10828288B2 · Augeri et al. · 2020 [cited by applicant]
US 20080118576A1 · Theodorescu et al. · 2008 [cited by applicant]
US 20130345164A1 · Vazquez et al. · 2013 [cited by applicant]
US 20140142266A1 · Sakamoto et al. · 2014 [cited by applicant]
US 20180000772A1 · Augeri et al. · 2018 [cited by applicant]
US 20180000806A1 · Augeri et al. · 2018 [cited by applicant]
US 20180002279A1 · Augeri et al. · 2018 [cited by applicant]
US 20180002280A1 · Augeri et al. · 2018 [cited by applicant]
US 20200096492A1 · Loriau et al. · 2020 [cited by applicant]
WO 2001094340A1 · 2001 [cited by applicant]
WO 2006019955A2 · 2006 [cited by applicant]
WO 2006101740A2 · 2006 [cited by applicant]
WO 2007035489A2 · 2007 [cited by applicant]
WO 2009039553A1 · 2009 [cited by applicant]
WO 2012175962A1 · 2012 [cited by applicant]
WO 2015021456A1 · 2015 [cited by applicant]
WO 2016123242A1 · 2016 [cited by applicant]
WO 2016123246A1 · 2016 [cited by applicant]
WO 2016123250A1 · 2016 [cited by applicant]
WO 2016123253A1 · 2016 [cited by applicant]
WO 2020219589A1 · 2020 [cited by applicant]
Loh, S , “Follow the Mutations: Toward Class-Specific, Small-Molecule Reactivation of p53”, Biomolecules 10, 303, 1-14 (2020). [cited by applicant]
Agrawal, K , et al., “Potential antitumor agents. 13. 4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone”, Journal of Medicinal Chemistry 19(7), 970-972 (1976). [cited by applicant]
Antonini, I , et al., “Elucidation of the structure of the antineoplastic agents, 2-formylpyridine and 1-formylisoquinoline thiosemicarbazones”, Journal of Medicinal Chemistry 20(3), 447-449 (1977). [cited by applicant]
Bellitto, C , et al., “Conformational Studies of Some Potentially Bidentate Thiosemicarba-zones and Related Complexes of Zinc(II)”, J.C.S. Dalton 68570(21), 758-762 (1976). [cited by applicant]
Bermejo, E , et al., “Complexes of Grup 12 Metals with 2-Acetylpyridine 4N-Dimethyl-thiosemiearbazone and with 2-Acetyipyridine-N-oxide 4N-Dimethyl-thiosemiearbazone: Synthesis, Structure and Antifungal Activity”, Zeits… [cited by applicant]
Bjelogrlic, S , et al., “Synthesis, structure and characterization of novel Cd(II) and Zn(II) complexes with the condensation product of 2-formylpyridine and selenosemicarbazide Antiproliferative activity of the synthes… [cited by applicant]
Blanden, A , et al., “Synthetic Metallochaperone ZMC1 Rescues Mutant p53 Conformation by Transporting Zinc into Cells as an lonophore”, Mol Pharmacol 87, 825-831 (2015). [cited by applicant]
Chhabra, N , et al., “A review of drug isomerism and its significance”, Int J Appl Basic Med Res 3(1), 16-18 (2013). [cited by applicant]
Chun-Ying, D , et al., “Synthesis, Crystal Structure and Nonlinear Optical Properties of Thiosemicarbazone Zinc Complex”, J Coord Chem 47, 433-439 (1999). [cited by applicant]
Easmon, J , et al., “2-benzoxazolyl and 2-benzimidazolyl hydrazones derived from 2-acetylpyridine: a novel class of antitumor agents”, Int J Cancer 94, 89-96 (2001). [cited by applicant]
Easmon, J , et al., “Synthesis, Structure—Activity Relationships, and Antitumor Studies of 2-Benzoxazolyl Hydrazones Derived from Alpha-(N)-acyl Heteroaromatics”, J Med Chem 49, 6343-6350 (2006). [cited by applicant]
Easmon, J , et al., “Thiazolyl and benzothiazolyl hydrazones derived from α-(N)-acetylpyridines and diazines: synthesis, antiproliferative activity and CoMFA studies”, Eur J Med Chem 32, 397-408 (1997). [cited by applicant]
File Caplus , “Preparation and characterization of vanillin thiosemicarbazone complexes with cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), and mercury(II)”, STN CA Caesar Accession No. 1170, 2 pages (1984). [cited by applicant]
File Caplus , “Synthesis and crystal structure of zinc(II) complex [Zn(25-MBTSC)212]”, STN CA Caesar Accession No. 1162, 1 page (2013). [cited by applicant]
File Caplus , “Synthesis and structure of 1.5Zn(phen)3.cntdot.L.cntdot..3N03 supramolecule (phen=o-phenanthroline, L=4-aminoacetophenone thiosemicarbazone”, STN CA Caesar Accession No. 1176, 2 pages (2008). [cited by applicant]
Gudasi, K , et al., “Synthesis and spectral investigation of some transition metal complexes containing pentadentate macroacyclic NNNNN-donor Schiff base ligands”, Transition Metal Chemistry 30, 726-732 (2005). [cited by applicant]
Hall, I, et al., “Investigations on the Mechanism of Action of the Novel Antitumor Agents 2-Benzothiazolyl, 2-Benzoxazolyl, and 2-Benzimidazolyl Hydrazones Derived from 2-Acetylpyridine”, Arch Pharm Pharm Med Chem 332 (… [cited by applicant]
Heit , et al., “Substituted Hydrazones as Tridentate Chelating Agents”, Analytica Chimica Acta 32, 448-455 (1965). [cited by applicant]
Huang, H , et al., “A Series of α-Heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase IIα Catalytic Activity”, Journal of Medicinal Chemistry 53, 3048-3064 (2010). [cited by applicant]
Huang, Y , et al., “Correlating gene expression with chemical scaffolds of cytotoxic agents: ellipticines as substrates and inhibitors of MDR1”, Pharmacogenomics Journal 5, 112-125 (2005). [cited by applicant]
Ibrahim, A , et al., “Indole-7-carbaldehyde thiosemicarbazone as a flexidentate ligand toward ZnII, CdII, PdII and PtII ions: cytotoxic and apoptosis-inducing properties of the PtII complex”, Dalton Trans 43, 3860-3860 … [cited by applicant]
Kalinowski, D , et al., “Design, Synthesis, and Characterization of Novel Iron Chelators: Structure—Activity Relationships of the 2-Benzoylpyridine Thiosemicarbazone Series and Their 3-Nitrobenzoyl Analogues as Potent A… [cited by applicant]
Khalaji, A , et al., “Synthesis and Characterization of Zinc(II) Complexes with 3,4-Dimethoxybenzaldehyde Thiosemicarbazone: The Crystal Structure of [Zn(34-MBTSC) 2 CI 2 ]”, Phosphorus, Sulfur, and Silicon 188, 1119-11… [cited by applicant]
Khaled, S , et al., “Synthesis and Spectroscopic Characterization of Some NOvel Polypyridine and Phenanthroline Complexes of Mn(II), Fe(II), Co(II) and Zn(II) Incorporating a Bidentate Benzothiazolyl Hydrazone Ligand”, … [cited by applicant]
Kodela, R , et al., “Positional Isomers of Aspirin are Equally Potent in Inhibiting Colon Cancer Cell Growth: Differences in Mode of Cyclooxygenase Inhibition”, J Pharmacol Exp Ther 346, 85-94 (2013). [cited by applicant]
Kovala-Demertzi, D , et al., “Zinc(II) complexes derived from pyridine-2-carbaldehyde thiosemicarbazone and (1E)-1-pyridin-2-ylethan-1-one thiosemicarbazone. Synthesis, crystal structures and antiproliferative activity … [cited by applicant]
Mohan, M , et al., “Synthesis, Characterization, and Antitumor Properties of some Metal Complexes of 2,6-Diacetylpyridine Bis(N4-azacyclic Thiosemicarbazone)”, Journal of Inorganic Biochemistry 34, 41-54 (1988). [cited by applicant]
Moorthy, N , et al., “QSAR analysis of 2-benzoxazolyl hydrazone derivatives for anticancer activity and its possible target prediction”, Med Chem Res 21, 133-144 (2012). [cited by applicant]
Mrozek-Wilczkiewicz, A , et al., “Iron Chelators in Photodynamic Therapy Revisited: Synergistic Effect by Novel Highly Active Thiosemicarbazones”, ACS Medicinal Chemistry Letters 5(4), 336-339 (2014). [cited by applicant]
Odashima, T , et al., “Determination of Microamounts of Iron by Extraction-Spectrophotometry with 2-Acetylpyridine-2-benzothiazolylhydrazone and Its Sensitization by Employing an Analog Derivative Technique”, Microchemi… [cited by applicant]
Patani, George A., et al., “Bioisosterism: A Rational Approach in Drug Design”, Chern Rev 96, 3147-3176 (1996). [cited by applicant]
Patent Cooperation Treaty , International Search Report and Written Opinion for PCT/US2000/029379, 10 pages, dated Sep. 9, 2020. [cited by applicant]
Priyadharsini, R , et al., “Docking, synthesis, characterization and evaluation of novel cdk2 inhibitors: benzothiazole derivatives”, International Journal of Pharmacy and Pharmaceutical Sciences 4(3), 574-585 (2012). [cited by applicant]
Pubchem , “[(Z)-(5-Amino-4-morpholin-4-ylisoquinolin-1-yl)methylideneamino]thiourea”, PubChem CID: 44355883, 8 pages, (Nov. 19, 2009). [cited by applicant]
Rao, P , et al., “Synthesis and Spectroscopic Studies on a Dibasic Pent Dentate Ligand”, Inorganic Chemistry 1 (3), 47-52 (2006). [cited by applicant]
Ren, P , et al., “A new approach to suppress nonlinearity-transparency trade-off through coordination chemistry: syntheses and spectroscopic study on second-order nonlinear optical properties of a series of square-pyram… [cited by applicant]
Richardson, D , et al., “Dipyridyl Thiosemicarbazone Chelators with Potent and Selective Antitumor Activity Form Iron Complexes with Redox Activity”, J Med Chem 49, 6510-6521 (2006). [cited by applicant]
Ruangpornvisuti, V , et al., “A DFT investigation of conformational geometries and interconversion equilibria of phenylthiosemicarbazone and its complexation with zinc”, J Mol Model 10, 418-426 (2004). [cited by applicant]
Singh, K , et al., “Stereochemistry and Its Role in Drug Design”, IJPSR 5(11), 4644-4659 (2014). [cited by applicant]
Sleebs, B , et al., “Discovery of Potent and Selective Benzothiazole Hydrazone Inhibitors of Bcl-XL”, J Med Chem 56, 5514-5540 (2013). [cited by applicant]
STN Record , Accession No. 1975:461709, JP49126728, 1 page (1975). [cited by applicant]
Tian, Y , et al., “Structural characterization and second-order nonlinear optical properties of zinc halide thiosemicarbazone complexes”, Polyhedron 21, 1217-1222 (2002). [cited by applicant]
Todorovic, T. , et al., “Synthesis and characterization of Zn(II) and Cd(II) complexes with 2,6-diacetylpyridine-bis (selenosemicarbazone). Crystal structure of a Ni(II) complex with a modified 2,6-diacetylpyridine-bis … [cited by applicant]
Vartale, S , et al., “Synthesis and Antimicrobial Activity of 6/7/8-Substituted-1-[ARYL/6′ Substituted-2′-Benzothiazolyl]-Pyrazolo [4,5-b] Quinolines”, Indian Journal of Heterocyclic Chemistry 16, 163-166 (2006). [cited by applicant]
Webster, D , et al., “Synthesis and characterization of novel pentagonal bipyramidal compleses of iron(II), cobalt(II), and zinc(II)”, Journal of American Chemical Society 95(19), 6505-6506 (1973). [cited by applicant]
Yu, X , et al., “Allele-Specific p53 Mutant Reactivation”, Cancer Cell 21, 614-625 (2012). [cited by applicant]
Yu, X , et al., “Small molecule restoration of wildtype structure and function of mutant p53 using a novel zinc-metallochaperone based mechanism”, Oncotarget 5(19), 8879-8892 (2014). [cited by applicant]
U.S. Appl. No. 15/545,966, U.S. Pat. No. 10,221,133. [cited by applicant]
U.S. Appl. No. 16/253,126, U.S. Pat. No. 10,604,481. [cited by applicant]
U.S. Appl. No. 15/545,968, U.S. Pat. No. 10,604,480. [cited by applicant]
U.S. Appl. No. 15/545,971, U.S. Pat. No. 10,828,288. [cited by applicant]
U.S. Appl. No. 15/545,975, U.S. Pat. No. 10,729,671. [cited by applicant]
U.S. Appl. No. 17/605,750, 2022-0096492. [cited by applicant]
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