IP Library › Granted Patent US 12,370,200
Granted Patent B2
US 12,370,200 · App. 17/610,236 · Granted Jul 29, 2025

Pharmaceutical composition containing brexanolone, ganaxolone, or zuranolone, and use thereof

Inventors: Robert G. Strickley (Durham, NC); Lianhong Xu (Durham, NC); Zhi Hong (Durham, NC)
Assignee: Brii Biosciences, Inc.
A61K31/568A61K9/145A61K31/57A61K31/573A61K31/575A61K31/58
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Quick Facts
Patent No.
US 12,370,200
App. No.
17/610,236
Filed
Nov 10, 2021
Granted
Jul 29, 2025
Kind
B2
Art Unit
1627
USPC
514/170
Abstract

Disclosed herein is a pharmaceutical composition comprising a pharmaceutically effective amount of a neuroactive steroid that is a positive modulator of γ aminobutyric acid type A (GABA A ) receptors. Also disclosed are methods of treating diseases using the pharmaceutical composition and processes of producing the pharmaceutical composition.

Claims (43)

1. A pharmaceutical composition comprising brexanolone,

wherein said brexanolone is brexanolone polymorph Form A, characterized by having at least three peaks selected from the group consisting of 7.25±0.1°2θ, 8.88±0.1° 2θ, 11.46±0.1 °2θ, 14.50±0.1 °2θ, 14.78±0.1 °2θ, 17.77±0.1° 20, 18.15±0.1 °2θ, 18.32±0.1 °2θ, 18.61±0.1° 2θ, and 19.99±0.1° 2θ in an X-ray Powder Diffraction (XRPD) diffractogram; and

wherein a single dose of said pharmaceutical composition by intramuscular or subcutaneous injection provides a maximum plasma concentration (C max ) of brexanolone in about 30 minutes to about 6 hours and maintains a plasma concentration of brexanolone of more than about 5% of said C max for at least about 5 days, after the injection.

2. The pharmaceutical composition of claim 1 , wherein said single dose comprises about 0.5 mg to about 50 mg of brexanolone per kilogram of body weight.

3. The pharmaceutical composition of claim 2 , wherein said single dose comprises about 1 mg to about 8 mg of brexanolone per kilogram of body weight.

4. The pharmaceutical composition of claim 1 , wherein said single dose comprises about 50 mg to about 800 mg of brexanolone per unit dose.

5. The pharmaceutical composition of claim 1 , wherein the concentration of said brexanolone in the pharmaceutical composition is (a) in a range of from about 100 mg/mL to about 800 mg/mL or (b) about 300 mg/mL.

6. The pharmaceutical composition of claim 1 , wherein said single dose of said pharmaceutical composition by intramuscular or subcutaneous injection provides a C max of brexanolone in about 30 minutes to about 300 minutes after the injection.

7. The pharmaceutical composition of claim 1 , wherein said single dose of said pharmaceutical composition by intramuscular or subcutaneous injection maintains a plasma concentration of brexanolone of more than about 10% of said C max for at least about 10 days after the injection.

8. The pharmaceutical composition of claim 1 , wherein said single dose of said pharmaceutical composition by intramuscular or subcutaneous injection provides a C max of more than 10 ng/ml.

9. The pharmaceutical composition of claim 1 , wherein said single dose of said pharmaceutical composition comprises about 3 mg to about 5 mg of brexanolone per kilogram of body weight, wherein said single dose maintains a plasma concentration of brexanolone of more than about 10 ng/mL for at least about 5 days after the injection.

10. The pharmaceutical composition of claim 9 , wherein said single dose of said pharmaceutical composition by intramuscular or subcutaneous injection maintains a plasma concentration of brexanolone of more than about 10 ng/ml for at least about 10 days after the injection.

11. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition releases less than about 5% to about 50% of said brexanolone within about 1 hour of said single dose of said pharmaceutical composition by intramuscular or subcutaneous injection.

12. The pharmaceutical composition claim 1 , wherein said pharmaceutical composition provides a relative bioavailability of the brexanolone of about 2% to about 50% at 24 hours after said single dose by intramuscular or subcutaneous injection, in comparison to the same dose by intravenous administration.

13. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises a population of particles comprising said brexanolone, wherein said particles have a mean (D50) particle size of about 0.2 μm to about 15 μm.

14. The pharmaceutical composition of claim 13 , wherein said particles have D50 particle size of about 1.2 μm to about 6 μm.

15. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is substantially free of cyclodextrins.

16. The pharmaceutical composition of claim 15 , wherein said pharmaceutical composition is substantially free of sulfobutyl ether β-cyclodextrin.

17. The pharmaceutical composition of claim 1 , further comprising one or more pharmaceutically acceptable excipients.

18. The pharmaceutical composition of claim 17 , wherein said one or more pharmaceutically acceptable excipients comprise a binder, lubricant, glidant, disintegrant, diluent, coloring agent, surfactant, emulsifier, filler, carrier, isotonicifier, dispersing agent, viscosity modifier, resuspending agent, buffer, or any combination thereof.

19. The pharmaceutical composition of claim 17 , wherein said one or more pharmaceutically acceptable excipients comprise acacia, animal oil, benzyl alcohol, benzyl benzoate, calcium stearate, carbomer, cetostearyl alcohol, cetyl alcohol, cholesterol, dextrose, diethanolamine, emulsifying wax, ethylene glycol palmitostearate, glycerin, glycerin monostearate, glycerol stearate, glyceryl monooleate, glyceryl monostearate, hydrous, histidine, hydrochloric acid, hydroxpropyl cellulose, hypromellose (hydroxypropyl methylcellulose (HPMC)), lanolin, lanolin alcohols, lecithin, medium-chain triglycerides, metallic soaps, methylcellulose, mineral oil, monobasic sodium phosphate, monoethanolamine, oleic acid, polyethylene glycol, polyoxyethylene-polyoxypropylene copolymer (poloxamer), polyoxyethylene alkyl ethers, polyoxyethylene castor oil, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polysorbate, polyoxyethylene (20) sorbitan monolaurate (Tween 20, Polysorbate 20), polyoxyethylene (20) sorbitan monooleate (Tween 80, Polysorbate 80), povidone, propylene glycol alginate, saline, sodium chloride, sodium citrate, sodium citrate dihydrate, sodium hydroxide, sodium lauryl sulfate, sodium phosphate monobasic, sodium phosphate dibasic, sorbitan esters, stearic acid, stearyl alcohol, sunflower oil, tragacanth, triethanolamine, vegetable oil, water, xanthan gum, or any combination thereof.

20. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is a liquid suspension for intramuscular or subcutaneous injection.

21. The pharmaceutical composition of claim 1 , wherein the brexanolone polymorph Form A has a chemical purity of greater than 90%.

22. The pharmaceutical composition of claim 1 , wherein the brexanolone polymorph Form A has a melting point of about 170-180° C.

23. The pharmaceutical composition of claim 1 , wherein the brexanolone polymorph Form A is characterized by having the following peaks in an X-ray Powder Diffraction (XRPD) diffractogram: 7.25±0.1, 8.88±0.1, 11.46±0.1, 14.50±0.1, 14.78±0.1, 17.77±0.1, 18.15±0.1, 18.32±0.1, 18.61±0.1, and 19.99±0.1° 2θ.

24. A method of treating a disease in a subject in need thereof, comprising administering to said subject by intramuscular or subcutaneous injection the pharmaceutical composition of claim 1 .

25. The method of claim 24 , wherein the pharmaceutical composition is administered to said subject by a single dose comprising 0.5 mg to 10 mg of brexanolone per kilogram of body weight.

26. The method of claim 24 , wherein said disease is selected from the group consisting of anxiety, mood disorder, postpartum disorder, Alzheimer's disease, Parkinson's disease, epilepsy, CDKL5 Deficiency Disorder (CDD), Fragile X syndrome, depression, and premenstrual syndrome.

27. The method of claim 24 , wherein said disease is postpartum depression.

28. The method of claim 27 , wherein said subject has prior history of depression.

29. The method of claim 27 , wherein said subject has prior history of postpartum depression.

30. The method of claim 24 , wherein said administering is by a single intramuscular or subcutaneous injection.

31. The method of claim 24 , wherein said pharmaceutical composition is administered to said subject within a time period in a range of from 1 second to about 180 minutes.

32. A process for producing the pharmaceutical composition of claim 1 , comprising:

a) mixing said brexanolone with one or more pharmaceutically acceptable excipients to form a mixture; and

b) milling said mixture to produce a population of particles of said pharmaceutical composition.

33. A process for producing the pharmaceutical composition of claim 1 , comprising:

a) milling brexanolone to produce a population of particles; and

b) mixing said particles with one or more pharmaceutically acceptable excipients to produce said pharmaceutical composition.

34. A process for producing the pharmaceutical composition of claim 1 , comprising: crystalizing the brexanolone polymorph Form A from one or more solvents selected from the group consisting of dichloromethane (DCM), tetrahydrofuran (THF), ethyl acetate (EtOAc), dimethyl sulfoxide (DMSO), toluene, 2-propanol: water (9:1), methanol (MeOH), 2-propanol (IPA), methyl t-butyl ether (MTBE), isopropyl ether (IPE), and water.

35. The method of claim 26 , wherein said depression is postpartum depression or massive depression disorder.

36. The method of claim 26 , wherein said epilepsy comprises focal onset seizures, PCDH19 pediatric epilepsy, catamenial epilepsy, infantile spasms, or pediatric genetic epilepsies.

37. The method of claim 24 , wherein said administering is by two or more intramuscular or subcutaneous injections.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2022
From: STRICKLEY, ROBERT; XU, LIANHONG; HONG, ZHI
To: BRII BIOSCIENCES, INC.
Reel/Frame 060951/0456 →
Continuity (3)
Provisional Application 63018815 · May 1, 2020
Provisional Application 62846576 · May 10, 2019
Related Publication 20220241295A1 · Aug 4, 2022
References Cited (106)
US 3174970A · Georges et al. · 1965 [cited by applicant]
US 3574198A · Radscheit et al. · 1971 [cited by applicant]
US 9029355B2 · Shaw et al. · 2015 [cited by applicant]
US 9452176B2 · Shaw et al. · 2016 [cited by applicant]
US 9512165B2 · Martinez Botella et al. · 2016 [cited by applicant]
US 9777037B2 · Gravanis et al. · 2017 [cited by applicant]
US 10172870B2 · Reddy · 2019 [cited by applicant]
US 10251894B2 · Rogawski et al. · 2019 [cited by applicant]
US 10711030B2 · Torregrossa et al. · 2020 [cited by applicant]
US 11266663B2 · Pinna et al. · 2022 [cited by applicant]
US 20160228454A1 · Zhang et al. · 2016 [cited by applicant]
US 20180071315A1 · Cashman et al. · 2018 [cited by applicant]
US 20180296487A1 · Saporito et al. · 2018 [cited by applicant]
US 20180340005A1 · Marx et al. · 2018 [cited by applicant]
US 20190117673A1 · Shaw et al. · 2019 [cited by applicant]
US 20200377547A1 · Salituro et al. · 2020 [cited by applicant]
US 20230118577A1 · Xu et al. · 2023 [cited by applicant]
US 20240009121A1 · Hong et al. · 2024 [cited by applicant]
CN 107106574A · 2017 [cited by applicant]
GB 1409239A · 1975 [cited by applicant]
JP S4867263A · 1973 [cited by applicant]
WO WO2013112605A2 · 2013 [cited by applicant]
WO WO2014169833A1 · 2014 [cited by applicant]
WO WO2016040322A1 · 2016 [cited by applicant]
WO WO2016127170A1 · 2016 [cited by applicant]
WO WO2017066626A1 · 2017 [cited by examiner]
WO WO2017156103A1 · 2017 [cited by applicant]
WO WO2018013613A1 · 2018 [cited by applicant]
WO WO2018103626A1 · 2018 [cited by applicant]
WO WO2018195186A1 · 2018 [cited by applicant]
WO WO2020118142A1 · 2020 [cited by applicant]
WO WO2020206462A1 · 2020 [cited by applicant]
WO WO2020231837A1 · 2020 [cited by applicant]
WO WO2020243488A1 · 2020 [cited by applicant]
WO WO2021142477A1 · 2021 [cited by applicant]
WO WO2021174205A1 · 2021 [cited by applicant]
WO WO2022040216A9 · 2022 [cited by applicant]
Andreen et al., Psychoneuroendocrinology (2009) 34, 1121-1132 (Year: 2009). [cited by examiner]
Brittain, H.G., et al. “Polymorphism in pharmaceutical solids” edited by H. G. Brittain, Marcel Dekker, D.J.W., Grant (chapter 1), p. 1-10 and J. K. Guillory (chapter 5); p. 183-226 (1999). [cited by applicant]
Byrn, S., et al., “Pharmaceutical solids: a strategic approach to regulatory considerations”, Pharmaceutical Research (1995); 12(7): 945-954. [cited by applicant]
Kharkevich, D.A., “Pharmacology”, 8th ed. M.: GEOTAR-Media, 2005; 3 pages. [cited by applicant]
Dyson, G., et al., “Chemistry of Synthetic Drugs”, Moscow, MIR, 1964, pp. 12-19; 25 pages, with English machine translation. [cited by applicant]
Hirayama, Y., “Handbook for organic compound crystal—Principle and know-how,” 2008, 28 pages. [cited by applicant]
Hoag et al., “Chapter 2: Particle and Power Bed Properties”, Pharmaceutical Dosage Forms: Tablets 3rd edition, Jun. 3, 2008, 58 pages. [cited by applicant]
Knigochey “Popular Medical Encyclopedia”, editor-in-chief V.I. Pokrovsky, 4th ed., St, 1997, 2 pages. [cited by applicant]
Notice of Reasons for Refusal for Japanese Application No. JP20210566976 mailed Jun. 5, 2024, with English translation, 8 Pages. [cited by applicant]
Office Action and Search Report for Russian Application No. RU2022121496 mailed Jun. 7, 2024, with English translation, 23 pages. [cited by applicant]
Office Action and Search Report for Taiwan Application No. TW112103512 mailed Sep. 12, 2024, with English translation, 7 pages. [cited by applicant]
Office Action for Indian Patent Application No. IN202117056325 dated Apr. 19, 2024, with English translation, 6 pages. [cited by applicant]
Office Action for Israel Application No. 287905 mailed Jul. 17, 2024, 7 pages. [cited by applicant]
Office Action for Mexican Application No. MX/a/2021/013695 mailed Jul. 11, 2024, with partial English translation, 10 pages. [cited by applicant]
Office Action for Russian Application No. RU2021136231 dated Apr. 9, 2024, 16 pages. [cited by applicant]
Office Action for the Mexican Application No. MX/a/2022/008614 dated Apr. 2, 2024, with partial English translation, 15 pages. [cited by applicant]
Search Report and Written Opinion for Singapore Application No. 11202251136H mailed Sep. 9, 2024, 12 pages. [cited by applicant]
Extended European Search Report for European Application No. EP20210738878 dated Jan. 30, 2024, 15 pages. [cited by applicant]
Lewbart “Synthesis of the four pairs of side-chain epoxides epimeric at C-20 derived from 5. beta.-pregnan-3. alpha.-ol”. The Journal of Organic Chemistry. May 1968; 33(5): 1695-706. [cited by applicant]
Office Action for Chinese Patent Application No. CN202080042380.9 dated Mar. 7, 2024, 12 pages. [cited by applicant]
Gunduz-Bruce, H. et al., “Trial of SAGE-217 in patients with major depressive disorder,” The New England Journal of Medicine, Sep. 2019, 381(10), pp. 903-911. [cited by applicant]
Harrison et al., “Alphaxalone selectively potentiates responses to GABA and muscimol in rat cuneate nucleus in vitro,” Journal of the Physiology-London, Jan. 1984, vol. 346, p. 42-p. 42. [cited by applicant]
Majewska et al., “Steroid Hormone Metabolites Are Barbiturate-Like Modulators of the GABA Receptor,” Science, 232, May 1986, pp. 1004-1007, PubMed: 2422758. [cited by applicant]
Zorumski et al., “Neurosteroids, stress and depression: Potential therapeutic opportunities,” Neuroscience and Biobehavioral Reviews, Jan. 2013, 37(1), pp. 109-122, DOI: 10.1016/j.neubiorev.2012.10.005. [cited by applicant]
Office Action for Chinese Patent Application No. CN202080042380.9 dated Oct. 24, 2024, with English translation, 8 pages. [cited by applicant]
Beck, CT, “Revision of the Postpartum Depression Predictors Inventory,” Journal of Obstetric, Gynecologic & Neonatal Nursing, Jul. 2002, 31(4), pp. 394-402. [cited by applicant]
Cox JL, et al., “A controlled study of the onset, duration and prevalence of postnatal depression,” British Journal of Psychiatry, Jul. 1993, 163, pp. 27-31. [cited by applicant]
Extended European Search Report for European Application No. EP20200805552 dated Apr. 11, 2023, 7 pages. [cited by applicant]
Fisher SD, et al., “Four maternal characteristics determine the 12-month course of chronic severe postpartum depressive symptoms,” Depress Anxiety, Apr. 2019, 36(4), pp. 375-383. https://doi.org/10.1002/da.22879. [cited by applicant]
Hoffmann E., “Brexanolone Injection Administration to Lactating Women: Breast Milk Allopregnanolone Levels [30J],” Obstetrics & Gynecology, vol. 133, No. 5 Supplement, May 2019, 115S, 1 page. [cited by applicant]
Hoffmann, et al., “Evaluation of breast milk concentrations following brexanolone iv administration to healthy lactating woman,” American Journal of Obstetrics & Gynecology, S554 Supplement to Jan. 2019, 1 page. [cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/US2021/046347, mailed Mar. 2, 2023, 9 pages. [cited by applicant]
McEvoy et al., “Neuroactive Steroids and Perinatal Depression: a Review of Recent Literature,” Current Psychiatry Reports, 20:78, Sep. 2018, pp. 1-9, https://doi.org/10.1007/s 11920-018-0937-4. [cited by applicant]
Moreira, MWL et al., “Postpartum depression prediction through pregnancy data analysis for emotion-aware smart systems,” Information Fusion, May 2019, vol. 47, pp. 23-31, doi: 10.1016/j.inffus.2018.07.001. [cited by applicant]
Munk-Olsen, “Population-Based Assessment of the Recurrence Risk of Postpartum Mental Disorders: Will It Happen Again?,” JAMA Psychiatry, 77(2), pp. 213-214, Feb. 2020 (2019 online), doi: 10.1001/jamapsychiatry.2019.3208. [cited by applicant]
Schiller, et al., “Allopregnanolone as a mediator of affective switching in reproductive mood disorders,” Psychopharmacology, 231(17), pp. 3557-3567, Sep. 2014, doi: 10.1007/s00213-014-3599-x. [cited by applicant]
Werner, et al., “Preventing postpartum depression: review and recommendations,” Archives of Women's Mental Health, 18(1), Feb. 2015 (ePub 2014), pp. 41-60, doi: 10.1007/s00737-014-0475-y 2014. [cited by applicant]
Caira “Crystalline Polymorphism of Organic Compounds”, Topics in Current Chemistry (Jan. 1, 1998); 198:163-208. [cited by applicant]
Morissette et al., “High-Throughput Crystallization: Polymorphs, Salts, Co-Crystals and Solvates of Pharmaceutical Solids,” Advanced Drug Delivery Reviews, vol. 56, No. 3, Feb. 2004, pp. 275-300. [cited by applicant]
Office Action and Search Report for Russian Application No. RU2021136231 dated Oct. 12, 2023, 22 pages. [cited by applicant]
Pertsev “Pharmaceutical and Medico-biological Aspects of Drugs”, Kharkiv, UkrFA Publishing House (1999); 1: 253-254; 7 pages. [cited by applicant]
Smirnova et al., Clinical pharmacokinetics: theoretical, applied and analytical aspects: a guide / Ed. V.G. Kukes. (Chapter 11.2. Relationship of the Crystal Structure of a Substance, Pharmacokinetics and Effectiveness … [cited by applicant]
Chen, W. et al., “Effect of Particle Size on Drug Loading and Release Kinetics of Gefitinib-Loaded PLGA Microspheres” Mol. Pharmaceutics, Dec. 14, 2016, vol. 14, No. 2, pp. 459-467. [cited by applicant]
Hoshyar, N. et al., “The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction” Nanomedicine, Mar. 22, 2016, vol. 11, No. 6, pp. 673-692. [cited by applicant]
Office Action and Search Report for Chinese Application No. CN202080042380.9 dated Jul. 18, 2023, 23 pages. [cited by applicant]
Office Action for Singapore Application No. SG11202112111W mailed Aug. 4, 2023, 12 pages. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2020/023172, mailed Jul. 31, 2020, 9 pages. [cited by applicant]
International Search Report and Written Opinion for Application No. PCT/US2021/046347, mailed Dec. 8, 2021, 12 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/013112, mailed Apr. 13, 2021, 8 pages. [cited by applicant]
Irwin et al., “Allopregnanolone Preclinical Acute Pharmacokinetic and Pharmacodynamic Studies to Predict Tolerability and Efficacy for Alzheimer's Disease,” Plos One, vol. 10, No. 6, Jun. 3, 2015, p. e0128313, 31 pages,… [cited by applicant]
Kanes et al., “Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression,” Human Psychopharmacology, Clinical and Experimental., vol. 32, No. 2, Mar. 1, 2017 (Mar. 1, 2017), pp. … [cited by applicant]
Ligsay et al., “A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome,” Journal of Neurodevelopmental Disorders, 9:26, Dec. 2017, 13 pages. [cited by applicant]
Mares et al., “Anticonvulsant action of allopregnanolone in immature rats,” Epilepsy Research, Elsevier Science Publishers, Amsterdam, NL, vol. 70, No. 2-3, Aug. 1, 2006 (Aug. 1, 2006), pp. 110-117, XP027974309. [cited by applicant]
Metcalf et al. “Indices of ovulation: Comparison of Plasma and Salivary Levels of Progesterone with Urinary Pregnanediol”, J. Endocr. 1984. vol. 100, pp. 75-80. [cited by applicant]
Office Action and Search Report for Taiwan Application No. 109115629, mailed Sep. 14, 2021, 17 pages. [cited by applicant]
PubChem-CID-57390981, Modify Date: Apr. 23, 2022 (Apr. 23, 2022), p. 2. [cited by applicant]
PubChem-SID-275053753, Modify Date: Nov. 21, 2016 (Nov. 21, 2016), p. 2, Fig. [cited by applicant]
Rasmusson et al., “A randomized controlled trial of ganaxolone in posttraumatic stress disorder,” Psychopharmacology, 234:2245-2257, Aug. 2017. [cited by applicant]
Hartmann et al., Synthesis and Evaluation of Aliphatic Heterocycle-substituted Steroidal Inhibitors of Alpha-hydroxylase/c17-20-lyase (P450 17). Journal of medicinal chemistry. Nov. 16, 2000;43(23):4437-45. [cited by applicant]
Kabat “A novel route to 2-fluoromethyl-and 2-hydroxymethyl-4-alkyl furans via allene oxides”. Tetrahedron letters. Oct. 7, 1996;37(41):7437-40. [cited by applicant]
Li et al., “Synthesis and evaluation of pregnane derivatives as inhibitors of human testicular 17α-hydroxylase/C17, 20-lyase”. Journal of medicinal chemistry. Oct. 11, 1996;39(21):4335-9. [cited by applicant]
Office Action for Australian Application No. 2020275291 mailed Dec. 19, 2024, 5 pages. [cited by applicant]
Office Action for European Application No. 20805552.5 mailed Feb. 19, 2025, 4 pages. [cited by applicant]
Office Action for Japanese Application No. 2022-542380 mailed Mar. 3, 2025, with English Translation, 6 pages. [cited by applicant]
Office Action for Mexican Application No. MX/a/2021/013695 mailed Feb. 25, 2025, with English translation, 11 pages. [cited by applicant]
Office Action for Mexican Application No. MX/a/2021/013695 mailed Nov. 28, 2024, with English translation, 12 pages. [cited by applicant]
Office Action for Russian Application No. 2021136231 mailed Dec. 2, 2024, with English translation, 25 pages. [cited by applicant]
Office Action for Russian Application No. 2022121496 mailed Dec. 19, 2024, with English translation, 12 pages. [cited by applicant]
Office Action for Taiwan Application No. 110130362, mailed Feb. 19, 2025, with partial English translation, 8 pages. [cited by applicant]