IP Library › Granted Patent US 12,447,132
Granted Patent B2
US 12,447,132 · App. 18/652,380 · Granted Oct 21, 2025

Metal oxide encapsulated drug compositions and methods of preparing the same

Inventors: Colin C. Neikirk (Mountain View, CA); Jonathan Frankel (Los Gatos, CA)
Assignee: Applied Materials, Inc.
A61K9/5089A61J3/07A61K9/501A61K31/405A61K31/424A61K31/43A61K31/506A61K31/519A61K31/7048A61K47/58C07K16/22C07K16/2833C07K16/32C23C16/40C23C16/403C23C16/405C23C16/4417C23C16/45525C23C16/45555C23C16/458C07K2317/24C07K2317/94
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 12,447,132
App. No.
18/652,380
Granted
Oct 21, 2025
Kind
B2
Abstract

A method of preparing a pharmaceutical composition having a drug-containing core enclosed by one or more metal oxide materials is provided. The method includes the sequential steps of (a) loading the particles comprising the drug into a reactor, (b) applying a vaporous or gaseous metal precursor to the particles in the reactor, (c) performing one or more pump-purge cycles of the reactor using inert gas, (d) applying a vaporous or gaseous oxidant to the particles in the reactor, and (e) performing one or more pump-purge cycles of the reactor using inert gas. The temperature of the particles does not exceed 35° C. This produces a pharmaceutical composition comprising a drug containing core enclosed by one or more metal oxide materials.

Claims (27)

1. A composition comprising coated particles comprising an antibody-containing core enclosed by a coating layer, wherein the antibody-containing core comprises a lyophilized or spray-dried antibody, wherein the coating layer is conformal and comprises an inorganic oxide selected from the group consisting of aluminum oxide, titanium oxide, and zinc oxide, wherein the coating layer is 0.1 nm-100 nm thick.

2. The composition of claim 1 , wherein the antibody-containing core comprises a lyophilized antibody.

3. The composition of claim 1 , wherein the antibody-containing core comprises a spray-dried antibody.

4. The composition of claim 1 , wherein the coating layer is uniform.

5. The composition of claim 1 , wherein the particles consist essentially of the antibody.

6. The composition of claim 1 , wherein the antibody is structurally intact.

7. The composition of claim 1 , wherein the antibody specifically binds to its target antigen.

8. The composition of claim 1 , wherein the coated particles have a median particle size, on a volume average basis between 0.1 um and 1000 um.

9. The composition of claim 1 , wherein the coating layer is about 10 nm thick.

10. The composition of claim 1 , wherein the coating layer consists of titanium oxide.

11. A method of preparing a pharmaceutical composition coated particles comprising an antibody-containing core enclosed by one or more metal oxide materials, wherein the antibody-containing core comprises an antibody, the method comprising the sequential steps of:

(a) loading particles comprising an antibody into a reactor;

(b) applying a vaporous or gaseous metal precursor to the particles in the reactor;

(c) performing one or more pump-purge cycles of the reactor using an inert gas;

(d) applying vaporous or gaseous water as an oxidant to the particles in the reactor;

(e) performing one or more pump-purge cycles of the reactor using the inert gas; and

(f) repeating steps (b)-(e) one or more times to increase the total thickness of the one or more metal oxide materials that enclose the core

wherein each pump-purge cycle comprises flowing the inert gas into the reactor chamber to a desired pressure and after a delay time pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr and repeating the steps of flowing the inert gas into the reactor chamber to a desired pressure and after a delay time pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr, and the temperature of the particles does not exceed 35° C.

12. The method of claim 11 , wherein the particles in step (a) comprises an antibody and at least one pharmaceutically acceptable excipient.

13. The method of claim 11 , wherein the antibody is a lyophilized antibody.

14. The method of claim 11 , wherein the particles remain in the reactor during the repeated steps.

15. The method of claim 11 , wherein the particles have a median particle size, on a volume average basis between 0.1 um and 1000 um.

16. The method of claim 11 , wherein the temperature of the particles remains between 22° C. and 35° C.

17. The method of claim 11 , wherein the reactor contents are agitated prior to and/or during step (b), step (c), and/or step (e), thereby producing a pharmaceutical composition comprising an antibody-containing core enclosed by one or more metal oxide materials.

18. The method of claim 11 , wherein the reactor pressure is allowed to stabilize following step (a), step (b), and/or step (d).

19. The method of claim 11 , wherein a subset of vapor or gaseous content is pumped out prior to step (c) and/or step (e).

20. The method of claim 11 , wherein the pharmaceutical composition is removed from the reactor and admixed with a pharmaceutically acceptable diluent or carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2024
From: NEIKIRK, COLIN C.; FRANKEL, JONATHAN
To: APPLIED MATERIALS, INC.
Reel/Frame 067428/0951 →
Priority Claims (1)
IN 201841001745 · Jan 16, 2018 · national
Continuity (3)
Division 17695687 · Mar 15, 2022
Continuation 16249885 · Jan 16, 2019
Related Publication 20240285542A1 · Aug 29, 2024
References Cited (129)
US 4289871A · Rowan et al. · 1981 [cited by applicant]
US 4522811A · Eppstein et al. · 1985 [cited by applicant]
US 6165512A · Mezaache et al. · 2000 [cited by applicant]
US 6613383B1 · George et al. · 2003 [cited by applicant]
US 7357910B2 · Phillips et al. · 2008 [cited by applicant]
US 8524772B2 · Arad et al. · 2013 [cited by applicant]
US 8697097B2 · Nonomura et al. · 2014 [cited by applicant]
US 9795576B2 · Kolter et al. · 2017 [cited by applicant]
US 10166198B2 · Carlsson et al. · 2019 [cited by applicant]
US 10373820B2 · Tois et al. · 2019 [cited by applicant]
US 10478402B2 · Carlsson et al. · 2019 [cited by applicant]
US 10512796B2 · Toledano et al. · 2019 [cited by applicant]
US 10603284B2 · Hoppu et al. · 2020 [cited by applicant]
US 11311491B2 · Neikirk et al. · 2022 [cited by applicant]
US 12005145B2 · Hoppu et al. · 2024 [cited by applicant]
US 20030026989A1 · George et al. · 2003 [cited by applicant]
US 20030118642A1 · Norman et al. · 2003 [cited by applicant]
US 20040037883A1 · Zhou et al. · 2004 [cited by applicant]
US 20050266078A1 · Jorda et al. · 2005 [cited by applicant]
US 20060263479A1 · Boghani et al. · 2006 [cited by applicant]
US 20070036850A1 · Roehrich et al. · 2007 [cited by applicant]
US 20070280895A1 · Weimer et al. · 2007 [cited by applicant]
US 20090186968A1 · Zong et al. · 2009 [cited by applicant]
US 20100136110A1 · Tasaki et al. · 2010 [cited by applicant]
US 20100297251A1 · Timmons et al. · 2010 [cited by applicant]
US 20100303722A1 · Jin et al. · 2010 [cited by applicant]
US 20110091563A1 · Kurasawa et al. · 2011 [cited by applicant]
US 20110300224A1 · Murpani et al. · 2011 [cited by applicant]
US 20120201860A1 · Weimer et al. · 2012 [cited by applicant]
US 20130202790A1 · Li et al. · 2013 [cited by applicant]
US 20130336866A1 · Soeger et al. · 2013 [cited by applicant]
US 20130337056A1 · Lehtonen et al. · 2013 [cited by applicant]
US 20150250731A1 · Hoppu et al. · 2015 [cited by applicant]
US 20160081945A1 · Carlsson et al. · 2016 [cited by applicant]
US 20170007545A1 · Hoppu et al. · 2017 [cited by applicant]
US 20170333359A1 · Goldstein et al. · 2017 [cited by applicant]
US 20190216742A1 · Neikirk et al. · 2019 [cited by applicant]
US 20190279870A1 · Mane et al. · 2019 [cited by applicant]
US 20200197313A1 · Hoppu et al. · 2020 [cited by applicant]
US 20200338008A1 · Wang et al. · 2020 [cited by applicant]
US 20210217609A1 · Kagaya · 2021 [cited by applicant]
US 20210378971A1 · Wang et al. · 2021 [cited by applicant]
US 20220105048A1 · Wang et al. · 2022 [cited by applicant]
US 20220296530A1 · Neikirk · 2022 [cited by applicant]
US 20230059964A1 · Hoppu et al. · 2023 [cited by applicant]
US 20230097519A1 · Wang et al. · 2023 [cited by applicant]
US 20230355536A1 · Wang · 2023 [cited by applicant]
US 20230364023A1 · Wang et al. · 2023 [cited by applicant]
US 20240226018A1 · Hoppu et al. · 2024 [cited by applicant]
US 20240390286A1 · Wang et al. · 2024 [cited by applicant]
DE 10307568 · 2004 [cited by applicant]
EP 1621187 · 2006 [cited by applicant]
IN 802MUM200 · 2005 [cited by applicant]
JP 2004269384 · 2004 [cited by applicant]
JP 2005060309 · 2005 [cited by applicant]
JP 2005520796 · 2005 [cited by applicant]
JP 2008013480 · 2008 [cited by applicant]
JP 2008539801 · 2008 [cited by applicant]
JP 2010501538 · 2010 [cited by applicant]
JP 2011063627 · 2011 [cited by applicant]
JP 2012051810 · 2012 [cited by applicant]
JP 2014510066 · 2014 [cited by applicant]
JP 2015528487 · 2015 [cited by applicant]
JP 2016519155 · 2016 [cited by applicant]
KR 1020140011358 · 2014 [cited by applicant]
KR 1020160013050 · 2016 [cited by applicant]
KR 1020160090478 · 2016 [cited by applicant]
KR 1020170094046 · 2017 [cited by applicant]
WO WO1990002546 · 1990 [cited by applicant]
WO WO1996022030 · 1996 [cited by applicant]
WO WO2005044224 · 2005 [cited by applicant]
WO WO2006090640 · 2006 [cited by applicant]
WO WO2007015243 · 2007 [cited by applicant]
WO WO2008023184 · 2008 [cited by applicant]
WO WO2010135107 · 2010 [cited by applicant]
WO WO2011011207 · 2011 [cited by applicant]
WO WO2011141486 · 2011 [cited by applicant]
WO WO2012116814 · 2012 [cited by applicant]
WO WO2019143744 · 2019 [cited by applicant]
WO WO2020219583 · 2020 [cited by applicant]
[No Author Listed], Pharmaceutical Preparations, European Pharmacopoeia 8.0, Apr. 2013, 756-758. [cited by applicant]
Andrew et al., “Sustained Release of a Monoclonal Antibody from Electrochemically Prepared Mesoporous Silicon Oxide,” Advanced Functional Materials, Dec. 2010, 20(23):4168-4174. [cited by applicant]
Arin et al., “Characterization of ZnO—TiO2 and zinc titanate nanoparticles synthesized by hydrothermal process,” Res Chem Intermed, 2017, 43:3183-3195. [cited by applicant]
Arl et al., “SiO2 thin film growth through a pure atomic layer deposition technique at room temperature,” Royal Society of Chemistry, May 2020, 10:18073-18081. [cited by applicant]
Arya R et al., Zirconia Biomaterials, StatPearls, Jan. 2022, 4 pages. [cited by applicant]
Azad et al., “Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations,” AAPS PharmSciTech, Apr. 2021, 22(3):1-11. [cited by applicant]
Balaji et al., “Nano-zirconia-Evaluation of its antioxidant and anticancer activity,” Journal of Photochemistry & Photobiology, B: Biology, May 1, 2017, 170: 125-133. [cited by applicant]
Choi et al., “Rapid vapor deposition SiO2 thin film deposited at a low temperature using tris (tert-pentoxy) silanol and trimethyl-aluminum,” Materials Chemistry and Physics, Nov. 15, 2013, 142(2-3):614-8. [cited by applicant]
Extended European Search Report in European Appln. No. 19741437.8, dated Oct. 12, 2021, 10 pages. [cited by applicant]
Groner et al., “Low-temperature Al2O3 atomic layer deposition,” Chemistry of Materials, Chemistry of Materials, American Chemical Society, US, Feb. 24, 2004, 16(4):639-645. [cited by applicant]
Hakim et al., “Conformal nanocoating of zirconia nanoparticles by atomic layer deposition in a fluidized bed reactor,” Nanotechnology, 2005, 16:S375-S381. [cited by applicant]
Huo et al., “Pre-Treatment with Zirconia Nanoparticles Reduces Inflammation Induced by the Pathogenic H5N1 Influenza Virus,” International Journal of Nanomedicine, 2020, 15:661-674. [cited by applicant]
International Search Report and Written Opinion in International Application No. PCT/US2019/013881, dated May 8, 2019, 11 pages. [cited by applicant]
Kaariainen et al., “Surface modification of acetaminophen particles by atomic layer deposition,” International Journal of Pharmaceutics, Apr. 18, 2017, 525(1):160-174. [cited by applicant]
Klaus et al., “SiO2 Chemical Vapor Deposition at Room Temperature Using SiCl4 and H20 with an NH 3 Catalyst,” Journal of the Electrochemical Society, 2000, 147(7):2658-2664. [cited by applicant]
Knez et al., “Synthesis and Surface Engineering of Complex Nanostructures by Atomic Layer Deposition,” Advanced Materials, Nov. 5, 2007, 19(21):3425-3438. [cited by applicant]
Knez et al., “Atomic Layer Deposition on Biological Macromolecules: Metal Oxide Coating of Tobacco Mosaic Virus and Ferritin,” Nano Letters, 2006, 6(6):1172-1177. [cited by applicant]
Lee et al., “Low temperature atomic layer deposition of SiO2 thin films using diisopropylaminosilane and ozone,” Ceramics International, Feb. 1, 2017, 43(2):2095-2099. [cited by applicant]
Li et al, “Micro and Nano Powder Post-Processing Technology and Application,” Defense Industry Press, Sep. 2005, pp. 315-318 (with English translation). [cited by applicant]
Li et al., “Nanoparticle Multilayers: Surface Modification of Photosensitive Drug Microparticles for Increased Stability and in Vitro Bioavailability,” Journal of Nanoscience and Nanotechnology, Sep. 2006, 6(9-10):3252-… [cited by applicant]
Li et al., “Oxide bioceramics: inert ceramic materials in medicine and dentistry,” Handbook of Biomaterial Properties, 1998, 4 pages. [cited by applicant]
Martino et al., “A new pure paracetamol for direct compression: The orthorhombic form,” International Journal of Pharmaceutics, 1996, 128:1-8. [cited by applicant]
Mftah et al., “Physicochemical properties, cytotoxicity, and antimicrobial activity of sulphated zirconia nanoparticles,” International Journal of Nanomedicine, 2015:10 765-774. [cited by applicant]
Nam et al., “Low-temperature, high-growth-rate ALD of SiO2 using aminodisilane precursor,” Applied Surface Science, Aug. 15, 2019, 485:381-390. [cited by applicant]
Office Action in Chinese Appln. No. 201980012924.4, dated May 6, 2022, 6 pages (with English translation). [cited by applicant]
Office Action in Chinese Appln. No. 201980012924.4, dated Nov. 23, 2021, 12 pages (with English translation). [cited by applicant]
Office Action in Indian Appln. No. 202047034175, dated Nov. 26, 2020, 6 pages. [cited by applicant]
Office Action in Japanese Appln. No. 2020-560122, dated Sep. 14, 2021, 12 pages (with English translation). [cited by applicant]
Office Action in Korean Appln. No. 10-2020-7023286, dated Jan. 25, 2022, 10 pages (with English translation). [cited by applicant]
Patel et al., “Ensuring Better Control of Granulation,” Pharmaceutical Manufacturing, Aug. 7, 2008, http://www.pharmamanufacturing/com/articles/2008/096/, 11 pages. [cited by applicant]
Prescott et al., “On Powder Flowability,” Pharmaceutical Technology, Oct. 2000, 14 pages. [cited by applicant]
Shah et al., “Comparative Evaluation of Flow for Pharmaceutical Powders and Granules,” AAPS PharmSciTech, 2008, 9(1):250-258. [cited by applicant]
Siddiqi et al., “Properties of Zinc Oxide Nanoparticles and Their Activity Against Microbes,” Nanoscale Research Letters, 2018, 13:141, 13 pages. [cited by applicant]
Singh et al., “Area-Selective Atomic Layer Deposition of Metal Oxides on Noble Metals through Catalytic Oxygen Activation,” Chem. Mater., 2018, 30:663-670. [cited by applicant]
Singh et al., “Microencapsulation: A promising technique for controlled drug delivery,” Res. Pharnn. Sci., 2010, 5(2):65-77. [cited by applicant]
Verheezen et al., “Milling of agglomerates in an impact mill,” Int. J. Pharm., 2004, 278:165-172. [cited by applicant]
wikipedia.com [online], “Titanium Oxide,” retrieved on Aug. 20, 2021, retrieved from URL <https://en.wikipedia.org/wiki/Titanium_oxide>, 1 page. [cited by applicant]
Won et al., “Effect of Catalyst Layer Density and Growth Temperature in Rapid Atomic Layer Deposition of Silica Using Tris (tert-pentoxy) silanol,” ACS Applied Materials & Interfaces, May 25, 2011, 3(5):1633-9. [cited by applicant]
Wu et al., “Preparation and properties of composite particles made by nano zinc oxide coated with titanium dioxide,” J. Mater. Sci., 2006, 41:5845-5850. [cited by applicant]
www.ahdictionary.com [online], “Granule,” retrieved on Aug. 9, 2019, retrieved from URL <https:www.ahdictionary.com/word/search/html?q=granule>, 3 pages. [cited by applicant]
Xie et al., “Atomic layer deposition of TiO2 from tetrakis-dimethyl-amido titanium or Ti isopropoxide precursors and H20,” Journal of Applied Physics, 2007, 102:7 pages. [cited by applicant]
Xu et al., “China's Strategic Emerging Industries: New Materials. High-Performance Separation Membrane Materials,” China Railway Press, Dec. 2017, p. 60 (with English translation). [cited by applicant]
Wu et al., “Optical and Electrical Properties of Al-doped ZnO Thin Films by Atomic Layer Deposition,” Journal of Materials Science: Materials in Electronics, Aug. 31, 2020, 31:17365-17374. [cited by applicant]
Zhao et al., “Investigation on Transparent, Conductive ZnO:Al Films Deposited by Atomic Layer Deposition Process,” Nanomaterials, Jan. 5, 2022, 12(1):1-10. [cited by applicant]
U.S. Appl. No. 18/212,599, filed Jun. 21, 2023, Frankel et al. [cited by applicant]
Johnson, et al., “A brief review of atomic layer deposition: from fundamentals to applications,” Materials Today, 2014, 17(5):236-246. [cited by applicant]
Lee, et al., “Effect of the pressure on the chemical vapor deposition of copper from copper hexafluoracetylacetoneate trimethylvinylsilane,” Thin Solid Films, 1997, 305:254-258. [cited by applicant]
Office Action in European Appln. No. 19 741 437.8, mailed May 13, 2025, 5 pages. [cited by applicant]
Office Action in Japanese Appln. No. 2023-210166, dated Feb. 12, 2025, 14 pages (with English Translation). [cited by applicant]