IP Library › Granted Patent US 12,419,951
Granted Patent B2
US 12,419,951 · App. 17/615,493 · Granted Sep 23, 2025

Preparation of zinc risedronate micro/nano adjuvant and use thereof as vaccine adjuvant

Inventors: Qinjian Zhao (Fujian, CN); Xiaofen Huang (Fujian, CN); Yike Li (Fujian, CN); Meifeng Nie (Fujian, CN); Siyi Chen (Fujian, CN); Ningshao Xia (Fujian, CN)
Assignees: Xiamen University; Xiamen Innovax Biotech Co., Ltd.
A61K39/39A61K39/25A61P31/22A61P37/04A61K2039/55511A61K2039/55516
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Quick Facts
Patent No.
US 12,419,951
App. No.
17/615,493
Granted
Sep 23, 2025
Kind
B2
Abstract

The present invention pertains to the field of pharmaceutical technology. Specifically, the present invention relates to a zinc risedronate micro/nano adjuvant with sustained-release function formed by mineralization of zinc ions and risedronic acid as main components and its use as a vaccine adjuvant. The present invention also relates to a method for preparing zinc risedronate micro/nano adjuvant. The present invention also relates to a chemical composition, vaccine adjuvant and vaccine composition comprising zinc risedronate micro/nano adjuvant. The present invention also relates to a use of zinc risedronate micro/nano adjuvant as a vaccine adjuvant.

Claims (23)

1. A vaccination method for treatment or prevention of infection in a mammal, said method comprising administering a vaccine composition intramuscularly to a mammal, wherein said vaccine composition comprises an antigen and an adjuvant, the adjuvant comprising zinc risedronate micro/nanoparticles, wherein the zinc risedronate micro/nanoparticles consist of zinc and risedronic acid and, optionally phosphate, and wherein the zinc risedronate micro/nanoparticles have a molar concentration ratio of zinc: risedronic acid of 1-8:1.

2. The vaccination method according to claim 1 , wherein said zinc risedronate micro/nanoparticles have a molar concentration ratio of zinc: risedronic acid selected from 1:1, 4:1 and 8:1.

3. The vaccination method according to claim 1 , characterized in any one of the following:

(1) said zinc risedronate micro/nanoparticles consist of a phosphate at a molar concentration ratio of zinc: phosphate of 1-8:1; and

(2) said zinc risedronate micro/nanoparticles consist of a phosphate at a molar concentration ratio of zinc: phosphate selected from 1.5:1 and 4:1.

4. The vaccination method according to claim 1 , wherein the zinc risedronate micro/nanoparticles are prepared by a method comprising the following steps:

a) providing a soluble salt solution containing zinc ions;

b) evenly mixing the soluble salt solution of step a) with a risedronic acid and a sodium hydroxide; or

evenly mixing the soluble salt solution of step a) with a risedronic acid, a sodium hydroxide, and a sodium phosphate solution,

in a manner of sequential precipitation, separated precipitation followed by mixing, or co-precipitation, to obtain the adjuvant comprising zinc risedronate micro/nanoparticles.

5. The vaccination method according to claim 4 , characterized in one or more of the following:

(1) said soluble salt solution comprises a solution of hydrochloric acid; and

(2) said method further comprises subjecting the mixture of step b) to sterilization, and storing at 2° C. to 8° C. for later use.

6. The vaccination method according to claim 5 , characterized in any one of the following:

(1) said sterilization comprises a sterilization using a high temperature and high pressure sterilization technique; and

(2) said sterilization comprises a sterilization performed at 121° C. for 30 to 60 minutes.

7. The vaccination method according to claim 1 , characterized in one or more of the following:

(1) said adjuvant has a pH of 8.0-9.0 before sterilization;

(2) said adjuvant has a pH of 6.0-8.0 after sterilization;

(3) said zinc risedronate micro/nanoparticles have a particle size of 1-10 μm;

(4) said adjuvant has a particle zero charge point of 4.0-11.4; and

(5) said adjuvant has a protein adsorption rate of >60%.

8. The vaccination method according to claim 7 , wherein said protein comprises bovine serum albumin.

Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE OMISSION SECOND ASSIGNEE'S NAME PREVIOUSLY RECORDED AT REEL: 058879 FRAME: 0883. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT . Recorded Mar 14, 2022
From: ZHAO, QINJIAN; HUANG, XIAOFEN; LI, YIKE; NIE, MEIFENG; CHEN, SIYI; XIA, NINGSHAO
To: XIAMEN UNIVERSITY; XIAMEN INNOVAX BIOTECH CO., LTD.
Reel/Frame 059364/0782 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 3, 2022
From: ZHAO, QINJIAN; HUANG, XIAOFEN; LI, YIKE; NIE, MEIFENG; CHEN, SIYI; XIA, NINGSHAO
To: XIAMEN UNIVERSITY
Reel/Frame 058879/0883 →
Priority Claims (1)
CN 201910459715.6 · May 30, 2019 · national
Continuity (1)
Related Publication 20220233687A1 · Jul 28, 2022
References Cited (42)
US 8445718B2 · Suwa et al. · 2013 [cited by applicant]
US 9573811B2 · Thiriot · 2017 [cited by applicant]
US 9649372B2 · Harper et al. · 2017 [cited by applicant]
US 10471141B2 · Shishido et al. · 2019 [cited by applicant]
US 10925936B2 · Shishido · 2021 [cited by examiner]
US 20110034418A1 · Beltz et al. · 2011 [cited by applicant]
US 20170281759A1 · Shishido et al. · 2017 [cited by applicant]
US 20190321465A1 · Zhang et al. · 2019 [cited by applicant]
US 20200254089A1 · Asari et al. · 2020 [cited by applicant]
US 20220193231A1 · Zhao · 2022 [cited by examiner]
US 20240000813A1 · Zhao · 2024 [cited by examiner]
CN 101972477A · 2011 [cited by applicant]
CN 102046152A · 2011 [cited by applicant]
CN 102421785A · 2012 [cited by applicant]
CN 102939105A · 2013 [cited by applicant]
CN 103768595B · 2016 [cited by applicant]
CN 105669838A · 2016 [cited by applicant]
CN 106687127A · 2017 [cited by applicant]
CN 106687138A · 2017 [cited by applicant]
CN 108289902A · 2018 [cited by applicant]
CN 110665000A · 2020 [cited by applicant]
DE 4244422A1 · 1992 [cited by applicant]
WO 2018225784A1 · 2018 [cited by applicant]
Kharuja et al. (Materials Science and Engineering, 2016, p. 78-87). [cited by examiner]
English Abstract of Lin et al., “Application and Mechanism of Calcium Phosphate Nanoparticles as Vaccine Adjuvant,” Chinese Master's Theses Full-Text Database, Medicine & Health Sciences. Published Jul. 21, 2019. [cited by applicant]
Tonti et al., “Bisphosphonates Target B Cells to Enhance Humoral Immune Responses,” Cell Reports 5:323-330 (2013). [cited by applicant]
Xia et al., “The Mevalonate Pathway Is a Druggable Target for Vaccine Adjuvant Discovery,” Cell 175:1059-1073 (2018). [cited by applicant]
English translation of the International Search Report in PCT/CN2020/082443, mailed Jun. 28, 2020. [cited by applicant]
Ai et al., “Analysis of physicochemical properties of three aluminum hydroxide adjuvant,” Chinese Journal of Biologicals 28(1):44-47 (2015). [cited by applicant]
Gao et al., “The Role of Zinc and Zinc Homeostasis in Macrophage Function,” Journal of Immunological Research 2018:6872621 (2018). [cited by applicant]
Goldenthal et al., “Safety evaluation of vaccine adjuvants: National Cooperative Vaccine Development Working Group,” AIDS Res Hum Retroviruses 9(1):S47-S51 (1993). [cited by applicant]
Lin et al., “Calcium Phosphate Nanoparticles as a New Generation Vaccine Adjuvant,” Expert Review of Vaccines 16(9):895-906 (Jul. 25, 2017). [cited by applicant]
Lin et al., “Application and Mechanism of Calcium Phosphate Nanoparticles as Vaccine Adjuvant,” Jul. 15, 2019; pp. 58-63. Chinese Master's Theses Full-Text Database, Medicine & Health Sciences; English Abstract. [cited by applicant]
Luzuriaga et al., “Enhanced Stability and Controlled Delivery of MOF-Encapsulated Vaccines and Their Immunogenic Response In Vivo,” ACS Applied Materials & Interfaces, 11(10): 9740-9746 (2019). [cited by applicant]
Malyala et al., “The Preparation and Physicochemical Characterization of Aluminum Hydroxide/TLR7a, a Novel Vaccine Adjuvant Comprising a Small Molecule Adsorbed to Aluminum Hydroxide,” J Pharm Sci 107(6): 1577-1585 (201… [cited by applicant]
Masson et al., “Calcium Phosphate: a Substitute for Aluminum Adjuvants,” Expert Review of Vaccines 16(3):289-299 (2016). [cited by applicant]
Prasad et al., “Effects of zinc deficiency on Th1 and Th2 cytokine shifts,” J Infect Dis 182 Suppl 1:S62-68 (2000). [cited by applicant]
Sanna et al., “Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis,” Nutrients 10(1):68 (2018). [cited by applicant]
Sun et al., “Bisphosphonate Stabilized Calcium Phosphate Nanoparticles for Effective Delivery of Plasmid DNA to Macrophages,” ACS Applied Bio Materials 3:986-996 (Jan. 6, 2020). [cited by applicant]
Wessels et al., “Zinc as a Gatekeeper of Immune Function,” Nutrients 9(12):1286 (2017). [cited by applicant]
Wu et al., “Rational design of small molecules as vaccine adjuvants,” Science Translational Medicine 6(263):263ra160 (2014). [cited by applicant]
Zhao et al., “Surface Phosphophilicity of Aluminum-Containing Adjuvants Probed byEfficiency for Catalyzing the P—O Bond Cleavage with Chromogenic and Fluorogenic Substrates,” Analytical Biochemistry 295(1):76-81 (2001). [cited by applicant]