The repeated examples use ICE, DOPE and DMG-PEG2000 without a separate cholesterol helper lipid.
The first rapid-injection paragraph contains an inconsistent mention of cholesterol while giving only the three-part 60:35:5 ratio; the repeated pump examples resolve the operational composition. · Paragraphs [0246]-[0259]sales@dcchemicals.com
Imidazole cholesterol ester (ICE)
Formulation & Performance
Literature-reported formulation composition
| Component | mol% | Role |
|---|---|---|
| Imidazole cholesterol ester (ICE) | 60 | Ionizable lipid |
| DOPE | 35 | Helper phospholipid |
| DMG-PEG2000 | 5 | PEG lipid |
| Reported total | 100 | Source values retained |
Formulation calculator unavailable. The 3 reported lipid components total 100 mol%. Obtain and verify the complete composition and component molecular weights before planning component quantities.
Literature-reported performance for the cited formulation
Literature-reportedAbout 86% encapsulation; 89 nm; PDI 0.1230 mg scale; 60/35/5 mol%; N/P 4Paragraphs [0251]-[0252]
Literature-reported85-97% encapsulation and 50-89 nm across selected examplesN/P 4; scale and cargo variedParagraphs [0249]-[0262]
Literature-reportedDetected in bronchial epithelial and alveolar regionsRodent lung, 24 h after intratracheal aerosol or nebulizationParagraphs [0264]-[0281], Figs. 1-6
Literature-reportedStrongest staining at 24-72 h; detectable signal reported to 28 days in the rat dose studySingle pulmonary exposureParagraphs [0292]-[0299], Figs. 10-13
Selected ICE patent formulation examples
| Example | Condition | Reported result |
|---|---|---|
| 15 mg | 60/35/5 mol%; N/P 4 | 85% encapsulation; 65 nm; PDI 0.13 |
| 30 mg | 60/35/5 mol%; N/P 4 | 86% encapsulation; 89 nm; PDI 0.12 |
| 60 mg | 60/35/5 mol%; N/P 4 | 97% encapsulation; 67 nm; PDI 0.12 |
| 3.5 g | 60/35/5 mol%; N/P 4 | 91% encapsulation; 50 nm; PDI 0.17 |
WO2018/089790 A1, paragraphs [0249]-[0258].
Additional reported findings
In the reported rat comparison, ICE-CFTR mRNA formulations did not increase respiratory rate or lung weight relative to buffer, unlike the branched-PEI comparator.
Single-dose inhalation patent example; group sizes were not stated in the reviewed text. · Paragraph [0300], Fig. 14Literature Data DisclaimerAll formulation parameters and performance values shown in this section are derived from the cited publication and are provided for reference only. These results were obtained using the specific materials, formulation process, cargo, dose, analytical method, model and administration route described in that study. Unless otherwise stated, the data were not generated or independently verified by DC Chemicals. DC Chemicals supplies the lipid compound only and does not guarantee that customers will reproduce the reported LNP properties or biological performance.
The administration route shown above was used in the cited study and is not a clinical-use instruction or recommendation by DC Chemicals.
The administration route shown above was used in the cited study and is not a clinical-use instruction or recommendation by DC Chemicals.
Cited literature for this formulation and performance datasetTranslate Bio, Inc. Improved ICE-based lipid nanoparticle formulation for delivery of mRNA. WO2018/089790 A1. Published 17 May 2018. DOI: https://patents.google.com/patent/WO2018089790A1/en
All formulation and biological statements are limited to the ICE examples in WO2018/089790 A1 and are labeled as patent-reported preclinical evidence.
All formulation and biological statements are limited to the ICE examples in WO2018/089790 A1 and are labeled as patent-reported preclinical evidence.