IP Library › Granted Patent US 12,194,055
Granted Patent B2
US 12,194,055 · App. 17/582,594 · Granted Jan 14, 2025

Solute carrier family 46 member 3 (SLC46A3) as marker for lipid-based nanoparticle cancer therapy and diagnostics

Inventors: Natalie Boehnke (Cambridge, MA); Joelle Payne Straehla (Cambridge, MA); Angela Koehler (Cambridge, MA); Paula Hammond (Cambridge, MA)
Assignees: MASSACHUSETTS INSTITUTE OF TECHNOLOGY; DANA-FARBER CANCER INSTITUTE, INC.
A61K31/7105A61K9/1271A61K9/1617A61K9/1635A61K9/1647A61K38/465A61K45/06A61P35/00C12N15/1135C12Q1/6886G01N33/574C12N2320/34C12Q2600/106C12Q2600/158
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Quick Facts
Patent No.
US 12,194,055
App. No.
17/582,594
Granted
Jan 14, 2025
Kind
B2
Abstract

SLC46A3 has been identified as a lipid-based nanoparticle-specific biomarker predictive of nanoparticle-cancer cell affinity. SLC46A3 has a strong inverse association with lipid-based nanoparticle uptake across multiple nanoparticle formulations. Tissues with decreased expression levels of SLC46A3 have a greater uptake of lipid-based nanoparticles. The inverse relationship of SLC46A3 expression in tumor tissue and affinity for lipid-based nanoparticles has therapeutic and diagnostic implications, including cancer therapy and diagnosis, and identification of patients most likely to benefit from a lipid-based nanotherapeutic for improved stratification in clinical trials.

Claims (10)

1. A method of identifying a subject who is susceptible to treatment for cancer with lipid-based nanoparticle therapies, the method comprising determining expression levels of solute carrier family 46 member 3 (SLC46A3) in a plurality of cancer cells from a subject having cancer, wherein a subject with decreased SLC46A3 expression levels as compared to a control is susceptible to treatment with lipid-based nanoparticles, wherein the control is selected from the group consisting of (i) a reference range of expression levels from control cells expressing SLC46A3, (ii) a contemporaneous measurement of SLC46A3 expression in control cells known to express SLC46A3, (iii) a cohort of controls profiled and publicly available through a publicly available database, (iv) a reference level determined for a particular cancer type or subtype, and (v) a reference level determined from an individual patient from an earlier timepoint; and

wherein the method further comprises administering to a subject identified as susceptible to treatment with lipid-based nanoparticle therapies or identified as having cancer cells susceptible to treatment with nanoparticles, an amount of a lipid-based cancer therapy nanoparticle effective to treat or diagnose cancer.

2. The method of claim 1 , wherein the SLC46A3 expression level of the subject is increased or unchanged after the administering, wherein the method further comprises administering to the subject a non-lipid cancer therapy nanoparticle to treat or diagnose the cancer.

3. The method of claim 1 , wherein the SLC46A3 expression level of the subject is increased or unchanged after the administering, wherein the method further comprises administering to the subject an increased dosage or total amount of the lipid-based cancer nanoparticle to treat or diagnose the cancer.

4. The method of claim 1 , wherein the lipid-based nanoparticle comprises a liposomal nanoparticle.

5. The method of claim 4 , wherein the liposomal nanoparticle comprises an anionic liposomal nanoparticle.

6. The method of claim 5 , wherein the anionic liposomal nanoparticle comprises an electrostatic coating.

7. The method of claim 6 , wherein the electrostatic coating comprises one or more polyanions selected from the group consisting of polyacrylic acid (PAA), poly-L-aspartate (PLD), poly-L-glutamate (PLE), hyaluronate (HA), dextran sulfate (DXS), fucoidan (FUC), alginate (ALG), chondroitin sulfate (CS), carboxylate ions, and sulfate ions.

8. The method of claim 1 , wherein the lipid-based nanoparticle comprises a solid lipid nanoparticle.

9. The method of claim 8 , wherein the solid lipid nanoparticle core comprises an ionizable, neutral, or cationic nanoparticle.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2022
From: BOEHNKE, NATALIE; KOEHLER, ANGELA; HAMMOND, PAULA
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Reel/Frame 060498/0134 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 14, 2022
From: STRAEHLA, JOELLE PAYNE
To: MASSACHUSETTS INSTITUTE OF TECHNOLOGY; DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 060198/0179 →
CONFIRMATORY LICENSE Recorded Apr 26, 2022
From: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
To: UNITED STATES GOVERNMENT
Reel/Frame 059791/0813 →
Continuity (4)
Provisional Application 63248438 · Sep 25, 2021
Provisional Application 63170874 · Apr 5, 2021
Provisional Application 63140315 · Jan 22, 2021
Related Publication 20220233576A1 · Jul 28, 2022
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