Enhanced pH-Sensitive Liposome Compositions for Targeted Cargo Delivery

Publication ID: 24-11857509_0001_PTD
Published: October 28, 2025
Category:Direct Improvements & Enhancements

Legal Citation

pr1or.art Inc., “Enhanced pH-Sensitive Liposome Compositions for Targeted Cargo Delivery,” Published Technical Disclosure No. 24-11857509_0001_PTD, Published October 28, 2025, available at https://archive.pr1or.art/24-11857509_0001_PTD
This technical disclosure describes improvements that would be readily apparent to a Person Having Ordinary Skill In The Art (PHOSITA) when considered in combination with the foundational architecture disclosed in U.S. Patent No. 11,857,509.

Summary of the Inventive Concept

Improved liposome compositions and methods for targeted cargo delivery, featuring modified pHLIP polypeptides that enhance membrane fusion efficiency, stability, and specificity, resulting in increased cargo delivery efficiency and reduced off-target effects.

Background and Problem Solved

The original patent disclosed liposome compositions and methods for delivering molecules to cells, but faced limitations in terms of membrane fusion efficiency, liposome stability, and targeting specificity. The new inventive concept addresses these limitations by introducing modified pHLIP polypeptides that improve the overall performance of the liposome-based cargo delivery system.

Detailed Description of the Inventive Concept

The enhanced pH-sensitive liposome compositions comprise modified pHLIP polypeptides with increased membrane fusion efficiency, achieved through modifications that enhance binding affinity to target cell membranes. Additionally, the liposomes are stabilized by attaching the pHLIP polypeptide to a polymer with a molecular weight of at least 10,000 Da, reducing aggregation and increasing cargo delivery efficiency. Furthermore, the modified pHLIP polypeptides selectively target cancer cells with low extracellular pH, reducing off-target effects. The system also enables real-time monitoring of cargo delivery through the release of a fluorescent marker upon membrane fusion.

Novelty and Inventive Step

The new claims introduce novel modifications to the pHLIP polypeptide, including increased membrane fusion efficiency, improved stability, and enhanced targeting specificity, which are not obvious from the original patent. These modifications provide a significant improvement over the existing technology, enabling more efficient and targeted cargo delivery.

Alternative Embodiments and Variations

Alternative embodiments of the inventive concept could include using different types of polymers or molecular weights to stabilize the liposomes, or modifying the pHLIP polypeptide to target different cell types or diseases. Additionally, the system could be adapted for use with different types of cargo, such as nucleic acids or small molecules.

Potential Commercial Applications and Market

The enhanced pH-sensitive liposome compositions and methods have significant commercial potential in the fields of cancer therapy, gene therapy, and vaccine development, where targeted and efficient cargo delivery is crucial. The market for liposome-based delivery systems is expected to grow significantly in the coming years, driven by the increasing need for effective and targeted therapies.

CPC Classifications

SectionClassGroup
A A61 A61K9/1271
A A61 A61K9/127
A A61 A61K31/20
A A61 A61K31/337
A A61 A61K31/704
A A61 A61K31/711
A A61 A61K31/713
A A61 A61K31/7105
A A61 A61K47/6911
A A61 A61P35/00

Field of Art

Pharmaceutical drug delivery systems, specifically liposomal cargo delivery technologies with pH-sensitive targeting mechanisms, requiring expertise in biochemistry, molecular engineering, and pharmaceutical formulation

Person of Ordinary Skill (PHOSITA) Profile

A researcher with advanced degrees in biochemistry or pharmaceutical sciences, experienced in liposomal drug delivery, familiar with peptide modification techniques, membrane fusion mechanisms, and targeted drug delivery strategies

Obviousness Rationale

A person of ordinary skill would recognize that the PTD's modifications to pHLIP liposomes represent predictable variations of the source patent's core technology. The enhancements in membrane fusion efficiency, stability, and targeting specificity are logical extensions of known liposomal drug delivery principles. These modifications would be considered routine optimization within the state of the art for targeted drug delivery systems.

Obvious Combinations & Variations

Source Patent Element
pH-sensitive liposomes with pHLIP polypeptides for targeted cargo delivery
PTD Variation
Adding polymer stabilization to pHLIP liposomes with molecular weight of at least 10,000 Da
Obviousness Reasoning
Polymer stabilization of liposomes is a known technique for improving drug delivery system stability, representing a predictable design choice for enhancing cargo retention and delivery efficiency
Source Patent Element
Cargo delivery to cells with low pH microenvironments
PTD Variation
Modifying pHLIP polypeptides to increase membrane fusion efficiency by 20%
Obviousness Reasoning
Incremental improvements in peptide design to enhance membrane interactions are standard engineering approaches in drug delivery, representing obvious technical optimization
Source Patent Element
Liposome-based cargo delivery mechanisms
PTD Variation
Adding fluorescent marker for real-time cargo delivery monitoring
Obviousness Reasoning
Incorporating tracking mechanisms is a well-known strategy in pharmaceutical research, representing a predictable solution for improving delivery system characterization
Source Patent Element
pH-sensitive targeting of specific cell types
PTD Variation
Enhanced specificity for cancer cells with low extracellular pH
Obviousness Reasoning
Refining targeting mechanisms through peptide modification is a standard approach in developing more precise drug delivery systems, representing an obvious technical improvement
Source Patent Element
Basic pHLIP liposome composition for cargo delivery
PTD Variation
Expanding cargo types to include nucleic acids and small molecules
Obviousness Reasoning
Adapting delivery systems to multiple cargo types is a predictable extension of existing technology, representing a routine engineering adaptation
35 U.S.C. § 103 Summary: Pursuant to 35 U.S.C. ยง 103, the variations disclosed in this Published Technical Disclosure would have been obvious to a person having ordinary skill in the art at the time of invention, when considered in light of US Patent 11857509. The incremental modifications to pH-sensitive liposomal drug delivery systems represent predictable technical variations that do not rise to the level of non-obvious innovation, thereby establishing this disclosure as anticipatory prior art against subsequent patent claims in this technological domain.

Original Patent Information

Patent NumberUS 11,857,509
TitleLiposome compositions and methods of use thereof
Assignee(s)Yale University, University of Rhode Island Board of Trustees