US Patent 5,769,080: Gas-Filled Liposomes, Claim Scope, Expiration, and Patent Landscape

US Patent 5,769,080 covers gas-filled lipid vesicles intended primarily for ultrasound contrast imaging. Its three independent claims target: (1) liposomes made by vacuum-drying and gas-instillation, (2) gas-filled liposomes substantially devoid of internal liquid, and (3) injectable contrast agents containing lipid-encapsulated gas bubbles. The patent issued June 23, 1998, and its enforceable term expired in 2015. It is therefore no longer a current blocking patent in the United States, although its claim structure remains relevant to freedom-to-operate analyses involving ultrasound microbubbles and dry-stored contrast agents.

What technology does US Patent 5,769,080 protect?

The patent protects lipid-encapsulated gas structures that can be used as ultrasound contrast agents. Its technical focus is the creation of gas-filled liposomes with improved storage stability, acoustic reflectivity, and resistance to pressure changes.

The disclosed platform has four principal elements:

A lipid shell.
A gas-containing interior.
A substantially liquid-free interior in many claims.
Preparation by vacuum drying followed by gas instillation in the broadest method-linked product claim.

The technology differs from conventional aqueous liposomes, which normally contain an aqueous internal phase. The claimed structures are closer to gas-filled lipid vesicles or early-generation lipid microbubbles.

The patent is assigned to the Board of Regents of the University of Texas System and is associated with the early development of lipid-encapsulated ultrasound contrast technology (U.S. Patent No. 5,769,080, 1998).

When did US Patent 5,769,080 expire?

US Patent 5,769,080 expired in 2015, based on the patent’s statutory term and issue date. The patent issued on June 23, 1998. For patents governed by the pre-Uruguay Round Agreement Act term rules, the term generally ran for 17 years from issuance unless an earlier expiration applied.

Item	Data
Patent	US 5,769,080
Issue date	June 23, 1998
Technology	Gas-filled liposomes and injectable ultrasound contrast agents
Patent holder	Board of Regents of the University of Texas System
US status	Expired
Estimated statutory expiration	June 23, 2015
Current blocking effect	None based on this patent alone
FDA exclusivity	None remaining
Orange Book effect	No current exclusivity created by this expired platform patent

The patent’s expiration eliminates infringement risk based solely on US Patent 5,769,080. It does not eliminate risk from later patents covering specific gases, shell compositions, manufacturing processes, formulations, doses, imaging indications, or commercial products.

How many independent claims does US Patent 5,769,080 have?

The supplied claims contain three independent claims: claims 1, 21, and 41.

Independent claim	Claimed subject matter	Main limiting feature
Claim 1	Gas-filled liposome	Prepared by vacuum drying and gas instillation
Claim 21	Gas-filled liposome	Substantially devoid of liquid internally
Claim 41	Injectable contrast agent	Stabilized gas bubbles encapsulated by lipid material and substantially devoid of liquid

Claims 2-20 depend from claim 1. Claims 22-40 depend from claim 21. Claims 42-56 depend from claim 41.

The three independent claims create overlapping but distinct claim groups. Claim 1 is process-linked. Claim 21 is directed to a product defined by its internal structure. Claim 41 is directed to an injectable contrast-agent composition and does not expressly require preparation by vacuum drying and gas instillation.

What is the scope of claim 1?

Claim 1 covers:

A gas-filled liposome prepared by a vacuum-drying gas-instillation method.

The claim has both product and process characteristics. The product must be a gas-filled liposome, but the claim also specifies how it was prepared. A competing product made by a materially different process could argue that it does not satisfy the process limitation, although product-by-process interpretation depends on the applicable infringement analysis and whether the claimed product is distinguishable from conventionally produced products.

The claim does not expressly limit:

The gas species.
The lipid composition.
The liposome size.
The lamellarity.
The storage state.
The ultrasound frequency.
The injection route.
The clinical indication.
The presence of a drug or targeting ligand.

Those limitations are introduced in dependent claims.

Claim 1 dependent-claim hierarchy

Claims 2-20 narrow claim 1 through the following technical features:

Claims	Limitation
2	Specified lipid classes
3	Dipalmitoylphosphatidylcholine, or DPPC
4	Polymerized lipids
5	Polyethylene glycol
6	Specified gases
7	Nitrogen
8	Aqueous suspension storage
9	Dry storage
10	Stability exceeding about three weeks
11-12	Acoustic reflectivity above 2 dB, including 2-20 dB
13-14	In vivo targeting material, including carbohydrates
15	Stability to pressure changes
16-18	Oligolamellar or unilamellar structures
19-20	Phospholipid-containing structures

The broadest commercially relevant subclaims are likely claims 3, 5, 9, 10, 11-12, and 16-20 because they map onto practical formulation, storage, and imaging attributes.

What is the scope of claim 21?

Claim 21 covers:

A gas-filled liposome substantially devoid of liquid in the interior.

This claim removes the express vacuum-drying and gas-instillation limitation found in claim 1. It therefore focuses on the physical structure of the product rather than the manufacturing route.

Claim 21 may be broader than claim 1 for products that have a substantially liquid-free interior but were manufactured by another process. The key construction issue is the meaning of "substantially devoid of liquid." The phrase does not require absolute absence of liquid. Residual water, hydration layers, or incidental liquid may not defeat the claim if the overall interior is functionally gas-filled and lacks a conventional aqueous core.

Claims 22-40 repeat the principal narrowing categories from the first claim group:

Lipid identity.
DPPC.
Polymerized lipid.
Polyethylene glycol.
Gas identity.
Dry or aqueous storage.
Shelf life.
Reflectivity.
Targeting.
Pressure stability.
Lamellarity.
Phospholipid content.

Claim 24 contains the apparent phrase "polymerize lipids." In context, this appears to be a drafting error or typographical variation referring to polymerized lipids. The issued patent text, prosecution history, and any certificate of correction control the legally operative wording.

What is the scope of claim 41?

Claim 41 covers an injectable contrast agent comprising stabilized gas bubbles in which gas is encapsulated by one or more lipid materials and the bubbles are substantially devoid of liquid internally.

This is the most commercially significant independent claim because it is directed to an injectable product rather than only to an isolated liposome. It does not expressly require:

Vacuum drying.
Gas instillation.
A specific gas.
A specific lipid.
A particular liposome morphology.
A reflectivity threshold.
A minimum shelf life.
A targeting ligand.

Claim 41 uses "stabilized gas bubbles" and "one or more lipid materials." That wording can reach structures described commercially as lipid-coated microbubbles, depending on the construction of "encapsulated" and "substantially devoid of liquid." Claims 42-46 narrow the structure to oligolamellar or unilamellar liposomes and phospholipid-containing forms.

Claims 47-50 narrow the lipid and excipient composition. Claims 51-52 cover targeting materials, including carbohydrates. Claim 53 limits the gas to air, nitrogen, carbon dioxide, oxygen, argon, xenon, helium, or neon. Claims 54-55 cover aqueous suspension or dry storage. Claim 56 covers pressure stability.

Which lipid materials are covered?

The claims recite a broad Markush group of lipid materials:

Fatty acids.
Lysolipids.
DPPC.
Phosphatidylcholine.
Phosphatidic acid.
Sphingomyelin.
Cholesterol.
Cholesterol hemisuccinate.
Tocopherol hemisuccinate.
Phosphatidylethanolamine.
Phosphatidylinositol.
Glycosphingolipids.
Glucolipids.
Glycolipids.
Sulfatides.
Ether- and ester-linked fatty-acid lipids.
Polymerized lipids.

DPPC receives a specific dependent claim. This is commercially relevant because DPPC and related phospholipids are common shell materials in modern ultrasound contrast agents.

The lipid list is broad, but claim scope is constrained by the requirement that the lipid material encapsulate gas in the claimed substantially liquid-free bubble or liposome. A product containing one listed lipid as a minor excipient would not automatically satisfy every claim. The lipid must perform the claimed encapsulating or shell-forming function.

What gases are covered by the patent?

Claims 6, 26, and 53 recite:

Air.
Nitrogen.
Carbon dioxide.
Oxygen.
Argon.
Xenon.
Helium.
Neon.

Nitrogen is claimed separately in claims 7 and 27. The claims do not expressly recite fluorinated gases such as perfluoropropane, perfluorobutane, or sulfur hexafluoride.

That omission is important. Several later commercial ultrasound contrast agents use fluorinated or sulfur-containing gases because of their persistence and acoustic performance. A product using a gas outside the listed group could still fall within an independent claim if the independent claim does not require a listed gas. The gas Markush limitation applies only to the dependent claims that expressly incorporate it.

What formulations and dosage forms are protected?

The patent covers both dry and aqueous presentations.

Dry-stored products

Claims 9, 29, and 55 cover products stored dry. This supports a reconstitution model in which a dry lipid structure is exposed to gas and then suspended before administration. Dry storage is commercially important because it can improve shelf life and reduce degradation during transport.

Aqueous suspensions

Claims 8, 28, and 54 cover gas-filled structures stored suspended in an aqueous medium. These claims target ready-to-use or liquid-stored contrast products.

Polyethylene glycol formulations

Claims 5 and 25 expressly include polyethylene glycol. PEG may be used to modify circulation time, steric stabilization, aggregation behavior, or biodistribution.

Targeted formulations

Claims 13-14 and 33-34 cover in vivo targeting materials, including carbohydrates. The claims are not limited to a particular receptor, tissue, ligand density, or imaging indication.

What performance characteristics are claimed?

The patent includes two principal performance limitations.

Shelf-life and stability

Claims 10 and 30 require stability greater than about three weeks. The specification and prosecution history would be important in determining the test conditions, storage temperature, acceptable gas loss, and definition of "stability."

Claims 15 and 35 require stability to pressure changes. This could be relevant to injection through a syringe or catheter, passage through the cardiovascular system, or exposure to changing hydrostatic pressure.

Acoustic reflectivity

Claims 11, 12, 31, and 32 require reflectivity greater than about 2 dB or between about 2 dB and about 20 dB.

The measurement method matters. Acoustic reflectivity can vary with:

Ultrasound frequency.
Acoustic pressure.
Bubble concentration.
Temperature.
Imaging mode.
Reference standard.
Sample geometry.
Measurement timing.

The terms "about 2 dB" and "about 20 dB" introduce potential claim-construction issues. A competitor’s product could require testing against the patent’s disclosed method rather than relying on a product label or general acoustic-performance data.

How does US Patent 5,769,080 compare with modern ultrasound contrast agents?

Modern products generally use lipid-, protein-, or polymer-coated microbubbles rather than classical aqueous-core liposomes. They also commonly use high-molecular-weight gases with low blood solubility.

Product	Manufacturer	Shell type	Gas	US regulatory status
Optison	GE HealthCare	Human serum albumin	Perflutren	FDA-approved ultrasound contrast agent
Definity	Lantheus Medical Imaging	Lipid-based	Perflutren	FDA-approved ultrasound contrast agent
Lumason	Bracco Diagnostics	Phospholipid	Sulfur hexafluoride	FDA-approved ultrasound contrast agent
SonoVue	Bracco	Phospholipid	Sulfur hexafluoride	Approved outside the US under the SonoVue name
Sonazoid	GE HealthCare	Lipid-based	Perfluorobutane	Approved in selected non-US markets

FDA approvals for Optison, Definity, and Lumason are product-specific and do not establish that the products practice every limitation of US Patent 5,769,080. Their commercial formulations also contain gases and shell materials that are not expressly recited in some dependent claims (FDA, 1997, 2001, 2014).

The expired patent is best viewed as foundational platform prior art, not as a current product-level barrier for these agents.

What is the patent landscape for lipid ultrasound contrast agents?

The patent landscape developed in several technical layers.

Early gas-liposome patents

Early patents focused on:

Gas-filled liposomes.
Vacuum drying and gas instillation.
Liquid-free internal cavities.
Acoustic reflectivity.
Pressure stability.
Targeted liposome contrast agents.

US Patent 5,769,080 sits in this foundational group. Its claim language is broad at the platform level but limited by the historical formulations and gases described in the specification.

Later lipid-microbubble patents

Later patent families focused on:

Perfluorocarbon gases.
Sulfur hexafluoride.
Specific phospholipid mixtures.
PEGylated shells.
Lyophilized or reconstitutable products.
Controlled particle-size distributions.
Activation devices and vial systems.
Tissue-specific targeting.
Therapeutic delivery combined with imaging.

These later patents are more likely to affect current freedom to operate than US Patent 5,769,080.

Commercial product patents

Commercial product estates typically include several layers:

Patent layer	Typical subject matter
Composition	Shell lipids, gas, stabilizers
Manufacturing	Emulsification, lyophilization, gas loading, vial activation
Product profile	Size, concentration, particle distribution
Use	Echocardiography, liver imaging, molecular imaging
Device	Reconstitution and activation systems
Formulation	Buffer, tonicity, storage, container closure
Method of use	Specific imaging protocols or diagnostic indications

An expired platform patent does not prevent a company from asserting later formulation, manufacturing, or method-of-use patents.

What is the FDA and Orange Book status of US Patent 5,769,080?

US Patent 5,769,080 is not a current FDA regulatory exclusivity right. Patent expiration does not itself approve a generic or follow-on contrast agent. A new sponsor still must satisfy the applicable FDA requirements for a drug product, including chemistry, manufacturing, controls, clinical or bridging evidence, labeling, and safety.

The patent is also not a substitute for an Orange Book-listed product patent. The Orange Book lists patents associated with approved drug products and their approved uses. A broad research platform patent issued decades before current ultrasound contrast NDAs would not, by itself, create an active Orange Book barrier.

For current contrast agents, regulatory pathways may include:

A 505(b)(1) NDA for a new contrast agent.
A 505(b)(2) application relying partly on existing findings.
An ANDA only where the product can meet applicable sameness and equivalence requirements.
A supplemental NDA for modifications to an approved product.

No biosimilar pathway applies because these agents are nonbiologic drug products. Biosimilar risk is therefore not the relevant competitive framework. Generic, 505(b)(2), and reformulated contrast-agent competition are more relevant.

Which companies challenged or litigated US Patent 5,769,080?

The patent is expired, and no current Paragraph IV exposure arises from it. A Paragraph IV certification is relevant to an active Orange Book-listed patent, not to a platform patent whose statutory term has ended.

The public commercial record does not establish an active US infringement dispute involving this patent. The principal business significance now lies in historical technology licensing and in the patent families that followed it.

The University of Texas System’s early gas-liposome work was commercially relevant to companies developing ultrasound contrast agents, including companies associated with the development of lipid-encapsulated products. Licensing conclusions must be drawn from recorded assignments, security interests, and license agreements because a patent assignment does not itself prove that a particular commercial product practiced the patent.

How strong was the patent estate, and what is its current strength?

Historical strength

The patent had meaningful historical breadth because it claimed:

The gas-filled liposome structure.
A liquid-free internal cavity.
Injectable contrast agents.
Broad lipid classes.
Multiple gases.
Dry and aqueous storage.
Targeting materials.
Pressure stability.
Acoustic performance.

Its main vulnerability points would have included:

Enablement across the large lipid and gas lists.
Written description support for all combinations.
The meaning of "substantially devoid of liquid."
The meaning of "stability."
The testing conditions for reflectivity.
Whether a product-by-process limitation in claim 1 distinguishes the claimed product.
Anticipation by earlier gas-filled vesicle and microbubble disclosures.

Current strength

The patent has no remaining exclusionary value in the United States because it is expired. Its current value is limited to:

Prior-art relevance.
Technology-history analysis.
Interpretation of later patent claims.
Licensing due diligence for historical portfolios.
Identification of technical concepts that may reappear in later patents.

Patent strength must now be assessed at the family and continuation level. A later patent covering a specific gas, shell formulation, manufacturing process, or clinical use may remain enforceable even though US Patent 5,769,080 does not.

What generic launch risks exist for products related to this patent?

A competitor can generally launch a gas-filled lipid contrast agent without infringing the expired patent. The remaining risk categories are separate:

Risk category	Relevance
Expired US 5,769,080 claims	No current term-based barrier
Later US composition patents	Potentially significant
Manufacturing patents	Significant for lyophilization, gas loading, and reconstitution
Method-of-use patents	Relevant to selected imaging indications
Orange Book patents	Product-specific and must be assessed by NDA
Trade secrets	Potentially important for scale-up and quality control
FDA approval	Independent launch requirement
Non-US patents	Must be assessed jurisdiction by jurisdiction

A launch strategy should not rely on the expiration of US Patent 5,769,080 alone. The highest-risk areas are likely to be proprietary gas-shell combinations, lyophilized presentation, reconstitution systems, and narrow clinical-use claims.

What geographic coverage remains?

US Patent 5,769,080 provides no current US patent protection. Foreign counterparts may have had different expiration dates, prosecution outcomes, or terminal disclaimers, but any remaining rights would require country-specific verification.

For international planning, the relevant review should separate:

United States.
European Patent Convention states.
Japan.
China.
Canada.
Australia.
South Korea.
Countries where SonoVue, Lumason, Definity, Optison, or related products are marketed.

Patent expiration is territorial. The US expiration does not establish expiration in every foreign jurisdiction.

Key Takeaways

US Patent 5,769,080 covers gas-filled liposomes and injectable lipid-encapsulated gas bubbles for ultrasound contrast imaging.
Claims 1, 21, and 41 are the independent claims.
Claim 1 is linked to vacuum drying and gas instillation.
Claim 21 focuses on gas-filled liposomes substantially devoid of internal liquid.
Claim 41 covers injectable contrast agents containing stabilized lipid-encapsulated gas bubbles.
The patent claims DPPC, phospholipids, PEG, selected gases, dry storage, aqueous suspension, targeting materials, reflectivity, shelf-life stability, and pressure stability.
The patent issued June 23, 1998, and expired in 2015.
It creates no current US blocking right and no current Paragraph IV or biosimilar issue.
Modern agents such as Definity, Lumason, and Optison are governed by later product, formulation, manufacturing, and regulatory frameworks.
Current freedom to operate depends on later patent families, not on US Patent 5,769,080 alone.

FAQs About US Patent 5,769,080 and Gas-Filled Liposomes

Does US Patent 5,769,080 cover Definity?

Not by patent expiration alone. Definity is a lipid-encapsulated perflutren microbubble product, but infringement would have required satisfaction of every asserted claim limitation during the patent term. The patent is now expired.

Does the patent cover sulfur hexafluoride liposomes?

The dependent gas claims list nitrogen and several other gases but do not list sulfur hexafluoride. An independent claim could raise a different analysis if all of its non-gas limitations were met, but the patent does not expressly claim sulfur hexafluoride in the cited dependent claims.

Can a company commercialize a dry-stored ultrasound contrast agent now?

The expired patent does not prevent commercialization. A company must still clear later patents and obtain FDA authorization for the specific product and indication.

Are gas-filled liposomes eligible for an ANDA?

Some products may qualify for an ANDA, but the pathway depends on dosage form, composition, route, active ingredient, equivalence standards, and the reference product. A 505(b)(2) NDA may be more appropriate for a materially different contrast agent.

What is the main technical distinction between a liposome and a microbubble?

A conventional liposome generally has an aqueous interior surrounded by one or more lipid bilayers. A gas microbubble has a gas core surrounded by a stabilizing shell. US Patent 5,769,080 uses liposome terminology while claiming structures that overlap technically with gas-filled lipid bubbles.

References

Board of Regents of the University of Texas System. (1998). Gas-filled liposomes and contrast agents comprising same (U.S. Patent No. 5,769,080). United States Patent and Trademark Office.
U.S. Food and Drug Administration. (1997). Optison prescribing information. FDA.
U.S. Food and Drug Administration. (2001). Definity prescribing information. FDA.
U.S. Food and Drug Administration. (2014). Lumason prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
United States Patent and Trademark Office. (2024). Patent Center and patent term information for U.S. Patent No. 5,769,080. USPTO.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0712293	⤷ Start Trial	91325	Luxembourg	⤷ Start Trial
European Patent Office	0712293	⤷ Start Trial	CA 2007 00027	Denmark	⤷ Start Trial
European Patent Office	0712293	⤷ Start Trial	300267	Netherlands	⤷ Start Trial
European Patent Office	0712293	⤷ Start Trial	SPC018/2007	Ireland	⤷ Start Trial
European Patent Office	0712293	⤷ Start Trial	SPC/GB07/031	United Kingdom	⤷ Start Trial
European Patent Office	0712293	⤷ Start Trial	0790017-8	Sweden	⤷ Start Trial
European Patent Office	0712293	⤷ Start Trial	C300267	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,769,080