U.S. Patent 5,527,521: Claim Scope, Expiration, Enforceability, and Contrast-Agent Patent Landscape

U.S. Patent No. 5,527,521 covers aqueous contrast suspensions and diagnostic-imaging kits containing a biocompatible polymer associated with a perfluorocarbon gas to form gas-filled microspheres. The claims target gastrointestinal and body-cavity imaging, broader diagnostic imaging, and methods of administering the suspension before CT or other scanning.

The patent was granted June 18, 1996. Based on the pre-Uruguay Round patent-term regime applicable to the filing, its ordinary 17-year term expired June 18, 2013, absent an unusual term adjustment or extension. The patent therefore does not present a current U.S. blocking right. Its historical claim scope remains relevant for prior-art, freedom-to-operate, and patent-family analysis. [1]

What technology does U.S. Patent 5,527,521 protect?

The patent protects a formulation architecture with four principal elements:

An aqueous vehicle.
A biocompatible polymer.
A perfluorocarbon gas.
A thickening or suspending agent.

The core technical requirement is that the polymer “associates” with the perfluorocarbon gas to form one or more gas-filled microspheres. The formulation may also contain simethicone or another antifoaming, antiflatulent, antacid, or surfactant component.

The patent is directed primarily to an oral or cavity-administered contrast medium for computed tomography, but several claims extend to diagnostic imaging without limiting the modality to CT.

What is the central inventive concept?

The central concept is a polymer-associated gas microsphere dispersed in a thickened aqueous suspension. The microspheres are intended to create an imaging contrast interface, particularly in the gastrointestinal tract or other body cavities.

The claims do not require:

A particular microsphere diameter.
A defined gas volume fraction.
A specified polymer molecular weight.
A prescribed polymer-to-gas ratio.
A particular manufacturing process.
A specific CT scanning protocol.
A defined concentration of methylcellulose or simethicone.

This drafting approach gives the independent claims broad conceptual coverage but leaves several claim terms dependent on specification context and ordinary technical meaning.

How many independent claims does Patent 5,527,521 contain?

The patent contains nine apparent independent claims:

Claim	Category	Primary subject matter
1	Composition	CT contrast medium for gastrointestinal or body-cavity imaging
20	Composition	Contrast medium for diagnostic imaging
39	Composition	Aqueous suspension
58	Kit	Kit for CT imaging
59	Kit	Kit for diagnostic imaging
60	Method	CT imaging of gastrointestinal or body-cavity regions
61	Method	Diagnostic imaging of a patient
62	Method	Diagnosing diseased tissue using CT
63	Method	Diagnosing diseased tissue using diagnostic imaging

Claims 1, 20, and 39 establish three substantially overlapping composition claim groups. Claims 58 and 59 cover kits. Claims 60 through 63 cover administration and imaging methods.

The remaining claims are dependent claims that narrow the polymer, gas, suspending agent, additive, or imaging use.

What polymers are covered by the claims?

The polymer coverage is unusually broad and appears in two principal forms.

Monomer-based Markush coverage

Claims 2, 3, 21, 22, 40, and 41 identify polymers or copolymers prepared from a long list of monomers. The list includes:

Acrylic acid and methacrylic acid.
Acrylamide and substituted acrylamides.
Ethylene oxide and ethylene glycol.
Lactic acid and glycolic acid.
Epsilon-caprolactone.
Vinyl pyrrolidone.
Styrene and substituted styrenes.
Siloxane and dimethylsiloxane.
Cyanoacrylate.
Vinyl acetate.
Acrylonitrile.
Methacrylate derivatives.
Crosslinking monomers such as divinylbenzene and methylenebisacrylamide.

These claims attempt to capture a large polymer universe rather than one defined commercial polymer product.

Named-polymer coverage

Claims 4, 23, and 42 identify particular polymer classes, including:

Polyacrylic acid.
Polyethyleneimine.
Polymethacrylic acid.
Polymethyl methacrylate.
Polysiloxane.
Polydimethylsiloxane.
Polylactic acid.
Poly-epsilon-caprolactone.
Epoxy resin.
Polyethylene oxide.
Polyethylene glycol.
Polyamide.
Polyvinylidene-polyacrylonitrile.
Polyvinylidene-polyacrylonitrile-polymethyl methacrylate.
Polystyrene-polyacrylonitrile.

Claims 5 and 24 narrow the polymer to a polyvinylidene-polyacrylonitrile copolymer. Claims 6 and 25 cover a polyoxypropylene-polyoxyethylene copolymer.

The most commercially recognizable formulation-specific polymer limitation is the polyoxypropylene-polyoxyethylene copolymer recited in claims 19, 38, and 57.

What perfluorocarbon gases are covered?

Claims 7, 26, and 45 define a broad class of perfluorocarbons having:

One to approximately nine carbon atoms.
Approximately four to 20 fluorine atoms.

Claims 8, 27, and 46 narrow that class to compounds having fewer than approximately four carbon atoms and fewer than approximately 10 fluorine atoms.

The specifically claimed gases are:

Claims	Gas	Formula
9, 28, 47	Perfluoropropane	C3F8
10, 29, 48	Perfluorobutane	C4F10
11, 30, 49	Perfluoropentane	C5F12

C3F8 and C4F10 are conventionally gaseous perfluorocarbons under ordinary conditions. C5F12 has a boiling point near ambient temperature and may require handling conditions that support gas formation or microsphere generation.

The gas claims are not limited to a single isomer, particle size, encapsulation mechanism, or gas-loading process.

What is the narrowest formulation claimed?

Claims 19, 38, and 57 recite the most specific formulation combination:

Polyoxypropylene-polyoxyethylene copolymer.
C5F12.
Methylcellulose.
Simethicone.

This combination is important for infringement analysis because it provides a concrete formulation target within the otherwise broad genus claims.

A product using all four components could fall within the literal language of these claims if it also satisfies the aqueous-suspension and gas-filled-microsphere requirements. A product using a different polymer, gas, or suspending agent would not literally meet this narrow species claim but could remain relevant to the broader independent claims.

What suspending agents and additives are protected?

Claims 12, 31, and 50 cover a broad suspending-agent genus that includes:

Alginates.
Xanthan gum.
Guar.
Pectin.
Tragacanth.
Gum arabic.
Casein.
Gelatin.
Cellulose.
Carboxymethylcellulose.
Methylcellulose.
Methylhydroxycellulose.
Bentonite.
Colloidal silicic acid.
Carrageenin.
Polyethylene glycol.
Polypropylene glycol.
Polyvinylpyrrolidone.

Claims 13, 32, and 51 narrow the field to cellulose derivatives. Claims 14, 33, and 52 select methylcellulose.

Claims 15, 34, and 53 add antacids, antiflatulents, antifoaming agents, or surfactants. Claims 16 through 18 and 35 through 37 specify polymeric siloxane, dimethylpolysiloxane, and simethicone.

Simethicone is therefore a separately claimed optional component and part of the narrow formulation claims.

How broad are the composition claims?

The three main composition claims have overlapping but distinct scopes.

Claim	Required use or format	Practical scope
1	CT imaging of gastrointestinal region or body cavities	Broad CT-focused formulation claim
20	Diagnostic imaging	Broader imaging claim, not expressly limited to CT
39	Aqueous suspension	Broadest formulation-oriented claim, with no express imaging-use limitation

Claim 39 is particularly important because it does not expressly require that the suspension be labeled or used as a contrast medium. It requires the aqueous suspension, polymer, perfluorocarbon gas, thickening or suspending agent, and formation of gas-filled microspheres.

That claim could potentially reach a formulation before administration. Its scope would still depend on construction of “associates” and “gas-filled microspheres.”

What do the method claims cover?

Claims 60 through 63 require:

Administering the claimed aqueous suspension to a patient.
Scanning the patient.
Obtaining visible images.

Claims 60 and 62 focus on the gastrointestinal region, body cavities, and CT. Claims 61 and 63 use broader “diagnostic imaging” language.

The method claims do not identify:

A particular administration route.
A required dose.
A minimum image-enhancement threshold.
A specific disease.
A specific CT energy level or reconstruction method.

Claims 62 and 63 refer to diagnosing diseased tissue. That language may raise divided-infringement and inducement issues because infringement would depend on how the product is administered, promoted, and used by healthcare providers.

What do the kit claims cover?

Claims 58 and 59 cover kits containing the polymer, perfluorocarbon gas, and thickening or suspending agent. The claims do not specify:

A vial or container configuration.
Separate versus premixed components.
Packaging materials.
Instructions for use.
Dosage volumes.
A shelf-life period.
A reconstitution device.

The claim language says the components form gas-filled microspheres “in said suspension,” which creates a potential issue for kits in which the components are supplied separately and mixed only immediately before administration.

A kit containing a preformed suspension is the clearest literal target. A dry kit requiring reconstitution could present a more complicated claim-construction issue.

What claim defects or drafting issues affect enforceability?

Several transcription and dependency issues appear in the supplied claim text.

Typographical errors

The text includes apparent OCR or transcription errors such as:

“salad perfluorocarbon gas” instead of “said perfluorocarbon gas.”
“poller” instead of “polymer.”
“perftuorocarbon” instead of “perfluorocarbon.”
“Ant aqueous suspension” instead of “An aqueous suspension.”
“bentonire” instead of “bentonite.”
“provided-an image” instead of “providing an image.”

The issued patent and prosecution history, rather than a transcription, control the legal text. [1]

Potential dependency error

Claim 42 is supplied as depending on claim 34, although its wording concerns a polymer limitation and appears structurally inconsistent with the claim sequence. That may be a transcription error or an issue in the issued claim set. The official patent document controls.

Functional language

“Associates with” is a broad functional phrase. It does not state whether the polymer must form:

A continuous shell.
A matrix.
An interfacial film.
A covalent association.
A physically adsorbed coating.
A stable microsphere under storage and administration.

This term may create claim-construction disputes. A competitor could argue that its gas-containing particles are stabilized by a lipid, protein, surfactant, or inorganic shell rather than by the claimed polymer.

When did U.S. Patent 5,527,521 lose exclusivity?

The patent’s ordinary term expired June 18, 2013, 17 years after its June 18, 1996 grant date. The patent was issued under the pre-1995 application-term framework, under which the term generally ran 17 years from grant rather than 20 years from the earliest effective nonprovisional filing date. [1]

The expired patent has no current enforceable exclusionary term. A patent-term adjustment or extension could alter the calculation, but no such extension is reflected in the ordinary grant-date term analysis.

Exclusivity timeline

Event	Date
Patent grant	June 18, 1996
Ordinary 17-year expiration	June 18, 2013
Current status for ordinary enforcement	Expired
Current Orange Book exclusivity relevance	None identified

Patent expiration does not erase the patent as prior art. The disclosure and claims remain relevant to novelty, obviousness, written-description, enablement, and freedom-to-operate analyses.

What is the Orange Book status of Patent 5,527,521?

U.S. Patent 5,527,521 is not an effective Orange Book exclusivity right today. The FDA Orange Book lists patents and exclusivity associated with approved drug products, not every patent that has ever covered a pharmaceutical or diagnostic formulation. [2]

The patent’s subject matter also appears directed to a specialized diagnostic contrast suspension rather than a currently marketed FDA-approved product with an active listed patent. There is no current Paragraph IV value after expiration.

An ANDA applicant cannot create a live Paragraph IV dispute against an expired patent. Paragraph IV certifications are relevant to unexpired listed patents covering an approved reference product. [2]

Were there Paragraph IV challenges, litigation, or settlements?

A current Paragraph IV challenge is not commercially relevant because the patent expired in 2013.

The patent number does not, by itself, establish that a Paragraph IV certification, district-court infringement action, Hatch-Waxman settlement, or license agreement existed. Public litigation and assignment records must be read separately from the patent document. The patent’s expired status means any historical dispute would have no continuing exclusionary effect against present-day generic or competing contrast-agent development.

Which companies are most exposed to this patent?

No current commercial company has material U.S. launch exposure to this patent solely because of the patent’s expiration. Historical exposure would have depended on whether a product used the claimed combination of:

An aqueous suspension.
A biocompatible polymer.
A perfluorocarbon gas.
A thickening or suspending agent.
Gas-filled microspheres formed through polymer-gas association.

Potentially relevant commercial categories include:

Product category	Relationship to the patent
Oral CT contrast agents using barium or iodinated materials	Generally outside the claimed perfluorocarbon microsphere architecture
Intravenous ultrasound microbubbles using lipid shells	Often outside the polymer-shell limitation
Protein-shelled perfluorocarbon agents	Potentially outside literal polymer association claims
Polymer-shelled perfluorocarbon agents	Technically closer to the claims
Experimental oral gas-microsphere CT agents	Historically the closest category

Current revenue exposure from this patent is zero as an enforceable U.S. patent right. Historical revenue cannot be calculated from the patent alone.

How does this patent compare with modern ultrasound contrast patents?

The patent overlaps conceptually with the broader contrast-microbubble field but differs from many commercial ultrasound agents in four ways.

Issue	U.S. 5,527,521	Many modern ultrasound agents
Primary imaging target	CT and gastrointestinal imaging	Ultrasound, often intravenous
Shell or stabilizer	Biocompatible polymer	Lipid, protein, or polymer
Gas	Perfluorocarbon	Perfluorocarbon or sulfur hexafluoride
Administration	Oral or body-cavity use is central	Intravenous use is common
Formulation viscosity	Thickening or suspending agent required	Often injectable suspension with different excipients
Current patent status	Expired	Depends on individual product and patent family

FDA-approved ultrasound contrast agents include products such as DEFINITY, OPTISON, and LUMASON. Their approved indications, shell technologies, gases, and administration routes differ from the gastrointestinal CT focus of Patent 5,527,521. [3-5]

This distinction reduces the likelihood that a conventional approved intravenous ultrasound product would have been a direct commercial embodiment of the expired claims.

What geographic coverage does the patent provide?

The patent provides U.S. coverage only. A U.S. patent does not automatically create rights in Europe, Japan, Canada, China, or other jurisdictions.

International protection would require separate national or regional patent applications. The supplied U.S. claims do not establish:

An international application.
A European patent.
Foreign granted claims.
Foreign expiration dates.
Foreign assignments.
Foreign litigation.
Foreign regulatory exclusivity.

A global freedom-to-operate review must therefore analyze the patent family and national records separately.

How strong was the patent estate?

The patent had meaningful breadth at issuance but a limited estate structure.

Strengths

Three overlapping composition claim groups.
Broad polymer Markush language.
Broad perfluorocarbon genus.
Specific claims to C3F8, C4F10, and C5F12.
Specific claims to methylcellulose and simethicone.
Separate kit and method claims.
No express particle-size or concentration limitation.

Weaknesses

The patent is expired.
“Associates with” is functionally broad and potentially ambiguous.
The polymer list is expansive relative to the specific formulation examples.
The claims do not define a clear microsphere architecture.
Kit claims provide limited packaging specificity.
Method claims depend on administration and use behavior.
Several claim-text inconsistencies require reliance on the official issued patent.
The claims may face historical written-description, enablement, anticipation, and obviousness challenges depending on the prior art.

The practical rating is therefore:

Dimension	Assessment
Historical composition breadth	High
Historical species coverage	Moderate to high
Current exclusionary value	None
Design-around difficulty	Moderate
Claim-term certainty	Moderate to low
Relevance as prior art	High within the claimed technical field
Current licensing leverage	None based solely on the expired patent

What generic launch risks exist?

There is no current generic-launch risk from Patent 5,527,521 because the patent has expired.

A current developer could generally commercialize a U.S. product without obtaining a license under this patent. Remaining risks would arise from:

Later patents in the same technology area.
FDA approval requirements.
Product-specific patents not identified by this patent.
Trade-secret manufacturing methods.
Regulatory exclusivity attached to a later approved product.
Foreign patents with later expiration dates.
Third-party patents covering a particular polymer, shell, gas, device, or manufacturing process.

The expired patent may still affect prosecution strategy. A later applicant cannot obtain a valid patent that merely repackages the same disclosed combination without a patentable distinction.

What manufacturing and intellectual-property barriers remain?

The patent does not claim a detailed manufacturing process. It claims the resulting suspension, kit, and use.

The principal technical barriers likely lie outside the expired claim set:

Controlling microsphere size and distribution.
Maintaining gas retention during storage.
Preventing coalescence.
Achieving reproducible viscosity.
Controlling polymer adsorption or association.
Manufacturing under pharmaceutical quality standards.
Demonstrating gastrointestinal safety and tolerability.
Establishing consistent CT attenuation.
Packaging a volatile or near-boiling perfluorocarbon.
Proving batch stability and dose uniformity.

A competitor that uses a different shell chemistry or forms microspheres through a different mechanism may avoid the historical claims while still facing later process or formulation patents.

Key Takeaways

U.S. Patent 5,527,521 covers aqueous polymer-associated perfluorocarbon gas microsphere suspensions.
The claims cover compositions, kits, CT imaging, diagnostic imaging, and disease-detection methods.
The broadest technical elements are the polymer genus, perfluorocarbon genus, and thickening-agent genus.
The narrowest disclosed formulation combines a polyoxypropylene-polyoxyethylene copolymer, C5F12, methylcellulose, and simethicone.
The patent’s ordinary term expired June 18, 2013.
It has no current U.S. blocking or Paragraph IV value.
Conventional lipid- or protein-shelled intravenous ultrasound agents are technically distinct from the claimed gastrointestinal CT formulation architecture.
Current commercial risk must be assessed against later patent families, not this expired patent.
The patent remains relevant as prior art for later polymeric gas-microsphere and diagnostic-contrast applications.

FAQs

Does Patent 5,527,521 cover all perfluorocarbon contrast agents?

No. It requires an aqueous suspension containing a biocompatible polymer, a perfluorocarbon gas, a thickening or suspending agent, and gas-filled microspheres formed through polymer-gas association. Agents using different shell materials or lacking the claimed suspending-agent structure may fall outside the claims.

Does the patent cover barium sulfate oral CT contrast?

Generally no. Conventional barium sulfate contrast does not ordinarily contain polymer-associated perfluorocarbon gas microspheres as required by the claims.

Is C5F12 the only perfluorocarbon gas covered?

No. The claims cover broad perfluorocarbon classes and specifically recite C3F8, C4F10, and C5F12.

Can a company develop a polymeric perfluorocarbon microsphere product without licensing this patent?

Yes, from a U.S. patent-term perspective, because the patent expired in 2013. The developer must still evaluate later patents covering the specific polymer, gas, formulation, manufacturing process, device, or approved indication.

Does expiration eliminate the patent from a freedom-to-operate search?

No. Expiration eliminates current infringement liability under the patent, but the patent remains relevant as prior art and may identify related continuations, foreign counterparts, or later patent families.

References

United States Patent and Trademark Office. (1996). U.S. Patent No. 5,527,521. Washington, DC: U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (2023). DEFINITY (perflutren lipid microsphere) injectable suspension prescribing information. Lantheus Medical Imaging, Inc.
U.S. Food and Drug Administration. (2023). OPTISON (perflutren protein-type A microspheres) injectable suspension prescribing information. GE Healthcare.
U.S. Food and Drug Administration. (2023). LUMASON (sulfur hexafluoride lipid-type A microspheres) for injectable suspension prescribing information. Bracco Diagnostics Inc.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	180794	⤷ Start Trial
Austria	201217	⤷ Start Trial
Australia	1428099	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,527,521