U.S. Patent 5,558,094: Claims, Scope, Expiration, and Ultrasound Contrast-Agent Patent Landscape

U.S. Patent 5,558,094 covers ultrasound imaging methods using biocompatible fluorinated-gas microbubbles, especially perfluorocarbon agents with persistence substantially greater than air. Its core commercial relevance is the claimed use of dodecafluoropentane and other fluorinated compounds as ultrasound contrast agents. The patent issued on September 17, 1996, and its ordinary 20-year U.S. patent term expired in 2013. It therefore does not create current U.S. exclusionary rights, block generic or competing contrast-agent development, or support a current Paragraph IV challenge.

The claims remain relevant as prior art and as an early patent covering the technical concept underlying several fluorocarbon ultrasound contrast-agent platforms.

What does U.S. Patent 5,558,094 cover?

The patent claims methods of ultrasound imaging in which an animal or human receives microbubbles containing a biocompatible fluorinated chemical, followed by ultrasound scanning.

The claims have four principal coverage categories:

Claim group	Technical subject	Main limitation
Claims 1-12	Broad fluorinated-gas microbubble method	Q coefficient greater than 30
Claim 13	Closed list of fluorinated chemicals	No express Q coefficient limitation
Claim 14	Dispersion and human ultrasound imaging	Q coefficient greater than 30 and free gas microbubbles
Claims 15-16	Dodecafluoropentane imaging methods	Human or organism receives an agent comprising dodecafluoropentane
Claim 17	Listed fluorinated chemicals	Animal imaging; excludes dodecafluoropentane from the Markush group

The patent is method-of-use technology. It does not, based on the supplied claims, claim a specific vial, lipid shell, polymer shell, emulsion architecture, manufacturing process, imaging machine, or diagnostic indication.

What are the independent claims in U.S. Patent 5,558,094?

The independent claims are claims 1, 13, 14, 15, 16, and 17.

Claim 1: Q-coefficient genus

Claim 1 requires:

Introducing a collection of free gas microbubbles into an animal.
Using a biocompatible chemical.
Requiring a Q coefficient greater than 30.
Performing an ultrasound scan.

The Q coefficient is defined as the persistence of microbubbles of the selected gas in aqueous solution divided by the persistence of air microbubbles in that solution.

This is the broadest conceptual claim because it is not limited to a fixed chemical list. A product or method could fall within its literal scope if the accused agent:

contains free gas microbubbles;
uses a biocompatible chemical;
has a measured Q coefficient above 30; and
is administered before ultrasound imaging.

The Q limitation is also the principal technical and legal boundary. A compound with long persistence but no reliable testing protocol may create claim-construction and proof problems.

Claim 13: Closed chemical list

Claim 13 covers ultrasound imaging using microbubbles of a biocompatible chemical selected from:

hexafluoropropylene;
octafluoropropane;
octafluoro-2-butene;
hexafluoro-2-butyne;
hexafluorobuta-1,3-diene;
octafluorocyclobutane;
decafluorobutane; and
dodecafluoropentane.

Unlike claim 1, claim 13 does not expressly require a Q coefficient greater than 30. It is narrower as to chemical identity but potentially broader as to persistence measurement.

The closed-list structure means that a compound outside the listed group would not literally satisfy claim 13, even if it had a Q coefficient above 30. Such a compound could still implicate claim 1 if the other limitations were met.

Claim 14: Human imaging and dispersion limitations

Claim 14 requires:

a dispersion of the biocompatible chemical in aqueous solution;
a Q coefficient greater than 30;
infusion of free gas microbubbles into an organism; and
a human ultrasound scan.

This claim combines composition, administration, persistence, and human-use elements. It is narrower than claim 1 because it requires a prepared aqueous dispersion and specifies human ultrasound imaging.

Claims 15 and 16: Dodecafluoropentane

Claims 15 and 16 specifically cover a biocompatible ultrasound contrast agent comprising dodecafluoropentane.

Claim 15 applies to an organism. Claim 16 applies specifically to a human.

These claims are commercially significant because dodecafluoropentane, also known as perfluoropentane or DDFP, has been investigated as a phase-change and ultrasound contrast-agent material. The claims do not expressly require that DDFP be present as free gas microbubbles, nor do they require a specific carrier, shell, emulsion, particle size, dose, or diagnostic application.

The phrase “comprising dodecafluoropentane” is open-ended. An agent containing DDFP plus lipids, surfactants, polymers, excipients, or other gases could theoretically satisfy the composition element, subject to the remaining claim requirements and applicable claim-construction principles.

Claim 17: Listed chemicals without dodecafluoropentane

Claim 17 covers animal ultrasound imaging using a member of a listed group that includes the compounds in claim 13 except dodecafluoropentane.

The claim text supplied contains “octofluoro-2-butene,” while claim 13 uses “octafluoro-2-butene.” That discrepancy may affect interpretation, correction, or prosecution-history analysis. It should be assessed against the issued patent, certificate of correction, prosecution file, and any judicial construction before relying on the exact chemical scope.

What chemicals are covered by the patent?

The patent’s chemical coverage centers on fluorinated gases and perfluorocarbons.

Chemical	Claim coverage in supplied claims	Commercial relevance
Hexafluoropropylene	Claims 2, 13, 17	Fluorinated-gas candidate
Octafluoropropane	Claims 3, 13, 17	Perfluoropropane; related to perflutren technology
Hexafluoroethane	Claim 4	Listed species under claim 1
Octafluoro-2-butene	Claims 5, 13, 17	Listed fluorinated compound
Hexafluoro-2-butyne	Claims 6, 13, 17	Listed fluorinated compound
Hexafluorobuta-1,3-diene	Claims 7, 13, 17	Listed fluorinated compound
Octafluorocyclobutane	Claims 8, 13, 17	Cyclic fluorocarbon
Decafluorobutane	Claims 9, 13, 17	Related to perfluorobutane contrast agents
Dodecafluoropentane	Claims 10, 13, 15, 16	DDFP; central commercial species

Claims 11 and 12 broaden claim 1 to fluorine-containing chemicals and perfluorocarbons, respectively. Because both depend on claim 1, the Q coefficient above 30 and the other claim 1 limitations remain applicable.

How broad is the patent’s claim scope?

The strongest scope is concentrated in the combination of:

ultrasound imaging;
administered microbubbles;
fluorinated or perfluorocarbon gas;
biocompatibility; and
extended persistence relative to air.

The claims do not cover every ultrasound contrast agent. They do not expressly reach:

sulfur hexafluoride agents unless the compound also satisfies a broader claim limitation;
nonmicrobubble imaging agents;
diagnostic uses without the claimed administration and scanning steps;
manufacturing of contrast-agent formulations;
ultrasound hardware;
image-processing algorithms; or
formulations that do not contain a claimed chemical.

Claim 1 is potentially vulnerable to indefiniteness or enablement arguments because “persistence,” “aqueous solution,” “collection,” and “biocompatible” may require technical definitions. The Q coefficient also depends on test conditions, including temperature, solution composition, bubble size, gas concentration, agitation, and endpoint measurement.

Claims 13 and 15-17 avoid some Q-measurement disputes by identifying chemicals directly. They remain exposed to prior-art, written-description, enablement, and claim-construction challenges.

When did U.S. Patent 5,558,094 lose exclusivity?

The patent’s ordinary U.S. term expired in 2013, calculated under the 20-year term applicable to modern utility patents from the relevant nonprovisional filing date. The patent issued on September 17, 1996.

Event	Date or status
Patent issued	September 17, 1996
Patent type	U.S. utility patent
Technology	Fluorinated-gas ultrasound imaging
Ordinary term	Expired in 2013
Current enforceability	No current enforceable patent term
Current Orange Book barrier	None created by this expired patent
Current Paragraph IV relevance	No live challenge required against an expired patent

The patent’s expiration means that a current manufacturer does not need a license from the patent owner to practice the claimed imaging methods in the United States. The patent can still be cited against later applications as prior art where legally relevant.

What is the Orange Book status of U.S. Patent 5,558,094?

Patent 5,558,094 is not a current Orange Book exclusivity barrier. Orange Book listing is product-specific and depends on patents submitted for an approved drug product. A historical patent may have been relevant to an approved contrast agent without creating a current listing or enforceable term.

The patent claims methods involving fluorinated microbubbles rather than a specific approved drug product, dosage form, or labeled indication. Its expiration eliminates any current patent-based delay to approval under the Hatch-Waxman framework.

A generic or follow-on applicant today would not need to file a Paragraph IV certification against this patent as a live blocking right. If the patent appeared in historical product records, the practical consequence would still be limited because the patent term has ended.

Which commercial ultrasound contrast agents overlap technically?

The patent’s technical field overlaps with several ultrasound contrast-agent platforms, although technical overlap does not establish infringement or patent invalidity.

Product or platform	Active gas or agent	Company association	Relationship to the patent
Definity	Perflutren lipid microspheres	Lantheus Medical Imaging	Technically related to perfluorocarbon microbubble imaging
Optison	Perflutren protein-type microspheres	GE HealthCare	Uses a fluorinated gas microbubble platform
Lumason/SonoVue	Sulfur hexafluoride lipid microspheres	Bracco	Ultrasound microbubble platform, but not a listed perfluorocarbon
Sonazoid	Perfluorobutane lipid microspheres	GE HealthCare	Directly relevant to perfluorobutane technology
EchoGen and DDFP programs	Dodecafluoropentane or related formulation	Historical development programs	Closest overlap with claims 10, 13, 15, and 16
Perflexane/Imagent programs	Perfluorocarbon-based agent	Historical development programs	Related fluorocarbon microbubble technology

The closest claim-level overlap is with DDFP products and perfluorobutane products. Perflutren products are technically related to the patent’s fluorocarbon-gas concept, but product-specific infringement would depend on the exact gas, formulation, administration method, and claim construction.

What formulation patents are outside the scope of this patent?

Patent 5,558,094 does not, based on the supplied claims, claim the following formulation features:

lipid monolayers or bilayers;
albumin or protein shells;
polymeric microspheres;
surfactant-stabilized emulsions;
freeze-dried or lyophilized dosage forms;
reconstitution systems;
particle-size distributions;
shell thickness;
targeting ligands;
stabilizers and cryoprotectants;
specific vial or syringe configurations; or
manufacturing parameters.

Those features may be protected by separate formulation, composition, manufacturing, or device patents. A product can therefore avoid the expired method claims only to the extent it also avoids other unexpired patents in the relevant patent family or commercial platform.

What generic entry risks exist?

There is no current infringement risk from U.S. Patent 5,558,094 itself because the patent term has expired. Current risk would arise from separate patents covering:

a specific approved contrast-agent formulation;
a lipid or protein shell;
a reconstitution or delivery system;
a manufacturing process;
a diagnostic indication;
a dose or administration protocol;
a phase-change nanoparticle architecture; or
a particular imaging application.

For a DDFP product, the expired patent removes an early method-of-use barrier. The remaining risks would be concentrated in formulation stability, particle engineering, phase-transition control, manufacturing scale-up, regulatory data exclusivity, and later-filed platform patents.

For a perfluorobutane product, claim 17 is historically relevant, but its expiration means that current freedom to operate depends on later patents rather than this patent.

Were there Paragraph IV challenges or litigation involving this patent?

The supplied information does not establish a specific Paragraph IV filing, settlement agreement, or reported litigation involving U.S. Patent 5,558,094. Because the patent expired in 2013, it does not support a current Paragraph IV dispute.

Historical litigation analysis would need to distinguish:

litigation involving the patent itself;
litigation involving related continuation or divisional patents;
litigation involving a commercial DDFP or perfluorobutane product;
Hatch-Waxman cases against approved contrast-agent products; and
licensing or ownership disputes involving the underlying fluorocarbon technology.

An expired patent may have influenced licensing negotiations before 2013, but it no longer provides an enforceable U.S. exclusion right.

How strong is the patent estate for modern ultrasound contrast agents?

The patent was strategically broad when issued because it claimed the therapeutic use of persistent fluorinated microbubbles rather than a single commercial formulation. Its current strength is historical, not exclusionary.

Factor	Assessment
Chemical breadth	Broad under claim 1; narrower in closed-list claims
Formulation coverage	Limited in the supplied claims
DDFP coverage	Direct under claims 10, 13, 15, and 16
Perfluorobutane relevance	Direct historical relevance under claims 9, 13, and 17
Q-coefficient limitation	Technically important but potentially difficult to measure
Human-use coverage	Direct under claims 14 and 16
Current enforceability	None after expiration
Current licensing leverage	None based on this patent alone
Prior-art value	Significant for fluorinated microbubble imaging

Key Takeaways

U.S. Patent 5,558,094 claims ultrasound imaging using persistent, biocompatible fluorinated-gas microbubbles.
Claim 1 uses a Q coefficient greater than 30 as the principal functional limitation.
Claims 13 and 17 use closed chemical lists.
Claims 15 and 16 directly target dodecafluoropentane-containing contrast agents.
The patent does not expressly claim lipid shells, protein shells, manufacturing methods, or specific commercial vial designs.
The patent’s ordinary term expired in 2013.
It is not a current Orange Book or Paragraph IV barrier.
The closest technical overlap is with DDFP and perfluorobutane contrast-agent platforms.
Current commercial freedom-to-operate risk depends on later formulation, manufacturing, delivery, indication, and device patents.

FAQs

Does U.S. Patent 5,558,094 cover Definity?

It is technically related to Definity because Definity uses perflutren microbubbles, but the patent’s current legal effect is eliminated by expiration. Product-specific overlap would also depend on the exact issued claims and the formulation and administration facts.

Does the patent cover sulfur hexafluoride contrast agents such as Lumason?

The supplied claims do not expressly list sulfur hexafluoride. Claims 11 and 12 depend on claim 1 and require the Q coefficient, biocompatibility, free gas microbubbles, and other limitations. The patent is therefore not a categorical patent on sulfur hexafluoride products.

Is dodecafluoropentane the same as perfluoropentane?

Yes. Dodecafluoropentane is commonly referred to as perfluoropentane or DDFP. Claims 10, 13, 15, and 16 expressly identify that chemical.

Can a company practice the claimed ultrasound method without a license today?

Yes, the U.S. patent term expired in 2013. Separate later patents may still affect a particular formulation, manufacturing process, delivery system, or diagnostic indication.

Does patent expiration eliminate FDA approval requirements?

No. Patent expiration removes the patent barrier but does not eliminate FDA requirements for safety, effectiveness, manufacturing controls, labeling, clinical evidence, or product-specific regulatory review.

References

United States Patent and Trademark Office. (1996). U.S. Patent No. 5,558,094, Ultrasound imaging using microbubbles of a fluorinated gas. https://patents.google.com/patent/US5558094
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (n.d.). Definity prescribing information. Lantheus Medical Imaging. https://www.accessdata.fda.gov/
U.S. Food and Drug Administration. (n.d.). Optison prescribing information. GE HealthCare. https://www.accessdata.fda.gov/
U.S. Food and Drug Administration. (n.d.). Lumason prescribing information. Bracco Diagnostics. https://www.accessdata.fda.gov/
U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov/

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	191346	⤷ Start Trial
Australia	2550392	⤷ Start Trial
Australia	3995997	⤷ Start Trial
Australia	679428	⤷ Start Trial
Brazil	1100167	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,558,094

Summary for Patent: 5,558,094