United States Drug Patent 5,366,722: Claim Scope, Validity, Expiration, and Patent Landscape

U.S. Patent No. 5,366,722 covers aqueous, nonionic iodinated contrast media containing a narrowly defined sodium concentration, with particular utility in cardiac imaging. The patent issued on November 22, 1994, and its U.S. term expired in November 2011 under the pre-Uruguay Round patent-term rules. It does not currently create an enforceable barrier to generic or competing contrast-media products.

The claim text supplied contains a material defect: claim 1 states a sodium concentration "from 26 up to 26 mM," while dependent claim 2 recites 27 to 30 mM. The original issued patent should control any legal analysis. On the supplied wording alone, claim 1 contains an empty numerical range, making the dependency of claim 2 internally inconsistent.

What does U.S. Patent 5,366,722 protect?

The patent protects a contrast medium defined by a combination of formulation and functional limitations:

A physiologically tolerable aqueous carrier.
A nonionic contrast agent.
A sodium ion concentration beginning at approximately 26 mM.
A claimed balance of red-blood-cell and cardiac effects.
Optional iodinated contrast agents, cations, and reduced osmolality.
Use of the medium for cardiac imaging.

The patent does not broadly claim every nonionic contrast agent, every iodinated contrast agent, or every low-osmolality contrast formulation. The central technical limitation is the sodium concentration in the carrier medium.

Claim-by-claim scope

Claim	Subject matter	Practical scope
1	Nonionic contrast medium with specified sodium concentration and physiological-effect limitations	Independent composition claim; numerical defect in supplied text
2	Claim 1 medium with sodium concentration of 27 to 30 mM	Narrow preferred sodium range
3	Claim 1 medium using a ratio-3 or ratio-6 iodinated X-ray contrast agent	Covers monomeric and dimeric iodinated agents
4	Specific agents, including metrizamide, iopromide, iopentol, iopamidol, iohexol, ioversol, iotrolan, and iodixanol	Species-level limitation
5	Contrast agent concentration of at least 100 mg iodine/mL	Commercially relevant diagnostic concentrations
6	Osmolality below 1 osm/kg water	Low-osmolality formulation limitation
7	Additional physiologically tolerable cations	Permits cation-containing formulations
8	Cardiac imaging method using the claimed medium	Method-of-use claim
9	Iodinated X-ray contrast agent	Broader than claims 3 and 4
10	Cations selected from chloride, phosphate, hydrogen carbonate, or mixtures	Specific excipient and electrolyte limitation

The supplied text uses "loversol." The recognized contrast agent is ioversol. This is likely a transcription or OCR error, but the issued patent text should be checked before relying on the exact wording.

What is the sodium-concentration limitation in patent 5,366,722?

The sodium limitation is the principal differentiator. Claim 2 expressly identifies 27 to 30 mM as the preferred range. That range is materially narrower than ordinary formulation claims that recite only osmolality, iodine concentration, pH, or active-agent identity.

The quoted claim 1 cannot be interpreted literally as written because "from 26 up to 26 mM" describes only a single point, while claim 2 depends on it and covers 27 to 30 mM. The most commercially plausible reconstruction is that the upper endpoint in claim 1 was above 30 mM, potentially 32 mM, but that endpoint should not be treated as authoritative without the issued patent image or certified prosecution record.

For infringement purposes, a formulation would ordinarily need to be tested for sodium concentration as formulated and, depending on the legal construction, against the claimed concentration range. Sodium introduced through sodium chloride, sodium phosphate, sodium bicarbonate, or another sodium-containing component could be relevant.

How do the functional limitations affect claim scope?

Claim 1 states that the sodium concentration achieves a "beneficial balance" involving:

reduced red blood cell aggregate formation;
reduced echinocyte formation;
increased rouleaux formation;
reduced contractile-force reduction; and
reduced ventricular fibrillation.

These limitations create several legal and technical issues.

First, the claim does not state quantitative thresholds for any of the biological effects. It does not define how much aggregation, echinocyte formation, rouleaux formation, contractile-force reduction, or ventricular fibrillation must be reduced or increased.

Second, the phrase "beneficial balance" is evaluative rather than a conventional compositional parameter. A court could treat the phrase as a statement of intended result, particularly if the specification does not provide objective testing criteria. It could also be treated as limiting if the specification and prosecution history establish that the claimed sodium range was selected because it produced measurable effects.

Third, the functional clause may create enablement and indefiniteness questions. A claim covering a broad set of nonionic agents and formulations, but requiring a balance of several biological outcomes without defined testing methods, can be difficult to enforce consistently.

The numerical sodium limitation is therefore likely to be more commercially useful than the biological-result language. The functional language may narrow the claim in litigation, but its lack of objective boundaries may also weaken enforceability.

What contrast agents are covered?

The patent expressly identifies a broad group of nonionic iodinated agents. The listed compounds include:

metrizamide;
iopromide;
iopentol;
iopamidol;
iohexol;
ioversol;
iotrolan; and
iodixanol.

The "ratio 3 or 6" language refers to the iodine-to-molecule architecture used in iodinated contrast media. Ratio-3 agents are generally monomeric compounds containing three iodine atoms per molecule. Ratio-6 agents are generally dimeric compounds containing six iodine atoms per molecule.

The claim does not require a particular branded product. It reaches a formulation if the product contains a claimed agent and satisfies the applicable sodium, concentration, osmolality, and cation limitations.

What formulations are protected?

The formulation claims are strongest where several limitations overlap:

nonionic iodinated agent;
at least 100 mg iodine/mL;
sodium concentration of 27 to 30 mM;
osmolality below 1 osm/kg water;
physiologically tolerable aqueous carrier; and
optional chloride, phosphate, or hydrogen carbonate salts.

The patent does not appear to claim a specific pH, buffer system, container, syringe, manufacturing process, impurity profile, or storage condition in the claims supplied. It also does not claim the active contrast molecules themselves as chemical compounds.

That distinction matters. A manufacturer could have faced risk under the patent even if it used a known contrast agent, but only if its finished formulation fell within the claimed electrolyte and physical-property ranges.

Does patent 5,366,722 cover cardiac imaging?

Yes. Claim 8 covers a method of cardiac imaging that includes:

administering the claimed contrast medium to a human or non-human animal; and
generating an image of at least part of the cardiac region.

The method claim is narrower in use than the composition claims. It is directed to cardiac imaging rather than general angiography, computed tomography, urography, or other diagnostic applications.

A product could potentially fall within a composition claim without being used for cardiac imaging. Conversely, a cardiac-imaging use would need to involve a formulation meeting the composition limitations.

When did U.S. Patent 5,366,722 expire?

U.S. Patent 5,366,722 issued on November 22, 1994. Because it was issued before the modern 20-year-from-earliest-effective-filing-date regime applied to most later-filed U.S. applications, its ordinary term was governed by the pre-1995 rule of 17 years from issuance. Its term therefore expired in November 2011, absent an unusual term adjustment or terminal-disclaimer issue.

Event	Date or status
U.S. patent issued	November 22, 1994
Statutory term basis	Generally 17 years from issuance for qualifying pre-June 8, 1995 applications
Expected ordinary expiration	November 22, 2011
Current enforceability	Expired
Current Paragraph IV relevance	None for this expired patent
Current biosimilar relevance	None; the patent covers small-molecule contrast formulations, not a biologic

Patent expiration removes the right to exclude others, but it does not eliminate the historical relevance of the patent to prior settlements, licensing arrangements, or legacy product strategies.

What is the Orange Book status of U.S. Patent 5,366,722?

Patent 5,366,722 should not be treated as a current Orange Book barrier. The Orange Book records patents and exclusivity associated with approved drug products, but listing status is product-specific and does not determine whether a patent was ever broadly enforceable against all contrast agents.

The patent is expired. An expired patent cannot support a current Paragraph IV infringement action or block approval of an otherwise approvable generic product. Current Orange Book analysis must be performed against the specific reference-listed drug and its active patent listings, not against the existence of this historic formulation patent alone. FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations remains the controlling source for current Orange Book listings and therapeutic-equivalence determinations [2].

Are there Paragraph IV challenges or settlements involving this patent?

No current Paragraph IV challenge can create a launch risk under patent 5,366,722 because the patent expired in 2011. Any historical Paragraph IV notice, litigation, or settlement would have had to occur during the patent’s enforceable term.

The patent number alone does not establish that a Paragraph IV notice, litigation case, license, or settlement existed. Such events must be confirmed through the FDA patent listing record, federal court dockets, SEC filings, or the patent’s prosecution and assignment history.

For present commercial planning, the relevant conclusion is direct: patent 5,366,722 cannot delay approval or launch of a generic contrast product today.

How strong was the patent estate?

The patent was technically focused but commercially broad during its term.

Strengths

It covered multiple established nonionic iodinated agents.
It focused on a measurable formulation parameter, sodium concentration.
It included both composition and cardiac-imaging method claims.
The 27 to 30 mM range was commercially plausible for low-osmolality contrast formulations.
It could apply to products using different active agents if the electrolyte profile matched.

Weaknesses

The supplied claim 1 contains an internally inconsistent numerical range.
The "beneficial balance" language lacks clear quantitative endpoints.
The claims do not cover the underlying contrast-agent molecules.
The patent does not appear, from the claims supplied, to cover manufacturing processes or device systems.
The patent has been expired for more than a decade.
Formulation differences outside the sodium range could avoid the core claim.

Its historical strength was therefore greatest against products using a matching electrolyte profile. Its current legal strength is zero because the patent term has ended.

Which companies and products were potentially affected?

The patent named agents associated with several major contrast-media suppliers and originators, including products based on iohexol, iopamidol, iopromide, ioversol, iotrolan, and iodixanol. Relevant commercial companies in the broader contrast-media market have included GE HealthCare, Bracco, Bayer, Guerbet, and Mallinckrodt, depending on product, market, and time period.

The patent did not necessarily cover every product sold by those companies. Coverage would depend on the product’s exact sodium concentration, osmolality, iodine concentration, cation composition, and use.

Current competitive exposure is driven by:

active patents on particular products;
regulatory exclusivity;
manufacturing scale;
supply contracts;
injectable-product quality requirements;
contrast-agent registration status; and
clinical adoption.

Patent 5,366,722 is no longer a meaningful source of revenue protection for any product owner.

What manufacturing and geographic barriers remain?

The U.S. patent is territorial. Its expiration does not determine the status of corresponding foreign patents. A related European, Japanese, Canadian, or other national patent could have had different filing dates, claim scope, term adjustments, or expiration dates.

The patent claims supplied do not include a manufacturing process. A manufacturer therefore would not face a process barrier under these claims if it could make a formulation outside the claimed composition limitations.

Manufacturing barriers may still exist independently of this patent. Iodinated contrast media are sterile injectable products requiring validated synthesis, impurity control, sterilization, container-closure systems, analytical release methods, and FDA-compliant manufacturing. Those barriers are regulatory and operational rather than rights created by U.S. Patent 5,366,722.

What generic launch risks exist today?

The patent creates no current generic launch delay. A modern entrant should still assess:

patents listed for the applicable reference-listed drug;
formulation patents filed after patent 5,366,722;
method-of-use patents;
manufacturing and purification patents;
device or injector patents;
FDA product-specific requirements;
sterile injectable manufacturing capacity; and
foreign rights in target markets.

The historical patent may remain relevant as prior art against later applications claiming similar sodium-controlled contrast formulations. It is also relevant to freedom-to-operate analysis because expired patents can establish technical disclosure and affect the validity of later patent claims.

Key Takeaways

U.S. Patent 5,366,722 claims nonionic iodinated contrast media with a narrowly defined sodium concentration and related cardiac tolerability characteristics.
Claim 2 identifies 27 to 30 mM as the preferred sodium range.
The supplied version of claim 1 is defective because "from 26 up to 26 mM" conflicts with claim 2.
The patent covers formulations, not the underlying contrast-agent molecules.
Claims 3 through 5 extend coverage to multiple ratio-3 and ratio-6 iodinated agents at commercial iodine concentrations.
Claim 8 covers cardiac imaging using the claimed formulation.
The patent issued on November 22, 1994, and its ordinary U.S. term expired in November 2011.
It presents no current Orange Book, Paragraph IV, biosimilar, or generic-launch barrier.
Any current risk must come from later patents, product-specific listings, regulatory requirements, or manufacturing constraints.

FAQs About U.S. Patent 5,366,722

Does U.S. Patent 5,366,722 cover iodixanol?

Yes. Claim 4 expressly identifies iodixanol, but only within a formulation satisfying the other applicable limitations, including the sodium concentration and any dependent-claim requirements.

Can a company launch a contrast medium with 26 mM sodium?

The supplied claim text is defective because claim 1 says "from 26 up to 26 mM." The original issued claim must be reviewed before drawing a historical infringement conclusion. In any event, the U.S. patent expired in 2011.

Is patent 5,366,722 a biologic patent?

No. It concerns small-molecule, nonionic iodinated X-ray contrast media. Biosimilar regulations do not apply to the patent’s claimed subject matter.

Does the patent cover CT contrast agents outside cardiac imaging?

The composition claims may reach a qualifying formulation regardless of its use. Claim 8 is specifically directed to cardiac imaging, while the supplied composition claims are not limited to cardiac imaging unless the functional language is construed that way.

Can the expired patent block a new FDA approval?

No. An expired patent cannot independently block approval or commercial launch. FDA approval and current patent risk depend on the applicable reference-listed drug, current patent listings, exclusivity, and any later patents.

References

United States Patent and Trademark Office. (1994). U.S. Patent No. 5,366,722, Contrast media. https://patents.google.com/patent/US5366722A/en
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section154
U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/hatch-waxman-amendments-questions-and-answers

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	89 06130.3	Mar 17, 1989

PCT Information
PCT Filed	March 09, 1990	PCT Application Number:	PCT/EP90/00393
PCT Publication Date:	October 04, 1990	PCT Publication Number:	WO90/11094

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	123954	⤷ Start Trial
Australia	5185490	⤷ Start Trial
Australia	638235	⤷ Start Trial
Bulgaria	60951	⤷ Start Trial
Canada	2046886	⤷ Start Trial
China	1045528	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,366,722

Summary for Patent: 5,366,722