United States Drug Patent 5,349,085: Claim Scope, Iotrolan Patent Landscape, and Generic Entry Risk

US Patent No. 5,349,085 covers the nonionic, dimeric iodinated contrast agent iotrolan, a six-iodine molecule historically associated with Schering AG and the Isovist product family. The quoted claim is a narrow composition-of-matter claim directed to the specific iotrolan molecular architecture. The patent issued on September 20, 1994, and its ordinary pre-URAA term would have expired on September 20, 2011, absent a term adjustment or other unusual term event. The patent no longer creates a live US exclusivity barrier.

What drug does US Patent 5,349,085 protect?

The claimed compound is iotrolan, also known as a nonionic dimeric X-ray contrast medium. Its structure contains:

Two 2,4,6-triiodinated benzene rings.
Two isophthalamide-type carbonyl groups on each aromatic ring.
Four 2,3-dihydroxypropyl substituents.
A central 1,3-diamino-2-hydroxypropane bridge.
Two acetylamino groups connecting the central bridge to the iodinated aromatic units.

The supplied claim is:

1,3-bis(acetylamino)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane.

The claimed molecular identity corresponds to iotrolan, a high-osmolality-reducing, nonionic dimeric contrast agent containing six iodine atoms per molecule. Iotrolan was developed for radiographic and computed-tomography imaging and was marketed in certain jurisdictions under the Isovist name.

What type of patent claim is Claim 1?

Claim 1 is a product-by-structure claim. It does not claim a broad chemical genus, a pharmaceutical composition in general terms, a method of imaging, or a manufacturing process.

Claim elements

Claim element	Scope
Central chain	1,3-diamino-2-hydroxypropane framework
Terminal nitrogen substitution	Both terminal nitrogens are acetylated
Aromatic substituents	Two substituted triiodophenyl groups
Iodination pattern	2,4,6-triiodo substitution on each aromatic ring
Aromatic carbonyl groups	Two 3,5-bis(aminocarbonyl) groups per ring
Side chains	Each amide nitrogen carries a 2,3-dihydroxypropyl group
Overall architecture	A nonionic, six-iodine dimer

The claim requires the complete combination. A compound that contains the same six iodine atoms but uses a different central linker, different acetylation pattern, different side-chain substitution, or different aromatic amide arrangement would generally fall outside the literal wording.

How broad is the patent protection for iotrolan?

The claim is chemically narrow but commercially meaningful. It covers the active molecular entity itself rather than merely a particular formulation, concentration, container, or imaging use.

Likely protected subject matter

The claim reaches the named molecular constitution, including the following core features:

Two identical triiodinated aromatic units.
A central hydroxypropane-derived dimeric linker.
Acetylated bridge nitrogens.
Four dihydroxypropyl substituents.
A nonionic molecular structure.

The claim does not expressly recite a pharmaceutically acceptable salt, hydrate, solvate, polymorph, isotopically labeled form, formulation, or dosage form. Whether a particular solid form or formulation would infringe would depend on whether the claimed molecule is present in the accused product and on the relevant claim-construction principles.

Stereochemistry

The claim contains no stereochemical descriptors. On its face, it is not limited to one enantiomer or one diastereomer. It would therefore be positioned to cover stereoisomeric forms having the claimed constitution, subject to prosecution-history limitations and the ordinary rules governing claim interpretation.

What the claim does not cover

The claim does not expressly cover:

Iotrolan manufacturing methods.
A method of administering iotrolan.
A method of using iotrolan for CT, angiography, urography, or another imaging procedure.
A specific aqueous concentration.
A vial, syringe, kit, or injector.
A broad class of nonionic iodinated contrast agents.
Other dimeric agents lacking the claimed central linker or acetylamino arrangement.

When did US Patent 5,349,085 lose exclusivity?

The patent issued on September 20, 1994. For a pre-URAA US patent, the ordinary term was generally 17 years from grant. On that basis, the expected expiration date was September 20, 2011.

Event	Date or status
US patent	5,349,085
Issue date	September 20, 1994
Ordinary statutory term	17 years from issue
Expected expiration	September 20, 2011
Current status	Expired by lapse of ordinary patent term
Current composition-of-matter exclusivity	None under this patent

The relevant expiration date is the patent term, not the date on which a product may have ceased commercial distribution. Patent expiration also does not establish FDA approval or market availability.

What is the Orange Book status of iotrolan?

Iotrolan does not have the same US Orange Book profile as approved contrast agents such as iohexol, iopamidol, iopromide, ioversol, and iodixanol. The patent did not create a continuing Orange Book-listed barrier to an ANDA pathway.

Regulatory implications

The principal regulatory points are:

Iotrolan is not a current US reference product with a conventional Orange Book patent-and-exclusivity listing comparable to major approved nonionic contrast agents.
US generic applicants cannot rely on a conventional Paragraph IV challenge to an active Orange Book patent if there is no listed reference product and no unexpired listed patent.
The expired patent would not support a current Hatch-Waxman injunction against an ANDA applicant.
A new sponsor seeking US approval would face the ordinary NDA or applicable regulatory pathway for the proposed product, including clinical, quality, manufacturing, and safety requirements.

The absence of an active Orange Book patent does not eliminate regulatory barriers. It means that the principal barrier is not current small-molecule patent exclusivity.

What Paragraph IV challenges and litigation affect US Patent 5,349,085?

No material current Paragraph IV risk attaches to this patent because its ordinary term expired in 2011 and iotrolan lacks the active US Orange Book framework associated with a currently marketed US reference drug.

Litigation assessment

Issue	Assessment
Active patent term	No
Current Paragraph IV exposure	No meaningful exposure
Orange Book injunction risk	No meaningful risk from this patent
Patent-expiration litigation	Historical litigation, if any, would no longer preserve exclusivity
Settlement leverage	Minimal after expiration
Current launch injunction	Not supported by US 5,349,085 alone

A historical infringement action could still matter for damages, validity, or claim construction during the period before expiration. It would not restore exclusivity after the statutory term ended.

How does the iotrolan patent estate compare with competing contrast agents?

Iotrolan belongs to the same broad commercial field as several nonionic iodinated contrast media, but its molecular architecture is distinct.

Agent	Structural class	Iodine content	Typical commercial status
Iotrolan	Nonionic dimer	Six iodine atoms	Historical or jurisdiction-specific use
Iodixanol	Nonionic dimer	Six iodine atoms	Commercially important; Visipaque
Iohexol	Nonionic monomer	Three iodine atoms	Commercially important; Omnipaque
Iopamidol	Nonionic monomer	Three iodine atoms	Commercially important
Iopromide	Nonionic monomer	Three iodine atoms	Commercially important; Ultravist
Ioversol	Nonionic monomer	Three iodine atoms	Commercially important; Optiray

Iotrolan and iodixanol are both dimeric six-iodine agents, but they do not have the same chemical structure. A patent covering one does not automatically cover the other. Competitor patent estates generally include combinations of:

Active-ingredient composition claims.
Specific stereoisomer claims.
Preparation and purification processes.
Stable aqueous formulations.
Concentration and viscosity controls.
Container and delivery-system claims.
Method-of-use claims.

The commercial strength of a contrast-agent estate depends less on a single expired compound claim and more on whether formulation, process, device, or use patents remain active.

What formulations are protected by US Patent 5,349,085?

The quoted claim does not specifically claim a formulation. It covers the compound as a chemical entity.

A product containing iotrolan in an aqueous injectable formulation could potentially practice the claim because the formulation contains the claimed compound. However, the patent does not require:

A specified iodine concentration.
A particular osmolality.
A pH range.
A stabilizer.
A buffer.
A preservative.
A specific container.
A particular route of administration.

A formulation patent would require separate claim language. The existence of the compound claim does not establish protection for every formulation attribute associated with an iotrolan product.

What method-of-use protection exists for iotrolan?

The quoted claim contains no method-of-use limitation. It does not require administration to a patient, imaging of a particular organ, or use with a specific imaging modality.

Potential method claims in the broader iotrolan landscape could have addressed:

Contrast-enhanced X-ray imaging.
Computed tomography.
Digital subtraction angiography.
Urography.
Vascular imaging.
Administration at a specified dose or concentration.

Such claims would need to be analyzed separately from US 5,349,085. The composition claim remains independent of the clinical indication.

How strong is the patent estate for iotrolan?

The estate represented by US 5,349,085 was strong during its active term because the claim targeted the active ingredient itself. Its current strength is zero as an exclusivity barrier because the patent has expired.

Strength during the patent term

The claim had several advantages:

It covered the active molecular entity.
It did not depend on a narrow use or dosage limitation.
It could reach products containing the compound regardless of formulation.
It would have been difficult to avoid while retaining the exact iotrolan structure.

Weaknesses of the claim

The claim was also vulnerable in several respects:

It covered a single defined compound rather than a broad genus.
Structural changes to the central linker could avoid literal infringement.
Changes to acetylation or hydroxypropyl substitution could create noninfringing analogues.
The claim did not independently protect manufacturing know-how.
The claim did not create permanent regulatory exclusivity.
Its commercial value depended on regulatory approval and market adoption.

What generic launch risks exist for iotrolan?

A generic or follow-on manufacturer would face limited patent risk from US 5,349,085 itself. The principal risks would be technical and regulatory.

Patent risk

The patent-specific risk is low because:

The patent is expired.
There is no current composition-of-matter exclusivity.
A Paragraph IV certification would not be the central barrier absent an active Orange Book-listed reference patent.
Any later patent would need to claim a separate formulation, process, use, device, or solid form.

Manufacturing risk

Iotrolan manufacturing may remain difficult because the molecule contains:

Two heavily iodinated aromatic units.
Multiple amide linkages.
Four dihydroxypropyl side chains.
A dimeric structure with high molecular weight.
Potential stereochemical and impurity-control requirements.
A demanding purification profile for injectable use.

Commercial manufacture would require control of iodine substitution, coupling efficiency, residual intermediates, color bodies, endotoxins, particulate matter, and stability in the final aqueous product.

Regulatory risk

The regulatory burden would include:

Demonstrating pharmaceutical-grade identity and purity.
Establishing injectable-product safety.
Controlling osmolality, viscosity, pH, and particulate content.
Providing validated analytical methods.
Demonstrating manufacturing consistency.
Addressing the absence of a straightforward current US reference-product pathway, if applicable.

What licensing deals and commercial exposure are relevant?

Iotrolan was associated with Schering's contrast-media business. The principal commercial issue is historical, not current US patent leverage. Because US 5,349,085 expired in 2011, a license to that patent alone would not provide current US exclusivity.

Any present licensing value would have to derive from separate assets, such as:

Proprietary manufacturing technology.
Regulatory dossiers.
Trademarks and branding.
Know-how for impurity control.
Non-US patents with unexpired terms.
Device or formulation technology.
Rights to clinical or pharmaceutical data.

Revenue exposure from this patent is therefore historical. The patent could have protected sales during its term, but it does not support a current US royalty claim based solely on manufacture or sale of the claimed compound.

What is the geographic coverage of the iotrolan patent landscape?

US 5,349,085 provides protection only in the United States. Parallel protection would require separate national or regional patents.

Relevant jurisdictions for a full iotrolan freedom-to-operate review would include:

European Patent Office member states.
Germany, where Schering AG was based.
Japan.
Canada.
Australia.
South Korea.
China.
Brazil.
Major Middle Eastern markets.

The expiration analysis must be performed jurisdiction by jurisdiction. Foreign patents may have had different filing dates, supplementary protection certificates, patent-term adjustments, or lapse events. US expiration does not establish global freedom to operate.

Key Takeaways

US Patent 5,349,085 covers iotrolan, a nonionic dimeric six-iodine contrast agent.
Claim 1 is a narrow product-by-structure claim directed to the complete molecular entity.
The claim does not independently cover formulations, imaging methods, manufacturing processes, or delivery devices.
The patent issued on September 20, 1994, and its ordinary term would have expired on September 20, 2011.
The patent presents no current US composition-of-matter exclusivity.
Iotrolan does not have the same active Orange Book patent framework as major FDA-approved contrast agents.
Current generic-entry risk is driven primarily by regulatory, manufacturing, quality, and market-access issues rather than this expired patent.
Any current licensing value would need to come from separate know-how, regulatory, formulation, process, trademark, or foreign-rights assets.

Frequently Asked Questions

Is US Patent 5,349,085 still enforceable?

No. Based on its 1994 issue date and ordinary 17-year pre-URAA term, the patent expired on September 20, 2011.

Is iotrolan the same drug as iodixanol?

No. Both are nonionic dimeric iodinated contrast agents, but they have different chemical structures and were protected by different patent families.

Does the patent cover iotrolan injections?

The claim covers the iotrolan molecule present in an injection, but it does not expressly claim a particular injectable formulation or concentration.

Can a company manufacture iotrolan without a patent license?

US 5,349,085 alone does not require a current license because the patent has expired. Separate active patents, regulatory rights, trade secrets, or foreign patents could still affect the commercial analysis.

Does an expired composition patent eliminate FDA approval requirements?

No. Patent expiration removes the patent barrier. It does not eliminate requirements for product quality, safety, manufacturing validation, clinical support, or regulatory authorization.

References

United States Patent No. 5,349,085. (1994). 1,3-bis(acetylamino)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
National Center for Biotechnology Information. (n.d.). PubChem compound database: Iotrolan. National Library of Medicine.
U.S. Patent and Trademark Office. (n.d.). Patent term calculator. U.S. Department of Commerce.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8231796	Nov 08, 1982

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0108638	⤷ Start Trial	SPC/GB93/150	United Kingdom	⤷ Start Trial
European Patent Office	0108638	⤷ Start Trial	97C0101	Belgium	⤷ Start Trial
Austria	20733	⤷ Start Trial
Germany	3364536	⤷ Start Trial
Denmark	160868	⤷ Start Trial
Denmark	508283	⤷ Start Trial
Hong Kong	46791	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,349,085

Summary for Patent: 5,349,085