Details for Patent: 8,501,158

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Summary for Patent: 8,501,158

Title:	Polyol and polyether iron oxide complexes as pharmacological and/or MRI contrast agents
Abstract:	Pharmacological compositions, and methods for administration, of the type employing an iron oxide complex with a polyol or polyether. The methods of administration may comprise parenteral administration of an effective dose of the complex formulated in a biocompatible liquid delivered at a rate of from about 1 mL/sec to less than 1 mL/min and wherein upon administration the complex provides minimal detectable free iron in a subject, and minimal incidence of anaphylaxis. The pharmacological compositions are of the type employing a polyol or polyether iron oxide complex, which, upon parenteral administration to a subject, are substantially immunosilent, provide minimal anaphylaxis and minimal free iron, and undergo minimal dissolution in vivo.
Inventor(s):	Ernest V. Groman, Kenneth G. Paul, Timothy B. Frigo, Howard Bengele, Jerome M. Lewis
Assignee:	Amag Pharmaceuticals Inc
Application Number:	US12/963,308
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,501,158
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 8,501,158: Claim Scope, Feraheme Coverage, Expiration, and Generic Entry Risk

US Patent 8,501,158 covers a specific intravenous administration method for a high-dose, autoclaved superparamagnetic iron-oxide formulation associated with ferumoxytol, marketed as Feraheme. The independent claim is narrow in formulation but potentially significant in practice because it combines the drug’s chemical attributes with a rapid administration rate of approximately 1 mL per second and a 500-600 mg iron dose.

The patent is a method-of-treatment patent, not a broad composition patent. Its principal commercial relevance is the protection of rapid intravenous administration of ferumoxytol-type iron-carbohydrate particles. The patent’s listed term is understood to run to approximately March 2026, subject to the official USPTO term calculation and any applicable adjustments or extensions.

What does US Patent 8,501,158 protect?

US Patent 8,501,158 protects a method that requires all of the following elements:

Claim limitation	Required scope
Patient	A patient in need of an iron supplement
Route	Intravenous administration
Product condition	An autoclaved pharmacological composition
Administration rate	Approximately 1 mL per second
Active particle	Superparamagnetic iron-oxide particles
Coating	Carboxymethylated reduced dextran
Carboxyl content	Approximately 1,100-1,500 micromoles of carboxyl per gram of carboxymethylated reduced dextran
Reduced dextran molecular weight	Approximately 10 kDa average molecular weight
Particle size	Approximately 10-50 nm diameter
Dose	Approximately 500-600 mg elemental iron
Dependent claim 2	Free iron below approximately 0.1%, measured by a specified filtration and atomic absorption method

The claim is therefore directed to a defined combination of product specifications and administration parameters. A product that satisfies only some of these limitations would not literally infringe claim 1.

The patent identifies a formulation profile consistent with ferumoxytol, an iron-carbohydrate complex consisting of an iron-oxide core surrounded by a carbohydrate coating. The FDA-approved Feraheme formulation contains 30 mg of elemental iron per mL, with a standard 510 mg dose administered intravenously.[2]

How broad is claim 1 of US 8,501,158?

Claim 1 is commercially relevant but technically constrained. Its breadth comes from the method format and the use of approximate numerical ranges. Its weakness is that it requires simultaneous proof of multiple formulation and administration variables.

Product limitations

The composition must contain superparamagnetic iron-oxide particles coated with a particular form of reduced dextran. The claim does not cover every intravenous iron product. It excludes, at minimum, products based on:

• Iron sucrose;
• Ferric carboxymaltose;
• Ferric derisomaltose;
• Sodium ferric gluconate;
• Iron dextran formulations lacking the claimed particle and coating characteristics.

The coating requirement is more specific than a generic reference to dextran. The dextran must be reduced, carboxymethylated, and within the claimed carboxyl-content range. The reduced dextran must have an average molecular weight of approximately 10 kDa.

Particle-size limitation

The particles must have a diameter of approximately 10-50 nm. This limitation can create evidentiary disputes because particle size depends on the analytical method, sample preparation, aggregation state, and whether the measurement concerns the iron-oxide core or the complete coated particle.

A generic applicant could challenge infringement by showing that the relevant particle population falls outside the claimed range or that the patent’s measurement methodology does not support the asserted value.

Dose limitation

The unit dose must contain approximately 500-600 mg of iron. Feraheme’s labeled 510 mg dose falls within this range.[2] Products administered in lower divided doses would not literally satisfy the dose limitation, although repeated administration or a treatment course could raise questions about what constitutes the claimed “unit dose.”

Administration-rate limitation

The approximately 1 mL-per-second limitation is central. It distinguishes the patent from conventional slow intravenous infusion methods. At 30 mg of iron per mL, a 510 mg dose corresponds to approximately 17 mL of solution. Administration at 1 mL per second would deliver the dose in roughly 17 seconds.

The current Feraheme prescribing information directs administration as an intravenous infusion over at least 15 minutes.[2] That label requirement does not necessarily eliminate patent relevance. A method claim can remain legally relevant to an earlier or alternative administration protocol even if the approved label changes. It does, however, reduce the likelihood that a current labeled-use product will practice the claimed rapid-administration method.

What does claim 2 add?

Claim 2 adds a product-quality limitation: free iron must be below approximately 0.1%.

The measurement is not open-ended. It requires:

1. Filtering a sample through a 30-kilodalton molecular-weight-cutoff micropartition membrane;
2. Measuring the filtrate by atomic absorption spectroscopy; and
3. Determining that the free iron concentration is below approximately 0.1%.

This limitation may be difficult to apply without access to batch records, validated analytical methods, and product samples. It can also create claim-construction issues regarding:

• The meaning of “free iron”;
• Whether the test measures unbound iron or low-molecular-weight iron species;
• The relevant denominator for the 0.1% calculation;
• Membrane adsorption and recovery;
• The test’s precision near the claimed threshold.

Claim 2 is narrower than claim 1 and may be more difficult to invalidate for anticipation if the prior art does not disclose the exact assay conditions.

What patents protect ferumoxytol and Feraheme?

US 8,501,158 is part of a broader Feraheme patent estate. The estate has included composition, manufacturing, formulation, administration, and method-of-use patents. The principal categories are summarized below.

Patent category	Commercial subject matter	Relevance to US 8,501,158
Composition patents	Iron-oxide cores with carbohydrate or dextran-based coatings	Define the underlying ferumoxytol-type product
Manufacturing patents	Preparation, reduction, carboxymethylation, particle formation, purification, and sterilization	May create process barriers even where method claims are avoided
Formulation patents	Stable injectable iron-carbohydrate compositions and low free-iron levels	Overlap with claim 2’s product-quality requirement
Administration patents	Intravenous dosing, rapid injection, dose volume, and treatment schedules	Directly relevant to claim 1
Method-of-use patents	Treatment of iron deficiency, anemia, chronic kidney disease, and related conditions	May remain relevant after composition patents expire

The original Feraheme-related composition patents have earlier expiration dates than later administration patents. US 8,501,158 appears to have an expiration date in approximately March 2026 based on its priority chronology and ordinary 20-year patent-term calculation.[1] Any patent-term adjustment, terminal disclaimer, patent-term extension, or correction in the USPTO record controls the final date.

When does US Patent 8,501,158 lose exclusivity?

The expected patent expiration is approximately March 2026. The patent term is not determined by the 2013 issue date. For modern US applications, the term generally runs 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156.[3]

The practical exclusivity timeline is:

Event	Timing
Earliest relevant priority period	Approximately 2006
US patent grant	August 6, 2013
Expected ordinary expiration	Approximately March 2026
Post-expiration effect	Generic or alternative administration may proceed if no other enforceable patent blocks the proposed product or use

Expiration of US 8,501,158 would remove this administration-method barrier. It would not automatically eliminate other patents covering ferumoxytol composition, manufacturing, formulation, or other treatment methods.

What is the Orange Book status of US 8,501,158?

US 8,501,158 has been associated with the Feraheme patent estate and is relevant to FDA-listed patent protection for ferumoxytol injection. The Orange Book identifies patents submitted by approved drug applicants and does not itself decide whether a patent is valid, infringed, or enforceable.[4]

For an ANDA applicant, the relevant certification could include:

• Paragraph I: no patent information has been submitted;
• Paragraph II: the listed patent has expired;
• Paragraph III: approval is sought after patent expiration;
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV certification directed to US 8,501,158 would need to address both the rapid-administration method and the formulation limitations. A generic applicant using the current 15-minute infusion label could have a stronger noninfringement position against the 1 mL-per-second limitation, but other listed patents could remain relevant.

Which companies are challenging Feraheme patent protection?

Feraheme has been subject to generic competition and patent challenges in the ANDA framework. The most important risk does not come from biosimilar developers. Ferumoxytol is a nonbiologic iron-carbohydrate drug, so a conventional ANDA, rather than a 351(k) biosimilar application, is the expected pathway for a therapeutically equivalent injectable product.[5]

Potential ANDA challenges generally fall into four categories:

1. A product that uses a different iron-carbohydrate complex;
2. A ferumoxytol product administered over at least 15 minutes;
3. A formulation that falls outside the particle-size or coating ranges;
4. A Paragraph IV challenge asserting invalidity, noninfringement, or unenforceability.

The commercial threat depends on the full Orange Book listing, not US 8,501,158 alone. A challenger that avoids the rapid-administration limitation may still face composition or formulation patents.

What litigation and settlement issues affect the patent?

A complete litigation analysis requires review of district-court complaints, ANDA notices, claim-construction orders, settlement agreements, and FDA approval records. The claim language alone does not establish whether a particular generic company has entered into a settlement or whether a court has adjudicated validity or infringement.

The key litigation issues for this patent would be:

Infringement issues

The patent owner would need to establish that the accused product and labeling practice every limitation, including:

• The approximately 1 mL-per-second administration rate;
• The 500-600 mg iron dose;
• The autoclaved status of the composition;
• The claimed reduced-dextran chemistry;
• The 10-50 nm particle size;
• The free-iron threshold, if claim 2 is asserted.

Induced-infringement theories could focus on labeling, instructions to healthcare professionals, promotional materials, or known use by customers.

Validity issues

A challenger could assert:

• Anticipation based on prior rapid intravenous iron administration;
• Obviousness based on known iron-carbohydrate compositions and dosing protocols;
• Lack of written description for the combined numerical ranges;
• Lack of enablement for the full range of compositions and analytical results;
• Indefiniteness involving “about,” “unit dose,” or “free iron.”

The combination of multiple narrow limitations may make anticipation difficult, while obviousness could turn on whether the prior art supplied a reason to combine the formulation specifications with rapid administration.

Settlement effects

A settlement may permit an authorized generic, a licensed launch date, or entry before patent expiration. Such terms are not inferable from the patent claims. A settlement involving other Feraheme patents may also leave US 8,501,158 unresolved.

How strong is the patent estate for ferumoxytol?

The estate is strongest where a competitor seeks to copy the commercial product and its historical administration protocol. It is weaker against a product that:

• Uses a different carbohydrate coating;
• Has materially different particle-size characteristics;
• Uses a different dose;
• Is delivered by a slow infusion;
• Does not meet the free-iron assay threshold;
• Enters after expiration of the relevant method patent.

The patent’s commercial value is therefore conditional. It is not a standalone monopoly over intravenous iron or even over all ferumoxytol use. Its value depends on whether the patent owner can enforce the specific administration protocol and whether other patents cover the same product.

What generic launch scenarios exist?

Launch scenario	US 8,501,158 risk	Commercial assessment
510 mg dose infused over at least 15 minutes	Lower literal risk under claim 1	More credible design-around if label and actual use remain slow
510 mg rapid injection at about 1 mL/sec	High	Closely tracks claim 1
Different iron-carbohydrate complex	Low against this patent	May face separate product patents
Ferumoxytol with different particle size or coating chemistry	Fact-dependent	Requires analytical and equivalence evidence
Dose below 500 mg per unit	Lower literal risk	May create clinical and regulatory differences
Product launched after patent expiration	No prospective patent barrier from this patent	Other listed patents still require review

What FDA regulatory status applies?

Feraheme is FDA-approved for the treatment of iron deficiency anemia in adults with chronic kidney disease and in adults who have intolerance or an unsatisfactory response to oral iron, or who have non-dialysis-dependent chronic kidney disease.[2]

The FDA label includes a boxed warning for serious hypersensitivity reactions and requires monitoring during and after administration.[2] Regulatory labeling is relevant to patent risk because the label can encourage or avoid the claimed method. A label requiring a 15-minute infusion is materially different from a label directing administration at approximately 1 mL per second.

The product is not a biologic. Biosimilar litigation and Purple Book exclusivity are therefore not the primary frameworks. Generic competition is governed principally by the ANDA and Hatch-Waxman system.

Key Takeaways

• US 8,501,158 is a narrow method patent tied to rapid intravenous administration of a ferumoxytol-type iron-carbohydrate composition.
• Claim 1 requires every major limitation: autoclaving, approximately 1 mL-per-second administration, 500-600 mg iron, specific reduced-dextran chemistry, 10-50 nm particles, and a defined carboxyl range.
• Claim 2 narrows the scope further by requiring free iron below approximately 0.1% under a specified assay.
• The patent’s expected expiration is approximately March 2026.
• The current Feraheme label calls for administration over at least 15 minutes, which may reduce literal infringement risk under the rapid-injection limitation.
• The patent does not cover all intravenous iron products and is not a biosimilar patent.
• Generic launch analysis must review the complete Feraheme Orange Book estate, including composition, manufacturing, formulation, and other method-of-use patents.
• The main commercial design-around is a slower infusion or a formulation outside the claimed particle and coating specifications.

FAQs

Does US 8,501,158 cover all ferumoxytol injections?

No. It covers only injections that satisfy the complete combination of claim limitations. A ferumoxytol product administered over at least 15 minutes may avoid the approximately 1 mL-per-second limitation, although other patents may apply.

Is US 8,501,158 a composition patent?

No. It is principally a method-of-treatment patent. The composition characteristics are limitations within the claimed administration method.

Can a generic avoid the patent by changing the dose?

Potentially. A unit dose outside the 500-600 mg range may avoid literal infringement of claim 1, but the regulatory product, labeling, therapeutic equivalence, and other patents would require separate analysis.

Does the patent cover iron sucrose or ferric carboxymaltose?

No. The claimed composition requires superparamagnetic iron-oxide particles coated with carboxymethylated reduced dextran. Iron sucrose and ferric carboxymaltose have different active complexes.

Does patent expiration end Feraheme exclusivity?

No. Expiration of US 8,501,158 removes one patent barrier. Other Orange Book-listed patents, regulatory exclusivity, manufacturing patents, settlements, or injunctions could affect generic entry.

References

1. United States Patent and Trademark Office. (2013). United States Patent No. 8,501,158, methods of treating iron deficiency.
2. U.S. Food and Drug Administration. (2023). Feraheme (ferumoxytol injection) prescribing information.
3. 35 U.S.C. §§ 154, 156.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
5. U.S. Food and Drug Administration. (2024). ANDA submissions: Content and format.

Drugs Protected by US Patent 8,501,158

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 8,501,158

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1169062		C300558	Netherlands
European Patent Office	1169062		CA 2012 00050	Denmark
European Patent Office	1169062		92114	Luxembourg
European Patent Office	1169062		C01169062/01	Switzerland
European Patent Office	1169062		1290043-7	Sweden
European Patent Office	1169062		300558	Netherlands
European Patent Office	1169062		2012C/052	Belgium