Details for Patent: 7,871,597

Summary for Patent: 7,871,597

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:	Covis Pharma GmbH
Application Number:	US10/410,527
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,871,597
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

United States Patent 7,871,597: Claim Scope, Ferumoxytol Coverage, Exclusivity and Patent Landscape

U.S. Patent No. 7,871,597 is directed to high-concentration, rapidly administered parenteral iron oxide-carbohydrate complexes, with claim limitations focused on terminal sterilization, dose and volume, rapid injection, low free iron, low dissolution, and reduced anaphylaxis. The claims closely track the commercial attributes of ferumoxytol, marketed in the United States as Feraheme by AMAG Pharmaceuticals and later by Covis Pharma.

The patent is commercially important because it does not rely only on the chemical identity of the iron complex. Its protection is built around a combination of formulation characteristics and clinical-administration outcomes. A competing product may avoid infringement by using a different iron-carbohydrate complex, a different dose or volume, a slower administration protocol, or a formulation that does not satisfy the claimed stability and functional limitations.

What does U.S. Patent 7,871,597 protect?

The patent protects two related categories:

1. A unit dosage of a terminally sterilizable, autoclavable reduced carboxymethylated dextran iron oxide complex.
2. A method of administering that dosage rapidly while producing low detectable free iron and a low incidence of anaphylaxis.

The independent claims are claims 1 and 5.

Claim	Category	Principal limitations
1	Unit dosage composition	Reduced carboxymethylated dextran iron oxide complex; terminally sterilizable and autoclavable; stable at 121°C; 1-15 mL volume; 50-600 mg dose; parenteral administration above 1 mL/min; minimal detectable free iron; minimal anaphylaxis
2	Composition	Claim 1 plus minimal dissolution in a human subject
3	Composition	Claim 1 plus minimal incidence of anaphylaxis in a human subject
4	Composition	Claim 3 plus substantially immunosilent administration
5	Method	Parenteral administration of claim 1 at a rate above 1 mL/min
6	Method	Claim 5 plus administration at approximately 1 mL/sec
7	Method	Claim 5 plus minimal dissolution in a human subject
8	Method	Claim 7 plus substantial immunosilence

The patent therefore covers more than a conventional iron injection. It claims a specific product profile capable of rapid parenteral delivery without the free-iron and hypersensitivity problems historically associated with intravenous iron products. (U.S. Patent No. 7,871,597, 2011)

How broad are the composition claims?

Claim 1 is a combination claim with several mandatory limitations. Each limitation must be satisfied for literal infringement.

Chemical limitation

The complex must be a "reduced carboxymethylated dextran iron oxide complex." This language is directed to a carbohydrate-stabilized iron oxide structure, rather than to all intravenous iron products.

The claim does not cover every iron-carbohydrate complex. Products based on iron sucrose, ferric carboxymaltose, ferric derisomaltose, or iron dextran would generally require a separate analysis because their carbohydrate components and chemical structures differ.

The key technical question is whether the accused product contains the claimed reduced carboxymethylated dextran iron oxide complex, either by product labeling, regulatory chemistry information, manufacturing records, or expert chemical analysis.

Sterilization and thermal-stability limitation

The dosage must be:

• Terminally sterilizable;
• Autoclavable; and
• Stable at 121°C.

This limitation narrows the claim materially. It requires more than ordinary shelf stability or aseptic manufacture. The formulation must tolerate terminal heat sterilization at the specified temperature without unacceptable degradation or loss of pharmaceutical performance.

A formulation made only by sterile filtration could present a noninfringement position if it cannot withstand terminal autoclaving. That position would depend on the meaning of "terminally sterilizable" and "stable" in the patent specification and prosecution history.

Dose and volume limitations

Claim 1 requires both:

• A total volume of approximately 1 mL to approximately 15 mL; and
• A total single dose of approximately 50 mg to approximately 600 mg.

These ranges are central to the commercial relevance of the patent. Feraheme is supplied as 510 mg of elemental iron in a 17 mL vial, administered as a 510 mg dose. The marketed vial volume therefore requires careful claim mapping because the claim recites approximately 1 mL to approximately 15 mL, while the commercial presentation has commonly been described as 17 mL. The relevant analysis may turn on whether the claimed volume is the administered formulation volume, the effective unit dosage volume, or another volume defined in the patent specification.

This volume issue can be a significant defense against literal infringement. The dose limitation is more directly aligned with a 510 mg ferumoxytol dose.

Administration-rate limitation

Claim 1 requires a composition capable of parenteral administration at a rate "substantially greater than 1 mL/min." Claims 5 and 6 convert that product limitation into an express method limitation, with claim 6 specifying approximately 1 mL/sec.

The rate limitation distinguishes the claimed dosage from older intravenous iron products typically administered slowly or by infusion. It also creates a potential design-around route: a product administered below the claimed rate may avoid the method claims, although it may still raise issues under the composition claims if the product is capable of rapid administration.

Functional clinical limitations

Claim 1 requires that administration provide:

• Minimal detectable free iron; and
• Minimal incidence of anaphylaxis.

Claims 2 through 4 add minimal dissolution and substantial immunosilence.

These limitations create claim-construction and proof issues. "Minimal" and "substantially immunosilent" are functional terms. Their scope depends on the intrinsic evidence, including the specification, examples, assay methods, comparative products, and prosecution record.

A patent owner would likely rely on comparative pharmacology and clinical data. An accused party would likely challenge whether the claimed outcomes are objectively measurable, whether they are inherent properties of the product, and whether the claim provides a sufficiently definite boundary under 35 U.S.C. §112(b).

How do claims 1 and 5 differ?

Claim 1 is primarily a product claim. It requires a unit dosage with specified chemical, physical, thermal, dosing, and functional properties.

Claim 5 is a method-of-use claim. It requires:

1. Administering an effective dose;
2. Using the claimed iron oxide complex in a biocompatible liquid;
3. Achieving minimal detectable free iron and minimal anaphylaxis; and
4. Administering at a rate above 1 mL/min.

The method claims are potentially easier to enforce against a labeled product if the prescribing information instructs rapid administration. They are also vulnerable to a divided-infringement argument where no single entity performs every step, although physician or healthcare-provider administration normally supplies a direct-infringement theory.

Claim 6 is particularly targeted because it specifies approximately 1 mL/sec. A label authorizing rapid intravenous injection at roughly that rate would create a stronger literal infringement case than a label authorizing only slow infusion.

What products are most closely associated with the patent?

Ferumoxytol and Feraheme

Ferumoxytol is the product most closely associated with the claimed technology. Feraheme was approved by the FDA in 2009 for the treatment of iron-deficiency anemia in adult patients with chronic kidney disease. Its formulation uses an iron oxide core with a carbohydrate coating commonly described as polyglucose sorbitol carboxymethylether. The product is administered intravenously and was developed for high-dose delivery with a short administration time. (FDA, 2023)

Feraheme's clinical and commercial profile aligns with several claimed attributes:

Feraheme attribute	Relationship to Patent 7,871,597
Ferumoxytol iron oxide-carbohydrate complex	Closely related to the claimed reduced carboxymethylated dextran complex
High iron dose	Within the claimed 50-600 mg range for a 510 mg dose
Parenteral administration	Expressly required
Rapid intravenous delivery	Relevant to claims 1, 5 and 6
Low free iron profile	Directly relevant to claim 1
Low hypersensitivity incidence	Directly relevant to claims 1, 3 and 4
Sterile injectable product	Relevant to terminal-sterilization limitations

The volume limitation must be evaluated against the actual dosage unit and the patent's construction of the claimed volume. That issue prevents a simple conclusion that every Feraheme presentation necessarily satisfies every limitation.

Venofer

Venofer contains iron sucrose. It is chemically distinct from ferumoxytol and is not an obvious literal match for the reduced carboxymethylated dextran iron oxide limitation. Its principal patent risks would arise from separate formulation, manufacturing, or method patents, not from the core claims of Patent 7,871,597.

Injectafer

Injectafer contains ferric carboxymaltose. It is a distinct iron-carbohydrate complex. Its high-dose intravenous administration creates commercial overlap with Feraheme, but chemical nonidentity is a substantial distinction under Patent 7,871,597.

Monoferric

Monoferric contains ferric derisomaltose. It also uses a different iron-carbohydrate structure and has its own regulatory and patent history. Its high-dose infusion profile creates competitive overlap, but the product does not appear to be the principal target of the patent's composition claims.

What is the Orange Book status of Patent 7,871,597?

The patent was associated with the Feraheme product patent estate and was relevant to FDA-listed patent protection for ferumoxytol. Orange Book relevance depends on whether the patent was listed for the specific approved product and whether the listed claims covered the approved use or product.

Regulatory issue	Assessment
Reference product	Feraheme
Active ingredient	Ferumoxytol
FDA pathway	New drug application
Patent type	Product/formulation and method-of-administration protection
Orange Book relevance	Associated with Feraheme patent protection
Generic pathway	ANDA applicants could address listed patents through Paragraph IV certifications
Biosimilar pathway	Not applicable; ferumoxytol is a small-molecule drug, not a biologic

A patent's appearance in the Orange Book does not itself establish infringement. It determines the statutory notice and litigation consequences for an ANDA applicant that makes a Paragraph IV certification. FDA Orange Book listing data and the Feraheme prescribing information are the relevant regulatory sources. (FDA, 2024a; FDA, 2024b)

When does Patent 7,871,597 lose exclusivity?

The patent's enforceable term is governed by the 20-year term rules under 35 U.S.C. §154, measured from the applicable nonprovisional filing date, with possible adjustment for USPTO examination delay and possible patent-term extension for regulatory review. The issue date, January 18, 2011, does not determine the expiration date. (35 U.S.C. §154)

Because Patent 7,871,597 is part of a continuation-oriented pharmaceutical patent family, the controlling expiration date must be taken from the USPTO patent record and any applicable term-adjustment calculation. The commercial exclusivity period may also differ from the patent term because:

• FDA new-drug exclusivity may expire earlier;
• A listed patent may expire while other Feraheme patents remain enforceable;
• A Paragraph IV lawsuit may trigger a 30-month stay;
• An ANDA applicant may receive a 180-day generic exclusivity period; and
• Pediatric or regulatory extensions may affect the effective barrier.

The practical conclusion is that Patent 7,871,597 should be analyzed as one layer of the Feraheme estate rather than as the sole determinant of generic entry.

Which companies challenged or competed against Feraheme?

The competitive landscape has three groups.

Ferumoxytol generic applicants

Generic manufacturers that filed ANDAs for ferumoxytol could challenge Orange Book-listed patents through Paragraph IV certifications. Potential applicants and litigation parties must be identified from FDA ANDA records and PACER or district-court filings because company participation can change over time.

The principal generic risk is direct substitution with the same active ingredient. A ferumoxytol ANDA product is more exposed to this patent than Injectafer or Monoferric because it uses the same active pharmaceutical ingredient and is likely to seek the same or a closely related administration profile.

Competing branded intravenous iron products

Feraheme competes with:

• Injectafer, marketed by American Regent;
• Monoferric, marketed by Pharmacosmos;
• Venofer, marketed by CSL Vifor; and
• Other iron sucrose, sodium ferric gluconate, iron dextran and ferric carboxymaltose products.

These products compete on dose size, infusion time, safety profile, renal-disease use, hematology prescribing, hospital formulary status and reimbursement.

Biosimilar challengers

There is no biosimilar pathway for ferumoxytol. FDA approval proceeds through the ANDA pathway because ferumoxytol is a chemically defined small-molecule drug rather than a biologic subject to the Public Health Service Act. The relevant competitive risk is generic ferumoxytol, not a biosimilar.

How strong is the patent estate?

Patent 7,871,597 has moderate strength as a targeted formulation and administration patent, but it is not equivalent to a broad composition-of-matter patent.

Strengths

• It covers a commercially valuable high-dose intravenous iron profile.
• Claims 1 and 5 combine chemical, formulation and administration limitations.
• The rapid-administration feature can map closely to product labeling.
• The low-free-iron and low-anaphylaxis limitations address clinically relevant differentiators.
• The claims may reach both the product and the labeled method of use.

Vulnerabilities

• The claim uses potentially subjective terms such as "minimal" and "substantially immunosilent."
• The 1-15 mL volume range may create a product-specific noninfringement issue.
• "Capable of" rapid administration may require proof of the product's physical capability rather than actual routine use.
• The chemical limitation may exclude structurally different iron-carbohydrate complexes.
• Clinical-outcome limitations can create enablement, written-description and definiteness disputes.
• A generic applicant may use a slower administration label or different dosage presentation.
• Patent expiration or Orange Book delisting can remove the principal statutory barrier even if the patent historically covered Feraheme.

What generic launch scenarios exist?

Scenario	Likely effect
Same ferumoxytol composition, same 510 mg dose and rapid administration	Highest exposure to claims 1, 5 and 6
Same ferumoxytol, different labeled administration rate	Reduces method-claim exposure but may not resolve composition claims
Same active ingredient, different concentration or container volume	May avoid one or more numerical limitations
Different iron-carbohydrate complex	Stronger chemical noninfringement position
Slow infusion-only label	Reduces exposure to rapid-administration method claims
Launch after patent expiry or successful Paragraph IV litigation	Removes the relevant patent barrier
Launch under a section viii carve-out	Possible only if the patented method is not required for the proposed labeling

A generic applicant's most important technical work would be to map the proposed formulation against the carbohydrate structure, autoclave stability, dose volume, free-iron assay, dissolution profile and administration rate.

What manufacturing and geographic barriers apply?

The patent is a U.S. patent and directly affects U.S. manufacture, importation, sale, offers for sale and use. Foreign equivalents must be analyzed separately in each jurisdiction. Patent-family protection may exist in Europe, Canada, Japan and other markets, but filing and grant status, claim scope and expiration dates vary by country.

Manufacturing risk is concentrated in:

• Control of the iron oxide core;
• Carbohydrate reduction and carboxymethylation chemistry;
• Particle-size distribution;
• Carbohydrate-to-iron ratio;
• Sterilization-cycle validation;
• Free-iron control;
• Aggregation and dissolution testing; and
• Container-closure compatibility.

Even if a competing product avoids literal infringement, regulatory comparability and manufacturing reproducibility remain commercial barriers. Ferumoxytol is a complex iron-carbohydrate product, and FDA approval may require extensive characterization beyond ordinary small-molecule active-ingredient identity. FDA has recognized that complex iron-carbohydrate products can present product-specific equivalence issues. (FDA, 2013)

What litigation and settlement issues matter?

For an ANDA applicant, a Paragraph IV certification can trigger patent litigation under the Hatch-Waxman framework. The commercial consequences include:

• A potential 30-month FDA approval stay;
• Discovery into formulation and manufacturing records;
• Expert disputes over claim construction and analytical methods;
• Challenges to the patent's validity under Sections 101, 102, 103 and 112;
• A possible at-risk launch after expiration of the stay; and
• A settlement establishing a future generic-entry date.

A settlement can preserve the patent owner's revenue while allowing an authorized or first-filed generic launch before patent expiry. Its commercial value depends on the remaining patent term, the number of ANDA filers, 180-day exclusivity, damages exposure and the strength of the formulation evidence.

Key Takeaways

• Patent 7,871,597 targets a reduced carboxymethylated dextran iron oxide dosage capable of rapid parenteral administration.
• The patent is closely associated with ferumoxytol and Feraheme.
• The claims require a combination of chemical identity, terminal sterilizability, 121°C stability, dose, volume, administration rate and clinical-performance limitations.
• Claims 1 and 5 are the principal enforcement claims.
• Claims 2-4 and 7-8 add dissolution and immunosilence limitations.
• Iron sucrose, ferric carboxymaltose and ferric derisomaltose products are chemically distinct and are not automatically within the claims.
• Generic ferumoxytol presents a materially greater risk than competing non-ferumoxytol iron products.
• The 1-15 mL volume range and functional terms such as "minimal" create important claim-construction and noninfringement issues.
• Ferumoxytol is subject to the ANDA pathway, not biosimilar approval.
• Patent 7,871,597 must be evaluated with the full Feraheme patent family, Orange Book listings, patent-term data and any Paragraph IV litigation.

FAQs

Does Patent 7,871,597 cover all intravenous iron products?

No. Its chemical limitation is directed to a reduced carboxymethylated dextran iron oxide complex. Iron sucrose, ferric carboxymaltose and ferric derisomaltose are structurally different products.

Can a generic ferumoxytol avoid the patent by using a slower infusion?

A slower label may reduce exposure to claims 5 and 6, which expressly require administration above 1 mL/min or approximately 1 mL/sec. It may not eliminate risk under claim 1 if the product remains capable of rapid administration and satisfies the other limitations.

Is ferumoxytol eligible for a biosimilar application?

No. Ferumoxytol is a chemically defined small-molecule drug. A competing product generally proceeds through an ANDA rather than a biosimilar application.

Why is the 121°C limitation commercially important?

It requires the formulation to tolerate terminal autoclave sterilization. A product manufactured only by aseptic filtration may have a noninfringement position if it does not meet the claim's thermal-sterilization requirement.

Does expiration of Patent 7,871,597 guarantee immediate generic entry?

No. Other Feraheme patents, regulatory exclusivity, litigation stays, settlement agreements or separate manufacturing patents may affect the actual launch date.

References

1. Food and Drug Administration. (2013). Guidance for industry: Iron sucrose injection, draft guidance on iron sucrose equivalence. U.S. Department of Health and Human Services.

2. Food and Drug Administration. (2023). Feraheme (ferumoxytol injection) prescribing information. U.S. Department of Health and Human Services.

3. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. U.S. Department of Health and Human Services.

4. Food and Drug Administration. (2024b). Drugs@FDA: Feraheme NDA 022180. U.S. Department of Health and Human Services.

5. United States Code. (2024). 35 U.S.C. §154: Contents and term of patent; provisional rights.

6. U.S. Patent No. 7,871,597. (2011). Iron oxide carbohydrate complex compositions and methods of use. United States Patent and Trademark Office.

Drugs Protected by US Patent 7,871,597

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 7,871,597

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