United States Patent 8,592,480: Scope, Claims, Expiration, Orange Book Status, and Generic Entry Risk

U.S. Patent No. 8,592,480 protects a liquid calcium acetate therapy used to bind gastrointestinal phosphate, particularly in patients with renal disease, end-stage renal disease, or hyperphosphatemia. The patent does not broadly cover calcium acetate as a phosphate binder. Its enforceable scope is directed to a specific oral liquid formulation used according to a method of treatment.

The core combination requires:

An aqueous liquid composition;
Calcium acetate at 7% to 16% w/v;
A sweetener;
A polyol; and
A taste-masking agent.

The patent issued November 26, 2013, from an application claiming priority to March 12, 2007. Its listed expiration date is March 12, 2027, subject to any applicable patent-term adjustment or other statutory modification recorded by the USPTO.[1]

What does U.S. Patent 8,592,480 protect?

The patent protects a method of binding phosphorus by orally administering a liquid calcium acetate formulation meeting the claim limitations. It is principally a formulation-and-use patent rather than a composition claim.

Independent claim 1 requires all of the following:

Claim element	Scope
Therapeutic action	Binding phosphorus within the gastrointestinal tract
Route	Oral administration
Dosage form	Liquid pharmaceutical composition
Vehicle	Aqueous solution
Active ingredient	Calcium acetate
Calcium acetate concentration	7% to 16% w/v
Sweetening component	Required
Polyol	Required
Taste-masking agent	Required

The claim uses the transitional term “comprising.” A competing product can therefore contain additional excipients and remain within the literal scope if it includes every required element.

The claim is narrower than a claim covering every oral calcium acetate product. A capsule, tablet, powder, suspension outside the claimed concentration range, or liquid without the required sweetener, polyol, or taste-masking agent would not satisfy claim 1 as written.

How do the dependent claims narrow the patent’s scope?

The dependent claims create multiple formulation pathways. They also increase the likelihood that a commercial product will fall within at least one claim if it resembles the claimed liquid formulation.

Calcium acetate concentration claims

Claims 3 and 4 narrow the active concentration to approximately 12% to 16% w/v and approximately 14% w/v, respectively.

At 14% w/v, the formulation contains approximately:

140 mg calcium acetate per mL;
700 mg calcium acetate per 5 mL before accounting for hydrate or assay conventions;
Approximately 2.1 g calcium acetate per 15 mL tablespoon.

Claims 29 through 31 use a product-strength format rather than only a percentage concentration:

Claim 29: approximately 710 mg hydrous calcium acetate per 5 mL;
Claim 30: approximately 667 mg anhydrous calcium acetate per 5 mL;
Claim 31: approximately 169 mg calcium per 5 mL.

Claim 35 further specifies approximately 8 milliequivalents of calcium.

These claims are commercially important because a generic developer could avoid a percentage limitation but still encounter a claim based on the 5-mL dose strength if the formulation uses substantially the same calcium content.

Polyol claims

Claim 5 requires 15% to 50% w/v total polyol. Claim 6 identifies the permitted polyol class:

Sorbitol;
Glycerine;
Propylene glycol;
Xylitol;
Maltitol; or
Combinations.

Claims 7 and 8 focus on sorbitol at approximately 15% to 40% w/v and approximately 21% w/v. Claims 9 and 10 cover maltitol at approximately 15% to 25% w/v and approximately 20% w/v.

Claim 11 separately covers glycerine at 1% to 25% w/v, with claim 12 specifying approximately 5% w/v. Claim 26 covers propylene glycol.

The polyol limitation is a significant design-around issue. A formulation using neither a listed polyol nor a combination that falls within the claim language may avoid literal infringement of claim 1. The doctrine of equivalents could still create risk if the substitute performs substantially the same function in substantially the same way, but the result would depend on claim construction and the facts of the formulation.

Sweetener and flavoring claims

Claim 13 requires an artificial sweetener. Claim 14 identifies:

Sucralose;
Acesulfame potassium;
Aspartame; or
Saccharin.

Claim 15 narrows the group to sucralose or saccharin. Claim 16 specifies approximately:

0.35% w/v sucralose; or
0.15% w/v saccharin.

Claims 17 through 21 cover flavoring agents, including black cherry flavor and combinations with menthol. These claims give the patent additional coverage over commercial taste systems, although claim 1 itself requires only a sweetener and a taste-masking agent, not a particular flavor.

Taste masking, pH, preservatives, and excipients

Claim 28 identifies monoammonium glycyrrhizinate as the taste-masking agent. This is one of the more formulation-specific limitations in the patent.

Other dependent claims cover:

pH of approximately 6.0 to 7.2;
Methylparaben and other preservatives;
Polyvinylpyrrolidone, or PVP;
PVP concentration of approximately 0.5% to 1.0% w/v;
Sugar-free, low-calorie, and calorie-free compositions.

These limitations appear directed to the practical problems of making a palatable, stable, concentrated calcium acetate liquid. Calcium acetate formulations can present taste, viscosity, precipitation, preservative, and patient-acceptability issues. The patent’s claim architecture protects several solutions to those problems.

What therapeutic uses are covered by the patent?

Claims 2 and 36 connect the formulation to its principal clinical population.

The claims cover administration to an individual who:

Needs dialysis;
Has renal disease;
Has kidney disease;
Has end-stage renal disease;
Has chronic kidney disease; or
Is suffering from hyperphosphatemia.

Claims 37 and 38 add administration parameters:

Approximately 15 mL three times daily; and
Administration around the time of a meal.

These limitations align with the labeled use of calcium acetate as a phosphate binder administered with meals. The method claims do not require a specific dialysis modality. They also do not require a particular serum phosphorus threshold beyond the dependent hyperphosphatemia limitation.

When does U.S. Patent 8,592,480 expire?

Event	Date
Earliest claimed priority	March 12, 2007
U.S. application filing	March 12, 2008
Patent grant	November 26, 2013
Listed patent expiration	March 12, 2027

The critical commercial date is March 12, 2027. The patent term is measured from the earliest effective nonprovisional filing date under the modern patent-term statute, not from the grant date.[1]

The patent does not create perpetual exclusivity for liquid calcium acetate. After expiration, the patent-based barrier to a formulation that meets these limitations falls away, although regulatory exclusivity, other patents, trade secrets, manufacturing controls, and product-specific regulatory requirements may still affect entry.

What is the Orange Book status of Patent 8,592,480?

U.S. Patent 8,592,480 has been associated with Phoslyra, an oral calcium acetate solution marketed by Fresenius Medical Care North America. Phoslyra is a 667 mg/5 mL calcium acetate oral solution, equivalent to approximately 169 mg elemental calcium per 5 mL.[2]

The relevant Orange Book issues are:

Regulatory issue	Assessment
Reference product	Phoslyra calcium acetate oral solution
Sponsor	Fresenius Medical Care North America
FDA pathway	New drug application
Patent type	Formulation and method-of-use patent
Orange Book relevance	Product-specific patent listing
Biosimilar pathway	Not applicable
Generic pathway	ANDA, subject to applicable patent certifications

The Orange Book does not make a patent valid or enforceable. It records patents submitted by the NDA holder and accepted for listing under FDA regulations. Generic applicants must address listed patents through Paragraph I, II, III, or IV certifications, depending on the patent and the proposed product.[3]

What Paragraph IV challenges and generic litigation affect the patent?

A generic applicant seeking approval before patent expiration could submit a Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed. For an Orange Book-listed patent, the NDA holder could bring an infringement action within 45 days of receiving the certification. A timely suit generally triggers a statutory stay of ANDA approval for up to 30 months, subject to statutory exceptions and court action.[3]

The practical Paragraph IV risk is formulation-specific. A generic product would need to assess:

Whether its liquid is an aqueous solution rather than a suspension;
Whether calcium acetate falls within 7% to 16% w/v;
Whether the product includes both a sweetener and a polyol;
Whether its excipient performs a taste-masking function;
Whether its dose strength meets claims 29 through 31;
Whether the proposed labeling induces use covered by the method claims.

A product outside the 7% to 16% range may avoid claim 1, but concentration alone is not sufficient if another asserted claim captures the dose strength or formulation composition. Conversely, a product containing calcium acetate, sorbitol, sucralose, and a taste-masking agent would present a high literal-infringement risk if its concentrations fall within the claimed ranges.

Publicly available FDA and USPTO records identify the patent and reference-product relationship. No broadly reported settlement terms or license agreement allocating early generic entry rights are reflected in the cited regulatory and patent records.[1-3]

How strong is the patent estate for liquid calcium acetate?

The estate is concentrated rather than broad. Its commercial strength comes from the combination of a narrow liquid dosage form and multiple dependent claims covering common formulation choices.

Strengths

Claim 1 captures the central formulation concept.
The “comprising” language allows additional excipients.
Claims cover the principal commercial strength of approximately 667 mg/5 mL.
Multiple polyols are listed.
The patent covers both formulation characteristics and administration for renal patients.
Taste masking is a functional limitation that may be difficult to avoid while maintaining patient acceptability.

Vulnerabilities

All claims depend on a liquid formulation.
Claim 1 requires both a sweetener and a polyol.
A competing product may use a different concentration, excipient system, or dosage form.
Method claims require proof of the accused administration or induced use.
Functional language such as “taste masking agent” may create claim-construction disputes.
Prior-art combinations involving calcium acetate liquids and conventional sweetening or flavoring agents may support obviousness arguments.

The strongest enforcement position would generally involve a product that closely matches the claimed 5-mL strength and excipient system. The most practical design-around would use a different dosage form or a liquid formulation outside the concentration and polyol requirements, provided the alternative does not remain equivalent under applicable infringement principles.

What other patents and barriers affect calcium acetate phosphate binders?

The broader calcium acetate landscape includes several distinct product categories.

Product category	Primary barrier
Calcium acetate capsules	Product formulation, labeling, and any listed patents
Calcium acetate tablets	Tablet formulation and manufacturing
Calcium acetate oral solution	U.S. Patent 8,592,480 and product-specific regulatory requirements
Sevelamer products	Separate composition, formulation, and method patents
Lanthanum carbonate	Separate active-ingredient and formulation estate
Sucroferric oxyhydroxide	Separate composition and manufacturing patents
Ferric citrate	Separate composition, method, and formulation patents

Biosimilar risk is not relevant because calcium acetate is a defined small-molecule salt, not a biologic. The relevant competitive threat is an ANDA-approved generic or an alternative phosphate binder.

Manufacturing barriers for the patented formulation are moderate. Calcium acetate itself is not a difficult active ingredient to synthesize, but a concentrated palatable liquid requires control of:

Calcium acetate hydration state;
Assay and elemental-calcium equivalence;
pH;
Preservative performance;
Flavor and taste-masking consistency;
Microbial limits;
Container compatibility;
Precipitation and storage stability.

These are primarily formulation-development and regulatory barriers rather than durable manufacturing trade secrets.

How does Phoslyra compare with other phosphate binders?

Phoslyra’s commercial differentiation is the liquid dosage form. It may be useful for patients who have difficulty swallowing capsules or tablets, but it carries a high excipient and palatability burden.

Product	Active ingredient	Dosage form	Patent risk profile
Phoslyra	Calcium acetate	Oral solution	Patent 8,592,480; concentration and excipient limitations
PhosLo and calcium acetate generics	Calcium acetate	Capsules or tablets	Different formulation profile
Renvela	Sevelamer carbonate	Tablets and powder	Separate sevelamer patent estate
Fosrenol	Lanthanum carbonate	Chewable tablets and powder	Separate lanthanum estate
Velphoro	Sucroferric oxyhydroxide	Chewable tablet	Separate iron-based binder estate
Auryxia	Ferric citrate	Tablets	Separate composition and method estate

The patent’s competitive value is therefore linked to the liquid presentation rather than calcium acetate generally.

What generic launch scenarios exist after patent expiration?

Three principal launch scenarios exist:

Pre-expiration Paragraph IV launch. A generic applicant challenges the patent and prevails, obtains a settlement permitting entry, or launches at risk after litigation developments.
Post-expiration launch. A generic enters after March 12, 2027, subject to FDA approval and any other applicable exclusivity.
Design-around launch. A generic uses a formulation outside the key concentration, polyol, sweetener, or taste-masking limitations.

A product that exactly reproduces the 667 mg/5 mL commercial strength faces greater risk than one using a materially different liquid concentration or dosage form. The principal commercial question is whether the market rewards the liquid format enough to justify a formulation-specific Paragraph IV challenge.

What is the revenue exposure from this patent?

The patent’s revenue exposure is limited to the liquid calcium acetate segment. It does not block generic calcium acetate capsules or tablets that do not practice the claimed method.

Revenue risk increases as the patent approaches expiration because:

Calcium acetate is a mature phosphate-binder category;
The active ingredient is comparatively inexpensive;
A liquid product can be developed without the manufacturing complexity associated with biologics;
Generic substitution can produce rapid price compression after approval.

Revenue protection is stronger where the branded product has established patient preference for a liquid formulation and where the generic must reproduce taste, stability, and dose equivalence. It is weaker where prescribers can substitute capsules, tablets, or other phosphate binders.

Key Takeaways

U.S. Patent 8,592,480 covers oral administration of an aqueous liquid calcium acetate phosphate binder with 7% to 16% w/v calcium acetate, a sweetener, a polyol, and a taste-masking agent.
Claims 29 through 31 are commercially important because they target the approximately 667 mg/5 mL to 710 mg/5 mL product-strength range.
The patent covers Phoslyra’s liquid calcium acetate formulation and is distinct from patents covering calcium acetate capsules or tablets.
The listed expiration date is March 12, 2027.
A generic applicant would likely need to address the patent through an ANDA patent certification, potentially including Paragraph IV.
Biosimilar competition is not applicable.
The most credible design-around routes are a non-liquid dosage form, a different calcium acetate concentration, or an alternative excipient system that avoids the required sweetener-polyol-taste-masking combination.
The estate is commercially relevant but narrow and formulation-dependent.

FAQs

Does Patent 8,592,480 cover calcium acetate capsules?

No. The claims require a liquid pharmaceutical composition that is an aqueous solution. Conventional calcium acetate capsules and tablets do not fall within the literal dosage-form requirement.

Does the patent cover every calcium acetate oral solution?

No. The formulation must satisfy the calcium acetate concentration and excipient requirements in claim 1 or a dependent claim. A liquid outside the concentration range or lacking a required sweetener, polyol, or taste-masking agent may avoid literal infringement.

Is Phoslyra a biologic subject to biosimilar competition?

No. Phoslyra contains calcium acetate, a small-molecule active ingredient. A competing product would generally proceed through the generic-drug framework rather than the biosimilar pathway.

Can a generic launch before March 12, 2027?

Potentially, but the applicant would need to address the listed patent and obtain approval through a permissible route. A Paragraph IV challenge, settlement, patent invalidity ruling, or noninfringing design-around could affect the launch date.

Does using a different flavor avoid the patent?

Not necessarily. Flavor is addressed in dependent claims, but claim 1 requires a taste-masking agent rather than a particular flavor. Changing black cherry flavor to another flavor would not avoid claim 1 if the remaining formulation limitations are present.

References

United States Patent and Trademark Office. (2013). U.S. Patent No. 8,592,480, Liquid pharmaceutical compositions comprising calcium acetate.
U.S. Food and Drug Administration. (n.d.). Phoslyra calcium acetate oral solution prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Fresenius Medcl Care	PHOSLYRA	calcium acetate	SOLUTION;ORAL	022581-001	Apr 18, 2011		DISCN	Yes	No	⤷ Start Trial	⤷ Start Trial				USE OF PHOSLYRA FOR REDUCTION OF SERUM PHOSPHOROUS IN PATIENTS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	E547099	⤷ Start Trial
Australia	2007275606	⤷ Start Trial
Brazil	PI0714882	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,592,480

Which drugs does patent 8,592,480 protect, and when does it expire?

Summary for Patent: 8,592,480