US Patent 8,568,747: Enalapril Powder-for-Reconstitution Patent Scope, Claims, Expiration, and Competitive Landscape

US Patent No. 8,568,747 protects a narrowly defined enalapril powder intended for reconstitution into an oral liquid. Its core limitation is a three-component composition containing approximately 14% enalapril, 85% mannitol, and 1% colloidal silicon dioxide, combined with homogeneity and stability requirements after reconstitution. The patent is formulation-specific rather than an enalapril molecule patent.

The patent is commercially relevant to liquid enalapril products, particularly Epaned, because it covers a dry formulation that can be converted into an oral solution using water or syrup. It does not broadly cover every liquid enalapril formulation, every enalapril salt, or every powder containing enalapril.

What does US Patent 8,568,747 protect?

The independent claim protects a pharmaceutical powder with four material elements:

Enalapril or a pharmaceutically acceptable salt.
Approximately 14% w/w enalapril.
Approximately 85% w/w mannitol.
Approximately 1% w/w colloidal silicon dioxide.

The reconstituted product must also be homogeneous and stable for at least 12 weeks under approximately 25 +/- 5 degrees Celsius and 55 +/- 10% relative humidity.

The claim is therefore both composition-based and performance-limited. A competing product must satisfy the component and concentration limitations and the post-reconstitution stability limitation to fall within the literal scope of claim 1.

Claim element	Requirement
Dosage form	Pharmaceutical powder
Active ingredient	Enalapril or pharmaceutically acceptable salt
Enalapril concentration	About 14% w/w
Bulking agent	About 85% w/w mannitol
Glidant or stabilizing excipient	About 1% w/w colloidal silicon dioxide
Reconstitution	Oral liquid
Reconstituted-product performance	Homogeneous and stable for at least 12 weeks
Environmental condition	About 25 +/- 5 degrees Celsius and 55 +/- 10% relative humidity

The use of "consisting of" is significant. It generally closes the claimed composition to the listed components, subject to the legal treatment of incidental materials, impurities, residual solvents, manufacturing aids, and claim construction. A formulation containing a material additional to enalapril, mannitol, and colloidal silicon dioxide could present a stronger noninfringement position than a formulation using the same three components.

How narrow is claim 1?

Claim 1 is narrow in formulation architecture but potentially meaningful in product enforcement.

The claim is narrow because it requires a particular excipient system and approximate ratios. It does not claim:

Enalapril as an active pharmaceutical ingredient generally.
Enalapril tablets.
Any oral solution containing enalapril.
Any dry powder containing enalapril and a pharmaceutically acceptable excipient.
Formulations using sucrose, lactose, microcrystalline cellulose, starch, or other substitutes for mannitol.
Formulations using silicon dioxide at materially different levels.
A liquid formulation made directly without an intermediate powder.
A formulation that fails the specified stability or homogeneity limitation.

The claim may be broader in operation because "about" can cover a range around each stated percentage. The patent does not define the permissible numerical boundaries in the supplied claim text. The scope would depend on the specification, prosecution history, technical meaning of "about," and the degree of variation accepted by a court.

The three percentages nominally total 100%. That structure suggests the claim is directed to a substantially three-component powder rather than a formulation with a large quantity of unlisted excipients.

What do claims 2 through 6 add?

Claims 2 through 6 narrow claim 1 in different ways.

Claim	Added limitation	Commercial significance
2	Enalapril maleate	Targets the principal marketed salt used in oral enalapril products
3	Reconstitution in water	Covers water-based preparation
4	Reconstitution in syrup	Covers preparation using syrup as the liquid vehicle
5	Powder stable for at least six months at ambient, accelerated, or refrigerated conditions	Adds a powder shelf-life limitation
6	150 mg enalapril, 890 mg mannitol, and 10 mg colloidal silicon dioxide	Covers a specific unit quantity or batch composition

Claim 2 is commercially important because enalapril maleate is the conventional pharmaceutical form of enalapril in approved oral products. A generic using enalapril maleate would still need to satisfy the concentration, excipient, and performance limitations of claim 1.

Claim 3 and claim 4 are alternative reconstitution limitations. A product reconstituted only in water may fall within claim 3 but not necessarily claim 4. A product supplied for reconstitution in syrup may fall within claim 4. The distinction matters if the approved labeling specifies a particular diluent.

Claim 5 addresses powder stability rather than only stability after reconstitution. It may be relevant to commercial packaging, storage, distribution, and expiration dating. The wording "ambient, accelerated or refrigerated conditions" should be read with the patent specification and prosecution history because the claim text does not state a uniform time period for each condition.

Claim 6 identifies a specific formulation quantity:

150 mg enalapril
890 mg mannitol
10 mg colloidal silicon dioxide
1,050 mg total powder

The nominal enalapril concentration is approximately 14.29% of total powder, which is consistent with the "about 14%" limitation in claim 1.

Does claim 6 create an internal ambiguity?

Yes. Claim 6 states "150 mg enalapril," while claim 2 separately identifies enalapril maleate. The claim set does not, from the supplied text alone, clarify whether the 150 mg amount refers to:

150 mg of enalapril free base;
150 mg of enalapril maleate;
150 mg expressed as enalapril equivalent; or
a nominal labeled amount.

That distinction can affect both literal infringement and product comparison. Enalapril maleate has a higher molecular weight than enalapril free base, so the salt mass and active-equivalent mass are not interchangeable. The specification, examples, formulation records, and prosecution history would control the interpretation.

What patent expiration date applies to US 8,568,747?

US Patent 8,568,747 was issued on October 29, 2013. Its enforceable term is governed by the earliest effective nonprovisional filing date, applicable patent-term-adjustment provisions, terminal disclaimers, and any other term adjustment shown in the official patent record.[1]

The patent is generally associated with a 2030 expiration horizon. A definitive day-level expiration date should be taken from the USPTO patent-term record and the Orange Book listing for the relevant approved product. Patent issuance in 2013 does not mean the patent expires 20 years after issuance.

Event	Date or status
Patent issued	October 29, 2013
Patent type	Utility patent
Subject matter	Enalapril powder for oral-liquid reconstitution
Expected term horizon	2030
Generic-relevant issue	Whether the listed patent remains enforceable against the proposed product and whether the ANDA applicant makes a Paragraph IV certification

The patent does not receive a new chemical entity term because enalapril was approved decades before this formulation patent. Any FDA exclusivity associated with the product would be separate from the patent term.

What is the Orange Book status of US 8,568,747?

US 8,568,747 is relevant to the FDA-approved enalapril oral solution Epaned, marketed by Silvergate Pharmaceuticals. Epaned is an oral solution of enalapril maleate and is approved for treatment of hypertension.[2]

A listed formulation patent can require an ANDA applicant to address the patent through one of four certifications:

Paragraph I: no patent information has been submitted.
Paragraph II: the patent has expired.
Paragraph III: the applicant will not market until patent expiration.
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

The practical effect of a Paragraph IV filing depends on the reference product, the specific patent listing, FDA notification, and whether the patent owner files an infringement action within the statutory period. A valid and timely patent litigation action can trigger a 30-month stay of final ANDA approval under the Hatch-Waxman framework, subject to statutory exceptions.[3]

The patent is not a broad Orange Book barrier for all enalapril products. Its relevance is greatest for an ANDA or other product that uses the same dry-powder formulation or an equivalent composition.

Does US 8,568,747 cover Epaned?

The claim structure closely corresponds to a dry powder that can be reconstituted into an enalapril oral liquid. Epaned is supplied as an oral solution product, and its formulation and labeling must be assessed against the patent claims and the product's regulatory records.

A product may be covered even if the finished dosage form is a liquid when the patented article is the powder used to make that liquid. Conversely, a liquid product manufactured directly as a solution, without the claimed powder intermediate, may have a stronger noninfringement argument depending on the supply chain and manufacturing process.

The relevant comparison is not simply whether both products contain enalapril. It is whether the accused product has the claimed powder composition and satisfies the claimed reconstitution and stability characteristics.

What formulations are protected by the patent?

The patent's strongest coverage is directed to the following formulation profile:

Formulation characteristic	Covered position
Active	Enalapril, especially enalapril maleate
Physical form before use	Dry pharmaceutical powder
Main excipient	Mannitol
Silicon dioxide	Approximately 1% w/w
Enalapril level	Approximately 14% w/w
Reconstituted vehicle	Water or syrup
Reconstituted quality	Homogeneous oral liquid
Reconstituted stability	At least 12 weeks under the claimed conditions
Powder stability	At least six months under claim 5 conditions

The patent's formulation rationale is likely tied to the difficulty of producing a stable, homogeneous liquid enalapril dosage form. Enalapril-containing liquids can raise problems involving degradation, pH control, taste, solubility, sedimentation, dose uniformity, and storage stability. The claimed powder approach shifts part of the stability burden to the dry product and permits preparation of the liquid closer to the time of use.

What formulations are outside the most likely literal scope?

Potential design-around categories include:

A powder with a materially different ratio of enalapril, mannitol, or colloidal silicon dioxide.
A powder using a different primary excipient instead of mannitol.
A formulation containing additional excipients that avoids the closed "consisting of" language.
A liquid manufactured and packaged without a claimed powder intermediate.
A formulation that uses a different enalapril salt or active concentration, provided the claim limitations are not met.
A formulation that does not produce the claimed homogeneity or stability profile.

These are risk categories, not automatic noninfringement conclusions. The doctrine of equivalents could become relevant if a proposed product uses technically different components that perform substantially the same function in substantially the same way with substantially the same result. The closed transitional language and prosecution history could limit that argument.

How does this patent compare with enalapril molecule patents?

US 8,568,747 is a secondary patent covering a dosage-form technology. It is materially different from an original compound patent.

Patent category	Typical subject matter	Relevance to enalapril
Compound patent	Enalapril molecule or salt	Historical protection; expired long before this patent
Tablet formulation patent	Compression, coating, release, or excipient system	Relevant to solid oral products
Liquid formulation patent	Direct oral solution, pH, preservatives, or stability system	Relevant to ready-to-use liquids
Powder-for-reconstitution patent	Dry composition converted into a liquid	Core subject of US 8,568,747
Method-of-use patent	Treatment of hypertension or heart failure	Generally weak or expired for old enalapril indications
Manufacturing patent	Mixing, granulation, drying, or packaging	Potential process barrier if separately claimed

Because enalapril is an established generic active ingredient, commercial protection depends more heavily on formulation, regulatory, manufacturing, supply, and brand differentiation than on compound exclusivity.

What generic entry risks exist?

A generic entrant faces different risks depending on its proposed dosage form.

Generic oral solution

A ready-to-use oral solution may avoid the powder claims if it is not manufactured from the claimed dry composition. Risk increases if the product's manufacturing process uses the patented powder as an intermediate or if the formulation is sold in a kit containing the claimed powder.

Powder for reconstitution

A powder product using approximately 14% enalapril, 85% mannitol, and 1% colloidal silicon dioxide presents the highest infringement risk. A Paragraph IV challenge would likely focus on claim construction, prior art, indefiniteness, written description, enablement, and the meaning of "about."

Enalapril tablets

Conventional tablets are outside the principal product configuration unless the tablet or manufacturing process also incorporates the claimed powder and reconstitution features.

Alternative liquid formulation

A formulation using a different vehicle, stabilizer system, concentration, or manufacturing pathway may reduce literal infringement risk. Regulatory comparability, bioequivalence, dose uniformity, and stability remain separate approval issues.

What prior-art issues affect patent strength?

The patent's strength is likely to turn on whether the claimed combination was predictable from earlier enalapril formulations and oral-liquid technologies.

Potential prior-art categories include:

Earlier enalapril maleate powders.
Mannitol-based pharmaceutical powders.
Colloidal silicon dioxide as a flow aid or stabilizer.
Oral liquid formulations of ACE inhibitors.
Dry formulations designed to improve liquid stability.
Published pharmaceutical composition applications.
Foreign patent-family publications.
Product development records predating the effective filing date.

The strongest validity challenge would identify prior art disclosing all or nearly all of the following in one reference: the approximate component ratios, the powder form, reconstitution into an oral liquid, and the claimed homogeneity and stability result.

A weaker prior-art reference may disclose the ingredients but not the claimed ratios or performance. In that situation, the challenger would need to establish that the claimed formulation was obvious to a skilled pharmaceutical formulator and that the stability result was expected or insufficiently unexpected.

Are there method-of-use patents for enalapril?

The supplied claims are not method-of-use claims. They claim a composition and its reconstitution characteristics. They do not require administration to a patient or treatment of a specific disease.

Historical enalapril method-of-use patents are unlikely to create meaningful exclusivity for ordinary hypertension treatment because the active ingredient and principal therapeutic uses are long established. A later patent could still cover a narrowly defined patient population, dosing regimen, combination therapy, or pediatric use, but that would require a separate patent and FDA listing analysis.

What licensing and ownership issues matter?

Commercial risk should be assessed across four rights layers:

Patent ownership and assignment.
FDA reference-product ownership.
Manufacturing and contract-manufacturing rights.
Trademark and distribution rights for the marketed product.

The patent owner, approved-product sponsor, and manufacturer are not necessarily the same entity. A patent assignment does not itself establish a license to market a product, and an FDA approval does not eliminate patent infringement risk.

For licensing diligence, the critical documents are the USPTO assignment history, any recorded security interests, FDA patent listing, product-label ownership, and publicly disclosed settlement or license agreements. A private license or settlement may not be visible in the patent file.

What litigation or settlement agreements affect the patent?

The supplied information does not establish a reported infringement action, Paragraph IV settlement, or court judgment specifically involving US 8,568,747. Litigation status should be determined from PACER, district court dockets, Federal Circuit opinions, and FDA Paragraph IV litigation records.

A litigation search should use:

US Patent No. 8,568,747.
Epaned.
Silvergate Pharmaceuticals.
Enalapril maleate oral solution.
ANDA litigation involving the listed patent.
Any patent-family member asserted outside the United States.

Absent a reported case, the principal legal risk remains prospective: an ANDA applicant could challenge the patent, and the sponsor could bring an infringement action after receiving a Paragraph IV notice.

What is the geographic coverage of the patent estate?

US 8,568,747 provides rights only in the United States. International protection depends on related applications and granted patents in jurisdictions such as:

European Patent Office member states.
Canada.
Japan.
Australia.
China.
India.
Brazil.

A US patent does not establish protection in those markets. The international landscape must be reviewed through the patent family, national-phase records, legal-status databases, and country-specific expiration rules. Patent-term adjustments, supplementary protection certificates, annuity payments, and local prosecution outcomes can produce different expiration dates.

What manufacturing and IP barriers remain after patent expiration?

Patent expiration would remove the ordinary infringement barrier for the expired claims, but several commercial barriers could remain:

FDA approval requirements.
Bioequivalence or comparative clinical requirements.
Stability data.
Dose uniformity and reconstitution performance.
Manufacturing validation.
Supply of pharmaceutical-grade enalapril maleate.
Control of packaging components.
Product-specific labeling.
Trademark restrictions.
Trade secrets relating to manufacturing or scale-up.

Trade-secret manufacturing information can remain protected after patent expiration if it was not disclosed in the patent and is maintained confidentially. It cannot, however, be used to extend an expired patent claim.

Key Takeaways

US 8,568,747 is a formulation patent, not an enalapril compound patent.
Its core claim covers a powder containing approximately 14% enalapril, 85% mannitol, and 1% colloidal silicon dioxide.
The reconstituted oral liquid must be homogeneous and stable for at least 12 weeks under the claimed conditions.
Claim 2 specifically targets enalapril maleate.
Claim 6 identifies a 150 mg/890 mg/10 mg formulation corresponding to an approximately 14.29% enalapril powder.
The patent has a 2030 expiration horizon, subject to the official USPTO patent-term record.
The patent is most relevant to powder-for-reconstitution products and may be relevant to Epaned.
Directly manufactured liquid formulations and conventional tablets present different infringement profiles.
A Paragraph IV challenge would likely focus on the meaning of "about," the closed "consisting of" language, prior art, and the claimed stability results.
The US patent does not establish foreign-market protection; related national patents must be assessed separately.
No specific litigation or settlement involving this patent is established by the supplied record.

FAQs About US Patent 8,568,747

Does US 8,568,747 cover all enalapril oral solutions?

No. It is directed to a specific powder composition and requires reconstitution into a homogeneous, stable oral liquid. A directly manufactured enalapril solution may fall outside the claims.

Does using enalapril maleate automatically infringe the patent?

No. Enalapril maleate is expressly covered by dependent claim 2, but infringement also requires satisfaction of the independent claim's composition, concentration, powder, reconstitution, and stability limitations.

Can a generic avoid the patent by replacing mannitol?

Potentially. Replacing mannitol with another excipient may avoid literal infringement, but the resulting product must still satisfy FDA requirements and could face a doctrine-of-equivalents argument.

Does patent expiration eliminate FDA exclusivity?

No. Patent expiration and FDA exclusivity are separate rights. Enalapril's original drug exclusivity expired long ago, but any product-specific regulatory exclusivity must be assessed independently.

Is a six-month powder shelf life required for every infringement case?

No. Six-month stability is expressly added by claim 5. A product may still be evaluated under claim 1 without satisfying claim 5, provided it meets claim 1's composition and 12-week reconstituted-liquid stability requirements.

References

United States Patent and Trademark Office. (2013). US Patent No. 8,568,747, pharmaceutical powder for reconstitution into an oral liquid formulation. USPTO Patent Center.
U.S. Food and Drug Administration. (n.d.). Epaned (enalapril maleate) oral solution prescribing information. FDA-approved labeling.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.
United States Code. (2023). 35 U.S.C. §§ 154 and 156: Patent term and patent term extension.
United States Code. (2023). 21 U.S.C. § 355(j): Abbreviated applications and patent certifications under the Hatch-Waxman Act.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	EPANED KIT	enalapril maleate	FOR SOLUTION;ORAL	204308-001	Aug 13, 2013		DISCN	Yes	No	8,568,747	⤷ Start Trial	Y				⤷ 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
Brazil	112015007592	⤷ Start Trial
Canada	2887379	⤷ Start Trial
European Patent Office	2903690	⤷ Start Trial
Spain	2770403	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2014055667	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,568,747

Which drugs does patent 8,568,747 protect, and when does it expire?

Summary for Patent: 8,568,747