# US Patent 10,039,745: Enalapril Oral Liquid Formulation Claims, Patent Scope, and Generic Entry Risk

US Patent 10,039,745 protects a refrigerated, stable oral liquid formulation of enalapril based on a defined citric acid/sodium citrate buffer system and sodium benzoate preservative. The patent does not claim enalapril itself, enalapril maleate as an active pharmaceutical ingredient, or the treatment of hypertension. Its commercial value is concentrated in the formulation of pediatric or dysphagia-friendly enalapril oral solution products.

The strongest claim elements are the combination of:

Enalapril at approximately 0.6-1.2 mg/mL;
Citric acid and sodium citrate within specified concentration ranges;
Sodium benzoate at approximately 0.7-1.2 mg/mL;
Refrigerated stability at approximately 5°C for at least 12 months;
At least 95% of the initial enalapril remaining; and
No more than 5% total impurities or related substances.

Claims 1-10 express the formulation in mg/mL. Claims 11-20 provide a separate concentration framework based on the percentage of total solids.

What does US Patent 10,039,745 cover?

The patent covers a stable aqueous enalapril formulation, not every liquid enalapril product. A potentially infringing product would need to satisfy every limitation of at least one asserted claim, either literally or under the doctrine of equivalents.

Independent claim 1

Claim 1 requires all of the following:

Element	Claimed scope
Active ingredient	About 0.6-1.2 mg/mL enalapril or acceptable salt/solvate
Buffer	About 0.8-3.5 mg/mL citric acid
Buffer	About 0.1-0.8 mg/mL sodium citrate
Preservative	About 0.7-1.2 mg/mL sodium benzoate
Vehicle	Water
Storage condition	About 5±3°C
Storage period	At least 12 months
Assay stability	At least 95% of initial enalapril
Degradation limit	No more than 5% total impurity or related substances

The stability limitations are substantive claim requirements. A formulation containing the listed ingredients may fall outside claim 1 if it cannot satisfy the claimed stability result. Conversely, the stability language can create evidentiary issues because infringement may require analytical testing after the relevant storage period.

The phrase “about” gives the patentee some tolerance around the numerical limits. The scope is not necessarily restricted to exact endpoints, but the permissible variation would depend on claim construction, prosecution history, and the technical meaning of “about” in the patent specification.

Independent claim 11

Claim 11 covers a second formulation defined by the composition of the total solids:

Element	Claimed scope as percentage of solids
Enalapril or salt/solvate	About 10%-25%
Citric acid	About 17%-47%
Sodium citrate	About 1%-11%
Sodium benzoate	About 3%-25%
Vehicle	Water
Stability	At least 12 months at about 5±3°C
Enalapril remaining	At least 95%
Total impurities	No more than 5%

Claim 11 is not merely a restatement of claim 1. It uses a different measurement basis. A product can fall within the absolute mg/mL ranges of claim 1 but outside the percentage-of-solids ranges of claim 11, or the reverse, depending on the amount of water and total dissolved solids.

For freedom-to-operate analysis, both independent claim sets should be tested separately.

Which dependent claims create the narrowest formulation scope?

Claims 2-10 and 12-20 narrow the independent claims through taste masking, excipient exclusions, pH, and extended stability.

Sucralose claims

Claims 2 and 12 require sucralose:

Claim 2: approximately 0.5-0.9 mg/mL;
Claim 12: approximately 8%-18% of total solids.

Sucralose is not required by claims 1 or 11. A formulation without sucralose can still infringe an independent claim if the other elements are present.

Flavoring-agent claims

Claims 3 and 13 require a flavoring agent. The claims do not specify a particular flavor. A flavoring agent could include a commercially acceptable fruit or sweet flavor, subject to the patent specification and ordinary pharmaceutical interpretation.

These claims are narrower than claims 1 and 11 and are less likely to be central where a generic applicant uses an unflavored product.

Negative limitations

Claims 4 and 14 require that the formulation not contain mannitol. Claims 5 and 15 require that it not contain silicon dioxide.

These limitations do not apply to claims 1 or 11. A formulation containing mannitol or silicon dioxide may therefore remain exposed to the independent claims. The negative limitations are most relevant to products that otherwise satisfy the base formulation but intentionally include one of those excipients.

pH limitations

Claims 6-8 and 16-18 create a hierarchy:

Claims 6 and 16: pH below approximately 3.5;
Claims 7 and 17: pH approximately 3.0-3.5;
Claims 8 and 18: pH approximately 3.3.

Claims 7 and 8 are narrower than claim 6. A product at pH 3.3 would generally fall within each applicable pH limitation, assuming the other elements are satisfied. A product at pH 3.6 would not satisfy the literal pH limitations in claims 6-8, although it could still implicate claims 1 or 11.

Extended refrigerated stability

Claims 9 and 19 require at least 18 months of stability. Claims 10 and 20 require at least 24 months.

These claims can be commercially important because a marketed product may carry a 12-, 18-, or 24-month refrigerated shelf life. A product with only 12 months of supported stability may avoid the 18- and 24-month claims while remaining exposed to claims 1 and 11.

What formulation features are required, and which are optional?

The following table separates mandatory and optional features.

Feature	Required by claims 1 and 11?	Required only by dependent claims?
Enalapril or acceptable salt/solvate	Yes	No
Water	Yes	No
Citric acid	Yes	No
Sodium citrate	Yes	No
Sodium benzoate	Yes	No
Refrigerated stability	Yes	No
Sucralose	No	Claims 2 and 12
Flavoring agent	No	Claims 3 and 13
Absence of mannitol	No	Claims 4 and 14
Absence of silicon dioxide	No	Claims 5 and 15
pH below 3.5	No	Claims 6 and 16
pH 3.0-3.5	No	Claims 7 and 17
pH approximately 3.3	No	Claims 8 and 18
18-month stability	No	Claims 9 and 19
24-month stability	No	Claims 10 and 20

The core patent position is therefore broader than a claim limited to a particular commercial flavor, sweetener, or pH. The independent claims do not require sucralose, a flavor, a particular shelf life beyond 12 months, or the exclusion of mannitol and silicon dioxide.

How strong is the patent estate for enalapril oral solution?

US Patent 10,039,745 has meaningful formulation protection because it combines composition ranges with performance-based stability requirements. A competitor cannot necessarily avoid the patent by changing only one minor excipient if it continues to use the claimed buffer-preservative system and meets the stability limitations.

The estate is stronger against a directly substitutable product that has:

Enalapril concentration near 1 mg/mL;
Citric acid and sodium citrate as the buffer;
Sodium benzoate as preservative;
Acidic pH near 3.3;
Refrigerated storage;
A 12- to 24-month shelf life; and
Low enalapril degradation.

The estate is weaker against a product that changes the preservation or buffer architecture. Potential design-around paths include:

Replacing sodium benzoate with another preservative;
Using a different buffer system;
Moving outside the claimed enalapril concentration ranges;
Using a nonaqueous or mixed-solvent system;
Developing a product that does not satisfy the claimed refrigerated stability result;
Using a materially different pH, subject to formulation and tolerability constraints; or
Marketing a dosage form other than an oral liquid.

A design-around must be assessed against both the literal claim language and equivalents. Simply moving a concentration marginally outside a claimed range may not eliminate litigation risk.

How does this patent compare with enalapril API and method-of-use patents?

US Patent 10,039,745 is a formulation patent. It does not appear from the supplied claims to cover:

Enalapril’s chemical composition;
Enalapril maleate manufacture;
A crystalline form of enalapril maleate;
A dosing regimen;
Treatment of hypertension or heart failure;
A tablet or capsule;
A transdermal or injectable formulation; or
A manufacturing process for the active ingredient.

This distinction matters for generic entry. Enalapril tablets and capsules may not practice these claims because they do not contain the claimed aqueous oral liquid formulation. A competing oral solution, however, faces the principal risk.

The claims also do not require a particular route of administration beyond the formulation being oral. They are not method-of-treatment claims, so a product applicant’s regulatory certification would primarily concern listed formulation patents rather than a method-of-use carve-out.

What is the likely Orange Book significance?

Enalapril oral solution products are generally regulated as prescription drugs under an approved new drug application. The commercial reference product associated with this formulation technology has been marketed as Epaned, an enalapril maleate oral solution. FDA labeling identifies Epaned as an oral solution used for hypertension and heart failure indications.[2]

A patent can be relevant to the Orange Book only if it meets FDA listing requirements and is submitted for the approved drug. The supplied claims alone do not establish the patent’s current Orange Book listing status, whether it is listed against a particular NDA, or whether any listing has been delisted. Those matters are determined from the current FDA Orange Book and the applicable NDA patent submission.

If US Patent 10,039,745 is listed against the reference product, an ANDA applicant seeking approval before patent expiry could face a Paragraph IV certification. The applicant would assert that the patent is invalid, unenforceable, or not infringed. A timely patent-holder lawsuit could trigger the statutory 30-month stay under Hatch-Waxman, subject to the details of the certification, notice, litigation timing, and applicable FDA rules.[3]

When does US Patent 10,039,745 lose exclusivity?

The patent issued on July 31, 2018.[1] The exact expiration date depends on the patent’s earliest effective nonprovisional priority date, continuity chain, patent term adjustment, and any patent term extension.

The claims supplied do not identify those term records. A grant date alone cannot establish the legally operative expiration date. The relevant date must be taken from USPTO Patent Center and the patent’s official term calculation. Regulatory exclusivity is separate from patent term. FDA orphan-drug, pediatric, new chemical entity, or other exclusivity periods do not automatically follow from the formulation patent.

For commercial planning, three dates should be tracked separately:

Exclusivity item	Relevance
Patent expiration	Determines ordinary patent-based exclusion
FDA regulatory exclusivity	May block approval independent of patent rights
Litigation stay	Can delay approval after a Paragraph IV challenge

What generic entry risks exist?

A generic or follow-on oral solution could pursue several entry strategies:

Direct formulation challenge

The applicant uses substantially the same buffer and preservative system and files a Paragraph IV certification. This creates the highest infringement exposure but may preserve bioavailability, taste, stability, and manufacturing advantages.

Non-infringing formulation

The applicant changes the preservative, buffer, pH, or concentration profile. This can reduce patent risk but may require new stability, palatability, preservative-effectiveness, and bioequivalence work.

Paragraph III strategy

The applicant accepts the patent’s validity and waits until the relevant patent expiration date. This reduces litigation risk but delays commercial entry.

Indication carve-out

A section viii statement may remove a patented method of use from labeling where legally available. That strategy is less relevant to the supplied claims because they are directed to the formulation rather than a treatment method.

What patent litigation or settlements affect the patent?

The supplied claim text does not identify a Paragraph IV notice, district-court action, judgment, or settlement agreement. Litigation exposure must be assessed from the Orange Book listing, FDA Paragraph IV records, PACER, and relevant district-court and Federal Circuit dockets.

A settlement could include a licensed early-entry date, a non-assert covenant, manufacturing restrictions, or supply terms. None of those commercial terms can be inferred from the claims. A patent analysis should not treat the existence of the patent as proof that litigation occurred or that a generic launch date has been agreed.

Key Takeaways

US Patent 10,039,745 is directed to a stable aqueous oral enalapril formulation.
The core combination is enalapril, citric acid, sodium citrate, sodium benzoate, water, and defined refrigerated stability.
Claims 1-10 use mg/mL ranges; claims 11-20 use percentages of total solids.
Sucralose, flavoring, pH near 3.3, exclusion of mannitol or silicon dioxide, and 18- or 24-month stability are dependent limitations.
Claims 1 and 11 do not require sucralose or flavoring and do not exclude mannitol or silicon dioxide.
The principal generic risk concerns a 1 mg/mL-class oral solution using the same acidic citrate buffer and sodium benzoate system.
Replacing the preservative or buffer is the clearest formulation-level design-around path.
The patent is not, based on the supplied claims, a patent on enalapril, enalapril maleate, tablets, capsules, or treatment methods.
Exact patent expiration, current Orange Book listing, Paragraph IV activity, and settlement status require the current USPTO, FDA, and court records.

FAQs About US Patent 10,039,745

Does US Patent 10,039,745 cover Epaned?

It may be relevant to Epaned because Epaned is an enalapril maleate oral solution, but product coverage depends on the marketed formulation, patent listing, and whether the commercial product satisfies every limitation of an asserted claim.

Can a liquid enalapril product avoid the patent by omitting sucralose?

Yes, potentially. Claims 1 and 11 do not require sucralose. Omitting sucralose avoids claims 2 and 12, but it does not avoid the independent claims if the remaining formulation and stability limitations are met.

Does adding mannitol avoid US Patent 10,039,745?

Not necessarily. The exclusion of mannitol appears only in claims 4 and 14. Claims 1 and 11 do not prohibit mannitol, so a product containing mannitol could still fall within an independent claim.

Is a product at pH 3.6 outside all claims?

It would likely fall outside the express pH limitations in claims 6-8 and 16-18, but pH is not a limitation of independent claims 1 and 11. The product could still face those claims if the other elements are present.

Does the patent block enalapril tablets?

The supplied claims are directed to a stable oral liquid formulation containing water and defined liquid-formulation components. Enalapril tablets would generally not satisfy those formulation limitations.

References

United States Patent No. 10,039,745 B2. (2018, July 31). Stable liquid formulations of enalapril. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Epaned (enalapril maleate) oral solution prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Orange Book.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).

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	enalapril maleate	SOLUTION;ORAL	208686-001	Sep 20, 2016	AB	RX	Yes	Yes	⤷ Start Trial	⤷ 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	112018068960	⤷ Start Trial
European Patent Office	3429581	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2017161339	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,039,745

Which drugs does patent 10,039,745 protect, and when does it expire?

Summary for Patent: 10,039,745