United States Drug Patent 7,223,387: Claim Scope, Expiration, Orange Book Status, and Generic Risk

US Patent 7,223,387 protects a narrow topical oil-in-water emulsion combining hydrocortisone with acyclovir, penciclovir, or a specified related antiviral. The claims require specific phase placement, excipient classes, concentration ranges, and carrier components. The patent’s nominal 20-year term has expired, eliminating current U.S. patent-based launch barriers from this patent. The commercial product most closely associated with the claimed formulation is Xerese, an acyclovir 5% and hydrocortisone 1% cream.

What does US Patent 7,223,387 cover?

US 7,223,387 covers topical compositions and treatment methods for herpesvirus infections. The independent composition claim requires every limitation below:

Required element	Claim requirement
Dosage form	Topical oil-in-water emulsion
Corticosteroid	Lipophilic hydrocortisone
Antiviral	Acyclovir, penciclovir, or 9-(4-hydroxy-2-(hydroxymethyl)butyl)guanine
Hydrocortisone location	Oil phase
Antiviral location	Water phase
Emulsifier	0.05% to 5% by weight
Propylene glycol	18% to 22% by weight
Isopropyl ester	12% to 18% by weight
Isopropyl ester scope	Isopropyl dodecanoate, myristate, palmitate, stearate, eicosanoate, behenoate, or mixtures
Hydrocortisone concentration	0.5% to 2% by weight
Antiviral concentration	1% to 7% by weight

The patent does not claim acyclovir generally, hydrocortisone generally, or every topical combination of an antiviral and corticosteroid. Infringement requires a product to satisfy the claimed composition and concentration limitations, subject to claim construction and the applicable doctrine of equivalents.

The patent issued May 29, 2007, from an application filed in December 2002. Its subject matter concerns formulation engineering intended to place the lipophilic corticosteroid and relatively water-compatible antiviral in an emulsion system with defined penetration-enhancing and carrier components. [1]

How narrow is independent claim 1?

Independent claim 1 is commercially relevant but structurally narrow. A competing product can avoid literal infringement by omitting or changing any material limitation.

The main design-around variables are:

Using a water-in-oil emulsion, gel, ointment, solution, suspension, or non-emulsion cream.
Moving hydrocortisone out of the oil phase.
Moving the antiviral out of the water phase.
Omitting propylene glycol.
Using propylene glycol outside the 18% to 22% range.
Omitting the specified isopropyl C12-C22 alkanoate.
Using an ester outside the listed carbon-chain or positional-isomer scope.
Reducing or increasing hydrocortisone outside the 0.5% to 2% range.
Using antiviral concentrations outside the claimed range.
Substituting a different emulsifier or an emulsifier concentration outside 0.05% to 5%.

The ranges are particularly important. A formulation containing 17% isopropyl myristate or 23% propylene glycol would fall outside the literal numerical scope of claim 1, although infringement analysis would still depend on the specification, prosecution history, measurement conventions, and equivalents law.

What do the dependent claims add?

The dependent claims identify commercial formulation embodiments and further narrow the claim set.

Claims	Added limitation
2	Isopropyl myristate
3	Acyclovir
4	Acyclovir or penciclovir
5	Acyclovir at 4% to 7%; hydrocortisone at 0.5% to 2%
6	Penciclovir at 1% to 7%; hydrocortisone at 0.5% to 2%
8	Propylene glycol at 20%
9	Isopropyl alkanoic ester at 15%
10	Antiviral at 4% to 7%
11	Isopropyl myristate at 15%
12	Vaseline or liquid paraffin as mineral oil
13	Stearic acid
14	Cetostearyl alcohol
15	Poloxamer 188 or sodium lauryl sulfate
16	Cetostearyl alcohol, vaseline, and liquid paraffin in the oil phase
17	Poloxamer 188 and sodium lauryl sulfate
18	Acyclovir at 5%
19	Acyclovir at 5% and hydrocortisone at 1%

Claims 18 and 19 are the most commercially significant because they correspond closely to the 5% acyclovir and 1% hydrocortisone strength used in Xerese. Claim 19 also preserves the carrier limitations inherited from claim 5 and, through the dependency chain, claim 1. [1]

Does the patent cover Xerese?

Xerese is an acyclovir 5% and hydrocortisone 1% topical cream approved by the FDA for the early treatment of recurrent herpes labialis to reduce the likelihood of ulcerative cold sores and shorten lesion healing time. The product’s active-ingredient strengths match claim 19 of US 7,223,387. [2]

A strength match alone does not establish infringement. A commercial product must also satisfy the patent’s formulation limitations, including:

Oil-in-water emulsion structure.
Hydrocortisone in the oil phase.
Acyclovir in the water phase.
Propylene glycol at 18% to 22%.
Isopropyl C12-C22 alkanoate at 12% to 18%.
Emulsifier concentration within 0.05% to 5%.

Public labeling generally does not disclose the complete quantitative composition or phase partitioning needed to perform a definitive claim chart. The patent, however, is plainly directed to the formulation architecture used by the acyclovir/hydrocortisone product class. [1,2]

When did US 7,223,387 expire?

The patent’s nominal term ended in December 2022, based on the 20-year term measured from the relevant U.S. nonprovisional filing date. US 7,223,387 therefore no longer provides an enforceable U.S. patent exclusion right in 2026. [1]

Event	Date
U.S. application filing	December 2002
Patent grant	May 29, 2007
Nominal 20-year expiration	December 2022
Current status	Expired by term

Any patent-term adjustment or terminal disclaimer would need to be confirmed from the USPTO patent-term record. The expiration conclusion is not changed by the patent’s 2007 grant date because post-1995 U.S. utility patents generally run from the earliest relevant nonprovisional filing date rather than 20 years from issuance. [1,3]

What was the FDA exclusivity period for the product?

The FDA approved Xerese under NDA 022436 in 2009. The product contains previously known active ingredients, acyclovir and hydrocortisone, and therefore did not receive five-year new chemical entity exclusivity. Any FDA exclusivity associated with the approval was separate from the patent term and did not extend the patent’s enforceable life. [2,4]

The key distinction is:

Protection type	Relevance to Xerese
New chemical entity exclusivity	Not applicable to the known active ingredients
New formulation or clinical-approval exclusivity	Limited regulatory period, if granted
US 7,223,387 patent	Expired in December 2022
Trade secret protection	Potentially relevant to manufacturing know-how, not listed patent scope
Trademark protection	May continue separately for the Xerese brand

FDA exclusivity prevents certain abbreviated approvals for a defined period. It does not revive an expired patent or create a perpetual barrier to a formulation that no longer falls within enforceable patent claims.

What is the Orange Book status of US 7,223,387?

US 7,223,387 was listed in connection with the Xerese NDA as a product patent covering the acyclovir/hydrocortisone cream formulation. Orange Book listing affects the timing and certification requirements for an ANDA while the listed patent is enforceable. It does not extend the patent beyond its statutory term. [3]

After expiration, an ANDA applicant no longer faces a patent-term delay from that patent. A generic applicant may still need to address:

Patent certification requirements applicable at the time of submission.
Current FDA labeling requirements.
Bioequivalence or pharmaceutical-equivalence requirements.
Product-specific guidance, if applicable.
Any other unexpired patents or exclusivities associated with the reference product.

The Orange Book is the controlling FDA source for current listed-patent status. [3]

Were there Paragraph IV challenges to the patent?

A Paragraph IV certification would assert that a listed patent is invalid, unenforceable, or not infringed. For US 7,223,387, the commercial importance of a Paragraph IV challenge was greatest before the December 2022 expiration date.

A formulation-specific ANDA applicant could have pursued several positions:

Challenge position	Potential theory
Non-infringement	Product lacks the claimed ester, phase arrangement, or concentration range
Invalidity for anticipation	Earlier topical emulsion disclosed all claim elements
Invalidity for obviousness	Combining known acyclovir, hydrocortisone, emulsifiers, and penetration enhancers was routine
Indefiniteness	Disputed meaning of phase-location or formulation terms
Written description	Genus and concentration-range coverage exceeds the original disclosure
Enablement	Full claimed genus may not be enabled across all listed esters and antivirals

The claims contain multiple narrowing limitations, which can make anticipation more difficult but can also create obviousness arguments if prior art disclosed the same excipients and ranges. The strength of any Paragraph IV case would depend heavily on the patent specification, prosecution record, expert formulation evidence, and the cited prior art.

No current Paragraph IV launch barrier remains from this expired patent.

What patent litigation affects US 7,223,387?

The patent’s principal litigation significance was tied to potential generic versions of acyclovir/hydrocortisone cream before expiration. Once the patent expired, a case based solely on future infringement of US 7,223,387 would generally lack prospective exclusion value.

A complete litigation assessment must distinguish:

Patent-infringement actions involving the patent.
ANDA litigation under the Hatch-Waxman Act.
Trademark disputes involving Xerese.
Product-liability claims.
Licensing or settlement agreements.
Post-expiration disputes involving damages for pre-expiration sales.

The patent number alone does not establish that a settlement, covenant not to sue, or launch agreement existed. Any settlement would have to be evaluated for its entry date, authorized-generic provisions, launch restrictions, and Federal Trade Commission or Department of Justice review where applicable.

How strong was the patent estate?

The patent estate was strongest against products that copied the full commercial formulation, including the 5% acyclovir/1% hydrocortisone strength, 20% propylene glycol, 15% isopropyl myristate, and the specified emulsion system.

Its strength was lower against products using different delivery systems or materially different excipient profiles.

Risk factor	Assessment
Claim breadth	Narrow to moderate
Formulation specificity	High
Coverage of acyclovir 5%/hydrocortisone 1%	Strong if all carrier limits were met
Coverage of alternative creams	Limited
Design-around potential	Meaningful
Biosimilar relevance	None
Current enforceability	None after term expiration
Manufacturing barrier	Possible know-how barrier, not established by this patent alone

The patent does not cover biologics, long-acting delivery systems, oral antivirals, injectable products, or acyclovir products lacking the claimed hydrocortisone and carrier system.

What geographic protection existed?

US 7,223,387 provided protection only in the United States. Corresponding foreign applications may have created separate rights in Europe and other jurisdictions, but each foreign right required independent review of:

National-stage status.
Grant date.
Validity proceedings.
Patent-term adjustment or supplementary protection.
Annual maintenance payments.
Local claim scope.
Local expiry.

A U.S. expiration did not automatically terminate foreign family members. Conversely, a live foreign family member did not create U.S. infringement risk.

What generic launch scenarios exist after expiration?

Three commercial pathways are available after patent expiration:

Direct generic cream

A manufacturer can develop an acyclovir/hydrocortisone cream with the same active strengths while designing around any surviving formulation patents. If no unexpired patents or exclusivities block approval, the product may proceed through the applicable ANDA pathway.

Alternative formulation

A company can use a different emulsion system, gel, ointment, solvent system, or excipient profile. This approach reduces reliance on the expired patent’s exact formulation architecture but may create additional development and bioequivalence work.

Authorized or branded-generic strategy

The reference-product sponsor or a licensee may commercialize an authorized generic or licensed product. This can preserve distribution access after patent expiry but does not extend the expired patent.

The main remaining barriers are regulatory approval, manufacturing scale, supply reliability, clinical positioning, and payer access. The expired patent itself is no longer a launch barrier.

How does this patent compare with ordinary acyclovir patents?

US 7,223,387 differs from basic acyclovir patents in three respects:

Issue	US 7,223,387	Basic acyclovir patent
Protected subject matter	Combination topical formulation	Active ingredient, synthesis, or broad use
Key limitation	Hydrocortisone plus specified emulsion/carrier system	Acyclovir molecule or general antiviral use
Product relevance	Acyclovir/hydrocortisone cream	Broad acyclovir products
Design-around route	Change carrier, phase, excipient, or concentration	More difficult if active-ingredient claims are valid
Current status	Expired in the U.S.	Depends on the individual patent

The patent’s commercial value was tied to formulation differentiation rather than control of acyclovir as an active pharmaceutical ingredient.

Key Takeaways

US 7,223,387 claims a specific oil-in-water topical emulsion containing hydrocortisone and acyclovir, penciclovir, or a related antiviral.
Claim 1 requires defined phase placement, emulsifier content, propylene glycol concentration, isopropyl ester concentration, and active-ingredient ranges.
Claims 18 and 19 are particularly relevant to a 5% acyclovir/1% hydrocortisone product.
Matching the active strengths does not alone establish infringement.
The patent’s nominal U.S. term ended in December 2022.
The patent no longer creates a current U.S. generic-launch barrier.
No biosimilar pathway is relevant because the products are small-molecule topical drugs.
Foreign family members must be analyzed separately by jurisdiction.
Remaining commercial barriers are primarily regulatory, manufacturing, formulation-development, and market-access issues.

FAQs About US Patent 7,223,387

Does US 7,223,387 cover all acyclovir and hydrocortisone creams?

No. It covers only products meeting the claim limitations, including the oil-in-water emulsion, specified carrier components, phase placement, emulsifier range, and concentration ranges.

Can a generic use 5% acyclovir and 1% hydrocortisone after patent expiration?

Yes, subject to FDA approval and any other applicable unexpired patents or regulatory exclusivities. The expiration of US 7,223,387 removes that patent as a U.S. exclusion right.

Is penciclovir independently protected by the patent?

Penciclovir is included within the claimed antiviral alternatives, but only in the claimed topical composition and concentration framework. The patent does not claim all penciclovir products.

Does the patent cover a gel containing acyclovir and hydrocortisone?

Not on the face of claim 1. Claim 1 requires an oil-in-water emulsion. A gel could raise infringement issues only if it legally met the emulsion and other limitations, which depends on its actual formulation and claim construction.

Does expiration of the U.S. patent end protection in Europe?

No. U.S. expiration does not determine the status of corresponding patents in Europe or other countries. Each national or regional patent must be checked independently.

References

United States Patent and Trademark Office. (2007). US Patent No. 7,223,387, topical composition comprising an antiviral and a corticosteroid.
U.S. Food and Drug Administration. (2009). Xerese prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database, NDA 022436.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	9803929	Nov 18, 1998

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	023705	⤷ Start Trial
Austria	288283	⤷ Start Trial
Australia	1436400	⤷ Start Trial
Australia	772435	⤷ Start Trial
Canada	2351463	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,223,387

Summary for Patent: 7,223,387