United States Patent RE39264: Claim Scope, Expiration, FDA Status, and Herpes Combination Patent Landscape

U.S. Patent RE39264 covers topical pharmaceutical compositions and treatment methods combining an antiviral agent with an anti-inflammatory glucocorticoid for herpesvirus infections. Its broadest practical commercial scope reaches topical acyclovir-hydrocortisone products, including the formulation associated with XERESE. The patent is a reissue and cannot extend the term of the original patent. The enforceable term of RE39264 has ended, so it does not provide a current U.S. barrier to generic development or launch.

What does U.S. Patent RE39264 cover?

RE39264 covers four principal subject-matter groups:

Topical compositions containing an antiviral and a glucocorticoid.
Specific antiviral-glucocorticoid combinations, particularly acyclovir or foscarnet with hydrocortisone.
Defined concentration ranges for foscarnet, acyclovir, hydrocortisone, and budesonide.
Methods for preventing or treating herpesvirus infections of skin or mucous membranes.

The claims are drafted around a synergistic combination. That limitation is central. A product containing an antiviral and a corticosteroid may fall within the chemical definition of the claims but still require proof that the claimed combination is "more effective" than either ingredient alone, particularly under claims 2, 18, and 37.

Core claim architecture

Claim group	Subject matter	Practical scope
Claims 1, 3, 6, 7	Broad topical compositions	Antiviral plus broad glucocorticoid classes
Claims 2, 4, 5, 8-15	Specific compositions and concentrations	Foscarnet, acyclovir, hydrocortisone, and budesonide combinations
Claim 16	Dosage forms	Cream, lotion, gel, ointment, plaster, stick, or pen
Claims 17-23	Treatment methods	Topical prophylaxis or treatment of herpesvirus infections
Claims 24-37	Narrower treatment regimens	Specified compositions, recurrent infection, dosing frequency, and acyclovir-hydrocortisone use

The patent therefore has both product claims and method-of-use claims. A competing product could face different infringement theories depending on its formulation, labeling, promotional materials, and actual use.

What antiviral substances are covered by RE39264?

The claims identify a broad group of antiviral ingredients:

Foscarnet
Acyclovir
Cidofovir
Desciclovir
Famciclovir
Ganciclovir
Lobucavir
Penciclovir
PMEA
Valacyclovir
PAA
PFA
Compound 2242
H2G, identified as 9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine

Claims 1 and 17 use a functional and class-based definition covering herpes-specific nucleoside analogues preferentially phosphorylated in infected cells, as well as cidofovir, PMEA, PAA, and PFA.

Claims 2 and 18 use a more explicit list. The scope includes salts, esters, and solvates where the claim language permits them. That language can reach prodrug or salt forms, but it does not automatically cover every derivative. The derivative must satisfy the applicable claim construction and remain a topically acceptable antiviral substance.

Commercial relevance of the antiviral list

The commercially important species is acyclovir. The other listed compounds have materially different development profiles:

Antiviral	Commercial relevance to topical herpes treatment
Acyclovir	High; established topical herpes antiviral and central commercial species
Foscarnet	Limited topical commercial use; formulation and tolerability issues
Penciclovir	Commercially relevant in topical penciclovir products, but not necessarily within every claim combination
Famciclovir	Primarily systemic use; topical product relevance is limited
Valacyclovir	Primarily systemic prodrug; topical implementation raises formulation questions
Cidofovir	Investigational or specialized topical use; toxicity and compounding issues
Ganciclovir	More closely associated with cytomegalovirus treatment
PMEA, PAA, PFA, H2G, 2242, lobucavir, desciclovir	Limited current commercial relevance

The broad list increases theoretical claim reach but does not create equal commercial significance for every listed antiviral.

What glucocorticoids are protected by RE39264?

Claims 3, 4, 19, and 20 identify a wide glucocorticoid group, including:

Hydrocortisone
Alclometasone
Desonide
Fluprednidene
Flumethasone
Hydrocortisone butyrate
Clobetasone
Triamcinolone acetonide
Betamethasone
Budesonide
Desoximetasone
Diflorasone
Fluocinolone
Fluocortolone
Fluticasone
Methylprednisolone aceponate
Mometasone
Rofleponide

The commercially significant corticosteroid is hydrocortisone. Claims 5, 7, 21, 23, and 37 narrow the combinations to either foscarnet-hydrocortisone or acyclovir-hydrocortisone. Claim 6 and claim 22 separately identify foscarnet-budesonide.

The presence of a corticosteroid in a topical herpes product does not by itself establish infringement. The product must also satisfy the antiviral, topical carrier, combination, and, where applicable, synergy limitations.

What formulations are protected by RE39264?

Claim 16 expressly covers:

Creams
Lotions
Gels
Ointments
Plasters
Sticks
Pens

The claims are not limited to a particular excipient system. A formulation can therefore use different penetration enhancers, emulsifiers, solvents, preservatives, buffering systems, or rheology modifiers, provided the composition otherwise satisfies the relevant claim.

Concentration ranges

The most commercially relevant concentration limitations are:

Claim	Antiviral concentration	Glucocorticoid concentration
Claim 8	Foscarnet: 0.1%-10% w/w	Hydrocortisone: 0.005%-3% w/w
Claim 9	Foscarnet: 1%-5% w/w	Within claim 8 range
Claim 10	Foscarnet: 0.3%-3% w/w	Hydrocortisone: 0.25%-1% w/w
Claim 11	Foscarnet: 0.1%-10%	Budesonide: 0.005%-3%
Claim 12	Foscarnet: 1%-5%	Within claim 11 range
Claim 13	Acyclovir: 0.1%-10% w/w	Hydrocortisone: 0.005%-3% w/w
Claim 14	Acyclovir: 1%-5% w/w	Within claim 13 range
Claim 15	Within claim 14	Hydrocortisone: 0.25%-1% w/w

An acyclovir 5% and hydrocortisone 1% cream falls within the numerical ranges of claims 13-15, assuming the other limitations are met. Those concentrations are commercially associated with the acyclovir-hydrocortisone product XERESE.

How strong are the composition claims?

The broad composition claims have potentially wide literal coverage but face several validity and enforcement constraints.

Claim 1

Claim 1 requires:

A pharmaceutical composition
Topical administration
A topically acceptable antiviral
A defined antiviral category
An anti-inflammatory glucocorticoid
A pharmaceutically acceptable carrier
A synergistic combination

The claim is broad because it combines a functional antiviral category with a long list of corticosteroids. Its principal weaknesses are breadth, written-description support, enablement, and the meaning of "synergistic."

A challenger could argue that the specification does not adequately support every antiviral-glucocorticoid pairing across the full claim scope. The broader the asserted combination, the more important the experimental disclosure becomes.

Claim 2

Claim 2 is narrower because it requires:

Treatment of recurrent herpes infections
The antiviral and glucocorticoid as the sole active drug substances
Hydrocortisone or an ester thereof
A showing that the combination is more effective than either component alone

The "sole active drug substances" requirement may exclude products containing another pharmacologically active ingredient. It also creates a potential design-around route through a product with an additional active component, although such a strategy introduces regulatory and commercial complications.

Claims 5 and 7

Claims 5 and 7 identify specific combinations:

Foscarnet plus hydrocortisone
Acyclovir plus hydrocortisone

Claim 7 is the most commercially important because acyclovir is widely used and hydrocortisone is a common topical corticosteroid. Claim 37 further isolates the acyclovir-hydrocortisone method.

What method-of-use rights does RE39264 claim?

The method claims cover topical administration for:

Prophylaxis of herpesvirus infection
Treatment of herpesvirus infection
Recurrent herpesvirus infection
Skin or mucous membrane infections
Mammalian patients having or at risk of developing the infection

Claims 17 and 18 allow administration "in combination or in sequence." This language is broader than a requirement that both ingredients be physically premixed. Separate administration of the antiviral and glucocorticoid could fall within scope if the other limitations are satisfied.

Claims 27-30 and 33-36 add administration frequency limitations of one to 10 times per day, with dependent claims narrowing the regimen to three to four times per day.

Labeling and induced infringement

For an active patent, a generic label directing use of an acyclovir-hydrocortisone product for recurrent herpes labialis could create induced-infringement exposure if the asserted method claims remained enforceable. Promotional materials, physician instructions, and patient labeling would be relevant.

Because RE39264 has expired, these method claims no longer create current U.S. infringement exposure. The same analysis remains relevant to expired-patent validity review and to later patents with overlapping method claims.

When did RE39264 lose exclusivity?

RE39264 lost exclusivity when the term of the original patent ended. Reissue does not restart or extend the original patent term under 35 U.S.C. § 251. The operative expiration date is determined from the original patent and applicable term-adjustment or term-extension rules, not from the reissue grant date.

RE39264 is therefore an expired patent as of 2026. No current U.S. exclusivity remains under RE39264, and a generic applicant does not need a Paragraph IV certification directed to an expired patent.

Reissue significance

A reissue can correct an error in an issued patent and can broaden or narrow claims within statutory limits. It cannot be used to create a new patent term. The reissue claims must also remain tied to the disclosure and original patent rights.

The claim text supplied contains apparent transcription artifacts, including:

"claim 1 2"
"claim 26 40"
"administration ring"
"topically administration"
Duplicate or inconsistent dependent-claim references

Those errors should be checked against the certified USPTO reissue document before relying on a particular dependency or limitation. They do not change the central scope of the patent: topical antiviral-glucocorticoid combinations for herpesvirus infections.

What is the FDA status of acyclovir-hydrocortisone products?

FDA approved XERESE, an acyclovir 5% and hydrocortisone 1% cream, under NDA 022436 for the early treatment of recurrent herpes labialis to reduce the likelihood of ulcerative cold sores and shorten lesion healing time. The product combines an antiviral with a corticosteroid and is the clearest commercial embodiment of the acyclovir-hydrocortisone subject matter described in RE39264 (FDA, 2009).

The FDA approval does not establish patent validity or infringement. Regulatory approval and patent rights are separate systems. A product can be FDA-approved after the relevant patent expires, and an FDA-approved product can remain subject to other later-issued patents.

Orange Book status

RE39264 should not be treated as a current Orange Book barrier solely because it covers the XERESE-type combination. Orange Book listing is tied to approved products and patents submitted for listing by the NDA holder. The relevant inquiry is the current Orange Book entry for NDA 022436 and any unexpired patents listed for the product.

An expired RE39264 patent cannot block an ANDA launch. Any current Paragraph IV risk must be evaluated against later unexpired formulation, manufacturing, or method patents, not against RE39264 itself (FDA, 2026).

Are there Paragraph IV challenges to RE39264?

No current Paragraph IV challenge is required for RE39264 because the patent term has ended. Paragraph IV certifications apply to listed patents that have not expired. A generic applicant seeking approval of an acyclovir-hydrocortisone product could instead face:

A Paragraph IV certification against an unexpired listed patent
A section viii statement carving out patented indications
A certification that no relevant patent is listed
No certification directed to RE39264 itself because it is expired

The commercial launch date would depend on the remaining Orange Book patents, regulatory exclusivity, ANDA approval, and any litigation involving later patents.

Which companies compete with the RE39264 technology?

The relevant competitive groups are:

Competitive group	Products or technology	Patent risk relative to RE39264
Acyclovir manufacturers	Generic acyclovir creams and tablets	RE39264 expired; later combination patents require review
XERESE sponsor and licensees	Acyclovir 5%/hydrocortisone 1% cream	Commercial reference product
Penciclovir manufacturers	Topical penciclovir products	Different antiviral, but may implicate broad combination concepts if paired with a steroid
Compounding pharmacies	Customized antiviral-corticosteroid creams	Regulatory, quality, and formulation issues
Specialty topical developers	New delivery systems and mucosal formulations	Potential later formulation and manufacturing patents

The strongest practical design-around options are:

Use a topical antiviral without a glucocorticoid.
Use a glucocorticoid without an antiviral.
Use a non-glucocorticoid anti-inflammatory agent.
Change the indication or labeling, subject to regulatory and induced-infringement considerations.
Use a different dosage form or concentration where no later patent covers the alternative.
Develop a formulation with a distinct delivery mechanism.

The expired status of RE39264 does not eliminate patent risk from later patents covering particle size, emulsion architecture, stability, packaging, manufacturing, or specific clinical indications.

What manufacturing and formulation barriers remain?

RE39264 itself does not create a current manufacturing barrier. Its claims generally cover the presence of the active ingredients and topical carrier, rather than a narrow manufacturing process.

Current development barriers may still include:

Acyclovir solubility and suspension control
Uniform distribution of hydrocortisone
Physical stability during storage
Preservative compatibility
Microbial limits for semisolid products
Skin irritation and sensitization
Batch-to-batch content uniformity
Scale-up of emulsion or gel systems
Container-closure compatibility
Demonstration of pharmaceutical equivalence for an ANDA

For a generic acyclovir-hydrocortisone cream, formulation similarity and bioequivalence may be more significant than RE39264. The FDA may require comparative quality data, in vitro release testing, characterization of the dosage form, and other product-specific evidence.

How does RE39264 compare with later acyclovir-hydrocortisone patents?

RE39264 is broad and combination-focused. Later patents may be narrower and commercially more relevant because they can claim:

Specific acyclovir and hydrocortisone concentrations
Particular particle-size distributions
Emulsion or suspension structures
Stabilizers and preservatives
Enhanced skin penetration
Improved stability
Packaging systems
Specific clinical regimens
Manufacturing processes

The analytical priority is therefore chronological. RE39264 establishes the early combination concept, but current freedom-to-operate analysis must identify the full U.S. family and later patents associated with the marketed product.

Key Takeaways

RE39264 covers topical antiviral-glucocorticoid combinations for herpesvirus infections.
The key commercial embodiment is acyclovir 5% with hydrocortisone 1%.
Claims cover compositions, dosage forms, treatment methods, recurrent infections, and dosing frequency.
The broadest claims depend on a synergy or enhanced-effect limitation.
Claims 13-15 and 37 are particularly relevant to acyclovir-hydrocortisone products.
RE39264 is expired; its reissue status does not extend the original patent term.
No current Paragraph IV certification is directed to RE39264 itself.
XERESE was FDA-approved under NDA 022436 for recurrent herpes labialis.
Current generic-launch risk depends on later unexpired Orange Book patents, regulatory requirements, and litigation, not on RE39264.
The main remaining development challenges are formulation performance, product quality, and later patent rights.

FAQs

Does RE39264 cover acyclovir 5% and hydrocortisone 1% cream?

Yes. The concentrations fall within the ranges recited in claims 13-15, and claim 37 specifically addresses acyclovir with hydrocortisone for recurrent herpesvirus infection. The patent is expired, however.

Can a company launch an acyclovir-hydrocortisone generic without challenging RE39264?

Yes. An expired patent does not require a Paragraph IV challenge. The applicant must still address any unexpired patents listed for the relevant FDA reference product.

Does RE39264 cover separate sequential use of acyclovir and hydrocortisone?

The method claims expressly include administration "in combination or in sequence." During the patent term, sequential administration could have raised infringement issues if the remaining claim limitations were satisfied.

Does a product containing penciclovir and a corticosteroid fall within RE39264?

It could fall within certain broad combination claims if the formulation, topical carrier, glucocorticoid, and synergy limitations are met. The expired status of RE39264 eliminates current infringement liability under that patent.

Is foscarnet-hydrocortisone a commercially important claim combination?

No. It is technically claimed, including defined concentration ranges, but acyclovir-hydrocortisone is the commercially relevant combination. Foscarnet’s topical formulation, tolerability, and market position limit its practical importance.

References

Food and Drug Administration. (2009). XERESE (acyclovir and hydrocortisone) cream prescribing information. U.S. Department of Health and Human Services.
Food and Drug Administration. (2026). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (2006). U.S. Patent No. RE39,264, pharmaceutical compositions and methods for treatment of herpes infections. U.S. Department of Commerce.
U.S. Patent Act, 35 U.S.C. §§ 154, 251.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulations and patent certification requirements, 21 C.F.R. § 314.101 and § 314.107.

PCT Information
PCT Filed	February 02, 1996	PCT Application Number:	PCT/SE96/00124
PCT Publication Date:	August 15, 1996	PCT Publication Number:	WO96/24355

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0809498	⤷ Start Trial	CA 2010 00009	Denmark	⤷ Start Trial
European Patent Office	0809498	⤷ Start Trial	10C0038	France	⤷ Start Trial
European Patent Office	0809498	⤷ Start Trial	SPC/GB10/012	United Kingdom	⤷ Start Trial
Argentina	002030	⤷ Start Trial
Austria	262907	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE39264

Summary for Patent: RE39264