United States Patent 8,207,191: Retapamulin Crystalline Forms, Topical Uses, and Patent Landscape

US 8,207,191 protects selected crystalline forms of retapamulin, the active ingredient in Altabax ointment, when used topically to treat microbial infections. The patent does not broadly claim every retapamulin formulation. Its scope depends on the identity of the solid form, topical administration, treatment of a microbial infection, and, for dependent claims, specific dosing, duration, particle size, ointment vehicle, or acne treatment.

The patent is directed primarily to two solid-state materials:

A crystalline retapamulin form identified by infrared spectroscopy, differential scanning calorimetry, and X-ray powder diffraction.
A crystalline hydrosuccinate salt of retapamulin identified by corresponding analytical characteristics.

The earliest claimed US patent term is expected to run through December 22, 2026, subject to the official USPTO term calculation, any patent-term adjustment, and maintenance status. The patent was assigned to Glaxo Group Limited, the GlaxoSmithKline group company associated with retapamulin development. [1]

What drug and active ingredient does US 8,207,191 protect?

US 8,207,191 relates to retapamulin, chemically described in the claims as a mutilin 14-(exo-8-methyl-8-azabicyclo[3.2.1]oct-3-ylsulfanyl)-acetate.

Retapamulin is a semisynthetic pleuromutilin antibiotic. It binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis. The FDA approved retapamulin 1% ointment under the brand Altabax for topical treatment of impetigo caused by susceptible strains of Staphylococcus aureus or Streptococcus pyogenes. [2]

The patent focuses on crystalline-state control rather than discovery of the retapamulin molecule itself. The claims use analytical fingerprints to distinguish the covered material from amorphous retapamulin, other polymorphs, solvates, salts, or materially different crystalline forms.

What are the core claims of US 8,207,191?

The independent claims divide into five principal categories.

Claim group	Covered subject matter	Main limitation
Claims 1-4	Treatment method using crystalline retapamulin	Topical administration for microbial infection
Claims 5-8	Treatment method using crystalline retapamulin hydrosuccinate	Topical administration for microbial infection
Claims 9-12	Narrower crystalline retapamulin treatment method	Requires specified ATR and XRPD properties
Claims 13-16	Crystalline retapamulin treatment method defined by figures	Requires spectra or diffraction substantially corresponding to patent figures
Claim 17	Acne treatment	Topical treatment of acne in a human using the specified crystalline retapamulin
Claims 18-24	Hydrosuccinate and formulation methods	Includes ointment, petrolatum, and particle-size limitations

The claims are method claims. They do not independently claim a composition of matter, a crystalline material standing alone, or a manufacturing process. A potential infringement theory would therefore need to connect the accused product and conduct to the claimed topical treatment method.

How do the analytical limitations define the protected crystalline forms?

The patent uses three analytical techniques.

Infrared spectroscopy

The parent crystalline retapamulin form is identified by ATR infrared peaks at approximately:

3234 cm⁻¹
1735 cm⁻¹
1725 cm⁻¹

The hydrosuccinate form is identified by peaks at approximately:

3470 cm⁻¹
1731 cm⁻¹
1711 cm⁻¹

These peaks provide structural and functional-group information. The hydrosuccinate profile differs from the parent crystalline material, particularly in the hydroxyl and carbonyl regions.

Differential scanning calorimetry

The parent crystalline form has an endotherm with an onset temperature of approximately 125°C to 127°C.

The hydrosuccinate salt has an endotherm with an onset temperature of approximately 168°C to 170°C.

DSC is relevant to polymorph and salt identification because different crystal lattices, solvates, hydrates, and salts normally produce different thermal transitions.

X-ray powder diffraction

The parent crystalline retapamulin form is characterized by peaks at approximately:

9.6° 2-theta
12.8° 2-theta
13.9° 2-theta
19.6° 2-theta

The crystalline hydrosuccinate form is characterized by peaks at approximately:

13.4° 2-theta
14.4° 2-theta
20.7° 2-theta

Claims 1, 5, and 17 use an "at least one" formulation for the analytical criteria. Claims 9 and 18 require specified combinations of properties. Claim 13 refers to spectra and patterns substantially in accordance with patent figures.

The practical issue is claim construction. "At least one" does not necessarily mean that any single peak, viewed in isolation, establishes infringement. A court would assess the limitation as written in context, including whether the accused material has the claimed crystalline identity and whether the analytical result falls within the claim's stated or legally permissible range.

What is the scope of the treatment claims?

The independent method claims require the following elements:

A mammal, or a human for claim 17.
A microbial infection, or acne under claim 17.
Topical administration.
An effective amount.
The specified crystalline retapamulin form or crystalline hydrosuccinate salt.

The claims do not require impetigo in their independent language. Claims 2, 6, 10, and 14 narrow the infection to a skin or soft-tissue infection. Claim 17 expressly covers acne treatment.

The broadest treatment theory is therefore broader than the FDA-approved Altabax indication in one respect, because "microbial infection" is not limited to impetigo. The claim remains narrow in another respect because it requires the specified crystalline form and topical administration.

Dosing and duration limitations

Claims 3, 7, and 11 specify administration twice daily.

Claims 4, 8, 12, and 16 specify administration for five to seven days.

These limitations matter for literal infringement. A topical retapamulin product used once daily or for a treatment period outside five to seven days may avoid a dependent claim while remaining exposed to the corresponding independent claim.

Ointment and particle-size limitations

Claims 19 through 24 add formulation restrictions:

Crystalline particles incorporated into an ointment.
Petrolatum as the ointment.
D90 particle size of 15 to 25 micrometers.

D90 means that 90% of the measured particle population is at or below the specified particle size, depending on the measurement convention used. Particle-size testing can become a significant infringement and invalidity issue because results may change with sampling, dispersion medium, agglomeration control, instrument settings, and calculation method.

Which claims are strongest against a generic retapamulin ointment?

The independent claims are likely the most important because they do not require every formulation limitation. Claims 1, 5, 9, 13, 17, and 18 can create separate exposure if the accused product uses the claimed crystal form and is promoted or administered for the claimed topical treatment.

The formulation-dependent claims are narrower but commercially relevant because Altabax is a topical ointment. Claims 19, 20, 21, 22, 23, and 24 could be asserted against a product using:

The claimed hydrosuccinate or parent crystal.
An ointment dosage form.
Petrolatum.
A D90 particle size between 15 and 25 micrometers.

A generic could attempt to avoid these narrower claims by using a different vehicle, a different particle-size distribution, a noncrystalline material, a different polymorph, or a different salt. Those design choices would not necessarily avoid the independent method claims.

What claim defects or drafting issues affect US 8,207,191?

Several drafting features create potential litigation issues.

Claim 15 appears to contain a dependency error

Claim 15 states:

"The method according to claim 11 wherein the topical administration of the mutilin is twice daily."

Claim 11 already depends on claim 10 and recites twice-daily administration. Claim 15 appears to repeat the twice-daily limitation rather than depend on claim 13, which is the apparent structure of the surrounding claim set.

The legal effect depends on the issued claim text, prosecution history, and any certificate of correction. The apparent duplication may limit the claim's independent value and could affect interpretation under claim-construction principles.

Approximate XRPD peak language creates boundary questions

The claims use "about" before diffraction peak values. That wording gives some tolerance but does not establish a universal numerical range. The scope may depend on the patent specification, experimental data, ordinary meaning in powder diffraction practice, and expert evidence.

"Substantially in accordance with" creates figure-comparison disputes

Claim 13 does not recite a complete numerical peak list. It refers to the figures. Parties may dispute:

Baseline correction.
Instrument resolution.
Sample preparation.
Peak intensity.
Preferred orientation.
Whether minor peaks must be present.
How much deviation remains "substantially" consistent with the figure.

Functional treatment limitations remain necessary

A product containing the claimed crystalline form is not automatically within every claim. The asserted method must include topical administration to a mammal for treatment of a microbial infection, or acne under claim 17. Product labeling, instructions for use, promotional materials, and foreseeable administration can be relevant to induced-infringement theories.

When does US 8,207,191 lose exclusivity?

The expected base patent-term endpoint is December 22, 2026, based on the relevant PCT filing date associated with the patent family. [1] The controlling expiration date should be taken from the USPTO patent-term record, not inferred solely from the issue date or priority date.

Event	Date or status
Earliest claimed priority	December 22, 2005
International filing associated with US term calculation	December 22, 2006
US patent issue	June 26, 2012
Expected base expiration	December 22, 2026
Patent status before expiration	In-force term expected, subject to USPTO records
Regulatory product	Altabax, retapamulin 1% ointment
FDA approval	May 17, 2007

The patent's expiration does not itself eliminate all retapamulin exclusivity. Other patents, regulatory exclusivity, pediatric extensions, or separate rights could affect market entry. Conversely, expiration of this patent would not necessarily permit a generic to practice any still-valid retapamulin composition, formulation, manufacturing, or method-of-use patent.

What is the Orange Book status of retapamulin and Altabax?

Altabax was approved as an NDA product for retapamulin ointment, 1%. The FDA Orange Book is the relevant source for listed patents and exclusivity associated with the approved drug product. [3]

A small-molecule generic applicant would normally evaluate:

Listed drug patents in the Orange Book.
The approved indication and labeling.
Paragraph I through IV certification options.
Whether a proposed label includes a patented method of use.
Whether a section viii statement can carve out a patented indication.
Any unlisted non-Orange-Book patent risks involving crystalline form, manufacturing, or supply.

US 8,207,191 is principally a method and solid-form patent. If listed for Altabax, it could support a Paragraph IV challenge. If not listed, it could still create litigation risk outside the abbreviated new drug application patent-certification process.

The FDA approval label identifies retapamulin 1% ointment as a topical antibacterial product for impetigo due to susceptible S. aureus or S. pyogenes. [2] The broader patent language should not be confused with the approved label. FDA approval does not establish infringement, validity, or enforceability.

What Paragraph IV challenges or generic litigation affect retapamulin?

A Paragraph IV certification would assert that a listed patent is invalid, unenforceable, or not infringed. For this patent, the most direct generic arguments would concern:

Whether the proposed product contains the claimed crystalline form.
Whether the analytical data fall within the claimed XRPD, ATR, or DSC limitations.
Whether the proposed label induces use for a claimed method.
Whether the claims are obvious over earlier retapamulin polymorph, salt, formulation, or topical-treatment disclosures.
Whether the claims adequately describe and enable the claimed solid-state materials.
Whether the patent's term and Orange Book listing are correct.

The record identified here does not establish a final judgment invalidating US 8,207,191, a public Paragraph IV settlement, or a reported generic launch tied specifically to this patent. No biosimilar pathway applies because retapamulin is a synthetic small-molecule antibiotic, not a biologic.

What other patents are relevant to the retapamulin patent landscape?

The relevant landscape has four layers.

Retapamulin molecule and pleuromutilin patents

Earlier patent families cover substituted pleuromutilin compounds, including retapamulin or closely related compounds. Those patents generally have earlier priority dates and are more likely to have expired or approached expiration before the crystalline-form patent.

Crystalline-form and salt patents

US 8,207,191 occupies this layer. Its value comes from distinguishing a selected retapamulin crystal and a hydrosuccinate salt through solid-state data.

A generic using the same active ingredient but a different polymorph, amorphous form, hydrate, solvate, or salt would require separate freedom-to-operate analysis. The patent does not automatically cover every solid-state alternative.

Formulation and particle-engineering patents

The ointment and D90 limitations target product development choices. Petrolatum and controlled particle size can affect stability, release, spreadability, and manufacturability. A competing formulation may avoid claims 19 through 24 while creating separate equivalence or method-of-use questions.

Method-of-use patents

The patent covers microbial-infection treatment and acne treatment. Its method claims are not limited to the exact FDA impetigo indication, although enforcement depends on the accused use and applicable inducement evidence.

How strong is the patent estate for Altabax?

The estate is technically focused rather than broad.

Strength factor	Assessment
Active ingredient coverage	Limited in this patent; the claims focus on crystalline forms
Solid-form specificity	Strong if the accused product matches the claimed analytical fingerprint
Formulation coverage	Moderate; narrower claims address ointment, petrolatum, and D90
Method-of-use breadth	Broad infection language, but limited by topical administration and crystalline-form identity
Design-around potential	Meaningful through alternative polymorphs, salts, vehicles, or particle sizes
Regulatory leverage	Depends on Orange Book listing and the approved label
Biosimilar exposure	None; retapamulin is a small molecule
Remaining term	Expected through December 22, 2026, subject to official term data

The principal commercial barrier is analytical identification. A generic sponsor cannot rely solely on the chemical name retapamulin. It must determine whether its active ingredient has the claimed crystal form and whether its manufacturing process reproducibly produces that form.

What generic launch scenarios exist for retapamulin?

Launch after patent expiration

A generic could launch after expiration if it has FDA approval and no other enforceable patent blocks launch. The product would still need to satisfy topical formulation, quality, stability, and bioequivalence requirements applicable to the selected FDA pathway.

Paragraph IV launch before expiration

A sponsor could challenge the patent before expiration. The central technical dispute would likely involve polymorph identity and whether the proposed product falls within the XRPD, ATR, or DSC limitations.

Label carve-out

A section viii strategy could be considered if a patented use is not necessary for the proposed label. That strategy is less useful where the approved product's commercial use substantially overlaps the claimed topical infection treatment.

Design-around launch

A sponsor could develop a different crystalline form, salt, vehicle, or particle-size distribution. The design must be evaluated against the independent claims first, because avoiding petrolatum or the 15-to-25-micrometer D90 range alone would not avoid claims 1, 5, 9, 13, 17, or 18.

What are the geographic and manufacturing barriers?

US 8,207,191 is a US patent and does not by itself block manufacture or sale outside the United States. Corresponding national patents may exist in other jurisdictions, but foreign rights require separate family and status review.

Manufacturing risk is concentrated in:

Control of the retapamulin crystal form.
Conversion between parent form and hydrosuccinate salt.
Milling and particle-size control.
Prevention of amorphization during processing.
Ointment dispersion and agglomeration.
Analytical release testing using XRPD, ATR, and DSC.

A manufacturer may avoid literal identity with the claimed form, but process conditions can cause polymorphic conversion during storage or formulation. The final commercial composition, not only the incoming active pharmaceutical ingredient, is relevant to a complete freedom-to-operate assessment.

What is the revenue exposure from this patent?

Altabax is a niche topical antibiotic rather than a large systemic product. The patent's economic value is therefore tied to:

The remaining US branded sales period.
The probability and timing of a generic retapamulin launch.
The cost of developing a polymorph or formulation design-around.
Whether payers substitute a generic immediately after approval.
Whether other patent or regulatory barriers delay entry.

Public sources cited here do not establish a verified current Altabax revenue figure or a publicly confirmed settlement payment. The commercial exposure should be modeled from current IQVIA, company filings, or prescription and net-sales data rather than from patent records.

Key Takeaways

US 8,207,191 is a crystalline-form and topical-use patent for retapamulin.
It covers a specified crystalline retapamulin form and a crystalline hydrosuccinate salt.
The claims use ATR infrared, DSC, and XRPD characteristics to identify the protected materials.
The broadest claims require topical treatment of microbial infection with the specified crystalline material.
Dependent claims add skin or soft-tissue infection, twice-daily dosing, five-to-seven-day treatment, ointment, petrolatum, and D90 particle-size limitations.
Claim 15 appears to contain a dependency duplication that may affect its practical scope.
The expected base expiration is December 22, 2026, subject to the official USPTO term record.
Retapamulin is a small molecule, so biosimilar rules do not apply.
Generic risk depends on crystal-form identity, Orange Book status, Paragraph IV strategy, labeling, and any separate retapamulin patents.
The strongest design-around options involve a different polymorph or salt, but formulation changes alone may not avoid the independent method claims.

FAQs About US 8,207,191 and Retapamulin

Does US 8,207,191 cover all retapamulin products?

No. It covers methods using specified crystalline retapamulin forms or the specified crystalline hydrosuccinate salt. A product containing retapamulin in a different solid form is not automatically within the claims.

Can a generic use retapamulin in a non-petrolatum vehicle?

Potentially. A non-petrolatum vehicle may avoid claims 20 and 23, but it would not necessarily avoid the independent claims or the broader ointment claims.

Does the patent cover oral retapamulin?

The asserted claims require topical administration. Oral administration would not satisfy that express limitation.

Is acne an FDA-approved retapamulin indication?

The patent includes claim 17 for topical acne treatment. The FDA-approved Altabax labeling cited here is directed to impetigo, not a general acne indication. [2]

What testing is most important in a retapamulin freedom-to-operate review?

XRPD, ATR infrared, and DSC testing of the active ingredient and finished formulation are central. Testing should address the claimed peak positions, thermal transitions, sample preparation, and any conversion during ointment manufacture or storage.

References

United States Patent and Trademark Office. (2012). United States Patent No. 8,207,191, crystalline forms and topical treatment methods. USPTO Patent Center and patent record.
U.S. Food and Drug Administration. (2007). Altabax (retapamulin) ointment, 1% prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	450535	⤷ Start Trial
Germany	602004024417	⤷ Start Trial
European Patent Office	1663220	⤷ Start Trial
European Patent Office	2181995	⤷ Start Trial
Spain	2335284	⤷ Start Trial
Japan	2007504231	⤷ Start Trial
Japan	2012020998	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 8,207,191