United States Patent 6,710,066: Scope, Claims, Expiration, and 5-Aminolevulinic Acid Photodynamic Therapy Patent Landscape

U.S. Patent No. 6,710,066 covers photodynamic treatment and detection of non-malignant hyperproliferative skin lesions using a compound that causes protoporphyrin IX accumulation, followed by photoactivation with light. The patent’s central commercial concept is topical 5-aminolevulinic acid, or ALA, photodynamic therapy for actinic keratosis and related lesions.

The patent is expired and does not currently create enforceable U.S. exclusivity. Its claims remain relevant as prior art and as a framework for understanding later formulation, device, treatment-regimen, and combination patents.

What does U.S. Patent 6,710,066 cover?

The patent covers a two-stage photodynamic therapy method:

Administer a precursor or other compound that induces accumulation of photoactive protoporphyrin IX in a skin lesion.
Expose the lesion to light within the photoactivating spectrum of protoporphyrin IX.

The claims are directed to non-malignant, hyperproliferative skin lesions in humans. The claim set includes treatment, lesion detection, topical administration, ALA-specific treatment, artificial light sources, wavelength limits, and red or blue light.

The commercial technology most closely associated with the claims is topical ALA followed by blue or red light exposure. ALA is metabolized intracellularly to protoporphyrin IX, which acts as the photosensitizing agent. Light activation produces reactive oxygen species capable of damaging treated cells.

Core technical elements

Claim element	Covered subject matter
Patient	Human patient
Lesion	Non-malignant, hyperproliferative skin lesion
Active pathway	Accumulation or production of protoporphyrin IX
Precursor	Broadly, a precursor of protoporphyrin IX; claims 5 and 6 specify ALA
Administration	Broad in claim 1; topical in claims 2 and 4
Light	Light capable of photoactivating protoporphyrin IX
Wavelength	350-700 nm in claims 10 and 14
Spectral limitation	Red and blue regions in claims 11 and 15
Light source	Artificial source in claims 8 and 13
Diagnostic use	Detection of lesions in claims 3, 4 and 6

How should the independent claims be construed?

Claims 1, 3, 7 and 12 are the principal claim groups. Each has a different infringement structure.

Claim 1: precursor administration followed by treatment light

Claim 1 requires:

A human patient;
A non-malignant hyperproliferative skin lesion;
Preferential accumulation of a photoactivatable porphyrin;
Administration of an effective amount of a protoporphyrin IX precursor;
Accumulation of therapeutic protoporphyrin IX levels; and
Subsequent exposure to photoactivating light.

This is the broadest treatment claim in the patent because it does not expressly restrict the precursor to ALA, topical delivery, artificial light, or a particular wavelength range.

A competing therapy would need to avoid at least one claim limitation. Potential design-around positions could involve a photosensitizer that does not rely on protoporphyrin IX, a lesion outside the claimed disease category, or a treatment protocol that does not involve the claimed precursor-to-PpIX sequence.

Claim 3: detection rather than treatment

Claim 3 recites the same general administration and light sequence but requires detectable rather than therapeutic levels of protoporphyrin IX. It is directed to identifying a non-malignant hyperproliferative skin lesion.

The claim does not require a therapeutic outcome. A diagnostic or imaging system that administers ALA and uses fluorescence or photoactivation to identify lesions could fall within the claim’s literal scope if all other limitations are met.

Claim 7: light exposure after endogenous production of PpIX

Claim 7 is structurally different. It does not expressly require the accused party to administer ALA. It requires treatment of a lesion in which PpIX is produced from ALA, followed by exposure to photoactivating light.

This creates a potentially broader step structure than claim 1. The claim focuses on the biological condition of the lesion and the light-treatment step. Claims 8 through 11 narrow claim 7 by adding artificial light, wavelength limits, and red or blue light.

Claim 12: compound-induced PpIX accumulation

Claim 12 requires:

A non-malignant hyperproliferative skin lesion;
Administration of a compound that induces PpIX accumulation; and
Exposure to photoactivating light.

Unlike claim 1, claim 12 does not expressly use the term “precursor of protoporphyrin IX.” It uses the broader functional language of a compound that induces accumulation of PpIX. Claims 13 through 15 narrow the light source and spectrum.

What do the dependent claims add?

Claim	Added limitation	Commercial relevance
2	Topical precursor administration	Directly relevant to topical ALA products
4	Topical administration for detection	Relevant to topical diagnostic protocols
5	Precursor is ALA	Links the claim to 5-aminolevulinic acid
6	Precursor is ALA in a detection method	Diagnostic ALA use
8	Artificial light source	Covers clinical lamps and light-emitting devices
9	Light only within PpIX absorption spectrum	Narrows the light source functionally
10	350-700 nm	Captures blue, red and intermediate visible wavelengths
11	Red and blue spectral regions	Tracks commercial PDT light systems
13	Artificial source for claim 12	Covers equipment-based treatment
14	350-700 nm for claim 12	Wavelength-limited treatment
15	Red and blue light for claim 12	Commercially important spectral limitation

What lesions and indications fall within the patent?

The claim language is not limited to actinic keratosis. It covers a category of “non-malignant hyperproliferative skin lesions” that preferentially accumulate a photoactivatable porphyrin or in which PpIX is produced from ALA.

Potentially relevant lesion categories include:

Actinic keratoses;
Bowen’s disease or superficial squamous cell carcinoma in situ;
Sebaceous hyperplasia;
Psoriasis plaques;
Certain benign epithelial proliferations; and
Other non-malignant lesions with the claimed PpIX accumulation behavior.

The patent does not claim malignant lesions. It also does not expressly limit treatment to facial, scalp, upper-extremity or trunk lesions. Product labeling and regulatory indications can be narrower than the patent claims.

The strongest commercial connection is actinic keratosis. The FDA approved Levulan Kerastick for topical ALA photodynamic treatment of minimally to moderately thick actinic keratoses on the face or scalp, using blue light from the BLU-U system [2]. The FDA later approved Ameluz, a topical ALA formulation, for actinic keratoses of the face and scalp in combination with photodynamic therapy [3].

What is the patent expiration date and current legal status?

U.S. Patent No. 6,710,066 is expired. Public patent records identify the patent as an ALA/PpIX photodynamic therapy patent with a term that ended in the early 2020s. The patent is no longer an enforceable barrier to a U.S. generic or competing treatment method.

Event	Date or status
U.S. patent	6,710,066
Issue date	March 23, 2004
Technology	ALA-induced PpIX photodynamic therapy
Patent type	Utility patent
Principal claim category	Method of treatment and detection
Current status	Expired
Remaining enforceable term	None
Current blocking effect	None from this patent alone

The patent’s expiration means that a company can practice the claimed ALA/PpIX treatment method in the United States without infringing this patent. Separate patents may still cover a particular formulation, applicator, light device, treatment regimen, manufacturing process, or combination product.

Patent expiration does not invalidate the claims historically. It removes the right to exclude others after the statutory term ends.

When did ALA photodynamic therapy lose foundational U.S. exclusivity?

The first-generation ALA/PDT patent estate matured and expired before the current formulation-focused landscape. Earlier patents covering ALA use, topical delivery, and photodynamic treatment reached the end of their terms during the 2000s and 2010s. U.S. Patent 6,710,066 remained relevant for a later period but is now expired.

Commercial timeline

Year	Event
1990s	ALA-induced PpIX photodynamic therapy patents filed and prosecuted
1999	FDA approved Levulan Kerastick for actinic keratosis [2]
2004	U.S. Patent 6,710,066 issued
2010s	Later patents focused on formulations, emulsions, devices and treatment protocols
2016	FDA approved Ameluz for actinic keratosis [3]
Early 2020s	U.S. Patent 6,710,066 expired
Current	Foundational ALA/PpIX method claims are public-domain technology

The commercial effect is a shift from foundational method protection to product-specific protection. A company can use the basic ALA-plus-light concept, but it may still face patents directed to a branded formulation or a specific delivery system.

What is the Orange Book status of U.S. Patent 6,710,066?

The patent should not be treated as a current Orange Book barrier. The Orange Book lists patents submitted by sponsors for approved drug products, but an expired patent does not provide current market exclusivity.

Levulan’s FDA-approved product is a topical ALA system used with a separate blue-light source. Ameluz is a distinct topical ALA formulation. The relevant patent analysis therefore requires product-by-product review of current listings, including:

Drug substance or active-ingredient claims;
Formulation claims;
Method-of-use claims;
Device or applicator claims; and
Patent expiration dates and pediatric extensions.

The presence of a patent number in an Orange Book history does not establish that the patent currently blocks approval or launch. Expiration and listing status must be evaluated together [4].

Which later patents protect competing ALA products?

The principal U.S. commercial competitors are Levulan and Ameluz. Both use ALA, but they differ in formulation, delivery system, light source and product presentation.

Product	Sponsor	Active ingredient	Formulation or delivery	Approved use	Patent risk profile
Levulan Kerastick	DUSA Pharmaceuticals, a subsidiary of Sun Pharmaceutical Industries	ALA hydrochloride	Topical solution generated from a drug-device system	Actinic keratosis with blue light	Foundational method patents largely expired; product-specific rights require current review
Ameluz	Biofrontera	ALA	Topical nanoemulsion gel	Actinic keratosis with photodynamic therapy	Greater exposure to formulation, emulsion, manufacturing and regimen patents
Generic or compounded ALA	Multiple potential manufacturers	ALA	Variable	Depends on FDA pathway and labeling	Formulation, bioequivalence, device and method-of-use issues remain

Formulation patents

The most important distinction is between the expired method claims of U.S. Patent 6,710,066 and later formulation claims.

A formulation patent may cover:

A specific ALA concentration;
A nanoemulsion or oil-in-water emulsion;
Particle size or droplet distribution;
Stabilizers and antioxidants;
Preservatives;
pH range;
Penetration enhancers;
Packaging that protects ALA from degradation;
Storage stability;
A defined topical gel or cream; or
A formulation used with a specified light source.

A generic ALA product can avoid the expired foundational patent yet still infringe a live formulation patent. Product substitution therefore depends on more than the active ingredient.

Are biosimilars relevant to this patent?

No. ALA is a small-molecule active ingredient, not a biologic. The biosimilar pathway under the Public Health Service Act is not the relevant regulatory route.

Potential competitors would generally evaluate:

An abbreviated new drug application for a small-molecule product;
A 505(b)(2) application for a materially different formulation, delivery system or combination;
A drug-device pathway where the applicator or light system is integral to the product; and
State-law issues for compounded preparations.

The absence of biosimilar risk does not eliminate patent risk. The relevant threats are generic substitution, 505(b)(2) applications, formulation challenges, device competition and branded product differentiation.

What Paragraph IV challenges and litigation affect this patent?

U.S. Patent 6,710,066 is expired, so a new Paragraph IV challenge to this patent would have no practical commercial value. Paragraph IV litigation is relevant only while a listed patent is unexpired and enforceable.

The more important litigation questions concern later patents covering:

Ameluz’s nanoemulsion formulation;
Topical ALA stability;
Treatment protocols;
Light-dose parameters;
Product-device combinations; and
Competing topical PDT products.

An ANDA applicant may still make a Paragraph IV certification against an unexpired Orange Book patent covering a reference product. The applicant would need to address each listed patent separately. A certification against expired U.S. Patent 6,710,066 would not delay FDA approval under the Hatch-Waxman framework.

There is no current enforceable litigation position attributable to the expired patent itself. Settlement agreements tied solely to this patent would have limited present commercial value unless they also address later patents, supply arrangements, territories or formulation rights.

What licensing deals shaped the ALA photodynamic therapy market?

The ALA/PDT market developed through university-originated technology, sponsor-specific product development and later formulation commercialization. The patent record and FDA product history identify different rights holders across patent families and products.

The commercial rights relevant to a diligence review include:

Ownership or assignment of foundational ALA/PDT patents;
Licenses supporting Levulan commercialization;
Product and formulation rights held by Biofrontera for Ameluz;
Rights to proprietary light devices;
Territory-specific distribution agreements; and
Improvements covering topical delivery and stability.

A license to use an expired foundational patent does not create patent exclusivity. It may still matter for know-how, trademarks, manufacturing specifications, regulatory files or access to proprietary devices.

How strong is the patent estate around ALA photodynamic therapy?

The estate is weak at the foundational method level and stronger at the product-specific level.

Patent layer	Current strength
ALA converted to PpIX and activated by light	Weak; foundational claims are expired
Broad treatment of non-malignant hyperproliferative lesions	Weak for this patent because it is expired
Topical ALA delivery	Depends on later patent families
Specific gel, cream or nanoemulsion	Potentially strong if claims remain unexpired and technically narrow
Light device	Potentially strong, particularly for integrated drug-device systems
Treatment regimen	Moderate to strong depending on dosing, incubation and illumination limitations
Manufacturing and stability	Potentially strong for complex formulations
Diagnostic PpIX detection	Limited commercial significance unless tied to a current device or diagnostic product

The key diligence issue is claim overlap. A competitor using plain ALA and a conventional PpIX-activating light source may be clear of the expired patent, but a competitor copying a branded nanoemulsion, applicator, or treatment protocol may encounter live rights.

What generic launch scenarios exist after expiration?

Scenario 1: Plain topical ALA product

A manufacturer could develop a topical ALA product using the public-domain ALA/PpIX method. The principal barriers would be FDA approval, product quality, stability, skin penetration, labeling and clinical comparability.

Scenario 2: Generic equivalent to Levulan

A Levulan-like product would need to address the active ingredient, concentration, dosage form, container, application method and use with the relevant light source. The drug-device configuration could complicate ordinary ANDA substitution.

Scenario 3: Alternative ALA formulation

A 505(b)(2) applicant could pursue a new gel, cream, emulsion or delivery vehicle. This route may avoid direct duplication of the reference product but would increase exposure to formulation and method patents.

Scenario 4: Compounded ALA

Compounded preparations may compete in limited settings but do not necessarily provide the same FDA-approved labeling, manufacturing controls or reimbursement profile as an approved product.

What geographic coverage does the patent have?

U.S. Patent 6,710,066 covers only the United States. Foreign counterparts would require separate validity and expiration analysis. European, Canadian, Australian and other national patents may have different:

Filing dates;
Claim scopes;
Prosecution histories;
Supplementary protection certificates;
Patent-term adjustments;
Oppositions; and
Expiration dates.

The expiration of the U.S. patent does not establish freedom to operate outside the United States.

What manufacturing and intellectual-property barriers remain?

The principal remaining barriers are technical and product-specific rather than foundational.

Manufacturers must control:

ALA degradation;
Oxidation and light sensitivity;
Formulation uniformity;
Skin penetration;
Lot-to-lot concentration;
Packaging and storage conditions;
Microbiological quality;
Application time;
Light dose and wavelength; and
Compatibility between the drug and illumination device.

The most defensible later patent positions generally relate to formulation performance, stability, manufacturing controls and integrated treatment systems. These claims are narrower than claim 1 of U.S. Patent 6,710,066 but may be more commercially important because they attach to a specific approved product.

Key Takeaways

U.S. Patent 6,710,066 covers treatment and detection of non-malignant hyperproliferative skin lesions through PpIX accumulation and photoactivation.
Claims 1 and 12 are the main broad treatment claims.
Claims 5 and 6 specifically identify 5-aminolevulinic acid.
Claims 2 and 4 cover topical administration.
Claims 8, 10, 11, 13, 14 and 15 narrow the light source or wavelength.
The patent is expired and no longer blocks U.S. commercialization.
ALA/PpIX photodynamic therapy is not subject to biosimilar regulation.
Current patent risk is concentrated in formulations, nanoemulsions, devices, manufacturing processes and treatment regimens.
Levulan and Ameluz require separate Orange Book and patent-family analysis.
Expiration of this patent does not establish freedom to operate for later branded formulations or drug-device combinations.

Frequently Asked Questions

Can a company use topical 5-aminolevulinic acid and blue light without infringing U.S. Patent 6,710,066?

Yes. The patent is expired. The same conduct may still implicate later formulation, device or method-of-use patents.

Does U.S. Patent 6,710,066 cover aminolevulinate salts?

The claims expressly identify ALA in claims 5 and 6, while the broader claims refer to a precursor of PpIX or a compound that induces PpIX accumulation. Salt, ester and derivative coverage depends on whether the specific compound satisfies the claim language and on the scope of later patents.

Does the patent cover daylight photodynamic therapy?

The claims recite light capable of photoactivating PpIX. Claims 8 and 13 require an artificial light source, while claims 7 and 12 do not. Daylight protocols must be analyzed against the unqualified light limitations and any later daylight-PDT patents.

Is a light-emitting device required to practice the patent?

No. Claims 1, 3, 7 and 12 do not universally require an artificial source. Artificial-light limitations appear in claims 8 and 13. The light must still be capable of photoactivating PpIX.

Does patent expiration permit FDA approval of a generic ALA product?

No. Expiration removes the patent barrier but does not determine the FDA approval pathway. The applicant must still satisfy the applicable ANDA, 505(b)(2) or other regulatory requirements.

References

United States Patent and Trademark Office. (2004). U.S. Patent No. 6,710,066, Photodynamic therapy using 5-aminolevulinic acid.
U.S. Food and Drug Administration. (1999). Levulan Kerastick for topical solution: Prescribing information.
U.S. Food and Drug Administration. (2016). Ameluz: Prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	287709	⤷ Start Trial
Australia	3883293	⤷ Start Trial
Australia	5888796	⤷ Start Trial
Australia	6034390	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,710,066

Summary for Patent: 6,710,066