United States Patent 6,034,267: Scope, Claims, Expiration, and ALA Photodynamic-Therapy Patent Landscape

U.S. Patent 6,034,267 covers aminolevulinic acid, or ALA, esters and related N-substituted derivatives used for photodynamic diagnosis, photochemotherapy, pharmaceutical compositions, in-vitro fluorescence assays, and diagnostic or treatment kits. The most commercially relevant embodiments are methyl aminolevulinate, ethyl aminolevulinate, and other simple ALA alkyl esters.

The patent issued March 7, 2000. Its statutory patent term has expired. The patent therefore presents no current U.S. infringement risk based on the issued claims, although later patents covering specific formulations, devices, manufacturing processes, or approved products must be assessed separately. The patent is also distinct from FDA regulatory exclusivity and from Orange Book-listed patents for ALA hydrochloride products.

What does U.S. Patent 6,034,267 cover?

U.S. Patent 6,034,267 covers the use and formulation of compounds having the following general structure:

[ (R_2)_2N-CH_2COCH_2CH_2COOR_1 ]

The formula corresponds to ALA derivatives in which:

R1 is an alkyl group;
each R2 is independently hydrogen or alkyl;
the alkyl groups may contain hydroxy, alkoxy, acyloxy, alkoxycarbonyloxy, amino, aryl, oxo, or fluoro substitution;
alkyl chains may be interrupted by oxygen atoms; and
the compound may be used as a salt.

When both R2 groups are hydrogen, the core compound is an ALA ester. The most important species identified in the claims are:

Claimed species	Structural description	Commercial relevance
ALA-methyl ester	Methyl aminolevulinate	High; associated with Metvix-type photodynamic products
ALA-ethyl ester	Ethyl aminolevulinate	Potential topical PDT use
ALA-propyl ester	Propyl aminolevulinate	Covered species
ALA-hexyl ester	Hexyl aminolevulinate	Covered species
ALA-heptyl ester	Heptyl aminolevulinate	Covered species
ALA-octyl ester	Octyl aminolevulinate	Covered species

The patent does not claim only one formulation or one indication. Its claim set extends across composition, treatment, diagnosis, fluorescence testing, and kit formats.

How broad are the independent claims?

The principal independent claims are claims 1, 8, 13, and 15.

Claim	Claim category	Core limitation
1	In-vivo method	Administering the ALA derivative to an external or internal body surface and exposing the site to light
8	Pharmaceutical composition	ALA derivative plus a pharmaceutical carrier or excipient
13	In-vitro diagnosis	Mixing the compound with body fluid or tissue, exposing the mixture to light, measuring fluorescence, and comparing it with controls
15	Kit	A first container with the compound and a second container with a surface-penetration agent, with optional chelating agent

Claim 1: photodynamic diagnosis and treatment

Claim 1 requires four functional elements:

A disorder or abnormality of an external or internal body surface.
Administration of the claimed compound composition to the investigation or treatment site.
Exposure of the site to light.
Use of a compound within the defined formula or a salt.

The claim covers both diagnostic fluorescence and photochemotherapy. It is not limited to cancer. The wording “disorders or abnormalities” can encompass a broad range of pathological or dermatological conditions, provided the remaining claim elements are met.

Claim 7 narrows the light source to the 500-700 nanometer range. This wavelength range is commercially relevant to photodynamic therapy because ALA-induced protoporphyrin IX is activated by visible light, particularly blue and red light depending on the treatment protocol.

Claims 3 through 6: compound limitations

Claims 3-6 narrow the chemical scope:

Claim 3 requires unsubstituted R1 and hydrogen at both R2 positions.
Claim 4 covers either an unsubstituted R1 group or hydrogen at both R2 positions.
Claim 5 limits alkyl groups to up to 10 carbon atoms.
Claim 6 identifies six named ALA esters.

Claim 6 is the most commercially useful species claim because it provides a closed list of named esters. It does not, however, create a new composition-of-matter claim independent of the method claim. The listed esters are claimed only in the context of the methods or compositions recited in the relevant dependent claims.

What formulations are protected by U.S. Patent 6,034,267?

Claim 8 covers a pharmaceutical composition containing:

an effective diagnostic or therapeutic amount of the ALA derivative; and
at least one pharmaceutical carrier or excipient.

Claim 10 adds a surface-penetration assisting agent and optionally a chelating agent. Claim 11 specifically identifies dimethyl sulfoxide, or DMSO, as the penetration enhancer.

The formulation claims therefore reach topical products containing an ALA ester, a carrier, and, in narrower embodiments, DMSO or a chelating agent.

The claims do not require a particular:

cream, gel, ointment, lotion, solution, or emulsion;
concentration;
pH;
preservative;
packaging system;
light source;
treatment duration; or
lesion type.

That breadth increases the theoretical scope of the formulation claims. The claims are nevertheless limited by the requirement that the active ingredient fall within the formula and that the composition be pharmaceutical and diagnostically or therapeutically effective.

Formulation design-around considerations

A product designed around the patent before expiration could have challenged the claims by:

using unsubstituted ALA rather than an alkyl ester;
using a structurally different prodrug;
omitting the claimed penetration-enhancer configuration;
avoiding a kit with separate containers;
using a non-photodynamic mechanism; or
challenging enablement, written description, anticipation, or obviousness.

Those design-around considerations have no current U.S. enforcement value because the patent term has expired.

What are the method-of-use claims?

The patent contains three method categories.

In-vivo photodynamic therapy

The treatment claims cover administering the compound and then exposing the treated site to light. The claims are broad enough to include topical or local administration and treatment of external or internal surfaces.

In-vivo diagnosis

The same basic treatment architecture can be used diagnostically by detecting fluorescence generated after administration and light exposure. The claim language does not limit diagnosis to a particular cancer, lesion, organ, or imaging instrument.

In-vitro fluorescence diagnosis

Claim 13 is directed to an assay method involving:

a body-fluid or tissue sample;
admixture with the claimed compound;
light exposure;
fluorescence measurement; and
comparison against control levels.

This claim category is materially different from topical photodynamic therapy. It could cover laboratory diagnostic workflows if the assay uses a covered ALA derivative and follows the claimed fluorescence-comparison steps.

How does the claim hierarchy affect infringement analysis?

The dependent claims narrow the independent claims rather than expand them.

Claim group	Practical limitation
Claims 1-7	In-vivo diagnosis or photochemotherapy
Claims 8-12	Pharmaceutical composition and penetration-enhancer formulations
Claims 13-14	In-vitro fluorescence diagnosis
Claims 15-16	Multi-container diagnostic or treatment kits

A product containing methyl aminolevulinate would not automatically infringe every claim. For example:

a vial containing methyl aminolevulinate alone would not necessarily meet claim 15’s kit architecture;
a composition without DMSO would not meet claim 11;
a product using ALA hydrochloride rather than an alkyl ester would require separate analysis under the formula language;
a product used without light would not meet claims 1 or 13;
a product used solely for a non-photodynamic purpose would generally fall outside the method claims.

When did U.S. Patent 6,034,267 expire?

U.S. Patent 6,034,267 issued on March 7, 2000. Its term was governed by the 20-year patent-term rules applicable to the relevant application and international filing history. The patent’s statutory term expired in 2015.

Event	Date or status
U.S. patent number	6,034,267
Issue date	March 7, 2000
Patent term	20-year statutory term
Current status	Expired
Current U.S. blocking right	None from this patent

Patent expiration eliminates the exclusionary right under the patent. It does not eliminate regulatory requirements, trade-secret protection, later patent rights, or contractual restrictions.

The expiration analysis should not be confused with FDA exclusivity. FDA exclusivity is granted under the Federal Food, Drug, and Cosmetic Act and can expire independently of patent rights. The patent also does not establish current exclusivity for methyl aminolevulinate or for ALA hydrochloride products.

What is the Orange Book status of ALA products?

FDA-approved ALA photodynamic products include:

Levulan Kerastick, containing aminolevulinic acid hydrochloride, approved for actinic keratoses;
Ameluz, containing aminolevulinic acid hydrochloride, approved for actinic keratoses.

These products use ALA hydrochloride rather than the alkyl ALA esters emphasized in claims 6, 9, 12, 14, and 16.

The Orange Book status of an ALA hydrochloride product must be reviewed separately from U.S. Patent 6,034,267. A patent covering methyl aminolevulinate is not automatically an Orange Book patent for Levulan or Ameluz. Orange Book listing depends on whether the patent claims the approved drug, its formulation, or an approved method of use and whether the NDA holder submits the required certification information under FDA regulations.

Product or active ingredient	U.S. regulatory position	Relationship to Patent 6,034,267
ALA hydrochloride	FDA-approved photodynamic active ingredient	Chemically distinct from the claimed alkyl ALA esters
Levulan Kerastick	FDA-approved product	Requires separate Orange Book and patent review
Ameluz	FDA-approved product	Requires separate Orange Book and patent review
Methyl aminolevulinate	Used in non-U.S. photodynamic products	Not equivalent to ALA hydrochloride for claim or regulatory analysis

Are there Paragraph IV challenges or generic-entry risks?

There is no current Paragraph IV risk arising from Patent 6,034,267 because the patent has expired. A generic applicant could not be required to certify against an expired patent as a live barrier to approval.

For ALA hydrochloride products, Paragraph IV risk depends on currently listed Orange Book patents, not on this expired patent. For a methyl aminolevulinate product, the principal current barriers are likely to be:

clinical and regulatory requirements;
product-specific formulation patents filed after the 6,034,267 family;
manufacturing patents;
device or light-source patents;
trademark and commercial agreements; and
market access and reimbursement.

The product is a small molecule. Biosimilar analysis is not applicable. Any follow-on product would proceed through an abbreviated or full small-molecule drug pathway, depending on the reference product and FDA designation.

Which companies and products are most relevant?

The commercial landscape includes several distinct ALA product strategies.

Company or product category	Active ingredient or technology	Strategic relevance
Biofrontera, Ameluz	ALA hydrochloride	U.S. approved photodynamic product
DUSA Pharmaceuticals, Levulan	ALA hydrochloride	U.S. approved photodynamic product
Galderma or former PhotoCure-related Metvix operations	Methyl aminolevulinate	Major non-U.S. ALA-ester product lineage
Generic manufacturers	ALA hydrochloride or future ALA products	Potential price competition after applicable regulatory barriers
Device manufacturers	Blue or red photodynamic light systems	May hold separate device patents and regulatory clearances

The patent landscape is therefore segmented into four layers:

Core ALA and ALA-derivative chemistry.
Photodynamic treatment methods.
Topical formulations and penetration systems.
Light-delivery devices, dosing protocols, and product-specific regulatory patents.

Patent 6,034,267 occupied the second and third layers, with additional coverage for diagnostic assays and kits.

What patent litigation or settlements affect this patent?

The expiration of Patent 6,034,267 removes it as a present litigation asset. No current Paragraph IV settlement can extend its statutory term. Any historical litigation involving ALA photodynamic products would need to be analyzed separately by patent family, defendant, product, and settlement date.

A settlement concerning another ALA patent would not revive or extend the rights in Patent 6,034,267. Likewise, a later patent covering an ALA formulation or approved method could remain enforceable after this patent’s expiration.

How strong was the patent estate?

The patent was commercially meaningful because it combined:

a broad derivative genus;
named ALA ester species;
treatment and diagnostic uses;
pharmaceutical compositions;
DMSO-assisted topical delivery;
chelating-agent embodiments; and
multi-container kits.

Its strongest practical claims were likely the named-ester composition and use claims tied to photodynamic treatment. The broad genus claims presented greater potential validity pressure because they covered numerous substitutions and oxygen-interrupted alkyl structures.

Its current strength is zero as an exclusionary U.S. patent right because the patent is expired. Its historical value remains relevant for:

identifying the original ALA-ester technology;
tracing commercial product development;
assessing prior art;
interpreting later ALA patents; and
evaluating freedom to operate during the patent term.

Does the patent create current manufacturing or geographic barriers?

No current U.S. manufacturing barrier arises from Patent 6,034,267. The patent’s territorial rights were limited to the jurisdictions in which corresponding patents issued and remained in force.

Manufacturing risk may still arise from:

later process patents;
polymorph or salt patents;
impurity-control patents;
formulation manufacturing methods;
proprietary light devices;
regional patents outside the United States; and
confidential know-how.

A U.S. manufacturer can generally make an ALA ester product without infringing this expired patent. Export and sale in other jurisdictions require separate family-by-family expiration analysis.

Key Takeaways

U.S. Patent 6,034,267 covers ALA esters and related derivatives for photodynamic diagnosis, photochemotherapy, pharmaceutical compositions, fluorescence assays, and kits.
The central commercial species include methyl, ethyl, propyl, hexyl, heptyl, and octyl aminolevulinate.
Claim 10 covers formulations with penetration-enhancing agents, and claim 11 specifically identifies DMSO.
Claim 13 covers in-vitro fluorescence diagnosis using body fluid or tissue samples.
The patent issued March 7, 2000 and expired in 2015.
It creates no current U.S. patent barrier and no current Paragraph IV risk.
The patent is distinct from Orange Book patents and FDA exclusivity for Levulan and Ameluz, which contain ALA hydrochloride.
Biosimilar analysis does not apply because ALA products are small-molecule drugs.
Current diligence should focus on later formulation, manufacturing, device, method-of-use, and regional patents.

FAQs About U.S. Patent 6,034,267

Is methyl aminolevulinate covered by Patent 6,034,267?

Yes. Methyl aminolevulinate is expressly identified in dependent claims 6, 9, 12, 14, and 16. The patent is expired, so that coverage no longer creates a current U.S. exclusionary right.

Does the patent cover ALA hydrochloride?

The patent claims salts of the defined formula, but its named species are alkyl ALA esters. ALA hydrochloride is not automatically equivalent to methyl aminolevulinate or another alkyl ester. Product-specific chemical and claim construction analysis is required.

Can a company launch a methyl aminolevulinate product in the United States?

The expired patent does not prevent launch. FDA approval, drug-substance manufacturing, formulation development, clinical requirements, labeling, and later patent rights remain separate issues.

Does the patent cover the blue or red light device used in photodynamic therapy?

No. The patent claims the compound, treatment method, composition, assay, and kit. It does not claim a particular light apparatus as presented in the supplied claims.

Does expiration of this patent eliminate all ALA photodynamic-therapy IP risk?

No. Expiration eliminates the rights in this patent only. Later patents may cover formulations, dosing regimens, manufacturing processes, light devices, packaging, combinations, or approved methods of use.

References

U.S. Patent No. 6,034,267. (2000). Photodynamic therapy. United States Patent and Trademark Office.
United States Code, 35 U.S.C. § 154. Patent term.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Orange Book.
U.S. Food and Drug Administration. (1999). Levulan Kerastick prescribing information.
U.S. Food and Drug Administration. (2012). Ameluz prescribing information.
U.S. Food and Drug Administration. (n.d.). Patent and exclusivity information. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9504948	Mar 10, 1995
United Kingdom	9525822	Dec 18, 1995

PCT Information
PCT Filed	March 08, 1996	PCT Application Number:	PCT/GB96/00553
PCT Publication Date:	September 19, 1996	PCT Publication Number:	WO96/28412

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0820432	⤷ Start Trial	SPC024/2002	Ireland	⤷ Start Trial
European Patent Office	0820432	⤷ Start Trial	SPC/GB02/038	United Kingdom	⤷ Start Trial
European Patent Office	0820432	⤷ Start Trial	300176	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,034,267

Summary for Patent: 6,034,267