United States Patent 5,798,349: Scope, Expiration, Orange Book Status, and Verteporfin Patent Landscape

U.S. Patent No. 5,798,349 covered photodynamic treatment of ocular neovascularization using a green porphyrin, principally verteporfin, followed by laser irradiation. The patent claims targeted therapy for choroidal neovascularization and age-related macular degeneration, including liposomal and low-density-lipoprotein formulations.

The patent’s term expired on November 7, 2014. Its claims therefore no longer create an enforceable U.S. patent barrier to generic verteporfin or competing photodynamic therapy products. The patent remains commercially important because it established the core treatment method later commercialized as Visudyne, but current entry risk depends on later formulation, manufacturing, labeling, regulatory, and device-related rights rather than on Patent 5,798,349 itself. [1][2][3]

What invention does U.S. Patent 5,798,349 cover?

The patent covers a photodynamic therapy sequence:

Administer a green porphyrin to a primate patient.
Allow the compound to localize in ocular neovasculature or the choroid.
Irradiate the target tissue with laser light absorbed by the porphyrin.
Occlude the abnormal blood vessels.

The patent is directed principally to verteporfin-mediated photodynamic therapy, although the claims use broader chemical and formulation language in several places.

The commercial product most closely associated with the patent is verteporfin, also known as benzoporphyrin derivative monoacid ring A, or BPD-MA. Visudyne is an intravenous verteporfin formulation used with a nonthermal laser for selected retinal vascular disorders. [3][4]

Who owned Patent 5,798,349 and what was its prosecution history?

The patent was assigned to Quadra Logic Technologies, Inc., now associated with the QLT/Visudyne intellectual-property program. The patent issued on August 25, 1998, from an application claiming priority to earlier work on green porphyrins and photodynamic therapy. [1]

Field	Patent 5,798,349 data
Patent number	U.S. 5,798,349
Title	Photodynamic therapy of neovascularization using green porphyrins
Issue date	August 25, 1998
Principal commercial compound	Verteporfin, or BPD-MA
Primary field	Ocular photodynamic therapy
Principal disease target	Choroidal neovascularization and AMD
Original commercial sponsor	QLT, later commercialized with Novartis
U.S. term end	November 7, 2014
Current enforceability	Expired
Patent type	Method-of-use and treatment-regimen patent

The patent is distinct from patents directed solely to the chemical synthesis of verteporfin, pharmaceutical composition design, or laser apparatus. Its central legal contribution was the use of green porphyrins in an ocular neovascularization treatment protocol.

How broad are the independent claims?

The patent has three principal independent claim groups: claims 1, 7, and 14.

Claim 1: liposomal treatment of ocular neovasculature

Claim 1 requires all of the following:

A primate subject.
An eye condition characterized by unwanted neovasculature.
Administration of a liposomal green porphyrin formulation.
Localization of an effective amount in the neovasculature.
Laser irradiation.
Absorption of the laser light by the green porphyrin.
Occlusion of the neovasculature.

Claim 1 is narrower than the other independent claims because the administered compound must be in a liposomal formulation. A product using free verteporfin, a nonliposomal carrier, or another delivery system would not satisfy the literal formulation limitation of claim 1.

The claim is also functionally limited. The administered dose must be sufficient to allow effective localization, and the irradiation must occlude the abnormal vessels. Mere administration of a green porphyrin followed by light exposure would not automatically satisfy the claim if the required localization and vascular occlusion did not occur.

Claim 7: choroidal neovascularization

Claim 7 removes the express liposomal limitation. It covers treatment of unwanted choroidal neovasculature by:

Administering green porphyrin;
Waiting for localization in the choroidal neovasculature; and
Irradiating the target with absorbed laser light to occlude the vessels.

Claims 8 and 9 narrow claim 7 by requiring, respectively:

Complexing the green porphyrin with low-density lipoprotein; or
Incorporating it in a liposomal preparation.

Claim 7 is therefore the broadest practical treatment claim for choroidal neovascularization. It is not limited to one carrier system. A competing product using a different formulation could still fall within the claim if it used a qualifying green porphyrin and the same localization-and-laser treatment sequence. That issue is now historical in the United States because the claim has expired.

Claim 14: treatment of AMD

Claim 14 covers treating age-related macular degeneration by:

Administering green porphyrin;
Permitting localization in the choroid; and
Irradiating the choroid with absorbed laser light.

Unlike claim 1 and claim 7, claim 14 does not expressly require that the laser irradiation occlude neovasculature. It also does not require a liposomal formulation or LDL complex. Claims 15 and 16 add those delivery limitations.

Claim 14 is disease-specific and potentially broad in formulation scope. It reaches treatment of AMD using green porphyrin photodynamic therapy even where the claim language does not specify a particular chemical species, carrier, laser wavelength, dose, or treatment interval.

Which claims specifically cover verteporfin?

Claims 6, 13, and 20 identify the most commercially important compound through a detailed structural definition. The claimed structure includes:

Two methoxycarbonyl substituents;
One free propionic acid substituent;
One methyl ester of a propionic acid substituent; and
A vinyl group.

That structure corresponds to verteporfin or BPD-MA, the active ingredient in Visudyne.

The narrower dependent claims are important because they tie the broad “green porphyrin” language to the specific commercial drug. Their scope is substantially more limited than claims 7 and 14, which do not require the full structural definition.

Claim group	Subject matter	Practical scope
Claims 1-6	Ocular neovascularization with liposomal green porphyrin	Broad disease scope, narrower formulation scope
Claims 7-13	Choroidal neovascularization	Broad treatment scope; dependent claims add LDL, liposome, and verteporfin structures
Claims 14-20	AMD treatment	Broad disease-specific method; dependent claims add formulation and chemical limitations

What formulations are protected by Patent 5,798,349?

The patent addresses three formulation categories.

Liposomal formulations

Claims 1, 9, 16, and related dependent claims cover green porphyrin contained in a liposomal preparation. This language concerns drug delivery and biodistribution. Liposomes can improve solubility, circulation characteristics, and localization behavior.

The claims do not appear limited to one lipid composition, particle size, phospholipid, cholesterol ratio, or manufacturing process. That gives the formulation limitations breadth at the conceptual level, but it also creates potential written-description and claim-construction constraints if a dispute required identifying the boundaries of “liposomal preparation.”

LDL-complexed green porphyrin

Claims 8 and 15 cover green porphyrin complexed with low-density lipoprotein. This is a distinct delivery approach from liposomal encapsulation. LDL targeting was relevant to the invention’s theory of preferential localization in proliferating vascular tissue.

A formulation using a different plasma protein, polymer, nanoparticle, or lipid carrier would not literally satisfy the LDL limitation, although it could have been relevant to the broader independent claims.

Non-liposomal verteporfin

Claims 7 and 14 do not require liposomes or LDL. A nonliposomal product could have implicated those claims if the other elements were met. This distinction matters for historical freedom-to-operate analysis because a generic manufacturer could not have avoided every claim merely by changing the carrier.

What laser treatment is required?

The claims require laser irradiation, but they do not recite a specific wavelength in the claim text provided. The commercial Visudyne protocol uses activation of verteporfin with a 689-nanometer laser. The FDA label specifies intravenous infusion followed by laser treatment, with the laser applied to the target lesion after drug administration. [3]

The patent claims are therefore broader than the commercial protocol in several respects:

No express 689-nanometer limitation.
No express fluence limitation.
No express spot size.
No express irradiation duration.
No express drug dose.
No express infusion duration.
No express retreatment interval.

The requirement that light be absorbed by the green porphyrin provides a functional constraint. A laser wavelength that does not meaningfully activate the selected porphyrin would not satisfy the intended treatment mechanism.

What was the FDA regulatory status of verteporfin?

The FDA approved Visudyne, verteporfin for injection, under NDA 21-119 on April 12, 2000. The approved use was photodynamic treatment of predominantly classic subfoveal choroidal neovascularization due to AMD, with later labeling covering additional forms of ocular neovascular disease. [3][4]

The FDA-approved treatment involves:

Intravenous administration of verteporfin;
A defined waiting period for drug distribution;
Laser activation of the lesion;
Vascular closure through photochemical mechanisms.

The FDA approval does not create continuing patent rights. Regulatory exclusivity and patent exclusivity are separate. Any original regulatory exclusivity for the NDA expired long before the present date.

What is the Orange Book status of Patent 5,798,349?

Patent 5,798,349 was historically associated with the Visudyne product and the treatment method for ocular neovascularization. The patent’s expiration date was November 7, 2014. Once the patent expired, its Orange Book listing no longer created a continuing patent-based block to ANDA approval or generic launch. [2]

Orange Book issue	Status
Product	Visudyne, verteporfin
NDA	21-119
Patent 5,798,349	Historically listed or associated with the product
Expiration	November 7, 2014
Current blocking effect	None after expiration
Remaining regulatory question	Whether later-listed patents or exclusivities apply to a particular ANDA

An Orange Book listing is not itself an extension of patent term. It identifies patents submitted by an NDA holder and accepted for listing under FDA rules. The enforceability of the patent depends on its statutory term and any applicable terminal disclaimer, disclaimer, or adjustment.

Were there Paragraph IV challenges to this patent?

A Paragraph IV certification would have been relevant when an ANDA applicant sought approval for a generic verteporfin product before expiration of the listed patent. Such a certification asserts that the patent is invalid, unenforceable, or not infringed.

For Patent 5,798,349, any Paragraph IV risk is now extinguished by expiration. A later ANDA applicant does not need to defeat the patent in litigation to launch after the term end.

The historical competitive framework involved the originator and its commercial partners, including QLT and Novartis, against potential generic manufacturers seeking to develop verteporfin for injection. The more important current question is whether a generic applicant faces later formulation or process patents, rather than whether it can launch under Patent 5,798,349.

Which companies challenged or competed with the Visudyne franchise?

The principal commercial parties were:

Company	Role
Quadra Logic Technologies, Inc.	Original developer and patent holder associated with verteporfin
Novartis	Commercialization partner for Visudyne in major markets
Bausch + Lomb and other ophthalmic companies	Later commercial and distribution participants in ophthalmic markets
Generic injectable manufacturers	Potential or actual competitors after product and patent barriers declined

The relevant competitive set includes therapies for neovascular AMD rather than only photodynamic products. Anti-VEGF medicines, including ranibizumab, aflibercept, and off-label bevacizumab, displaced photodynamic therapy as the dominant treatment approach for many patients with neovascular AMD. Photodynamic therapy remains clinically relevant in selected lesion types and retinal vascular conditions. [3][5]

How does Patent 5,798,349 compare with later verteporfin patents?

Patent 5,798,349 is best classified as a core method-of-use patent. The broader verteporfin estate also included patents directed to:

Benzoporphyrin compounds;
Specific BPD-MA compositions;
Photodynamic treatment protocols;
Injectable formulations;
Manufacturing processes;
Stabilization and storage;
Combination treatment with ophthalmic therapies.

Patent 5,798,349 should not be treated as the entire U.S. patent estate. A product could be outside the expired claims but still have faced later patent issues involving formulation or manufacturing technology. Those later rights also require separate validity and expiration analysis.

Patent category	Typical protected subject matter	Relevance after 2014
Core treatment method	Green porphyrin plus laser treatment	Expired for Patent 5,798,349
Chemical compound	Verteporfin or related porphyrins	Depends on separate patent family and term
Formulation	Liposome, injectable composition, stabilizer	May create later-term risk
Manufacturing	Synthesis, purification, crystallization	May affect supply-chain entry
Labeling	AMD or specific retinal indications	Later method claims may affect skinny-label strategy
Device	Laser wavelength and delivery system	Generally separate from drug patent claims

How strong was the patent estate?

Patent 5,798,349 had strong historical commercial relevance because its claims aligned with the approved use of Visudyne and covered the therapeutic sequence rather than only a research use.

Its historical strengths were:

Direct coverage of choroidal neovascularization.
A disease-specific AMD claim.
Claims directed to verteporfin-like structures.
Claims covering both liposomal and non-liposomal treatment pathways.
Functional alignment with the approved photodynamic mechanism.

Its limitations were:

The method claims required laser irradiation.
Several claims required localization and therapeutic occlusion.
Liposomal and LDL claims were narrower than the broad treatment claims.
The chemical genus included structural limitations that could exclude unrelated photosensitizers.
Expiration eliminated all enforcement value in the United States.

As of 2026, the patent has no remaining blocking strength. Its value is historical and evidentiary: it documents the foundational method underlying the Visudyne franchise and may remain relevant to patent-family mapping, prosecution history, inventorship, and prior-art analysis.

What generic launch scenarios exist for verteporfin?

A generic manufacturer can generally pursue a conventional ANDA for verteporfin for injection if it can demonstrate pharmaceutical equivalence, bioequivalence, quality, and an acceptable labeling strategy under FDA requirements.

The main launch scenarios are:

Post-expiry launch

This is the lowest patent-risk scenario for Patent 5,798,349. The applicant can launch without resolving the expired patent.

Pre-expiry Paragraph IV launch

This would have required certification against any still-listed patent and potentially exposed the applicant to a Hatch-Waxman infringement action. That scenario is no longer relevant to Patent 5,798,349.

Skinny-label launch

A generic could seek approval for nonpatented indications if later method-of-use patents covered only particular uses. The feasibility depends on the Orange Book use code, FDA labeling, prescribing information, and the scope of any later method claims.

Formulation-around strategy

A manufacturer could use a formulation that differs from a patented liposomal or stabilized composition. That strategy would not be necessary to avoid Patent 5,798,349 itself, but it could matter for later patents.

What biosimilar risk exists for verteporfin?

There is no biosimilar pathway issue for verteporfin. Verteporfin is a chemically defined small-molecule photosensitizer, not a biologic subject to the Public Health Service Act biosimilar framework.

Competitive entry occurs through the generic drug pathway, principally an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act. The principal regulatory risks are pharmaceutical equivalence, injectable-product quality, sterility, stability, container closure, and manufacturing consistency.

What geographic coverage did the patent have?

Patent 5,798,349 provided rights only in the United States. Parallel protection could exist in Canada, Europe, Japan, and other jurisdictions through related national applications or PCT filings, but the U.S. expiration did not automatically terminate foreign rights.

For international freedom-to-operate work, the relevant analysis must separate:

U.S. Patent 5,798,349;
Foreign counterparts;
Continuations and divisionals;
National-phase patents;
Patent-term adjustments or supplementary protection certificates;
Country-specific regulatory exclusivity.

The U.S. patent’s expiration therefore supports U.S. generic entry but does not establish freedom to launch verteporfin products globally.

Key Takeaways

Patent 5,798,349 covered photodynamic treatment of ocular neovascularization using green porphyrins, principally verteporfin.
Claims 1, 7, and 14 are the core independent treatment claims.
Claim 1 requires a liposomal formulation.
Claim 7 covers choroidal neovascularization and does not require a liposome or LDL carrier.
Claim 14 covers AMD treatment and is broad regarding formulation and laser parameters.
Claims 6, 13, and 20 narrow the invention to the verteporfin/BPD-MA structure.
The patent expired on November 7, 2014.
It no longer blocks U.S. generic verteporfin entry.
Verteporfin is regulated as a small-molecule drug, so biosimilar analysis does not apply.
Current risk must be assessed against later patents covering formulations, manufacturing, labeling, or delivery systems.
The principal competitive threat to Visudyne has been anti-VEGF therapy, not another porphyrin product.

FAQs

Does Patent 5,798,349 cover all verteporfin uses?

No. It covers specified photodynamic treatment methods involving ocular neovascularization, choroidal neovascularization, or AMD. It does not automatically cover every verteporfin use, formulation, disease, or laser application.

Can a generic manufacturer launch verteporfin in the United States without licensing this patent?

Yes. The patent expired on November 7, 2014, so a license to Patent 5,798,349 is no longer required for U.S. activities covered only by its expired claims.

Does the patent require the use of a 689-nanometer laser?

No. The claims provided require laser light absorbed by the green porphyrin but do not expressly recite 689 nanometers. The 689-nanometer wavelength is part of the commercial Visudyne protocol and FDA labeling.

Is liposomal verteporfin required for the AMD claims?

No. Claim 14 does not require a liposomal formulation. Claims 16 and related dependent claims add the liposomal limitation.

Could a new retinal photodynamic drug infringe Patent 5,798,349?

Not in the United States after expiration. Before expiration, infringement would have depended on whether the new drug was a claimed green porphyrin and whether the treatment satisfied the disease, localization, laser, and occlusion limitations.

References

United States Patent and Trademark Office. (1998). U.S. Patent No. 5,798,349: Photodynamic therapy of neovascularization using green porphyrins.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2023). Visudyne (verteporfin for injection) prescribing information.
U.S. Food and Drug Administration. (2000). NDA 21-119, Visudyne approval information.
Comparison of Age-related Macular Degeneration Treatments Trials Research Group. (2016). Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: Two-year results. Ophthalmology, 123(8), 1751-1761.

Details for Patent: 5,798,349

Summary for Patent: 5,798,349