US Patent 6,613,355: Claim Scope, Expiration, and Polyorthoester Patent Landscape

US Patent 6,613,355 covers a semi-solid drug-delivery vehicle built from a defined polyorthoester and a compatible liquid excipient. The patent is platform technology rather than a patent directed to a named active pharmaceutical ingredient. Its broadest claim reaches compositions containing as little as 0.1 mol% of a specified R1 structural unit, while dependent claims narrow the polymer concentration, molecular weight, PEG content, and selected polyorthoester architecture.

The patent issued on September 2, 2003. Based on the statutory 20-year patent term measured from the earliest effective nonprovisional filing date, the patent is expired and does not provide current US exclusionary rights. No FDA Orange Book, Paragraph IV, biosimilar, or drug-specific exclusivity issue follows directly from this patent. The technology may still have commercial relevance through know-how, later patents, manufacturing controls, or contract rights.

What does US Patent 6,613,355 cover?

The patent covers a two-component semi-solid delivery vehicle:

A biodegradable or bioerodible polyorthoester having a prescribed formula and at least one R1-derived A unit.
A pharmaceutically acceptable liquid excipient compatible with the polyorthoester.

The liquid excipient categories include:

Polyethylene glycol ether derivatives with molecular weights from 200 to 4,000.
Polyethylene glycol copolymers with molecular weights from 400 to 4,000.
Mono-, di-, or triglycerides of C2-C19 aliphatic carboxylic acids.
Alkoxylated tetrahydrofurfuryl alcohols, their C1-C4 ethers, and their C2-C19 carboxylic acid esters.
Biocompatible oils.

The claim is directed to the delivery vehicle itself. It does not require a drug, biologic, therapeutic indication, route of administration, dosage regimen, or particular release profile.

Claim 1: the principal scope

Claim 1 is the key enforceable claim historically. A composition falls within the claim only if it satisfies both polymer and excipient requirements.

The polymer must have:

The claimed polyorthoester backbone.
R, R*, n, and A substituents within the stated ranges.
At least 0.1 mol% of A units having the R1 structure.
The permitted R1, R2, R3, or R4 structural options.
A diol-derived R4 option containing an amide, imide, urea, or urethane group where that alternative is used.

The composition must also contain one of the listed compatible liquid excipients.

The 0.1 mol% threshold is commercially important. A formulation does not need to contain a large proportion of the R1 unit to fall within the literal scope of claim 1. This allows the claim to reach polymers in which the R1-containing comonomer is a relatively minor structural component.

Claims 2 through 4: quantitative limitations

Claim	Limitation	Practical effect
2	Polyorthoester concentration of 1% to 99% by weight	Covers dilute liquid-like systems through highly polymer-loaded semi-solids
3	Polyorthoester molecular weight of 1,000 to 20,000	Targets delivery polymers within a moderate molecular-weight range
4	R1 fraction of 1 to 90 mol% of A units	Narrows the broad 0.1 mol% threshold while retaining substantial breadth

Claim 2 is broad because nearly the entire practical concentration range is included. Claim 3 is useful for formulations using controlled molecular-weight polymer batches. Claim 4 materially increases the R1 content but still covers a wide range of polymer compositions.

What formulations are protected by US 6,613,355?

The protected formulations are semi-solid vehicles containing the claimed polyorthoester and a compatible liquid phase. The claims do not require a specific viscosity, gel strength, syringeability, depot duration, particle size, sterilization process, or release-rate parameter.

A formulation is most exposed when it contains:

A polyorthoester with PEG-containing or otherwise claimed A units.
At least 0.1 mol% R1 units.
A PEG-based excipient, glyceride, alkoxylated tetrahydrofurfuryl derivative, or biocompatible oil.
Polymer content between 1% and 99% by weight.
Polymer molecular weight between 1,000 and 20,000.

The formulation may contain an active ingredient without losing coverage. Because the claim is vehicle-based, adding a drug does not avoid infringement if the vehicle already meets the limitations.

Claim 5: restricted formula I embodiment

Claim 5 narrows claim 1 in several ways:

The polyorthoester must be of formula I.
No A units may have A equal to R2.
R3 is limited to a structure with x from 0 to 10 and y from 2 to 30.
R6 is limited to a structure with s from 0 to 10 and t from 2 to 30.
R5, R7, and R8 are independently hydrogen or methyl.

This claim is narrower in chemical scope but more useful for evaluating specific PEG-containing polyorthoesters.

Claims 6 and 7: defined PEG spacer structures

Claims 6 and 7 identify particularly specific embodiments:

R3 and R6 each contain a bis-ethylene glycol spacer in claim 6.
R3 and R6 each contain a longer nona-ethylene glycol spacer in claim 7.
R5 is methyl.
p is 1 or 2.

Claim 7 is chemically narrower than claim 6 because it requires the longer PEG9-type segment. These claims are easier to test analytically and more vulnerable to design-around using different PEG chain lengths, different terminal groups, or non-PEG hydrophilic segments.

How should the claims be construed for infringement analysis?

Literal infringement requires every limitation of at least one asserted claim to be present in the accused formulation. The principal elements are:

Claim element	Evidence likely required
Semi-solid delivery vehicle	Rheology, viscosity, composition, and product specifications
Polyorthoester of formula I or II	NMR, mass spectrometry, synthesis records, and structural characterization
R, R*, n, and A within claimed ranges	Polymer design and analytical data
At least 0.1 mol% R1 units	Monomer feed records, NMR integration, or validated composition analysis
Compatible liquid excipient	Formulation records and excipient identity
Claimed concentration or molecular weight	Batch specifications, SEC/GPC, and manufacturing records

The molecular-weight limitation in claim 3 is particularly dependent on claim construction. A formulation may contain a polymer population rather than a single molecular species. SEC/GPC method selection, calibration standards, number-average versus weight-average molecular weight, and batch variability could affect the analysis.

The “at least 0.1 mol percent” limitation may also create an evidentiary issue. A claimant would need to establish the composition of the polymer, not merely the presence of an R1-type reagent in the manufacturing process.

When did US Patent 6,613,355 lose exclusivity?

US Patent 6,613,355 is expired. Its issue date was September 2, 2003, and its term was governed by the post-1995 20-year patent-term regime, subject to any patent-term adjustment or extension recorded by the USPTO.[1][2]

The patent therefore does not create a current US blocking right against a new formulation. A freedom-to-operate analysis must instead examine:

Continuations and divisionals.
Related patents with later effective filing dates.
Improvements covering specific drugs or delivery systems.
Manufacturing-process patents.
Formulation-specific patents.
Trade secrets and contractual restrictions.

Expiration of this patent does not place the underlying technology into a regulatory category equivalent to FDA approval or generic approval. It removes patent exclusivity only for the claims that actually expired.

Is patent-term extension relevant?

Patent-term extension under 35 U.S.C. §156 is generally associated with regulatory review of a specific approved product. US 6,613,355 claims a delivery vehicle and does not identify a specific drug product in the provided claims. There is no apparent basis from the claim set for assuming a product-specific extension.

Patent-term adjustment under 35 U.S.C. §154 can affect the precise end date, but it does not alter the current conclusion that the patent is expired.[1]

What is the Orange Book status of US 6,613,355?

US 6,613,355 is not, by itself, an Orange Book patent listing. The FDA Orange Book identifies patents and regulatory exclusivities associated with approved drug products, usually through product-specific listing by an NDA holder.[3]

This patent:

Does not claim an active ingredient.
Does not claim a particular approved drug.
Does not recite a dosage regimen.
Does not establish a method-of-use exclusivity period.
Does not create an automatic ANDA certification issue.

A drug product using a polyorthoester vehicle could have separate Orange Book-listed patents if the NDA holder listed patents directed to the product, formulation, method of use, or delivery system. The existence of US 6,613,355 would not establish that such listings exist.

Are Paragraph IV challenges associated with this patent?

No drug-specific Paragraph IV issue follows from the claims provided. Paragraph IV certifications arise when an ANDA applicant challenges a patent listed in the Orange Book for a reference listed drug.[4]

Because US 6,613,355 is a platform delivery-vehicle patent rather than an identified drug patent:

It is not inherently subject to an ANDA Paragraph IV challenge.
It does not create a 30-month stay by itself.
It does not determine generic entry timing for any named drug.
It does not establish exclusivity for a reference listed drug.

A separate Paragraph IV dispute could arise only if a related, unexpired formulation or product patent were listed for an approved drug.

Does US 6,613,355 create biosimilar risk?

No. Biosimilar litigation under the Biologics Price Competition and Innovation Act concerns patents associated with biological products and reference products.[5] US 6,613,355 claims a synthetic polymeric delivery vehicle and does not claim a biologic molecule, antibody, cell therapy, protein sequence, or biological manufacturing process.

A biologic delivered using a polyorthoester could face separate formulation or delivery-system patent issues. Those issues would arise from other patents, not from biosimilar status under this patent.

How strong is the patent estate for the claimed technology?

The individual claim architecture is technically broad but legally vulnerable in several areas.

Strengths

Claim 1 covers a composition rather than a particular drug, creating broad platform reach.
The R1 threshold begins at 0.1 mol%, which captures polymers containing a small amount of the specified unit.
The excipient list covers multiple commercially relevant liquid phases.
The claims do not require a particular therapeutic use or release duration.
Claims 2 and 3 encompass broad practical concentration and molecular-weight ranges.

Vulnerabilities

The chemical definitions are complex and may create claim-construction disputes.
The 0.1 mol% R1 threshold requires reliable polymer-composition evidence.
Semi-solid status may be disputed for formulations near the liquid or gel boundary.
The compatible-excipient requirement may exclude alternative solvents, plasticizers, and oils.
Claims 6 and 7 are narrow and can often be avoided through spacer-length or terminal-group changes.
Prior-art risk is significant for polyorthoester drug-delivery systems, PEG-containing polymers, biodegradable depots, and semi-solid injectable vehicles.

The expired status eliminates current infringement leverage in the United States, but the claims remain relevant for historical validity analysis, patent-family mapping, and interpretation of later continuation patents.

What design-arounds could avoid the claim set?

A competitor seeking to avoid the historical claim scope could consider several technical routes:

Use a polymer other than a polyorthoester.
Use a polyorthoester without the claimed R1 unit.
Keep the R1 fraction below 0.1 mol%, subject to reliable analytical confirmation.
Use an A unit outside the claimed R1-R4 structures.
Use a liquid excipient outside the listed PEG, glyceride, alkoxylated tetrahydrofurfuryl, and biocompatible-oil categories.
Use a solid implant, microparticle, nanoparticle, or aqueous suspension rather than the claimed semi-solid vehicle.
Use a different spacer length or terminal substitution to avoid claims 6 and 7.
Use a molecular weight outside the claim 3 range where that claim is being relied upon.
Use a concentration outside the claim 2 range, although practical delivery considerations may limit this option.

Because claim 1 is expired, these design-arounds have current commercial significance mainly where they also avoid later patent claims.

What patent landscape surrounds polyorthoester delivery systems?

The relevant landscape is broader than US 6,613,355 and normally divides into five patent groups.

Landscape segment	Typical protected subject matter	Relevance
Polyorthoester composition patents	Backbone chemistry, monomers, comonomer units, degradation control	Determines whether the polymer itself is covered
Semi-solid vehicle patents	Polymer-liquid combinations, viscosity, injectable depots	Closest technical category to US 6,613,355
Drug-loaded depot patents	Specific active ingredients in polymer matrices	Can create product-specific barriers
Method-of-use patents	Injection site, dosing schedule, sustained delivery, therapeutic indication	Potential Orange Book relevance
Manufacturing patents	Polymer synthesis, purification, sterilization, filling, scale-up	Can remain important after composition patents expire

The most important competitive distinction is between an expired platform patent and later product-specific patents. A company may freely practice the expired vehicle claims while still facing blocking rights covering a particular drug, formulation ratio, injection protocol, or manufacturing method.

What litigation, licensing, or commercial barriers affect the technology?

The claim set alone does not establish a current litigation or licensing barrier. No Orange Book or biologic exclusivity consequence can be inferred from the patent.

Commercial diligence should separate four categories:

Expired US composition claims.
Unexpired foreign counterparts.
Later US continuation or improvement patents.
Non-patent barriers, including formulation know-how, polymer reproducibility, sterilization validation, and regulatory data.

Geographic rights are jurisdiction-specific. Expiration in the United States does not determine the status of corresponding patents in Europe, Japan, Canada, China, or other jurisdictions. Foreign family members require separate review of national grant, maintenance, disclaimer, and expiration records.

Manufacturing may remain a practical barrier because polyorthoester performance depends on molecular-weight control, residual monomer levels, water sensitivity, batch consistency, and depot rheology. Those factors can support regulatory and commercial differentiation even after patent expiration.

How does this patent compare with a drug-specific formulation patent?

Issue	US 6,613,355	Drug-specific formulation patent
Subject matter	Polymer vehicle platform	Named drug or defined drug formulation
Active ingredient required	No	Usually yes
Orange Book relevance	Limited and indirect	Potentially direct
Paragraph IV relevance	None inherent	Common if listed for an NDA product
Biosimilar relevance	None	Possible for biologic delivery products
Design-around	Chemical and excipient changes	Drug loading, ratio, dosage, process, or use changes
Commercial value after expiration	Know-how and later patents	May remain material if later patents survive

Key Takeaways

US Patent 6,613,355 claims semi-solid polyorthoester delivery vehicles combined with specified liquid excipients.
Claim 1 is broad because it requires only 0.1 mol% of the R1 unit and covers a wide excipient set.
Claims 2 through 4 add concentration, molecular-weight, and R1-fraction limits.
Claims 5 through 7 narrow the polymer to defined formula I and PEG-containing structures.
The patent issued September 2, 2003 and is expired under the applicable US patent-term framework.
The patent is not inherently an Orange Book, Paragraph IV, or biosimilar patent.
Current freedom to operate depends primarily on later family members, drug-specific patents, manufacturing patents, and foreign rights.
The principal historical validity issues are claim construction, polymer-composition proof, semi-solid classification, and prior art involving polyorthoesters and PEG-containing depot systems.

FAQs

Does US 6,613,355 cover a specific drug?

No. The claims cover a delivery vehicle and do not require a particular active pharmaceutical ingredient.

Can a company commercialize a polyorthoester depot after this patent expired?

Yes, expiration removes the US exclusionary rights of the expired claims. Later patents, foreign rights, and regulatory requirements may still affect commercialization.

Is a PEG excipient alone enough to infringe US 6,613,355?

No. The formulation must also contain a polyorthoester meeting the structural limitations and the other limitations of an asserted claim.

Are claims 6 and 7 limited to exactly PEG2 and PEG9 structures?

The supplied claim language identifies the relevant ethylene glycol repeat structures. Claim 6 is narrower than claim 5, and claim 7 requires the longer defined structure. Exact infringement depends on chemical interpretation and analytical characterization.

Does patent expiration eliminate manufacturing risk?

No. Manufacturing risk can remain through later process patents, trade secrets, polymer-quality requirements, residual-solvent controls, sterilization validation, and regulatory comparability obligations.

References

United States Code. (2024). 35 U.S.C. §§ 154, 156. https://uscode.house.gov
United States Patent and Trademark Office. (2003). US Patent No. 6,613,355, “Semi-solid delivery vehicles.” https://patents.google.com/patent/US6613355
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Code. (2024). 21 U.S.C. § 355(j). https://uscode.house.gov
U.S. Food and Drug Administration. (2024). Biosimilar and interchangeable products. https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilar-product-information

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005289425	⤷ Start Trial
Canada	2579297	⤷ Start Trial
China	101052376	⤷ Start Trial
European Patent Office	1796629	⤷ Start Trial
European Patent Office	2902012	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,613,355

Summary for Patent: 6,613,355