United States Patent 5,023,082: Claim Scope, Expiration, Patent Landscape, and Generic Entry Risk

U.S. Patent No. 5,023,082 covers biodegradable sustained-release compositions built from a cross-linked, water-insoluble protein matrix containing an active agent, a plasticizer, and a cross-linking agent. The patent reaches precursor liquids, preformed compositions, administration methods, and periodontal treatment uses. Its ordinary patent term expired on June 11, 2008, 17 years after issuance. The patent therefore has no current blocking force in the United States, although later patents covering specific products, formulations, manufacturing processes, or clinical uses may remain relevant.

What does U.S. Patent 5,023,082 disclose?

The patent is directed to biodegradable drug-delivery systems that solidify into a sustained-release matrix. The matrix is based on a water-soluble protein that becomes water-insoluble after cross-linking.

The principal technical components are:

Element	Claimed scope
Matrix-forming material	Cross-linked water-soluble protein
Exemplary proteins	Gelatin, collagen, albumin, enzymes, fibrinogen
Preferred protein	Gelatin, including hydrolyzed gelatin
Plasticizer	Phthalate ester, phosphate ester, glycol derivative, hydrocarbon, oil, or fatty acid
Preferred plasticizer	Glycerin or sorbitol
Cross-linking agent	Aldehydes, alcohols, metals, acyl chloride, urea derivatives, and other listed agents
Preferred cross-linker	Formaldehyde or glutaraldehyde
Active agent	Broadly defined therapeutic, agricultural, or catalytic agent
Delivery formats	Film, implant, topical dosage form, injectable or administered precursor
Exemplary medical use	Periodontal-pocket treatment using an antibacterial agent
Stated composition ranges	Cross-linker: about 0.01% to 26%; protein: about 14% to 93%; plasticizer: about 0.01% to 52%

The patent is platform-oriented. It does not claim only chlorhexidine, periodontal disease, or dental implants. Those features appear in dependent claims and treatment claims, while the broad independent claims cover a wider range of active agents and delivery applications.

What are the independent claims in U.S. 5,023,082?

Claims 1, 2, 3, 10, and 35 are the principal independent claims.

Claim 1: Liquid precursor composition

Claim 1 covers a liquid precursor that contains:

A plasticizing agent.
An active agent.
A cross-linking agent.
A water-soluble protein capable of becoming a water-insoluble biodegradable polymeric matrix.

The precursor must solidify after administration to form the sustained-release composition. This claim is directed to an in situ delivery approach. A product that is administered as a liquid and then cross-links in the body could fall within the literal structure of this claim if all listed elements are present.

The claim contains functional limitations requiring the protein concentration to provide structural stability while preserving biodegradability and active-agent release. Those limitations narrow the claim relative to a formulation containing the same ingredients but failing to perform the required functions.

Claim 2: Preformed sustained-release composition

Claim 2 covers the solid composition itself. It requires:

A plasticizer.
An active agent.
A cross-linking agent.
A biodegradable polymeric matrix comprising cross-linked, water-insoluble protein.

Unlike claim 1, claim 2 does not require administration of a liquid precursor or in situ solidification. It can reach a preformed film, implant, insert, or other solid dosage form.

Claim 3: Administration of the liquid precursor

Claim 3 is a method claim requiring administration of the liquid precursor described in claim 1. The precursor must solidify after administration.

This claim is potentially relevant to injectable or locally administered systems in which the formulation is delivered before the sustained-release matrix has formed.

Claim 10: Administration of the preformed composition

Claim 10 covers administering the already formed biodegradable composition. It is broader than claim 3 regarding the timing of solidification because the composition is already a cross-linked matrix before administration.

Claim 35: Treatment method

Claim 35 covers treating a condition by providing the claimed composition to a patient. The composition must contain a pharmacological agent in an amount sufficient to produce a therapeutic effect.

Claims 36 through 42 narrow this method to periodontal and dental uses, including:

Implantation in a periodontal pocket.
Treatment of periodontal disease.
Use of an antibacterial agent.
Treatment of pericoronitis.
Adjunctive endodontic treatment.
Adjunctive tooth implantation procedures.
Adjunctive epiectomy procedures.

How broad is the claim scope?

The claims are broad in ingredient selection but narrower in combination.

A competing product generally must satisfy all material limitations of an asserted claim. The patent does not cover every biodegradable sustained-release composition. A formulation lacking any one of the following may fall outside the literal scope:

A protein matrix.
Cross-linking of a water-soluble protein into a water-insoluble matrix.
A listed plasticizer.
A listed cross-linking agent.
The claimed functional release and biodegradation properties.
For method claims, the specified administration or treatment activity.

The most important scope limitation is the protein matrix. A product based solely on poly(lactic-co-glycolic acid), ethylene-vinyl acetate, polycaprolactone, chitosan, alginate, or another non-protein polymer would not literally satisfy the cross-linked protein limitation.

The claims also use broad Markush groups. A formulation using glycerin as a plasticizer and glutaraldehyde as the cross-linker would fall within expressly identified preferred embodiments if the remaining limitations were satisfied.

What formulations are protected by U.S. 5,023,082?

The dependent claims identify several commercially meaningful formulation categories.

Gelatin and hydrolyzed gelatin matrices

Claims 11 through 13 cover gelatin, collagen, albumin, enzymes, fibrinogen, and hydrolyzed gelatin. Gelatin is the most commercially significant embodiment because it can be processed into films and can be cross-linked to control water penetration, erosion, and drug release.

A gelatin film containing an antibacterial agent, glycerin, and glutaraldehyde is close to the patent's preferred technical profile.

Plasticized films

Claims 15 through 19 address plasticizer concentration and function. The plasticizer must improve handling and flexibility without preventing release of the active agent.

Glycerin and sorbitol are expressly claimed. The claimed concentration range for plasticizer is about 0.01% to 52%, although infringement analysis would depend on the applicable basis for calculating the percentage and the construction of the claim language.

Cross-linker-controlled release

Claims 4 through 9 require sufficient cross-linking to render the protein insoluble while preserving release of the active agent. The patent therefore links matrix strength and release kinetics to cross-linker concentration and processing conditions.

The patent identifies:

Formaldehyde.
Glutaraldehyde.
Heat.
Pressure.
Radiation.
Cross-linker vapors.

A manufacturer could attempt to design around the claims by using a different matrix-forming mechanism, a non-listed cross-linker, or a protein that is not water-soluble before processing. Those strategies would require a separate analysis of equivalents and later patents.

Thin films and inserts

Claims 27 and 28 cover substantially two-dimensional films measuring approximately:

3 to 10 mm in length.
1 to 5 mm in width.
0.01 to 0.5 mm in depth.

This dimensional limitation is relevant to dental inserts, periodontal-pocket chips, and other localized dosage forms. A product outside these dimensions may still fall within broader claims 1, 2, 10, or 35.

Does the patent cover chlorhexidine periodontal inserts?

The patent expressly identifies chlorhexidine as an antibacterial agent in claims 22 through 24. Claim 24 is directed to a composition containing chlorhexidine.

The chlorhexidine claim is not limited to a single commercial product. It also requires the broader composition architecture, including the cross-linked protein matrix, plasticizer, and cross-linking agent. A chlorhexidine product using a non-protein matrix would not satisfy claim 24 literally.

The claim set is consistent with the technical design of biodegradable periodontal inserts that release chlorhexidine locally in a periodontal pocket. Commercial chlorhexidine inserts, including PerioChip-type products, have been associated with later product-specific patents and regulatory rights. The existence of the '082 patent alone does not establish that a particular marketed product practiced every claim or that the product depended exclusively on this patent.

What are the key dependent claims?

Claims	Subject matter
4	Cross-linker renders protein insoluble without preventing release
5	Cross-linker concentration of about 0.01% to 26%
6-7	Formaldehyde or glutaraldehyde, specifically glutaraldehyde
8-9	Heat, pressure, radiation, or cross-linker vapor processing
11-13	Protein selection, including gelatin and hydrolyzed gelatin
14	Protein concentration of about 14% to 93%
15-19	Plasticizer function, selection, and concentration
20-26	Pharmacological agents and multiple-agent compositions
27-28	Two-dimensional films and specific dimensions
29-31	Drug-to-protein ratio, plasticizer-to-protein ratio, and flexibility
32-34	Intranasal, intraocular, intra-aural, subcutaneous, transdermal, topical, parenteral, gingival, vaginal, and testicular administration
35-42	Patient treatment, periodontal disease, pericoronitis, endodontic treatment, tooth implantation, and epiectomy

The claim structure creates multiple fallback positions. A broad composition claim may be difficult to enforce if the accused product uses a different protein or cross-linker, but the narrower gelatin, glycerin, glutaraldehyde, film, chlorhexidine, and periodontal-use claims provide more technically specific combinations.

When did U.S. Patent 5,023,082 expire?

The patent issued on June 11, 1991. Because it was issued from a pre-June 8, 1995 application regime, its ordinary term was 17 years from issuance rather than 20 years from the earliest effective nonprovisional filing date. On that basis, the patent expired on June 11, 2008, subject to any terminal disclaimer or unusual patent-term adjustment shown in the official patent file.

The patent is therefore expired and cannot presently support a U.S. infringement action for post-expiration conduct. Under patent law, expired claims remain relevant to prior-art, prosecution-history, and freedom-to-operate analysis, but they do not create current exclusivity.

What is the Orange Book status of U.S. 5,023,082?

U.S. Patent 5,023,082 is not a current Orange Book exclusivity asset for a marketed small-molecule drug. It is a platform patent covering drug-delivery compositions and methods rather than a patent tied exclusively to one approved drug product.

Orange Book listing depends on the relationship between a patent and an approved New Drug Application. The FDA generally lists qualifying drug-substance, drug-product, and method-of-use patents submitted by the NDA holder. A broad expired delivery-system patent does not create current Orange Book protection even if it was historically relevant to a drug-delivery product (FDA, 2024a).

For a present-day generic applicant, any relevant Orange Book risk would come from later, unexpired patents listed against the specific reference product, not from the '082 patent.

Are Paragraph IV challenges relevant?

A Paragraph IV certification is relevant only when a generic applicant seeks approval under an ANDA referencing an FDA-listed drug product with an asserted patent listed in the Orange Book. Because the '082 patent expired in 2008, it cannot support a current Paragraph IV challenge or a 30-month stay.

A generic or follow-on applicant for a chlorhexidine insert, antibiotic periodontal insert, or related dosage form may still confront:

Later formulation patents.
Manufacturing-process patents.
Device or applicator patents.
Method-of-use patents.
Drug-release profile patents.
Patents covering particle size, excipients, or matrix architecture.
Regulatory exclusivity associated with the reference product.

A Paragraph IV certification against a later patent would require an element-by-element analysis of the later patent, not reliance on the expired '082 claims.

What patent litigation and settlement risk exists?

The '082 patent itself presents no current litigation risk because its ordinary term ended in 2008. Historical litigation or licensing activity could still matter for ownership, prosecution history, and the interpretation of related continuation patents, but the expired patent cannot be used as a current exclusion right.

For dental sustained-release products, litigation risk is more likely to arise from later patents covering:

Chlorhexidine concentration and release duration.
Gelatin cross-linking conditions.
Specific film dimensions.
Periodontal-pocket placement.
Adhesive or mucoadhesive excipients.
Applicator systems.
Combination treatment with scaling and root planing.
Alternative antibiotics such as doxycycline or minocycline.

Publicly identified commercial competitors in localized periodontal drug delivery include chlorhexidine inserts, doxycycline gel systems, and minocycline microsphere products. Their patent estates are product-specific and should not be treated as coextensive with U.S. 5,023,082.

How does the patent compare with competing periodontal drug-delivery products?

Product category	Active agent	Delivery technology	Relationship to '082
Chlorhexidine insert	Chlorhexidine gluconate	Biodegradable localized insert	Technically closest to the claimed gelatin-film embodiments
Doxycycline periodontal gel	Doxycycline hyclate	Injectable biodegradable gel	May avoid protein-matrix claims depending on formulation
Minocycline microspheres	Minocycline hydrochloride	Biodegradable polymeric microspheres	Generally distinct from a cross-linked protein film
Conventional systemic antibiotic	Various	Oral or injectable systemic dosage form	Usually outside the localized protein-matrix claims
Non-protein biodegradable implant	Various	PLGA, PCL, EVA, or other polymer	Typically outside literal protein limitations

The closest technical competitors are chlorhexidine inserts and other protein-based local implants. PLGA microspheres and injectable synthetic-polymer gels generally present a stronger literal design-around position, although later patents may cover those technologies separately.

Is there biosimilar risk?

There is no biosimilar issue for U.S. Patent 5,023,082. The patent covers small-molecule drugs, broad pharmacological agents, and delivery matrices. Biosimilar regulation under section 351(k) applies to biological products, not to ordinary chlorhexidine, doxycycline, minocycline, or gelatin-based combination products as such.

Regulatory classification is more likely to involve:

An ANDA for a pharmaceutically equivalent drug product.
A 505(b)(2) application for a product relying partly on published or FDA findings but differing in formulation, route, or dosage form.
A drug-device or combination-product pathway where the delivery system materially affects safety or effectiveness.

The patent's expiration removes one historical barrier, but it does not guarantee ANDA eligibility. FDA may require comparative studies for locally administered products where release, placement, retention, or local exposure differs materially from the reference product (FDA, 2024b).

What manufacturing and intellectual-property barriers remain?

The expired patent does not eliminate technical barriers. Important manufacturing issues include:

Reproducible protein molecular-weight distribution.
Control of glutaraldehyde or other cross-linker residuals.
Uniform active-agent loading.
Film thickness and mechanical strength.
Sterilization without loss of drug potency.
Control of cross-linking time and temperature.
Release-rate consistency.
Biodegradation and erosion testing.
Packaging against moisture and oxidation.
Local tolerability in periodontal tissue.

Later patents may claim these process parameters even when the basic concept is old. A freedom-to-operate review should therefore separate the expired platform claims from later patent families directed to a specific product and manufacturing process.

How strong is the patent estate today?

The current enforceability strength of U.S. 5,023,082 is zero because the patent is expired. Its historical technical breadth was substantial, particularly for gelatin-based, plasticized, cross-linked sustained-release films containing antibacterial agents.

Its historical strengths were:

Multiple independent claim categories.
Broad active-agent language.
Broad cross-linker and plasticizer Markush groups.
Specific chlorhexidine claims.
Periodontal treatment claims.
Claims covering both precursor and finished dosage forms.

Its limitations included:

Dependence on a cross-linked protein matrix.
Functional requirements for biodegradation and release.
Potential written-description and enablement issues across the large active-agent and cross-linker lists.
Narrower coverage for specific film dimensions and concentration ranges.
Lack of current enforceability after expiration.

What generic launch scenarios exist?

A generic or follow-on developer would generally face three scenarios.

Scenario 1: Generic product using a non-protein matrix

A PLGA, polycaprolactone, or other synthetic-polymer system would likely avoid literal infringement of the '082 patent because it lacks the cross-linked protein matrix. Later patents and FDA product-specific requirements would control the commercial risk.

Scenario 2: Protein-based periodontal insert

A gelatin or collagen insert containing chlorhexidine, glycerin, and glutaraldehyde could have historically practiced several claims. Today, the '082 patent is expired, so the principal risks would be later patents, regulatory comparability, manufacturing know-how, and product liability.

Scenario 3: Liquid in situ-forming precursor

A liquid precursor containing protein, active agent, plasticizer, and cross-linker that solidifies after administration would have been closely aligned with claims 1 and 3. Current development would focus on local safety, injection-site control, cross-linker toxicity, residuals, and FDA product classification.

Key Takeaways

U.S. Patent 5,023,082 covers biodegradable sustained-release systems based on cross-linked water-soluble proteins.
The independent claims reach precursor liquids, preformed compositions, administration methods, and therapeutic treatment methods.
Gelatin, hydrolyzed gelatin, glycerin, sorbitol, glutaraldehyde, chlorhexidine, thin films, and periodontal-pocket implants are expressly addressed.
The patent is broader than a chlorhexidine periodontal insert but narrower than all biodegradable drug-delivery systems.
The ordinary patent term expired on June 11, 2008.
The patent has no current U.S. blocking effect and cannot support a current Paragraph IV challenge.
No biosimilar pathway is implicated.
Current commercial risk must be assessed against later patents covering specific products, formulations, processes, applicators, and approved uses.
A synthetic-polymer system without a cross-linked protein matrix would generally have a strong literal design-around position against the expired claims.

FAQs

Does U.S. Patent 5,023,082 cover PerioChip?

It covers claim elements technically associated with a chlorhexidine-containing biodegradable periodontal insert, including cross-linked protein, plasticizer, cross-linker, and antibacterial agent. It is not a current blocking patent because it expired in 2008.

Can a company launch a gelatin-based chlorhexidine periodontal insert today?

The '082 patent alone would not prevent launch. The company would still need to address later patents, FDA requirements, formulation equivalence, local safety, manufacturing controls, and any product-specific exclusivity.

Does the patent cover PLGA microspheres containing minocycline?

Not literally if the product lacks a cross-linked water-insoluble protein matrix. PLGA microspheres are structurally different from the claimed protein-based compositions.

What is the most commercially important claim in the patent?

Historically, the combination of a biodegradable cross-linked gelatin matrix, plasticizer, cross-linker, antibacterial agent, and periodontal-pocket administration was the most commercially relevant claim group.

Can the expired patent still be cited in patent prosecution?

Yes. The patent may be cited as prior art or used to assess novelty, obviousness, written description, enablement, or prosecution strategy. Its expiration does not remove its evidentiary value.

References

Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024b). Applications covered by section 505(b)(2). U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (1991). U.S. Patent No. 5,023,082: Biodegradable sustained-release compositions and methods of use thereof. U.S. Department of Commerce.
United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, Chapter 2700: Patent terms and extensions. U.S. Department of Commerce.
United States Code. (2024). 35 U.S.C. §§ 154, 156, and 271. Government Publishing Office.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Israel	78826	May 18, 1986

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	80996	⤷ Start Trial
Australia	605487	⤷ Start Trial
Australia	7480687	⤷ Start Trial
Canada	1307463	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,023,082