US Patent 5,599,552: Claim Scope, Expiration, and In-Situ Biodegradable Implant Patent Landscape

US Patent 5,599,552 covers injectable or otherwise administrable biodegradable polymer systems that form porous implants inside the body. Its core inventive concept is an in-situ forming implant with a porous outer skin and porous inner core, produced either by solvent-induced coagulation of a thermoplastic polymer or by curing a thermoset polymer. The patent is expired and does not currently create an enforceable US patent barrier.

What does US Patent 5,599,552 protect?

The patent protects compositions and administration methods for forming biodegradable, microporous implants in vivo. The claims reach two principal technologies:

Thermoplastic polymer formulations dissolved or dispersed in a body-fluid-miscible organic solvent.
Liquid biodegradable thermoset polymer formulations that cure in situ.

The claimed implant has a distinctive morphology: a porous core surrounded by a porous skin. The claims also cover pore-forming agents, drug-loaded formulations, polymer classes, solvents, curing agents and therapeutic uses.

The broadest practical claim concepts are:

Claim group	Technology	Principal limitations
Claims 1, 2, 4-10, 12	Thermoplastic in-situ precipitation	Biodegradable thermoplastic polymer, water-miscible or water-dispersible organic solvent, solidification in body fluid, porous core and porous skin
Claims 3, 11, 14, 16-21	Thermoset in-situ curing	Liquid biodegradable thermoset polymer, in-situ curing, microporous core and skin
Claims 13, 22-26	Therapeutic and tissue-use methods	Administration to form an implant, biological activity, tissue regeneration, tissue-defect filling or reproductive-system effects

The claims are platform claims. They are not limited to a particular active pharmaceutical ingredient, disease, dosage strength or commercial product.

How many independent claims does US 5,599,552 have?

The patent has four principal independent claim sets: claims 1, 3, 11 and 13.

Claim 1: thermoplastic solvent system

Claim 1 requires a composition containing:

A biodegradable thermoplastic polymer;
A polymer that is insoluble in aqueous or body fluid;
An organic solvent that is miscible to dispersible in aqueous or body fluid;
In-vivo coagulation or solidification;
A microporous implant;
A porous core surrounded by a porous skin.

This is the central solvent-exchange claim. A formulation that remains dissolved after administration, without forming the claimed porous core-and-skin structure, would present a weaker infringement case.

Claim 1 does not require a drug. It also does not expressly require a pore-forming agent. The polymer and solvent limitations are functional and structural at the same time: the polymer must be biodegradable and insoluble in body fluid, while the solvent must leave or disperse into body fluid sufficiently to cause polymer precipitation.

Claim 3: thermoset implant method

Claim 3 covers administering a liquid formulation of a biodegradable thermoset polymer that cures into a microporous matrix with a porous core and porous skin.

Unlike claim 1, claim 3 does not depend on solvent-driven coagulation. It focuses on chemical curing or cross-linking after administration. The claim also requires an amount effective to form an implant that alters a biological or physiological activity.

Claim 11: broad thermoset composition

Claim 11 covers a liquid biodegradable thermoset polymer formulation capable of forming the claimed porous matrix. It is broader than claim 16 because it does not require the polymer to be an acrylic ester-terminated prepolymer.

The absence of an express solvent limitation gives claim 11 potentially broad coverage of multi-component or internally curing systems. Its principal constraint remains the claimed porous morphology.

Claim 13: thermoplastic administration method

Claim 13 is the principal method counterpart to claim 1. It requires:

Administration to an animal;
A biodegradable, bioerodible and biocompatible thermoplastic polymer;
Insolubility of the polymer in aqueous or body fluid;
An organic solvent miscible to dispersible in body fluid;
Solvent dispersion and polymer coagulation or solidification;
A porous core surrounded by a porous skin.

The added "bioerodible" and "biocompatible" limitations may narrow claim 13 relative to claim 1, depending on the construction applied to the corresponding terms.

What polymer classes are protected?

Claims 6, 12 and 17 enumerate extensive polymer classes. The listed materials include:

Polylactides;
Polyglycolides;
Polycaprolactones;
Polyanhydrides;
Polyamides;
Polyurethanes;
Polyesteramides;
Polyorthoesters;
Polydioxanones;
Polyacetals and polyketals;
Polycarbonates and polyorthocarbonates;
Polyphosphazenes;
Polyhydroxybutyrates and polyhydroxyvalerates;
Polyalkylene oxalates and succinates;
Polyamino acids;
Polymethyl vinyl ether;
Chitin and chitosan for the thermoset-prepolymer claim;
Copolymers, terpolymers and combinations.

Claim 12 specifically identifies lactide copolymers with glycolide or caprolactone, including terpolymers. This limitation is commercially important because lactide-glycolide and lactide-caprolactone systems are common biodegradable depot and tissue-repair polymers.

The polymer list does not by itself establish infringement. A candidate formulation must also satisfy the in-situ formation and porous core-and-skin limitations.

What solvents are protected?

Claim 7 lists the following solvents or solvent combinations:

N-methyl-2-pyrrolidone;
2-pyrrolidone;
Propylene carbonate;
Acetone;
Acetic acid;
Ethyl acetate;
Ethyl lactate;
Methyl acetate;
Methyl ethyl ketone;
Dimethylformamide;
Dimethyl sulfoxide;
Dimethyl sulfone;
Tetrahydrofuran;
Caprolactam;
Decylmethylsulfoxide;
Oleic acid;
N,N-diethyl-m-toluamide;
1-dodecylazacycloheptan-2-one.

Claim 2 narrows the solvent system to a mixture of:

A good solvent for the thermoplastic polymer; and
A poorer solvent or nonsolvent for that polymer.

The mixture must maintain polymer solubility before administration but permit coagulation after solvent diffusion into body fluid. This good-solvent/poor-solvent architecture is a meaningful technical limitation and may distinguish conventional polymer solutions that do not rely on controlled solvent quality.

N-methyl-2-pyrrolidone, or NMP, is particularly relevant to commercial in-situ biodegradable implant systems because it dissolves several lactide-glycolide polymers and is miscible with water.

What formulations are protected by US 5,599,552?

The formulation claims cover several categories.

Thermoplastic solvent-exchange formulations

These formulations contain a biodegradable polymer dissolved in an organic solvent. After injection, body fluid enters the formulation and solvent leaves it. The polymer precipitates into a porous implant.

A formulation may fall within the technical scope if it uses:

PLGA or another listed polymer;
NMP or another listed solvent;
An injectable liquid;
In-vivo precipitation;
A porous outer skin and porous inner core.

Thermoset prepolymer formulations

Claims 16 and 17 cover acrylic ester-terminated biodegradable prepolymers capable of cross-linking. Claim 18 adds a curing agent. Claim 19 covers biologically active agents that do not contain functional groups interfering with the thermosetting reaction.

These claims target systems in which the polymer is administered before cross-linking and cures within the body.

Pore-forming formulations

Claims 4, 5, 14 and 15 cover pore-forming agents, including:

Sugars;
Salts;
Water-soluble polymers;
Water-soluble organic solvents;
Water-insoluble substances that degrade into water-soluble substances.

A pore-forming agent is not required by the independent thermoplastic claims. It is required only where a dependent claim is asserted.

Does the porous core-and-skin limitation materially narrow the claims?

Yes. The core-and-skin requirement is one of the most important limitations in the patent.

The implant must have:

A core that is porous; and
A surrounding skin that is also porous.

A dense, nonporous coating surrounding a porous depot may not satisfy the literal limitation that both regions are porous. A formulation that forms a uniform porous mass without a distinct skin may also create a claim-construction issue.

The patent specification's description of skin formation likely relates to solvent and water exchange at the implant surface. The outer region can have different pore dimensions, polymer density or solvent exposure from the interior, but the claims as supplied require porosity in both regions.

For freedom-to-operate analysis, morphology testing is central. Relevant evidence would include cross-sectional microscopy, porosimetry, micro-CT, solvent-exchange studies and implant recovery analysis.

What biological agents and therapeutic uses are protected?

Claims 8-10 and 19-21 cover drug-loaded systems. The listed active categories include:

Anti-inflammatory agents;
Antibacterial agents;
Antiparasitic agents;
Antifungal agents;
Antiviral agents;
Antineoplastic agents;
Analgesics and anesthetics;
Vaccines;
Central nervous system agents;
Growth factors;
Hormones;
Antihistamines;
Osteoinductive agents;
Cardiovascular agents;
Anti-ulcer agents;
Bronchodilators and vasodilators;
Birth-control agents;
Fertility-enhancing agents.

Claims 9 and 20 expressly cover polypeptides from natural, synthetic or recombinant DNA sources. Claims 19 and 20 apply to thermoset formulations and require the active agent to be free of functional groups that interfere with curing.

Claims 22-26 extend the method claims to:

Tissue regeneration;
Filling tissue defects;
Delivery of biological agents;
Alteration of reproductive-system activity.

These claims are broad field-of-use claims. They do not identify a specific molecule, anatomical site or clinical indication.

When did US Patent 5,599,552 lose exclusivity?

US Patent 5,599,552 is expired. Its nominal US patent term ran approximately 20 years from the effective nonprovisional filing date, subject to any patent-term adjustment or terminal-disclaimer issue reflected in the USPTO record.

The patent was issued on February 4, 1997. Based on the reported May 31, 1995 US filing date, the ordinary term would have ended around May 31, 2015. A provisional priority date, if present, generally does not determine the 20-year patent term under the post-Uruguay Round patent-term regime. The USPTO Patent Center record controls the precise term calculation.[1][2]

Event	Date or status
US filing	May 31, 1995, based on available patent bibliographic data
Patent issued	February 4, 1997
Expected ordinary expiration	Approximately May 31, 2015
Current status	Expired
Current enforceability	No enforceable US patent exclusivity from US 5,599,552

The expiration of this patent does not eliminate separate rights in later continuations, divisionals, improvements, formulation patents, drug patents, trademarks, regulatory exclusivity or trade secrets.

What is the Orange Book status of US 5,599,552?

US 5,599,552 is not itself an Orange Book drug patent. It is a platform patent covering implant-forming compositions and methods.

The FDA Orange Book lists patents submitted for approved drug products, including patents directed to active ingredients, formulations, compositions, methods of use and, in certain cases, drug-device combinations.[3] A platform patent may be relevant to an approved product without being listed for that product.

The patent therefore does not independently create a Paragraph IV filing requirement. A generic applicant would analyze Orange Book-listed patents for the specific reference listed drug. If the reference product relied on an in-situ biodegradable implant technology, later product-specific patents could be listed even though US 5,599,552 had expired.

Did US 5,599,552 create Paragraph IV or biosimilar risk?

Paragraph IV risk

The patent was not a conventional small-molecule drug patent. A Paragraph IV challenge would arise only if a product-specific patent covering an FDA-approved drug were listed in the Orange Book and a generic applicant certified that the patent was invalid, unenforceable or not infringed.

For a generic or follow-on implant product, the practical analysis is:

Identify the reference listed drug;
Review current Orange Book listings;
Separate expired platform patents from live product patents;
Evaluate formulation, manufacturing and method-of-use patents;
Assess whether the proposed product forms the same porous core-and-skin structure.

An expired platform patent may reduce historical litigation exposure but does not guarantee freedom to operate.

Biosimilar risk

Biosimilar litigation under the Biologics Price Competition and Innovation Act does not ordinarily center on this patent. US 5,599,552 is not a biologic composition-of-matter patent. Its relevance to biologics would be limited to a delivery system in which a protein, peptide, growth factor or other biologic is incorporated into the implant.

A biologic sponsor could still assert later formulation, delivery-device, manufacturing or method-of-use patents.

Which companies and products are associated with this technology?

The technology is closely associated with the commercial development of in-situ biodegradable delivery systems, including the Atrigel platform and products such as Atridox. Atridox used doxycycline in a biodegradable polymer delivery system for periodontal treatment. FDA product records and historical company disclosures should be reviewed separately for the exact approval holder, manufacturing entity and current marketing status.[4][5]

The commercial landscape has included:

Biodegradable injectable depots;
Periodontal drug delivery;
Local antibiotic delivery;
Long-acting peptide and protein delivery;
Tissue-regeneration matrices;
Bone and soft-tissue defect fillers;
Injectable surgical sealants and scaffolds.

The patent landscape is therefore broader than drug patents. It includes polymer chemistry, solvent systems, implant morphology, active-agent compatibility, manufacturing processes, applicators and clinical uses.

How strong is the patent estate for this technology?

US 5,599,552 was technically broad but commercially vulnerable in several respects.

Strengths

Multiple independent claim categories;
Coverage of both thermoplastic and thermoset systems;
Broad polymer and solvent Markush groups;
Drug-loaded and tissue-regeneration embodiments;
Coverage of in-situ formation rather than a single dosage form;
Morphological limitation that could distinguish ordinary polymer solutions.

Weaknesses

The patent is expired;
The claims depend on difficult-to-measure structural features;
"Microporous," "skin" and "core" may require expert evidence;
Functional language creates claim-construction disputes;
Many polymer and solvent combinations were known in biodegradable drug delivery;
Product-specific competitors may avoid the claims through preformed implants, nonporous matrices, alternative curing chemistry or different solvent systems.

The strongest historical enforcement position would likely have involved a commercial formulation using a listed polymer and solvent that visibly formed the claimed porous core-and-skin implant. The weakest position would have involved an unrelated preformed implant or a system that did not coagulate or cure in situ.

What manufacturing and IP barriers remain after expiration?

Expiration removes the patent's direct exclusionary force, but technical barriers remain.

Key manufacturing barriers include:

Achieving reproducible polymer molecular weight;
Controlling residual solvent;
Maintaining sterile manufacturing conditions;
Managing polymer degradation during storage;
Controlling injection force and delivery-device compatibility;
Producing consistent porosity;
Preventing burst release;
Preserving protein or peptide activity;
Demonstrating biocompatibility and local tissue tolerance.

Later patents may cover:

Specific polymer molecular-weight ranges;
Polymer end groups;
Solvent ratios;
Drug loading;
Release profiles;
Sterilization;
Applicator systems;
Tissue-specific use;
Combination products;
Manufacturing controls.

Trade secrets may also protect polymer synthesis, mixing, filling, sterilization and release testing even after the platform patent expires.

How does US 5,599,552 compare with conventional biodegradable implants?

Attribute	US 5,599,552 platform	Preformed biodegradable implant	Conventional injectable polymer solution
Implant formation	In situ	Manufactured before administration	May remain liquid or gel
Polymer state before administration	Dissolved thermoplastic or liquid thermoset	Solid	Usually dissolved or dispersed
Porous skin and core	Expressly required	Not necessarily present	Not necessarily present
Solvent exchange	Central to thermoplastic claims	Usually absent at implantation	May occur without claimed morphology
Drug loading	Expressly covered	Common	Common
Tissue regeneration	Expressly covered in method claims	Common	Possible
Current US 5,599,552 exclusivity	Expired	Depends on later patents	Depends on later patents

What generic launch scenarios exist?

A generic or follow-on entrant would face different risks depending on product design.

Lower-risk design

A product may reduce exposure by using:

A preformed implant;
A nonporous or materially different matrix;
A polymer not within the asserted claim construction;
A curing mechanism unrelated to the claimed thermoset system;
A delivery system that does not form a porous skin;
A formulation that does not use solvent-induced precipitation.

Higher historical risk

The greatest historical exposure would have involved an injectable PLGA/NMP product that formed a porous implant in situ and delivered an antibiotic, peptide, hormone or growth factor.

Because US 5,599,552 is expired, present commercial risk would ordinarily shift to later family members, product-specific patents, FDA exclusivity and non-patent manufacturing barriers.

What geographic coverage did US 5,599,552 provide?

The patent provided rights only in the United States. Foreign counterparts, if any, required separate analysis by jurisdiction. Patent term, claim scope, maintenance status and enforceability would differ in Europe, Canada, Japan, Australia and other markets.

A US expiration does not establish freedom to operate internationally. A global launch requires a country-by-country review of:

National-phase counterparts;
Continuations and divisionals;
Patent-term extensions;
Supplementary protection certificates;
Local formulation patents;
Device patents;
Regulatory exclusivity.

Key Takeaways

US 5,599,552 covers in-situ forming biodegradable implants.
Its central technical limitation is a microporous implant with both a porous core and porous surrounding skin.
Claims 1 and 13 target solvent-induced coagulation of biodegradable thermoplastics.
Claims 3 and 11 target curing of biodegradable thermoset polymers.
Claims 4, 5, 14 and 15 cover pore-forming agents.
Claims 8-10 and 19-21 cover drug-loaded systems, including peptide and protein delivery.
Claims 22-26 cover tissue regeneration, defect filling and reproductive-system uses.
The patent's ordinary term ended approximately in 2015.
It is not an Orange Book patent in its own right and does not independently support a current Paragraph IV challenge.
Current freedom-to-operate risk depends primarily on later patents, product-specific claims, manufacturing IP and regulatory exclusivity.
The most relevant commercial technology is the injectable biodegradable polymer depot platform associated with Atrigel-type products.

FAQs About US Patent 5,599,552

Can an expired US 5,599,552 patent block a new injectable implant?

No. An expired patent cannot be enforced to block a new product. Later patents covering specific polymers, drugs, formulations, devices or manufacturing processes may still apply.

Does using NMP in a biodegradable implant infringe US 5,599,552?

Not by itself. NMP is listed in a dependent claim, but infringement would require satisfaction of the applicable polymer, in-situ formation and porous core-and-skin limitations, along with the dependency requirements.

Are PLGA microspheres covered by US 5,599,552?

Not automatically. A conventional preformed PLGA microsphere product may not form the claimed in-situ implant with a porous core surrounded by a porous skin. The product's actual structure and administration process control the analysis.

Does the patent cover injectable tissue fillers?

It can cover certain biodegradable injectable tissue-filling systems if they satisfy the independent claim requirements. Claim 23 specifically addresses filling tissue defects, but the core-and-skin and in-situ formation limitations remain relevant.

Is a biologic delivered from an in-situ implant subject to biosimilar patent risk under this patent?

US 5,599,552 is not a biologic patent and does not independently create a BPCIA patent dispute. A biologic delivery product may face later formulation, manufacturing, device or method-of-use patents.

References

United States Patent and Trademark Office. (n.d.). Patent term calculator and patent term resources. https://www.uspto.gov/patents/laws/patent-term-calculator
United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/
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
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
United States Patent and Trademark Office. (1997). U.S. Patent No. 5,599,552, in-situ forming biodegradable implant compositions and methods. https://patents.google.com/patent/US5599552A/en

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	100308	⤷ Start Trial
Austria	163261	⤷ Start Trial
Austria	212866	⤷ Start Trial
Austria	268611	⤷ Start Trial
Australia	2605492	⤷ Start Trial
Australia	6071890	⤷ Start Trial
Australia	653498	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,599,552