United States Patent 6,395,293: Claim Scope, Expiration, and Patent Landscape for In Situ Formed Implants

US 6,395,293 protects an injectable, in situ-forming implant based on a biodegradable, water-coagulable thermoplastic polymer. Its core concept is a two-part implant structure: an outer polymeric sac and liquid or viscous internal content. The claims cover drug-loaded and drug-free implants, direct tissue administration, solvent-driven solidification, release-rate modifiers, and ester-based organic substances.

The patent is a platform-delivery patent rather than a patent limited to one active pharmaceutical ingredient. Its practical value historically extended to injectable depot products using polymers such as poly(lactide-co-glycolide) and water-miscible or tissue-diffusible organic solvents. The patent term has expired, so US 6,395,293 does not currently block generic, branded, or platform competition in the United States.

What does US Patent 6,395,293 cover?

US 6,395,293 covers an implant precursor or implant formed inside body tissue from a liquid polymer formulation. The formulation contains:

A biocompatible, biodegradable, water-coagulable thermoplastic polymer.
A pharmaceutically acceptable organic solvent capable of diffusing into tissue fluid.
A release-rate modification agent.
In many claims, a biologically active agent.

The claimed implant develops an outer sac or shell while retaining liquid or viscous contents. Over time, the implant may become substantially solid as the solvent diffuses into surrounding tissue and water enters or interacts with the polymer phase.

The patent therefore covers both the composition administered into tissue and the resulting implant structure.

Core technical concept

The invention is directed to a liquid polymer solution that can be injected directly into tissue. After administration, solvent exchange with tissue fluid produces phase separation or coagulation. The polymer forms a surrounding sac, while the internal phase remains liquid or viscous before later solidification.

This differs from a conventional preformed implant because the implant is generated at the administration site. It also differs from a simple microsphere suspension because the claims require a two-part structure involving an outer sac and liquid content.

How are the claims organized?

The claims contain three principal claim groups.

Claim group	Claims	Main subject matter
Implant precursor	1-4, 7-13	Polymer, solvent and release-rate modifier before or during tissue formation
In situ formed implant	5-6, 14-23, 26-28	Drug-loaded implant with an outer sac and liquid or viscous content
Solvent and release-rate limitations	9, 12, 16, 20-25	Solvent identity, ester compounds and solubility parameters

Independent claim 1: implant precursor

Claim 1 requires a mixture of:

A biodegradable, biocompatible, water-coagulable thermoplastic polymer;
A pharmaceutically acceptable organic solvent capable of diffusing into tissue fluid; and
A release-rate modification agent.

The formulation must have an “outer sac and a liquid content.” This structural limitation is significant. A formulation that merely forms a homogeneous solid depot without an outer sac and liquid interior could fall outside the literal scope of claim 1.

Claim 1 does not expressly require a drug. A drug-free formulation can satisfy the claim if the other limitations are met.

Independent claim 5: drug-loaded in situ implant

Claim 5 requires:

A biodegradable, biocompatible, water-coagulable thermoplastic polymer;
A biologically active agent;
A release-rate modification agent; and
A two-part structure consisting of an outer sac and liquid content.

This claim is narrower than claim 1 because it requires a biologically active agent and expressly claims the implant after formation.

Independent claim 14: solvent-containing implant

Claim 14 requires:

The biodegradable polymer;
A biologically active agent;
An organic solvent capable of diffusing into body fluid; and
The outer-sac/liquid-content structure.

Unlike claim 5, claim 14 does not initially require a separate release-rate modification agent. Claims 15 and 16 add that limitation and permit the organic solvent and release-rate modification agent to be the same substance.

Process-oriented claim 11

Claim 11 covers an implant precursor formed by direct administration into body tissue of a liquid polymer solution containing:

The polymer;
The organic solvent; and
The release-rate modification agent.

This claim reaches the administration method and the resulting precursor. It is particularly relevant to injectable depot products administered by syringe or cannula.

What formulation characteristics are protected?

Biodegradable water-coagulable thermoplastic polymer

The polymer limitation requires more than biodegradability. The polymer must also be capable of coagulating or precipitating when exposed to water or tissue fluid.

Potentially relevant polymer classes include aliphatic polyesters, such as:

Polylactide;
Polyglycolide;
Poly(lactide-co-glycolide);
Polycaprolactone; and
Related biodegradable copolymers.

The claim language is functional and compositionally broad. It does not limit the patent to one molecular weight, monomer ratio, end group, crystallinity, or polymer concentration.

Organic solvent

The solvent must be pharmaceutically acceptable and capable of diffusing into tissue fluid. Claim 24 narrows the solvent in specified embodiments to a Hildebrand solubility parameter of about 9 to about 13.

The solvent limitation is central to the in situ formation mechanism. The solvent must dissolve or carry the polymer during injection but must also migrate into the aqueous tissue environment after administration.

Release-rate modification agent

Claim 20 defines the release-rate modification agent broadly as a water-soluble, water-miscible, or water-insoluble organic substance. Claim 21 narrows this to a water-insoluble organic substance, while claim 22 specifies an ester of a mono-, di-, or tricarboxylic acid.

The release-rate modifier can alter:

Solvent exchange;
Polymer precipitation;
Pore formation;
Drug diffusion;
Initial burst release;
Depot persistence; and
The transition from liquid or viscous content to a solid implant.

Claims 9, 12, 16, 23 and 25 permit the organic solvent and release-rate modifier to be the same substance. That feature is commercially important because it can simplify formulation design while retaining control over depot morphology and release kinetics.

What drug classes are covered by claim 3?

Claim 3 contains a broad Markush group of biologically active agents. It covers, among others:

Antibacterial, antifungal and antiviral agents;
Anti-inflammatory and antiparasitic agents;
Antineoplastic and analgesic agents;
Vaccines;
Central nervous system agents;
Growth factors and hormones;
Antihistamines;
Osteoinductive agents;
Cardiovascular and anti-ulcer agents;
Bronchodilators and vasodilators; and
Birth-control and fertility-enhancing agents.

The claim is not limited to a named drug or therapeutic indication. A product analysis therefore turns on whether the active ingredient is incorporated into a formulation meeting the polymer, solvent, release-rate and structural limitations.

How broad are the outer-sac and liquid-content limitations?

The outer-sac requirement is the principal structural boundary in the claims.

A potentially infringing product would need to be shown to form:

An external polymer-rich sac or shell; and
A liquid or viscous internal phase.

Claims 17, 18, 26 and 27 expressly cover watery and viscous liquid contents. Claims 19 and 28 cover embodiments in which the implant has become solid.

The claims therefore cover a time-dependent product:

Formation stage	Relevant claim concept
Before administration	Implant precursor
Immediately after administration	Outer sac with liquid or viscous content
After solvent dissipation	Precursor with reduced or absent organic solvent
Later depot stage	Solidified implant

Claims 7 and 8 are notable because they cover a tissue-surrounded precursor with no organic solvent present or with the solvent dissipated into tissue. Those claims extend beyond the initial liquid polymer solution and reach later stages of depot formation.

What products and technologies could fall within the claim scope?

The patent is relevant to injectable depot systems that use solvent exchange and polymer precipitation. Potentially relevant product categories include:

Product type	Relevance
Injectable biodegradable depots	High, if formed by solvent exchange in tissue
In situ forming microspheres or implants	Potentially high, depending on outer-sac structure
Long-acting hormone depots	Potentially high
Injectable antibiotic depots	Potentially high
Injectable analgesic or anti-inflammatory depots	Potentially high
Preformed PLGA microspheres	Usually requires separate analysis; outer-sac/liquid-content limitations may not be met
Hydrogels	Often outside the claims unless the claimed polymer and sac structure are present
Solid implants inserted surgically	Usually outside the direct-administration limitations, but composition claims may remain relevant
Liposomal injections	Usually outside the claims unless the claimed biodegradable thermoplastic polymer system is used

A product does not necessarily infringe merely because it uses PLGA, a biodegradable polymer, or an injectable depot. The strongest design-around positions would avoid one or more of the following:

A water-coagulable thermoplastic polymer;
A tissue-diffusible organic solvent;
A separate or combined release-rate modification agent;
Direct administration as a liquid polymer solution; or
The claimed outer sac and liquid or viscous content.

When did US 6,395,293 lose exclusivity?

US 6,395,293 issued on May 28, 2002. Its US patent term expired based on the applicable 20-year term measured from the earliest effective nonprovisional filing date in the priority chain. Public patent records identify the patent as expired, and the patent is no longer an enforceable US exclusion right.[1]

Event	Date or status
US patent number	6,395,293
Title	In situ formed implant
Issue date	May 28, 2002
Patent term	Expired
Current blocking effect in the US	None as an enforceable patent right

The expiration conclusion is more important than the historical claim breadth for current market-entry analysis. A formulation that would have presented infringement risk during the patent term is no longer blocked by this patent alone.

What is the Orange Book status of US 6,395,293?

US 6,395,293 is a drug-delivery platform patent, not an active-ingredient composition patent. Its Orange Book relevance depends on whether a sponsor submitted the patent for listing against a specific approved drug product and whether FDA accepted the listing under the applicable patent-listing rules.

The patent number should not be treated as an automatic Orange Book barrier. A current generic applicant would need to evaluate:

Whether the patent was listed for a particular drug product;
Whether the listed patent was timely submitted;
Whether the patent claims the approved formulation, method of use or drug substance;
Whether the listing remains legally operative; and
Whether any FDA exclusivity remains separate from patent protection.

Because the patent has expired, it cannot support a current Paragraph IV exclusion period or block an ANDA on its own. Any historic Orange Book listing would have only historical significance.

Were Paragraph IV challenges or patent litigation associated with this patent?

The patent formed part of the broader Atrix in situ depot technology estate. That estate was commercially associated with products including Atridox and Eligard-related depot technology. Public litigation and regulatory disputes involving those products generally required analysis of multiple patents, product claims and formulation patents rather than US 6,395,293 alone.

Issue	Current assessment
Active US infringement litigation based solely on US 6,395,293	No current enforceable patent basis
Current Paragraph IV risk from this patent	None
Historic Paragraph IV relevance	Possible only in the context of a listed drug product and during the patent term
Settlement leverage today	None from this expired patent alone
Continuing relevance	Prior-art, freedom-to-operate history and technology genealogy

A Paragraph IV certification against an expired patent would not create the same commercial blocking effect as a certification against an unexpired listed patent. Generic entrants must instead assess surviving patents, regulatory exclusivity, trademarks, manufacturing patents and product-specific formulation claims.

How does US 6,395,293 compare with competing patent estates?

US 6,395,293 is a foundational platform patent. Later patents in the same technology area could have narrowed the technology through specific:

Active ingredients;
Polymer compositions;
Drug-loading ranges;
Solvent combinations;
Injection devices;
Release profiles;
Manufacturing processes;
Depot dimensions; or
Treatment methods.

A later patent could remain enforceable after US 6,395,293 expired if it has a later priority date and has not itself expired. The patent landscape must therefore be separated into three layers:

Layer	Scope	Current significance
Platform claims	Injectable polymer/solvent/sac structure	Historical; US 6,395,293 expired
Product-specific claims	Drug, dosage form and release profile	Potentially relevant if unexpired
Manufacturing and device claims	Production, filling, injection and packaging	Potentially relevant if unexpired

The expiration of the platform patent does not establish freedom to operate for a specific commercial product. It removes one patent from the analysis.

What licensing deals and commercial products were connected to the technology?

Atrix Laboratories developed the Atrigel delivery platform. The platform was used in commercial and development programs involving injectable and localized drug delivery. Atridox, a doxycycline periodontal product, is one of the clearest commercial examples of an Atrigel-related product. Leuprolide depot products, including Eligard, also relied on in situ depot technology and associated intellectual property developed through Atrix-related commercial relationships.[2][3]

The commercial arrangements changed over time through licensing, product rights transfers and corporate transactions. Those agreements should be analyzed separately from patent ownership because:

A license may cover expired and unexpired patents differently;
Know-how and manufacturing rights can survive patent expiration;
Product rights may be assigned independently of patent title; and
Regulatory approvals may remain with a different company from the patent owner.

How strong was the patent estate?

Historical strength

The patent was historically strong as a platform claim because it combined broad material classes with a distinctive morphology limitation. It did not depend on one named drug. It could reach multiple therapeutic categories and product programs.

The principal weaknesses were technical proof and claim construction:

Whether the polymer was “water-coagulable”;
Whether the solvent was capable of diffusing into tissue fluid;
Whether a separate release-rate modifier was present;
Whether the product formed an “outer sac”;
Whether the internal phase was liquid or viscous at the relevant time; and
Whether a later product had become a solid implant.

Current strength

Its current enforceability is zero because the patent has expired. Its remaining value is informational:

Prior-art analysis;
Patent-family mapping;
Historical licensing diligence;
Product-development genealogy;
Invalidity research against later patents; and
Identification of formulation design-arounds.

What generic launch scenarios exist?

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

Scenario 1: Same platform, expired patent

A competing injectable depot can use a formulation that appears to fall within US 6,395,293 without facing infringement liability under this patent. The entrant must still clear any later patents covering the drug, formulation, device or manufacturing process.

Scenario 2: Different depot mechanism

A competitor can avoid the historical platform architecture by using:

Preformed microspheres;
A hydrogel;
A lipid depot;
A solid implant;
A different solvent-free system; or
A non-coagulating polymer matrix.

Scenario 3: Same delivery concept with a different product patent estate

A product may use the same broad in situ formation principle but remain protected by later patents directed to a particular API, dose, release period, polymer ratio or indication.

What geographic coverage remains?

US 6,395,293 has no current US exclusivity. Foreign counterparts must be assessed independently because patent expiration dates, terminal disclaimers, supplementary protection certificates and national-phase prosecution may differ.

The relevant geographic review should include:

US national patent and maintenance records;
PCT publication and national-phase entries;
European Patent Office family members;
Canada;
Japan;
Australia; and
Markets where the relevant depot product is sold.

A US expiration does not establish that every foreign family member has expired, although patents with the same priority chain often have broadly comparable term endpoints.

Key Takeaways

US 6,395,293 is an expired platform patent covering in situ formed biodegradable polymer implants.
Its central limitation is a two-part implant with an outer sac and liquid or viscous internal content.
The patent covers drug-free and drug-loaded embodiments.
Claim 3 broadly covers numerous therapeutic categories through a Markush definition of biologically active agents.
Claims 9, 12, 16, 23 and 25 cover embodiments where the solvent and release-rate modifier are the same ester-based organic substance.
Claims 7 and 8 reach later stages in which solvent is absent or has dissipated into tissue.
The patent is historically associated with Atrix’s Atrigel delivery technology and products such as Atridox and Eligard-related depot systems.
The patent is expired and creates no current US Paragraph IV barrier or enforceable infringement risk.
Current freedom-to-operate analysis must focus on later formulation, method-of-use, device, manufacturing and product-specific patents.

FAQs About US Patent 6,395,293

Does US 6,395,293 cover PLGA implants?

Potentially. PLGA may satisfy the biodegradable thermoplastic polymer limitation, but infringement would also require the solvent, release-rate modifier and outer-sac/liquid-content limitations.

Does the patent cover Eligard?

It may have been part of the historical technology estate relevant to Eligard-related depot systems, but the patent itself is expired. Product-specific and later patents require separate analysis.

Can a generic company rely on the expiration of US 6,395,293?

Yes, as to this patent. Expiration does not clear later patents, FDA exclusivity, trademarks, manufacturing rights or confidential know-how.

Is US 6,395,293 an API patent?

No. It is a drug-delivery and implant-platform patent. Its claims are directed primarily to polymeric implant composition, structure and formation.

What is the principal design-around limitation?

The most important design-around issue is avoiding the claimed outer-sac and liquid-content structure, although changing the polymer, solvent, release-rate modifier or administration method can also remove a product from the literal claim scope.

References

United States Patent and Trademark Office. (2002). U.S. Patent No. 6,395,293, In situ formed implant.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs and product labeling for Atridox and Eligard.
Atrix Laboratories, Inc. (2004). Annual report and corporate disclosures describing the Atrigel delivery system and related commercial programs.
World Intellectual Property Organization. (n.d.). PATENTSCOPE: International patent family records for in situ formed implant technology.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	100308	⤷ Start Trial
Austria	163261	⤷ Start Trial
Austria	212866	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,395,293