United States Patent 6,773,714: Scope, Claim Construction, Expiration, and Leuprolide Depot Patent Landscape

U.S. Patent No. 6,773,714 covers leuprolide acetate delivered through an in situ-forming biodegradable implant. The core technology combines a lactide, glycolide, or caprolactone polymer with a water-miscible or water-dispersible polar aprotic solvent, producing a depot after injection as the solvent diffuses into surrounding tissue. The claims extend across composition, manufacture, in situ implant formation, therapeutic use, packaging, implant morphology, and selected polymer architectures.

The patent issued on August 10, 2004. Its commercial relevance was closely associated with Eligard, the leuprolide acetate product using the Atrigel delivery platform. The patent term has expired, subject to confirmation from the official USPTO and FDA records for any terminal disclaimer, patent-term adjustment, or regulatory extension. Patent expiration does not eliminate other patent, regulatory, manufacturing, formulation, or trade-secret barriers affecting leuprolide depot competition.

What technology does U.S. Patent 6,773,714 protect?

The patent protects a solvent-exchange implant system in which a polymer solution or dispersion is injected as a flowable composition. After administration, the solvent dissipates into aqueous body fluid and the polymer precipitates or solidifies in situ. Leuprolide acetate is incorporated into the resulting biodegradable matrix.

The principal technical combination is:

Element	Claimed requirement
Active ingredient	Leuprolide acetate
Polymer	Biodegradable thermoplastic polyester
Polymer families	Lactide, glycolide, caprolactone, or combinations
Polymer end-group limitation	Monofunctional alcohol or diol residue; no carboxylic acid terminus
Solvent	Biocompatible polar aprotic solvent
Solvent behavior	Miscible to dispersible in aqueous medium or body fluid
Administration	Injectable, generally subcutaneous
Depot formation	Solvent dissipation creates a solid biodegradable implant
Release mechanism	Diffusion, erosion, or both
Administration intervals	Monthly through approximately six months in dependent claims

The no-carboxylic-acid-terminus limitation is central. It narrows the claims to polymers having particular end-group chemistry, including hydroxyl-terminated polymers produced with monofunctional alcohols or diols. A leuprolide depot using a conventional acid-terminated polyester may fall outside claims that require the claimed end-group structure, although infringement would depend on the actual polymer, claim construction, and applicable doctrine of equivalents.

How broad is independent claim 1?

Claim 1 is the principal composition claim. It requires three components:

A specified biodegradable thermoplastic polymer;
A specified biocompatible polar aprotic solvent; and
Leuprolide acetate.

The polymer limitation is functional and structural. The polymer must be substantially insoluble in aqueous medium or body fluid, yet be dissolved or dispersed in the selected solvent before injection. The solvent must be sufficiently compatible with the body and sufficiently water-miscible or water-dispersible to leave the polymer behind after administration.

The claim does not require a particular dosage strength, release profile, injection volume, polymer-to-solvent ratio, or treatment indication. Those parameters appear in dependent claims or in the specification. As a result, claim 1 potentially reaches a wide range of leuprolide acetate in situ depots if the accused product uses the claimed polymer-end-group and solvent characteristics.

What polymer structures fall within claim 1?

The claim covers:

Lactide homopolymers;
Glycolide homopolymers;
Caprolactone homopolymers;
Lactide-glycolide copolymers;
Lactide-caprolactone copolymers;
Glycolide-caprolactone copolymers; and
Copolymers containing all three monomer families.

The polymer must include a monofunctional alcohol or diol residue and must lack a carboxylic acid terminus. Dependent claims identify hydroxyl-terminated polymers and use of 1,6-hexanediol or polyethylene glycol as chain extenders.

The claims therefore focus on polymer molecular architecture, not merely the presence of PLGA or another biodegradable polyester.

What solvents are covered?

Claim 1 covers polar aprotic solvents classified as:

Amides;
Esters;
Carbonates;
Ketones;
Ethers; and
Sulfonyl compounds.

Dependent claim 8 identifies N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethylformamide, dimethyl sulfoxide, propylene carbonate, caprolactam, and triacetin. Claim 9 narrows to N-methyl-2-pyrrolidone, commonly known as NMP.

NMP is commercially important because it dissolves relevant biodegradable polyesters and diffuses into tissue fluid after injection. A formulation using a different solvent is not automatically outside claim 1 because the independent claim contains broad solvent genus language. It would need to be evaluated against the listed chemical classes and the miscibility or dispersibility requirement.

What do the dependent composition claims add?

Claims 2 through 19 narrow the composition by polymer chemistry, concentration, molecular weight, formulation volume, and administration frequency.

Claims	Limitation
2	Diol chain extender and hydroxyl termini
3	1,6-hexanediol or polyethylene glycol
4	Approximately 50/50 copolymer
5	Approximately 75/25 copolymer
6	Polymer at about 30 to 50 wt.%
7	Polymer molecular weight about 15,000 to 45,000
8	Enumerated solvent list
9	NMP specifically
10	Solvent at about 60 to 70 wt.%
11	Solvent at about 50 to 60 wt.%
12	Leuprolide acetate at about 2 to 4 wt.%
13	Leuprolide acetate at about 4 to 8 wt.%
14	Injectable subcutaneous delivery system
15	Volume about 0.20 to 0.40 mL
16	Volume about 0.30 to 0.50 mL
17	Approximately monthly administration
18	Approximately three-month administration
19	Approximately four- to six-month administration

Claims 10 and 11 overlap at the 60 wt.% boundary. Claims 12 and 13 overlap at the 4 wt.% boundary. Such overlapping ranges are not unusual in issued patent claims and can create multiple infringement theories for a formulation falling at the shared endpoint.

The concentration limitations may be commercially significant because a competitor could alter the polymer, solvent, drug loading, or injection volume while preserving the same general in situ implant mechanism. A formulation outside a dependent range may remain within claim 1.

What manufacturing methods are protected?

Claims 20 and 21 cover making the flowable composition by mixing the polymer, solvent, and leuprolide acetate.

Claim 20 allows mixing in any order. Claim 21 narrows the process to:

Mixing polymer and solvent; and
Mixing the resulting solution or mixture with leuprolide acetate.

The process claims are relevant to manufacturing operations and potentially to inducement or contributory infringement theories. They do not require a particular mixing temperature, vessel, residence time, agitation rate, or sterilization process. Claim 20 requires mixing for a sufficient period to form the flowable composition.

A manufacturer using a different sequence may avoid claim 21 but could still fall within claim 20. Because claim 20 permits any order, changing the order alone is unlikely to provide a complete design-around.

What do claims 22 through 27 protect?

Claims 22 through 27 cover the in situ implant and its formation in a patient.

The claimed sequence is:

Inject the flowable leuprolide composition into the body;
Allow the polar aprotic solvent to dissipate; and
Produce a solid biodegradable implant.

Dependent claims add:

Human administration;
Release of leuprolide as the implant biodegrades;
Tissue adhesion;
Release by diffusion, erosion, or both.

These claims are method and product-by-process-style provisions directed to the clinical operation of the depot. They are particularly relevant to a product using the same solvent-exchange principle but marketed with a different label or dose.

Claim 24 describes release as the implant biodegrades. Claim 27 is broader in mechanism because it includes diffusion, erosion, or a combination. A product that initially releases drug by diffusion and later by polymer erosion may fall within that language if the remaining limitations are met.

What therapeutic uses are claimed?

Claims 28 through 32 cover methods of treatment and hormone suppression.

Claim	Claimed use
28	Treating cancer
29	Treating prostate cancer
30	Human patient
31	Reducing LHRH levels
32	LHRH reduction useful for treating endometriosis

The treatment claims rely on administering the composition of claim 1. They do not independently broaden the formulation requirements. A competing product may face method-of-use issues if its approved labeling includes prostate cancer, endometriosis, or another indication involving suppression of the hypothalamic-pituitary-gonadal axis.

Leuprolide is a gonadotropin-releasing hormone agonist. Its clinical applications include androgen-deprivation therapy for prostate cancer and suppression of ovarian function in certain gynecologic indications. The method claims are therefore linked to the labeled uses of the relevant leuprolide product.

What kit and packaging claims are included?

Claims 33 through 39 cover a two-container kit. The first container includes the polymer and solvent. The second contains leuprolide acetate. The claims contemplate:

Separate storage before administration;
Syringe-based containers;
Lyophilized leuprolide;
Instructions;
Connectable containers; and
Containers directly configured for connection.

These claims target dual-syringe or two-chamber delivery systems. They may matter where polymer solution stability and peptide stability require separate storage. A ready-to-use single-container product could avoid the separate-container limitations but would still require analysis under the composition and method claims.

The kit claims also reflect a practical manufacturing problem: leuprolide acetate and the polymer-solvent system may have different stability requirements. Separating the components until administration can reduce peptide exposure to the solvent and simplify shelf-life control.

What implant morphology is protected?

Claims 40 through 46 cover a solid implant with a microporous matrix consisting of a core surrounded by a skin.

The morphology includes:

A solid or gelatinous matrix;
Core pores from about 1 to 1,000 microns;
Skin pores smaller than core pores;
A skin that is functionally nonporous compared with the core;
Optional residual organic solvent; and
Decreasing solvent content over time.

These limitations describe the physical structure created during solvent exchange. The relatively dense outer skin can act as a diffusion barrier, while the more porous core affects fluid ingress, polymer degradation, and drug release.

The morphology claims may be difficult to assess without microscopy, porosimetry, solvent-content testing, and cross-sectional analysis. A product can have substantially the same gross depot behavior while differing in pore distribution. Conversely, a competitor could inadvertently create a core-and-skin structure even if its formulation differs in nominal composition.

What is the significance of claim 47?

Claim 47 covers a different polymer definition from claims 1 through 46. It requires a biodegradable thermoplastic copolymer of lactide dimer and glycolide dimer that includes a single lactic or glycolic acid residue, together with the same general solvent and leuprolide acetate combination.

This claim appears directed to a distinct polymer architecture or synthesis route. It should be analyzed separately from the hydroxyl-terminated and diol-containing polymer limitations in claim 1. A product may avoid claims 1 through 46 but still require analysis under claim 47 if its polymer has the specified dimer and acid-residue structure.

When did U.S. Patent 6,773,714 expire?

The patent issued on August 10, 2004. The ordinary U.S. patent term is generally 20 years from the earliest effective nonprovisional filing date for applications filed after June 8, 1995, subject to patent-term adjustment, terminal disclaimers, and certain patent-term extensions.[1]

Public patent databases commonly identify the patent as having an expiration date in 2022. The practical conclusion is that the patent is no longer an enforceable barrier as of the current date, assuming no exceptional term adjustment or extension changed the recorded expiration. The official USPTO Patent Center record controls the final term calculation.[2]

Event	Date or status
Patent issued	August 10, 2004
Patent number	U.S. 6,773,714
Core technology	Leuprolide acetate in situ biodegradable depot
Commercial association	Atrigel-based Eligard delivery platform
Reported expiration window	2022
Current status	Expired by ordinary term, subject to official USPTO record

The expiration of this patent does not place leuprolide products in an unrestricted market. Separate patents may cover product-specific formulations, applicators, manufacturing processes, dosing regimens, or improvements.

What was the Orange Book status of the patent?

Eligard is an FDA-approved leuprolide acetate product administered through the Atrigel delivery system. FDA Orange Book records have historically listed patents associated with Eligard, including U.S. Patent 6,773,714.[3]

Orange Book listing creates a statutory patent-notice and abbreviated new drug application framework. A generic applicant referencing a listed drug must address listed patents through one of the certifications under section 505(j) of the Federal Food, Drug, and Cosmetic Act:

Paragraph I: no patent information has been submitted;
Paragraph II: the patent has expired;
Paragraph III: approval is requested after the patent expiration date; or
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

Because U.S. Patent 6,773,714 has reached its ordinary expiration period, a current applicant would generally address the patent as expired rather than mount a live Paragraph IV challenge to this patent. The Orange Book record should be checked for the exact listed patent status and any remaining patents associated with the relevant Eligard strength.

Which companies are associated with the product and patent estate?

The patent was associated with the Atrix in situ implant platform. Eligard was commercialized through the Atrigel platform and is marketed by Tolmar Pharmaceuticals in the United States. The relevant commercial and intellectual-property entities have changed over time through corporate transactions and product rights arrangements.

Entity	Relevance
Atrix Laboratories	Originator of the Atrigel in situ implant platform and associated patent filings
Tolmar Pharmaceuticals	U.S. commercial entity associated with Eligard
Sanofi	Historically associated with commercial rights and distribution of Eligard in certain periods
FDA	NDA approval, labeling, Orange Book, and regulatory exclusivity records
USPTO	Patent prosecution, term, maintenance, and legal-status records

Corporate ownership and marketing rights should not be equated with patent ownership. Assignment records, exclusive licenses, and product commercialization agreements can allocate rights differently.

What Paragraph IV and generic-entry risks exist?

The principal generic-entry risks historically involved whether a follow-on product could reproduce the clinical and commercial performance of Eligard without infringing active patents.

Potential challenge points included:

Use of a different biodegradable polymer;
Use of a different polymer end group;
Use of a different solvent;
Altered polymer molecular weight;
Different drug loading;
Different injection volume;
Different release interval;
A single-container rather than dual-container presentation;
A different pore structure; and
A non-Atrigel delivery mechanism.

A Paragraph IV applicant could have challenged validity, enforceability, or infringement of U.S. Patent 6,773,714 while the patent remained listed and unexpired. Possible validity issues would have included anticipation, obviousness, written description, enablement, indefiniteness, and double-patenting. The breadth of the solvent and polymer genera would have been balanced against the specific no-carboxylic-acid-terminus limitation and the technical evidence required to show possession and enablement across the full scope.

The commercial risk was not limited to this patent. A generic applicant would have needed to map the full Orange Book estate for each Eligard dosage and treatment schedule.

How does this patent compare with conventional leuprolide depots?

The patent differs from conventional preformed implants and microsphere systems because it creates the depot after injection.

Technology	Depot formation	Typical technical issue
U.S. 6,773,714-type system	Polymer precipitates in situ after solvent exchange	Solvent dissipation, depot morphology, injection force
Preformed implant	Solid implant inserted with an applicator	Implantation procedure and device design
Microsphere injection	Drug-loaded particles injected in suspension	Particle size, burst release, syringeability
Aqueous solution	No biodegradable depot	Frequent dosing and rapid clearance
Conventional PLGA microsphere	Solid particles degrade after injection	Manufacturing complexity and release variability

The in situ system reduces the need to manufacture and insert a preformed implant. It also creates risks involving precipitation kinetics, tissue exposure to solvent, depot geometry, burst release, and reproducibility.

What manufacturing and intellectual-property barriers remain after expiration?

Expiration of the patent removes one legal barrier but leaves several technical barriers:

Polymer control

The polymer must meet molecular-weight, end-group, residual-monomer, solvent-content, and degradation specifications. Small changes can affect depot formation and release.

Sterility and stability

A product may require aseptic processing, sterilizing filtration where feasible, validated component sterilization, or terminal sterilization compatible with the peptide and polymer. Separate storage can be necessary because leuprolide may not remain stable in the polymer-solvent phase for the full shelf life.

Injection performance

High-viscosity polymer solutions can create substantial injection-force requirements. Needle gauge, syringe design, temperature, formulation viscosity, and mixing uniformity affect administration.

Release-profile control

Leuprolide products must control initial burst, duration of suppression, late-stage release, and dose reproducibility. The release profile is influenced by polymer composition, molecular weight, end groups, porosity, drug loading, solvent exchange, and depot size.

Regulatory comparability

A generic or follow-on product may need to demonstrate pharmaceutical equivalence and bioequivalence under an FDA-approved pathway. Complex long-acting injectables can require extensive comparative characterization, pharmacokinetic data, pharmacodynamic data, or clinical evidence depending on FDA requirements.[4]

Trade secrets

Manufacturing details such as polymer synthesis, drying, residual-solvent control, mixing order, filling, and syringe connectivity may remain protected as trade secrets even after patent expiration.

How strong is the patent estate today?

The strength of U.S. Patent 6,773,714 as a current exclusionary right is low because the patent term has expired. Its historical claim scope was substantial because it covered the complete product architecture rather than a narrow release-rate parameter.

Dimension	Assessment
Composition breadth	High historically
Polymer limitation	Meaningfully narrowed by end-group requirements
Solvent coverage	Broad genus, with specific NMP claims
Product coverage	Broad across leuprolide in situ depots
Manufacturing coverage	Moderate, particularly for mixing operations
Method-of-use coverage	Focused on cancer and LHRH reduction
Morphology coverage	Technically specific and evidence-intensive
Current enforceability	Expired by ordinary term
Residual commercial significance	Prior-art, freedom-to-operate, and technology-history relevance

The patent remains relevant as prior art in assessing later patent validity and as a technical disclosure for understanding Atrigel-based product design. It should not be treated as a current blocking patent without an official term-status review.

What generic launch scenarios are plausible?

Scenario 1: Direct formulation follow-on

A competitor uses a similar polymer-solvent-leuprolide system with equivalent dosage intervals. The expired patent would not block launch, but later formulation or device patents could.

Scenario 2: Non-Atrigel long-acting injectable

A competitor uses microspheres, a preformed implant, or another depot technology. This may reduce dependence on the expired patent but can increase development and regulatory complexity.

Scenario 3: Reformulated in situ depot

A competitor changes the polymer end group, solvent, drug loading, or container configuration. The principal questions become FDA comparability, manufacturing reproducibility, and any later patent claims.

Scenario 4: Biosimilar pathway

Biosimilar risk is not the main framework for leuprolide acetate. Leuprolide acetate is a chemically defined peptide drug rather than a biologic regulated through the principal biosimilar pathway under section 351(k) of the Public Health Service Act. Follow-on products generally proceed through drug pathways, including ANDA or, where appropriate, another FDA application route.[5]

What is the revenue exposure from this patent?

The patent was commercially relevant to Eligard, a long-acting prostate-cancer treatment. Revenue exposure depends on:

Eligard sales by dosage strength;
Remaining market exclusivity;
Availability of generic or therapeutic alternatives;
Product switching;
Reimbursement;
Physician preference;
Supply reliability; and
The presence of later patents.

The patent itself no longer supports prospective patent exclusivity. Any current revenue protection must come from other patents, regulatory exclusivity, market access, manufacturing advantages, brand loyalty, or clinical and commercial differentiation.

Key Takeaways

U.S. Patent 6,773,714 covers leuprolide acetate in a biodegradable, solvent-exchange implant formed after injection.
Claim 1 requires a biodegradable lactide, glycolide, or caprolactone polymer, a compatible polar aprotic solvent, and leuprolide acetate.
The no-carboxylic-acid-terminus requirement is a central structural limitation.
Dependent claims cover hydroxyl-terminated polymers, diol chain extenders, NMP, polymer and solvent concentrations, injection volumes, and dosing intervals.
Separate claim groups cover manufacturing, in situ implant formation, treatment methods, kits, and core-and-skin microporous implant morphology.
The patent issued in 2004 and is generally reported as expiring in 2022.
It is no longer a current blocking patent by ordinary term, subject to verification in the official USPTO record.
Generic competition remains subject to other patents, FDA requirements, manufacturing controls, device considerations, and release-profile comparability.
Biosimilar analysis is generally inapposite because leuprolide acetate is a chemically defined peptide drug, not a conventional biologic product.

FAQs About U.S. Patent 6,773,714

Is U.S. Patent 6,773,714 still enforceable?

It is generally reported to have expired in 2022. The official USPTO patent-term record controls the final legal status.

Does the patent cover all leuprolide injections?

No. It covers leuprolide acetate combined with specified biodegradable polymers and polar aprotic solvents, particularly in an injectable in situ implant system.

Does using NMP create infringement by itself?

No. NMP is only one required element in the claimed combination. A product must also satisfy the polymer, end-group, aqueous-insolubility, leuprolide, and other applicable limitations.

Does the patent cover Eligard’s monthly and three-month products?

The claims expressly include monthly and approximately three-month administration in dependent claims. Product-specific freedom-to-operate analysis also requires review of later patents and FDA listings.

Can a competitor avoid the patent with a PLGA microsphere?

Historically, a microsphere product could potentially avoid the in situ solvent-exchange limitations, depending on its formulation and manufacturing process. Current analysis must also consider later patents and regulatory requirements.

References

United States Code. (2011). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
United States Patent and Trademark Office. (n.d.). Patent Center and patent term adjustment records for U.S. Patent No. 6,773,714.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book: Eligard.
U.S. Food and Drug Administration. (2023). Product-specific guidance documents for generic drug development.
U.S. Food and Drug Administration. (n.d.). Generic drugs and biosimilar and interchangeable biosimilar products: Regulatory pathways.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	259217	⤷ Start Trial
Austria	296088	⤷ Start Trial
Austria	458469	⤷ Start Trial
Australia	1331200	⤷ Start Trial
Australia	2001292931	⤷ Start Trial
Australia	2006241376	⤷ Start Trial
Australia	2010201645	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,773,714