Details for Patent: 6,479,065

Summary for Patent: 6,479,065

Title:	Process for the preparation of polymer-based sustained release compositions
Abstract:	The invention relates to a sustained release composition and methods of forming and using said composition for the sustained release of biologically active agent. The sustained release compositions of the invention comprise a biocompatible polymer and a biologically active agent characterized by a porous center and a less porous outer layer wherein the center and outer layer consist of essentially the same materials. The sustained release compositions can be prepared by annealing at least a substantial portion of the exterior surface of a polymer/active agent matrix. The compositions which have been annealed exhibit a decrease in the release of agent over the first 24 hours following administration (i.e., reduced burst) and as a result can show an increase in the duration of sustained release thereby providing increased therapeutic benefits.
Inventor(s):	Warren E. Jaworowicz, James I. Wright
Assignee:	Alkermes Pharma Ireland Ltd , Alkermes Controlled Therapeutics Inc
Application Number:	US09/801,272
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 6,479,065: Scope, claim construction, and US patent landscape for sustained-release microparticles with porous cores and less-porous outer layers

US Drug Patent 6,479,065 covers sustained-release microparticles that embed a biologically active protein in a porous structure: a porous center and a less porous outer layer, with the center and outer layer made from essentially the same materials. Dependent claims narrow the polymer classes to biodegradable or non-biodegradable families, specify PLGA as an example polymer, and include a therapeutic method-of-use administration claim plus a quantitative porosity/weight-thickness limitation for the outer layer.

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What does US 6,479,065 claim protect for sustained-release protein microparticles?

Core inventive concept (independent claim 1)
Claim 1 protects a sustained release composition defined by structural and material constraints:

1. Form factor: microparticles.
2. Constituent polymer: a biocompatible polymer matrix.
3. Active payload: a biologically active protein.
4. Internal architecture:
   • porous center
   • less porous outer layer
5. Material unity: the center and outer layer consist of essentially the same materials.

Practical implication: To practice the claim, the accused product must meet the porous gradient architecture and keep chemistry consistent across the core and shell. Pure “protein-loaded microparticles” without a porous center/less-porous outer-layer gradient falls outside claim 1. Protein-loaded microparticles with a porous shell and dense core also fall outside, because claim language is specific to directionality (porous center, less porous outer layer).

How is “porous” likely construed relative to “less porous”?

Claim 1 does not provide a numerical porosity threshold in the independent claim. Enforceability typically turns on:

• intrinsic evidence (porosity characterization methods in the patent specification)
• expert interpretation of “porous” vs “less porous”
• whether the accused product’s measured structure supports the qualitative gradient

The presence of claim 7, which introduces a 5% to 30% by weight limitation tied to the outer layer, suggests the patent drafters expected measurable structural distinctions.

What does “essentially the same materials” mean for infringement?

“Essentially the same materials” is a material-identity concept. It typically captures minor compositional differences but bars wholly different polymer chemistries in core vs shell. In litigation, this phrase usually drives claim construction around:

• whether the core and shell polymer compositions are substantially the same
• whether additives, molecular weight distributions, or minor comonomer content differences defeat “essentially the same materials”
• whether a formulation that changes polymer type across layers avoids claim 1 by using different polymers for the core and shell

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What are the scope limits of dependent claims 2–5 on biodegradable vs non-biodegradable polymers?

Claim 2: Biodegradable polymer requirement

Claim 2 limits claim 1 to cases where the biocompatible polymer is biodegradable.

This narrows the infringement surface substantially. A polymer that is biocompatible but not biodegradable (for example, certain permanent polymers) would not meet claim 2. If a product is biodegradable, it potentially falls within claim 2, but still must meet claim 1’s porous-center/less-porous-outer-layer architecture and the “same materials” constraint.

Claim 3: Enumerated biodegradable polymer families

Claim 3 lists biodegradable polymer classes, including:

• poly(lactide)s
• poly(glycolide)s
• poly(lactide-co-glycolide)s (also expressed as poly(lactic acid-co-glycolic acid))
• poly(caprolactone)
• polycarbonates
• polyesteramides
• polyanhydrides
• poly(amino acid)s
• poly(ortho ester)s
• polycyanoacrylates
• polyamides
• polyacetals
• poly(ether ester)s
• copolymers of poly(ethylene glycol) and poly(ortho ester)
• poly(dioxanone)s
• poly(alkylene alkylate)s
• biodegradable polyurethanes
• blends and copolymers thereof

This is an explicit genus-list claim. It captures broad biodegradable polymer chemistry but still excludes biodegradable polymers outside the enumerated list unless the claim construction treats the list as exhaustive.

Claim 4: PLGA specific embodiment

Claim 4 further narrows to poly(lactide-co-glycolide).

For freedom-to-operate (FTO), PLGA-based protein microparticles with the required porous gradient and same-material core/shell are the highest-risk configuration because claim 4 is a direct target embodiment.

Claim 5: Non-biodegradable polymer alternative

Claim 5 is a second pathway back to broader coverage: it covers claim 1 where the biocompatible polymer is non-biodegradable.

So the patent does not restrict protection to biodegradable platforms only. The landscape risk includes:

• biodegradable polymer microspheres (risk for claims 2–4)
• non-biodegradable polymer microspheres (risk under claim 5)

Commercial takeaway: protein depot microparticles using either biodegradable or non-biodegradable polymers can still fall into claim 1 if they satisfy the structural porous architecture and “same materials” across core and shell.

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What does claim 6 cover for therapeutic use and what does it imply for “method-of-use” infringement?

Claim 6 protects a method of providing a therapeutically effective level of an active agent for a sustained period by administering a dose of the composition of claim 1.

Key scope features:

• It is a use claim tied to a composition definition (claim 1).
• It targets sustained therapeutic exposure, not just formulation existence.
• It is likely to be infringed by clinical/regimen administration of an accused formulation, even if the accused parties argue the formulation design alone is not infringing.

Implication for litigation: method claims often expand the infringement surface to include downstream parties who administer or cause administration (for example, hospitals, clinics, or sponsors), depending on direct infringement standards and induced/contributory theories.

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What does claim 7 limit about outer layer proportion and how does it affect claim coverage?

Claim 7 limits the microparticles of claim 1 where the porous outer layer comprises:

• about 5% to about 30% by weight of the microparticles

This limitation is important because it introduces a quantifiable outer layer parameter. It also resolves an ambiguity present in claim 1: claim 1 says “less porous outer layer,” while claim 7 describes the “porous outer layer.” That internal tension is typically handled by construction consistent with the specification (for example, outer layer is still porous but has lower porosity than the center).

Infringement impact:

• A product where the outer layer mass fraction is below 5% or above 30% may avoid claim 7 even if it meets the porous gradient concept of claim 1.
• However, claim 7 is dependent; avoiding claim 7 does not avoid claim 1 if the broader structural elements are met. Practically, claim 7 supports narrower infringement arguments and also supports validity arguments depending on prior art disclosures of graded microstructures.

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Claim scope mapping: which product attributes trigger inclusion vs avoidance?

High-risk inclusion criteria (must all be present)

• Microparticles (not implants, not gels)
• Contain a biologically active protein
• Biocompatible polymer matrix
• Porous center
• Less porous outer layer
• Core and shell made from essentially the same materials
• Sustained release behavior (as required by claim 1)
• For dependent claims: biodegradable polymer (claims 2–4) or non-biodegradable polymer (claim 5)
• Outer layer mass fraction between 5% and 30% (claim 7)

Likely avoidance patterns

• Different polymer chemistries or substantial material differences between core and outer layer (defeats “essentially the same materials”)
• Reversed porosity gradient (dense center + porous shell)
• No porous structure (uniform porosity or essentially non-porous particles)
• Outer layer substantially outside 5%–30% by weight (only affects claim 7 directly, not claim 1)

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What US patent estate surround 6,479,065 for similar porous-gradient protein microparticles?

Without external record retrieval in this environment, the only robust, complete, and auditable landscape statement is that US 6,479,065 itself protects a combination of:

• porous-core / less-porous-shell architecture
• same-material core and shell
• sustained release of biologically active proteins
• polymer-class dependent coverage (biodegradable and non-biodegradable)

No other specific US application numbers, assignees, or expiration dates can be reliably listed here without risking fabrication.

Business implication: In portfolio strategy for depot proteins, this patent’s claim architecture typically overlaps with other filings on:

• controlled porosity microparticles
• core-shell microsphere manufacturing
• protein encapsulation stabilization and release kinetics
• biodegradable vs non-biodegradable sustained release depots

Those overlaps are expected in the market, but specific “which patents” and “how many” cannot be supplied without referencing the Orange Book and USPTO patent family data for this specific patent.

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When does US 6,479,065 lose exclusivity and how does term interact with typical depot proteins?

This patent’s term schedule depends on:

• the filing date and whether it is based on pre-URAA timing or has later adjustments
• any patent term adjustment
• any terminal disclaimer

No specific expiration date can be stated from the claim text alone. Without the filing and priority dates and any PTA data, providing an exclusivity loss timeline would be incomplete.

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What would a Paragraph IV or generic entry risk look like for this patent?

If a product is a biologic protein administered as a sustained-release depot, typical “generic” pathways are not always straightforward. For risk modeling against US 6,479,065, the factual inquiry is product-structure and administration, not just label and API identity:

• Formulation risk: whether the generic/competitor version uses microparticles with porous center and less porous outer layer, with “essentially the same materials” in core and shell.
• Porosity characterization risk: whether the competitor can characterize and measure a porosity gradient that avoids “less porous outer layer.”
• Outer layer mass fraction: whether the outer layer is within 5%–30% by weight for claim 7.
• Method claim risk: whether marketed administration regimens deliver sustained therapeutic levels consistent with claim 6.

Without knowing the competitor’s formulation details, the only defensible statement is that risk is structural and usage-driven.

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How strong is the patent estate for 6,479,065 based on claim breadth?

Strength drivers

• The architecture is specific (porous core vs less porous outer layer).
• It is not limited to one protein or one polymer family because claim 1 is broad to “biologically active protein” and claim 5 extends beyond biodegradability.
• It includes a measurable dependent parameter (outer layer mass fraction) that can narrow proof issues in infringement.

Strength vulnerabilities

• “Porous” and “less porous” can become factual disputes requiring technical characterization.
• “Essentially the same materials” creates room for design-arounds using different polymer compositions across layers.
• If prior art discloses core-shell microparticles with graded porosity using same materials and protein payloads, validity arguments may be plausible. The presence of the outer-layer weight fraction suggests an expected differentiation point, but it also signals the possibility that earlier art focused on similar architectures.

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How to use US 6,479,065 in an FTO or licensing decision (decision-grade checklist)

FTO checklist for sustained-release protein depot microparticles

1. Does the product use microparticles (not alternative depot formats)?
2. Is there a porous center and less porous outer layer?
3. Are core and outer layer made from essentially the same materials?
4. Is the polymer biodegradable (claims 2–4) or non-biodegradable (claim 5)?
5. If seeking claim 7 coverage, is outer layer 5%–30% by weight?
6. For method claim exposure, does administration aim to provide sustained therapeutic levels using the accused composition?

Licensing leverage points embedded in the claims

• Structural design features (porous gradient and same-material core/shell) create clearer infringement pathways than broad “sustained release” claims alone.
• Claim 6 creates downstream enforcement leverage in clinical use if an accused product meets claim 1.

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Key Takeaways

• US 6,479,065 protects sustained-release protein-loaded microparticles defined by a porous center and a less porous outer layer made from essentially the same materials.
• Dependent claims split polymer scope into biodegradable (with extensive enumerated polymer families including PLGA) and non-biodegradable alternatives.
• The method claim (claim 6) ties infringement to administering the composition to achieve sustained therapeutic levels.
• The quantitative dependent limitation (claim 7) adds a 5%–30% by weight outer layer constraint that affects narrower infringement proof.
• The patent’s practical strength is structural specificity; its main design-around axes are reversing the porosity gradient or changing core versus shell material composition.

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FAQs

1. Does US 6,479,065 cover any protein, or is it limited to specific biologics?
   Claim 1 covers “a biologically active protein” without naming specific proteins, so protection is protein-class broad.

2. What design change most effectively avoids claim 1 of US 6,479,065?
   Changing the core and outer layer so they are not “essentially the same materials,” or removing the porous-core/less-porous-shell gradient, are the most direct avoidance levers.

3. If a product avoids claim 7’s 5%–30% outer layer by weight, is it still at risk under claim 1?
   Yes. Claim 7 is dependent; avoiding the outer-layer proportion does not avoid claim 1 if the porous architecture and material-identity limitations are met.

4. How does US 6,479,065 treat biodegradable versus non-biodegradable polymers?
   It covers both via claim 2–4 for biodegradable polymers and claim 5 for non-biodegradable polymers.

5. Is US 6,479,065 a formulation-only patent or does it cover how the drug is used?
   It includes a method-of-use claim (claim 6) covering administration to achieve sustained therapeutic levels using the claimed composition.

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References (APA)

1. United States Patent No. 6,479,065.

Drugs Protected by US Patent 6,479,065

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,479,065

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	7812301
World Intellectual Property Organization (WIPO)	0213783