Details for Patent: 7,223,440

Summary for Patent: 7,223,440

Title:	Residual solvent extraction method and microparticles produced thereby
Abstract:	Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.
Inventor(s):	Michael E. Rickey, J. Michael Ramstack, Rajesh Kumar
Assignee:	Alkermes Pharma Ireland Ltd
Application Number:	US11/312,371
Patent Claim Types: see list of patent claims	Use; Formulation;

Patent 7,223,440 Scope & US Patent Landscape for Microparticle Manufacturing Using Halogenated Solvent Removal with 100% Heptane

Executive summary: US Patent 7,223,440 claims a microparticle manufacturing workflow in which biodegradable/bio-compatible polymer + peptide are processed via emulsion/coacervation using a halogenated solvent (notably methylene chloride), followed by solvent extraction with a non-solvent for the polymer that dissolves the halogenated solvent and coacervating agent, then post-extraction rinsing, then a specific non-aqueous wash using 100% heptane to drive residual halogenated solvent below ~0.06 wt% (dependent claims). The patent’s practical enforceability is concentrated on method-of-making steps, not on the microparticles’ end-use, and is most likely to be implicated where competitors reproduce the same solvent system architecture (halogenated solvent phase, solvent extraction medium, then heptane wash) and hit similar residual solvent targets.

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What patents protect microparticles made with peptide-loaded biodegradable polymer using halogenated solvent extraction and heptane washing (US 7,223,440)?

Answer (scope center of gravity): US 7,223,440 protects a method that combines:

1. Emulsion: aqueous peptide solution + biodegradable polymer dissolved in a halogenated solvent
2. Coacervation: add coacervating agent free of solvent for the polymer to form a combined phase
3. Extraction: remove halogenated solvent from the combined phase using an extraction medium that is non-solvent for the polymer and solvent for halogenated solvent + coacervating agent, causing microparticles to precipitate
4. Rinse precipitated microparticles
5. Post-rinse wash in non-aqueous washing system comprising 100% heptane to reduce residual halogenated solvent

Claim-level mapping to enforceable elements

The independent claim (claim 1) is a stepwise process. For infringement, a challenger must show performance of the entire method, including the 100% heptane wash and the residual solvent reduction purpose (and, depending on claim construction, likely the functional result if relied on for “thereby” limitations).

Independent claim structure (claim 1 and close variants)

• Materials
  • Peptide in aqueous phase
  • Biodegradable, biocompatible polymer dissolved in halogenated solvent
    • Dependent specification in claim 6: poly(glycolic acid), poly(d,l-lactic acid), poly(l-lactic acid), copolymers
• Halogenated solvent
  • Dependent claim 2: methylene chloride
• Coacervating agent
  • Dependent claim 4: silicone oil
  • Coacervating agent must be “free from solvents for the polymer”
• Extraction medium
  • Must be a non-solvent for the polymer
  • Must dissolve the halogenated solvent and the coacervating agent
  • Dependent claim 5: ethanol:heptane = 1:9
• Washing system
  • Post-rinse washing step in a non-aqueous washing system comprising 100% heptane
• Residual target
  • Dependent claim 7: residual halogenated solvent in washed microparticles less than ~0.06 wt%
• Optional drying
  • Dependent claim 8

How claim 9 and claim 14 broaden or refine coverage

Claim 9: expands to washing of “rinsed finished microparticles” that already contain polymer matrix with peptide and halogenated solvent, then washing with a non-aqueous washing system comprising 100% heptane, followed by recovery. This is important because it captures modular downstream solvent replacement operations, even if the earlier emulsion/coacervation/extraction steps differ.

Claim 14: reinserts the full earlier workflow (first phase polymer + halogenated solvent; aqueous peptide second phase; mixer) and again ends with the 100% heptane wash.

Claim 13 as product-by-process hook

Claim 13: “Microparticles prepared by the method of claim 1.” In US practice, this can be a limited product-by-process claim. Enforceability typically depends on how the product-by-process language is construed (product identity vs process steps). Practically, it is a litigation leverage point for distinguishing competitor microparticle attributes when process fingerprints map to residual solvent content or matrix structure.

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When does US 7,223,440 lose exclusivity (patent expiration timing for US method claims)?

Answer: No expiration schedule can be calculated from the claim text alone. The patent’s legal life depends on:

• Filing date / priority chain
• Term adjustments (PTA)
• Any terminal disclaimers
• Continuations or related family members

Because you provided only claim language and not bibliographic data, a deterministic exclusivity timeline cannot be produced.

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What is the Orange Book status of US 7,223,440 (is it tied to an FDA-approved drug product)?

Answer: The Orange Book status cannot be determined without identifying:

• the referenced FDA application (NDA/ANDA/BLA)
• the listed active ingredient(s)
• the Orange Book “patent numbers” mapping

Method patents like US 7,223,440 are often listed only when tied to a specific drug product approval, but that linkage cannot be established from claims alone.

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What generic entry risks exist for peptide microparticles using polymer/coacervation/halogenated solvent extraction with heptane washing?

Answer: The entry risk is concentrated on whether generic or contract manufacturers can make peptide-loaded biodegradable polymer microparticles without practicing the claimed method steps, especially:

• whether they use the same solvent architecture (halogenated solvent + extraction medium criteria)
• whether they perform the post-rinse wash using 100% heptane
• whether they achieve a comparable residual halogenated solvent level (the ~0.06 wt% dependent threshold)

Design-around vectors (conceptual, derived from claim elements)

1. Replace the post-rinse heptane wash
   • Use a different non-aqueous wash solvent (or a heptane mixture not “100%”)
2. Change the extraction medium composition
   • The dependent claim nails an ethanol:heptane 1:9 ratio. A different ratio might avoid those dependents, though the independent extraction-medium requirement remains broad (“non-solvent for polymer” + “solvent for halogenated solvent and coacervating agent”).
3. Change the halogenated solvent
   • Claim 2 specifies methylene chloride. Use another halogenated solvent could avoid dependents, but not necessarily the independent “halogenated solvent” limitation.
4. Change the coacervating agent
   • Claim 4 specifies silicone oil; the independent requires only “coacervating agent free from solvents for the polymer.” Substitution could avoid dependents while still practicing the broad independent if the agent meets the functional requirement.

Litigation leverage points likely to be asserted

• Demonstrate direct performance of the full process steps by the accused manufacturer
• Use residual solvent testing to tie operations to claim outcomes where the “thereby” language supports result-oriented limitation arguments
• Use process evidence: batch records, solvent specs, and validated washing/extraction recipes

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How strong is the patent estate for solvent removal in peptide-loaded biodegradable microparticle manufacturing?

Answer: Within US 7,223,440 itself, claim scope is concentrated but not “single-element trivial.” Strength is driven by:

• The independent claim requiring a specific sequence: emulsion → coacervation → extraction → rinsing → heptane wash
• Multiple dependents narrowing to concrete commercial parameters:
  • methylene chloride
  • silicone oil
  • ethanol:heptane extraction medium (1:9)
  • 10–26 °C washing temperature
  • <0.06 wt% residual halogenated solvent
  • specific polymer family

However, enforcement strength against a competitor depends on whether competitors replicate:

• 100% heptane as the wash solvent system
• similar residual solvent targets
• the same halogenated solvent extraction platform

A patent estate-wide strength score (number of family members, continuations, surviving claims, and similar independent coverage) requires the family and citation set, which is not supplied.

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What formulations are protected by US 7,223,440 (microparticle structure vs manufacturing steps)?

Answer: The claims protect manufacturing methods for microparticles, not a fixed dosage formulation in the traditional “capsule/tablet formulation” sense. The protected “formulation” aspects are structural descriptors embedded in the process:

• biodegradable, biocompatible polymer matrix (poly(glycolic acid) and PLA family and copolymers)
• peptide incorporated in the matrix
• residual halogenated solvent reduction after washing

What the claim does not lock down

• particle size distribution
• peptide identity or concentration range
• polymer molecular weight or end group
• explicit process parameters for mixing speed/time except where dependent claims mention static mixer (claim 15) and temperature band (claim 3/11/17)

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Which companies are challenging US 7,223,440 via Paragraph IV or similar mechanisms?

Answer: Not computable from the claim text alone. Company challengers would require:

• Orange Book listing for the relevant drug product
• Patent certification records
• district court filings for the patent number
• ANDA/505(b)(2) connection

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What patent litigation affects US 7,223,440 (case captions, filings, settlements)?

Answer: No litigation docket can be produced from claim text alone. Case status requires:

• the patent number-to-case mapping
• PACER/RECAP docket retrieval
• settlement/consent decree identification

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How does US 7,223,440 compare with other patents on microparticle solvent extraction and residual solvent control?

Answer: A comparative landscape cannot be computed without a prior-art set or patent family search results. What can be stated from the claim language is the differentiator pattern:

Differentiator pattern in US 7,223,440

• uses halogenated solvent in polymer dissolution
• uses coacervating agent free of polymer solvent
• extracts halogenated solvent using a non-solvent extraction medium for polymer
• then performs a specific 100% heptane non-aqueous washing step to lower residual halogenated solvent

This makes the heptane wash and residual target the likely claim-comparison focal points when aligning against competing microparticle manufacturing patents.

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US 7,223,440 claim-by-claim scope (what each claim adds)

Claim	What it adds vs base method	Practical coverage implication
1	Full emulsion/coacervation/extraction/rinse + post-rinse wash in non-aqueous system comprising 100% heptane	Core enforceable method, sequencing required
2	Halogenated solvent = methylene chloride	Narrows to a concrete solvent variant
3	Washing temperature 10–26 °C	Narrows operational envelope
4	Coacervating agent = silicone oil	Narrows coacervating agent identity
5	Extraction medium = ethanol:heptane 1:9	Narrows extraction medium composition
6	Polymer family specified (PGA, PDLLA, PLLA, copolymers)	Narrows polymer selection
7	Residual halogenated solvent < 0.06 wt%	Adds a measurable result threshold
8	Add final drying	Captures drying post-wash
9	Wash step applied to rinsed finished microparticles; then recover washed microparticles; wash uses 100% heptane	Captures downstream modular washing operation
10	Halogenated solvent = methylene chloride	Dependent narrowing
11	Temperature 10–26 °C	Dependent narrowing
12	Residual halogenated solvent <0.06 wt%	Dependent narrowing
13	Microparticles “prepared by” method of claim 1	Product-by-process hook
14	Assembles first phase polymer + halogenated solvent; aqueous peptide second phase; mixer influence; then coacervation/extraction/rinse + heptane wash	Adds mixing step identity and reinstates full flow
15	Mixer = static mixer	Dependent narrowing
16	Halogenated solvent = methylene chloride	Dependent narrowing
17	Temperature 10–26 °C	Dependent narrowing
18	Coacervating agent = silicone oil	Dependent narrowing
19	Extraction medium = ethanol:heptane 1:9	Dependent narrowing
20	Polymer family specified	Dependent narrowing
21	Residual halogenated solvent <0.06 wt%	Dependent narrowing
22	Similar but ends with “washing system comprises heptane” (not expressly “100%”)	Potentially broader than claim 1 on the “100%” literal element, depending on construction
23	Extraction uses “a solvent” (not necessarily halogenated) plus heptane wash	Potential overbreadth in claim text vs dependent scheme; requires construction

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Which jurisdiction matters most for enforcement of US 7,223,440?

Answer: Enforcement is US-centric because the patent is US 7,223,440, but competitive relevance often extends to:

• related family patents in Europe/WO and national phase jurisdictions
• whether those counterparts include the same heptane wash requirement and residual solvent thresholds

A jurisdiction-by-jurisdiction mapping requires the patent family documents, which are not provided.

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Key Takeaways

• US 7,223,440 is a method-of-preparing microparticles patent anchored on halogenated-solvent polymer dissolution, coacervation, non-solvent extraction precipitating microparticles, and a post-rinse wash using a non-aqueous washing system comprising 100% heptane to reduce residual halogenated solvent.
• The most enforceable differentiator is the 100% heptane washing step (independent claim 1 and claim 9), with key dependent claim support via:
  • methylene chloride (claim 2/10/16)
  • silicone oil coacervant (claim 4/18)
  • ethanol:heptane 1:9 extraction medium (claim 5/19)
  • 10–26 °C washing temperature (claim 3/11/17)
  • residual halogenated solvent target <0.06 wt% (claim 7/12/21)
• Competitive entry risk turns on whether manufacturers can avoid performing the heptane wash (and ideally avoid the measured residual solvent target) while still matching solvent extraction chemistry and precipitation behavior.
• A complete landscape on expiries, Orange Book ties, Paragraph IV challenges, and litigation cannot be determined from claim text alone.

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FAQs

1. Is US 7,223,440 limited to methylene chloride or any halogenated solvent?
   Claim 1 covers a halogenated solvent generally; methylene chloride is specified only in dependent claims.

2. Does the heptane wash need to be 100% heptane to fall within the core claim?
   Claim 1 and claim 9 explicitly require a washing system comprising 100% heptane; claim 22 uses “heptane” wording that may broaden coverage depending on claim construction.

3. What measurement most directly supports dependent claim 7 (<0.06 wt% residual solvent)?
   Residual halogenated solvent analysis in the washed microparticles, as specified by the threshold in dependent claim 7.

4. Can a competitor avoid infringement by changing the extraction medium ratio but keeping heptane washing?
   Changing extraction medium could avoid dependent claims (like the 1:9 ratio) but not necessarily the independent if the extraction medium still meets the functional requirements (non-solvent for polymer and solvent for halogenated solvent/coacervant) and the 100% heptane wash is still performed.

5. Do claims 13 (microparticles prepared by method) create a direct product patent?
   It is a product-by-process style hook; enforceability typically focuses on whether the accused product is distinguishable and whether process constraints are treated as limiting under claim construction.

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References

No sources were provided or cited.

Drugs Protected by US Patent 7,223,440

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 7,223,440

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	501711
Canada	2454027
Cyprus	1112348
Germany	60239469