Details for Patent: 7,799,345
Summary for Patent: 7,799,345
| Title: | Preparation of injectable suspensions having improved injectability | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | Injectable compositions having improved injectability. The injectable compositions include microparticles suspended in an aqueous injection vehicle having a viscosity of at least 20 cp at 20° C. The increased viscosity of the injection vehicle that constitutes the fluid phase of the suspension significantly reduces in vivo injectability failures. The injectable compositions can be made by mixing dry microparticles with an aqueous injection vehicle to form a suspension, and then mixing the suspension with a viscosity enhancing agent to increase the viscosity of the fluid phase of the suspension to the desired level for improved injectability. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Stephen E. Zale, J. Michael Ramstack, Joyce M. Hotz, M. Gary I. Riley, OluFunmi L. Johnson | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Alkermes Pharma Ireland Ltd | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US11/826,994 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Patent Claim Types: see list of patent claims | Composition; Compound; | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | US Patent 7,799,345: Naltrexone Microparticle Injection Composition, Claim Scope, Expiration, and Patent LandscapeUS Patent 7,799,345 protects a specific injectable suspension of naltrexone-containing biodegradable microparticles. Its commercial relevance is tied to extended-release naltrexone products such as Vivitrol. The core claim requires all of the following: naltrexone microparticles, a defined biodegradable polymer, a four-component injection vehicle, microparticle loading above 30 mg/mL, fluid-phase viscosity above 30 cP and below 600 cP, and injectability through an 18- to 22-gauge needle. The patent does not broadly cover every long-acting naltrexone formulation. Its principal risk is concentrated on formulations that reproduce the claimed suspension architecture, excipient system, particle-size range, polymer composition, and rheological profile. What does US Patent 7,799,345 protect?The independent claim protects a composition for injection containing:
The claim is a formulation claim rather than a method-of-treatment claim. It does not require a particular release period, therapeutic indication, dosing interval, clinical outcome, or manufacturing process. The patent’s commercial focus is a suspension that can deliver a high concentration of biodegradable naltrexone microparticles through a relatively narrow injection needle. The viscosity and injectability limitations distinguish the claim from broader sustained-release microsphere concepts. How should the key claim language be construed?What does “consisting of” limit?Claim 1 states that the injection vehicle “consists of” water, a viscosity-enhancing agent, a wetting agent, and a tonicity-adjusting agent. This closed transitional phrase is significant. A formulation containing an additional vehicle component may fall outside the literal scope of claim 1 if the additional component does not fit one of the four defined categories. The analysis depends on whether the added ingredient is properly characterized as part of an existing category or as an additional material. For example, a formulation with water, sodium carboxymethyl cellulose, polysorbate 20, sodium chloride, and a separate buffer could raise a literal-scope issue. A buffer may not be a viscosity enhancer, wetting agent, or tonicity-adjusting agent. The “consisting of” language therefore creates a design-around opportunity, although the doctrine of equivalents could remain relevant. What does “consisting essentially of” mean for the microparticles?The microparticles must consist essentially of naltrexone and the selected polymeric binder. This permits components that do not materially alter the basic and novel characteristics of the microparticles, but it creates a potential boundary for additional excipients, stabilizers, residual solvents, or other active ingredients. The claim is narrower than a formulation claim using “comprising.” A competing product that embeds naltrexone with a third structural excipient or a second active compound could dispute literal infringement if that material materially changes the claimed microparticle composition. Is naltrexone salt coverage clear?The claim recites “naltrexone” without expressly reciting a salt, hydrate, solvate, ester, or prodrug. The strongest literal position is directed to naltrexone itself. Coverage of a specific salt or chemically modified derivative would depend on the specification, prosecution history, claim construction, and whether the material is treated as naltrexone under applicable pharmaceutical and patent-law principles. A product using naltrexone base in poly(lactide-co-glycolide) is the clearest target. A product using a distinct naltrexone salt or derivative presents a greater construction risk for the patent holder. What polymers are covered by US 7,799,345?Claim 1 includes a closed Markush group of biodegradable polymers:
The dependent claims narrow the preferred commercial embodiment to poly(lactide-co-glycolide), also known as PLGA. Claim 12 further limits the polymer to poly(d,l-lactide-co-glycolide) having a lactide-to-glycolide molar ratio from approximately 85:15 to 50:50. This range covers common PLGA compositions, including 75:25 and 50:50 grades used in controlled-release microspheres.
A polymer outside the Markush group may avoid literal infringement of claim 1, subject to any applicable equivalents analysis. Polymer identity, molecular weight, end-group chemistry, lactide stereochemistry, and copolymer ratio are important technical diligence points. What injection vehicle is protected?Claims 3 through 6 identify the principal excipient system.
Claim 6 is commercially important because it consolidates the likely practical vehicle into a defined four-component system. A product using sodium carboxymethyl cellulose, polysorbate 20, sodium chloride, and water is a direct claim-mapping candidate if it also satisfies the particle, concentration, viscosity, polymer, and needle limitations. A formulation using a different viscosity enhancer, such as hydroxypropyl methylcellulose, may avoid claims 3, 6, and 9, but it could remain within claim 1 if the substitute is a viscosity-enhancing agent and all other requirements are met. What particle sizes are covered?Claims 7, 8, 10, and 11 establish a particle-size hierarchy:
Claims 8 and 11 are narrower but commercially relevant because they combine a controlled particle-size range with the PLGA and vehicle limitations. The claim uses mass median diameter rather than a simple maximum particle size. Testing methodology matters. Laser diffraction, microscopy, and sieve analysis can produce different reported distributions. A freedom-to-operate review should identify the measurement method disclosed in the patent and compare it with the accused product’s validated release specification. How do the concentration and viscosity limitations affect infringement?The concentration window in claim 1 is greater than about 30 mg/mL and up to about 300 mg/mL. A formulation at exactly 30 mg/mL may raise a boundary issue because the claim requires more than about 30 mg/mL. A formulation above 300 mg/mL is outside the literal stated range, although “about” introduces a fact-dependent tolerance. The viscosity window is greater than 30 cP and less than 600 cP at 20°C. A composition at 30 cP or 600 cP may dispute literal infringement, but the measurement conditions must be replicated precisely. Relevant variables include:
The claim refers to the viscosity of the fluid phase of the suspension. That language may require separating or otherwise characterizing the continuous phase rather than relying only on the apparent viscosity of the complete suspension. What is the commercial relationship to Vivitrol?Vivitrol is an extended-release injectable naltrexone product marketed by Alkermes. The FDA-approved product is administered intramuscularly and uses biodegradable microspheres to provide sustained naltrexone exposure. The approved indications include alcohol dependence and prevention of opioid relapse after detoxification, subject to the product labeling and prescribing conditions. [1] The claimed formulation architecture is consistent with the technical requirements of a high-concentration, injectable naltrexone microsphere product. The patent should therefore be analyzed together with the Vivitrol label, FDA approval history, Orange Book records, and other Alkermes patent families rather than in isolation. What is the Orange Book status of US 7,799,345?The Orange Book is the controlling FDA source for patents listed against an approved small-molecule drug product. Patent listing, delisting, expiration, and pediatric exclusivity must be verified against the current FDA Orange Book record for the relevant Vivitrol strength and dosage form. [2] A patent’s presence in the patent family does not by itself establish that it is currently listed in the Orange Book. Conversely, an Orange Book listing does not establish validity or infringement. It identifies the patent information submitted by the NDA holder for the approved product. For diligence purposes, the relevant FDA review should confirm:
The patent number should be checked in the FDA Orange Book patent listing and in USPTO Patent Center because the enforceable term depends on patent-term adjustment, terminal disclaimers, maintenance fees, and any post-grant record. [2, 3] When does US 7,799,345 lose exclusivity?The patent term is generally measured from the applicable nonprovisional filing date or the earliest effective priority date for the claimed subject matter, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory modifications. [3] The grant date, September 2010, is not the expiration date. A 20-year term analysis must be performed from the relevant filing chain. Because the claims may derive from an earlier family filing, the operative date cannot be determined reliably from the patent number alone. The principal exclusivity categories are:
A current legal opinion should use the USPTO Patent Center continuity and term records, not a third-party patent webpage. [3] What Paragraph IV challenges and generic-entry risks exist?A generic applicant seeking approval of an equivalent injectable naltrexone product could submit an ANDA with a Paragraph IV certification alleging that the listed patent is invalid, unenforceable, or not infringed. The product-specific risk depends on whether the proposed formulation reproduces each limitation. The highest-risk generic design would likely include:
A generic could reduce risk by changing one or more high-value limitations:
The needle limitation is unlikely to be a complete design-around by itself if the product remains capable of injection through an 18- to 22-gauge needle. The practical question is whether the claim requires actual labeled use through that range or merely technical capability. Which companies are likely to challenge the Vivitrol patent estate?Potential challengers include generic injectable manufacturers, specialty pharmaceutical companies, and developers of long-acting opioid-use-disorder products. Public challenge activity should be evaluated through FDA Paragraph IV notices, federal district court dockets, ANDA litigation records, and Alkermes’ securities filings. The most relevant litigation venues are typically the District of Delaware and the District of New Jersey, although venue can vary. A litigation search should include:
No conclusion about a Paragraph IV challenge should be drawn solely from a patent-family record. A filed ANDA, notice letter, complaint, settlement, consent judgment, or Orange Book stay record is required. How strong is the patent estate?US 7,799,345 has moderate formulation-specific strength and limited platform breadth. Strengths
Weaknesses
The patent is stronger against a copycat formulation than against a redesigned long-acting naltrexone product. Its practical value depends on whether the approved product and the proposed competing formulation fall within the same narrow intersection of polymer, vehicle, particle size, concentration, viscosity, and injection conditions. What manufacturing and geographic barriers matter?The patent does not claim a manufacturing process. It therefore does not directly prevent manufacture of a non-infringing formulation made by the same or a different process. Manufacturing know-how may still create a separate barrier. Relevant technical variables include:
US patent rights are territorial. A US patent does not independently block manufacture, sale, or use outside the United States. Foreign counterpart patents must be reviewed country by country. Regulatory approval, manufacturing-site qualification, trade secrets, and supply agreements can create separate non-patent barriers. How does this patent compare with method-of-use and platform patents?US 7,799,345 is materially different from a method-of-treatment patent. A method patent generally focuses on administering naltrexone microspheres for alcohol dependence, opioid dependence, relapse prevention, or another indication. A platform patent may cover biodegradable microspheres or sustained-release formulations across multiple active ingredients. This patent instead targets the physical composition and injection performance of a naltrexone suspension. A competing product could avoid this patent but still encounter:
A complete freedom-to-operate opinion therefore requires a family-level review rather than a single-number search. Key Takeaways
FAQsDoes US 7,799,345 cover oral naltrexone?No. The claims require a composition for injection containing naltrexone microparticles suspended in an injection vehicle. Does the patent cover naltrexone implants?Not on the face of the supplied claims. The claims require microparticles suspended in an injection vehicle and injectable through a needle. Can a competitor avoid the patent by using a 16-gauge needle?Not necessarily. The claim requires injectability through an 18- to 22-gauge needle. A formulation that is also injectable through that range may still satisfy the limitation, even if it can be administered through a larger needle. Are all PLGA naltrexone microspheres covered?No. The product must satisfy the remaining limitations, including the vehicle, microparticle concentration, viscosity, and needle-injectability requirements. Dependent claims add particle-size and polymer-ratio limitations. Does expiration of the patent eliminate all Vivitrol generic-entry barriers?No. Other patents, Orange Book listings, regulatory exclusivity, manufacturing patents, device rights, formulation patents, litigation settlements, and trade secrets may continue to affect entry. References
More… ↓ |
Drugs Protected by US Patent 7,799,345
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| >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 7,799,345
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Austria | 363891 | ⤷ Start Trial | |||
| Australia | 2001255463 | ⤷ Start Trial | |||
| Australia | 5546301 | ⤷ Start Trial | |||
| Bulgaria | 107288 | ⤷ Start Trial | |||
| Bulgaria | 66023 | ⤷ Start Trial | |||
| Brazil | 0111060 | ⤷ Start Trial | |||
| Brazil | PI0111060 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
