Details for Patent: 8,030,313

Summary for Patent: 8,030,313

Title:	Controlled release sterile injectable aripiprazole formulation and method
Abstract:	A controlled release sterile freeze-dried aripiprazole formulation is provided which is formed of aripiprazole of a desired mean particle size and a vehicle therefor, which upon constitution with water and intramuscular injection releases aripiprazole over a period of at least about one week and up to about eight weeks. A method for preparing the controlled release freeze-dried aripiprazole formulation, and a method for treating schizophrenia employing the above formulation are also provided.
Inventor(s):	Janusz W. Kostanski, Takakuni Matsuda, Manoj Nerurkar, Vijay H. Naringrekar
Assignee:	Otsuka Pharmaceutical Co Ltd
Application Number:	US11/979,149
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,030,313
Patent Claim Types: see list of patent claims	Use; Formulation;

Scope and claims breakdown for US Patent 8,030,313 (aripiprazole freeze-dried controlled-release injectable) plus US patent landscape, exclusivity and generic-entry risk

US Patent 8,030,313 claims a specific dosing-and-manufacture package for treating schizophrenia with a sterile injectable aripiprazole controlled-release product made from reconstituting a freeze-dried “cake” into a homogeneous suspension. The claim set is dominated by: (i) particle-size-constrained aripiprazole (about 1–10 µm and narrower dependent ranges), (ii) formulation excipients (suspending agent plus bulking and buffering system in narrower dependent claims), (iii) defined freeze-dried “cake” form, and (iv) injection-release duration thresholds (at least about 2 weeks, 3 weeks, or 1 week depending on claim lineage), plus dose-concentration and dosing-frequency limits.

---

What does US Patent 8,030,313 claim for treating schizophrenia with freeze-dried controlled-release aripiprazole?

Core independent claim scope (Claim 1)

Claim 1 anchors the patent’s breadth. It covers a method of treating schizophrenia by administering a sterile injectable formulation obtained by reconstituting a homogeneous suspension from a sterile freeze-dried controlled release aripiprazole formulation that is characterized by all of the following limitations:

1. Therapeutic use

   • Administer to a subject in need of treatment for schizophrenia.

2. Reconstitution from a freeze-dried “cake”

   • The freeze-dried controlled release formulation is in the form of a cake obtained by freeze-drying a homogeneous aqueous suspension.
   • Upon reconstitution (adding water), the result is:
     • a sterile injectable formulation
     • that is a homogeneous suspension.

3. Active particle size

   • Aripiprazole has mean particle size about 1 to 10 microns.

4. Excipient architecture

   • Includes one or more suspending agents (at the independent level claim 1 does not lock the identity).

5. Dose concentration

   • The reconstituted sterile injectable contains about 0.1 to about 600 mg of aripiprazole per mL.

6. Release duration

   • After injection, releases aripiprazole over at least about two weeks from administration.

Practical read-through: claim 1 is a “process-formulation-function” method. It is not just “aripiprazole depot”; it is specifically freeze-dried cake → reconstituted homogeneous suspension → injected controlled release with ≥2 weeks. Any design-around needs to break at least one of: freeze-dried cake/reconstitution, mean particle size range, suspending-agent inclusion, concentration band, or ≥2-week release performance.

Independent claim scope variation (Claim 7)

Claim 7 is another method-of-treatment independent claim with a lower release threshold:

• Same freeze-dried cake and reconstitution into a homogeneous suspension.
• Same aripiprazole particle size about 1–10 µm.
• Same general suspension architecture.
• Release is at least about one week (instead of ≥2 weeks).

Net effect: the estate captures at least two release-duration bands (≥2 weeks and ≥1 week) through separate independent claim scaffolding. This matters for potential generic challenges: a challenger that argues a product releases under one band may still land in the other.

Dependent claims: administration route

• Claim 2/4/6/8: intramuscularly or subcutaneously.

Claim 1’s functional language plus route means infringement theory can be built around the product label and clinical use: if the generic or reference product is only IM for a particular regimen, it is still potentially within the “or subcutaneously” wording if any authorized regimen includes SC.

Dependent claims: excipient tightening to specific systems

• Claim 3/4/5/6: adds that freeze-dried formulation further comprises (c) one or more bulking agents and (d) one or more buffering agents.
• Claim 5 then narrows to a particular example system:
  • aripiprazole mean particle size about 1–10 µm (independent of the narrower crystal claims)
  • suspending agent: carboxymethyl cellulose or sodium salt
  • bulking agent: mannitol
  • buffer: sodium phosphate to adjust pH to about 7 (optionally sodium hydroxide also to adjust pH to about 7)
  • and it raises release threshold to at least about three weeks.

Claim 5 is a high-value narrowing dependent claim: it ties to a specific excipient identity and a longer release performance outcome (≥3 weeks). The claim strength depends on whether accused products match those identities and hit the ≥3-week profile.

Dependent claims: narrower particle size windows

• Claim 13: mean particle size about 2–4 µm
• Claim 14: mean particle size about 2.5 µm
• Claim 15–20: aripiprazole polymorph form:
  • anhydrous crystals or monohydrate
  • specifically “Aripiprazole Anhydride Crystals B” or “Aripiprazole Hydrate A”
• Claims 26–27: particle size distribution parameters for mean ~2.5 µm:
  • 95% < 20 µm
  • 90% < 15 µm
  • 50% < 10 µm
  • 10% < 2 µm

Landscape implication: if a competitor uses different aripiprazole particle engineering, polymorph, or PSD targets, it may avoid multiple dependent claims while still risking claim 1/7 if mean particle size remains within 1–10 µm.

Dependent claims: concentration and monthly regimen

• Claim 9–12: sterile injectable comprises 100 to 400 mg aripiprazole/mL and administered one to two times monthly.
• Claims 28–35: several recitations of mg per 2 mL or mg per mL bands (50–400 mg per 2 mL; 100–200 mg per mL; also correlated to claim 3/5/7 dependent scaffolds).

Key infringement hook: these claims align closely with real-world depot scheduling (monthly). If a product is approved on that schedule, the dose regimen typically becomes evidence for infringement in method claims.

Dependent claims: quantitative formulation % w/v ranges

• Claim 21: constrained multi-component ranges by wt/vol:
  • aripiprazole mean particle size 1–40% (but text says 1 to 40% in the claim)
  • suspending agent 0.2–10%
  • bulking agent 1–10%
  • buffering agent 0.02–2% to adjust pH 6–7.5
• Claim 22: identifies specific example categories:
  • suspending agent selected from CMC or sodium salt, HPMC / related grades, or PVP
  • bulking agent selected from mannitol/sucrose/maltose/lactose/xylitol/sorbitol
  • buffering agent selected from sodium phosphate, potassium phosphate, and TRIS buffer
• Claims 23: example “Formulations A, B, C” with specific mg values at 1 mL, including:
  • 100 mg / 200 mg / 400 mg aripiprazole per unit (as represented)
  • 9 mg CMC
  • 45 mg mannitol
  • 0.8 mg sodium phosphate
  • NaOH as needed
  • water qs to 1 mL
• Claims 24–25: narrower % ranges (including a dependent set where aripiprazole PSD targets are tied to 2.5 µm mean).

Design-around implication: claim 1 is broad enough that an alternative suspension may still infringe if particle size and release duration are within the limits. But for validity attacks or claim mapping, claim 21/24/25 and Formulation A/B/C are strong for narrowing the exact formulation envelope.

---

How far does the “freeze-dried controlled release” language extend across formulation and manufacturing methods?

The “cake” and reconstitution limitations

A key claim element is that the freeze-dried formulation is:

• cake obtained by freeze-drying a homogeneous aqueous suspension and
• reconstituted by adding water to yield a homogeneous suspension.

This is a relatively specific manufacturing/form-factor constraint. A product that is freeze-dried but reconstitutes into a non-homogeneous suspension, or that uses a different reconstitution medium/approach (e.g., non-aqueous diluents) can argue non-infringement against claim 1/7.

Release performance thresholds are outcome-linked

The claims require:

• ≥1 week (claim 7),
• ≥2 weeks (claim 1),
• ≥3 weeks (claim 5 dependent chain).

Because these are functional performance limits, accused infringers typically litigate through:

• in vivo release profile testing,
• or in vitro release correlation arguments.

Even if formulation identities match, release performance can be a dispute lever.

---

What are the most commercially relevant narrowing claim clusters in US 8,030,313?

Cluster 1: longer release (≥3 weeks) with defined excipients (Claim 5)

• Mean particle size about 1–10 µm
• CMC (or sodium salt) as suspending agent
• Mannitol as bulking agent
• Sodium phosphate to pH about 7 (optional NaOH for pH adjustment)
• Release at least about 3 weeks

This cluster is the most specific combination of:

• excipient identity,
• pH target,
• and release duration.

Cluster 2: particle size engineering to ~2.5 µm (Claims 14 and 26–27)

• Mean about 2.5 µm
• PSD distribution bands
• Optional polymorph specification (Claims 15–20)

This cluster can be used to argue both:

• infringement specificity (if a product matches PSD/polymorph), and
• non-infringement or invalidity (if a generic uses a different particle/polymorph profile).

Cluster 3: formulation composition envelope (Claims 21–25 and 23)

• % w/v ranges for aripiprazole, suspending agent, bulking agent, buffer
• Example compositions in Formulation A/B/C
• pH 6–7.5
• Buffer selection lists

This cluster becomes central if litigation focuses on whether the accused product’s composition matches exactly.

Cluster 4: dose concentration and dosing frequency (Claims 9–12 and 28–35)

• 100–400 mg aripiprazole/mL
• administered 1–2 times monthly
• plus mg/2 mL and mg/mL ranges

In method-of-treatment cases, these regimen constraints often map onto prescribing information and administration instructions.

---

What patent landscape does US 8,030,313 imply for US aripiprazole depot products?

US 8,030,313 is structurally aligned with the typical “depot formulation” patent family strategy:

• broad method claims tied to particle size, reconstitution, and release,
• plus cascading dependent claims specifying excipients, PSD, polymorph, and dosing.

Without a provided family listing or cited references, a complete claim-to-sibling patent mapping cannot be produced here. Still, the internal claim architecture indicates what adjacent protection likely exists:

• earlier or later formulation patents on:
  • aripiprazole PSD targets (mean and distribution),
  • specific polymorphs (anhydride/hydrate forms),
  • excipient systems (CMC/mannitol/phosphate),
  • freeze-drying “cake” and reconstitution into injectable suspensions,
  • in vitro/in vivo release windows, and
  • dose strength-specific embodiments (100/200/400 mg-style examples).

Actionable estate takeaway: if you are assessing generic entry risk, the critical question is whether an ANDA/505(b)(2) or Abbreviated pathway filer can land outside the claim boundaries on at least one “hard” limitation: freeze-dried cake reconstitution into homogeneous suspension, particle-size band, excipient system, polymorph, or the ≥1/2/3-week release performance.

---

Which parts of the claim set are most vulnerable in design-around and patent challenges?

Most difficult to design around

1. Reconstituted homogeneous suspension from freeze-dried cake
2. Particle size mean 1–10 µm (and narrower 2–4 µm and 2.5 µm)
3. Release duration threshold (≥1/2/3 weeks)

These are the “tripwires” that are both measurable and tied to the accused product’s real-world behavior.

Easier to design around

1. Polymorph-specific dependent claims

   • If an accused product uses a different aripiprazole form than “Anhydride Crystals B” or “Hydrate A,” dependent claims 15–20 and related PSD claim combinations may fall away.

2. Excipient identity-dependent claims

   • Claim 5 is narrow on excipient identity. Claim 22 also lists alternatives, but if an accused product uses a buffer/excipient outside the enumerated list and outside the functional “one or more” ranges in claim 3/1, a challenger may attack dependent claim coverage.

3. Specific formulation example embodiments

   • Formulation A/B/C (Claim 23) is a set of mg targets. Competitors can attempt to shift within the broader ranges of claim 21 while still staying within performance requirements.

---

Claim-by-claim infringement mapping framework (what to match first)

For fast freedom-to-operate assessment against 8,030,313:

1. Is it a freeze-dried cake reconstituted with water into a homogeneous suspension?

   • If no, claim 1 and claim 7 are off the table.

2. Does the aripiprazole mean particle size fall in 1–10 µm?

   • If no, claim 1 and claim 7 are off the table.
   • If yes, evaluate whether it further hits the 2–4 µm or 2.5 µm dependent ranges.

3. Does the injection release aripiprazole for ≥1 week? ≥2 weeks? ≥3 weeks?

   • If it fails all thresholds, the functional claims collapse.

4. Is CMC (sodium salt) + mannitol + sodium phosphate (pH ~7) used, and does it hit ≥3 weeks?

   • If yes, claim 5 and dependent clusters become likely targets.

5. Does dosing match the 100–400 mg/mL and 1–2 times monthly claims?

   • If the product uses a different dosing frequency or strength outside the bands, method claims can be harder to apply, though base method claim 1/7 still can be asserted if those specific regimen bands are not required.

---

Key takeaways

• US 8,030,313 is not a generic “aripiprazole depot” patent. It claims a tightly specified depot creation and performance profile: freeze-dried cake → water reconstitution → homogeneous suspension → controlled release over at least 1/2/3 weeks, tied to aripiprazole mean particle size 1–10 µm.
• The most litigable and design-around resistant elements are the freeze-dried cake/reconstitution form, particle size band, and release duration thresholds.
• The most commercially actionable narrowing embodiments are Claim 5’s excipient set (CMC/mannitol/sodium phosphate to pH ~7) with ≥3-week release, and the 2.5 µm PSD/polymorph dependent cluster.
• Competitors attempting entry must typically break at least one of: particle size, reconstitution format, release window, or the defined excipient/pH architecture that feeds the longer-release dependent claims.

---

FAQs

1) Can an injectable aripiprazole depot avoid US 8,030,313 by using different suspending agents?
Claim 1 requires “one or more suspending agents” but does not limit identity at the independent level. Changing suspending agent identity can reduce coverage under narrower dependent claims (e.g., Claim 5 or Claim 22 selections), but it does not automatically avoid Claim 1 unless other limitations (particle size, freeze-dried cake reconstitution, homogeneous suspension, release duration) are also outside the claim.

2) Does US 8,030,313 require a specific aripiprazole polymorph to infringe?
No. Polymorph is only required in dependent claims (Claims 15–20). Independent Claim 1 and independent Claim 7 do not require a specific polymorph, only mean particle size and the freeze-dried cake controlled release behavior.

3) If a generic matches excipients and particle size, can it still avoid infringement by altering release duration?
Yes. The claims include release-duration thresholds (≥1 week, ≥2 weeks, ≥3 weeks). If the accused product’s release does not meet the relevant threshold, the corresponding claim(s) fail on that element.

4) Are intramuscular and subcutaneous administrations both covered?
Yes. Route is covered in dependent claims that specify intramuscularly or subcutaneously.

5) Which claim elements are typically proven with product testing in litigation?
Mean particle size and PSD, homogeneity after reconstitution, freeze-dried cake characteristics, and release over time. Regimen-based claims also rely on dosing instructions and administration schedules.

---

References

No external sources were provided or cited.

Drugs Protected by US Patent 8,030,313

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 8,030,313

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1675573		CA 2014 00026	Denmark
European Patent Office	1675573		C300669	Netherlands
European Patent Office	1675573		92427	Luxembourg
European Patent Office	1675573		PA2014020	Lithuania