Details for Patent: 12,599,598

Which drugs does patent 12,599,598 protect, and when does it expire?

Patent 12,599,598 protects AUSTEDO XR and is included in one NDA.

Summary for Patent: 12,599,598

Title:	Osmotic dosage forms comprising deutetrabenazine and methods of use thereof
Abstract:	Provided herein are osmotic dosage forms containing deutetrabenazine for use in the treatment of, e.g., hyperkinetic movement disorders. When orally administered to a subject on a once-daily basis, the dosage forms provide a favorable pharmacokinetic profile for the active agent indicating treatment efficacy over an extended period of time.
Inventor(s):	Parag Shah, Mayank Joshi, Soumen Pattanayek, Divyang Patel, Sandeep Pandita
Assignee:	Auspex Pharmaceuticals Inc
Application Number:	US17/835,435
Patent Claim Types: see list of patent claims	Use; Dosage form;

Scope and claim construction for US Patent 12,599,598: deutetrabenazine once-daily osmotic transition methods using microparticle D90/D50/D10 distributions

Executive summary. US 12,599,598 claims a controlled clinical transition method that converts a patient from twice-daily deutetrabenazine (or from daily tetrabenazine) to a once-daily deutetrabenazine osmotic dosage form on the next day while maintaining abnormal involuntary movement control. The method claim is tied to a specific once-daily delivery system: an osmotic tablet core (active layer plus push layer), a surrounding semipermeable membrane with a port, and an external immediate-release coating containing a defined fraction of deutetrabenazine microparticles. The microparticles must meet particle-size cutoffs (D90 15 µm, D50 10 µm, and/or D10 3 µm) and a composition split (about 70% to 80% in the active layer; about 20% to 30% in the immediate-release coating). Dependent claims narrow daily dose ranges and the abnormal involuntary movement indications; claim 5 adds explicit tetrabenazine-to-deutetrabenazine conversion dose mappings.

How broad is US Patent 12,599,598 claim coverage for once-daily deutetrabenazine osmotic transition?

Core claim 1: what must be practiced

Claim 1 is a combination of (i) a treatment timing/transition protocol and (ii) a particular once-daily osmotic tablet architecture and microparticle specification. The claim’s scope is not just “use once daily.” It requires a specific transition event (last twice-daily dose followed by next-day once-daily osmotic dosing) and it requires that the once-daily dosage form used is the defined osmotic system.

Required elements of claim 1 (all are limiting):

1. Patient treatment state: human subject “being treated with” total daily deutetrabenazine dosed twice daily.
2. Transition protocol:
   • administer last dose of deutetrabenazine twice daily;
   • next day, administer once-daily total daily dose using the defined osmotic dosage form.
3. Dosage form must match:
   • Tablet core with active layer and push layer:
     • active layer contains deutetrabenazine microparticles plus an active layer control release agent;
     • push layer contains an osmotic agent plus a push layer control release agent;
     • optional tablet seal coat on outer surface of tablet core.
   • Semipermeable layer surrounding the tablet core.
   • Port through the semipermeable layer into the tablet core.
   • Immediate release coating external to semipermeable layer containing a second amount of deutetrabenazine microparticles.
4. Quantitative microparticle distribution split:
   • 70% to 80% of total deutetrabenazine microparticles in the dosage form in the active layer;
   • 20% to 30% in the immediate release coating.
5. Microparticle size specifications:
   • D90 15 µm, and/or D50 10 µm, and/or D10 3 µm (as written, these are stated as parameter cutoffs).
6. Dosage strength range:
   • total dosage comprises about 6 mg to about 48 mg deutetrabenazine in the form of microparticles.
7. Functional requirement:
   • control of abnormal involuntary movement is maintained during the transition from twice-daily to once-daily osmotic dosing.

Claim 2: dose range narrowing

Claim 2 narrows the total daily dose to specific values within 12–48 mg (including 12 mg, 18 mg, 24 mg, 30 mg, 36 mg, 42 mg, 48 mg). This matters for both infringement (patients at doses not listed may avoid the claim if they are not “from 12 mg to 48 mg” as claimed) and design-around (moving to non-listed dosing could be a route, depending on whether claim 2 is strictly limiting versus claim 1 already covers any 6–48 mg).

Claim 3: indication list narrowing

Claim 3 limits abnormal involuntary movement to specific disorders and presentations: chorea (including Huntington’s), akathisia, dyskinesia, tremor, tic (including Tourette), tardive dyskinesia, Parkinson’s levodopa-induced dyskinesia, and dyskinesia in cerebral palsy.

Claim 4: food condition

Claim 4 limits that once-daily dosage form can be administered with or without food. This is typical to avoid a food-dependent avoidance strategy.

What does claim 5 add to scope: tetrabenazine-to-deutetrabenazine conversion dose mapping and the same osmotic system?

Claim 5 is structurally similar to claim 1 but changes:

• the starting regimen: the subject is treated with a daily amount of tetrabenazine (not twice-daily deutetrabenazine);
• the transition: administer last tetrabenazine dose then next day administer once-daily deutetrabenazine osmotic dosage form;
• it includes explicit dose mapping pairs:
  • 25 mg tetrabenazine → 12 mg deutetrabenazine once daily
  • 37.5 mg → 18 mg
  • 50 mg → 24 mg
  • 62.5 mg → 30 mg
  • 75 mg → 36 mg
  • 87.5 mg → 42 mg
  • 100 mg → 48 mg

It also tightens the dosage form requirement by repeating the same osmotic architecture and microparticle distribution and size constraints (including D90/D50/D10 and 70/20 split). Claim 5 thus captures a second clinically relevant transition pathway, with explicit dose equivalence.

Claims 6 and 7 mirror claims 3 and 4 for indication list and “with or without food.”

How should the osmotic dosage form be construed under claim terms (active layer, push layer, port, semipermeable layer, immediate-release coating)?

Likely claim construction pressure points

1. “Immediate release coating external to the semipermeable layer”

   • This means the coating containing the “second amount” of microparticles must be positioned outside the membrane. A formulation with microparticles embedded in a membrane, or separated by a different layer sequence, can become a non-infringement argument depending on physical-layer construction.

2. “Semipermeable layer surrounding the tablet core” plus “port extending through”

   • A deliberate port location is limiting. A dosage form that lacks a formed port or uses a different release mechanism may fall outside.

3. “Active layer control release agent” and “push layer control release agent”

   • The claim does not name the control release agent chemistries. But it is limiting in that each specified layer must contain its respective control release agent. A push layer lacking a “control release agent” could be an avoidance path if supported by evidence.

4. Microparticle distribution split (70–80% / 20–30%)

   • This is a quantitatative requirement across “total amount… present in the dosage form.” Practically, it ties infringement to formulation manufacturing controls and assay results. It also creates a design-around path: if the microparticles in the immediate-release coating fall outside 20–30% (even if the rest is in the active layer), infringement risk drops.

5. Microparticle D90/D50/D10 values

   • The claim states particle parameters in a way that reads like targets or pass/fail specifications. It would be infringement-sensitive to the particle-size distribution of the microparticles actually used.

Dose strength and microparticle size

The claim defines total deutetrabenazine “from about 6 mg to about 48 mg” in the form of microparticles. This interacts with the particle specification: even if the same platform is used at different strengths, the microparticle distribution and layer allocation must still satisfy the specified fraction and size distribution.

What are the enforceable claim metrics for infringement exposure (treatment timing + dosage form + particle distribution)?

Infringement is likely a three-factor test

A generic or competitor would need to avoid all limiting components, not just the general indication or dosing frequency.

1. Treatment transition timing

   • “last dose… twice daily” then “next day” once daily.
   • A different transition pattern (tapering, same-day switch, extended washout) could reduce risk, but it would depend on how strictly “next day” is interpreted and whether clinical practice still “transitions” in a way that matches the claim language.

2. Dosage form platform

   • Osmotic tablet with active/push layers, semipermeable membrane, port, and external immediate-release coating with microparticles.
   • A different delivery technology (e.g., extended release without osmotic core-port architecture) likely avoids the dosage form limitations.

3. Formulation constraints

   • 70–80% microparticles in active layer and 20–30% in immediate-release coating.
   • Microparticle size distribution parameters.

What generic entry risks exist for once-daily deutetrabenazine osmotic transition methods?

Key risk: “method-of-use” coupled to dosage form

Even if a competitor’s label matches a once-daily indication, infringement risk for this patent depends on practicing the specific transition protocol and using a dosage form meeting the osmotic/microparticle constraints.

Practical risk pathways

1. Competitor uses the same osmotic microparticle platform

   • If a firm markets a once-daily deutetrabenazine osmotic tablet with the same layer split and particle size distributions, the dosage form limitations are likely met.

2. Competitor’s clinical dosing schedule matches the claim

   • If the prescribing information or clinical protocols support switching from twice daily to once daily on the next day at the total daily dose, the transition protocol aligns.

3. Dose strengths overlap 12–48 mg

   • Claims 1 and 2 cover 6–48 mg (claim 1 dosage range) and specific total daily dose values 12–48 mg (claim 2).

Design-around angles implied by the claims

• Move immediate-release coating microparticle fraction outside 20–30% (e.g., 15–18% or 31–35%).
• Use microparticles with D90/D50/D10 outside those targets.
• Alter layer sequencing so that microparticles intended for immediate release are not in a coating “external to” the semipermeable layer.
• Avoid port-based semipermeable osmotic extrusion architecture.

What is the Orange Book status of US 12,599,598 and what does that imply for FDA-approval timelines?

No reliable Orange Book listing, expiration date, or listed drug association is included in the provided data. A complete status mapping (Orange Book patent use codes, listed drug, and remaining term) cannot be produced from the record in your prompt alone.

What patent estate likely surrounds US 12,599,598 based on claim features (microparticles + osmotic controlled release + immediate-release overlay)?

A defensible landscape can’t be enumerated without the actual application/patent family details (priority dates, assignees, related filings, prosecution history). The claim language itself suggests a family cluster around:

• deutetrabenazine microparticle preparation and size distribution,
• an osmotic tablet platform with active/push layers, semipermeable membrane, and port,
• layering strategy where a portion of drug is in an immediate-release coating while the rest is in controlled-release layers,
• clinical conversion/titration transitions between tetrabenazine and deutetrabenazine, and between twice-daily and once-daily deutetrabenazine.

But without the patent numbers and jurisdictions, this cannot be turned into a numbered family map, expiration calendar, or FTO-ready “who owns what” chart.

What does the claim language say about prosecution limits and potential prosecution history estoppel?

No prosecution history, claim amendments, or examiner statements are included. Without those facts, the scope cannot be restricted or expanded based on file-wrapper content.

Key Takeaways

• US 12,599,598 is a method-of-transition patent that is inseparable from a specific once-daily osmotic deutetrabenazine tablet design and microparticle distribution/size specifications.
• Claim 1 covers transition from twice-daily deutetrabenazine to once-daily deutetrabenazine on the next day, using a dosage form where 70–80% of microparticles are in an active layer and 20–30% are in an external immediate-release coating, with microparticles meeting stated D90/D50/D10 parameters and an osmotic core with semipermeable layer + port.
• Claim 2 tightens to specific total daily dose values between 12 and 48 mg.
• Claim 3 narrows to a defined abnormal involuntary movement indication list.
• Claim 5 expands coverage to transition from daily tetrabenazine to once-daily deutetrabenazine, with explicit dose mapping pairs and the same osmotic/microparticle formulation constraints.
• For generic or competitor risk, infringement exposure hinges on meeting all limiting elements: transition timing, indication/dosing mapping, and the constrained dosage form architecture plus microparticle size and distribution.

FAQs

1. Does US 12,599,598 cover switching from twice-daily to once-daily over multiple days rather than “the next day”?
   The claim language requires the “next day” administration after the last twice-daily dose, making multi-day transitions non-matching to the stated timing element.

2. Can a competitor avoid infringement by changing only the microparticle split between active layer and immediate-release coating?
   Yes, because claim coverage is quantitatively limited to about 70–80% in the active layer and about 20–30% in the immediate-release coating.

3. Is the patent limited to specific dosing strengths beyond 6–48 mg?
   Claim 1 includes about 6–48 mg in the dosage form, while claim 2 further narrows total daily doses to specified values within 12–48 mg.

4. Does the patent require administration with food?
   No. Claim 4 and claim 7 explicitly permit administration with or without food.

5. Is the tetrabenazine-to-deutetrabenazine transition covered only at the listed dose pairs?
   Claim 5 recites specific pairs (25→12, 37.5→18, 50→24, 62.5→30, 75→36, 87.5→42, 100→48). The covered regimen is tied to those mappings as written.

References (APA)

1. US Patent 12,599,598 (claims as provided in user prompt).

Drugs Protected by US Patent 12,599,598

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Teva	AUSTEDO XR	deutetrabenazine	TABLET, EXTENDED RELEASE;ORAL	216354-001	Feb 17, 2023		RX	Yes	No						A METHOD OF TREATING HUNTINGTON'S CHOREA
Teva	AUSTEDO XR	deutetrabenazine	TABLET, EXTENDED RELEASE;ORAL	216354-001	Feb 17, 2023		RX	Yes	No						TREATMENT OF TARDIVE DYSKINESIA
Teva	AUSTEDO XR	deutetrabenazine	TABLET, EXTENDED RELEASE;ORAL	216354-002	Feb 17, 2023		RX	Yes	No						A METHOD OF TREATING HUNTINGTON'S CHOREA
Teva	AUSTEDO XR	deutetrabenazine	TABLET, EXTENDED RELEASE;ORAL	216354-002	Feb 17, 2023		RX	Yes	No						TREATMENT OF TARDIVE DYSKINESIA