Details for Patent: 8,895,617

Summary for Patent: 8,895,617

Title:	Composition and method for treating neurological disease
Abstract:	Disclosed are compositions comprising amantadine, or a pharmaceutically acceptable salt thereof, and one or more excipients, wherein at least one of the excipients modifies release of amantadine. Methods of administering the same are also provided.
Inventor(s):	Gregory T. Went, Timothy J. Fultz, Seth Porter, Laurence R. Meyerson, Timothy S. Burkoth
Assignee:	Adamas Pharma LLC
Application Number:	US14/451,273
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,895,617
Patent Claim Types: see list of patent claims	Use; Composition; Device;

United States Patent 8,895,617: What Do the Claims Really Cover?

US Drug Patent 8,895,617 is directed to a once-daily oral amantadine (or salt) regimen for Parkinson’s disease that uses an extended-release (ER) form engineered to reduce the early-time rate of change of plasma amantadine concentration versus the same amount in an immediate-release (IR) form. The claims tie ER performance to quantitative pharmacokinetic metrics measured in defined human single-dose PK windows.

At the core, the claims define three control axes:

1. Product exposure quantity and dose range
   • 200 mg to 500 mg per once-daily dose (Claims 1-3, with dependent narrowing in Claim 4)
2. Release form and fraction of ER
   • ER must be used as the primary form, with thresholds: ≥50% (Claim 5), ≥75% (Claim 6), ≥90% (Claim 7)
3. PK “steepness” limit versus immediate release
   • The ER product must deliver mean dC/dT < 40% of the mean dC/dT for the same quantity in IR, with the dC/dT measured over specified time windows:
     • 0 to 4 hours after administration (Claim 1)
     • administration to Tmax of the IR form (Claim 2)
     • 2 to 4 hours after administration for ER and a separate window administration to Tmax for IR (Claim 3)

From a landscape perspective, this claim architecture is designed to be composition-agnostic but formulation- and performance-bound: it does not require a specific ER polymer or device in the independent claims (device appears only in a dependent claim), but it forces ER-specific PK behavior that competitors must match or design around.

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What Is the Independent Claim Scope (Claims 1-3)?

How do Claims 1-3 define the invention?

All three independent claims require the same backbone:

• Method (not a composition claim)
• Oral administration to a human subject with Parkinson’s disease
• Once-daily dosing
• Dose contains:
  • (i) 200 mg to 500 mg of amantadine or a pharmaceutically acceptable salt
  • (ii) at least one excipient
• The amantadine in the dose is an extended release form
• The ER form must meet a PK slope reduction rule:
  • Mean dC/dT < 40% relative to IR for the same quantity in an IR form

Where Claims 1-3 differ is the PK measurement window and the comparison anchor.

Independent claim-by-claim PK measurement framing

Claim	ER dC/dT measurement window	IR comparator dC/dT measurement window	Relationship required
1	0 to 4 hours after administration	Same quantity IR measured for 0 to 4 hours	ER mean dC/dT is <40% of IR mean dC/dT
2	(not explicitly restricted to 0-4; uses “as a function of time” tied to single-dose study)	From administration to Tmax of IR	ER mean dC/dT <40% of IR dC/dT (same quantity)
3	2 to 4 hours after administration	From administration to Tmax of IR	ER dC/dT (2-4h) <40% of IR dC/dT (0 to IR Tmax)

Practical scope implication: the patent is not simply about “extended release.” It is about how quickly the early exposure rises, captured by a quantitative slope metric. Any competing ER amantadine product that produces an early plasma rise too steep (relative to IR) risks infringement.

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What Narrowing Parameters Expand or Constrain Enforceable Coverage?

How do the dependent claims narrow dose and ER fraction?

Claims 4-7 tighten the ER regimen into product-relevant boundaries.

Dependent claim	Limitation type	Claim language constraint
4	Dose	300 to 500 mg
5	ER fraction	At least 50% of drug is in ER form
6	ER fraction	At least 75% in ER form
7	ER fraction	At least 90% in ER form

Scope effect:

• Claims 1-3 already require ER form of the dose, but do not specify ER fraction.
• Dependent claims make it easier to capture variants where the ER proportion is known or controlled (e.g., blended IR/ER or partially ER formulations), by asserting ER dominance thresholds.

How do Claims 8 and 17 create alternative embodiments?

• Claim 8: the once-daily dose may additionally comprise amantadine in immediate release form.
  • This is important for design-around and for enforcement: the patent anticipates ER/IR combination within one daily dose, while still requiring the ER-driven dC/dT reduction.
• Claim 17: the ER regimen is administered at a therapeutically effective dose from onset of therapy.
  • That adds a temporal element that can matter for clinical practice and potential product labeling strategies.

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How Are Therapeutic Uses Framed (Claims 9-13)?

What Parkinson’s disease outcome limitations exist?

• Claim 9: therapeutic effectiveness for treatment of Parkinson’s disease (broad use qualifier).
• Claim 10: patient has dyskinesia.
• Claim 11: method reduces frequency or severity of dyskinesia.
• Claim 12: dyskinesia is levodopa-induced dyskinesia.
• Claim 13: can be combined with levodopa/carbidopa.

Enforcement implications:

• Claims 10-12 anchor to a specific patient phenotype (LDIC). Competitors that position ER amantadine for other indications, or that study PK without LDIC performance endpoints, may still fall within Claims 1-3 if the regimen matches the PK criteria. But LDIC-targeted clinical data can strengthen infringement positions for method claims that include patient selection and therapeutic outcome.

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What PK “Performance Anchors” Matter Most (Claim 14 and the dC/dT standard)?

How does Claim 14 extend the PK boundary beyond slope?

• Claim 14: requires a shift in amantadine Tmax of 2 hours to 16 hours relative to IR, based on a single-dose human PK study.

Scope effect:

• Claim 14 gives an alternate or additional measurable parameter (Tmax shift) that tracks with ER behavior.
• It also creates a clearer attack surface for infringement analyses and for potential non-infringement strategies: it is possible to reduce early slope (dC/dT) while not achieving the required Tmax shift, or vice versa, depending on formulation engineering.

Why is the dC/dT limit a strong constraint?

• The claim uses “mean change in amantadine plasma concentration as a function of time (dC/dT)”.
• It sets a hard threshold: <40% of the comparator IR dC/dT.
• It standardizes the comparison to the same quantity and specifies human single-dose PK windows.

Practical landscape insight: A competitor’s ER product can be outside the claim only if it fails the quantitative threshold in the relevant time window(s), fails the once-daily oral regimen, fails the dose range, or fails the PD population/use framing if those dependent claims are asserted.

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What Formulation/Device Specificity Exists (Claim 15)?

How specific is the extended release mechanism?

• Claim 15: the dose comprises an osmotic device that uses an osmotic driving force to provide ER.

Scope effect:

• Claim 15 is dependent on Claims 1-3, so it is narrower than the independent claims.
• Still, it identifies one formulation architecture explicitly and can matter if competitors use osmotic ER systems.

Key point: independent coverage does not require the osmotic device, so competitors using other ER technologies must still satisfy the PK slope and Tmax-related constraints to avoid infringement of Claims 1-3.

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How Broad Is the Overall Method Territory?

Where the claim boundaries are broad

• Amantadine can be used as a free base or salt.
• The independent claims focus on dose + ER behavior + PK slope limit, not on a specific excipient set or ER mechanism.
• Dependent claims include multiple thresholds (ER fraction, dose range narrowing, PK windows, patient subgroups).

Where the claim boundaries are constrained

• Dose range: 200-500 mg (and 300-500 mg in Claim 4).
• Once-daily regimen requirement.
• Quantitative dC/dT threshold versus IR.
• Human single-dose PK measurement requirement.
• In dependent claims, ER fraction (50/75/90%), LDIC outcomes, osmotic device presence, and Tmax shift.

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Patent Landscape Positioning for US 8,895,617 (US-relevant Freedom-to-Operate Map)

1) Claim-type profile

US 8,895,617 is a method-of-treatment patent with formulation-performance elements (ER PK slope metrics). This is a common structure for blocking follow-on formulations where standard “composition-only” searches miss performance-bound method claims.

Landscape impact:

• Generic and follow-on ER manufacturers must clear both:
  • product-specific PK performance (dC/dT and/or Tmax shifts) and
  • method conditions (once-daily, Parkinson’s patient population, dose range, and use framing in dependent claims).

2) Design-around levers competitors can use (based on the claim language)

Because the patent ties infringement to quantitative ER vs IR PK comparisons, practical design-around options are constrained by measurable endpoints:

• Adjust ER release profile so that ER mean dC/dT is not <40% of IR in the relevant window(s).
• Change the clinical regimen such that it is not “once-daily” or falls outside the 200-500 mg range.
• Use an ER fraction strategy where dependent claims are avoided:
  • if asserting Claim 5/6/7 thresholds, ensure ER fraction is below the asserted threshold (but independent Claims 1-3 still require ER form overall).
• Avoid LDIC-specific claim assertions by targeting different PD populations, though independent claims may still be asserted.

3) Device-based subgroup

If an ER product uses an osmotic device, Claim 15 becomes a likely enforcement hook. If a competing system uses a different ER mechanism (matrix diffusion, multiparticulates, polymer reservoir), Claim 15 is less relevant, but Claims 1-3 still apply if PK performance is within scope.

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What Is the Claim Coverage for Alternative Label Concepts?

If a product uses ER/IR blends

Claim 8 explicitly allows additional immediate release in the once-daily dose while maintaining the ER-driven dC/dT reduction standard.

Landscape impact: “We use a mixed IR/ER dose” is not enough to avoid the patent if the ER portion produces the required reduced dC/dT.

If a product is dosed at onset vs later

Claim 17 adds onset timing. A competitor delaying initiation could attempt to avoid dependent Claim 17, but again independent Claims 1-3 remain available.

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Key Takeaways

1. US 8,895,617 claims a once-daily oral amantadine (200-500 mg) ER regimen for Parkinson’s disease with a hard quantitative PK slope rule: ER mean dC/dT <40% vs IR, measured in specified single-dose human windows (Claims 1-3).
2. Dependent claims narrow enforceable scope through dose (300-500 mg) and ER fraction thresholds (≥50/75/90%), plus method-use constraints tied to dyskinesia and LDIC (Claims 10-13).
3. The patent is performance-bound rather than mechanism-bound: osmotic devices are only explicitly covered in dependent Claim 15, while independent Claims 1-3 do not require an osmotic ER technology.
4. The landscape risk for follow-on ER formulations centers on whether competitors can engineer an ER profile that fails the <40% dC/dT criterion in the relevant time window(s), and whether clinical use and dosing regimen match the claim framing.

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FAQs

1. Does US 8,895,617 require an osmotic device?

No. Osmotic device language appears only in dependent Claim 15. Independent Claims 1-3 only require an ER form that satisfies the dC/dT <40% PK relationship versus IR.

2. What determines infringement risk: dose or PK performance?

Both. The method must satisfy dose range (200-500 mg once daily) and the ER must meet the PK slope threshold (mean dC/dT <40% vs IR) in the claim-defined windows.

3. If a competitor matches dose but not the dC/dT threshold, does it fall outside the claims?

Yes for Claims 1-3, because the dC/dT comparison is a required limitation. The patent’s claim architecture makes PK slope performance a core gate.

4. Can the dose include both ER and IR amantadine?

Yes. Claim 8 allows the once-daily dose to include additional immediate release amantadine, while still requiring the ER-associated dC/dT reduction criteria.

5. Are dyskinesia and levodopa/carbidopa required for every claim?

No. Those are in dependent claims (Claims 10-13). Claims 1-3 cover broader Parkinson’s method use with the PK requirements, with LDIC specificity added only in later dependencies.

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References

[1] United States Patent 8,895,617.

Drugs Protected by US Patent 8,895,617

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 8,895,617

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2588296
European Patent Office	1845968
European Patent Office	2623099
World Intellectual Property Organization (WIPO)	2006058236