Details for Patent: 9,592,208

Which drugs does patent 9,592,208 protect, and when does it expire?

Patent 9,592,208 protects GILENYA and is included in one NDA.

Protection for GILENYA has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has fifty-six patent family members in thirty-seven countries.

Summary for Patent: 9,592,208

Title:	Formulations comprising 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol
Abstract:	A solid pharmaceutical composition suitable for oral administration, comprising:
Inventor(s):	Supriya Rane
Assignee:	Novartis AG
Application Number:	US14/009,241
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent 9,592,208: What’s Covered by the Solid Oral MS Composition, Cyclodextrin Stabilizer, and <0.5 mg Unit Dose Claims

U.S. Patent 9,592,208 is directed to an oral solid pharmaceutical composition for treating multiple sclerosis, built around (1) a specific active compound (2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol and salts/phosphate derivative) at low per-unit dose (<0.5 mg), (2) a defined formulation architecture (filler, optional binder and lubricant), and (3) a cyclodextrin-based stabilizer against formation of degradation products, with explicit ranges of cyclodextrin types. Claim 1 is the core independent claim; claim 11 is a method-of-use claim tied to MS outcomes (exacerbations, progression, disability accumulation). The claim scope is therefore split between formulation composition coverage and downstream therapeutic use coverage, with cyclodextrin stabilization and sub-0.5 mg unit dose acting as the key limiting features.

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What does US 9,592,208 claim cover for multiple sclerosis oral solid formulations?

Short answer: It covers an oral unit-dosage solid composition using the specified active (including salt and phosphate derivative) at <0.5 mg per unit, with a cyclodextrin (or derivative) stabilizer to inhibit degradation, plus a filler and optionally binder/lubricant, and it also claims a method of MS treatment using that composition.

Claim 1 (core composition claim) scope and limiting elements

Claim 1 requires all of the following, in combination:

1. Dosage form: “a solid pharmaceutical composition suitable for oral administration” and “in unit dosage form”
2. Active compound definition (exclusive list as written):
   • “a first compound selected from”
     • 2-amino-2-[2-(4-octylpheny)ethy]propane-1,3-diol (spelling in prompt appears truncated; claim 6 clarifies the intended compound), and
     • “a pharmaceutically acceptable salt thereof,” and
     • “a phosphate derivative thereof”
3. Unit dose limit: “each unit comprising less than 0.5 mg of the first compound”
4. Formulation components:
   • a filler, and
   • a stabilizer against the inducement of degradation products
5. Stabilizer definition (major limitation): stabilizer comprises cyclodextrin or derivative of cyclodextrin, where the cyclodextrin/derivative is within a defined set:
   • natural cyclodextrin
   • branched cyclodextrin
   • alkyl-cyclodextrin
   • hydroxyalkyl-cyclodextrin

Practical effect: to infringe claim 1, an accused product must plausibly be (i) an oral solid unit dose, (ii) formulated with the named active (or the permitted salt/phosphate derivative), (iii) dosed at <0.5 mg per unit, and (iv) includes a cyclodextrin (or derivative) used specifically as a stabilizer to reduce degradation products induced by formulation/storage/handling conditions.

Claim 11 (method-of-use) scope and limiting elements

Claim 11 is a classic dependence on claim 1:

• It covers a method of reducing clinical exacerbations, delaying progression of symptoms/disorders associated with MS, or delaying accumulation of physical disability in a patient with MS.
• The method includes administering “a therapeutically effective amount of the solid pharmaceutical composition according to claim 1.”

Practical effect: method infringement requires that the administered product falls within claim 1 (active, unit dose <0.5 mg, cyclodextrin stabilizer, filler etc.), then the therapeutic use is the MS outcome profile.

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How broad is the “cyclodextrin stabilizer” limitation in US 9,592,208?

The cyclodextrin element is the largest scope driver after the active and unit-dose threshold. The claim language and dependent claims narrow the set but keep meaningful flexibility.

What cyclodextrins are explicitly allowed?

Claim 1 states four functional categories (natural, branched, alkyl, hydroxyalkyl). Claim 9 then provides a closed “selected from the group consisting of” list (as written in the prompt), including:

• α-, β-, γ-cyclodextrin
• hydroxypropyl-cyclodextrin (and by category: hydroxyalkyl cyclodextrins)
• sulfobutylether β-cyclodextrin
• multiple multi-alkylated etherified cyclodextrins (dodecakis/tetradecakis/hexadecakis with 2,6-O-methyl; and 2,6-O-ethyl for β)
• partially etherized with 2-hydroxypropyl for α and β
• branched α-cyclodextrin and branched β-cyclodextrin, with a specific branching linkage description (α-1,6 glucoside bond)

Are “cyclodextrin stabilizer” and “used against degradation products” enforceable as functional limitations?

Claim 1 frames stabilizer functionally: “stabilizer against the inducement of degradation products.” Courts typically treat such language as a limitation if it implies structural/functional characteristics of the ingredient selection. Here, claim 1 simultaneously requires cyclodextrin (or derivative) that fits within categories. That combination narrows the ambiguity: the ingredient is cyclodextrin/derivative, and it is used in the formulation as a degradation-product stabilizer.

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What does the <0.5 mg per unit-dose requirement do to infringement risk?

Claim 1 limits each unit dosage form to “less than 0.5 mg of the first compound.” This is a hard numeric boundary.

Infringement implications

• A competitor reformulating to 0.5 mg per unit or higher may attempt to design around the numeric limit.
• If an accused product uses the same active but changes the unit size, the question becomes whether the “per unit” measure is tied to tablet, capsule, sachet, or another discrete unit. The claim is “unit dosage form,” which usually tracks marketed units (e.g., tablet/capsule contents), but the boundary behavior is critical for design-around.

Joint coverage with the dosage architecture

Even if unit dose is below the threshold, the competitor must still satisfy:

• oral solid unit dosage form,
• filler presence,
• cyclodextrin stabilizer,
• active definition (including salt and phosphate derivative),
• optional components (binder, lubricant) are not required unless the competitor is steered into dependent claim features.

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How are filler, binder, and lubricant features treated across the claim set?

Claim 2 (filler)

• “filler comprises a sugar alcohol”
• Claim 7 then specifies “sugar alcohol is mannitol”

Scope progression: Claim 1 only requires a filler broadly; claim 2 narrows to sugar alcohols; claim 7 narrows further to mannitol.

Claim 3 and Claim 8 (binder)

• Claim 3: further comprising a binder
• Claim 8: binder is “hydroxypropyl cellulose”

Scope progression: Claim 1 does not require a binder. If a product omits binder, it may still infringe claim 1 if all required elements are met. If a competitor uses a binder different from hydroxypropyl cellulose, it may avoid claim 8 but still fall within claim 1.

Claim 4 and Claim 10 (lubricant)

• Claim 4: further comprising a lubricant
• Claim 10: lubricant is magnesium stearate

As with binder, lubricant is optional in claim 1 but required for dependent claim 10.

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Which dependent claims further narrow scope beyond claim 1?

Claim 5 (specific stabilizer)

• “stabilizer comprises hydroxypropyl-beta-cyclodextrin”

This is a subset of claim 1/claim 9. A product using a different cyclodextrin derivative could avoid claim 5 while still meeting claim 1 and claim 9.

Claim 6 (specific active identity)

• “first compound is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol or a pharmaceutically acceptable salt thereof”

Claim 1 already includes this compound plus salts and phosphate derivatives; claim 6 narrows by emphasizing a specific identity variant (salt allowed) and is relevant if claim 1’s broader “selected from” language could be read to require inclusion of other forms.

Claim 9 (cyclodextrin derivative list)

• Narrows the permitted cyclodextrin/derivatives to the specifically enumerated group.

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What is covered under the method-of-use claim for MS outcomes (claim 11)?

Claim 11 ties the composition to three MS-related therapeutic endpoints:

1. Reducing frequency of clinical exacerbations
2. Delaying progression of symptoms or disorders
3. Delaying accumulation of physical disability induced by multiple sclerosis

This resembles claim drafting used to support therapeutic intent and is typically asserted in combination with composition/prescription practices. The method-of-use claim remains dependent on the composition claim 1, so the infringement hinge is still product/formulation identity and unit-dose constraints.

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How to map the claim set to a likely infringement “checklist” for generic or competitor products

A product is positioned to fall within claim 1 if it meets each required element:

1. Active: includes 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol (or pharmaceutically acceptable salt, or phosphate derivative)
2. Oral solid unit dosage form: tablet/capsule/similar discrete unit
3. Dose: <0.5 mg of active per unit
4. Filler present: at least one filler
5. Stabilizer: includes cyclodextrin or cyclodextrin derivative fitting the allowed categories
6. Functional role: used to stabilize against inducement of degradation products

Dependent-claim “extra blockers” if challengers want to narrow away from specific claim coverage:

• Avoid claim 2/7 by using a filler that is not a sugar alcohol (if sugar alcohol is used now)
• Avoid claim 3/8 by selecting a binder other than hydroxypropyl cellulose (or by omitting binder if feasible)
• Avoid claim 4/10 by avoiding lubricant or choosing non-magnesium stearate lubricant
• Avoid claim 5 by using a different cyclodextrin derivative than hydroxypropyl-beta-cyclodextrin

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What patent landscape dynamics typically surround a composition + stabilizer cyclodextrin claim like this?

Without the patent family record and the assignee/jurisdictional filings, the landscape can only be characterized at the claim-logic level rather than enumerated with other specific US application publications or continuation/divisional members.

Likely hotspots other patents target around this claim

1. Specific cyclodextrin identity (e.g., hydroxypropyl-beta-cyclodextrin vs alternative derivatives)
2. Manufacturing/process steps for blending/granulation/compression to minimize degradation
3. Particle size / polymorph / solid-state form of the active or drug substance-excipient complexes
4. Alternative unit-dose architectures to evade the <0.5 mg boundary
5. Alternative stabilizers beyond cyclodextrins (if the claim’s cyclodextrin limitation is designed around)

Likely generic entry risk pattern

• If the generic product has the same active and matches formulation architecture using cyclodextrin stabilizers and remains under <0.5 mg per unit, it faces direct claim 1 exposure.
• If it uses a non-cyclodextrin stabilizer, it may avoid the cyclodextrin limitation.
• If it changes unit-dose to reach or exceed 0.5 mg per unit, it may avoid the numeric boundary.
• If it matches composition but only uses a permitted cyclodextrin derivative outside the enumerated list in claim 9, a narrower design-around may exist unless claim 1’s broader “cyclodextrin or derivative” categories still capture it.

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How strong is the patent estate for this technology, based on claim structure alone?

Strength indicators in this claim set:

• Clear, explicit limitation on the active identity class (including salt and phosphate derivative).
• Clear numeric limitation (<0.5 mg) that can be used both offensively and defensively.
• Clear excipient functional limitation (cyclodextrin stabilizer) with an enumerated permitted list in claim 9.
• Composition claim plus method-of-use claim provides two litigation theories.
• Dependent claims create a structured ladder for partial design-around (a challenger may avoid claim 5/7/8/10 while still meeting claim 1).

Vulnerability indicators in this claim set:

• Claim 1’s cyclodextrin stabilizer has a functional component (“against inducement of degradation products”) that can be contested on product functionality, depending on evidence.
• Numeric boundary (<0.5 mg) can be attacked if measurement/“unit” definition is unclear in practice.
• If competitors use alternative stabilizers and do not include cyclodextrin, they can potentially avoid claim 1 entirely.

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What generic entry risks exist for products that match the active but change excipients or dose?

Scenario A: Same active, same unit dose, cyclodextrin stabilizer retained

High risk: claim 1 is likely implicated if all elements are met.

Scenario B: Same active, cyclodextrin removed or replaced with non-cyclodextrin stabilizer

Lower risk: claim 1 requires cyclodextrin or derivative as stabilizer.

Scenario C: Same active and cyclodextrin, but unit dose raised to ≥0.5 mg

Potentially lower risk: claim 1 is limited to “less than 0.5 mg.”

Scenario D: Same active and unit dose, cyclodextrin present but not within the claim 9 enumerated list

Mixed risk: depends on whether claim 1’s broader category language still captures it, but claim 9 suggests a limited universe for specific cyclodextrin derivatives.

Scenario E: Same active and dose, cyclodextrin present, filler/binder/lubricant different

Risk remains for claim 1 unless those changes also disrupt required elements (filler exists in claim 1; binder/lubricant are optional in claim 1).

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Key Takeaways

• U.S. Patent 9,592,208 is a formulation-focused IP right combining a specific MS-active ingredient class with a cyclodextrin-based stabilizer and a hard unit-dose limit (<0.5 mg per unit).
• Claim 1 requires the full set of composition elements. Dependent claims add narrower excipient identity requirements (mannitol, hydroxypropyl cellulose, magnesium stearate) and specific cyclodextrin (hydroxypropyl-beta-cyclodextrin).
• Claim 11 adds a therapeutic-use layer tied to MS clinical outcomes, but remains dependent on the claim 1 composition being administered.
• For competitor or generic design-around, the most direct levers are: (i) remove cyclodextrin stabilizer, (ii) change unit-dose above the <0.5 mg boundary, or (iii) materially alter solid-state/formulation architecture so that at least one claim 1 element is not met.

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FAQs

1. Does US 9,592,208 cover tablets and capsules or only one specific oral dosage form?
The claim covers “solid pharmaceutical composition suitable for oral administration” and “unit dosage form,” which typically encompasses conventional oral solids such as tablets and capsules, provided the formulation is in discrete units and meets the <0.5 mg per unit requirement.

2. Can a product infringe claim 1 if it uses a cyclodextrin derivative different from hydroxypropyl-beta-cyclodextrin?
Yes. Claim 1 requires cyclodextrin or derivative in general categories, and claim 9 enumerates multiple specific cyclodextrin types. Avoiding hydroxypropyl-beta-cyclodextrin alone does not avoid claim 1.

3. Is mannitol required for infringement of claim 1?
No. Mannitol is only specified in dependent claim 7. Claim 1 only requires “a filler,” without restricting it to sugar alcohols.

4. Is the method-of-use claim (claim 11) enforceable even if the composition does not include a binder or lubricant?
Claim 11 depends on claim 1, which does not require binder or lubricant. So omission of binder or lubricant does not, by itself, defeat claim 11 if claim 1 is still met.

5. What is the most direct design-around from a unit-dose perspective?
Changing the formulation so that each unit contains ≥0.5 mg of the active can target the key numeric limitation in claim 1, assuming “unit dosage form” is met and the claim element is avoided.

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References

1. U.S. Patent 9,592,208.

Drugs Protected by US Patent 9,592,208

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	GILENYA	fingolimod hydrochloride	CAPSULE;ORAL	022527-002	May 11, 2018		RX	Yes	No					Y

Foreign Priority and PCT Information for Patent: 9,592,208

PCT Information
PCT Filed	March 30, 2012	PCT Application Number:	PCT/US2012/031340
PCT Publication Date:	October 04, 2012	PCT Publication Number:	WO2012/135561

International Family Members for US Patent 9,592,208

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	085749
Argentina	124661
Australia	2012236357
Brazil	112013024430