Details for Patent: 10,105,335

Which drugs does patent 10,105,335 protect, and when does it expire?

Patent 10,105,335 protects BAFIERTAM and is included in one NDA.

This patent has nineteen patent family members in seven countries.

Summary for Patent: 10,105,335

Title:	Fumarate ester dosage forms
Abstract:	Described herein are pharmaceutical compositions comprising fumarate esters, methods for making the same, and methods for treating subjects in need thereof. In particular, oral controlled release pharmaceutical compositions comprising fumarate esters suspended in liquid matrices are described. One embodiment described herein is a pharmaceutical composition comprising fumarate esters suspended in a lipid or lipophilic liquid with enhanced bioavailability.
Inventor(s):	Jason M. Vaughn, Justin R. Hughey, Tanesha Roberts, Tatyana Dyakonov, Sunil Agnihotri, Aqeel A. Fatmi
Assignee:	Banner Life Sciences LLC
Application Number:	US15/730,825
Patent Claim Types: see list of patent claims	Composition; Compound; Dosage form;

Scope & Claims Analysis: US Patent 10,105,335 (Oral immediate-release non-aqueous fumarate ester compositions activating Nrf2)

US 10,105,335 claims an oral, immediate-releasing, single-phase, non-aqueous liquid pharmaceutical composition combining (i) a defined non-aqueous liquid vehicle and (ii) a fumarate ester (or salt) defined by a substituent-variable “R1/R2” structure. Independent claim scope is broad on ester substituent chemistry and narrower on vehicle composition, dose ranges, and capsule/delayed-release features. A core functional claim element links in-vivo activity to activation of an Nrf2-dependent pathway, which can be used to differentiate method-of-use and to narrow invalidity arguments against chemical variations that do not achieve Nrf2 activation.

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What is US Patent 10,105,335 about, and what does claim 1 cover?

Independent claim 1: oral immediate-release non-aqueous single-phase liquid + fumarate ester/salt

Claim 1 requires all of the following:

1. Oral pharmaceutical composition
2. Immediate releasing
3. Single phase non-aqueous liquid vehicle
4. Contains a fumarate ester or salt having a formula with:
   • R1 and R2 independently represent hydrogen or C1–C20 alkyl radicals (linear, branched, or cyclic), where the alkyl may be optionally substituted with halogen, hydroxy, C1–C4 alkoxy, nitro, or cyano.
5. The fumarate is present as an ester or a salt (salt not limited to a specific counterion in the claim excerpt you provided).

Practical read-through for freedom-to-operate (FTO):
Claim 1 is not limited to a single fumarate species. It captures a genus of fumarate esters/salts in an oral immediate-release non-aqueous single-phase liquid format. If a competitor uses a different vehicle class (not “single phase” or not “non-aqueous liquid”), uses an aqueous or biphasic system, or uses delayed/extended release instead of “immediate releasing,” it can fall outside claim 1 even if the same fumarate ester chemistry is used.

Claim 1 “genus” chemistry: how broad is the R1/R2 space?

On your provided claim language:

• R1: H or C1–C20 alkyl (optionally substituted)
• R2: H or C1–C20 alkyl (optionally substituted)

That is a two-position substitution framework that supports:

• mono-alkyl substituted fumarate esters (one of R1/R2 = alkyl; the other = H)
• dialkyl fumarate esters (both = alkyl)
• mixed alkyl/alkyl substitution patterns
• substituted alkyl groups up to C20 with halogen/hydroxy/C1–C4 alkoxy/nitro/cyano substitutions

This is a wide chemical genus for a formulation patent. The main enforcement leverage for claim 1 will likely come from formulation attributes (single-phase, non-aqueous, immediate release, oral).

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What do the dependent claims add, and where is the real narrowing?

Substituent-specific dependents (claims 2–10, 11–13)

These claims narrow R1/R2 combinations:

• Claim 2: R1 is C1–C4 alkyl
• Claim 3: R1 is methyl
• Claim 4: R2 is C1–C4 alkyl
• Claim 5: R2 is methyl
• Claim 6: R2 is hydrogen
• Claim 7: R1 C1–C4 alkyl and R2 C1–C4 alkyl
• Claim 8: R1 methyl and R2 methyl
• Claim 9: R1 C1–C4 alkyl and R2 hydrogen
• Claim 10: R1 methyl and R2 hydrogen

Implication: Even if a generic or competitor avoids the broad genus, the patent also covers common lower-alkyl variants (methyl and C1–C4 alkyl). From an invalidity standpoint, challengers often rely on prior art that discloses only one ester species; these dependents give the patent fallback positions.

Specific fumarate ester embodiments (claims 11–13)

Your excerpt indicates claim 11 and claim 12–13 contain embedded structures, including:

• “Wherein the fumarate ester is:” followed by formulas (not visible in full text you pasted)
• claim 12 includes “wherein R is any C1–20 alkyl, or a salt thereof”
• claim 13 is another structured variant

Implication: These dependents likely anchor to specific ester structures within the broader R1/R2 formula. For litigation, these can be used to argue that the asserted formulation practices not only the genus but also a specific embodiment.

Dose range dependents (claims 14–15)

• Claim 14: composition comprises about 80 mg to about 230 mg of fumarate ester or salt
• Claim 15: two narrower ranges:
  • about 80–115 mg, or
  • about 160–230 mg of fumarate ester or salt

Implication: Dose-range narrowing can be a significant infringement lever. A competitor choosing a different per-unit dose may attempt to avoid infringement of these dependents while still practicing claim 1 (depending on claim construction and whether the product is “about” these ranges and per capsule/tablet configuration).

Vehicle composition dependents (claim 16)

• Claim 16: liquid vehicle comprises mono- and di-glycerides, polyvinylpyrrolidone (PVP), and polyoxyl 40 hydrogenated castor oil

This is a concrete vehicle formulation reciting three specific excipients and a defined vehicle composition.

Implication:
The strongest practical claim narrowing for patent owners typically comes from excipient-level vehicle constraints. For challengers, replacing one excipient (for example, swapping PVP grade, using different solubilizer/emulsifier, or using a different hydrophobe) is a common design-around attempt.

Vehicle-to-actives ratio dependents (claim 17)

• Claim 17:
  • about 30% to 40% by weight fumarate ester (or salt)
  • about 55% to 65% by weight liquid vehicle

Implication: Again, design-around is possible by changing formulation composition while staying within the general “single-phase non-aqueous liquid vehicle” concept. The dependents create additional infringement hooks if the competitor mirrors these ratios.

Lactic acid content (claim 18)

• Claim 18: composition comprises about 5% by weight lactic acid

Implication: Adds another measurable excipient requirement. Competitors may omit or reduce lactic acid to avoid this dependent claim.

Capsule and release-delay dependents (claims 19–20)

• Claim 19: encapsulated in a capsule
• Claim 20: capsule provides delayed release of the fumarate ester/salt

Implication: This is notable because claim 1 is “immediate releasing.” Dependent claim 20 points to a delayed-release embodiment. This can matter in claim construction and in infringement proof: a product engineered for delayed release may fall outside claim 1 but could fall within claim 19/20 only if those claims are interpreted consistently with immediate release in claim 1 (for example, if “immediate releasing” is about the composition itself but “delayed release” is about capsule coating mechanics).

Functional pathway claim (claim 21)

• Claim 21: upon administration, activates a Nrf2-dependent pathway

Implication:
This is a method-of-use style functional limitation embedded in a product claim. It can constrain infringement where chemistry and formulation are similar but the biological activity profile differs. It also provides patent owners a route to argue that an accused formulation’s in-vivo effect satisfies the claim even if chemical substituent variations exist.

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How strong is the patent estate implied by claim structure, and what claim “anchors” matter most?

Anchor 1: formulation architecture (oral, immediate release, single-phase, non-aqueous)

These characteristics are often harder to “accidentally” satisfy. They create a clear boundary around:

• aqueous systems
• biphasic emulsions
• lyophilized or reconstituted forms
• immediate-release vs delayed/extended-release profiles
• multi-phase suspensions

Anchor 2: fumarate ester genus (R1/R2 with C1–C20 alkyl optional substitutions)

This supports broad chemical coverage, which reduces the value of substituent-only workarounds if the competitor keeps the same in-vivo Nrf2 biology and the same formulation architecture.

Anchor 3: vehicle excipient triangle (mono/di-glycerides + PVP + polyoxyl 40 hydrogenated castor oil)

If that excipient set is central to the commercial product’s formulation, it increases litigation leverage because it gives a clear experimental infringement test (composition analysis).

Anchor 4: dose and ratio dependents

These allow staged enforcement:

• primary theory: independent claim 1 (genus)
• fallback theories: dependents 14–18 and 16–17 if the accused product matches formulation specifics

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What prior art themes likely matter against US 10,105,335, based on the claim features?

Even without the specification text, the claim set signals the likely prior art buckets that would be argued in validity challenges:

1. Fumarate ester composition prior art

   • Prior disclosures of fumarate esters (various R1/R2 alkyl patterns)
   • Prior disclosed salts of fumarate esters

2. Nrf2 activation via fumarate esters

   • Pharmacology literature showing fumarate or fumarate-derivatives activate Nrf2 pathways
   • Method-of-use disclosures linking fumarates to oxidative stress response pathways

3. Non-aqueous single-phase immediate-release oral formulations

   • Solubilization systems using glycerides and surfactants/castor oil derivatives
   • Use of PVP and polyoxyl hydrogenated castor oil in liquid oral dosage forms

4. Dose-range and excipient-specific formulations

   • Prior art that matches the same or close dose mg ranges
   • Prior art disclosing lactic acid as a formulation component

From an infringement perspective, competitors can often mitigate risk by altering at least one of:

• immediate vs delayed release design
• vehicle phase behavior (single phase vs emulsion-like)
• vehicle excipient identity
• actives ratio and dosing

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Which commercial products and generic entry risks does this claim set map to?

What “generic” could look like under claim 1

A generic risk profile for claim 1 typically includes any oral immediate-release product that:

• uses a fumarate ester/salt within the R1/R2 genus and
• formulates it in a non-aqueous single-phase liquid vehicle

If an ANDA-type generic tried to submit a product with:

• aqueous suspension or emulsion
• different fumarate core not meeting the R1/R2 formula
• delayed release capsule when claim 1 requires immediate release then it could reduce exposure to the independent claim 1 theory.

What “formulation-only” workarounds could reduce infringement

• Remove lactic acid to avoid claim 18
• Change ratios away from the 30–40% actives / 55–65% vehicle zone of claim 17
• Replace PVP or polyoxyl 40 hydrogenated castor oil to avoid claim 16
• Change the mg amount per unit dose to avoid claim 14/15 dependent infringement
• Shift to delayed release to target ambiguity between claim 1 immediate release and claim 20 delayed release

Biosimilar risk

This patent is a small molecule composition patent, not a biologic. “Biosimilar risk” is not the correct analogue; the relevant risk is chemical generics and formulation generics.

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How does the Nrf2 functional limitation in claim 21 affect infringement and litigation strategy?

Claim 21 creates a biologic-performance test

Because claim 21 recites biological activity “upon administration,” enforcement can rely on:

• pharmacodynamic biomarkers of Nrf2 activation
• evidence that the accused fumarate ester/salt and formulation produces an Nrf2-dependent response

Design-around leverage

A competitor could attempt to keep chemistry and formulation close while altering release kinetics or excipient microenvironment to change bioavailability and downstream Nrf2 activation levels. If a product does not demonstrate Nrf2 pathway dependence at relevant dosing, claim 21 may be harder to prove.

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What patent claims are most likely asserted in practice, and what “claim stacking” matters?

Likely assertion ladder

1. Claim 1 for broad genus and formulation architecture
2. Claim 16 if the commercial vehicle matches the specific glyceride/PVP/polyoxyl-40 hydrogenated castor oil system
3. Claims 14–15 if dose per capsule falls within the specified mg bands
4. Claim 17 and 18 for ratio and lactic acid confirmation
5. Claim 21 as the functional proof component, especially against close chemical substitutes

Why dependents matter

Dependent claims let patent owners:

• plead multiple theories without needing the full breadth of claim 1 to be met in every element
• attack generic challenges incrementally (vehicle composition first, then dose/ratio, then biological activity)

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Key Takeaways

• US 10,105,335 claim 1 covers an oral immediate-release, single-phase non-aqueous liquid composition containing a fumarate ester/salt defined by an R1/R2 (H or C1–C20 alkyl with optional substitutions) genus.
• The patent’s practical enforcement leverage sits in formulation architecture (non-aqueous, single-phase, immediate release) and the dependent claim set covering specific vehicle excipients (mono/di-glycerides + PVP + polyoxyl 40 hydrogenated castor oil) and measurable composition parameters (mg dosing, actives-to-vehicle ratios, lactic acid).
• Claim 21 adds a functional Nrf2-dependent pathway activation requirement, which can narrow infringement for close chemical substitutes that do not achieve the same pharmacodynamic effect.
• Common design-arounds map to: changing release profile, avoiding the single-phase non-aqueous vehicle requirement, swapping excipients to dodge claim 16, and shifting dose/ratio to avoid claims 14–15 and 17, with biological proof remaining the critical battleground for claim 21.

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FAQs

How can an oral formulation avoid infringement of US 10,105,335 claim 1?

By changing any required element of claim 1, especially the immediate-release characteristic, the single-phase non-aqueous liquid vehicle requirement, or the inclusion of a fumarate ester/salt that falls outside the R1/R2 genus.

Do claims 14 and 15 create a “dose design-around” for generic developers?

They can. If an accused product’s per-unit dosing stays outside “about 80–115 mg” and “about 160–230 mg” bands, it weakens dependent-claim 14/15 theories, though claim 1 may still be asserted depending on exact dosing and construction of “about.”

Is avoiding lactic acid enough to escape claim coverage?

Avoiding or reducing lactic acid can eliminate infringement of dependent claim 18, but it does not remove exposure to claim 1 and other dependents unless the accused product also changes other required elements.

What is the highest-risk dependent claim for formulation copying?

Claim 16 is high-risk when the accused formulation uses the same excipient set: mono- and di-glycerides + PVP + polyoxyl 40 hydrogenated castor oil.

How does claim 21 affect litigation about close fumarate ester variants?

It turns infringement into a pharmacodynamic proof question. Close chemical variants that do not produce an Nrf2-dependent pathway activation at administered conditions can undermine claim 21.

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References

1. User-provided claim text for U.S. Patent 10,105,335 (claims 1–21).

Drugs Protected by US Patent 10,105,335

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Banner Life Sciences	BAFIERTAM	monomethyl fumarate	CAPSULE, DELAYED RELEASE;ORAL	210296-001	Apr 28, 2020		RX	Yes	Yes	10,105,335		Y

International Family Members for US Patent 10,105,335

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2015222880
Australia	2015328676
Australia	2016253548
Australia	2017204505
Canada	2939990
Canada	2962916