Details for Patent: 8,440,631

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Which drugs does patent 8,440,631 protect, and when does it expire?

Patent 8,440,631 protects TOSYMRA and is included in one NDA.

This patent has eighty-five patent family members in thirty-three countries.

Summary for Patent: 8,440,631

Title:	Compositions for drug administration
Abstract:	The present invention provides compositions and methods and for increasing the bioavailability of therapeutic agents in a subject, as well as compositions and methods for providing migraine pain relief. The compositions include at least one alkyl glycoside and at least one therapeutic agent, such as a 5-HT receptor agonist, wherein the alkylglycoside has an alkyl chain length from about 10 to about 16 carbon atoms.
Inventor(s):	Edward T. Maggio
Assignee:	Aegis Therapeutics LLC
Application Number:	US12/645,376
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 8,440,631: Claim Scope, Expiration, Orange Book Status, and Generic-Entry Risk

US Patent 8,440,631 protects intranasal administration of a triptan with a C10-C16 alkylsaccharide that produces a pharmacokinetic Tmax of 20 minutes or less. The claims are method-of-treatment claims rather than claims directed solely to a composition, device, or manufacturing process. The principal commercial risk is therefore tied to use of an infringing intranasal formulation, especially one containing dodecyl-beta-D-maltoside or a related maltoside absorption enhancer.

The patent does not broadly cover all intranasal triptan products. An accused product must satisfy the claimed triptan, alkylsaccharide, route, and rapid-Tmax limitations. Claims 4 and 5 add narrower sumatriptan, exposure, and pH limitations.

What does US Patent 8,440,631 claim?

The independent claims cover three related therapeutic outcomes:

Claim	Protected subject matter	Required result
1	Intranasal administration of a listed 5-HT agonist with a C10-C16 alkylsaccharide	Tmax of 20 minutes or less
6	Intranasal administration for rapid migraine pain relief	Tmax of 20 minutes or less
10	Intranasal administration to reduce migraine recurrence	Tmax of 20 minutes or less

The listed agonists are sumatriptan, naratriptan, rizatriptan, eletriptan, frovatriptan, almotriptan, zolmitriptan, their salts, or combinations.

The independent claims require all of the following:

1. A human subject or other subject receiving the treatment.
2. Intranasal administration.
3. A 5-HT receptor agonist from the recited triptan group.
4. An alkylsaccharide with an alkyl chain containing 10 to 16 carbon atoms.
5. A pharmacokinetic Tmax of 20 minutes or less.

The claims do not require a particular nasal device, spray volume, propellant, dose except where claim 4 applies, or concentration of the alkylsaccharide. This gives the independent claims technical breadth at the formulation level, but the Tmax limitation creates a substantial proof requirement.

Which alkylsaccharides are specifically protected?

Claims 2, 7, and 11 narrow the alkylsaccharide to five named compounds:

Claimed enhancer	Common technical description
Undecyl-beta-D-maltoside	C11 alkyl maltoside
Dodecyl-beta-D-maltoside	C12 alkyl maltoside, commonly called dodecyl maltoside
Tridecyl-beta-D-maltoside	C13 alkyl maltoside
Tetradecyl-beta-D-maltoside	C14 alkyl maltoside
Sucrose mono-dodecanoate	C12 sucrose ester

The spelling error "tfidecyl" in claim 11 appears to be a typographical error for tridecyl. It would ordinarily be analyzed in the context of the specification, prosecution history, and applicable claim-construction principles rather than treated automatically as an unrelated chemical limitation.

A formulation using a C10, C15, or C16 alkylsaccharide could fall within claim 1, 6, or 10 even if it does not use one of the five compounds listed in the dependent claims. Conversely, a formulation using a C9 or C17 alkylsaccharide would not satisfy the express C10-C16 limitation.

How broad is the triptan coverage?

The patent covers a class of marketed or clinically recognized triptans rather than sumatriptan alone. This is important because an alternative triptan does not necessarily avoid the patent.

A product using any of the following remains within the active-ingredient limitation if the other elements are met:

• Sumatriptan
• Naratriptan
• Rizatriptan
• Eletriptan
• Frovatriptan
• Almotriptan
• Zolmitriptan
• A salt of one of those compounds
• A combination of the listed agonists

The claims do not expressly cover non-triptan migraine agents such as lasmiditan or CGRP antagonists. They also do not cover an oral, injectable, transdermal, or buccal product unless it is also administered intranasally.

The phrase "5-HT agonist" is narrowed by the subsequent Markush list. A compound with serotonergic activity but outside the listed compounds would face a substantial argument that it falls outside the literal scope.

What formulations are protected by the patent?

The patent is formulation-agnostic in several respects. It does not require a specific liquid, powder, gel, suspension, emulsion, or device format. A liquid nasal spray could potentially satisfy the claims. A nasal powder or unit-dose nasal delivery system could also satisfy them if the formulation contains the claimed ingredients and produces the required Tmax.

The most important formulation variables are:

Variable	Requirement under independent claims
Route	Intranasal
Active ingredient	Listed triptan or salt
Absorption enhancer	Alkylsaccharide with C10-C16 chain
Pharmacokinetics	Tmax of 20 minutes or less
pH	Not required by independent claims
EDTA	Not required by independent claims
Dose	Not required except for claim 4
Device	Not specified

Claims 3, 8, and 12 add EDTA or an EDTA salt. EDTA may function as a chelating agent and can affect epithelial permeability or formulation stability, but the independent claims do not require it.

Claims 5, 9, and 13 require a pH of about 7.0 or less. These claims therefore create a narrower risk zone for neutral or mildly acidic formulations. A formulation above about pH 7.0 may avoid these dependent claims while remaining exposed to the independent claims.

What does claim 4 add for sumatriptan?

Claim 4 is materially narrower than claim 1. It requires:

• Sumatriptan;
• An amount of about 20 mg;
• AUC0-1hr of about 10 ng*hr/mL or more; and
• AUC0-4hr of about 40 ng*hr/mL.

This claim targets a specific rapid and sustained exposure profile. It may be relevant to a commercial intranasal sumatriptan product designed to achieve systemic exposure comparable to or better than an injectable or oral reference product.

The AUC limitations create several litigation issues:

1. The parties would need to define the assay, sampling schedule, subject population, and pharmacokinetic analysis.
2. "About" introduces a range rather than an exact numerical boundary.
3. Bioavailability may vary with nasal technique, mucosal condition, device performance, and formulation residence time.
4. A product may avoid claim 4 while still infringing claim 1 if it achieves Tmax of 20 minutes or less.

How does the Tmax limitation affect infringement?

The Tmax limitation is the central technical limitation in the patent. Tmax is the time at which the maximum observed plasma concentration occurs. The claims require a Tmax of 20 minutes or less in the subject.

This limitation can create both a design-around opportunity and a litigation vulnerability. A product containing the same triptan and alkylsaccharide may avoid literal infringement if its validated Tmax exceeds 20 minutes. That conclusion would depend on the testing protocol and how the court treats variability and the term "about" where applicable.

A complete infringement analysis would normally examine:

• The human pharmacokinetic study;
• Sampling intervals, such as 5, 10, 15, and 20 minutes;
• Whether Tmax is directly observed or interpolated;
• The mean, median, or individual-subject result;
• The formulation batch and device used;
• The administered dose;
• Whether the product is a liquid or powder;
• The statistical treatment of subjects with tied or delayed concentration peaks.

A sponsor cannot reliably avoid the patent merely by omitting Tmax from its label. A method claim can be infringed based on actual use and product design, and inducement theories may arise where labeling directs the patented administration method.

What method-of-use rights does the patent provide?

Claims 1, 6, and 10 have different therapeutic framing:

• Claim 1 covers providing a 5-HT agonist.
• Claim 6 covers rapid onset of migraine pain relief.
• Claim 10 covers reduced migraine pain recurrence.

The therapeutic-result language in claims 6 and 10 may require proof that the treatment produces the stated clinical result. The Tmax limitation remains an express requirement in both claims.

Claim 10 is commercially important because it reaches a treatment positioned around recurrence reduction, not merely initial pain relief. A product label that promotes rapid relief and reduced recurrence could create greater exposure than a label limited to generic intranasal administration.

When does US Patent 8,440,631 lose exclusivity?

The patent term is governed principally by 35 U.S.C. §154, which generally provides a 20-year term measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and other statutory modifications.

US Patent 8,440,631 issued on May 14, 2013. The issue date does not determine the expiration date. The relevant calculation is based on the patent family's effective filing history. A precise expiration date must be taken from the USPTO Patent Center record and the patent's term-adjustment information.

The practical exclusivity assessment is:

Issue	Effect
Patent term	Generally 20 years from the earliest effective nonprovisional filing
PTA	Can extend the ordinary term
Terminal disclaimer	Can shorten the term if present
PTE	No extension should be assumed without a specific regulatory order
Patent expiration	Must be confirmed from the USPTO term record
Post-expiration risk	No ordinary patent injunction for future use after expiration

Patent 8,440,631 should not be treated as enforceable solely because it appears in a patent database. The controlling questions are whether the patent remains in force, whether maintenance fees were paid, whether a terminal disclaimer applies, and whether any patent-term adjustment changes the calculated date. The USPTO provides the controlling public record for these issues.[1]

What is the Orange Book status of US Patent 8,440,631?

The patent claims a treatment method and formulation-use combination involving intranasal triptans. It is not automatically an Orange Book-listed patent merely because it covers a pharmaceutical formulation.

FDA listing depends on an approved NDA, the relationship between the patent claims and the approved product, and the sponsor's patent submission. The Orange Book generally identifies patents submitted for approved drug products and provides information relevant to abbreviated new drug applications and Paragraph IV certifications.[2]

The claims supplied do not identify an approved NDA, listed product, or specific commercial sponsor. Accordingly, the patent's litigation significance cannot be equated with Orange Book blocking status. If the patent is not listed against an approved reference product, it would not ordinarily create a conventional Orange Book Paragraph IV certification pathway.

Are Paragraph IV challenges likely?

A Paragraph IV challenge is available only when an ANDA applicant addresses a listed patent for the reference drug. If Patent 8,440,631 is not listed against the relevant NDA, an ANDA applicant would generally not certify Paragraph IV specifically to this patent through the Orange Book process.

Potential invalidity and noninfringement positions would include:

Issue	Potential argument
Anticipation	Prior art disclosed intranasal triptan plus the claimed alkylsaccharide and Tmax
Obviousness	It would have been routine to combine a known triptan with a known nasal absorption enhancer
Written description	The full C10-C16 genus or all listed triptans may not be adequately supported
Enablement	The specification may not enable every triptan, salt, enhancer, and device combination to achieve Tmax ≤20 minutes
Indefiniteness	Terms such as "about," "therapeutically effective amount," and "reduced incidence" may require construction
Noninfringement	The product lacks the claimed enhancer, route, triptan, or pharmacokinetic result

The best design-around strategy is usually to change one required limitation rather than merely change an inactive excipient. Candidates include a non-alkylsaccharide absorption enhancer, an alkylsaccharide outside the C10-C16 range, a different active ingredient, or a formulation whose validated Tmax exceeds 20 minutes.

Which companies are challenging the patent?

The claims supplied do not identify a pending district-court case, inter partes review, post-grant review, or settlement involving US Patent 8,440,631. Patent litigation should be checked by patent number and by the relevant product sponsor because cases may be filed under a parent company, licensing entity, or commercial affiliate.

The principal competitive categories are:

1. Branded intranasal sumatriptan developers.
2. Generic nasal-spray manufacturers.
3. Developers of nasal powders and breath-powered delivery systems.
4. Companies using alternative permeation enhancers.
5. Developers of non-triptan migraine therapies that avoid the claim's active-ingredient Markush group.

A company commercializing an intranasal triptan with dodecyl-beta-D-maltoside has materially greater exposure than a company using a non-alkylsaccharide enhancer or a different migraine mechanism.

How strong is the patent estate?

The strength of Patent 8,440,631 is mixed.

Strengths

• It covers several clinically relevant triptans.
• It reaches both composition use and therapeutic outcomes.
• It includes a broad C10-C16 alkylsaccharide genus.
• It does not require a specific device or concentration in the independent claims.
• It targets rapid Tmax, a commercially valuable performance attribute.

Weaknesses

• The claims depend heavily on a measurable pharmacokinetic result.
• The specification must support the full combination of triptans, salts, alkylsaccharides, formulations, and devices.
• Prior art concerning intranasal triptans and surfactant absorption enhancers may create obviousness pressure.
• Method claims are harder to enforce against a product whose label does not expressly promote the claimed use.
• A formulation can potentially design around the alkylsaccharide or Tmax limitation.

The strongest claim set is likely claims 1, 6, and 10 when a product clearly uses one of the named alkylsaccharides and clinical data show Tmax of 20 minutes or less. The dependent claims add useful fallback positions but cover narrower commercial configurations.

What generic launch scenarios exist?

Scenario 1: Conventional oral or injectable generic

A generic oral tablet, orally disintegrating tablet, or injectable sumatriptan does not satisfy the intranasal administration limitation. Patent 8,440,631 would not ordinarily block that launch.

Scenario 2: Intranasal product without an alkylsaccharide

A nasal triptan using a different absorption technology may avoid literal infringement, subject to any applicable equivalents analysis.

Scenario 3: Intranasal product using C10-C16 alkylsaccharide

This is the highest-risk scenario. The sponsor would need to address the triptan, alkylsaccharide, route, and Tmax elements. A Paragraph IV certification would be relevant only if the patent is listed against the applicable reference product.

Scenario 4: Intranasal product with delayed Tmax

A product with Tmax above 20 minutes may avoid the independent claims, but the result must be established under a defensible pharmacokinetic protocol.

Scenario 5: Nasal product using a non-listed active

Lasmiditan or a CGRP-pathway agent would not fall within the express triptan Markush group, although separate patents may apply.

What manufacturing and IP barriers remain?

The patent does not claim a manufacturing process. Manufacturing risk therefore arises indirectly from the need to produce a formulation that consistently delivers the required pharmacokinetic profile.

Commercial barriers may include:

• Control of alkylsaccharide grade and purity;
• Consistent nasal deposition;
• Stability of the active and enhancer;
• Device compatibility;
• Dose uniformity;
• Batch-to-batch Tmax performance;
• Human bioequivalence or clinical-performance requirements;
• Separate device patents;
• Separate formulation patents covering particle size, viscosity, preservatives, or unit-dose packaging.

A design-around that changes the enhancer may create new regulatory and manufacturing problems. A different enhancer may lower permeability, reduce dose consistency, or alter nasal tolerability.

Key Takeaways

• US Patent 8,440,631 is centered on intranasal triptan delivery using a C10-C16 alkylsaccharide.
• The core technical requirement is Tmax of 20 minutes or less.
• Sumatriptan is only one of seven expressly listed triptans.
• Dodecyl-beta-D-maltoside is a particularly important dependent-claim species.
• EDTA and pH of about 7.0 or less are narrower dependent-claim limitations.
• The patent does not cover oral, injectable, or non-intranasal triptan products.
• It is not possible to treat the patent as an Orange Book blocker without confirming an NDA listing.
• The principal design-around options are changing the enhancer, active ingredient, route, or pharmacokinetic profile.
• Patent enforceability depends on the USPTO term record, including PTA, terminal disclaimers, maintenance fees, and the effective filing date.
• The strongest infringement case would involve an intranasal sumatriptan product containing dodecyl-beta-D-maltoside and clinical data showing Tmax of 20 minutes or less.

FAQs

Does US Patent 8,440,631 cover all sumatriptan nasal sprays?

No. The product must also contain a C10-C16 alkylsaccharide and produce a Tmax of 20 minutes or less, among other requirements.

Can a nasal triptan avoid the patent by using EDTA alone?

Potentially. EDTA is a limitation only in dependent claims 3, 8, and 12. It does not replace the required alkylsaccharide in the independent claims.

Does a C8 or C18 alkylsaccharide fall within the patent?

Not literally within the express C10-C16 limitation. Separate equivalents and claim-construction issues could still arise, depending on the facts.

Does the patent cover a nasal powder device?

Potentially. The claims do not limit the delivery format. A nasal powder may fall within the claims if it contains the required triptan and alkylsaccharide and achieves the claimed Tmax.

Is a Paragraph IV certification automatically required for this patent?

No. Paragraph IV treatment depends on whether the patent is listed in the Orange Book for the relevant approved reference product.

References

1. United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/

2. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files

3. United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section154

4. U.S. Food and Drug Administration. (2017). Abbreviated new drug application submissions: Refuse-to-receive standards. https://www.fda.gov/regulatory-information/search-fda-guidance-documents

5. United States Patent and Trademark Office. (n.d.). Patent term adjustment. https://www.uspto.gov/patents/laws/patent-term-adjustment-patent-customer-number-estimator/Patent Term Adjustment Estimator

Drugs Protected by US Patent 8,440,631

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Tonix Meds	TOSYMRA	sumatriptan	SPRAY;NASAL	210884-001	Jan 25, 2019		RX	Yes	Yes	8,440,631		Y			ACUTE TREATMENT OF MIGRAINE

International Family Members for US Patent 8,440,631

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3678649		301317	Netherlands
European Patent Office	3678649		CA 2025 00007	Denmark
European Patent Office	3678649		PA2025507	Lithuania