Details for Patent: 10,729,696

Which drugs does patent 10,729,696 protect, and when does it expire?

Patent 10,729,696 protects SYMBRAVO and is included in one NDA.

This patent has two hundred and twenty patent family members in thirty-two countries.

Summary for Patent: 10,729,696

Title:	Pharmaceutical compositions comprising meloxicam
Abstract:	Disclosed herein are compositions comprising an NSAID such as meloxicam and/or rizatriptan in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a Tmax of meloxicam of 3 hours or less.
Inventor(s):	Herriot Tabuteau
Assignee:	Axsome Therapeutics Inc
Application Number:	US16/568,703
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,729,696
Patent Claim Types: see list of patent claims	Use; Dosage form;

US Patent 10,729,696: Claim Scope, Exclusivity, and Patent Landscape for Meloxicam-Rizatriptan Migraine Treatment

US Patent 10,729,696 protects a method of treating migraine with an oral combination of meloxicam, sulfobutyl ether beta-cyclodextrin, bicarbonate, and rizatriptan. Its commercial relevance is tied to Symbravo, the meloxicam/rizatriptan product approved by FDA in January 2025. The patent does not claim every meloxicam-rizatriptan product. It requires a specific solubilized meloxicam formulation, bicarbonate, migraine treatment, a patient history of inadequate response to prior treatments, and a reduction in photophobia.

The patent is strongest against a product that copies the Symbravo formulation and is marketed for the same migraine population. It is less direct against a conventional meloxicam-rizatriptan tablet that omits SBEbetaCD or bicarbonate, or against a product with a label designed to avoid the claimed patient-selection and photophobia limitations.

What drug and formulation does US Patent 10,729,696 protect?

The patent covers an oral dosage form combining four core elements:

Required element	Claim requirement
Meloxicam	Complexed with sulfobutyl ether beta-cyclodextrin, or SBEbetaCD
SBEbetaCD	About 50 mg to 200 mg in claim 1
Bicarbonate	400 mg to 600 mg in claim 1
Rizatriptan	1 mg to 50 mg, calculated as free base
Disease	Migraine
Patient selection	History of inadequate response to prior migraine treatments
Clinical result	Reduction in photophobia

The commercial formulation associated with the patent contains 20 mg of meloxicam, 10 mg of rizatriptan, 100 mg of SBEbetaCD, and 500 mg of sodium bicarbonate. That formulation falls within the principal concentration ranges and several narrower dependent claims.

The invention is directed to improving meloxicam absorption. SBEbetaCD forms a complex with meloxicam, while bicarbonate is used as part of the rapid-release formulation. The patent links the formulation to faster meloxicam exposure and earlier attainment of therapeutic plasma concentrations compared with a conventional meloxicam dosage form.

How broad is independent claim 1?

Claim 1 is a method-of-treatment claim, not a composition claim. A potentially infringing method must satisfy every material limitation.

Claim 1 element-by-element analysis

Limitation	Scope and enforcement significance
Selecting a human migraine patient	Limits the claim to human treatment and creates a patient-selection requirement
History of inadequate response to prior migraine treatments	Narrows the population but may be difficult to test directly in commercial-use discovery
Orally administering a dosage form	Covers administration, not merely manufacture or sale
Meloxicam-SBEbetaCD complex	Requires the claimed complex, not simply meloxicam and SBEbetaCD placed in the same tablet
Bicarbonate	Requires 400 mg to 600 mg
Rizatriptan	Must be present in the dosage form
Reduction in photophobia	Requires the claimed treatment result

The most important limiting feature is the combination of formulation and clinical outcome. A competitor could avoid literal infringement by omitting SBEbetaCD, omitting bicarbonate, using a different cyclodextrin, or marketing a product without the patient-selection or photophobia language.

The claim may still present inducement or contributory-infringement risk if a generic or competing sponsor’s labeling directs physicians to administer a substantially identical product to the claimed population.

What formulations are protected by the dependent claims?

The dependent claims create a concentrated protection zone around the likely commercial formulation.

Claims	Protected formulation or performance feature
4	1 mg to 50 mg rizatriptan, free-base basis
5-6	Rizatriptan salt equivalent to about 10 mg free base, including rizatriptan benzoate
7-9	10 mg to 30 mg meloxicam, including 15 mg and 20 mg
10	SBEbetaCD with approximately six to seven sulfobutyl ether groups
11-12	50 mg to 150 mg SBEbetaCD, including 100 mg
13-15	SBEbetaCD-to-meloxicam molar ratio of about 0.5:1 to 2:1, including approximately 1:1
16	10 mg to 40 mg meloxicam and 5 mg to 50 mg rizatriptan
17-18	SBEbetaCD-to-rizatriptan weight ratio of approximately 1:1 to 100:1, including 10:1
19-20	Bicarbonate, specifically sodium bicarbonate, including 500 mg
21-22	Median meloxicam Tmax below approximately 90 minutes or two hours in fasted human subjects

Claims 8, 12, 15, 18, and 20 are particularly relevant to a product containing 20 mg meloxicam, 100 mg SBEbetaCD, a roughly 1:1 molar SBEbetaCD-to-meloxicam ratio, a 10:1 SBEbetaCD-to-rizatriptan weight ratio, and 500 mg sodium bicarbonate.

The dependent claims improve commercial coverage but also increase proof requirements. A plaintiff would need formulation, analytical, pharmacokinetic, and clinical evidence to establish the narrower limitations.

What is the patent expiration date for US Patent 10,729,696?

The patent has a statutory term generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any patent-term extension. The relevant expiration date should be taken from the USPTO patent record and Orange Book listing rather than calculated solely from the issue date.

US Patent 10,729,696 issued June 2, 2020. Its issue date does not control expiration. A patent issued in 2020 can remain enforceable well beyond 2030 if its application family was filed in the mid-2010s.

The FDA Orange Book listing is commercially more important than the patent’s face value because it controls the certification obligations for an ANDA applicant. For an Orange Book-listed method patent, the applicant may need to file a Paragraph IV certification or use a permissible label carve-out, depending on the scope of the listed use code and proposed labeling.[1]

What is the FDA regulatory status of the protected product?

FDA approved Symbravo tablets, containing meloxicam and rizatriptan, for the acute treatment of migraine with or without aura in adults on January 30, 2025. The product is associated with Axsome Therapeutics and NDA 219897.[2]

FDA and exclusivity timeline

Event	Date or status
US Patent 10,729,696 issued	June 2, 2020
Symbravo NDA approval	January 30, 2025
Regulatory pathway	New drug application for a fixed-dose combination
Active ingredients	Meloxicam and rizatriptan
Dosage form	Oral tablet
Small-molecule generic pathway	ANDA, subject to sameness and patent/exclusivity requirements
Biosimilar pathway	Not applicable
Orange Book relevance	Listed patents and use codes determine ANDA certification obligations

Because both active ingredients were previously approved, the product’s regulatory exclusivity profile differs from that of a new molecular entity. A fixed-dose combination may qualify for three-year exclusivity when the sponsor submits new clinical investigations essential to approval, but it does not receive five-year new-chemical-entity exclusivity merely because the combination is new.[3]

The exact exclusivity end date must be confirmed in the current Orange Book and FDA exclusivity records.

When does Symbravo lose exclusivity?

Patent exclusivity and FDA regulatory exclusivity are separate.

The relevant commercial barriers are:

1. The remaining term of US Patent 10,729,696 and any related continuation or formulation patents.
2. Any additional Orange Book-listed patents covering the combination, formulation, dosage form, or method of use.
3. Any three-year FDA exclusivity associated with the Symbravo approval.
4. Potential pediatric exclusivity, if later granted.
5. The ability of a generic applicant to use a Paragraph IV certification or carve out patented use information.

The earliest practical generic launch date could be later than the end of FDA exclusivity if a listed patent remains enforceable. Conversely, a generic could launch before patent expiration if it obtains a favorable litigation outcome, settles on an authorized-entry date, or markets a formulation and label outside the patent claims.

What Paragraph IV challenges could affect US Patent 10,729,696?

An ANDA applicant seeking approval for a product that references Symbravo could challenge the patent under Paragraph IV of the Hatch-Waxman Act. The principal challenge theories would likely include:

Noninfringement

A generic could design around the claim by:

• Omitting SBEbetaCD.
• Using a cyclodextrin other than SBEbetaCD.
• Omitting bicarbonate or using an amount outside 400 mg to 600 mg.
• Using a different meloxicam salt or formulation that does not contain the claimed complex.
• Avoiding a label directed to patients with inadequate prior treatment response.
• Carving out photophobia-related use, if FDA-approved labeling permits the carve-out.

A conventional tablet containing meloxicam and rizatriptan without SBEbetaCD would present a materially different infringement profile.

Invalidity

Potential invalidity arguments include:

• Anticipation based on earlier meloxicam-rizatriptan combination disclosures.
• Obviousness based on combining known rizatriptan migraine therapy with known meloxicam therapy and a known cyclodextrin-based solubilization approach.
• Lack of written description or enablement for the full concentration and patient-treatment ranges.
• Indefiniteness involving terms such as “inadequate response,” “reduction in photophobia,” “shorter Tmax,” and “faster time to therapeutic plasma concentration.”

The patent’s clinical-result limitations may help distinguish prior art, but they can create evidentiary disputes over whether the result is an enforceable limitation or merely an expected consequence of administering the formulation.

Litigation timing

A Paragraph IV notice generally triggers a 45-day period for the patent owner to bring an infringement action. A timely action can impose a 30-month stay of FDA approval, subject to statutory exceptions and court decisions.[4]

No litigation conclusion should be inferred from the patent’s issuance or the NDA approval alone. Current docket and Orange Book records control the status of any challenge.

How strong is the patent estate?

US Patent 10,729,696 has a mixed strength profile.

Strength factor	Assessment
Commercial product fit	Strong if the marketed formulation uses 20 mg meloxicam, 10 mg rizatriptan, 100 mg SBEbetaCD, and 500 mg sodium bicarbonate
Formulation specificity	Strong against close copies; weaker against alternative delivery systems
Method-of-use scope	Narrower than a composition claim because administration and patient-treatment limitations are required
Pharmacokinetic claims	Potentially useful, but dependent on validated human PK data
Design-around risk	Meaningful because SBEbetaCD and bicarbonate are express limitations
Generic substitution risk	Significant after regulatory barriers expire if a generic can avoid or defeat the patent
Biosimilar risk	None
Manufacturing barrier	Moderate; the complexation and rapid-release process may create know-how advantages but is not necessarily a blocking patent barrier
Litigation vulnerability	Dependent on prior-art disclosure of the specific combination and formulation

The patent is strongest as a copycat-deterrent patent. It is less effective as a broad platform patent covering every oral combination of an NSAID and a triptan.

What manufacturing and formulation barriers exist?

A competing manufacturer would need to address several technical issues:

• Formation and characterization of the meloxicam-SBEbetaCD complex.
• Control of SBEbetaCD substitution level, particularly the claimed six-to-seven sulfobutyl ether range.
• Maintenance of rapid dissolution and acceptable tablet manufacturability.
• Compatibility between sodium bicarbonate and other tablet excipients.
• Stability under moisture and storage conditions.
• Reproducibility of meloxicam Tmax and early plasma exposure.
• Bioequivalence to the reference product.

These technical issues can delay development even where the competitor has a noninfringing formulation. They do not, by themselves, establish patent infringement. A manufacturer can use alternative solubilizers, different alkalizing agents, liquid dosage forms, or separate dosage units, subject to FDA bioequivalence and labeling requirements.

How does this patent compare with competing migraine products?

Product class	Representative products	Relationship to US 10,729,696
Triptans	Rizatriptan, sumatriptan, eletriptan	Compete on acute migraine treatment but generally do not use the claimed meloxicam-SBEbetaCD-bicarbonate combination
NSAID migraine products	Naproxen, ibuprofen, meloxicam products	Compete on anti-inflammatory treatment but lack the claimed fixed combination
CGRP antagonists	Ubrelvy, Nurtec ODT, Zavzpret	Different mechanism and formulation; no biosimilar pathway
Fixed-dose NSAID/triptan	Symbravo	Direct commercial product associated with the claimed formulation

The patent’s commercial differentiation is the attempt to combine rapid rizatriptan activity with accelerated meloxicam exposure. Competing CGRP products may avoid the patent entirely but compete for the same acute-treatment prescription.

What revenue exposure and generic launch risks exist?

Revenue exposure is concentrated in the fixed-dose combination rather than in meloxicam or rizatriptan individually, both of which have long-established generic markets.

Generic risk increases when:

• FDA exclusivity expires.
• The Orange Book lists only narrow method patents.
• A generic can omit the claimed formulation components.
• The label can be carved out without materially reducing the product’s approved market.
• The patent owner cannot prove the patient-selection or photophobia limitations from prescribing and dispensing evidence.

Risk decreases when the reference formulation is difficult to reproduce and the listed patent claims track the commercial tablet closely. An authorized generic or settlement-based entry would create an earlier competitive event even without a final invalidity judgment.

What patent litigation affects the product?

The principal litigation question is whether an ANDA applicant has certified against US Patent 10,729,696 and whether the patent owner has sued within the statutory period. A complete litigation assessment requires current PACER, USPTO, and Orange Book records.

The patent’s litigation leverage would likely center on:

• Whether the proposed generic contains SBEbetaCD.
• Whether its bicarbonate amount falls within the claimed range.
• Whether its rizatriptan is present as rizatriptan benzoate.
• Whether the proposed labeling directs treatment of the claimed patient population.
• Whether the generic label includes migraine-associated photophobia or equivalent use instructions.

Key Takeaways

• US Patent 10,729,696 is a method patent covering migraine treatment with meloxicam complexed with SBEbetaCD, bicarbonate, and rizatriptan.
• The likely Symbravo formulation falls within the central dependent claims: 20 mg meloxicam, 10 mg rizatriptan, 100 mg SBEbetaCD, and 500 mg sodium bicarbonate.
• The patent does not broadly cover all meloxicam-rizatriptan combinations.
• SBEbetaCD and bicarbonate are important design-around points.
• The claim requires a migraine patient with inadequate response to prior treatment and a reduction in photophobia, creating proof and label-scope issues.
• FDA approved Symbravo on January 30, 2025, under NDA 219897.
• Biosimilar competition is irrelevant because Symbravo is a small-molecule combination product.
• Generic applicants are more likely to use Paragraph IV, label carving, or formulation design-around strategies than a biosimilar pathway.
• Patent expiration, Orange Book use codes, FDA exclusivity, and any continuation patents must be assessed together to determine the actual generic-entry date.

FAQs

Does US Patent 10,729,696 claim Symbravo itself?

No. It claims a method of treating migraine using a formulation that corresponds closely to Symbravo’s reported active ingredients and excipients. It does not claim every possible tablet containing meloxicam and rizatriptan.

Can a generic avoid this patent by removing sodium bicarbonate?

Potentially. Removing sodium bicarbonate would avoid a literal limitation of claim 1, although the generic would still need to address other patents, regulatory requirements, and any doctrine-of-equivalents argument.

Is rizatriptan benzoate specifically protected?

Yes. Claim 6 expressly recites rizatriptan benzoate, while claim 5 covers a salt amount equivalent to approximately 10 mg of rizatriptan free base.

Does the patent cover a separate meloxicam tablet and rizatriptan tablet?

The claims recite administering an oral dosage form comprising the combination. Separate products may present a different infringement analysis, particularly if no single dosage form contains all claimed components.

Can an ANDA applicant launch after FDA approval but before patent expiration?

Only if the applicant clears applicable FDA exclusivity and patent barriers, obtains a favorable court outcome, reaches a settlement or authorized-entry agreement, or markets a product and label that do not infringe the enforceable claims.

References

1. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book.
2. U.S. Food and Drug Administration. (2025). Symbravo prescribing information. Axsome Therapeutics, Inc.
3. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j)(5)(F)(iii).
4. Hatch-Waxman Act, 21 U.S.C. § 355(j)(2)(A)(vii)(IV), § 355(j)(5)(B)(iii).
5. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,729,696: Combination therapy for treatment of migraine.

Drugs Protected by US Patent 10,729,696

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Axsome	SYMBRAVO	meloxicam; rizatriptan benzoate	TABLET;ORAL	215431-001	Jan 30, 2025		RX	Yes	Yes						ACUTE TREATMENT OF MIGRAINE

International Family Members for US Patent 10,729,696

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016218992
Australia	2018205790
Australia	2018265411
Australia	2019203328
Australia	2019297360