Details for Patent: 10,758,618

Which drugs does patent 10,758,618 protect, and when does it expire?

Patent 10,758,618 protects SYMBRAVO and is included in one NDA.

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

Summary for Patent: 10,758,618

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:	US16/843,490
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,758,618
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

US Patent 10,758,618: Scope, Claim Construction, Exclusivity, and Patent Landscape for Meloxicam-Rizatriptan Migraine Therapy

US Patent 10,758,618 protects a narrow method of treating acute migraine with a three-component oral combination: meloxicam complexed with sulfobutylether-beta-cyclodextrin, bicarbonate, and rizatriptan. The patent is directed primarily to clinical use, formulation architecture, rapid dissolution, patient selection, and comparative treatment outcomes. It does not broadly claim meloxicam, rizatriptan, or their independent use.

The commercial product most closely associated with the claimed combination is Axsome Therapeutics' Symbravo, formerly designated AXS-07, a fixed-dose meloxicam and rizatriptan product approved by the FDA in 2025 for the acute treatment of migraine in adults.[2]

What does US Patent 10,758,618 protect?

The independent claim requires every one of the following elements:

Required element	Claim 1 requirement
Therapeutic purpose	Relief of migraine pain
Patient	Human being in need of treatment
Disease state	Moderate to severe pain from an acute migraine
Timing and phenotype	Patient has morning migraine
Administration	Oral administration
Meloxicam component	Meloxicam complexed with sulfobutylether-beta-cyclodextrin
Bicarbonate component	Bicarbonate administered as part of the combination
Triptan component	Rizatriptan
Clinical result	Greater pain reduction at two hours than the same amount of meloxicam administered alone

This is a combination method-of-use claim with a comparative clinical-performance limitation. A potentially infringing product or treatment must satisfy the drug-composition limitations and the specified patient, administration, timing, and outcome limitations.

The patent therefore has a narrower scope than a conventional composition-of-matter patent. It does not cover:

• Rizatriptan alone;
• meloxicam alone;
• meloxicam with bicarbonate but without rizatriptan;
• rizatriptan with a different NSAID;
• a non-oral formulation;
• treatment of non-migraine pain;
• migraine prevention;
• treatment that does not involve the claimed meloxicam-cyclodextrin complex.

The patent is identified in the public patent record as US Patent No. 10,758,618, titled "Methods of treating migraine." Its claims are assigned to the Axsome-related AXS-07 development program.[1]

How should claim 1 be construed?

Claim 1 has several cumulative limitations that materially restrict enforcement scope.

Morning migraine limitation

The patient must have "morning migraine." This is a substantive limitation, not merely a statement of the intended use. A treatment administered to an afternoon or evening migraine may fall outside claim 1 unless the patient still meets the construction of having morning migraine.

The phrase may create litigation issues because the claims do not define whether morning migraine means:

• migraine pain that begins after waking;
• a migraine present in the morning;
• a migraine that is more frequent in the morning;
• a migraine associated with awakening; or
• a patient phenotype selected for morning attacks.

The narrower construction favors an accused infringer. The broader construction increases potential coverage but creates greater indefiniteness and claim-construction risk.

Comparative response limitation

The claim requires greater pain reduction two hours after the combination than two hours after the same amount of meloxicam administered alone. This is a result-based limitation. It compares the combination against a meloxicam monotherapy control.

The comparator must use the same amount of meloxicam. A clinical trial or infringement analysis would likely need to control, or reliably account for:

• meloxicam dose;
• rizatriptan dose;
• patient baseline pain;
• migraine severity;
• timing of administration;
• rescue medication;
• endpoint measurement;
• patient population;
• formulation and bioavailability.

The claim does not require that the combination outperform meloxicam alone in every treated patient. Its wording is compatible with a comparative clinical result demonstrated at the population level, but the precise evidentiary standard would depend on the litigation record and claim construction.

What do dependent claims add?

The dependent claims create several narrower enforcement positions.

Claims	Added limitation	Commercial significance
2	Greater two-hour pain reduction than rizatriptan alone	Protects superiority over triptan monotherapy
3	Greater two-hour improvement in nausea, phonophobia, or photophobia than rizatriptan alone	Extends protection to most bothersome symptoms
4	Superiority to rizatriptan at both two and 24 hours	Adds sustained treatment benefit
5-6	History or selection based on inadequate prior response	Covers treatment-resistant or suboptimally responsive patients
7-8	Two to eight moderate-to-severe migraine attacks per month	Defines a recurring migraine population
9	Single monolayer tablet	Protects a specific fixed-dose architecture
10-11	Approximately 10 mg rizatriptan, 20 mg meloxicam, and 400-600 mg bicarbonate; sodium bicarbonate specified in claim 11	Closely tracks a commercial dosage profile
12	Greater pain reduction than rizatriptan at 30 minutes	Protects rapid onset
13-14	Inadequate prior response in the 30-minute subgroup	Narrows rapid-response protection
15	Monolayer tablet in the claim 12 subgroup	Combines rapid onset and dosage form
16	Superiority to rizatriptan at two and 24 hours	Protects acute and sustained response
17	No rescue medication for at least 24 hours	Protects durable control
18	Pain freedom at two hours	Adds a clinically important endpoint
19	Absence of most bothersome symptom at two hours	Adds symptom-specific efficacy
20	Bicarbonate amount effective to increase meloxicam dissolution rate	Protects a functional formulation feature
21-22	Migraine accompanied by nausea and greater nausea reduction	Protects a nausea-specific population and outcome
23-25	Sodium bicarbonate, free-base meloxicam, and rizatriptan benzoate	Defines likely commercial chemical forms
26	Single dosage form	Covers co-formulated administration
27-28	Disturbed vision and absence of disturbed vision at two hours	Covers visual symptoms, potentially including aura-related presentations

Claims 10, 11, 15, 16, 20, 23, 24, 25, and 26 are particularly relevant to a marketed fixed-dose tablet. Claims 2 through 4, 12, 16, 18, and 19 are more dependent on clinical evidence and endpoint measurement.

What formulation is protected by US 10,758,618?

The central formulation concept is a single oral dosage form containing:

1. Meloxicam in a sulfobutylether-beta-cyclodextrin complex;
2. Bicarbonate, preferably sodium bicarbonate; and
3. Rizatriptan, preferably rizatriptan benzoate.

The claimed commercial-range formulation contains approximately:

• 20 mg meloxicam;
• 10 mg rizatriptan; and
• 400 mg to 600 mg bicarbonate.

The cyclodextrin is a solubilizing excipient. Meloxicam has limited aqueous solubility, and the cyclodextrin complex is intended to improve dissolution and absorption. The bicarbonate has a second technical role under claim 20: it must be present in an amount effective to increase the dissolution rate of meloxicam.

This creates two separate potential infringement theories:

• structural infringement based on the presence of the three components; and
• functional infringement based on the bicarbonate's effect on meloxicam dissolution.

A competing product could attempt design-around strategies involving a different solubilizer, a different alkalizing agent, separate dosage forms, or a formulation that does not meet the claimed dissolution limitation. Those strategies would require analysis of literal infringement and the doctrine of equivalents.

How strong is the patent estate?

US 10,758,618 has meaningful commercial value because it combines formulation and clinical-use limitations around a single product profile. Its principal strengths are:

• close alignment with the fixed-dose meloxicam-rizatriptan product;
• multiple dosage, patient-selection, and efficacy fallbacks;
• claims covering rapid response at 30 minutes;
• claims covering pain freedom and symptom relief;
• claims covering sustained benefit at 24 hours;
• claims directed to nausea, phonophobia, photophobia, and disturbed vision;
• a formulation limitation tied to meloxicam dissolution.

Its principal vulnerabilities are:

• narrow dependence on a meloxicam-cyclodextrin-bicarbonate-rizatriptan combination;
• possible obviousness arguments based on combining known migraine therapies;
• potential indefiniteness disputes involving "morning migraine," "greater reduction," and "most bothersome symptom";
• possible enablement questions across the full breadth of patient and clinical-response limitations;
• dependence on clinical evidence for comparative outcomes;
• potential difficulty proving that a particular patient or population satisfies the treatment-response limitations.

The patent is stronger against a generic that copies the same fixed-dose composition and labeling than against a competitor using a different formulation or a different triptan. Its strongest claims are likely the composition-linked treatment claims that correspond to the commercial tablet, particularly claims 10, 11, 15, 23, 25, and 26.

When does US Patent 10,758,618 lose exclusivity?

The issue date alone does not establish the patent's expiration date. Patent term is generally calculated from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, patent-term extension, and other statutory adjustments.[3]

The supplied claim text does not establish:

• the earliest priority date;
• patent-term adjustment;
• terminal disclaimer status;
• patent-term extension;
• any later-issued continuation or divisional patents;
• any FDA regulatory exclusivity period.

Those dates must be taken from the USPTO patent file and current Orange Book records. The patent's September 2020 issue date should not be treated as its expiration date.

FDA approval of Symbravo creates a separate regulatory milestone. FDA approval does not itself establish that US 10,758,618 is listed in the Orange Book or that the patent is enforceable against every generic presentation. Orange Book listing, if applicable, would affect the timing and procedure for an ANDA applicant's Paragraph IV certification.[4]

What is the Orange Book status of the meloxicam-rizatriptan product?

The FDA approved Symbravo, a fixed-dose combination of meloxicam and rizatriptan, for the acute treatment of migraine with or without aura in adults.[2] The product is not approved as a preventive migraine therapy.

A regulatory assessment should distinguish among:

Regulatory issue	Relevance
NDA approval	Establishes lawful marketing of the branded product
Orange Book patent listing	Determines whether an ANDA applicant must certify against listed patents
New chemical entity exclusivity	Depends on FDA's regulatory classification of the active ingredients and product
Three-year exclusivity	May apply to certain new clinical investigations supporting approval
Patent-term extension	May extend one eligible patent for regulatory review time
Label carve-out	May allow a generic to omit patented method-of-use language if FDA permits
REMS or device requirements	Not apparent from the supplied claims, but may affect generic approval

Because the claims are directed to treatment methods rather than a new chemical entity, regulatory exclusivity and patent protection should be analyzed separately. The commercial barrier is likely to depend more heavily on patent listing and product-specific formulation protection than on composition-of-matter exclusivity.

Which companies are likely to challenge the product?

The most relevant challengers would be generic manufacturers with experience in:

• rizatriptan tablets or orally disintegrating tablets;
• meloxicam products;
• fixed-dose combination products;
• ANDA litigation involving method-of-use and formulation patents.

Potential challengers could include major US generic companies such as Teva, Sandoz, Viatris, Amneal, Dr. Reddy's, and Lupin, although the claims provided do not establish that any particular company has filed a Paragraph IV certification or litigation.

A generic applicant could pursue several strategies:

1. Paragraph IV challenge to the listed patent;
2. Paragraph III certification with launch after patent expiration;
3. Section viii statement carving out a patented method of use;
4. formulation design-around using a different solubilizing system;
5. separate tablets rather than a monolayer tablet;
6. rizatriptan salt or dose variation;
7. omission of morning-migraine or treatment-resistant-patient language from labeling.

The strongest Paragraph IV case would likely combine obviousness arguments with attacks on the functional and clinical-result limitations. A generic using the same dosage, excipients, and indication would face greater infringement exposure than one using a materially different formulation or label.

What litigation and settlement issues affect US 10,758,618?

The supplied information identifies no litigation, Paragraph IV filing, or settlement agreement. The claims alone cannot establish whether litigation has been filed or whether a generic launch date has been negotiated.

If litigation arises, the main disputes are likely to involve:

• whether the accused product contains the claimed meloxicam-cyclodextrin complex;
• whether bicarbonate increases meloxicam dissolution;
• whether a fixed-dose product is a monolayer tablet or single dosage form;
• whether the label induces treatment of morning migraine;
• whether clinical superiority is a claim limitation or merely an intended result;
• whether the asserted claims are obvious over meloxicam, rizatriptan, cyclodextrin formulations, and bicarbonate-containing dosage forms.

Settlement terms would be commercially material if they provide a licensed launch date before patent expiration, authorized-generic rights, supply obligations, or restrictions on product formulation. No such terms are established by the claim text.

How does the patent compare with competing migraine patents?

Product or therapy	Active treatment	Protection profile relative to US 10,758,618
Symbravo	Meloxicam plus rizatriptan	Direct commercial alignment with the claimed combination
Maxalt	Rizatriptan	Separate rizatriptan product; does not contain the claimed meloxicam-cyclodextrin-bicarbonate combination
Elyxyb	Celecoxib oral solution	Competing NSAID-based acute migraine therapy; different active ingredient and formulation
Ubrelvy	Ubrogepant	CGRP receptor antagonist; separate chemical and method-of-use estate
Nurtec ODT	Rimegepant	CGRP antagonist in orally disintegrating form; different mechanism and dosage form
Triptan monotherapy	Various triptans	Comparator therapy expressly used in several patent claims

The patent estate is differentiated by combining an NSAID, an established triptan, a solubility-enhancing cyclodextrin, and bicarbonate in one oral product. It does not block the broader acute migraine market or prevent competitors from selling CGRP antagonists, other triptans, or NSAID-based products outside the claimed combination.

What generic launch risks exist?

A generic launch before patent expiry would likely fall into one of three scenarios.

Same-formulation launch

A product containing approximately 20 mg meloxicam, 10 mg rizatriptan, sodium bicarbonate, and the same or equivalent cyclodextrin complex would face the highest risk. Claims 10, 11, 23, 25, and 26 are directed toward this commercial configuration.

Label carve-out

A generic may attempt to omit morning-migraine, treatment-resistant-patient, nausea, visual-symptom, or rapid-response language. The viability of this strategy depends on the approved labeling, the Orange Book-listed use code, and whether the remaining label still induces the patented method.

Formulation design-around

A competitor could use a different solubilizer or alkalizing excipient, separate dosage forms, or a different triptan. This could reduce literal infringement risk but would also require separate bioequivalence, clinical, and regulatory analysis.

Key Takeaways

• US 10,758,618 is a method-of-use and formulation patent, not a broad patent on meloxicam or rizatriptan.
• Claim 1 requires oral administration of meloxicam-sulfobutylether-beta-cyclodextrin, bicarbonate, and rizatriptan for moderate-to-severe acute migraine in a patient with morning migraine.
• The claim also requires greater two-hour pain reduction than meloxicam alone.
• Dependent claims add superiority over rizatriptan, rapid 30-minute benefit, 24-hour durability, pain freedom, symptom relief, patient selection, sodium bicarbonate, and a monolayer tablet.
• Claims 10, 11, 15, 23, 25, and 26 most closely track the likely commercial fixed-dose product.
• The patent is commercially strongest against a generic copying the same formulation and indication.
• Its main legal vulnerabilities are obviousness, indefiniteness of clinical and patient-selection terms, and proof of functional dissolution and comparative-outcome limitations.
• FDA approval of Symbravo does not by itself establish the patent's expiration date, Orange Book listing, or litigation status.
• The claims do not block CGRP antagonists, other triptans, celecoxib products, or non-infringing acute migraine formulations.

FAQs

Does US 10,758,618 cover rizatriptan by itself?

No. The claims require rizatriptan as one component of a combination that also includes meloxicam complexed with sulfobutylether-beta-cyclodextrin and bicarbonate.

Does the patent cover migraine prevention?

No. The claims are directed to acute migraine treatment, including moderate-to-severe migraine pain and related symptoms.

Is sodium bicarbonate required in every claim?

No. Claim 1 requires bicarbonate generally. Sodium bicarbonate is expressly required by claims 11 and 23 and is included in the narrower commercial dosage claims.

Can a product infringe without using a monolayer tablet?

Potentially yes. Claims 1 and several other claims do not require a monolayer tablet. Claims 9 and 15 expressly add that limitation, while claim 26 requires a single dosage form.

Does a generic have to prove clinical superiority to obtain approval?

Not necessarily. An ANDA applicant may seek approval through bioequivalence and may challenge listed patents through the applicable certification pathway. The patent's clinical-result limitations could still create infringement and validity issues in subsequent litigation.

References

1. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,758,618, Methods of treating migraine.
2. U.S. Food and Drug Administration. (2025). Symbravo prescribing information: Meloxicam and rizatriptan tablets.
3. United States Code, 35 U.S.C. §§ 154, 156.
4. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations, Orange Book.

Drugs Protected by US Patent 10,758,618

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	10,758,618					ACUTE TREATMENT OF MIGRAINE

International Family Members for US Patent 10,758,618

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