Details for Patent: 10,583,144

Which drugs does patent 10,583,144 protect, and when does it expire?

Patent 10,583,144 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: 10,583,144

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:	US16/653,877
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,583,144
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 10,583,144: Claims, Exclusivity, Litigation Risk, and Patent Landscape for Meloxicam-Rizatriptan Migraine Therapy

U.S. Patent No. 10,583,144 protects a treatment method using an oral combination of meloxicam complexed with sulfobutyl ether beta-cyclodextrin, bicarbonate, and rizatriptan. Its strongest commercial relevance is to Symbravo, the meloxicam/rizatriptan product approved by the FDA for acute migraine treatment in adults. The patent is narrower than a composition patent because infringement depends on the prescribed treatment method, patient selection, formulation components, and claimed clinical outcome.

The patent’s nominal term appears to extend into the mid-2030s, subject to the patent’s terminal disclaimer, patent-term adjustment, patent-term extension, and the applicable earliest effective U.S. filing date. The claims do not cover all meloxicam-rizatriptan products. They focus on a specific fast-acting formulation and a patient population with inadequate response to prior migraine treatments.

What does U.S. Patent 10,583,144 protect?

The patent claims a method of treating migraine by orally administering a dosage form containing three required elements:

1. A complex of meloxicam with sulfobutyl ether beta-cyclodextrin, or SBEβCD.
2. A bicarbonate.
3. Rizatriptan.

The independent claim also requires two patient and clinical limitations:

• The patient has a history of inadequate response to prior migraine treatments.
• The patient is free of migraine pain 24 hours after administration.

The claim therefore combines formulation limitations with a treatment-response limitation. A product that contains meloxicam and rizatriptan but lacks SBEβCD or bicarbonate would fall outside the literal scope of claim 1. A product with the claimed ingredients but used in patients without the specified treatment history would present a different infringement analysis.

Core claim elements

Claim element	Scope and commercial significance
Migraine treatment	Limits the claim to therapeutic use for migraine
Human patient	Excludes nonhuman treatment
Inadequate response to prior treatments	Narrows the target population and affects induced-infringement analysis
Oral dosage form	Excludes nonoral delivery systems
Meloxicam-SBEβCD complex	Captures the solubilization and absorption-enhancement architecture
Bicarbonate	Requires an alkalinizing component, with sodium bicarbonate expressly covered by dependent claims
Rizatriptan	Requires the triptan component
Pain-free at 24 hours	Adds a clinical outcome limitation to the independent claim

The claim is not a broad claim to the pharmacological combination alone. It is a method claim directed to use of a defined dosage form in a defined clinical context.

How do claims 2 through 25 narrow the patent?

Claims 2 through 25 add quantitative, pharmacokinetic, salt-form, and formulation limitations. Many claims overlap commercially because the marketed dosage form can satisfy several limitations at the same time.

Dose and formulation limitations

Claim	Added limitation
2	400 mg to 600 mg bicarbonate
3	5 mg to 50 mg meloxicam
4	50 mg to 200 mg SBEβCD
7	1 mg to 50 mg rizatriptan, calculated as free base
8	Rizatriptan salt equivalent to approximately 10 mg free base
9	Rizatriptan benzoate
10	10 mg to 30 mg meloxicam
11	Approximately 20 mg meloxicam
12	Approximately 15 mg meloxicam
13	Approximately 6 to 7 sulfobutyl ether groups per beta-cyclodextrin
14	50 mg to 150 mg SBEβCD
15	Approximately 100 mg SBEβCD
22	Bicarbonate comprises sodium bicarbonate
23	500 mg sodium bicarbonate

Claims 2 and 23 are particularly relevant to a commercial tablet containing 500 mg sodium bicarbonate. Claims 8 and 9 address the common commercial presentation of rizatriptan as rizatriptan benzoate at a salt quantity equivalent to approximately 10 mg of rizatriptan free base.

Ratio limitations

Claims 16 through 18 require an SBEβCD-to-meloxicam molar ratio of:

• Approximately 0.5 to 2.
• Approximately 0.8 to 1.2.
• Approximately 1.

These claims target a relatively narrow complexation relationship. They can be important in formulation development because a competitor may avoid literal infringement by using a different cyclodextrin, a materially different ratio, or a noncomplexed meloxicam formulation.

Claims 20 and 21 impose an SBEβCD-to-rizatriptan weight ratio of approximately 1 to 100 or approximately 10. These limitations may be met by the same formulation that satisfies the meloxicam ratio claims.

What formulation technology is protected?

The patent’s technical center is the use of SBEβCD and bicarbonate to accelerate meloxicam exposure after oral administration.

Meloxicam has relatively slow and variable absorption compared with rapidly acting migraine therapies. Complexation with SBEβCD can improve apparent solubility. Bicarbonate can increase local pH and support dissolution of an acidic drug. The claimed formulation combines those mechanisms with rizatriptan, which provides triptan-mediated vasoconstrictive and serotonergic activity.

Claims 5 and 6 make the pharmacokinetic objective explicit. They require a solid oral dosage form with:

• A shorter meloxicam Tmax than a reference dosage form containing the same amount of meloxicam but no SBEβCD and no bicarbonate.
• Faster achievement of a therapeutic meloxicam plasma concentration than the reference dosage form.

Claims 24 and 25 add numerical Tmax thresholds:

• Median meloxicam Tmax below approximately 90 minutes in fasted human subjects.
• Median meloxicam Tmax below approximately two hours in fasted human subjects.

Why the pharmacokinetic claims matter

The claims do not merely require that SBEβCD and bicarbonate be present. Claims 5, 6, 24, and 25 connect the formulation to an observed pharmacokinetic result. That creates two competing effects:

• The claims may be difficult to design around if a competing product uses the same excipient strategy and produces the same rapid exposure.
• They may be more difficult to enforce because infringement may require reliable human pharmacokinetic evidence, defined testing conditions, and an appropriate reference formulation.

The phrase “has been shown to have” can raise claim-construction questions. Courts may assess whether the phrase imposes a present performance requirement, a historical testing requirement, or merely describes a characteristic of the dosage form.

When does U.S. Patent 10,583,144 lose exclusivity?

The patent issued on March 10, 2020. Its expiration date is determined by the earliest effective nonprovisional filing date in the relevant family, not by the issue date. A 20-year term from an early-to-mid-2010s priority or nonprovisional filing would place nominal expiration in the mid-2030s.

Exclusivity issue	Assessment
Patent type	U.S. utility patent
Issue date	March 10, 2020
Nominal patent term	Generally 20 years from the effective nonprovisional filing date
Expected expiration window	Mid-2030s, subject to official term calculation
Patent-term adjustment	May extend the calculated expiration date
Patent-term extension	Potentially relevant if statutory requirements are met following regulatory approval
Terminal disclaimer	Must be reviewed in the patent file and family records
Regulatory exclusivity	Separate from patent term and depends on the approved product and FDA designation

The official expiration date should be determined from the USPTO patent record and the Orange Book listing, if the patent is listed for the approved product. Patent-term extension is not automatic. It requires an application and satisfaction of statutory requirements under 35 U.S.C. § 156.

What is the FDA and Orange Book status of the covered product?

The commercial product associated with the claimed meloxicam-rizatriptan technology is Symbravo, approved by the FDA in January 2025 for the acute treatment of migraine with or without aura in adults.[2]

Symbravo contains meloxicam and rizatriptan. The product’s commercial positioning depends on rapid onset and treatment of migraine using an NSAID-triptan combination. The FDA-approved labeling, rather than the patent alone, controls the approved indication and dosing instructions.

Orange Book implications

If U.S. Patent 10,583,144 is listed in the Orange Book for Symbravo, an ANDA applicant seeking approval of a therapeutically equivalent generic may need to address the patent through one of the certifications under 21 U.S.C. § 355(j)(2)(A)(vii):

• Paragraph I: no patent information has been submitted.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will wait until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A method-of-use patent may be listed if it claims an FDA-approved method of using the drug. Listing does not establish validity or infringement. It creates a regulatory patent-certification mechanism.

What Paragraph IV challenges and generic entry risks exist?

A Paragraph IV filing would expose the applicant to patent litigation under the Hatch-Waxman statute. The patent holder could sue within 45 days of receiving notice, potentially triggering a 30-month stay of FDA approval, subject to statutory exceptions and court decisions.

Likely generic challenge theories

A generic applicant could challenge the patent through several routes:

1. Noninfringement based on formulation differences.
   The applicant could omit SBEβCD, replace it with another cyclodextrin, exclude bicarbonate, or use a different meloxicam delivery system.

2. Noninfringement based on patient labeling.
   The applicant could argue that its proposed label does not require treatment of patients with inadequate response to prior migraine therapies.

3. Noninfringement based on clinical outcome.
   The applicant could contest whether the 24-hour pain-free limitation is met or required by the proposed use.

4. Invalidity for obviousness.
   Prior art may disclose meloxicam for migraine, rizatriptan for migraine, cyclodextrins for solubilization, and bicarbonate-based dissolution enhancement. The central issue would be whether the claimed combination and rapid exposure produced an unexpected result.

5. Written-description or enablement challenges.
   The patent contains broad numerical ranges and a broad clinical response limitation. A challenger could argue that the specification does not support the full scope of all combinations or enable the claimed outcome across the entire range.

6. Indefiniteness.
   Terms such as “inadequate response,” “about,” “faster time to therapeutic plasma concentration,” and “free of migraine pain” may require construction based on the specification and clinical evidence.

The strongest practical barrier is likely the combination of the formulation requirement and the clinical-response limitation. A generic may be able to develop a noninfringing formulation, but a product intended to replicate the approved product’s rapid onset and clinical positioning could face greater risk.

Does the patent have method-of-use or composition coverage?

The patent is principally a method-of-use patent. Its claims require administering the formulation to a migraine patient. The claims do not independently claim:

• Meloxicam-SBEβCD as a composition.
• A tablet containing meloxicam, SBEβCD, bicarbonate, and rizatriptan.
• A manufacturing process.
• A specific tablet-coating system.
• A pharmaceutical kit.
• A broad method of treating pain unrelated to migraine.

The distinction is commercially material. A composition patent can cover manufacture, sale, and possession of the product more directly. A method patent generally creates infringement exposure when the product is made, sold, or labeled for the claimed use, or when the claimed method is performed.

How strong is the patent estate?

U.S. Patent 10,583,144 has meaningful but concentrated protection.

Strengths

• The independent claim requires a defined three-component formulation.
• SBEβCD and bicarbonate identify a specific absorption-enhancement strategy.
• The claim is tied to a clinically relevant patient population.
• Dependent claims cover commercial dose points, including 20 mg meloxicam, approximately 10 mg rizatriptan free-base equivalent, and 500 mg sodium bicarbonate.
• The pharmacokinetic claims support the rapid-onset product rationale.

Vulnerabilities

• The core pharmacological agents, meloxicam and rizatriptan, were individually known migraine-related compounds.
• Several excipient functions, including cyclodextrin complexation and alkalinization, may be found in prior pharmaceutical literature.
• The independent claim’s 24-hour pain-free limitation can create proof and claim-construction issues.
• The “inadequate response” requirement may limit enforcement against broad labels that do not expressly target that population.
• The patent does not necessarily block a materially different formulation using another solubilizer or absorption-enhancement approach.

Patent strength is therefore higher against a close copy of the approved formulation than against a differentiated acute-migraine product.

What manufacturing and intellectual-property barriers exist?

A competing manufacturer would need to address more than the patent claim. The relevant development barriers include:

• Reproducing rapid meloxicam dissolution without SBEβCD.
• Maintaining tablet stability with a high bicarbonate load.
• Controlling moisture sensitivity and excipient compatibility.
• Demonstrating bioequivalence under FDA requirements.
• Establishing rizatriptan salt equivalence.
• Avoiding infringement of related formulation, process, or method patents in the same family.
• Resolving any Orange Book-listed patent certifications.

A formulation that uses the same active ingredients but changes the complexation chemistry may require a new clinical or pharmacokinetic development program. That raises cost and delays market entry even where literal patent infringement can be avoided.

Which companies are most exposed to the patent?

Axsome Therapeutics is the primary commercial stakeholder associated with Symbravo and the AXS-07 development program. Potentially exposed parties include:

• ANDA applicants developing generic meloxicam-rizatriptan products.
• Contract manufacturers producing the approved or generic formulation.
• Licensed distributors with product-specific manufacturing or commercialization rights.
• Developers seeking to position a dual-mechanism acute migraine product against Symbravo.

Biosimilar competition is not relevant. Symbravo is a small-molecule drug, so competing products would proceed through the ANDA pathway rather than the 351(k) biosimilar pathway.

What litigation and settlement issues should investors monitor?

The key litigation indicators are:

1. Paragraph IV notices involving patents listed for Symbravo.
2. Hatch-Waxman complaints filed within the 45-day notice period.
3. Patent-term-extension applications or grants.
4. Orange Book delisting disputes.
5. Inter partes review petitions at the Patent Trial and Appeal Board.
6. Family continuations covering formulation, pharmacokinetics, or treatment response.
7. License or settlement agreements governing a permitted generic launch date.

A settlement could establish an authorized generic, a delayed generic entry date, or a license limited to particular formulations or indications. No settlement terms should be inferred solely from the existence of a patent or an FDA approval.

How does U.S. Patent 10,583,144 compare with competing migraine patents?

Protection category	U.S. Patent 10,583,144	Typical competing migraine patent
Active ingredients	Meloxicam plus rizatriptan	Often a CGRP antagonist, triptan, ditan, or NSAID
Main claim type	Treatment method	Composition, method, formulation, or salt
Delivery	Oral dosage form	Oral, injectable, nasal, or transdermal
Patient limitation	Inadequate response to prior treatment	May be broad adult migraine population
Pharmacokinetics	Rapid meloxicam Tmax and therapeutic exposure	Often absent or tied to delivery technology
Generic pathway	505(j) and Paragraph IV	505(j), with scope depending on listed claims
Biosimilar pathway	Not applicable	Not applicable for small molecules

The patent is more formulation-specific than a broad drug-combination patent. Its commercial value depends on whether the approved product and future generic labels map onto the claim limitations.

Key Takeaways

• U.S. Patent 10,583,144 claims a method using meloxicam-SBEβCD, bicarbonate, and rizatriptan for migraine.
• The patent is directed to a defined oral formulation and treatment population, not every meloxicam-rizatriptan product.
• Dependent claims cover commercially relevant quantities, including approximately 20 mg meloxicam, 100 mg SBEβCD, and 500 mg sodium bicarbonate.
• Claims 5, 6, 24, and 25 focus on faster meloxicam absorption and sub-two-hour or sub-90-minute Tmax performance.
• The patent is likely relevant to Symbravo, approved by the FDA in January 2025.
• The likely patent term reaches the mid-2030s, subject to the official term calculation and any extension.
• Generic applicants would likely use Paragraph IV, noninfringement, obviousness, written-description, enablement, or indefiniteness arguments.
• Biosimilar competition does not apply because the product is a small molecule.
• The strongest protection is against a close formulation copy using the same SBEβCD-bicarbonate absorption strategy.
• The principal risks are claim-construction disputes, prior-art obviousness challenges, and design-around formulations.

FAQs About U.S. Patent 10,583,144

Does U.S. Patent 10,583,144 cover rizatriptan alone?

No. The claims require a combination containing meloxicam complexed with SBEβCD, bicarbonate, and rizatriptan.

Does the patent cover a meloxicam-rizatriptan tablet without bicarbonate?

The supplied claims require bicarbonate in the dosage form. A product without bicarbonate would have a substantial literal noninfringement position against those claims, subject to any other patents in the family.

Is 20 mg meloxicam expressly protected?

Yes. Claim 11 recites approximately 20 mg of meloxicam. Claim 10 also covers a broader range of approximately 10 mg to 30 mg.

Is rizatriptan benzoate covered?

Yes. Claim 9 expressly recites rizatriptan benzoate, and claim 8 covers a salt amount equivalent to approximately 10 mg of rizatriptan free base.

Can a generic avoid the patent by changing the cyclodextrin?

Potentially. The claims specifically require SBEβCD. A formulation using a different cyclodextrin or another solubilization technology may avoid literal infringement, although other patent claims and regulatory requirements would remain relevant.

Does FDA approval make the patent valid?

No. FDA approval and patent validity are separate issues. A patent remains enforceable unless invalidated, rendered unenforceable, expired, or otherwise removed from the relevant legal framework.

References

1. U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,583,144, methods of treating migraine.
2. U.S. Food and Drug Administration. (2025). FDA approves Symbravo for acute treatment of migraine with or without aura in adults.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. U.S. Code, 21 U.S.C. § 355. (2024). New drugs and abbreviated new drug applications.
5. U.S. Code, 35 U.S.C. §§ 154, 156, 271, and 282. (2024). Patent term, patent-term extension, infringement, and presumptions of validity.
6. U.S. Patent and Trademark Office. (n.d.). Patent Center and Patent Examination Data System records.

Drugs Protected by US Patent 10,583,144

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 10,583,144

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