Details for Patent: 10,653,777

Which drugs does patent 10,653,777 protect, and when does it expire?

Patent 10,653,777 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: 10,653,777

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:	US16/688,491
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,653,777
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 10,653,777: Claim Scope, Exclusivity, Litigation, and AXS-07 Patent Landscape

U.S. Patent No. 10,653,777 protects a patient-treatment method using a fixed oral combination of meloxicam, sulfobutyl ether beta-cyclodextrin, bicarbonate, and rizatriptan. The broadest claim requires both a defined patient population and a clinical outcome: reduced nausea lasting at least 24 hours after administration. The patent does not cover meloxicam, rizatriptan, or sodium bicarbonate as standalone products. It targets the combination and its use in acute migraine treatment.

The patent is relevant to Axsome Therapeutics' AXS-07 program, an investigational oral migraine product combining meloxicam and rizatriptan. AXS-07 has not obtained FDA approval. No approved product currently provides an Orange Book listing or an approved generic pathway based on this patent.

What does U.S. Patent 10,653,777 protect?

The patent protects a method of treating migraine with a specific oral dosage form and a specified clinical response.

Claim 1 requires all of the following:

1. A human patient with migraine.
2. A history of inadequate response to prior migraine treatments.
3. Oral administration of the dosage form.
4. A meloxicam-SBEβCD complex.
5. A bicarbonate.
6. Rizatriptan.
7. Reduction in nausea lasting at least 24 hours after administration.

The claim is therefore narrower than a composition claim covering any tablet containing meloxicam and rizatriptan. A product containing the four ingredients may fall outside claim 1 if the accused use does not involve the specified patient history or does not produce the claimed nausea outcome.

The patent's dependent claims narrow the formulation and pharmacokinetic parameters:

Claim group	Protected limitation
Claims 2 and 23	400-600 mg bicarbonate; specifically 500 mg sodium bicarbonate in claim 23
Claims 3, 10-12, 19	Meloxicam ranges, including 5-50 mg, 10-30 mg, 20 mg, 15 mg, and 10-40 mg
Claims 4, 14-15	50-200 mg SBEβCD, including 50-150 mg and about 100 mg
Claims 7-9 and 19	Rizatriptan at 1-50 mg free-base equivalent, including a 10 mg equivalent and rizatriptan benzoate
Claims 13, 16-18	SBEβCD substitution level and approximately equimolar SBEβCD-to-meloxicam ratios
Claims 20-21	SBEβCD-to-rizatriptan weight ratios, including a ratio of about 10
Claims 5-6 and 24-25	Faster meloxicam absorption and a median meloxicam Tmax below 90 minutes or below two hours

The most commercially important embodiment is a solid oral dosage form containing approximately 20 mg meloxicam, 10 mg rizatriptan free-base equivalent, 100 mg SBEβCD, and 500 mg sodium bicarbonate.

How broad is claim 1 of Patent 10,653,777?

Claim 1 is a combination method claim with several cumulative limitations. Each limitation must generally be met for literal infringement.

Patient-selection limitation

The patient must have a history of inadequate response to prior migraine treatments. This limitation may distinguish the claimed method from general acute migraine treatment. It also creates proof issues because the prescriber, label, patient record, or clinical protocol must establish the prior-treatment history.

A generic manufacturer or competitor may argue that its product is prescribed broadly for acute migraine without selecting patients based on prior treatment failure. That argument would not automatically defeat infringement if the approved or promoted indication requires treatment of patients with inadequate response. The actual prescribing instructions and marketing conduct would matter.

Clinical-outcome limitation

The patient must experience reduced nausea lasting at least 24 hours. This is a demanding limitation because it requires a clinical result, not merely administration of the formulation.

The claim does not expressly require complete elimination of nausea. It requires a reduction in nausea lasting at least 24 hours. The patent specification and prosecution history would control the construction of terms such as "reduction," "nausea," and "lasts." Objective clinical data would likely be important in an infringement dispute.

The outcome limitation may strengthen validity against prior-art combination patents, but it can make enforcement more difficult. A patent owner would need to show that the accused method produces the claimed outcome, either through clinical evidence, labeling, promotional materials, or established pharmacologic data.

What formulations are protected by Patent 10,653,777?

The patent protects formulations using a meloxicam complex with SBEβCD, bicarbonate, and rizatriptan. The SBEβCD is not a generic cyclodextrin limitation. The claims specifically require sulfobutyl ether beta-cyclodextrin.

The principal formulation parameters are:

Component	Key claimed range or feature
Meloxicam	About 5-50 mg; narrower claims include 10-30 mg, 15 mg, and 20 mg
SBEβCD	About 50-200 mg; narrower claims include 50-150 mg and 100 mg
Bicarbonate	400-600 mg; specifically 500 mg sodium bicarbonate
Rizatriptan	About 1-50 mg free-base equivalent; about 10 mg salt-equivalent embodiment
SBEβCD substitution	About six to seven sulfobutyl ether groups per beta-cyclodextrin
SBEβCD:meloxicam molar ratio	About 0.5:1 to 2:1; narrower range 0.8:1 to 1.2:1; about 1:1
SBEβCD:rizatriptan weight ratio	About 1:1 to 100:1; narrower claim of about 10:1

The claims do not require a particular tablet manufacturing process, coating system, excipient, packaging configuration, or release profile unless those features are present in the specification or other claims. A formulation that uses a different solubilizer, omits bicarbonate, or substitutes a different triptan may avoid literal infringement, subject to equivalents analysis and other patent claims.

How do the pharmacokinetic claims affect infringement?

Claims 5, 6, 24, and 25 add absorption and pharmacokinetic limitations.

Claim 5 requires a solid oral dosage form with a shorter meloxicam Tmax than a reference formulation containing the same amount of meloxicam but lacking SBEβCD and bicarbonate. Claim 6 requires faster time to therapeutic plasma concentration compared with that reference.

Claims 24 and 25 require a median meloxicam Tmax below approximately 90 minutes or below two hours in fasted human subjects.

These claims create several technical questions:

• What reference formulation is used?
• Is the comparison made in the same subjects or in separate studies?
• Does "shorter Tmax" mean statistically shorter, numerically shorter, or merely less than the reference value?
• How is "therapeutic plasma concentration" defined?
• Does the claimed result need to be known before administration, or can it be established through later testing?

The claims may be useful against a competing formulation that copies the composition and demonstrates rapid absorption. They are less certain against a product where the sponsor does not disclose comparable pharmacokinetic data.

When does Patent 10,653,777 lose exclusivity?

U.S. Patent 10,653,777 was issued on May 19, 2020. Its ordinary patent term is tied to the relevant nonprovisional filing and priority history, not simply the issue date. Public patent records identify the patent as part of the AXS-07 meloxicam-rizatriptan technology area and show a priority history reaching the mid-2010s.[1]

The practical expiration date should be confirmed against the USPTO Patent Center record and any patent-term-adjustment calculation. A mid-2030s expiration is the reasonable commercial expectation for the patent family, subject to patent-term adjustment, terminal disclaimers, and any applicable extension. The patent cannot receive Hatch-Waxman patent-term extension unless the statutory requirements are met after an approved product and regulatory review period.

Because AXS-07 has not been approved, there is currently no approved-product exclusivity period attached to this patent. The patent provides potential technology exclusivity, but it has not created an FDA-recognized market monopoly.

Patent and regulatory exclusivity timeline

Event	Date or status
Core patent priority	Mid-2010s priority history reported in public patent records
U.S. patent issued	May 19, 2020
AXS-07 clinical development	Phase 3 program completed
AXS-07 NDA	Submitted to FDA and assigned NDA 214872
FDA regulatory status	Complete response letters issued; no approval
Orange Book status	No approved AXS-07 product listing identified
Generic entry	No FDA-approved ANDA entry based on AXS-07
Patent expiration	Expected in the mid-2030s, subject to USPTO term calculation

What is the Orange Book status of AXS-07 and Patent 10,653,777?

There is no Orange Book-listed approved drug product for AXS-07. Axsome submitted an NDA for AXS-07, but the FDA issued a complete response letter in 2022 concerning manufacturing and chemistry, manufacturing, and controls issues. The product was not approved for marketing.[2]

The Orange Book lists patents for approved drug products and does not function as a general registry for every pharmaceutical patent. Because AXS-07 lacks approval, Patent 10,653,777 does not currently operate as an Orange Book patent supporting a Paragraph IV certification against an approved reference listed drug.

This distinction is material. A patent may remain enforceable under ordinary patent law even when it is not listed in the Orange Book. The absence of an Orange Book listing, however, means that an ANDA applicant does not face the standard listed-patent certification process for AXS-07.

Which companies are challenging Patent 10,653,777?

No public, commercially significant Paragraph IV challenge against Patent 10,653,777 is identified in the available regulatory and litigation record. The principal reason is that AXS-07 has not reached the approved reference-product stage required for a conventional ANDA challenge.

A future generic or 505(b)(2) applicant could pursue several pathways:

Entry pathway	Potential patent issue
ANDA after approval	Paragraph IV challenge to listed patents, if the product becomes an RLD
505(b)(2) application	Patent certification and possible reliance on published clinical data
Non-infringing formulation	Avoidance of SBEβCD, bicarbonate, rizatriptan, or claimed ratios
Off-label or physician-directed use	Risk from induced infringement if use instructions promote the patented method
Competing combination product	Validity and infringement exposure under the full combination and outcome limitations

No identified settlement agreement or generic launch settlement involving this patent has been publicly reported.

What patent litigation affects AXS-07?

No major litigated decision concerning infringement or validity of U.S. Patent 10,653,777 is identified in the public record available for this analysis. The patent therefore has no established judicial claim construction, validity holding, or damages benchmark.

The main future litigation issues would likely be:

1. Whether the accused product contains a true meloxicam-SBEβCD complex.
2. Whether the bicarbonate and rizatriptan are present in the claimed amounts.
3. Whether the prescribed patient population satisfies the inadequate-response limitation.
4. Whether nausea reduction lasting 24 hours is attributable to the accused treatment.
5. Whether the pharmacokinetic comparison meets the claimed Tmax or therapeutic-concentration limitation.
6. Whether prior art discloses the same combination and clinical use.

The absence of litigation precedent reduces predictability. It does not, by itself, indicate that the patent is weak.

How strong is the patent estate for AXS-07?

The patent estate has a focused technical position rather than broad protection over all migraine combinations.

Strengths

• It combines composition, patient-selection, clinical-outcome, and pharmacokinetic limitations.
• The use of SBEβCD and bicarbonate is more specific than a basic meloxicam-rizatriptan combination claim.
• The 20 mg meloxicam and 10 mg rizatriptan embodiment maps to the principal AXS-07 clinical concept.
• The claims may distinguish prior art disclosing meloxicam or rizatriptan separately.
• Dependent claims provide multiple formulation positions if the broadest claim is narrowed.

Weaknesses

• Claim 1 is vulnerable to arguments that the claimed nausea result is an inherent or predictable consequence of known migraine therapy.
• The clinical-outcome limitation may raise enablement, written-description, or indefiniteness disputes depending on the specification and prosecution record.
• The individual active ingredients are old and widely available.
• Rizatriptan and meloxicam have no meaningful compound-level exclusivity remaining.
• A competitor may design around the SBEβCD or bicarbonate limitation.
• The patent does not necessarily block every meloxicam-rizatriptan formulation or every migraine-use method.
• No approved product currently supports Orange Book enforcement or commercial launch pressure.

The estate is strongest against an exact or near-exact AXS-07 copy using the claimed formulation and promoting treatment in the claimed patient population. It is weaker against a different fixed-dose combination, a different absorption technology, or a product without the claimed clinical-use instructions.

How does this patent compare with the legacy patents for meloxicam and rizatriptan?

Technology	Primary exclusivity type	Current position
Meloxicam molecule	Compound patent	Expired
Rizatriptan molecule	Compound patent	Expired
Rizatriptan benzoate	Salt and product protection	Expired or no longer commercially blocking in the U.S.
SBEβCD excipient technology	Formulation and solubilization technology	Depends on the specific patent family; many early rights are expired or narrow
Patent 10,653,777	Combination method and formulation-linked treatment	Potentially enforceable into the mid-2030s, subject to term and validity

The commercial value of Patent 10,653,777 comes from combining old ingredients in a specific delivery system and therapeutic-use protocol. It is not a compound patent.

What generic entry risks exist?

If AXS-07 were approved, generic entry would depend on whether a competitor copies the claimed formulation and seeks the same migraine indication.

An exact generic would face the greatest risk if its labeling recommends:

• use in patients inadequately responding to prior migraine therapy;
• a combination containing meloxicam, SBEβCD, bicarbonate, and rizatriptan;
• the claimed dose ranges;
• rapid meloxicam absorption; and
• relief of nausea lasting at least 24 hours.

A design-around product could reduce risk by changing the solubilizer, removing bicarbonate, using a different triptan, altering the meloxicam dose, or pursuing a different indication. Such changes could affect bioavailability and clinical performance.

A 505(b)(2) applicant may face a more complex risk profile because the applicant could rely on published data while developing a formulation that does not literally practice every claim limitation.

What manufacturing and geographic barriers apply?

The patent is a U.S. right. It does not directly block manufacture, sale, or use outside the United States. Equivalent patent families in Europe, Japan, Canada, and other markets would need separate review.

Manufacturing risk centers on:

• formation and characterization of the meloxicam-SBEβCD complex;
• uniform distribution of high-dose sodium bicarbonate;
• stability of rizatriptan benzoate with the other ingredients;
• tablet size and mechanical properties;
• dissolution and absorption performance;
• control of SBEβCD substitution level; and
• reproducibility of the claimed rapid Tmax.

Even if a competitor avoids literal infringement, reproducing the same pharmacokinetic profile may require comparable formulation know-how. That technical barrier is separate from patent enforceability.

What is the commercial exposure of Patent 10,653,777?

AXS-07 had no approved-product revenue at the time of the FDA complete response. Its commercial exposure is therefore prospective, not a currently protected revenue stream.

The patent could become commercially important if Axsome secures approval and demonstrates that the fixed combination offers a clinically meaningful advantage over separate administration of meloxicam and rizatriptan. Until approval, the patent's value is primarily strategic:

• it protects a differentiated formulation concept;
• it supports licensing or partnering discussions;
• it may deter direct copying during development;
• it preserves a potential mid-2030s exclusion period; and
• it provides leverage in future patent certification or litigation.

Key Takeaways

• U.S. Patent 10,653,777 is a method-of-treatment patent focused on an AXS-07-type migraine formulation.
• Claim 1 requires meloxicam-SBEβCD, bicarbonate, rizatriptan, a prior-treatment-failure patient population, and nausea reduction lasting at least 24 hours.
• The key commercial embodiment is approximately 20 mg meloxicam, 10 mg rizatriptan, 100 mg SBEβCD, and 500 mg sodium bicarbonate.
• The patent does not protect meloxicam or rizatriptan as standalone compounds.
• AXS-07 has not received FDA approval, and no Orange Book-listed product or approved generic pathway currently exists.
• No public Paragraph IV challenge, major infringement decision, or settlement involving this patent has been identified.
• The patent is strongest against an exact formulation and indication copy. Its enforcement position is less certain against a different solubilizer, triptan, dose, or treatment label.
• The expected patent term extends into the mid-2030s, subject to the USPTO's final patent-term calculation.

FAQs

Is Patent 10,653,777 a composition patent or a method patent?

It is principally a method-of-treating-migraine patent. The claims require administering the combination to a patient and, in claim 1, achieving a specified nausea-reduction outcome.

Does the patent block generic rizatriptan?

No. The patent does not block standalone rizatriptan or ordinary rizatriptan benzoate products. Its scope is limited to the claimed combination and treatment method.

Could a competitor avoid the patent by omitting sodium bicarbonate?

Potentially. Claims 22 and 23 specifically identify sodium bicarbonate, while claim 1 requires a bicarbonate generally. Omitting bicarbonate may avoid claim 1, but the full patent family and equivalents doctrine would require separate analysis.

Does FDA rejection cancel Patent 10,653,777?

No. An FDA complete response letter does not cancel an issued patent. The patent remains subject to ordinary validity, enforceability, maintenance-fee, and expiration rules.

Can a competitor sell meloxicam and rizatriptan as separate tablets?

Separate products may avoid the claimed dosage-form combination, but infringement risk would depend on the product labeling, physician instructions, induced-use theories, and any additional patents in the relevant family.

References

1. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,653,777, methods of treating migraine. https://patents.google.com/patent/US10653777B2/en

2. U.S. Food and Drug Administration. (2022). FDA issues complete response letter for AXS-07. FDA drug approval and regulatory communications database. https://www.fda.gov/

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

4. Axsome Therapeutics, Inc. (2023). Annual report on Form 10-K. U.S. Securities and Exchange Commission. https://www.sec.gov/edgar/browse/?CIK=0001627475

Drugs Protected by US Patent 10,653,777

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	10,653,777					ACUTE TREATMENT OF MIGRAINE

International Family Members for US Patent 10,653,777

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016218992
Australia	2018205790
Australia	2018265411
Australia	2019203328
Australia	2019297360
Australia	2020205306