US Patent 10,137,131: Scope, Claims, Expiration, and Patent Landscape for Meloxicam-Rizatriptan

US Patent No. 10,137,131 protects a solid oral migraine dosage form combining meloxicam, sulfobutyl ether beta-cyclodextrin, bicarbonate, and a triptan. The commercially relevant embodiment is a fast-acting combination of approximately 20 mg meloxicam, approximately 100-200 mg SBEβCD, approximately 500 mg sodium bicarbonate, and approximately 10 mg rizatriptan free-base equivalent.

The patent is associated with Axsome Therapeutics' AXS-07 program, which combines a solubility-enhanced meloxicam formulation with rizatriptan. Its strongest commercial position is the combination of composition, excipient ranges, rizatriptan identity and dose, and pharmacokinetic performance. The principal vulnerability is that claim 1 relies partly on comparative and clinical pharmacokinetic limitations rather than only on chemical composition. (U.S. Patent No. 10,137,131, 2018; Axsome Therapeutics, Inc., 2023).

What does US Patent 10,137,131 protect?

The patent has 29 claims divided into two groups:

Claim group	Claims	Protected subject matter
Composition claims	1-18	Solid oral dosage form containing meloxicam-SBEβCD complex, bicarbonate and triptan
Treatment claims	19-29	Treating migraine by administering the claimed dosage form

Claim 1 is the principal composition claim. It requires all of the following:

A complex of meloxicam with sulfobutyl ether beta-cyclodextrin.
Bicarbonate in an amount of 400 mg to 600 mg.
A triptan.
Meloxicam in an amount of approximately 5 mg to 50 mg.
SBEβCD in an amount of approximately 50 mg to 200 mg.
A solid oral dosage form.
A shorter meloxicam Tmax than a reference dosage form containing the same meloxicam amount but no SBEβCD and no bicarbonate.

The use of "comprising" makes the claims open-ended. An accused product can contain additional active ingredients, excipients, coatings, binders, disintegrants or manufacturing aids and still fall within the claim if it includes every required element.

Which claim is most important for infringement analysis?

Claim 1 is the broadest composition claim and establishes the core infringement test. Claims 2 through 18 narrow the claim through specific active ingredients, quantities and pharmacokinetic results.

The commercial target is likely the claim 2-5 chain:

Claim	Limitation
1	Meloxicam-SBEβCD complex, bicarbonate and triptan
2	Triptan is rizatriptan
3	Approximately 8-13 mg rizatriptan free-base equivalent
4	Salt amount equivalent to approximately 10 mg free-base rizatriptan
5	Rizatriptan benzoate

A product containing approximately 10 mg of rizatriptan free-base equivalent as rizatriptan benzoate, approximately 20 mg meloxicam, approximately 500 mg sodium bicarbonate and approximately 100-140 mg SBEβCD would map closely to claims 5, 7, 10 and 12.

What are the key dosage-form ranges?

The most commercially significant dependent claims are:

Ingredient or property	Broad range	Narrower claimed range
Meloxicam	Approximately 5-50 mg	Approximately 15-25 mg; approximately 20 mg
SBEβCD	Approximately 50-200 mg	Approximately 100-175 mg; approximately 100-140 mg
Bicarbonate	400-600 mg	Approximately 500 mg sodium bicarbonate
Rizatriptan	Triptan generally	Approximately 8-13 mg free-base equivalent; approximately 10 mg equivalent
SBE substitution	Not specified in claim 1	Approximately 6-7 sulfobutyl ether groups per beta-cyclodextrin
Meloxicam Tmax	Faster than reference	Less than 3, 2 or 1 hour
Meloxicam Cmax	Not specified in claim 1	At least 1,800 ng/mL
Meloxicam AUC0-6	Not specified in claim 1	At least 6,000 ng·hr/mL
Time to half-maximal concentration	Not specified in claim 1	Less than approximately 30 minutes

The claims do not require a specific tablet weight, tablet shape, coating, compression force, dissolution apparatus, manufacturing process or excipient system beyond the expressly required ingredients.

How does the SBEβCD limitation affect patent scope?

SBEβCD is not merely an optional solubilizer in the patent. Claim 1 requires a meloxicam complex with SBEβCD. A product containing meloxicam and SBEβCD as separate physical ingredients may avoid literal infringement if it does not contain the claimed complex, although the result would depend on the evidence and claim construction.

Claim 8 narrows the complex to SBEβCD having approximately 6-7 sulfobutyl ether groups per beta-cyclodextrin molecule. This limitation is directed to the degree of substitution of the cyclodextrin material. The commercial value of the claim depends on whether the relevant product uses a material within that substitution range and whether the specification defines how the average substitution is measured.

SBEβCD is widely used in pharmaceutical formulations, including injectable and oral solubilization systems. The patent's differentiation is therefore not the excipient alone. It is the combination of SBEβCD complexation with meloxicam, bicarbonate, a triptan and accelerated pharmacokinetics.

What pharmacokinetic results are required?

Claims 13-18 and 20-23 use clinical pharmacokinetic limitations. The principal thresholds are:

Median meloxicam Tmax below 3 hours.
Median meloxicam Tmax below 2 hours.
Median meloxicam Tmax below 1 hour.
Median meloxicam Cmax of at least 1,800 ng/mL.
Median meloxicam AUC0-6 of at least 6,000 ng·hr/mL.
Median time to half-maximal plasma concentration below approximately 30 minutes.

These limitations create both value and litigation risk.

A formulation that has the required composition may still dispute infringement of a pharmacokinetic-dependent claim if its clinical results do not meet the specified thresholds. Conversely, the broad claim 1 does not require the product to achieve a particular numerical Tmax. It requires a shorter Tmax than a defined reference dosage form.

The reference formulation is important. It must contain the same amount of meloxicam but lack both SBEβCD and bicarbonate. Evidence may be required to establish the comparator formulation, fasting conditions, human population, sampling schedule and statistical method used to determine median Tmax.

How strong is the patent estate for AXS-07?

The estate is strongest when viewed as a layered formulation portfolio rather than as a single patent.

Core composition protection

US 10,137,131 covers the central combination of:

Meloxicam;
SBEβCD;
Bicarbonate;
A triptan;
Solid oral administration; and
Accelerated meloxicam absorption relative to a defined reference.

Species protection

Claims 2-12 narrow the broad triptan concept to rizatriptan, rizatriptan benzoate, approximately 10 mg free-base equivalent, approximately 20 mg meloxicam, approximately 500 mg sodium bicarbonate and defined SBEβCD quantities.

These claims are easier to practice and test than the broad claim because the commercial formulation is expected to use a specific drug combination and approximate dose.

Pharmacokinetic protection

Claims 13-18 and 20-23 protect measured performance. These claims can be valuable against a product that copies the formulation architecture but modifies manufacturing, particle size or excipient processing to achieve similar exposure.

Their weakness is evidentiary. Pharmacokinetic claims depend on actual human data, batch selection, subject population and study design.

When does US Patent 10,137,131 expire?

The patent issued on November 27, 2018. Its earliest disclosed priority date is in 2015, and the patent term is generally calculated from the earliest effective nonprovisional filing date rather than from the grant date. The ordinary expected expiration is in 2035, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension. (U.S. Patent No. 10,137,131, 2018).

The patent should not be treated as providing a guaranteed 2035 exclusivity date without reviewing the USPTO patent-term calculation and the full continuation family. A continuation or divisional can have a different claim set but generally does not receive a new 20-year term.

What is the FDA and Orange Book status?

AXS-07 was submitted to the FDA as a new drug application for acute migraine treatment. The program received a complete response letter in 2022. Public company disclosures attributed the action to manufacturing deficiencies rather than a finding that the active ingredients were ineffective. (Axsome Therapeutics, Inc., 2022).

A key commercial consequence is that FDA approval and Orange Book listing determine the practical effect of the patent against ANDA applicants. A patent covering an unapproved product does not create an active generic-substitution barrier in the same way as a listed patent covering an approved reference listed drug.

Orange Book implications

The relevant questions are:

Issue	Effect
Approved reference listed drug	Required for an ANDA pathway
Orange Book patent listing	Enables a listed-patent Paragraph IV framework
Drug substance patent	May be listed if it meets FDA criteria
Formulation patent	May be listed if it claims the approved drug product
Method-of-use patent	May be listed for approved indications
Unapproved AXS-07	Limits immediate ANDA-driven litigation exposure
Future approval	Could activate listing and Paragraph IV litigation

No approved AXS-07 reference product means generic entry analysis must distinguish patent validity from regulatory exclusivity. The patent can remain enforceable even while the product lacks an approved commercial reference product, but an ANDA pathway may not be available until approval.

Which companies are challenging US 10,137,131?

No publicly established Paragraph IV challenge can be inferred solely from the patent number or the claim text. A Paragraph IV challenge requires an ANDA applicant, an FDA filing, a certification and, typically, litigation or a statutory notice process.

The likely challenger pool would include:

Generic manufacturers developing rizatriptan-meloxicam combinations;
Companies developing fast-acting oral meloxicam formulations;
Contract manufacturers supplying SBEβCD-based oral dosage forms;
Companies pursuing 505(b)(2) applications rather than ANDAs.

A 505(b)(2) applicant could face patent certification requirements, but its regulatory strategy would differ from a conventional ANDA because it may rely partly on published literature or an FDA-approved reference product.

What prior-art issues affect validity?

The patent combines several technologies that may individually have extensive prior art:

Meloxicam as a nonsteroidal anti-inflammatory drug.
Rizatriptan and other triptans for migraine.
Cyclodextrin inclusion complexes.
SBEβCD as a solubilizing excipient.
Bicarbonate-assisted dissolution or gastric delivery.
Combination treatment of migraine with an NSAID and a triptan.
Pharmacokinetic acceleration of meloxicam.

The validity question is therefore likely to focus on the combination and the claimed pharmacokinetic result. A challenger could argue:

Obviousness of combining meloxicam with a triptan for migraine;
Predictability of using SBEβCD to enhance meloxicam solubility;
Predictability of using bicarbonate to accelerate dissolution;
Lack of unexpected results across the full claimed ranges;
Insufficient written description for all triptans and all claimed concentration ranges;
Indefiniteness or ambiguity in "complex," "shorter Tmax" and "about";
Failure to demonstrate the claimed pharmacokinetic results across the full scope.

The patent holder would likely rely on the specific combination, the interaction between SBEβCD and bicarbonate, and clinical data showing rapid meloxicam absorption.

What generic entry risks exist?

Direct composition copy

A generic or follow-on product that copies the approximate AXS-07 composition has the highest literal infringement risk if it contains:

20 mg meloxicam;
10 mg rizatriptan free-base equivalent;
Rizatriptan benzoate;
500 mg sodium bicarbonate;
100-140 mg SBEβCD; and
A meloxicam-SBEβCD complex.

Excipient substitution

Replacing sodium bicarbonate with another bicarbonate salt may not avoid claim 1 because the claim recites "a bicarbonate." Claim 11 is narrower and specifies sodium bicarbonate, but claim 1 is broader.

Replacing SBEβCD with another cyclodextrin may avoid literal infringement of claim 1 because the claim specifically requires SBEβCD. The substitution could still raise doctrine-of-equivalents arguments, depending on the technical effect and prosecution history.

Dose engineering

Reducing meloxicam below 5 mg, increasing it above 50 mg, reducing bicarbonate below 400 mg or using less than 50 mg SBEβCD could avoid the literal numerical ranges. Such changes could also eliminate the commercial pharmacokinetic profile or therapeutic rationale.

Triptan substitution

Using sumatriptan, zolmitriptan, eletriptan or another triptan may avoid claims 2-5, but not necessarily claim 1. Claim 1 covers a triptan generically, subject to the other limitations.

What manufacturing and IP barriers matter?

The principal manufacturing barrier is not the tablet compression step. It is reproducibly producing the meloxicam-SBEβCD complex and maintaining rapid dissolution after combining it with a high bicarbonate load and a triptan salt.

Relevant technical controls include:

Degree of substitution of the SBEβCD;
Complexation method and stoichiometry;
Meloxicam particle size or amorphous content;
Moisture control;
Bicarbonate stability;
Gas evolution during manufacture or dissolution;
Tablet hardness and disintegration time;
Chemical compatibility between bicarbonate and rizatriptan benzoate;
Batch-to-batch Tmax and exposure.

A competitor may avoid one patent claim while still facing process know-how, formulation trade secrets, supplier qualification issues and separate family patents.

How does this patent compare with ordinary rizatriptan products?

Attribute	US 10,137,131 formulation	Conventional rizatriptan
Primary actives	Meloxicam plus rizatriptan	Rizatriptan alone
NSAID component	Required	Absent
SBEβCD	Required in core claim	Typically absent
Bicarbonate	Required in core claim	Typically absent
Therapeutic concept	Combined anti-inflammatory and serotonergic migraine treatment	Triptan-mediated migraine treatment
Patent risk	Combination and formulation claims	Rizatriptan product and method claims
Regulatory route	New combination product or 505(b)(2) strategy	Approved drug or generic route

The patent does not broadly block ordinary rizatriptan products that lack meloxicam, SBEβCD and bicarbonate. Its commercial reach is concentrated on fast-acting combination products.

Key Takeaways

US 10,137,131 protects a solid oral dosage form combining meloxicam-SBEβCD, bicarbonate and a triptan.
The commercially important species is approximately 20 mg meloxicam, approximately 10 mg rizatriptan free-base equivalent, approximately 500 mg sodium bicarbonate and approximately 100-140 mg SBEβCD.
Claims 1-12 provide composition coverage; claims 13-18 add pharmacokinetic performance; claims 19-29 cover migraine treatment.
The patent's ordinary expected term reaches into 2035, subject to USPTO term calculations and any extension or disclaimer.
AXS-07 received an FDA complete response letter in 2022, which affects current Orange Book and ANDA exposure.
The main validity issues are obviousness, written description, indefiniteness and proof of pharmacokinetic performance across the claimed ranges.
Generic design-around options include replacing SBEβCD, changing the bicarbonate system, substituting another triptan or moving outside the claimed dose ranges.
A product that copies the AXS-07 formulation and clinical performance has the highest infringement risk.

FAQs

Does US 10,137,131 cover meloxicam alone?

No. The claims require a combination dosage form containing meloxicam with SBEβCD, bicarbonate and a triptan.

Does the patent cover sumatriptan?

Claim 1 recites a triptan generally, so sumatriptan could fall within the broad composition claim if all other elements are present. The narrower claims directed to rizatriptan would not cover sumatriptan.

Can a product avoid the patent by replacing sodium bicarbonate with potassium bicarbonate?

It may avoid claims specifically limited to sodium bicarbonate, such as claim 11, but claim 1 recites a bicarbonate generally and could still be relevant.

Is a meloxicam-rizatriptan product automatically an AXS-07 product?

No. A product would need to match the relevant formulation, excipient, dosage-form and performance limitations. The brand or active-ingredient combination alone does not establish infringement.

Does FDA nonapproval invalidate US Patent 10,137,131?

No. FDA approval and patent validity are separate issues. Nonapproval affects commercial launch, Orange Book listing and generic regulatory pathways, but it does not by itself cancel the patent.

References

Axsome Therapeutics, Inc. (2022). Axsome Therapeutics receives complete response letter from FDA for AXS-07 new drug application. Company press release.
Axsome Therapeutics, Inc. (2023). Annual report on Form 10-K for the fiscal year ended December 31, 2022. U.S. Securities and Exchange Commission.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov
U.S. Patent No. 10,137,131. (2018). Pharmaceutical compositions comprising meloxicam and a triptan. United States Patent and Trademark Office.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension records. https://www.uspto.gov

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	⤷ Start Trial	⤷ Start Trial	Y			ACUTE TREATMENT OF MIGRAINE	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

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

Details for Patent: 10,137,131

Which drugs does patent 10,137,131 protect, and when does it expire?

Summary for Patent: 10,137,131