Details for Patent: 10,987,358

Which drugs does patent 10,987,358 protect, and when does it expire?

Patent 10,987,358 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: 10,987,358

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:	US16/857,435
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,987,358
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 10,987,358: Scope, Claim Strength, and US Landscape for Meloxicam + Rizatriptan Combination for Acute Migraine With Nausea

What does US Drug Patent 10,987,358 claim, at a structural level?

US 10,987,358 is a method-of-treatment patent for acute migraine (pain and/or aura) that combines meloxicam (NSAID) with rizatriptan (triptan) using specific dose ranges and pharmacokinetic constraints for meloxicam exposure and absorption timing, plus a clinical outcome comparator focused on nausea relief (and dependent migraine pain reduction).

At the independent-claim layer, the patent has two distinct administration formats:

• Claim set A (Claim 1): single dosage form

  • Meloxicam + rizatriptan in one dosage form.
  • Administration results in:
  • Meloxicam Tmax ≤ 110 minutes
  • Meloxicam AUC0-24 ~ 30 to 50 μg·hr/mL
  • Outcome:
  • In patients with migraine pain accompanied with nausea, at 2 hours patients experience greater relief from nausea versus receiving the same amount of meloxicam alone (control comparator).

• Claim set B (Claim 16): separate dosage forms but simultaneously administered

  • Meloxicam and rizatriptan are in separate dosage forms but taken simultaneously.
  • The same meloxicam PK cutoffs and the same nausea comparator at 2 hours.

Across the remaining claims, the patent narrows to:

• Rizatriptan salt forms (notably rizatriptan benzoate) and molar-equivalent dosing tied to a 10 mg free base equivalent.
• Fixed or narrower meloxicam ranges (notably ~20 mg, and generally 15–25 mg).
• Patient selection factors (history of inadequate response to prior migraine treatments).
• Additional dependent clinical outcome claim language for greater reduction in migraine pain at 2 hours vs either meloxicam alone or rizatriptan alone.

Key point for freedom-to-operate (FTO): the enforceable core is not only “meloxicam + rizatriptan for migraine,” but a very specific PK profile for meloxicam plus a two-hour relative nausea benefit claim frame, with format-specific claim coverage (single form vs separate forms taken simultaneously).

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What are the independent claim scopes (Claims 1 and 16)?

Claim 1 (single dosage form)

Claim 1 defines a migraine treatment method with all of the following limitations:

1. Indication and timing
   • Treat acute attack of migraine pain or migraine aura.
2. Dose selection
   • Administer meloxicam with about 8 mg to about 13 mg of rizatriptan, defined as a dose “based upon the weight of the free base form of rizatriptan.”
3. Form factor
   • Meloxicam and rizatriptan are in a single dosage form.
4. Meloxicam PK targets
   • Tmax of meloxicam ≤ 110 minutes
   • AUC0-24 of meloxicam about 30 to about 50 μg·hr/mL
5. Patient symptom context
   • Migraine pain is accompanied with nausea.
6. 2-hour relative outcome comparator
   • At 2 hours, greater relief from nausea than would occur after receiving the same amount of meloxicam without rizatriptan.

Claim 16 (separate dosage forms, simultaneously administered)

Claim 16 includes largely the same treatment architecture, except:

• Form factor
  • Meloxicam and rizatriptan are administered simultaneously but in separate dosage forms.
• Everything else is carried forward:
  • Rizatriptan dose range ~8–13 mg (free base weight basis)
  • Meloxicam PK constraints (Tmax ≤ 110 minutes; AUC0-24 ~ 30–50 μg·hr/mL)
  • Nausea context
  • 2-hour relative nausea relief vs meloxicam alone

Practical scope implication: A challenger cannot avoid infringement merely by selling two products (meloxicam and rizatriptan) if the regimen is marketed and used as simultaneous administration meeting the same meloxicam PK and clinical comparator framing.

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How do dependent claims narrow risk by salt form, exact dose, and patient selection?

The dependent claims tighten the independent claims along four axes: salt form, dose, selection criteria, and additional efficacy endpoints.

Rizatriptan salt form and molar-equivalent dosing

• Claim 2 / 17 / 24
  • Rizatriptan is in a salt form in an amount that is a molar equivalent to about 10 mg free base.
• Claim 3 / 18
  • Rizatriptan is specifically rizatriptan benzoate.

This matters because “about 8 to about 13 mg free base equivalent” in the independent claims is broad enough to capture multiple salt/mass combinations. Dependent claims then anchor to the molar-equivalent ~10 mg free base construct and to a specific salt identity.

Meloxicam dose narrowing

• Claim 4 / 19 / 25
  • ~15 mg to ~25 mg meloxicam.
• Claim 5 / 11 / 20 / 26
  • ~20 mg meloxicam.

So the strongest infringement targets (highest probability of meeting both PK ranges and clinical effects) are likely regimens built around the 20 mg meloxicam dose, especially if the formulation is engineered to yield Tmax ≤ 110 minutes and AUC0-24 ~30–50 μg·hr/mL.

Patient selection

• Claim 7 / 8 / 22 / 23
  • Human has a history of inadequate response to prior migraine treatments, and some claims frame selection for such history.

If a product is designed for broad migraine use, the independent claim does not require prior inadequate response. But if promotional or prescriber instructions include selection criteria, dependent claims become more relevant.

Additional efficacy comparator endpoint (pain reduction)

• Claim 14 and 29
  • Greater reduction in migraine pain at 2 hours vs would have occurred after receiving the same amount of meloxicam without rizatriptan.
• Claim 15 and 30
  • Greater reduction in migraine pain at 2 hours vs would have occurred after receiving the same amount of rizatriptan without meloxicam.

These add alternative infringement pathways if a regimen is evaluated or claimed under pain-reduction endpoints rather than nausea relief alone. But the independent claims already include the nausea relief comparator; the pain reduction claims offer additional dependent hooks.

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Where is the true claim “pressure point”? (PK limits + 2-hour comparator)

The combination of:

• Meloxicam Tmax ≤ 110 minutes
• Meloxicam AUC0-24 ~ 30–50 μg·hr/mL
• plus a 2-hour relative nausea relief comparator vs meloxicam alone

creates a claim structure that is harder to design around than a simple “use two drugs together” concept.

From an infringement analysis standpoint, the enforceability hinges on whether the accused regimen:

1. Produces meloxicam systemic exposure and rate consistent with the defined PK ranges.
2. Is used in a patient population where nausea relief is an observed and claimed outcome.
3. Relies on a regimen effect at the 2-hour timepoint framed as “greater relief than meloxicam alone.”

This tends to favor:

• formulations engineered for controlled absorption and consistent exposure,
• and clinical study designs that measure 2-hour nausea relief relative to monotherapy comparators.

It also tends to complicate:

• attempts to argue non-infringement based solely on label language, if the actual dosing behavior and formulation PK match the claim.

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What is covered and what is not (based on the textual limitations)?

Covered

• Acute migraine attacks (pain and/or aura) treated with:
  • meloxicam + rizatriptan at the specified dose windows,
  • in either single-form or simultaneous separate-form formats.
• The patient must have migraine pain accompanied with nausea.
• The regimen must meet meloxicam PK thresholds (Tmax and AUC0-24).
• The method must produce a greater 2-hour nausea relief relative to meloxicam alone.

Not necessarily covered

• Regimens where rizatriptan is not administered within the recited dose range.
• Regimens where meloxicam PK does not land within the AUC and Tmax constraints.
• Migraine pain without nausea (because independent claims require nausea accompaniment).
• Non-simultaneous co-administration (for Claim 16, the separate-form limitation specifies simultaneous administration).

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Patent landscape and likely design-around/avoidance strategies (US-focused, claim-anchored)

Without the underlying patent document (publication number, applicants, filing dates, prosecution history, related patents, and cited prior art), a complete US landscape map across all family members and all relevant continuations cannot be constructed to the standard required for an investment-grade “patent landscape” report.

Still, the claim text itself indicates where the risk concentrates in the competitive landscape:

1. Fixed formulation and dose-form engineering
   • Any competitor building meloxicam + rizatriptan co-products will need to ensure either:
     • their meloxicam formulation PK profile misses the Tmax ≤ 110 minutes and/or AUC0-24 30–50 windows, or
     • their clinical outcome framing does not meet the “greater relief from nausea at 2 hours” comparator logic.
2. Timing and dosing behavior
   • For separate dosage forms, simultaneity is a limitation. Competitors can reduce claim adjacency by using staggered regimens or different dosing intervals, assuming that design is consistent with their marketing and real-world administration.
3. Population and endpoint selection
   • The independent claims require nausea accompaniment and a 2-hour nausea relief comparison. Competitors that position the regimen around different patient phenotypes or different time endpoints may have a lower likelihood of fitting the claim structure, though that depends on how physicians actually use the regimen and what evidence supports it.
4. Salt form and dose equivalence
   • If marketed as a rizatriptan salt formulation, the dependent claim anchors to rizatriptan benzoate and molar-equivalent to 10 mg free base. This increases risk for any product launched around that standard conversion.

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How to read enforceability risk for a competitor portfolio

For a company considering an “NSAID + triptan” acute migraine product approach in the US, the enforceability risk for this patent is highest when the competitor has all of the following:

• A co-administered regimen where:
  • meloxicam dose is in the 15–25 mg band or around 20 mg, and
  • rizatriptan dose corresponds to ~8–13 mg free base equivalent (and particularly molar-equivalent ~10 mg free base).
• A formulation and/or co-product design that yields:
  • meloxicam Tmax ≤ 110 minutes
  • meloxicam AUC0-24 ~30–50 μg·hr/mL
• Clinical evidence (or at least label/DS) supporting:
  • 2-hour nausea relief superiority vs meloxicam alone.

Risk decreases most sharply if the competitor’s meloxicam formulation misses either the Tmax or AUC window, or if the regimen’s real-world administration is not simultaneous (for the separate-form scenario), or if the regimen is not used in nausea-accompanied migraine populations.

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Claim-by-claim scope matrix (operational view)

Claim	Administration format	Rizatriptan dose constraint	Meloxicam PK constraint	Required patient feature	Required 2-hour comparative endpoint
1	Single dosage form	~8–13 mg free base equivalent	Tmax ≤ 110 min; AUC0-24 ~30–50 μg·hr/mL	Nausea with migraine pain	Greater nausea relief vs same meloxicam alone
2	Adds	Salt form; amount molar eq to ~10 mg free base	Same	Same	Same
3	Adds	Rizatriptan benzoate	Same	Same	Same
4	Adds	Same	Same	Same	Same
5	Adds	Same	Same	Same	Same
6	Adds	Same	Same	Same	Same
7-8	Adds	Same	Same	History inadequate response; or selection	Same nausea comparator
9-11	Adds	Salt and dose narrowing	Same	Same	Same
12	Adds	Same	Same	Same	Same (instructions to take when acute attack occurs)
13	Adds	Same	Same	Selection with nausea with migraine pain	Same
14	Adds	Same	Same	Same	Greater migraine pain reduction vs meloxicam alone
15	Adds	Same	Same	Same	Greater migraine pain reduction vs rizatriptan alone
16	Separate dosage forms, simultaneous	~8–13 mg free base equivalent	Same	Nausea with migraine pain	Greater nausea relief vs same meloxicam alone
17-18	Adds	Salt form; then rizatriptan benzoate	Same	Same	Same
19-21	Adds	Meloxicam 15–25; then ~20 mg; then meloxicam free base	Same	Same	Same
22-23	Adds	Same	Same	History inadequate response; or selection	Same
24-26	Adds	Salt and meloxicam narrowing	Same	Same	Same
27	Adds	Same	Same	Same	Instructions for acute attack timing
28	Adds	Same	Same	Selection with nausea with migraine pain	Same
29	Adds	Same	Same	Same	Greater migraine pain reduction vs meloxicam alone
30	Adds	Same	Same	Same	Greater migraine pain reduction vs rizatriptan alone

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Key Takeaways

1. US 10,987,358 is a formulation- and exposure-driven method patent, not merely a combination-of-actives patent: it locks in meloxicam Tmax ≤ 110 minutes and AUC0-24 ~30–50 μg·hr/mL plus 2-hour nausea relief superiority versus meloxicam alone.
2. Two independent administration formats are covered: (i) single dosage form (Claim 1) and (ii) separate dosage forms administered simultaneously (Claim 16).
3. Dependent claims tighten into specific commercial design points: meloxicam 15–25 mg and particularly ~20 mg, rizatriptan salt forms and rizatriptan benzoate, and patient selection by history of inadequate response.
4. FTO risk is highest for competitors who launch a regimen that both meets the meloxicam PK window and is clinically positioned to show faster nausea relief at 2 hours versus meloxicam monotherapy.
5. Avoidance is most plausible through deliberate divergence in meloxicam exposure kinetics (Tmax/AUC) or through dosing behavior that defeats the “single form” or “simultaneous” limitation tied to the chosen claim set.

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FAQs

1. Does the patent require proof that the patient has nausea at treatment time?
   Yes. The independent claims require the human being has migraine pain “accompanied with nausea.”

2. Is simultaneity required when meloxicam and rizatriptan are in separate dosage forms?
   Yes. Claim 16 requires administering them “simultaneously” while keeping them in separate dosage forms.

3. What parameter most directly constrains formulation design?
   Meloxicam PK: Tmax ≤ 110 minutes and AUC0-24 about 30–50 μg·hr/mL.

4. Which rizatriptan dosing anchor is emphasized in dependent claims?
   Rizatriptan salt forms in an amount that is a molar equivalent to about 10 mg free base, with rizatriptan benzoate called out in dependent claims.

5. Can a competitor argue non-infringement by focusing only on pain relief rather than nausea?
   The independent claims require the 2-hour nausea relief comparator. Pain reduction endpoints appear in dependent claims, which do not remove the independent nausea requirement.

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References

1. US Patent 10,987,358, “method of treating migraine” (claims as provided in prompt).

Drugs Protected by US Patent 10,987,358

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	10,987,358					ACUTE TREATMENT OF MIGRAINE

International Family Members for US Patent 10,987,358

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