Details for Patent: 10,517,950

Which drugs does patent 10,517,950 protect, and when does it expire?

Patent 10,517,950 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: 10,517,950

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:	US16/567,859
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,517,950
Patent Claim Types: see list of patent claims	Use; Dosage form;

Scope and Claim Analysis for US Patent 10,517,950: Oral Migraine Treatment Using Meloxicam-SBEβCD, Bicarbonate, and Rizatriptan

Executive summary: US 10,517,950 claims a tightly defined oral migraine-treatment method that combines (i) a meloxicam–sulfobutyl ether β-cyclodextrin (SBEβCD) complex, (ii) a bicarbonate component, and (iii) rizatriptan, with a clinical outcome constraint requiring the patient to be “free of nausea two hours” post dosing. Dependent claims narrow the regimen by specifying quantitative component ranges (bicarbonate 400–600 mg; meloxicam ~5–50 mg; SBEβCD ~50–200 mg; rizatriptan ~1–50 mg; typical benzoate salt form; SBEβCD substitution ~6–7 sulfobutyl ether groups; and specific SBEβCD:meloxicam and bicarbonate specifics) and by requiring faster meloxicam absorption (shorter Tmax versus a reference product lacking SBEβCD and bicarbonate, with median Tmax targets <90 minutes or <2 hours in fasted subjects). The enforceable core is the specific three-component formulation architecture and the method outcome, with the largest potential design-around space located in the clinical outcome wording (“free of nausea” at 2 hours) and in substituting or removing any one of the three structural elements (complex, bicarbonate, or rizatriptan salt form), or materially changing absorption kinetics beyond the claimed comparison.

---

What is US Patent 10,517,950 and what do the claims actually cover?

US 10,517,950 is directed to a method of treating migraine using an orally administered dosage form comprising a defined formulation system and a defined patient-treatment context, plus a time-linked clinical endpoint.

Core independent claim 1: three-part formulation plus a 2-hour clinical endpoint

Claim 1 requires all of the following:

1. Patient selection and prior failure context

   • “selecting a human migraine patient with a history of inadequate response to prior migraine treatments”

2. Route and dosage form

   • “orally administering a dosage form”

3. The dosage form must contain a combination of three components in a specific architecture

   • (a) Complex of meloxicam with SBEβCD
     • “a complex of meloxicam with a sulfobutyl ether β-cyclodextrin (SBEβCD)”
   • (b) Bicarbonate
     • “a bicarbonate”
   • (c) Rizatriptan
     • “and a rizatriptan”

4. A clinical outcome timed to 2 hours

   • “wherein the human migraine patient is free of nausea two hours after the dosage form is orally administered”

Functional meaning for scope: claim 1 is both formulation-anchored (meloxicam–SBEβCD complex + bicarbonate + rizatriptan in one oral dosage form) and outcome-anchored (nausea-free status at a specified time point).

Dependent claim narrowing: quantitative and technical limits

Claims 2–25 narrow claim 1 in three ways:

1. Dose quantity ranges for each component (bicarbonate, meloxicam, SBEβCD, rizatriptan)
2. Technical characterization of SBEβCD substitution (6–7 sulfobutyl ether groups)
3. Absorption kinetics requirements using a specific “reference dosage form” comparison
4. Salt form specification for rizatriptan (rizatriptan benzoate)
5. Specific bicarbonate identity and quantity
6. Weight ratio constraints linking SBEβCD to rizatriptan
7. Specific median Tmax targets in fasted subjects

---

How broad is the claim scope: formulation architecture, patient selection, and clinical endpoint?

Patient selection limitation: “history of inadequate response”

This is a method claim; infringement depends on whether the treated population matches the selection criterion. The limitation is not merely “migraine patient,” but a subset: inadequate response to prior migraine treatments.

Practical effect: If an accused method treats patients without confirming inadequate prior response history, it may fall outside the claim as written.

Clinical endpoint limitation: “free of nausea two hours after”

This is the most unusual and potentially most decisive limitation from a scope perspective. It requires a binary patient condition at a fixed post-dose time.

Practical effect: A product could be compositionally similar but not yield the claimed outcome at 2 hours under the accused-use protocol and assessment method.

Formulation architecture limitation: all three elements must be present

The claim requires the dosage form contains:

• meloxicam–SBEβCD complex,
• bicarbonate,
• rizatriptan.

Practical effect: Removing any element creates a direct avoidance lever:

• no SBEβCD complex, or
• no bicarbonate, or
• no rizatriptan (or not in the claimed oral dosage form).

---

What exact formulation components are claimed: meloxicam–SBEβCD complex, bicarbonate, and rizatriptan?

Meloxicam–SBEβCD complex: what is required?

The claims require a complex of meloxicam with SBEβCD. The dependent claim 13 adds a specific structural characteristic of the SBEβCD:

• Claim 13: SBEβCD has about 6 to about 7 sulfobutyl ether groups per β-cyclodextrin molecule.

This ties the complex to a particular degree of substitution (DS).

Scope impact:

• Claim 1 does not state DS.
• Claim 13 creates a narrower, potentially separate infringement trigger only when DS matches.

Bicarbonate: identity and amount constraints

• Claim 2: bicarbonate 400–600 mg
• Claim 22: bicarbonate comprises sodium bicarbonate
• Claim 23: oral dosage form contains 500 mg sodium bicarbonate

Scope impact:

• Claim 1 only requires “a bicarbonate,” broadly.
• Dependent claims anchor to sodium bicarbonate and specific dosage.

Rizatriptan: amount and salt

• Claim 7: rizatriptan about 1 mg to 50 mg based on free base weight
• Claim 8: rizatriptan salt amount equals molar equivalent of about 10 mg free base
• Claim 9: rizatriptan present as rizatriptan benzoate
• Claim 10–12: meloxicam dose specifics also imply typical combined ratios
• Claim 19: meloxicam and rizatriptan ranges simultaneously
• Claims 20–21: weight ratio of SBEβCD to rizatriptan

Scope impact:

• Claim 1 is not restricted to benzoate salt, but Claim 9 is.
• A generic developer could attempt to use a different rizatriptan salt form (if clinically acceptable) as a design-around if the infringement analysis turns on dependent-claim pathways.

---

What are the quantitative claim ranges for meloxicam, SBEβCD, bicarbonate, and rizatriptan?

Component dose ranges and ratios (from dependent claims)

Claim	Parameter	Claimed range / specificity
2	Bicarbonate	400 mg to 600 mg
3	Meloxicam	~5 mg to ~50 mg
4	SBEβCD	~50 mg to ~200 mg
7	Rizatriptan (free base basis)	~1 mg to ~50 mg
10	Meloxicam (band)	10 mg to 30 mg
11	Meloxicam	~20 mg
12	Meloxicam	~15 mg
14	SBEβCD (band)	50 mg to 150 mg
15	SBEβCD	~100 mg
16–18	SBEβCD:meloxicam molar ratio	0.5–2; 0.8–1.2; or ~1
19	Combined band	meloxicam 10–40 mg and rizatriptan 5–50 mg
20–21	SBEβCD:rizatriptan weight ratio	1–100; or about 10
23	Sodium bicarbonate	500 mg
13	SBEβCD substitution	~6 to ~7 sulfobutyl ether groups

Interpretation for enforcement strategy

• The independent claim 1 does not require a particular bicarbonate dose, meloxicam dose, or SBEβCD dose, as long as the dosage form includes those components in the required architecture and achieves the nausea-free 2-hour endpoint.
• Dependent claims create narrower “sweet spots” where infringement is more straightforward for a product that matches known formulation targets (e.g., 500 mg sodium bicarbonate; ~20 mg meloxicam; ~100 mg SBEβCD; rizatriptan as benzoate).

---

How do the claims use Tmax comparisons: what is the “reference dosage form” and what kinetic thresholds are required?

Claims 5–6: faster absorption requirement with defined reference

• Claim 5 requires the solid oral dosage form has shorter Tmax of meloxicam than a reference product that:
  1. has the same amount of meloxicam
  2. does not contain SBEβCD
  3. does not contain bicarbonate

This makes the absorption-kinetics claim dependent on a comparative study against a specifically defined reference formulation.

• Claim 6 states faster time to therapeutic plasma concentration versus that reference product.

Claims 24–25: fasted median Tmax targets

• Claim 24: median Tmax of meloxicam < about 90 minutes in fasted humans
• Claim 25: median Tmax of meloxicam < about 2 hours in fasted humans

Scope impact:

• Even if a competitor matches the compositional elements, failure to demonstrate the claimed kinetic improvement relative to the defined reference (or not reaching these median Tmax thresholds) can support non-infringement of the dependent kinetic claims.

---

Which aspects are the primary “enforceability drivers” in US 10,517,950?

1. Presence of all three formulation elements in one oral dosage form

   • meloxicam–SBEβCD complex
   • bicarbonate
   • rizatriptan

2. Patient selection context

   • inadequate response history

3. 2-hour nausea-free outcome

   • operationally constraining for method infringement

4. Absorption kinetics comparison (for dependent claim pathways)

   • faster meloxicam Tmax versus a reference lacking SBEβCD and bicarbonate

5. SBEβCD substitution and salt form (for dependent claims)

   • DS 6–7 and rizatriptan benzoate, which can narrow enforcement if competitors select different materials or salts.

---

What design-around pathways exist based on claim language?

1) Remove or substitute one structural element

• Omit bicarbonate entirely
• Omit SBEβCD complexing step/material
• Replace rizatriptan with another triptan (outside claim scope)
• Use an oral dosage form where meloxicam is not administered as a meloxicam–SBEβCD complex

2) Change the clinical outcome profile at the 2-hour time point

Because Claim 1 requires “free of nausea two hours after,” a competitor could attempt to:

• use the same architecture but with altered release/absorption leading to nausea persistence at 2 hours in the studied endpoint window, or
• treat and measure endpoints in a manner that does not meet the claim’s “free of nausea” requirement.

This is often harder to engineer because it ties to clinical response and tolerability, not only PK.

3) Navigate around dependent-claim formulation quantitation

If the product does not match dependent ranges, it may still fall under Claim 1 if composition architecture and endpoint are met. But if Claim 1 is disputed, matching or deviating from dependent ranges can shift the infringement focus.

4) Navigate around kinetic dependent claims

Even if compositional elements are present, avoiding the claimed “shorter Tmax” requirement versus the defined reference product can help for Claims 5–6 and, if applicable, Claims 24–25.

5) Navigate around DS and salt form dependent claims

• Use an SBEβCD material with a DS outside 6–7 (to avoid Claim 13)
• Use a different rizatriptan salt than benzoate (to avoid Claim 9)

These do not negate Claim 1 unless the DS or salt form becomes central to proving the meloxicam–SBEβCD complex and the asserted architecture.

---

How would claim construction likely handle “complex of meloxicam with SBEβCD”?

The claim requires a complex. In litigation, the key question typically becomes whether the accused product contains:

• a true inclusion complex,
• a molecular association consistent with “complex” as understood by the patent, and
• whether formulation/process yields a complex at the relevant stage (solid state or upon administration).

The presence of SBEβCD plus meloxicam does not automatically mean “complex” unless the claims or patent specification define it. Since the prompt provides only claim text, the enforcement will hinge on how “complex” was defined in the patent’s specification and how the accused product is characterized.

---

What does this mean for generic entry risk and FDA pathway strategy?

Labeling and method-of-use constraints

Because the claims are framed as a method of treating migraine with a specific patient selection criterion and a clinical endpoint, a generic’s main exposure is if its “intended use” and clinical effect align with the claimed method. If the formulation is compositionally similar and the clinical endpoint is achievable under typical dosing, method claims can still be asserted even when the drug is marketed for migraine broadly.

Practical risk drivers for Paragraph IV style challenges

• If an ANDA or 505(b)(2) applicant seeks approval for a product that matches the compositional architecture and typical clinical effects, it can face higher risk of infringement theories tied to endpoint and formulation.
• If the applicant designs a product that avoids the claimed architecture (bicarbonate removal; no SBEβCD complex; different triptan approach) the infringement risk declines at the independent-claim level.

Settlement leverage

In practice, method claims that hinge on clinical endpoints can create negotiation leverage around evidence of nausea outcomes at 2 hours, endpoint definition, and study design used in the parties’ noninfringement/infringement positions.

---

How does US 10,517,950 compare against common migraine combination strategies (enforcement-relevant angles)?

Even without tying to specific third-party patents, the enforcement structure here is atypical compared with standard formulation patents:

• Many migraine patents cover drug combinations (e.g., triptans plus antiemetic or NSAID) without requiring a fixed patient endpoint at an exact time.
• Here, the combination is not only with an NSAID but with a specific solubilization/complexing system (SBEβCD) and an alkalinizing agent (bicarbonate) tied to improved meloxicam absorption and tolerability.

Net effect: The patent is drafted to capture both:

• delivery technology (meloxicam–SBEβCD complex + bicarbonate enabling faster Tmax), and
• patient tolerability (nausea-free status at 2 hours).

---

How strong is the patent estate for US 10,517,950 based on claim structure alone?

Strength is driven by three factors:

1. Multiple orthogonal constraints

   • formulation architecture
   • clinical endpoint
   • absorption kinetics comparison (in dependent claim paths)

2. Broad independent claim coverage with outcome anchor

   • Claim 1 is not limited to specific component amounts or Tmax thresholds, which broadens compositional coverage if endpoint is met.

3. Tight dependent-claim specifics

   • Quantitative ranges, DS, salt form, and median Tmax targets make it easier to map evidence onto the claims for an accused product that matches the patent’s intended formulation target.

---

What needs to be mapped in infringement analysis for US 10,517,950? (Claim-to-evidence checklist)

For Claim 1 (most important), infringement analysis must map:

• Product composition

  • meloxicam–SBEβCD complex
  • bicarbonate present
  • rizatriptan present in the oral dosage form

• Method practice

  • patient with inadequate response history
  • administration of the dosage form orally

• Clinical outcome

  • patient “free of nausea” at 2 hours post dose

For Claim 5 / 6, map:

• meloxicam Tmax in humans for the solid oral dosage form
• a defined reference comparator lacking SBEβCD and bicarbonate but containing same meloxicam amount

For Claims 13, 9, 2, 3, 4, 7, 22, 23, 24, 25, map:

• specific numeric amounts, DS, salt form, and fasted median Tmax criteria.

---

Key Takeaways

• US 10,517,950 is enforceable as a method-of-use claim that combines a specific oral formulation architecture (meloxicam–SBEβCD complex + bicarbonate + rizatriptan) with a timed clinical outcome (nausea-free at 2 hours) and a defined patient selection context (inadequate prior response).
• Dependent claims add enforceable narrowing on component amounts, SBEβCD substitution (DS 6–7), rizatriptan benzoate salt form, bicarbonate identity/quantity (sodium bicarbonate, e.g., 500 mg), weight and molar ratios, and meloxicam absorption kinetics (shorter Tmax versus a narrowly defined reference, with fasted median Tmax thresholds).
• The strongest independent-claim infringement path is composition-plus-endpoint: a product that has all three elements and delivers nausea-free status at 2 hours in the treated population.
• The best design-around levers are removing any one of the three architectural elements (complex, bicarbonate, rizatriptan) and/or changing clinical outcome at the 2-hour window; secondary levers exist for dependent kinetic, DS, and salt-form parameters.

---

FAQs

1. Does US 10,517,950 require the exact bicarbonate amount to infringe Claim 1?
   Claim 1 requires “a bicarbonate” but does not specify the bicarbonate quantity; the specific 400–600 mg and 500 mg sodium bicarbonate limits are in dependent claims.

2. Is rizatriptan required to be in benzoate form under the independent claim?
   No; rizatriptan benzoate is in dependent claim 9. Claim 1 requires “rizatriptan” generally.

3. Can a product with the same components avoid infringement by not improving meloxicam Tmax?
   The meloxicam Tmax requirements sit in dependent claims 5–6 and 24–25. Avoiding those can target those dependent claims, but Claim 1 can still be asserted if the endpoint and architecture are met.

4. How is the “reference dosage form” defined for the Tmax comparison?
   It must have the same meloxicam amount but lacks SBEβCD and lacks bicarbonate.

5. Does the independent claim require dokaz about “inadequate response” prior to dosing?
   Yes. Claim 1 requires selecting a human migraine patient with a history of inadequate response to prior migraine treatments.

---

References

1. U.S. Patent No. 10,517,950 (claims provided by user prompt).

Drugs Protected by US Patent 10,517,950

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 10,517,950

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