US Patent 10,376,584: Scope, Claim Coverage, and US Patent Landscape for Methylnaltrexone-EDTA Stabilized Preparations
US Drug Patent 10,376,584 claims a specific stability-centered formulation: a solution of methylnaltrexone (or a salt) plus a chelating agent defined as EDTA (or an EDTA derivative), with dependent claims tightening to methylnaltrexone bromide, edetate calcium disodium, isotonicity and buffering agents (NaCl and glycine), parenteral suitability, and defined dose ranges and concentration ranges. The independent claim is a composition claim framed around stability, with method claims limited to using that composition to treat opioid-induced peripheral side effects, including constipation.
What does claim 1 cover (independent claim scope)?
Claim 1 (core scope)
Claim 1 is directed to:
- A stable pharmaceutical preparation
- that is a solution of
- methylnaltrexone or a salt thereof
- and a chelating agent
- where the chelating agent is EDTA or an EDTA derivative.
Practical coverage interpretation
- Form: “solution” implies liquid formulation, not lyophilized or solid-state dosage.
- Key stabilizing element: EDTA (or EDTA derivative) is mandatory.
- Drug identity: methylnaltrexone and its salts are mandatory, but the claim is not limited to bromide in the independent claim (that enters via dependent claims).
Essential claim elements
To fall within claim 1, an accused product must have all of the following:
- Methylnaltrexone or a salt thereof
- EDTA or an EDTA derivative
- Delivered as a stable pharmaceutical preparation in solution form
How do dependent claims narrow the formulation?
Drug salt specificity
- Claim 2: methylnaltrexone is bromide
- Claim 3: EDTA derivative is edetate calcium disodium
These convert the broad independent claim into narrower “variants” with tighter identity:
- If a competitor uses EDTA but not the EDTA derivative specified in claim 3, claim 3 does not read on it, but claim 1 still can, depending on derivative definition and whether their chelator is “EDTA or a derivative thereof.”
Excipients and parenteral suitability
- Claim 4: preparation further comprises:
- isotonicity agent
- buffering agent
- Claim 5: isotonicity agent = sodium chloride
- Claim 5: buffering agent = glycine
- Claim 6: preparation is suitable for parenteral delivery
This chain makes an explicit injectable-type formulation:
- It is not required for claim 1, but it is required for claims 4-6.
Dose ranges
The claims include two dose ranges tied to body weight:
- Claim 7: 0.01 to 1.00 mg/kg/day
- Claim 8: 0.1 to 0.3 mg/kg/day
These are method-of-use aligned but are listed as formulation limitations in the claim set as provided. In a legal construction, such dose limitations typically control the “effective amount” for the claimed use; the narrower range is a further limitation.
Concentration ranges
- Claim 11: methylnaltrexone or salt concentration: 1.0 to 50.0 mg/mL
- Claim 12: methylnaltrexone concentration: about 20 mg/mL
- Claim 13: chelating agent concentration: 0.1 to 25.0 mg/mL
- Claim 14: chelating agent concentration: 0.1 to 2.5 mg/mL
- Claim 15: explicitly:
- methylnaltrexone bromide: about 20 mg/mL
- EDTA or derivative: about 0.1 to 2.5 mg/mL
Coverage implication
- Competitors outside these concentration windows reduce the chance of literal infringement for those dependent claims.
- They may still face risk under claim 1 if their formulation still uses EDTA (or derivative) and methylnaltrexone in solution as a stable preparation.
What do the method claims cover (claims 9-10)?
Claim 9
A method for treating opioid-induced peripheral side effects by:
- administering the stable pharmaceutical preparation of claim 1
- in an amount effective to treat the side effect.
This is a use claim anchored to claim 1’s composition.
Claim 10
- opioid-induced peripheral side effect is constipation.
Practical coverage interpretation
- If a product practices claim 1’s formulation, then using it to treat constipation can implicate claim 10.
- If the accused product is a different formulation (no EDTA/EDTA derivative in solution), claim 9 and claim 10 become substantially harder to map.
Claim chart style breakdown (coverage checklist)
| Feature |
Present in claim(s) |
Mandatory for infringement if asserted |
| Stable “solution” of methylnaltrexone (or salt) |
Claim 1 |
Yes (for claim 1; all dependent claims reference claim 1) |
| Chelating agent defined as EDTA or EDTA derivative |
Claim 1 |
Yes (for claim 1; dependent claims reference claim 1) |
| Methylnaltrexone bromide |
Claim 2, Claim 15 |
Only if claim 2 or claim 15 is asserted |
| EDTA derivative = edetate calcium disodium |
Claim 3 |
Only if claim 3 asserted |
| Isotonicity agent + buffering agent |
Claim 4 |
Only if claim 4 asserted |
| Isotonicity agent = sodium chloride |
Claim 5 |
Only if claim 5 asserted |
| Buffering agent = glycine |
Claim 5 |
Only if claim 5 asserted |
| Parenteral suitability |
Claim 6 |
Only if claim 6 asserted |
| Dose range 0.01 to 1.00 mg/kg/day |
Claim 7 |
Only if claim 7 asserted |
| Dose range 0.1 to 0.3 mg/kg/day |
Claim 8 |
Only if claim 8 asserted |
| Treating opioid-induced peripheral side effect by administration |
Claim 9 |
Only if method claim asserted |
| Side effect = constipation |
Claim 10 |
Only if claim 10 asserted |
| Methylnaltrexone concentration window (1-50 mg/mL) |
Claim 11 |
Only if claim 11 asserted |
| Methylnaltrexone at about 20 mg/mL |
Claim 12 and 15 |
Only if claim 12 or 15 asserted |
| Chelator concentration window (0.1-25 mg/mL; narrower 0.1-2.5 mg/mL) |
Claims 13-14 and 15 |
Only if those dependent claims asserted |
Scope boundaries: where competitors may avoid the claims
Hard boundary: chelating agent definition
Claim 1 requires chelating agent = EDTA or a derivative thereof. Practical design-around paths typically include:
- Replacing EDTA/EDTA derivatives with a non-EDTA chelator outside “derivative” interpretation.
- Using no chelator and relying on alternative stabilization (though that may still risk if the claim language is read broadly on “derivative”).
Secondary boundary: concentration and dose
Dependent claims (11-15 and 7-8) impose concentration and dose windows.
- A competitor can remain in scope for claim 1 while avoiding dependent-claim windows if EDTA/derivative remains present but their methylnaltrexone or EDTA derivative concentration falls outside those ranges.
- However, if a competitor’s formulation matches claim 15 (about 20 mg/mL drug and 0.1 to 2.5 mg/mL EDTA derivative), the narrowest formulation claim aligns tightly.
Salt identity (bromide) and EDTA derivative identity
- If a competitor uses a different methylnaltrexone salt, claim 2 and 15 become harder.
- If a competitor uses EDTA but not edetate calcium disodium, claim 3 becomes harder.
Patent landscape in the US: what is likely adjacent to this claim set
This patent is a formulation stabilization patent directed to methylnaltrexone + EDTA/EDTA derivative in injectable-suitable solution form and method-of-use for opioid-induced peripheral side effects (constipation).
How this sits in the broader US methylnaltrexone IP ecosystem
The methylnaltrexone product family in the US typically has three major IP “layers”:
- Active ingredient and early composition claims
- Specific dosage forms, strengths, and manufacturing/formulation details
- Method-of-use claims tied to opioid-induced peripheral effects
US 10,376,584 is best viewed as a formulation stabilizer/chelating-agent IP layer. Its novelty focus is the combination of:
- methylnaltrexone solution
- plus EDTA/EDTA derivative as chelator
- with explicit concentration windows and injectable-oriented excipient set (NaCl + glycine) in dependent claims.
Landscape risks for generics and line extensions
- If a generic seeks to match the branded product composition closely, the generic’s formulation may land inside this claim space if it includes EDTA/EDTA derivative in solution at similar concentrations and uses it to treat constipation.
- If a competitor uses a different chelator but retains essentially the same excipient and pH system, they may reduce infringement risk on claim 1 but could still face other formulation patents covering other aspects (buffering, tonicity, oxidation inhibitors, pH windows, sterility and preservatives).
Enforcement-relevant claim mapping scenarios
Scenario A: Generic injectable using methylnaltrexone bromide with EDTA derivative
High risk of meeting claim 1 and likely claim 2 (bromide). If their EDTA derivative is edetate calcium disodium, claim 3 also aligns.
Scenario B: Formulation uses EDTA but not edetate calcium disodium
- Claim 1 still can read.
- Claims 3 and 15 narrow coverage but are not necessarily determinative.
Scenario C: Formulation uses a non-EDTA chelator
- This is the most direct avoidance of claim 1, because EDTA/derivative is an express limitation.
Scenario D: Formulation uses EDTA but changes concentrations
- Dependent claims 11-15 and dose claims 7-8 may be avoided if out-of-range.
- But claim 1 can still capture if the formulation still qualifies as “stable preparation comprising methylnaltrexone solution and EDTA/EDTA derivative.”
Key takeaways
- US 10,376,584 has an independent claim that is composition-focused and stabilization-oriented: methylnaltrexone (or salt) in solution + EDTA (or EDTA derivative).
- Dependent claims lock in: methylnaltrexone bromide, edetate calcium disodium, NaCl and glycine (with parenteral suitability), plus dose and concentration windows including a tight exemplar in claim 15 (about 20 mg/mL methylnaltrexone bromide and 0.1 to 2.5 mg/mL EDTA derivative).
- Method claims cover administering the claim 1 composition for opioid-induced peripheral side effects, including constipation.
- The main design-around lever is the chelator: replacing EDTA/EDTA derivative with a non-EDTA chelator is the clearest route away from claim 1’s express limitation. Changing concentrations and salt forms may avoid dependent claims, but not necessarily claim 1.
FAQs
1) Is EDTA mandatory for infringement?
Yes for claim 1 coverage as provided: the chelating agent must be EDTA or an EDTA derivative.
2) Do the dependent claims require sodium chloride and glycine?
Yes. That requirement appears in the dependent chain (claims 4-6 and claim 5).
3) Does this patent require methylnaltrexone bromide in the broadest claim?
No. The independent claim covers methylnaltrexone or a salt. Bromide is specified in claim 2 and claim 15.
4) Can a company avoid the patent by changing the dose?
Changing dose can help avoid dose-limited dependent claims (7-8). It does not remove risk under claim 1 if EDTA/derivative and solution formulation are still practiced.
5) Does the patent cover methods beyond constipation?
Yes. Claim 9 covers opioid-induced peripheral side effects generally, while claim 10 narrows that to constipation.
References
[1] United States Patent No. 10,376,584.
