United States Patent 10,231,927 (Methotrexate Oral Composition): Scope, Claim-by-Claim Analysis, and US Patent Estate Outlook
US Patent 10,231,927 claims methods of treating rheumatoid arthritis and leukemia by administering an oral methotrexate composition with specific excipient and pH/buffer/preservative/sweetener parameters. The independent claims cover a composition-defined method regardless of dosage form beyond “oral administration” and regardless of a specific methotrexate salt identity beyond “pharmaceutically acceptable salt.” Dependent claims narrow to swallowing difficulty, pediatric/elderly populations, specific disease subtypes (active juvenile idiopathic arthritis for RA), and enumerated buffer/preservative/sweetener options and concentration windows.
The practical implication for US generic or authorized-derivative entry is that “design-around” is easiest only if the applicant can change at least one of the claim’s hard constraints: (i) pH window (6 to 7), (ii) presence and type of buffer agents within enumerated sets, (iii) inclusion of at least one agent from the preserving/flavoring/sweetening group, and (iv) the specific dosage concentration range if the applicant falls within that dependent tier.
What does US Patent 10,231,927 claim for methotrexate oral treatment of rheumatoid arthritis?
Independent claim 1: structure and scope
Claim 1 is a method-of-treatment claim that requires all elements below:
- Therapeutic area: treating rheumatoid arthritis in a patient.
- Route: administering a methotrexate composition for oral administration.
- Methotrexate form: the composition contains a pharmaceutically acceptable salt of methotrexate.
- Vehicle: contains purified water.
- pH/buffer system constraint: contains one or more buffer agents configured to adjust the composition pH to 6 to 7.
- Palatability/preservation constraint: contains at least one agent selected from:
- preserving agents
- flavoring compounds
- sweetening agents
Scope consequence: any oral methotrexate formulation with (a) purified water, (b) a methotrexate salt, (c) a buffer system that sets pH within 6 to 7, and (d) at least one preservative/flavor/sweetener agent in the claimed category will fall within claim 1 if used to treat rheumatoid arthritis.
Dependent claims 2–12: narrowing triggers
- Claim 2: patient has difficulty swallowing.
- Claims 3–4: claim 2 further narrows to child and elderly.
- Claim 5: RA limitation further narrows to polyarthritic forms of active juvenile idiopathic arthritis.
- Claim 6: buffer agent selection limited to an enumerated list, including:
- citric acid / citric acid monohydrate
- sodium citrate
- sodium dihydrogen phosphate, disodium hydrogen phosphate
- trometamol (Tris)
- hydrochloric acid
- ascorbic acid, sodium ascorbate
- corresponding potassium replacements of listed sodium salts
- Claim 7: allows two or more buffer agents as a buffer system.
- Claims 8–9: buffer strength narrowed by concentration ranges:
- 2 to 200 mM (claim 8)
- 2 to 20 mM (claim 9)
- Claim 10: preserving agents enumerated to combinations of:
- sodium methyl hydroxybenzoate
- sodium ethyl hydroxybenzoate
- sodium propyl hydroxybenzoate
- sodium benzoate
- potassium sorbate
- Claim 11: flavoring/sweetening limited to:
- sucralose
- acesulfame K
- “any other water soluble sweetener”
- raspberry flavor 545742E
- Claim 12: dosage concentration range:
- “pharmaceutically acceptable dosage” of methotrexate salt in range 0.05 mg/1 ml to 20 mg/1 ml
Scope consequence: these dependent claims create layered fallback positions. For infringement, an accused product need not meet dependent limitations if it already satisfies claim 1’s independent elements. But for validity/design-around, the dependent tiers matter because they define specific formulation “safe harbors” that a challenger can exploit.
What does US Patent 10,231,927 claim for methotrexate oral treatment of leukemia?
Independent claim 13: parallel structure with broader indication
Claim 13 mirrors claim 1 with two changes:
- Therapeutic area: treating leukemia
- The remaining composition architecture is the same:
- methotrexate salt
- purified water
- buffer agents to set pH 6 to 7
- at least one preserving/flavoring/sweetening agent
Dependent claims 14–24: narrowing by leukemia and patient population
- Claim 14: difficulty swallowing.
- Claims 15–16: pediatric and elderly.
- Claim 17: leukemia is acute.
- Claims 18–21: buffer agent list and buffer strength ranges identical to claims 6–9.
- Claims 22–23: preserving/flavoring/sweetening lists identical to claims 10–11.
- Claim 24: methotrexate salt dosage concentration range identical to claim 12.
Scope consequence: as with RA, the independent claim defines a formulation-characterized method for leukemia. The dependent claims add patient and leukemia subtype limitations that can matter in both infringement and patentability arguments.
Claim chart: element-by-element comparison across independent and dependent claims
| Claim element |
Claim 1 (RA) / Claim 13 (Leukemia) |
Dependent narrowing |
| Indication |
Rheumatoid arthritis (1) / leukemia (13) |
Acute leukemia (17); RA restricted via juvenile idiopathic arthritis polyarthritic forms (5) |
| Route |
Oral administration |
Difficulty swallowing (2,14); child (3,15); elderly (4,16) |
| Active |
Methotrexate as pharmaceutically acceptable salt |
None beyond “salt” |
| Vehicle |
Purified water |
None |
| pH |
Composition pH adjusted to 6 to 7 |
None |
| Buffer agent |
One or more buffer agents to reach pH 6–7 |
Enumerated buffers only (6,18); buffer strength windows 2–200 mM (8,20) or 2–20 mM (9,21); two or more buffers allowed (7) |
| Preserving/flavor/sweetening |
At least one agent selected from preserving agents, flavoring compounds, sweetening agents |
Preservatives enumerated (10,22); sweeteners/flavor enumerated (11,23); includes “water soluble sweetener” and specific raspberry flavor 545742E |
| Dosage concentration |
Not limited in independent claims |
Methotrexate salt in 0.05 mg/mL to 20 mg/mL (12,24) |
How narrow are the formulation features in US Patent 10,231,927? (design-around levers)
Hard constraints from independent claims
For infringement against claim 1 or claim 13, an accused method must use an oral methotrexate composition that satisfies:
- pH window 6 to 7 via buffer agents
- purified water
- methotrexate salt
- at least one agent from preserving/flavor/sweetening categories
The independent claims do not require:
- any particular buffer chemical beyond “buffer agents” (that level is in dependent claim 6/18)
- any specific preservative/sweetener identity beyond categories (identity lists are in dependent claims)
- any explicit methotrexate concentration range (that appears in claim 12/24)
Dependent claim-specific levers
Design-around is more plausible at the dependent level by altering:
- Buffer chemical class (move away from citric acid/citrate, phosphate salts, Tris, hydrochloric acid, ascorbate and potassium-salt equivalents)
- Buffer strength (exit 2–20 mM or 2–200 mM windows)
- Preservative selection (avoid the hydroxybenzoate/benzoate/sorbate enumerated set)
- Sweetener/flavor selection (avoid sucralose, acesulfame K, and raspberry flavor 545742E)
- Methotrexate concentration (escape 0.05–20 mg/mL if claim concentration is asserted)
But the cleanest non-infringement path targets the independent constraints:
- adjust pH outside 6 to 7, or
- remove purified water as the solvent, or
- remove the inclusion of at least one agent from the preserving/flavor/sweetening categories (for example, a formulation without preservatives and without flavor/sweetening, if that is commercially and physically feasible)
Which methotrexate salts and pH-adjusting buffer systems are explicitly within scope?
Buffer agents explicitly enumerated (dependent claims 6 and 18)
The following are within the enumerated set, including combinations and substitutions:
- Acids and salts
- citric acid
- citric acid monohydrate
- sodium citrate
- sodium dihydrogen phosphate
- disodium hydrogen phosphate
- ascorbic acid
- sodium ascorbate
- hydrochloric acid
- Trometamol (Tris)
- Potassium substitutions
- sodium salts replaced with potassium salts
Preserving agents explicitly enumerated (dependent claims 10 and 22)
- sodium methyl hydroxybenzoate
- sodium ethyl hydroxybenzoate
- sodium propyl hydroxybenzoate
- sodium benzoate
- potassium sorbate
Flavoring/sweetening agents explicitly enumerated (dependent claims 11 and 23)
- sucralose
- acesulfame K
- other water-soluble sweeteners
- raspberry flavor 545742E
What patent landscape risks exist around US 10,231,927 (composition for oral methotrexate)?
Because only claim text is provided, a complete, correct US landscape mapping (related patents, continuations, family members, assignees, and prosecution history) cannot be produced to an actionable standard. The landscape analysis below is therefore limited to the implications that can be derived directly from the claim scope itself.
Likely cluster: formulation/IP around oral methotrexate liquid
The claim’s combination of:
- oral liquid methotrexate composition (purified water vehicle + buffer + pH 6 to 7)
- taste masking/preservative palette (hydroxybenzoates/benzoates/sorbate and sucralose/acesulfame K plus a defined raspberry flavor)
- use directed to patients with swallowing difficulty and age-based subpopulations
…creates a predictable adjacency: formulation patents tend to be filed as families that cover:
- pH and buffer systems
- preservative systems
- flavor/sweetener selections
- concentration ranges and dosing regimens
- patient-centric use cases (dysphagia, pediatric administration)
Indication-driven protection
The claims are tied to rheumatoid arthritis and leukemia. In practice, that can limit generic risk assessments if an accused product is marketed for a different indication. However, infringement risk can still exist if the method is practiced for the claimed indications.
Does US 10,231,927 cover patient counseling or only formulation administration?
Both claim 1 and claim 13 are method of treating claims that require administration of a specified composition. The patient sub-elements (difficulty swallowing; child; elderly) are tied to the patient receiving the administration, not to any behavioral counseling or device use.
How strong is the claim set for enforcement? (scope vs. novelty leverage)
Strength drivers
- Independent claims have multiple hard constraints (pH window, purified water, buffer agents, presence of at least one preservative/flavor/sweetener agent).
- The dependent claims enumerate common formulation components and concentration ranges, providing layered fallbacks.
Where enforcement may be narrower than it looks
- The independent claims require that the pH is set to 6 to 7 by buffer agents. A small pH shift outside the window can be a strong technical non-infringement position if the buffer system is not engineered to meet the exact window.
- The “at least one agent selected from preserving agents, flavoring compounds, and sweetening agents” depends on whether the accused product includes any qualifying agent. A formulation that omits these categories may avoid the independent claim even if pH and buffers are otherwise matched.
Which generic entry scenarios could trigger infringement of US 10,231,927?
Scenario A: generic oral methotrexate liquid with pH 6–7 and palatability/preservation excipients
High risk if:
- the generic uses purified water,
- buffers to pH 6 to 7, and
- includes a preservative or flavor/sweetener system.
Scenario B: generic matches pH/buffer but uses a different excipient strategy
Risk remains if it still includes any preservative/flavor/sweetening agent qualifying under the claim categories.
Scenario C: generic adjusts pH outside 6–7
Low risk against independent claims if pH is definitively outside the 6 to 7 window and the buffers are not used to set the composition to 6–7.
Scenario D: generic matches composition but is used for an unclaimed indication
If the method is not practiced for rheumatoid arthritis or leukemia, the method claim may not be implicated. Market labeling and actual practice matter for enforcement.
Key Takeaways
- US 10,231,927 claims oral methotrexate salt compositions used to treat rheumatoid arthritis (claim 1) and leukemia (claim 13), requiring purified water, buffer agents setting pH to 6–7, and at least one of: preserving agents, flavoring compounds, sweetening agents.
- Dependent claims narrow to dysphagia, pediatric/elderly, and a specific RA/juvenile idiopathic arthritis polyarthritic subgroup, plus enumerated buffer/preservative/sweetener chemicals and specific buffer strength and methotrexate concentration 0.05–20 mg/mL.
- The strongest non-infringement levers are technical: pH outside 6–7, removal of “preserving/flavor/sweetening” qualifying agents, or substitution that breaks the required composition definition.
- A complete US patent landscape (family members, related patents, prosecution history, Orange Book status, litigation) cannot be computed from the claim text alone.
FAQs
- If a generic oral methotrexate liquid is pH 5.8, does it avoid claim 1/13?
- Do claim 1 and claim 13 require any specific methotrexate salt (e.g., disodium vs others)?
- Can a product avoid dependent claim 10/22 by using preservatives not in the hydroxybenzoate/benzoate/sorbate list while still meeting independent claim categories?
- Does the dysphagia limitation (claims 2 and 14) narrow infringement to only patients who have swallowing difficulty?
- How does using the product for a non-rheumatoid, non-leukemia indication affect exposure under these method claims?
References
No external sources were cited.
