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Patent landscape, scope, and claims: |
United States Patent 9,782,376 (Levothyroxine Liquid): Scope, Claim Architecture, and US Landscape
US Patent 9,782,376 protects alkaline, buffered liquid formulations of levothyroxine (and/or levothyroxine salts) with tromethamine and sodium iodide in specified concentrations, with controlled pH and shelf-life stability. The claim set is drafted as a formulation-concentration matrix with narrow dependent fallbacks (fixed concentrations, impurity caps, T3 cap, vial presentation) and a container-dependent commercialization layer (flint colored molded glass vial).
What is the core claim scope?
Independent claim 1: composition-by-components + pH + stability
Claim 1 covers a liquid formulation with the following essential elements:
| Element |
Requirement in claim 1 |
| Active |
levothyroxine or a pharmaceutically acceptable salt |
| Buffer/base |
tromethamine: about 1 mg/mL to about 50 mg/mL |
| Iodine source |
sodium iodide: about 10 mcg/mL to about 500 mcg/mL |
| Vehicle |
water |
| pH |
about 9.0 to about 11.5 |
| Stability |
stable for at least 12 months at 25 ± 2°C |
Key scope drivers
- The patent does not require a specific isotonicity adjuster or specific pH adjuster in claim 1.
- The pH window is broad in claim 1 (9.0 to 11.5) but later dependent claims narrow to 9.8 to 10.8.
- Shelf-life is a structural feature: 12 months minimum at 25 ± 2°C.
How is the claim set structured (and where are the “design-around” weak points)?
The claims fall into four layers:
- Base formulation (Claim 1)
- Active salt and concentration fallbacks (Claims 2-4, 18-19, 24-30)
- Stabilizing system + spec fallbacks (Claims 5-8, 13-15, 17, 20-23, 26-28, 30)
- Presentation and container (Claims 16, 22, 25, 27, 29)
Dependent claim map (high signal)
| Claim # |
What it narrows/defines |
| 2 |
Active is levothyroxine sodium |
| 3-4 |
Levothyroxine sodium: 20–100 mcg/mL, with specific points 20 / 40 / 100 mcg/mL |
| 5-6 |
Tromethamine: 5–20 mg/mL, with specific 10 mg/mL |
| 7-8 |
Sodium iodide: 100–300 mcg/mL, with specific 140 mcg/mL |
| 9-10 |
Adds isotonicity adjuster; example is sodium chloride |
| 11-12 |
Adds pH adjuster; examples HCl, NaOH |
| 13 |
pH narrowed to 9.8–10.8 |
| 14 |
T3 impurity cap: not more than 1.0% liothyronine (T3) |
| 15 |
Total impurities cap: not more than 2.5% |
| 16 |
Container layer: ready-to-use flint colored molded glass vial |
| 17 |
Shelf-life: at least 18 months at 25 ± 2°C |
| 18-23 |
A second independent-style formulation layer with explicit isotonicity NaCl and pH 9.8–10.8, plus the same stability/container fallbacks |
| 24-30 |
Third independent-style formulation layer with explicit fixed component set: levothyroxine sodium (20–100 mcg/mL) + tromethamine (10 mg/mL) + sodium iodide (140 mcg/mL) + NaCl + water + pH 9.8–10.8 and stability 12 months; plus vial size/concentration combinations and 18-month stability |
Practical takeaway on “weak points”
- If a competitor stays within claim 1’s pH and component ranges, the product likely still infringes claim 1 even if they avoid later dependent limitations (unless they exit the claim 1 ranges).
- The most meaningful design-around is to move outside claim 1’s pH range (9.0–11.5) or remove/replace the combination of tromethamine + sodium iodide at specified ranges (or both).
- Avoidance via not meeting the 12-month stability requirement is a classic formulation strategy, but it only matters if the product truly fails stability at the claimed condition; the claim language still reads as a product-by-function stability limitation.
What do the concentration bands imply for product formulation freedom?
Claim 1 ranges (broadest protected composition layer)
- Tromethamine: 1 to 50 mg/mL
- Sodium iodide: 10 to 500 mcg/mL
- pH: 9.0 to 11.5
- Levothyroxine: not explicitly quantified in claim 1 (but implicitly constrained by dependent claims)
Dependent quantizations (tight commercialization targets)
- Levothyroxine sodium: 20–100 mcg/mL, plus 20, 40, 100 mcg/mL
- Tromethamine: 5–20 mg/mL, plus 10 mg/mL
- Sodium iodide: 100–300 mcg/mL, plus 140 mcg/mL
- pH narrower: 9.8–10.8
- T3: ≤ 1.0%
- Total impurities: ≤ 2.5%
- Stability:
- Claim 1: ≥ 12 months
- Claim 17 and dependent commercialization claims: ≥ 18 months
Fixed formulation set in claims 24-30 (tightest “commercial” lock)
Claims 24-30 pin a particular composition set:
- Levothyroxine sodium: 20 to 100 mcg/mL (with examples at 20, 40, 100 mcg/mL)
- Tromethamine: 10 mg/mL
- Sodium iodide: 140 mcg/mL
- Sodium chloride: included
- pH: 9.8 to 10.8
- Stability: ≥ 12 months in claim 24, and ≥ 18 months in claims 26, 28, 30
- Vial: flint colored molded glass vial
- Example pack sizes:
- claim 25: 5 mL at 20 mcg/mL
- claim 27: 5 mL at 40 mcg/mL
- claim 29: 5 mL at 100 mcg/mL
Scope effect
- A competitor that matches claim 24’s composition set is exposed to a tightly layered infringement chain because claims 25/27/29 tie presentation (vial + volume + concentration) to longer stability fallbacks.
What is the “stability” and impurity claim relevance?
Shelf-life limits are explicit claim features
- Claim 1: stable at least 12 months at 25 ± 2°C
- Claim 17: stable at least 18 months at 25 ± 2°C
- Claim 23 / 26 / 28 / 30: stable at least 18 months at 25 ± 2°C for the narrower embodiments
Impurity controls create enforceable quality boundaries
- T3 cap (Claim 14): ≤ 1.0% liothyronine
- Total impurities cap (Claim 15): ≤ 2.5%
These matter in infringement because they are not “process” limitations; they are product-quality limitations embedded in the dependent claims. A competitor can still remain inside broad claim 1 while avoiding dependent claims by exceeding those impurity thresholds, but that does not eliminate exposure under claim 1 if claim 1 itself covers the base formulation and stability.
How broad is the container and “ready-to-use” layer?
Container/presentation is handled as:
- Claim 16: ready-to-use formulation in a flint colored molded glass vial
- Claim 22: same container layer tied to claim 18’s composition
- Claims 25, 27, 29: ready-to-use formulations in flint colored molded glass vial with a specific 5 mL fill volume and active concentration
This creates a practical enforcement pathway:
- If a generic manufacturer uses a different container type, it may avoid the container-specific dependent claims.
- But claim 1 does not require container specification, so the container layer is additive protection, not the sole enforcement hook.
What does the claim language say about pH adjustment mechanisms?
Two different approaches appear:
- Claim 11-12: allows inclusion of a pH adjuster selected from HCl, NaOH, and combinations
- Claim 13: narrows the pH window to 9.8–10.8
These do not require a specific “how” in claim 1. Dependent claims add optionality (pH adjuster present) and narrow the pH range.
What does this mean for a patent landscape in the US?
Protected technological field (what the patent likely anchors)
This US patent is anchored to a liquid levothyroxine stabilization formulation that uses:
- Alkaline pH (roughly 10 range) via tromethamine
- Iodide presence (sodium iodide)
- Controlled impurity profile (T3 and total impurities)
- Demonstrated room-temperature stability over 12 to 18 months
Landscape risk pattern for entrants (composition-first)
For US market participants, the claim structure implies a common risk pattern:
- If the formulation uses tromethamine and sodium iodide and hits alkaline pH with 12-month stability, claim 1 exposure is likely.
- If it further uses NaCl isotonicity and pH is 9.8–10.8, claims 18 and 24-based coverage increases.
- If it uses 10 mg/mL tromethamine and 140 mcg/mL sodium iodide, the formulation becomes aligned with the tight embodiments (claims 24-30).
Landscape risk pattern for container-only differentiation
- Container choice can avoid dependent claims (16, 22, 25/27/29) if the vial is not “flint colored molded glass,” but does not remove independent claim 1 coverage.
- Therefore, container-only workarounds have limited risk reduction unless the formulation itself is redesigned to exit claim 1’s pH or component ranges.
What are the most actionable infringement “touchpoints” in claims?
Highest-friction parameters
- pH of 9.0–11.5 (claim 1)
- tromethamine presence at ~1–50 mg/mL (claim 1)
- sodium iodide at ~10–500 mcg/mL (claim 1)
- 12-month stability at 25 ± 2°C (claim 1)
- T3 impurity ≤ 1.0% (claim 14) and total impurities ≤ 2.5% (claim 15) for narrower compliance
- pH 9.8–10.8 and NaCl in narrower independent-style claims (18 and 24)
- Fixed embodiments: 10 mg/mL tromethamine and 140 mcg/mL sodium iodide (claim 24 and dependents)
Claim set leverage for enforcement
The patent provides multiple “stacked” dependent constraints:
- concentration specificity (20/40/100 mcg/mL; 10 mg/mL tromethamine; 140 mcg/mL iodide)
- stability duration expansion (12 months up to 18 months)
- quality constraints (T3 and total impurities)
- packaging (flint colored molded glass vial; 5 mL fill)
This stack reduces the probability that a product will avoid every dependent claim while still falling under the independent base.
Key Takeaways
- US 9,782,376 protects a liquid alkaline levothyroxine formulation where tromethamine and sodium iodide are essential components and pH 9.0–11.5 plus 12-month stability at 25 ± 2°C define the core coverage (claim 1).
- Dependent claims tighten into a targetable commercial design space: pH 9.8–10.8, NaCl isotonicity, 10 mg/mL tromethamine, 140 mcg/mL sodium iodide, impurity caps (T3 ≤ 1.0%, total impurities ≤ 2.5%) and 18-month stability.
- Container specificity (flint colored molded glass vial; 5 mL fill) creates additional dependent coverage, but it does not eliminate exposure under claim 1.
- The most credible US design-around levers are exiting claim 1’s pH range and/or removing the tromethamine and sodium iodide combination in the claimed concentration windows while also disrupting the claimed stability benchmark.
FAQs
1) Does claim 1 require a specific levothyroxine concentration?
No. Claim 1 requires levothyroxine (or a salt) but does not specify its concentration in the independent claim. Concentration is defined in dependent claims (e.g., claims 3-4, 18-19, 24, and 25/27/29).
2) Which claim defines the broadest pH coverage?
Claim 1 defines the broadest pH range: about 9.0 to about 11.5.
3) What pH range appears in the narrower embodiments?
Claims 13, 18, and 24 use about 9.8 to about 10.8.
4) Are tromethamine and sodium iodide both required for infringement?
Yes. Claim 1 requires both tromethamine and sodium iodide within stated ranges, alongside water and levothyroxine.
5) Can a different vial avoid infringement?
A different vial may avoid the dependent claims that require a flint colored molded glass vial (claims 16, 22, 25, 27, 29), but claim 1 does not require the vial feature.
References
- United States Patent 9,782,376.
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