Scope and claims analysis for U.S. Patent 10,166,190: tacrolimus sustained-release tablets stabilized with oxalic acid and controlled 8-epitacrolimus degradation
U.S. Patent 10,166,190 claims sustained-release tacrolimus tablet compositions designed to suppress formation or persistence of 8-epitacrolimus during storage by using a metal-chelating organic acid (with oxalic acid as a preferred embodiment) and by controlling tablet pH. The core enforceable boundaries are (1) tacrolimus as the sole active ingredient, (2) inclusion of a metal chelating agent that is an organic acid, (3) tacrolimus solid dispersion and tablet “sustained release” structure, and (4) quantitative limits on 8-epitacrolimus after defined stability conditions, expressed relative to “100% total weight of tacrolimus.”
Because the limits are recited as compositional outcome measures after storage stress tests (e.g., 25° C./60% RH for 12 weeks or 10 months; and 40° C./75% RH for 5 weeks), the claims are best read as functional chemistry-to-performance claims. That structure tends to broaden infringement risk to any generic or licensed entrant whose product inevitably reaches those stability thresholds, regardless of how it is manufactured, as long as the product meets the claim-defined composition elements and stability endpoints.
What patents protect tacrolimus sustained-release tablets with low 8-epitacrolimus formation?
Quick answer: U.S. Patent 10,166,190 is centered on sustained-release tacrolimus tablets that include a dispersion/solid dispersion and an organic-acid metal chelator (notably oxalic acid), with explicit 8-epitacrolimus quantitative limits after storage.
Claim architecture: product-by-structure plus product-by-result
The claims fall into two layers:
-
Independent composition claims (1–4):
Each requires:
- sustained release tablet
- tacrolimus dispersed or in solid dispersion
- inclusion of 8-epitacrolimus (as a present species in the tablet system)
- an organic-acid metal chelating agent
- tacrolimus is the sole active ingredient
- 8-epitacrolimus is kept below a threshold after defined storage conditions, with thresholds expressed as wt% relative to “100% total weight of tacrolimus”
-
Dependent refinements (5–16):
- pH target: 2.5 to 4 after re-dispersing the tablet in water (claims 5–8)
- dispersion/vehicle configuration: chelator dissolved in the vehicle; tacrolimus dispersed in a vehicle (claims 9–12)
- specific chelator identity: oxalic acid (claims 13–16)
What does “tacrolimus is the sole active ingredient” exclude?
This phrase narrows the active set to tacrolimus as the only drug substance present at “active ingredient” status. It does not, by itself, prevent inclusion of excipients, but it can exclude tablets that use an additional active pharmaceutically meaningful compound. It also frames 8-epitacrolimus as not an “active ingredient,” even though it is chemically present and is measured in the stability limit.
How does “8-epitacrolimus” operate in the claims?
Every independent claim includes 8-epitacrolimus in the sustained-release tablet. Yet the enforceable boundary is the amount of 8-epitacrolimus remaining after storage (less than 0.5% or 0.2% depending on conditions; or no more than 0.5% after 5 weeks under a different condition set).
This structure indicates two practical infringement pathways:
- products that initially contain 8-epitacrolimus and are stabilized so it does not exceed the thresholds after storage; and/or
- products that generate or retain 8-epitacrolimus over time, with the chelator system controlling the endpoint.
What is the central chelation mechanism in the claim scope?
The claims require a “metal chelating agent that is an organic acid.” That does not demand a specific chelation ring structure or metal identity. It does, however, constrain the candidate list substantially:
- must be organic acid
- must function as a metal chelator (as claimed)
- must be present in sufficient amount to meet the endpoint 8-epitacrolimus limits
The preferred dependent embodiment explicitly selects oxalic acid (claims 13–16).
How broad are the claims: which elements are mandatory vs optional?
Quick answer: Elements that are mandatory in all independent claims are: sustained release tablet + tacrolimus dispersed/solid dispersed + organic-acid metal chelator + tacrolimus sole active ingredient + defined 8-epitacrolimus endpoint after specified storage. pH, vehicle dissolution architecture, and oxalic acid identity narrow further.
Mandatory elements in claims 1–4
- Form factor: sustained release tablet
- Drug system:
- tacrolimus dispersion (claims 1,2,9,10) or solid dispersion (claims 3,4,11,12)
- 8-epitacrolimus present as a species in the tablet system
- Stabilizing agent: a metal chelating agent that is an organic acid
- Regulatory framing: tacrolimus is the sole active ingredient
- Stability endpoint: quantitative 8-epitacrolimus after storage, using the “based upon 100% total weight of tacrolimus” measurement basis
Optional or narrowing dependent elements
- Tablet pH after re-dispersion in water: 2.5 to 4 (claims 5–8)
- Specific architecture of dispersion and chelator dissolution in vehicle:
- chelator dissolved in vehicle (claims 9,10,12,11)
- tacrolimus dispersed in vehicle (claims 9,10,12,10; depends)
- Specific chelator species: oxalic acid (claims 13–16)
Practical claim breadth takeaways for product design
- Replacing oxalic acid with another organic acid metal chelator could still fall within claims 1–4 if it qualifies as a “metal chelating agent” and achieves the same 8-epitacrolimus endpoints.
- Avoiding the claims through pH alone likely fails because pH limits are only in dependent claims (5–8).
- Avoiding through “not a dispersion” may be effective only if the product does not meet the claimed dispersion/solid dispersion definitions used in independent claims 1–4.
What are the key 8-epitacrolimus stability thresholds that define infringement risk?
Quick answer: The independent claims enforce specific numerical caps on 8-epitacrolimus after defined storage programs, with different durations and stress conditions.
Independent claim endpoint matrix
| Claim |
Tacrolimus presentation |
Chelator type |
Storage condition |
8-epitacrolimus limit (wt% relative to total tacrolimus) |
| 1 |
dispersion of tacrolimus |
organic-acid metal chelator |
25° C., 60% RH, 12 weeks |
< 0.5% |
| 2 |
dispersion of tacrolimus |
organic-acid metal chelator |
25° C., 60% RH, 10 months |
< 0.5% |
| 3 |
solid dispersion of tacrolimus in vehicle + chelator |
organic-acid metal chelator |
40° C., 75% RH, 5 weeks compared to pre-storage |
≤ 0.5% of pre-storage benchmark |
| 3 (alt) |
same |
same |
25° C., 60% RH, 5 weeks compared to pre-storage |
≤ 0.2% |
| 4 |
solid dispersion of tacrolimus + chelator |
organic-acid metal chelator |
25° C., 60% RH, 5 weeks |
≤ 0.5% |
Interpretation that matters for product comparisons:
Claim 3 uses a “compared to the tablet prior to storage” formulation for the endpoint, which imports a relative change measurement method. This can affect infringement analysis because a product with higher initial 8-epitacrolimus could be pushed above the relative cap even if it remains under 0.5% in absolute terms after storage.
How do “pH 2.5 to 4” and “re-dispersing in water” limit or strengthen enforceability?
Quick answer: pH is only required in dependent claims (5–8), measured after re-dispersing the tablet in water.
Dependent claim set
- Claims 5–8: tablet has pH 2.5 to 4 as measured after re-dispersing the tablet in water.
Practical enforceability impact
- If a competitor meets all independent claim elements but ends up outside pH 2.5–4, they could avoid infringement of the dependent claims but may still infringe the independent claims if the independent 8-epitacrolimus endpoint limits are met and the dispersion/chelator elements remain satisfied.
- Conversely, a product designed to satisfy independent claim endpoints likely will be tested for pH and could land within the dependent range if the formulation naturally drives acidic pH after re-dispersion.
What is the significance of “tacrolimus dispersed in a vehicle” and “metal chelating agent dissolved in the vehicle”?
Quick answer: Dependent claims (9–12) specify an internal organization of dispersion and dissolution that narrows those particular claim embodiments.
Dependent claims
- Claims 9–10: dispersion of tacrolimus comprises tacrolimus dispersed in a vehicle; metal chelating agent dissolved in the vehicle.
- Claims 11–12: chelator dissolved in the vehicle; and in claim 12 the tacrolimus dispersion in the vehicle is also specified.
Practical product design implication
If a generic uses a chelator present but not dissolved in the same vehicle or not meeting the dispersion-dissolution architecture, it may not infringe the dependent versions. It could still infringe independent claims if those independent claims do not require the same vehicle-specific arrangement beyond “dispersion” vs “solid dispersion.”
What formulations are protected: is oxalic acid required?
Quick answer: Oxalic acid is required only for the oxalic-acid-dependent claims (13–16). The independent claims require only an organic-acid metal chelator.
Oxalic acid dependent claims
- Claims 13–16: metal chelating agent is oxalic acid.
Scope consequence
- The independent claims have broader coverage for other organic acids that qualify as metal chelators and achieve the 8-epitacrolimus endpoint limits.
- The dependent claims capture oxalic acid formulations with the same endpoint and dispersion features.
How strong is the patent estate for this technology: what do the claim outcomes suggest about novelty?
Quick answer: The claims tie chemical composition design to quantified stability outcomes under defined humidity/temperature storage. That pattern suggests the inventors positioned the invention around stabilizing tacrolimus-containing sustained-release tablets by controlling 8-epitacrolimus through an organic-acid chelator system.
Why the outcome language increases practical breadth
- Generic developers cannot easily “design around” by changing process details if the finished tablet’s measured 8-epitacrolimus endpoints match the claim thresholds.
- Storage-tested endpoints can be satisfied by multiple formulation routes that converge on the required stability profile.
Why “metal chelating agent that is an organic acid” is a meaningful boundary
This limits the claim family to organic acids with metal chelation functionality, not generic pH modifiers or inert fillers unless those happen to qualify as chelators and meet the endpoint.
What generic entry risks exist for tacrolimus sustained-release tablets under this patent?
Quick answer: Any ANDA or 505(b)(2) entrant whose sustained-release tacrolimus tablet includes (i) the claimed dispersion/solid dispersion structure and (ii) an organic-acid metal chelator system such that the finished product shows the claimed 8-epitacrolimus endpoint after the specified storage programs faces direct compositional infringement exposure.
Risk amplifiers
- use of oxalic acid
- acidic pH regime consistent with 2.5–4 after re-dispersion
- formulation designs aimed at matching or improving stability profiles for 8-epitacrolimus
Risk mitigators
- non-organic-acid chelators, non-chelators, or chelators that do not meet the “organic acid metal chelator” limitation
- dispersion structures that avoid the “dispersion/solid dispersion” limitations (depending on claim construction of those terms)
- formulation outcomes that exceed the numeric 8-epitacrolimus thresholds under the claimed stability conditions
What litigation landscape exists for U.S. Patent 10,166,190?
Critical constraint: No litigation docket, parties, or settlement facts were provided with the patent number or in the input. Without those facts, a complete and accurate litigation landscape cannot be produced.
What is the Orange Book status of U.S. Patent 10,166,190?
Critical constraint: No FDA product name, NDA/ANDA number, Orange Book listing entry, or patent association details were provided. Without those, the Orange Book status cannot be stated accurately.
What patent expiration and exclusivity timeline applies?
Critical constraint: No filing date, priority date, or term-adjustment figures for U.S. Patent 10,166,190 were provided. Without those, expiration timing cannot be calculated accurately.
Key Takeaways
- U.S. Patent 10,166,190 claims sustained-release tacrolimus tablets with tacrolimus as the sole active ingredient, containing tacrolimus dispersed/solid dispersed and an organic-acid metal chelating agent to control 8-epitacrolimus levels after defined storage programs.
- Enforceability centers on quantitative 8-epitacrolimus limits after specified temperature/humidity/time conditions, including an endpoint defined relative to pre-storage levels (claim 3).
- Oxalic acid is required only in dependent claims (13–16). Independent coverage is broader for other organic-acid metal chelators that meet the stability endpoints.
- Dependent claim narrowing includes tablet pH 2.5–4 after re-dispersion, and vehicle/solubility architecture (chelator dissolved in vehicle; tacrolimus dispersed in vehicle).
- For generic risk, the strongest infringement case is a product that matches the composition elements and also matches the storage-tested 8-epitacrolimus endpoints, even if the manufacturing route differs.
FAQs
1. Does U.S. Patent 10,166,190 require that 8-epitacrolimus be an added ingredient?
The claims recite “comprising … 8-epitacrolimus” and define compliance via measured post-storage wt% limits, so the endpoint is central.
2. Can a formulation avoid infringement by targeting a different pH?
pH is required only in dependent claims (5–8). Avoiding pH alone may not avoid independent claim infringement if the 8-epitacrolimus endpoints and other composition elements are met.
3. Is oxalic acid necessary to fall within claim scope?
No. Oxalic acid is required only for claims 13–16. Independent claims require only an organic-acid metal chelating agent.
4. What storage conditions matter most for the endpoint measurements?
The claims specify 25° C./60% RH for 12 weeks or 10 months and 40° C./75% RH or 25° C./60% RH for 5 weeks, with claim 3 adding a “compared to prior to storage” measurement structure.
5. Does the claim protect manufacturing process steps?
The provided claims are product composition and performance-oriented (solid/dispersion structure and stability outcomes), not step-by-step manufacturing methods.
References
No external sources were provided in the prompt, and no citations are possible for U.S. Patent 10,166,190 beyond the user-supplied claim text.
