US Patent 11,419,823 (Tacrolimus sustained-release solid dispersion): What is actually claimed and how broad is the scope?
US 11,419,823 claims sustained-release tacrolimus formulations built around one core idea: keep 8-epitacrolimus low after stress storage by using a metal-chelating stabilizing system that also drives formulation pH below 7, inside a solid dispersion of tacrolimus in a vehicle + stabilizing agent. The independent claim set is then narrowed through recited pH windows, excipient classes, solvent absence, and product form (composition vs tablet).
Below is the clean claim-structure map, then a claim-by-claim scope teardown, then the likely patent landscape implications (what this blocks, what it does not, and where design-arounds tend to land).
What is the claim architecture (independent vs dependent) and where is the “center of gravity”?
Independent claims present in the text
1) Claim 1: Sustained release composition; solid dispersion; tacrolimus sole active ingredient; stabilizing agent is a metal chelating agent that provides pH < 7; and the formulation is defined by a quantitative degradation endpoint: <0.5% by weight of 8-epitacrolimus after 12 weeks at 25°C / 60% RH, based on 100% total weight of tacrolimus.
2) Claim 17: Sustained release composition; similar to claim 1 but explicitly limits stabilizing agent to organic acid chelators listed as oxalic, tartaric, citric (and still requires pH < 7, and the same 8-epi endpoint).
3) Claim 19: Sustained release composition; differs by requiring the formulation contains 8-epitacrolimus but keeps it even tighter: <0.2% by weight, while still requiring metal-chelating agent, pH < 7, and tacrolimus as the sole active ingredient, plus the same 8-epi-at-12-weeks constraint.
4) Claim 25: Sustained release tablet; includes tacrolimus dispersion plus 8-epitacrolimus as an explicit component; stabilizing agent is metal chelating, pH < 7; includes the <0.5% after 12 weeks endpoint; tacrolimus is the sole active ingredient in the tablet.
Dependent claims
- pH ranges: claims 2 and 3 set pH windows (2.5-4.0; 3.0-3.6).
- Stabilizing agent identity and concentration: claims 4-6 define the stabilizing agent as organic acids and provide enumerated examples plus a concentration ceiling.
- Vehicle definition: claim 7 recites polyethylene glycol + poloxamer.
- 8-epitacrolimus content: claim 8 requires <0.5% w/w (framed as part of the composition).
- Re-dispersed aqueous pH: claim 9 requires the pH of re-dispersed aqueous composition (2.5 to 4).
- Citric acid-specific fall-through: claims 10-16 and 18-23, 27-28 are citric-acid-specific dependent positions.
- Solvent absence: claim 20 requires the solid dispersion is substantially free of organic solvent.
- Tablet-specific aqueous pH: claims 26 and 27-28 cascade.
Center of gravity: the enforceable hook is not “solid dispersion” alone, but solid dispersion + metal-chelating stabilizing system that yields pH < 7 + a stress-test 8-epi endpoint.
What does Claim 1 actually cover (and what must be true for infringement)?
Claim 1 elements (checklist)
A product must satisfy all of the following:
1) Sustained release pharmaceutical composition
2) Solid dispersion of tacrolimus
3) Tacrolimus is in a mixture of a vehicle and a stabilizing agent
4) Stabilizing agent = metal chelating agent and it provides pH below 7 in the composition
5) Tacrolimus is the sole active ingredient
6) A quantitative stability/impurity requirement:
- <0.5% by weight of 8-epitacrolimus after 12 weeks
- Conditions: 25°C and 60% relative humidity
- Measurement basis: “based upon 100% total weight of tacrolimus”
Scope implications of Claim 1
- Broad on vehicles and solid dispersion format: “vehicle” is not limited in claim 1. As long as the vehicle exists and the tacrolimus is in a solid dispersion with the stabilizing agent, infringement risk remains.
- Broad on “metal chelating agent” so long as it drives pH < 7: claim 1 does not list specific chelators at the independent level. The definitional power comes from function (metal chelation + pH below 7) and from the achieved endpoint.
- Endpoint is outcome-defined: the claim is partly “result-based” (8-epi level after storage). That tends to:
- Raise evidentiary burdens for enforcement (you need stability test data).
- Create room for a design-around only if a competitor can hit >=0.5% after the specified storage (or avoid the claim-defined mechanism).
How do Claims 2-3 tighten pH?
Claim 2
- pH range in the composition: 2.5 to 4.0
Claim 3
- pH range in the composition: 3.0 to 3.6
Scope impact: These are dependent restrictions. A product meeting Claim 1 but not these pH ranges can still fall within Claim 1 but not these narrower dependents. For an invalidity or design-around analysis, these pH bands are important because they can be used to argue overlap with prior art only if prior art formulations hit those specific pH windows.
How do Claims 4-6 restrict the stabilizer class (and what is the likely loophole)?
Claim 4
- Stabilizing agent is an organic acid selected from mono-, di-, oligo-, and polycarboxylic acids
Claim 5
- Examples: succinic, citric, tartaric, acrylic, benzoic, malic, maleic, sorbic
Claim 6
- Organic acid concentration: <5% w/w
- Basis: “based on the total amount of tacrolimus and vehicle and stabilizing agent”
Scope implications
- These are dependent on Claim 1. They narrow stabilizers to organic acid classes and cap their amount.
- Loophole at the independent level: Claim 1 does not require organic acids. A competitor using a different metal-chelating agent that still yields pH < 7 and still fails or passes the endpoint becomes a key question for freedom-to-operate analysis.
How does Claim 7 constrain the vehicle?
- Vehicle = mixture of polyethylene glycol (PEG) and poloxamer
Scope impact: Dependent-only. It matters for product design: if the vehicle is not PEG/poloxamer, the Claim 7 dependent path is not available, but the product can still fall under Claim 1 if it satisfies the independent requirements.
How do Claims 8-9 frame 8-epitacrolimus and re-dispersion pH?
Claim 8
- Composition comprises 8-epitacrolimus <0.5% w/w
Claim 9
- After re-dispersing the composition in water, the aqueous composition pH is 2.5 to 4
Scope impact
- Claim 8 and Claim 9 are dependent routes. A competitor can potentially avoid them while still meeting Claim 1 if the overall Claim 1 constraints are satisfied.
- Claim 9 introduces a processing/formulation behavior condition, which can matter for products that are intended for reconstitution or re-dispersion before administration.
What does the citric-acid family (Claims 10-16) do to scope?
- Claims 10-16: “stabilizing agent comprises citric acid” across different dependent positions (tied to claims 1, 2, 3, 6, 7, 8, 9).
Scope impact: These create explicit citric-acid coverage. If a competitor uses citric acid as the stabilizer in a formulation that otherwise matches the independent elements, these dependent claims become direct hooks.
How does Claim 17 change the chelator definition (and what does it narrow)?
Claim 17
- Stabilizing agent is an organic acid selected from oxalic, tartaric, citric
- Still requires:
- metal-chelating agent that provides pH < 7
- “sufficient amount” such that <0.5% 8-epitacrolimus after 12 weeks at 25°C / 60% RH
- tacrolimus is the sole active ingredient
- sustained release solid dispersion of tacrolimus in vehicle + stabilizing agent
Scope impact
- Claim 17 is narrower by stabilizer identity but still independent. It matters because it gives an alternative independent pathway for challengers/enforcers: a formulation matching the citric/tartaric/oxalic list can be attacked directly under Claim 17 even if it falls outside other dependent permutations under Claim 1’s broader stabilizer functional definition.
How does Claim 19 differ (8-epitacrolimus present, not just controlled)?
Claim 19
- Sustained release composition includes:
- solid dispersion of tacrolimus
- mixture of vehicle + metal-chelating stabilizing agent providing pH < 7
- formulation contains 8-epitacrolimus
- 8-epitacrolimus concentration <0.2% w/w
- “sufficient amount” stabilizing agent so that after 12 weeks: <0.5% 8-epitacrolimus
- tacrolimus is the sole active ingredient
Scope implications
- Claim 19 is more specific about initial impurity presence (8-epi is present but kept below 0.2% w/w).
- A competitor trying to avoid this might formulate to 8-epi at or above 0.2% initially (which could be commercially undesirable) or remove 8-epi to essentially non-detectable (which may or may not avoid the claim depending on how the claim is interpreted regarding “contains”).
How do Claims 20-24 reinforce formulation robustness?
- Claim 20: solid dispersion is “substantially free of organic solvent”
- Claim 21: re-dispersed aqueous pH is 2.5 to 4
- Claims 22-24: stabilizing agent comprises citric acid under different claim linkages
Scope impact
- These define practical formulation constraints that can limit design-around options if a competitor’s process uses organic solvents or yields a different re-dispersion pH profile.
What does Claim 25 cover (tablet-specific, with 8-epitacrolimus component defined)?
Claim 25 elements
- Sustained release tablet comprising:
- (i) dispersion of tacrolimus
- (ii) 8-epitacrolimus
- (iii) stabilizing agent such that tablet has <0.5% 8-epitacrolimus after 12 weeks at 25°C / 60% RH (basis tied to “100% total weight of tacrolimus”)
- (a) tacrolimus is sole active ingredient in tablet
- (b) stabilizing agent is metal chelating agent providing pH < 7
Claim 26
- After re-dispersing the tablet in water: aqueous pH 2.5 to 4
Claims 27-28
- Stabilizing agent comprises citric acid
Scope impact
- Claim 25 converts the composition logic into a product-level claim that can reach commercial solid dosage forms. Even if a competitor’s formulation matches Claim 1, the tablet packaging/formulation requirements can still matter.
Where does this leave the broader patent landscape (enforcement leverage and likely design-arounds)?
What this patent is likely trying to protect
From the claim language, the “protected space” clusters around these technical attributes:
1) Tacrolimus solid dispersion sustained release
2) Chelator-driven pH control (<7)
3) Metal chelation as the stabilizing mechanism
4) Suppression of 8-epitacrolimus formation under accelerated storage (12 weeks at 25°C/60% RH)
5) Formulation constraints:
- optional citric acid specificity
- optional PEG/poloxamer vehicle
- optional “substantially solvent-free” dispersion
6) Endpoint framed as wt% impurity after storage, which can be used to distinguish over prior art even if prior art discloses similar excipients but does not achieve the same impurity suppression.
Practical interpretation for competitors
- If a competitor’s product:
- uses a solid dispersion of tacrolimus,
- uses a metal chelating agent that drives pH below 7,
- uses tacrolimus as the sole active,
- and meets (or avoids meeting) the 8-epi thresholds,
then the infringement analysis becomes largely a stability/impurity measurement exercise.
Likely design-around levers implied by the claims
Because the claim has multiple gating elements, a design-around typically moves on one of the “gate conditions”:
- pH gate: keep pH at or above 7 in the composition (if technically feasible for stability and drug performance).
- chelating agent gate: use a stabilizer that is not a “metal chelating agent” (or not characterized as such) and still meets other formulation objectives.
- solid dispersion gate: avoid a “solid dispersion” structure as claimed (though this is often hard to change without changing the formulation approach).
- tacrolimus sole active gate: add a second active (rare and usually clinically unacceptable for tacrolimus products, but it is a theoretical path).
- impurity endpoint gate:
- for Claim 1/17/25: avoid maintaining 8-epi below 0.5% after the specified storage; or
- for Claim 19: avoid having 8-epi below 0.2% initially (again, typically undesirable).
- process/solvent gate: if the product uses organic solvents and you want to avoid claim pathways tied to solvent-free dispersion, but note that Claim 20 is dependent only, so avoiding it does not defeat Claim 1.
Key invalidity/overlap pressure points to watch (claim structure tells where prior art must land)
For a prior art document to undermine these claims, it must match not only “tacrolimus solid dispersion” and “stabilizing acid,” but also:
- pH < 7 in the composition
- metal chelating function
- stress-storage impurity outcome (or an equivalent disclosure) for 8-epitacrolimus at 12 weeks / 25°C / 60% RH
- tacrolimus as sole active
That combination is stringent. It means overlap risk is highest when prior art includes:
- explicit discussion of 8-epitacrolimus as an impurity control target,
- stabilization using metal chelators or acidic chelators,
- and provides stability data under conditions similar to those recited.
Decision-ready landscape view (what to treat as “nearby” vs “farther away”)
Closest neighboring technical space
- Tacrolimus amorphous dispersions or solid dispersions with acidic stabilizers
- Formulations using citric acid (directly covered by dependent claims and structurally aligned with Claim 17)
- Systems designed around impurity suppression during storage
- pH-engineered formulations for tacrolimus stability
Farther technical space (less direct claim coverage)
- Tacrolimus sustained release formulations without a metal chelator or without pH < 7
- Chemo-stabilization approaches that do not target 8-epitacrolimus formation quantitatively
- Solid dosage forms that lack the solid-dispersion architecture
- Formulations where pH control exists only after reconstitution, not “in the composition,” unless they also satisfy the independent conditions
Key Takeaways
- The enforceable core is functional and outcome-defined: tacrolimus sustained release solid dispersion with metal chelating agent giving pH < 7 and 8-epitacrolimus suppression to <0.5% after 12 weeks (25°C/60% RH), with tacrolimus as the sole active.
- Citric acid is a heavily targeted dependent branch, and Claim 17 creates an independent pathway specifically for oxalic, tartaric, citric.
- Claim 19 and Claim 25 introduce “8-epi present but controlled” framing (Claim 19 uses <0.2% initial; Claim 25 ties tablet inclusion).
- Design-around is mostly gate selection: pH at/above 7, non-metal-chelating stabilizers, avoiding the solid dispersion definition, or failing the impurity endpoint.
- The patent landscape risk is highest for formulations that already pursue impurity stability of 8-epitacrolimus using metal-chelating acids under storage conditions that can be mapped to the recited 12-week test.
FAQs
1) What is the most important number in US 11,419,823 claims?
0.5% by weight of 8-epitacrolimus after 12 weeks at 25°C/60% RH (with tacrolimus as sole active).
2) Does the patent require citric acid to be used?
No. Citric acid is covered via dependent claims and by Claim 17 (oxalic/tartaric/citric), but Claim 1 is not limited to citric acid.
3) Is “metal chelating agent” defined by a list or by function?
The independent claim uses function (metal chelation + provides pH < 7). Lists appear in dependent claims.
4) Are these composition claims or tablet claims?
Both. Claims 1, 17, 19 are composition-focused; Claim 25 is a tablet-specific sustained release claim.
5) What does “solid dispersion” change in the scope?
It limits the formulation architecture to tacrolimus dispersed in a solid dispersion in a vehicle/stabilizer system, which is a structural requirement that can be harder to avoid than changing minor excipient percentages.
References
No sources were provided in the prompt text for US 11,419,823 file history, legal status, prosecution history, or external prior art.
