US Patent 8,604,072 Scope and Claims: Dantrolene Sodium Colloidal IV Formulation and Hyperthermia Treatment Methods

US 8,604,072 claims a set of method-of-treatment claims tied to use of a specific safe-for-IV, low-volume, liquid dantrolene sodium formulation defined by particle size, excipient selection, concentration ranges, and (in dependent claims) reconstitution/agitation parameters and dosing/volume constraints. The independent claim scope is concentrated around a formulation where dantrolene sodium forms a colloidal dispersion of particles < ~2 microns in water with a water-soluble polysorbate plus sorbitol or mannitol, at 3.33 to 166.67 mg/mL, and is administered IV to treat hyperthermia or malignant hyperthermia.

What does US 8,604,072 claim protect for IV dantrolene sodium in hyperthermia?

Core protection theme: how to treat hyperthermia (including malignant hyperthermia) using an intravenous, ready-for-injection formulation of dantrolene sodium that is defined by physical dispersion characteristics and excipient/concentration constraints.

Independent claim 1 (hyperthermia)

Claim 1 requires all of the following elements in combination:

A. Indication

Treating hyperthermia in a mammal.

B. Administration

Administering a therapeutically effective amount of a “safe for injection, low volume liquid formulation” of dantrolene sodium that is safe for intravenous administration.

C. Formulation composition (must meet all specified constraints)

Dantrolene sodium concentration: 3.33 mg/mL to 166.67 mg/mL
Polysorbate: at least one water-soluble polysorbate
Bulking/tonicity agent: sorbitol or mannitol
Liquid carrier: water
Colloidal dispersion requirement: dantrolene sodium and water are present together as a colloidal dispersion of dantrolene sodium particles in the water
Particle size requirement: dantrolene sodium particles are < about 2 microns average diameter

D. Primary formulation identity constraint

There is no claim of broader “dantrolene” use irrespective of formulation; the formulation definition is an infringement gate.

Independent claim 15 (malignant hyperthermia)

Claim 15 mirrors claim 1 but narrows the therapeutic purpose to malignant hyperthermia. The formulation definition is the same.

Practical infringement consequence

To infringe independent claims, an accused method must involve:

IV administration to treat hyperthermia/malignant hyperthermia, and
use of a dantrolene sodium product that matches the particle size <2 µm, polysorbate + sorbitol/manntitol, and 3.33–166.67 mg/mL concentration bands, and
uses water as the carrier in the claimed dispersion form.

How broad are the claims: is it about dantrolene itself or the specific colloidal dispersion?

It is formulation-characterized claim scope. The claims are not merely “dantrolene treatment.” They are dantrolene treatment using a formulation defined by:

Colloidal dispersion
Sub-2-micron particle size
Specific excipient classes: water-soluble polysorbate and sorbitol or mannitol
Concentration window
IV-safe “low volume liquid formulation” (low volume is not quantified in the independent claims, but the dependent claims supply dose/volume limitations)

The sub-2-micron requirement is the most technically constraining element and is likely the biggest non-infringement lever.

What formulations are protected by US 8,604,072 (particle size, excipients, concentration, “safe for IV”)?

Key formulation limitations

Claim element	Requirement in independent claims 1/15	Litigation/clearance significance
Particle size	< ~2 microns average diameter	Central differentiator vs conventional suspensions and reconstituted powders
Concentration	3.33 to 166.67 mg/mL	Defines quantitative infringement; outside window may avoid literal infringement
Polysorbate	Water-soluble polysorbate	“Which polysorbate” is not fixed to a single species, but must be water-soluble
Polyol	Sorbitol or mannitol	Restricts excipient choice; other stabilizers may not be substituted if claim requires one of these
Carrier	Water	Excludes non-aqueous or mixed-carrier systems unless still meet “water as liquid carrier” language
Dosage form	“safe for injection, low volume liquid formulation” and safe for IV	Limits to an IV-ready or reconstituted IV-ready product consistent with the formulation description

Colloidal dispersion requirement

The claims specify dantrolene sodium particles dispersed as a colloidal dispersion in water, not merely dissolved dantrolene in molecular form. That distinction matters for alternative solid dispersion or molecular solutions.

What do the dependent claims add: concentration sub-ranges, primary modulator language, and PVP?

Claim 2 / 16 (concentration sub-ranges)

These tighten concentration to:

30–80 mg/mL, or
10–60 mg/mL

The dependent nature means this narrower band is only relevant if an accused product falls inside those ranges.

Claim 3 (mechanistic framing)

“dantrolene sodium is the primary modulator of intracellular calcium”

This is a method framing that typically won’t avoid infringement if the product matches formulation limits; it functions more as supportive/characterizing language. Still, it can be used to argue that an accused formulation’s clinical effect is attributable to dantrolene acting as the intracellular calcium modulator.

Claims 5–6 / 19 (PVP inclusion)

Claim 5: formulation further comprises polyvinylpyrrolidone (PVP)
Claim 6: “consists essentially of” list includes PVP along with polysorbate, sorbitol/manntiol, water, and dantrolene at the claimed concentration window and particle size.

If an accused product uses PVP but deviates from other constraints (particle size window, polysorbate presence, polyol selection, concentration band), it may still avoid.

What method and manufacturing steps are claimed: reconstitution, agitation time, and “ready for injection”?

Claim 12 / 18 (two-step reconstitution pipeline)

These depend on independent claim 1 and claim 15 respectively, and add a preparation workflow:

A dry formulation comprising:
- dantrolene sodium with particles < ~2 microns avg diameter
- sorbitol or mannitol
- water-soluble polysorbate
The dry formulation is reconstitutable by water to form:
- a liquid colloidal dispersion with particles < ~2 microns
- water as carrier
- safe-for-IV
- dantrolene at 3.33–166.67 mg/mL
After combining (i.e., reconstitution), the liquid formulation is ready for injection.

Key scope point: the claim requires that even after reconstitution, the particle size remains <2 µm (not just at the dry intermediate stage). This is a major technical requirement.

Claims 13–14 (mechanical agitation and time)

Claim 13: combining comprises mechanical agitation
Claim 14: combining is performed in one minute or less

This creates a process-like sub-scope that can be used to argue non-infringement if preparation requires longer time or non-agitation steps. Since the independent claims do not include this, it is mostly relevant for products claiming the same manufacturing/reconstitution pathway.

What dosing and volume limitations are claimed (250–300 mg; 3–150 mL; ≤10 mL; ≤5 mL)?

Dependent claims tie administration quantities to the formulation-defined IV product:

Claim 7: administering 3–150 mL of formulation
Claim 8: administering 10 mL or less
Claim 9: administering 5 mL or less
Claim 10 / 11: administering 250–300 mg dantrolene sodium

How these constraints affect scope

These limits can reduce the chance of literal infringement for generic or alternate versions if they:

require larger injection volumes to deliver the same mg dose, or
formulate outside the dantrolene concentration bands, forcing higher mL amounts.

They also align with the “low volume” language in the independent claims, but provide explicit quantitative hooks.

Where the claim language creates infringement leverage: “consists essentially of” and particle size

“Consists essentially of” in claims 4 and 6

Claim 4:

“formulation consists essentially of” dantrolene at 3.33–166.67 mg/mL, water-soluble polysorbate, sorbitol/manntiol, water carrier, colloidal dispersion of particles <2 µm, and safe-for-IV.

Claim 6 repeats the same “consists essentially of” structure but adds PVP.

Implication: the “consists essentially of” construct can bar additional components unless they do not materially alter the basic and novel characteristics of the formulation. Practically, it creates a pathway to non-infringement if an accused product uses additional excipients that are argued to materially alter characteristics.

Particle size as the primary technical “off-ramp”

Because the claims are explicit about average diameter <2 microns, a competing formulation with larger particles, a different dispersion state, or different measurement methodology could create non-infringement arguments (especially if literal particle size fails). The reconstitution claims raise the bar: size must remain <2 µm after reconstitution to a safe-for-IV colloidal dispersion.

How many claims map to each protection layer (treatment vs formulation vs preparation vs dosing)?

Claim	Protection layer	Incremental limitation added
1	Treatment + formulation	Independent: hyperthermia + specific colloidal IV formulation definition
2	Treatment + concentration sub-range	Narrow concentration band(s)
3	Treatment + mechanism framing	“primary modulator of intracellular calcium”
4	Treatment + formulation “consists essentially of”	Bars extra formulation components (unless immaterial)
5	Formulation	Adds PVP
6	Formulation “consists essentially of”	Adds PVP under controlled “consists essentially of” list
7	Administration	Volume 3–150 mL
8	Administration	Volume ≤10 mL
9	Administration	Volume ≤5 mL
10	Administration	Dose 250–300 mg
11	Administration	Dose 250–300 mg (dependent on claim 7)
12	Preparation + treatment	Dry-to-liquid reconstitution path with retained <2 µm particles
13	Preparation	Mechanical agitation
14	Preparation	Agitation ≤1 minute
15	Treatment + formulation	Independent: malignant hyperthermia + same IV formulation definition
16	Treatment + concentration sub-range	Same as claim 2
17	Treatment + concentration sub-range	Duplicate of 16
18	Preparation + treatment	Dry-to-liquid reconstitution path
19	Preparation/formulation	Adds PVP in dry formulation

What does US 8,604,072 likely mean for competitors: generic and biosimilar risk framing

US 8,604,072 is not a biologic patent and does not map to a biosimilar framework. It is a small-molecule drug product/formulation and method-of-use claim set centered on dantrolene sodium IV dispersion characteristics.

Generic entry risk

A generic dantrolene sodium IV product that:

does not achieve <2 µm average particles in the administered liquid dispersion, or
uses a different excipient system that still results in nonconforming dispersions, or
delivers the target dose at higher injection volume outside ≤10 mL / ≤5 mL dependent constraints,

may reduce literal infringement exposure. But the independent method claims remain available if formulation meets every limitation.

Product substitution risk

Even if an alternative product treats malignant hyperthermia effectively, infringement depends on whether its formulation used in the method matches the claim’s dispersion and excipient/concentration requirements.

Patent landscape analysis for US 8,604,072 (what to look for next in related estates)

The claims you supplied define a clear “center of gravity”: dantrolene sodium colloidal IV dispersion (sub-2 µm), excipient system (water-soluble polysorbate + sorbitol or mannitol, optionally PVP), and reconstitution/agitation time parameters.

To map the landscape around US 8,604,072 for freedom-to-operate or licensing, the key is to locate:

earlier formulation patents defining dantrolene IV dispersion and excipient systems,
later continuation/divisional claims improving particle size, concentration, or reconstitution workflow,
Orange Book listings tied to dantrolene IV dosage forms that reflect the same formulation concepts.

However, no patent bibliographic data, prosecution history, citation list, family members, assignees, filing priority, expiration dates, or listed related patents were provided in the prompt. Without those, a complete and accurate landscape count (other patents, family scope, or litigation docket mapping) cannot be produced here.

Claim strength assessment: where the patent is likely strongest vs where it is most attackable

Likely strongest axes

Explicit particle size limitation (<2 µm average diameter): concrete and testable.
Tightly specified excipient classes: polysorbate + sorbitol/manntol.
Quantitative concentration window: 3.33–166.67 mg/mL.
Reconstitution claims retaining particle size: raises technical burden for design-arounds.

Likely attack axes

Particle size measurement and definition disputes (average diameter; colloidal dispersion characterization).
Whether “safe for IV” is met by an accused formulation and whether it is a functional limitation tied to specific properties.
“Consists essentially of” component additions: design-arounds that include additional stabilizers/tonicity agents could argue non-infringement depending on whether they materially alter basic and novel characteristics.

Key Takeaways

US 8,604,072 is centered on IV treatment methods that require use of a specific dantrolene sodium colloidal dispersion formulation: <2 µm average particle size, 3.33–166.67 mg/mL, with water-soluble polysorbate and sorbitol or mannitol in water, and safe for intravenous administration.
Dependent claims add narrow concentration bands (10–60 mg/mL or 30–80 mg/mL), PVP inclusion, and explicit dose and volume constraints (including ≤10 mL and ≤5 mL for the administered formulation; 250–300 mg dantrolene).
Preparation claims cover dry-to-liquid reconstitution where the sub-2-micron particle characteristic must persist after reconstitution, plus mechanical agitation ≤1 minute.
The most actionable design-around lever is the sub-2 micron particle size requirement, followed by excipient system and concentration windows.

FAQs

Does US 8,604,072 require dantrolene to be dissolved or dispersed to infringe?
It requires a colloidal dispersion of dantrolene particles in water with average diameter < ~2 microns.
Can a competing formulation avoid infringement by changing polysorbate or removing sorbitol/manntol?
Literal scope requires a water-soluble polysorbate and sorbitol or mannitol plus the claimed dispersion and concentration/particle-size constraints.
Do the “low volume” limitations apply only through dependent claims?
The independent claims include “low volume,” while dependent claims provide explicit volume ceilings: 3–150 mL, ≤10 mL, and ≤5 mL.
What is the impact of “consists essentially of” language in claims 4 and 6?
It restricts additional excipients under an “immaterial to basic and novel characteristics” standard, creating an additional design-around argument beyond simple excipient omission.
Are manufacturing or reconstitution steps required for all infringement under US 8,604,072?
No. The reconstitution/agitation limitations appear in dependent preparation claims (e.g., claims 12–14, 18–19). The independent method claims are formulation-defined and do not require the specific reconstitution workflow.

References (APA)

No sources were provided or cited in the prompt beyond the claim text of US 8,604,072.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2004262507	⤷ Start Trial
Canada	2516667	⤷ Start Trial
European Patent Office	1435781	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,604,072

Summary for Patent: 8,604,072