US Patent 6,375,986: What Do the Claims Actually Cover, and Where Does It Sit in the Landscape?

Scope of Claim Coverage

US 6,375,986 claims a specific formulation architecture for poorly soluble drugs made into a solid dose nanoparticulate product that redisperses after reconstitution into particles below specified size cutoffs. The independent claim (claim 1) is composition-focused; claims 17 and 27 are method and use-focused, with essentially the same technical limitations across them.

At a high level, the claimed technology is defined by four hard technical pillars:

Active agent solubility threshold
- “active agent” has solubility in the liquid dispersion medium of < about 10 mg/mL.
Stabilized nanoparticulate dispersion
- at least one polymeric surface stabilizer adsorbed on the active agent surface.
Mandatory surfactant excipient window
- dioctyl sodium sulfosuccinate (DOSS) at ~0.1% to ~20% w/w.
Bimodal particle size performance before and after solidification
- Before solid dose incorporation: effective average particle size of the nanoparticulate dispersion < about 1 micron (with dependent claim ranges down to <200 nm).
- After reconstitution in media representative of human physiological conditions: “90% of the active agent particles” are < about 5 microns (with dependent claim cutoffs down to <1 micron for the post-reconstitution 90% metric).

This combination is unusually specific because it locks in:

a surfactant identity (DOSS),
a solubility bracket (<10 mg/mL in the dispersion medium),
a polymer adsorption requirement, and
two distinct particle size outcomes (pre-solidification nanoparticle size and post-reconstitution 90% percentile size).

That structure limits claim reach against formulations that:

use different surfactants,
avoid polymer adsorption,
do not achieve the post-reconstitution 90% particle-size criteria, or
do not use the particle-size regime in the milling/dispersion stage.

Independent Claim 1: Composition Limits That Control Noninfringement

Claim 1 requires all of the following, in one composition:

Solid dose nanoparticulate composition
Active agent: solubility in the dispersion medium < 10 mg/mL
Polymeric surface stabilizer: “adsorbed on the surface of the active agent”
DOSS: 0.1% to 20% w/w
Effective average particle size of nanoparticulate dispersion prior to incorporation: < 1 micron
Redispersibility after reconstitution:
- in media representative of human physiological conditions
- 90% of active agent particles are < 5 microns

Key quantitative “gates” in claim 1

Parameter	Limitation in Claim 1	Practical meaning in freedom-to-operate
Active solubility in dispersion medium	< ~10 mg/mL	Excludes actives that meet higher solubility under the claimed dispersion conditions
DOSS content	~0.1% to ~20% w/w	Strong filter; different surfactant chemistries can avoid on composition identity unless equivalency is pursued
Pre-solid effective average particle size	< ~1 micron	Excludes coarse dispersions that do not mill below this level
Post-reconstitution redispersed particle size	90% < ~5 microns	Requires meaningful redispersibility, not just initial size reduction

Dependent Claims 2-16: Claim Refinement by Ingredient Ratios and Particle Size Bands

Active agent concentration windows (claims 2-4)

Claim 1 is broad on active loading, then dependent claims narrow:

Claim 2: active agent ~99.8% to ~0.1% (w/w)
Claim 3: active agent ~80% to ~5% (w/w)
Claim 4: active agent ~50% to ~10% (w/w)

These ranges can matter when evaluating competitor formulations with fixed loading targets.

Polymeric surface stabilizer loading (claims 5-7)

Claim 5: polymer ~0.01% to ~90% w/w
Claim 6: polymer ~1% to ~75% w/w
Claim 7: polymer ~10% to ~60% w/w

This gives room for polymer-rich and polymer-lean systems, but still anchors to a polymer being present in a meaningful range.

DOSS sub-range (claim 8)

Claim 8: DOSS ~1% to ~10% w/w

So even within the independent claim window (0.1% to 20%), the patent explicitly covers a mid-band commonly used for wetting/dispersing.

Particle size tightening (claims 9-12)

The patent steps down both the pre-solidification and post-reconstitution thresholds:

Dependent claim	Pre-incorporation effective average size	Post-reconstitution criterion (90% size)
Claim 9	< ~800 nm	90% < ~4 microns
Claim 10	< ~600 nm	90% < ~3 microns
Claim 11	< ~400 nm	90% < ~2 microns
Claim 12	< ~200 nm	90% < ~1 micron

This matters because many nanoparticle systems may achieve submicron size but fail the specific redispersibility distribution after reconstitution.

Active agent type coverage (claims 13-14)

Claim 13 includes phase diversity:

crystalline, semi-crystalline, or amorphous phase drugs.

Claim 14 is an extensive “selected from” list covering many therapeutic categories and agent classes. The list is broad enough that it functions more like support for generic applicability than a limitation that meaningfully narrows infringement risk by itself.

Polymer stabilizer identity (claims 15-16)

Claim 15 lists categories including:

PVP, cellulose ethers, polysaccharides, random vinyl acetate/vinyl pyrrolidone copolymers, PVA, and vinyl acetate/vinyl alcohol copolymers.

Claim 16 gives specific exemplars:

HPC, HPMC, CMC, methyl cellulose, HEC, dextrin, guar gum, starch, and a copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate (mass proportion 3:2).

For a competitor, this creates a potential sub-claim trap: even if they use polymers outside these groups, claim 1 still only requires “at least one polymeric surface stabilizer,” so non-infringement arguments would hinge on whether their polymer qualifies as “polymeric surface stabilizer” and whether it is adsorbed on the active surface.

What’s the Method Coverage (Claims 17-26) and How Broad Is It?

Method of making the nanoparticulate solid dose (claim 17)

Claim 17 recites a manufacturing sequence that maps to common milling/drying workflows but with required technical outcomes and required ingredient timing:

(a) Disperse particles of an active agent with solubility < 10 mg/mL in a liquid dispersion medium.
(b) Apply mechanical means with grinding media to reduce effective average particle size to < 1 micron.
- Add polymeric surface stabilizer and DOSS to the liquid dispersion medium before or after milling.
(c) Dry the nanoparticulate dispersion comprising:
- active agent
- polymeric surface stabilizer
- DOSS
(d) Formulate into a solid dose form.

Then the claim includes the functional redispersibility requirement:

after reconstitution in physiological-mimicking media, 90% of active agent particles are < 5 microns.

Method claim focus points (where infringement hinges)

Claim element	Manufacturing fact pattern that matters
Milling with grinding media	Whether the process achieves <1 micron effective average size
DOSS + polymer timing	Added before or after milling still fits; switching to a different surfactant identity is the main escape hatch
Drying into solid dose	Drying step is required, but does not specify spray drying vs other routes
Reconstitution performance	The product must redispersed to required particle size distribution

Dependent method claims

Claim 18: active agent ~99.8% to ~0.1%
Claim 19: polymer ~0.01% to ~90%
Claim 20: DOSS ~0.1% to ~20%
Claim 21: DOSS ~1% to ~10%
Claims 22-26: phase of active and additional particle-size tightening bands matching claims 13 and 9-12.

Method of treatment / use (claims 27-34)

Claim 27 uses essentially the composition of claim 1 as the administered entity and ties to:

a patient in need,
therapeutically effective amount,
and the same defined functional performance.

Dependent claims 28-34 mirror the same quantitative sub-ranges and tighter size bands as earlier.

Legal and business implication: claims 27-34 increase leverage because they cover the act of administering the composition, not just manufacturing or possessing it.

Patent Landscape: Where Does US 6,375,986 Sit, and What Blocks or Is Blocked?

Landscape drivers created by the claim structure

US 6,375,986 aligns with a recognizable segment of the drug delivery patent space:

poorly soluble drugs
nanoparticulate dispersions
polymeric stabilization
surfactant-assisted wetting/redispersion
conversion into a solid dosage that reconstitutes into nanoscale or sub-micron-to-micron distributions

What makes this patent land among the “strongly specific” entries in that landscape is the explicit DOSS requirement plus the two-point particle size performance definition.

Practical scope interactions

Against patents that use different surfactants (polysorbates, bile salts, sodium lauryl sulfate, poloxamers, or custom surfactant blends): competitors can often design around the surfactant identity while still using polymer-stabilized nanoparticles, unless their process/product falls into literal equivalence arguments.
Against patents that achieve nanoparticle size but fail redispersibility distribution: many systems degrade or aggregate on reconstitution, causing failure of the “90% < x microns” requirement.
Against “polymer-stabilized amorphous solid dispersions” without DOSS or without the defined reconstitution particle-size distribution: claim coverage narrows because the patent is about solid dose nanoparticulates with defined reconstitution performance, not amorphous solid dispersions per se.

Competitive design-around map (based strictly on claim limitations)

Claim limitation	Most direct design-around lever
DOSS identity (dioctyl sodium sulfosuccinate)	Replace DOSS with a different surfactant system; or remove DOSS entirely
DOSS loading 0.1% to 20% w/w	Use outside the window (but identity still matters)
Polymer “adsorbed on surface”	Use a stabilizer system that does not adsorb (e.g., a matrix-embedded stabilizer) or demonstrate different stabilization mechanism
Pre-solid effective average size < 1 micron (or <800/600/400/200 nm bands)	Maintain dispersion above thresholds or avoid milling/size reduction regime
Post-reconstitution redispersion: 90% < 5 microns (or <4/3/2/1 bands)	Induce controlled aggregation on reconstitution or use reconstitution media assumptions that avoid the distribution criterion

Claim Scope Summary for Commercial Clearance

If a candidate product matches all of the following, infringement risk is high:

poorly soluble active with solubility <10 mg/mL in its dispersion medium,
polymeric stabilizer that adsorbs onto particles,
DOSS present at 0.1% to 20% w/w,
pre-solidified nanoparticulate dispersion with effective average size <1 micron, and
reconstitution yields 90% of particles below the claimed micron cutoff.

If any one of these pillars is absent, the literal claim set is harder to meet. The tightest commercial lever is the DOSS identity and content, followed by the post-reconstitution 90% particle size distribution.

Key Takeaways

US 6,375,986 is built on four hard requirements: DOSS (0.1% to 20% w/w), polymer adsorption, poorly soluble actives (<10 mg/mL in dispersion medium), and a two-stage particle size/redispersion performance specification.
Dependent claims tighten coverage into smaller nanoparticle bands (down to <200 nm pre-solid) and stricter redispersion outcomes (down to 90% <1 micron post-reconstitution).
Method claims mirror composition claims with process constraints (milling with grinding media, ingredient addition before or after milling, drying into solid dose).
Use claims extend exposure to administration of the defined redispersible nanoparticulate solid dose.
Landscape positioning: the patent is likely to collide most with other drug delivery patents that also require DOSS and similar redispersion particle-size distributions; conflicts are less likely with systems that change surfactant identity or fail the post-reconstitution 90% micron thresholds.

FAQs

1) Which element is the sharpest discriminator for infringement risk?

The explicit inclusion of dioctyl sodium sulfosuccinate (DOSS) at 0.1% to 20% w/w, combined with the defined post-reconstitution 90% particle size outcome.

2) Do the claims cover both crystalline and amorphous actives?

Yes. Claim 13 explicitly includes crystalline, semi-crystalline, and amorphous phase drugs.

3) What post-reconstitution metric is required?

For claim 1, after reconstitution in physiological-mimicking media, 90% of the active agent particles must be < about 5 microns (with tighter thresholds in dependent claims).

4) Does the patent require a specific milling approach?

Claim 17 requires “mechanical means” with grinding media to reduce the effective average particle size to < about 1 micron prior to drying and solid-dose formulation.

5) Are polymer types limited or broad?

The patent includes both broad “polymeric surface stabilizer” coverage in claim 1 and specific polymer examples in dependent claims 15-16. The strongest literal hook is polymer presence that is adsorbed on the active agent surface.

References

[1] US Patent No. 6,375,986 (claims 1-34). United States Patent and Trademark Office (USPTO).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	040110	⤷ Start Trial
Argentina	072134	⤷ Start Trial
Argentina	072135	⤷ Start Trial
Argentina	111501	⤷ Start Trial
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Details for Patent: 6,375,986

Summary for Patent: 6,375,986