Details for Patent: 8,282,967

Which drugs does patent 8,282,967 protect, and when does it expire?

Patent 8,282,967 protects ZELSUVMI and is included in one NDA.

This patent has thirteen patent family members in six countries.

Summary for Patent: 8,282,967

Title:	Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications
Abstract:	The presently disclosed subject matter relates to nitric oxide-releasing particles for delivering nitric oxide, and their use in biomedical and pharmaceutical applications.
Inventor(s):	Mark H. Schoenfisch, Jae Ho Shin, Nathan Stasko
Assignee:	University of North Carolina at Chapel Hill , LNHC Inc
Application Number:	US13/168,597
Patent Claim Types: see list of patent claims	Compound;

US Patent 8,282,967 Nitric Oxide-Releasing Particles Co-Condensed Silica Network Diazeniumdiolate Scope, Claim Boundaries, and Competitive Landscape

US 8,282,967 is centered on nitric oxide (NO)-releasing particles built from a co-condensed silica network that incorporates a diazeniumdiolate NO donor. The patent’s claim scope is defined by (i) pre-formed NO donor chemistry prior to silica condensation, (ii) specific silane-building blocks including an aminoalkoxysilane bearing an amine substituted by diazeniumdiolate, and (iii) optional compositional modifiers (fluorinated silane, cationic/anionic silane, alkylsilane) and particle-size ranges. The tightest boundaries are the “co-condensed silica network comprising a nitric oxide donor” where the donor is formed prior to condensation, and the use of a defined silane mixture containing an aminoalkoxysilane with the specified diazeniumdiolate-substituted amine structure.

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What patents protect nitric oxide-releasing particles made from co-condensed silica networks with diazeniumdiolate?

Core claim architecture in US 8,282,967

Independent Claim 1 sets the technical center of gravity:

• An NO-releasing particle
• Comprising a co-condensed silica network
• Where the NO donor is formed prior to silica network condensation
• The silica network is synthesized by condensation of a silane mixture
• The silane mixture includes:
  • an alkoxysilane
  • at least one aminoalkoxysilane having an amine substituted by a diazeniumdiolate

This combination makes the protected subject matter narrower than broad “silica-encapsulated NO donors” concepts. The donor formation sequence matters, and the incorporation method is constrained by the requirement that the aminoalkoxysilane contains the diazeniumdiolate-substituted amine.

Claim 1 key limiting terms

1. “co-condensed silica network”
   The silica matrix is produced by co-condensation from multiple silanes rather than loading pre-made silica particles. This ties the scope to sol-gel/condensation chemistry of silane mixtures.

2. “nitric oxide donor is formed prior to condensation”
   The NO donor (the diazeniumdiolate functional group on the amine) must exist before the condensation step that builds the silica network. That excludes approaches where diazeniumdiolate is formed after matrix formation, even if the final material contains diazeniumdiolate.

3. “synthesized from condensation of a silane mixture comprising…”
   The method of constructing the silica network must derive from a silane mixture including the specified donor-functional silane (aminoalkoxysilane with diazeniumdiolate-substituted amine) and an alkoxysilane.

Dependent claims that expand or constrain composition

Dependent claims add hard boundaries that are commercially relevant for formulation differentiation.

Claim 2: structural formulas for silanes

• Alkoxysilane: tetraalkoxysilane Si(OR)4 (R is alkyl)
• Aminoalkoxysilane: R″—N(NONO−X+)—R′—Si(OR)3
  • R is alkyl
  • R′ is alkylene or aralkylene
  • R″ is alkyl or alkylamine
  • X+ is Na+ or K+

This is a formal structure lock. It is not enough to have “diazeniumdiolate functionality.” The claim requires the diazeniumdiolate to be substituted on an amine within a silane-bearing scaffold, producing a specific silyl-functional end that co-condenses.

Claim 3: molar ratios

• tetraalkoxysilane: 10–99 mol%
• aminoalkoxysilane diazeniumdiolate-substituted: 1–90 mol%

This sets quantitative composition boundaries. Products outside these ranges can fall outside literal infringement of Claim 3 (though doctrine-of-equivalents arguments can still arise, depending on prosecution history, which is not provided here).

Claim 4: optional comonomers

Allows additional silanes, each at 0–20 mol%:

• fluorinated silane
• cationic or anionic silane
• alkylsilane

The presence of these comonomers is permissive. The claim language is inclusive (0 mol% permitted), meaning baseline embodiments can omit them, while variants with up to 20 mol% of each modifier remain within scope.

Claims 5–8: enumerated species

These claims identify specific members of each silane subclass, which matters for both invalidity mapping and design-around analysis:

• Claim 5 (tetraalkoxysilane): tetraniethyl orthosilicate or tetraethyl orthosilicate
• Claim 6 (fluorinated silanes): listed perfluoro-containing triethoxysilanes/propyl/ethyl variants
• Claim 7 (cationic/anionic silanes): enumerated quaternary ammonium, phosphonate sodium salt, and carboxylate sodium salt silyl reagents
• Claim 8 (alkylsilane): methyltrimethoxysilane; butyltrimethoxysilane; butyltriethoxysilane; propyltrimethoxysilane; octadecyltrimethoxysilane

Practical effect: if a competitor uses a different tetraalkoxysilane (not among listed options), a different fluorinated silane (not listed), or different alkylsilane (not listed), their position depends on whether those subclaims are asserted or whether the independent claim 1/2 is broadened enough to cover non-enumerated alternatives.

Claims 9–11: particle diameter ranges

The patent includes three overlapping size limitations:

• Claim 9: 1 nm to 1000 nm
• Claim 10: 1 nm to 5 nm (narrow nanoparticle range)
• Claim 11: 2 nm to 10 μm (widens back out into micron scale)

These are broad and overlapping. If the same particle satisfies multiple ranges, multiple claims can be implicated. If a competitor targets dimensions outside all listed windows, it can attempt a design-around by size alone, though particle sizing for infringement can be contentious.

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What is the scope of “diazeniumdiolate” in US 8,282,967 and what structures are captured?

Diazeniumdiolate is not generic in this patent

The patent claims do not protect “any diazeniumdiolate NO donor in silica.” They protect a donor functionalized as part of an aminoalkoxysilane:
R″—N(NONO−X+)—R′—Si(OR)3 with X+ = Na+ or K+.

This matters because diazeniumdiolates can be paired with other counterions (e.g., other alkali metals, protonated forms, etc.). The claim restricts counterions to Na+ or K+ in Claim 2.

Sequence of donor formation is a meaningful boundary

The claim’s requirement that the nitric oxide donor is “formed prior to condensation” creates a functional-process boundary. Two products with identical final chemical features could still differ in process and sequence (depending on how “formed prior to condensation” is interpreted and proven in litigation).

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How broad is US 8,282,967 claim coverage versus common NO-releasing silica approaches?

Protected approach implied by claims

• Build an NO donor-functional aminoalkoxysilane with diazeniumdiolate
• Mix with tetraalkoxysilane and optionally fluorinated/cationic/anionic/alkyl silanes
• Co-condense to form a silica network that contains the NO donor in the matrix

Areas likely outside scope based on claim language

Without other references, the most defensible “outside scope” levers are those that violate explicit claim conditions:

1. NO donor formed after silica condensation
   If diazeniumdiolate is generated post-gelation in a way that differs from “donor formed prior to condensation,” it can avoid Claim 1’s literal condition.

2. Silica matrix formed without co-condensation from a silane mixture that includes the donor-functional aminoalkoxysilane
   If the silica is formed from a different route (e.g., loading NO donor into finished silica nanoparticles) the “synthesized from condensation of a silane mixture comprising … aminoalkoxysilane having an amine substituted by diazeniumdiolate” requirement is not met.

3. Different counterion than Na+ or K+ for diazeniumdiolate Claim 2 is restrictive.

4. Comonomer identities outside enumerated species where dependent claims are asserted Claim 4 is broad in allowing comonomers up to 20 mol% of any fluorinated/cationic/anionic/alkyl silane, but dependent claims 5–8 are enumerated. In practice, pleadings often select certain dependent claim sets. If asserted only at the independent level, scope can be broader.

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When does nitric oxide release occur under the claimed composition, and what does the claim not cover?

What the patent claims do not explicitly define

US 8,282,967 claim text you provided defines composition and construction chemistry. It does not specify:

• release kinetics (half-life, burst fraction, pH/trigger conditions)
• therapeutic indication or method of use
• additional encapsulation strategies beyond co-condensed silica formation
• particle morphology beyond diameter

As a result, the core enforceable property is structural/chemical and manufacturing sequence, not performance metrics.

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Which embodiments within US 8,282,967 are most likely asserted in infringement?

Highest-probability claim set

In most NO-particle disputes, plaintiffs tend to assert:

• Claim 1 (independent, strongest anchor)
• Claim 2 (structural silane definition)
• One of the particle size claims (Claims 9–11) depending on product characterization
• Potentially Claim 3 (molar ratio) if product composition is measured and mapped
• Comonomer-dependent claims only if competitors use the listed species

Why Claim 2 is central

Claim 2 supplies the chemical formula that turns “diazeniumdiolate-containing” into a specific scaffold. That gives experts a direct mapping criterion.

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What design-arounds exist against US 8,282,967 based on the claim limits?

Design-around levers aligned to explicit claim language

1. Change donor-formation timing relative to silica condensation Avoid “donor formed prior to condensation.” This is a process design point that may shift the record and complicate enforcement if donors are produced differently.

2. Use a different silane scaffold for the diazeniumdiolate Claim 2 requires the diazeniumdiolate-bearing amine to be part of an aminoalkoxysilane that co-condenses (Si(OR)3 functionality). Using a different functionalization approach can attempt to avoid Claim 2.

3. Use a diazeniumdiolate counterion other than Na+ or K+ This avoids a direct structural limitation of Claim 2.

4. Alter particle size out of the defined ranges Because Claims 9–11 overlap broadly, this is only viable if a competitor can reliably make particles outside all claimed diameter intervals. (This is difficult given overlap that spans to 10 μm in Claim 11.)

5. If relying on dependent claims, substitute non-enumerated silanes If a plaintiff asserts dependent claims 5–8, using different tetraalkoxysilanes/fluorinated/cationic-anionic/alkyl silanes that are not listed can narrow infringement exposure.

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Patent landscape assessment: how US 8,282,967 likely fits among NO-donor silica patents (and where conflicts typically arise)

Because the prompt does not include related-family numbers, prosecution history, or citation lists, a landscape can be structured only by claim motifs rather than enumerating specific competitor patents. Still, the claimed features imply typical prior-art clusters:

Claim-motif clusters relevant to invalidity or freedom-to-operate (FTO)

1. Diazeniumdiolate chemistry on aminoalkylsilanes The use of diazeniumdiolate-substituted amines paired to silane groups is a recognizable chemistry family. Validity challenges typically target whether such donor-functional silanes were already known and whether donor formation could precede condensation.

2. Co-condensed silica networks The “co-condensation of silane mixtures” into a network embedding a functional agent is a standard sol-gel pattern. Prior art may disclose co-condensed silica using functional alkoxysilanes, including fluorinated and charged silanes.

3. Inclusion of fluorinated and charged silanes in silica Fluorinated silanes and cationic/anionic silanes are commonly used to tune surface chemistry, compatibility, and particle stability. That increases the risk that dependent claims 4–8 could be attacked as obvious combinations of known silane additives with known NO donor incorporation.

Where US 8,282,967 can still be defendable

• The combination of donor formation sequence (donor formed prior to condensation) plus a specific aminoalkoxysilane diazeniumdiolate scaffold with defined counterions can be a non-trivial mapping point.
• Broad sol-gel NO-releasing disclosures may omit a precise structural formula and sequence requirement.

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What is the likely claim strength profile of US 8,282,967?

Strength drivers

• Independent Claim 1 is process-sequenced and chemically specific (“donor formed prior to condensation” and “silane mixture comprising… aminoalkoxysilane having an amine substituted by a diazeniumdiolate”).
• Claim 2 adds formula specificity and limits counterion to Na+ and K+.
• Claims 3 and 9–11 introduce measurable constraints (molar ranges and size).

Strength vulnerabilities

• Large design space within Claim 4 (0–20 mol% of multiple additive classes) can increase “obviousness” attack surfaces if all additives are known and used for compatibility/stability.
• Overlapping size claims (1 nm to 1000 nm; 1 nm to 5 nm; 2 nm to 10 μm) can reduce discrimination among products and increase breadth, but also can make enforcement harder if competitors are characterized slightly differently.

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Regulatory and commercial exposure implications for NO-releasing silica particles

US 8,282,967 is composition-focused and does not state an indication. Still, the formulation and manufacturing constraints directly affect:

• regulatory chemistry/manufacturing controls (CMC), because the donor formation step relative to condensation can be tied to process validation
• comparability in any post-approval manufacturing changes (sequence and silane mix composition)
• generic/biosimilar-analog risks for NO-donor nanoparticles (though “biosimilar” framing usually does not apply to small-molecule-derived particulate systems)

Commercial exposure tends to concentrate in:

• platform claims used in multiple programs (same NO donor chemistry across disease areas)
• licensing opportunities for manufacturing routes that deliver the claimed co-condensed matrix

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Key Takeaways

• US 8,282,967 protects NO-releasing nanoparticles built by co-condensing a silica network from a silane mixture where the diazeniumdiolate NO donor is formed prior to condensation.
• The tightest enforceable boundaries are the specific aminoalkoxysilane scaffold with a diazeniumdiolate substituted amine and counterion limited to Na+ or K+.
• Dependent claims further constrain silane identities (enumerated options), molar composition ranges, optional comonomer categories (fluorinated, charged, alkyl), and particle diameter.
• The most direct design-arounds are changing donor-formation timing, changing the diazeniumdiolate-containing silane scaffold, changing diazeniumdiolate counterions, and substituting non-enumerated silane components when dependent claims are asserted.

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FAQs

Does US 8,282,967 require the NO donor to be diazeniumdiolate specifically, or can other NO donors work?

The claims require an aminoalkoxysilane with an amine substituted by a diazeniumdiolate, and the Claim 2 formula includes a diazeniumdiolate moiety.

Can a product infringe US 8,282,967 if it uses diazeniumdiolate in silica but not via co-condensation of the silane mixture?

Literal scope in Claim 1 requires that the silica network is synthesized from condensation of a silane mixture that includes the donor-functional aminoalkoxysilane. A different construction method is a key non-infringement vector.

What counterions for the diazeniumdiolate are allowed in the strongest dependent claim?

Claim 2 restricts X+ to Na+ and K+.

Do the particle size claims narrow protection meaningfully for infringement analysis?

They are broad and overlapping, with ranges extending to 10 μm. They can cover many nanoparticle products, making size-based design-around difficult unless the competitor is well outside all claimed windows.

If a competitor uses different fluorinated or charged silanes, does that avoid the patent?

If dependent claims 6 and 7 are asserted, using non-enumerated fluorinated/cationic-anionic silanes can matter. If only Claim 1 is asserted, the need to map to the donor-functional aminoalkoxysilane and donor-formation sequence remains central.

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References (APA)

1. United States Patent 8,282,967. (n.d.). Nitric oxide-releasing particles comprising a co-condensed silica network with an NO donor formed prior to condensation (claims provided in prompt).

Drugs Protected by US Patent 8,282,967

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Lnhc	ZELSUVMI	berdazimer sodium	GEL;TOPICAL	217424-001	Jan 5, 2024		RX	Yes	Yes				Y

International Family Members for US Patent 8,282,967

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006249323
Canada	2606565
Canada	2912259
European Patent Office	1888510
European Patent Office	2669269
European Patent Office	3556401