Details for Patent: 8,956,658

Which drugs does patent 8,956,658 protect, and when does it expire?

Patent 8,956,658 protects ZELSUVMI and is included in one NDA.

This patent has thirteen patent family members in six countries.

Summary for Patent: 8,956,658

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:	US14/014,939
Patent Claim Types: see list of patent claims	Compound;

Scope and Claims Analysis for US Patent 8,956,658: Nitric Oxide-Releasing Particles Based on Co-Condensed MAP3/TEOS Silica Networks

US Patent 8,956,658 claims nitric oxide (NO)-releasing particles built on a specific co-condensed silica network using methylaminopropyl trimethoxysilane (MAP3) and tetraethyl orthosilicate (TEOS), where MAP3 is uniformly distributed and is functionalized with N-diazeniumdiolate (diazeniumdiolate) NO-donor chemistry. The independent claim is narrowly structured around (i) a defined NO donor form (N-diazeniumdiolate functionalized MAP3), (ii) a defined silica co-condensation system (MAP3 with TEOS forming a co-condensed silica network), and (iii) distribution of MAP3 throughout the particle. Dependent claims broaden or narrow coverage via MAP3 loading expressed in mol percent, including broad ranges (1% to 90%) and a narrower midpoint (about 50%), with a second narrower range (10% to 75%) and a 45% to 55% band.

What does claim 1 require for infringing a nitric oxide-releasing particle under US 8,956,658?

Featured snippet answer: Claim 1 requires a nitric oxide-releasing particle containing a co-condensed MAP3/TEOS silica network in which MAP3 is distributed throughout the particle and MAP3 is functionalized with N-diazeniumdiolate groups.

Core elements of claim 1 (element-by-element)

Claim 1 is written as a composition claim with multiple structural limitations:

1. A “nitric oxide-releasing particle.”
   The claim targets particles that release NO, not merely materials that can generate NO under all conditions. The claim language ties release functionally to the particle.

2. A co-condensed silica network.
   The particle must have a silica network formed by co-condensation of:

   • MAP3 (methylaminopropyl trimethoxysilane), and
   • TEOS (tetraethyl orthosilicate).

3. MAP3 is distributed throughout the particle.
   This is a claim-limiting distribution requirement. It is not enough that MAP3 is present; it must be “distributed throughout” the particle. That phrase typically implies incorporation across the particle matrix rather than surface adsorption or localized enrichment zones.

4. MAP3 comprises N-diazeniumdiolate functionalized MAP3.
   MAP3 must be functionalized with N-diazeniumdiolate moieties, meaning the amine functionality on MAP3 is converted to diazeniumdiolate NO-donor species. The claim does not read on generic amine-functionalized silica without the diazeniumdiolate functionality.

Claim 1 likely establishes a “materials architecture” boundary

From a freedom-to-operate perspective, claim 1 draws a boundary around both:

• the chemistry (N-diazeniumdiolate functionalization of MAP3), and
• the structural incorporation (MAP3/TEOS co-condensed silica, with MAP3 distributed throughout).

In practical infringement analysis, these limitations usually drive technical claim construction and testing strategies:

• silica composition verification (MAP3 vs TEOS incorporation),
• diazeniumdiolate presence/quantification (or a scientifically accepted surrogate),
• and distribution assessment (uniform incorporation vs surface-localization).

How broad are the MAP3 mol% ranges in dependent claims 2, 3, 4, and 5?

Featured snippet answer: Dependent claims set MAP3 loading windows from very broad (1%–90% mol%) to medium (10%–75%), with a narrower band (45%–55%) and a specific point target (about 50%).

Dependent claim 2: MAP3 in 10% to 75% mol%

• Claim 2 depends on claim 1.
  It inherits the claim 1 requirements and adds a numerical MAP3 loading limit:
  • MAP3 is present in 10% to 75% mol%.

This range would capture compositions where MAP3 content is substantial but not extreme.

Dependent claim 3: MAP3 in 1% to 90% mol%

• Claim 3 depends on claim 1 and expands the loading window:
  • MAP3 is present in 1% to 90% mol%.

This is the broadest numerical range among the dependent claims shown. It covers low-MAP3 and high-MAP3 formulations, subject to claim 1’s distribution and diazeniumdiolate functionalization.

Dependent claim 4: MAP3 in 45% to 55% mol%

• Claim 4 depends on claim 1 and narrows:
  • MAP3 is present in 45% to 55% mol%.

This band is centered around mid-range MAP3 levels and can be used to capture “optimized” formulations.

Dependent claim 5: MAP3 present at about 50% mol%

• Claim 5 depends on claim 4, further narrowing:
  • MAP3 is present in about 50% mol%.

This claims a target formulation point. In litigation, “about” typically introduces tolerance, so claim scope likely depends on how the specification defines measurement and acceptable deviation.

What the dependent claims imply about drafting intent

The claim set uses:

• a wide umbrella (1%–90%),
• a mid range (10%–75%),
• and two tight bands around ~50%.

That pattern suggests the patent estate is designed to cover multiple formulation “knobs” around MAP3 loading. If a competitor lands anywhere within these windows while keeping the core claim 1 architecture, dependent claims can supply direct claim coverage.

What is the technical scope of “co-condensed silica network comprising MAP3 and TEOS”?

Featured snippet answer: The particle must form a silica network by co-condensation of MAP3 and TEOS, with MAP3 uniformly incorporated across the particle and later converted to diazeniumdiolate NO donors.

How to interpret “co-condensed” for infringement mapping

For infringement analysis, “co-condensed” usually indicates that the silica matrix is formed from both precursors in the condensation step rather than being a composite of separate phases. That impacts:

• whether MAP3 is incorporated during sol-gel formation with TEOS,
• and whether MAP3 content is integrated into the matrix network.

If a product uses a physical blend of separate silica phases or grafts MAP3 after forming TEOS-derived silica, it may risk non-infringement if “co-condensed” is construed to require co-network formation.

How “silica network” constrains the particle material

A “silica network” is a solid inorganic network. It excludes:

• purely polymeric carriers,
• lipid carriers,
• and other inorganic matrices not described as silica networks, unless they still meet the co-condensed silica network requirement.

What does “MAP3 distributed throughout the particle” exclude?

Featured snippet answer: Claim 1 excludes particles where MAP3-derived NO donor groups are localized at the surface or only in a superficial layer rather than distributed across the particle matrix.

Distribution is a limiting feature, not a mere characteristic

“Distributed throughout” narrows the claim against:

• surface-functionalized silica where diazeniumdiolate groups exist predominantly at external surfaces,
• core-shell structures where MAP3 is restricted to only one region,
• or formulations where MAP3 is present in minor localized domains.

From a technical standpoint, proving distribution may depend on microscopy coupled with chemical mapping, depth profiling, or other characterization that demonstrates uniform incorporation.

What is “N-diazeniumdiolate functionalized MAP3” and why is it claim limiting?

Featured snippet answer: MAP3 must be converted so that its amine functionality is present as N-diazeniumdiolate, the NO-donor moiety.

Chemical specificity drives claim construction

The claim requires MAP3 “comprises N-diazeniumdiolate functionalized MAP3.” That implies:

• the amine-containing MAP3 moiety is converted to diazeniumdiolate form,
• and that this functionalization is part of MAP3 itself within the silica network.

The claim does not read on:

• amine-functionalized silica that releases NO via other chemistries,
• S-nitrosothiol systems,
• catalytic NO generation,
• or other NO donors not based on N-diazeniumdiolate functionalization of MAP3.

Which MAP3 mol% windows are most defensible against design-arounds?

Featured snippet answer: The broad 1%–90% mol% window (claim 3) offers the most coverage if competitors keep the same NO-donor chemistry and co-condensed network architecture. The mid-window 10%–75% (claim 2) and tight bands around ~50% (claims 4 and 5) provide additional layering that can capture optimization strategies.

Design-around logic from the numeric limits

If a competitor tries to avoid dependent claims by adjusting MAP3 loading, they must move outside:

• 1%–90% (for avoiding claim 3),
• 10%–75% (for avoiding claim 2),
• 45%–55% (for avoiding claim 4),
• and “about 50%” (for avoiding claim 5).

Practically, avoiding claim 3 requires MAP3 below 1% mol% or above 90% mol%, both of which may be hard to achieve while still forming a functional co-condensed silica network capable of diazeniumdiolate loading and NO release.

How does US 8,956,658 compare with common NO-releasing silica patent patterns?

Featured snippet answer: The claim set is anchored on diazeniumdiolate-functionalized amine-silane (MAP3) co-condensed with TEOS, with uniform distribution across the particle. Many competing NO donor silica systems vary by:

• the aminosilane precursor (different silanes),
• the co-condensation partner (different silica precursor than TEOS),
• the NO donor chemistry (non-diazeniumdiolate),
• or the particle architecture (surface-only functionalization).

Likely differentiation points competitors target

For risk assessment, competitor products typically attempt one or more of:

• replace MAP3 with a different aminosilane,
• replace TEOS with another silicon source (e.g., different ortho-silicate),
• use diazeniumdiolate formed on grafted amines rather than co-condensed MAP3,
• constrain MAP3 to the surface and accept non-uniform distribution,
• use different NO donors.

If those differences defeat the specific claim 1 limitations, dependent mol% claims become irrelevant.

What is the patent landscape around NO-releasing silica diazeniumdiolate MAP3/TEOS particles?

Featured snippet answer: Without the full USPTO bibliographic record, cited references, and specification text, a complete landscape cannot be reliably enumerated. Based on the claim language alone, US 8,956,658 sits in the niche of diazeniumdiolate-functionalized aminopropyl silane co-condensed silica particles, where the key competitive battleground is whether accused products match the MAP3/TEOS co-condensation and uniformly distributed diazeniumdiolate-functionalized MAP3.

What the claims suggest about prior-art clusters (high-level)

The landscape in this area typically groups into:

• diazeniumdiolate chemistry on amine-bearing silica,
• sol-gel co-condensation of aminosilanes with alkoxysilanes,
• particle and pore structure engineering for controlled NO release,
• formulation ranges for donor density.

US 8,956,658’s claim set focuses on donor density (MAP3 mol%) and distribution, which often becomes the litigation pivot when competitors adopt similar underlying NO-donor chemistry but different incorporation methods or loading targets.

What would a generic or competitor entry risk analysis look like for this patent?

Featured snippet answer: The main infringement risk is for competitors making NO-releasing silica particles that use MAP3 and TEOS co-condensation and contain diazeniumdiolate-functionalized MAP3 distributed through the particle at MAP3 mol% within 1% to 90% (and especially within 10%–75% and near 50%).

Risk categories based on claim mapping

1. High risk:
   Product meets claim 1’s architecture and chemistry, and MAP3 loading falls within any dependent ranges.

2. Medium risk:
   Product matches claim 1 but avoids some dependent numerical windows by moving outside MAP3 mol% ranges. Claim 1 remains the independent threat.

3. Lower risk:
   Product breaks claim 1 by changing at least one of:

   • MAP3 to a different precursor,
   • TEOS to a different co-condensation partner,
   • diazeniumdiolate chemistry to a different NO donor mechanism,
   • or the distribution to non-uniform incorporation.

Key Takeaways

• US 8,956,658 claim 1 is a tightly drafted composition claim requiring a nitric oxide-releasing particle with a co-condensed silica network from MAP3 + TEOS, where MAP3 is distributed throughout and is N-diazeniumdiolate functionalized.
• Dependent claims layer MAP3 loading in mol% windows: 10%–75% (claim 2), 1%–90% (claim 3), 45%–55% (claim 4), and about 50% (claim 5), each inheriting claim 1’s chemistry and distribution requirements.
• The strongest patent leverage is the specific diazeniumdiolate-functionalized MAP3 within a co-condensed MAP3/TEOS silica network with uniform distribution. Competitors most effectively mitigate risk by breaking one of those core limitations, not by minor adjustments to MAP3 mol%.

FAQs

1. What if a competitor uses diazeniumdiolate-functionalized aminosilane but not MAP3?
It may avoid claim 1 if the aminosilane is not MAP3 as recited, assuming “MAP3” is construed strictly as methylaminopropyl trimethoxysilane.

2. Can a product infringe claim 1 if MAP3 is only surface-functionalized?
Surface-localized MAP3 may fail the “distributed throughout the particle” requirement, depending on how distribution is construed and proven.

3. How do MAP3 mol% claims interact with claim 1 if MAP3 is present but outside the ranges?
Dependent claims require both claim 1 and the specific mol% limits. A product outside those windows may still infringe claim 1.

4. Does changing TEOS to another silica precursor avoid infringement?
Potentially, if the co-condensed silica network is required to comprise TEOS specifically. Substituting a different ortho-silicate may break the claim limitation.

5. What is the most litigation-relevant technical proof for claim 1?
Demonstrating (i) diazeniumdiolate functionalization of MAP3, (ii) co-condensation of MAP3 with TEOS into the silica network, and (iii) MAP3 distribution throughout the particle.

References

1. United States Patent 8,956,658. Claims as provided in the prompt.

Drugs Protected by US Patent 8,956,658

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 8,956,658

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