Details for Patent: 4,695,392

Summary for Patent: 4,695,392

Title:	Magnetic particles for use in separations
Abstract:	A process is provided for the preparation of magnetic particles to which a wide variety of molecules may be coupled. The magnetic particles can be dispersed in aqueous media without rapid settling and conveniently reclaimed from media with a magnetic field. Preferred particles do not become magnetic after application of a magnetic field and can be redispersed and reused. The magnetic particles are useful in biological systems involving separations.
Inventor(s):	Roy A. Whitehead, Mark S. Chagnon, Ernest V. Groman, Lee Josephson
Assignee:	Bayer Corp
Application Number:	US06/744,434
Patent Claim Types: see list of patent claims	Compound;

US Patent 4,695,392: Scope, Claims, and Landscape for Magnetically-Responsive Silane-Coated Oxide Particles

What is the patent scope of US 4,695,392?

US 4,695,392 claims magnetically-responsive solid particles engineered for two-part performance in water: (i) slow settling without a magnetic field and (ii) rapid clarification/separation with an applied magnetic field using a permanent magnet whose physical volume is smaller than the treated dispersion volume. The particles use magnetic metal oxide cores coated with silane-derived polymers that carry bifunctional groups: one set binds to the oxide core (adsorptively or covalently) and a second set reacts with organic molecules (covalent coupling).

Core scope elements (what the claims require, in combination)

Across independent claim 1 and claim 10 (and claim 11 as a variant), the claimed invention has the following required build:

1. Magnetically-responsive oxide core

   • Claim 1: magnetic metal oxide core generally surrounded by a silane coat.
   • Claim 2-3: limits core to superparamagnetic crystals (iron oxide; divalent and trivalent cations).
   • Claim 11: variant allows ferromagnetic metal oxide core.

2. Silane coat with bifunctional functionality

   • The coating is a silane coat comprising a bifunctional silane polymeric material:
     • first functionalities bind to the metal oxide core; and
     • second functionalities covalently couple to organic molecules.
   • Dependent claims list specific organofunctionalities and silane monomers (claims 5-6).

3. Particle size and surface area constraints

   • Mean diameter by light scattering: 0.1 µm to 1.5 µm (claim 7).
   • Nitrogen adsorption surface area: at least 100 m²/g (claim 8).
     These numerical limitations appear in claim 10 and claim 11; they are also supported by dependent claim 7 and 8 in the chain.

4. Suspension stability and magnetic separation kinetics

   • Dispersed in aqueous media to form an aqueous dispersion exhibiting:
     • 50% turbidity-decrease settling time > 1.5 hours in absence of a magnetic field; and
     • 95% turbidity-decrease separation time < 10 minutes in presence of a magnetic field.
   • The separation setup is structural/operational:
     • magnetic field applied by bringing a vessel containing the dispersion into contact with a pole face of a permanent magnet, where the magnet volume is less than the volume of the dispersion in the vessel.

Claim structure and practical “who-does-what” boundaries

• Independent claim 1 is the broadest operative definition: oxide core + silane coat with covalent coupling to organics + two kinetic/turbidity thresholds + permanent-magnet configuration.
• Dependent claim 2-3 narrows magnetic behavior and chemistry (superparamagnetic; iron oxide with divalent/trivalent cations).
• Dependent claim 4-6 narrows silane-coating chemistry (bifunctional silane polymer; binding functionalities for oxide; coupling functionalities for organics; specified organofunctionalities and specific monomers).
• Dependent claim 10 is an additional independent claim (functional and metric-limited): it requires superparamagnetic iron oxide crystals plus the same kinetic thresholds plus size/surface constraints.
• Independent claim 11 requires ferromagnetic metal oxide core plus the size/surface constraints plus the same kinetic thresholds and permanent-magnet geometry.

In effect, the claims target a product-by-process-like performance profile (turbidity-based settling and magnetic clarification times) combined with material architecture (oxide core + silane bifunctional coupling layer) and a specific magnetic handling method.

---

How do the claims read as enforceable elements?

Independent claim 1 (magnetic oxide + silane + turbidity kinetics + permanent magnet method)

Claim 1 can be parsed into enforceability buckets:

A. Composition

• “Magnetically-responsive particle” with:
  • magnetic metal oxide core
  • silane coat around the core
  • silane coat to which molecules can be covalently coupled

B. Dispersion behavior without magnetic field

• Aqueous dispersion has 50% turbidity-decrease settling time > about 1.5 hours (no field)

C. Separation behavior with permanent magnet

• Aqueous dispersion has 95% turbidity-decrease separation time < about 10 minutes (with field)

D. Permanent magnet operational condition

• Field applied by bringing vessel containing dispersion into contact with pole face
• permanent magnet volume < dispersion volume in vessel

This combination is a tight triangulation: an infringer must match both (i) architecture enabling covalent coupling and (ii) kinetic/turbidity performance under the specified magnetic arrangement.

Dependent claim 2-3 (superparamagnetic; iron oxide cations)

• Claim 2: metal oxide core includes “a group of superparamagnetic crystals.”
• Claim 3: those crystals are iron oxide including divalent and trivalent iron cations.

If a competing product uses magnetic cores that behave as ferromagnetic or does not meet the superparamagnetic characterization, it may avoid claims 2-3 while still potentially implicating claim 1.

Dependent claim 4-6 (bifunctional silane polymer and listed chemistries)

• Claim 4: silane coat comprises bifunctional silane polymeric material with:
  • first functionalities adsorptively/covalently binding to oxide core
  • second functionalities covalently coupling to organic molecules
• Claim 5: organofunctionalities selected from:
  • aminophenyl, amino, carboxylic acid, hydroxyl, sulfhydryl, phenolic, aliphatic moieties
• Claim 6: silane monomers selected from:
  • p-aminophenyltrimethoxysilane
  • 3-aminopropyltrimethoxysilane
  • N-2-aminoethyl-3-aminopropyltrimethoxysilane
  • n-dodecyltriethoxysilane
  • n-hexyltrimethoxysilane

These limits matter because they can be used in freedom-to-operate (FTO) screening at the chemistry level, not just functional level.

Dependent claim 7-9 (particle size and surface area; additional functional classes)

• Claim 7: mean diameter 0.1 µm to 1.5 µm (light scattering)
• Claim 8: surface area ≥ 100 m²/g (nitrogen adsorption)
• Claim 9: organofunctionalities selected from hydrophobic and amphipathic moieties

Independent claim 10 (superparamagnetic iron oxide + size/surface + turbidity kinetics + permanent magnet)

Claim 10 is a narrower but more specific package:

• superparamagnetic iron oxide core
• crystals of iron oxide
• silane coat for covalent coupling
• mean diameter 0.1-1.5 µm
• surface area ≥ 100 m²/g
• same turbidity-based settling/separation thresholds
• same permanent magnet handling geometry

Independent claim 11 (ferromagnetic metal oxide + size/surface + turbidity kinetics + permanent magnet)

Claim 11 replaces the magnetic chemistry:

• ferromagnetic metal oxide core
• crystals of metal oxide
• same silane coating and coupling concept
• same mean diameter and surface area requirements
• same turbidity kinetics and magnet-vessel relative volumes

---

What claim scope is the permanent magnet limitation likely to cover?

The magnetic-field application is not generic “use a magnet.” The claim ties the method to:

• bringing a vessel into contact with a pole face of a permanent magnet
• where magnet volume is less than dispersion volume in the vessel

This gives the claim two practical constraints:

1. The field is delivered from a permanent magnet pole face close-coupled to the container.
2. The magnet is not a large equal-volume electromagnet assembly; it is physically smaller than the treated dispersion volume.

From a landscape perspective, this narrows infringement exposure for systems that:

• use moving fields, electromagnets with different scaling, or fixed-bed magnet arrays not involving pole-face contact as recited; or
• use magnetic devices where the magnet assembly volume is not smaller than the treated dispersion volume (depending on how “volume of permanent magnet” is interpreted in practice).

---

How does the turbidity test define product performance in litigation terms?

The claims use turbidity-decrease timing as objective metrics:

• 50% turbidity-decrease settling time > 1.5 hours without magnetic field
• 95% turbidity-decrease separation time < 10 minutes with magnetic field

These metrics function as “performance gates.” That matters for both design-around and enforcement:

• A competitor could attempt to keep particles stable but slower to separate (failing the “<10 minutes” requirement).
• Or a competitor could achieve fast separation but with faster settling without magnetic field (failing the “>1.5 hours” requirement).

The claim is specific to “aqueous media” and “aqueous dispersion” and does not limit pH, ionic strength, or specific turbidity baseline in the provided claim text. In practice, those parameters can still be contested as affecting whether the measured times satisfy the thresholds.

---

What is the patent landscape around these claim themes in the US market?

Likely “adjacent” technology clusters that overlap the same inventive space

US 4,695,392 sits at the intersection of three US patent families that typically cross-cite:

1. Magnetic separable nanoparticles for aqueous processing

   • Uses oxide cores for magnetic response and aqueous dispersibility.
   • Usually also includes fast clarification/settling behavior with magnets.

2. Silane-functionalized magnetic particles for biomolecule coupling

   • Silane coupling agents are widely used to attach reactive groups (amines, carboxyls, thiols, etc.) to oxide surfaces.

3. Superparamagnetic iron oxide (SPION) particle engineering for colloidal stability

   • Particle size control (often submicron), high surface area, and coatings to manage dispersion stability.

In an enforcement and freedom-to-operate review, exposure risk concentrates where a product:

• uses oxide magnetic cores,
• uses silane-derived bifunctional coatings with covalent coupling to organics, and
• demonstrates the same turbidity kinetic thresholds with a permanent magnet contact method.

Landscape implication: the claim is likely to be “narrow by performance”

Because the claims require both:

• specific “magnet-to-dispersion” handling geometry, and
• quantified turbidity settling/separation times,

they are narrower than generic “magnetic separable particles with functional surfaces.” Many SPION and functionalized silica/silane magnetic particle patents in the field may not match the exact performance thresholds and/or the specific permanent magnet volume constraint.

Landscape implication: chemistry is a secondary narrowing axis

Even if kinetics and magnet handling match, dependent claims narrow coating chemistry to specified monomers and functional groups. That can reduce direct infringement probability against products using different silanes, different coupling chemistries, or non-covalent coupling layers.

---

Practical claim coverage summary for R&D and licensing

Product characteristics that map most cleanly into the claims

A product is aligned to US 4,695,392 if it has the following combined features:

• Magnetic oxide core (superparamagnetic iron oxide or ferromagnetic metal oxide depending on the target claim)
• Silane polymer coating that provides:
  • oxide-binding functionality and
  • covalent coupling functionality to organic molecules
• Colloidal performance in water meeting:

  • 1.5 hours for 50% turbidity decrease settling without a magnetic field

  • <10 minutes for 95% turbidity decrease separation with a permanent magnet pole-face contact
• Particle metrics (for claims 10-11):
  • 0.1-1.5 µm mean diameter (light scattering)
  • ≥100 m²/g surface area (nitrogen adsorption)
• Magnetic handling:
  • permanent magnet pole face brought into contact with the vessel
  • permanent magnet volume smaller than dispersion volume

Design-around levers that are most directly connected to the claim language

• Swap from permanent magnet contact to other field application architectures that do not meet the pole-face contact and relative volume condition.
• Tune colloidal stability vs. separation speed so at least one turbidity time threshold misses the claimed bounds.
• Change coating chemistry so it no longer uses bifunctional silane polymer structures that “covalently couple” organics in the way claimed, or so it uses different functional groups/monomers not captured by the dependent claim lists (depending on the target claim to avoid).
• Change core magnetic behavior (superparamagnetic vs. ferromagnetic) to avoid claims 2-3 and target only claim 1 exposure, or vice versa.

---

Key Takeaways

• US 4,695,392 claims silane-coated magnetic oxide particles with covalent coupling capability, plus quantified aqueous turbidity kinetics: settling without field >1.5 hours to 50% turbidity decrease, and separation with field <10 minutes to 95% turbidity decrease.
• The magnetic separation method is constrained to permanent magnet pole-face contact with the vessel and a permanent magnet volume smaller than the dispersion volume.
• Dependent claim scope locks in silane polymer bifunctional chemistry and, in narrower claims, superparamagnetic iron oxide versus ferromagnetic metal oxide, plus 0.1-1.5 µm particle size and ≥100 m²/g surface area.
• The performance-based turbidity limits likely narrow the claim compared with generic functionalized magnetic particle patents, making kinetics and magnet handling the highest-sensitivity elements in enforcement and FTO screening.

---

FAQs

1) Does US 4,695,392 claim the silane chemistry as a specific silane list?

Claim 1 broadly requires a silane coat made from a bifunctional silane polymeric material with core-binding and covalent coupling functionalities (via claim 4). The specific monomer list appears in dependent claim 6.

2) Can a product that separates quickly but settles fast avoid the claims?

Potentially. Claim 1 requires 50% turbidity-decrease settling time > about 1.5 hours without a magnetic field. A product that settles faster would miss at least that performance gate.

3) Is superparamagnetic versus ferromagnetic a differentiator across the independent claims?

Yes. Claim 10 is limited to a superparamagnetic iron oxide core, while claim 11 is limited to a ferromagnetic metal oxide core. Claim 1 covers a broader “magnetic metal oxide core” without specifying the magnetic regime.

4) What part of the magnetic separation setup is operationally limiting?

The claim requires application of the field by bringing the vessel into contact with a pole face of a permanent magnet, with permanent magnet volume less than dispersion volume.

5) What particle metrics are required in the narrower independent claims?

Claims 10 and 11 require:

• mean diameter 0.1-1.5 µm (light scattering)
• surface area ≥ 100 m²/g (nitrogen adsorption)

---

References

[1] US Patent 4,695,392. “Magnetically-responsive particles,” claims text as provided.

Drugs Protected by US Patent 4,695,392

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 4,695,392

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	70366
Canada	1254028
Canada	1266769