DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Acknowledgement of Receipt
Applicant’s Response, filed 11/24/2025, in reply to the Office Action mailed 8/22/2025, is acknowledged and has been entered. Claims 1, 2, 4, 5, 7-14, 16-19 and 21-24 are pending, of which claims 1, 2, 4, 5, 7-11, 18 and 19 are withdrawn from consideration at this time as being drawn to a non-elected invention. Claims 12-14, 16-17 and 21-24 encompass the elected invention and are examined herein on the merits for patentability.
Response to Arguments
Applicant’s arguments have been fully considered. Any rejection not reiterated herein has been withdrawn as being overcome by claim amendment. New grounds for rejection are set forth herein, necessitated by claim amendment.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 12, 16, 17, 21 and 23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Johnson et al. (US 2021/0265086).
Johnson discloses dispersions comprising iron nitride nanoparticles and a suitable solvent (paragraph 0007).
The nanoparticles may be passivated by controlled oxidation, forming a layer of iron oxide on the surface of the nanoparticles. The nanoparticles may also be passivated by coating the nanoparticles with another compound, such as aluminum oxide, silicon oxide, titanium oxide, aluminum nitride, and/or titanium nitride (paragraph 0051).
The iron nitride nanoparticles may be dispersed in a solution of one or more stabilizers and water. The resulting dispersion may be subjected to a process for deagglomerating the nanoparticles via mechanical agitation, followed by freeze drying. These processes of mechanical agitation may comprise, but are not limited to, ultrasonication and/or mechanical ball milling. Here, the one or more stabilizers may comprise stearic stabilizers such as polyethylene glycol. The one or more stabilizers may be an electrostatic stabilizer. An electrostatic stabilizer may include sodium citrate, sodium hexametaphosphate, or citric acid (paragraph 0056).
the annealed iron nitride nanoparticles may be dispersed in an organic solvent for further processing. Accordingly, the iron nitride nanoparticles may be dispersed in a solution of one or more stabilizers and an organic solvent, and subjected to ultrasonication and/or mechanical ball milling. Stabilizers that may accompany the organic solvent may comprise organic compounds. Suitable organic compounds may include, but are not limited to, oleic acid, stearic acid, or oleylamine. The organic solvent may include a polar solvent such as methanol or a nonpolar solvent such as heptane. A suitable polar solvent may include methanol. A suitable nonpolar solvent may include heptane (paragraph 0057).
Dispersing the iron nitride nanoparticles in a fluid includes: introducing the iron nitride nanoparticles to a mixture of water and one or more additives to provide an aqueous solution; and subjecting the aqueous solution to a process of ultrasonication and/or wet ball milling (paragraph 0105).
In one embodment, fluids comprise a surfactant to promote deagglomeration of the iron-containing nanoparticles (paragraph 0163).
See Table 1, sample 2.
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The effect of the milling process is to reduce the average size of the agglomerated iron oxide nanoparticles. The agglomerate size may be expressed as Dx, determined as the diameter below which x % of the cumulative size distribution is contained. Often, the agglomerate size is expressed as D50, determined as the diameter below which 50% of the cumulative size distribution is contained. For example, a D50 means that 50% of all particles have a particle size which is equal to or less than the value indicated. Correspondingly, a D99 means that 99% of all particles have a particle size which is equal to or less than the value indicated (paragraph 0133).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 12-14, 16-17 and 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (“Irregularly Shaped {\gamma}'-Fe4N Nanoparticles for Hyperthermia Treatment and T2 Contrast-Enhanced Magnetic Resonance Imaging with Minimum Dose," arXiv preprint arXiv:1910.06842, October, 2019) in view of Ohara et al. (JP 2014156411).
Wu teaches that magnetic nanoparticles (MNPs) have been extensively used in drug/gene delivery, hyperthermia therapy, magnetic particle imaging (MPI), magnetic resonance imaging (MRI), magnetic bioassays, etc. With proper surface chemical modifications, physicochemically stable and non-toxic MNPs are emerging contrast agents and tracers for in vivo MRI and MPI applications. Herein, we report the high magnetic moment, irregularly shaped γ'-Fe4N nanoparticles for enhanced
hyperthermia therapy and T2 contrast agent for MRI application. The static and dynamic magnetic properties of γ'-Fe4N nanoparticles are characterized by vibrating sample magnetometer (VSM) and magnetic particle spectroscopy (MPS) systems, respectively. Compared to the γ-Fe2O3 nanoparticles, γ'-Fe4N show at least 3 times higher saturation magnetization (in emu/g), which, as a result, gives rise to the stronger dynamic magnetic responses as proved in the MPS measurement results. In addition, {\gamma}'-Fe4N nanoparticles are functionalized with oleic acid layer by a wet
mechanical milling process, the morphologies of as-milled nanoparticles are characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and nanoparticle tracking analyzer (NTA). We report that with proper
surface chemical modification and tuning on morphologies, γ'-Fe4N nanoparticles could be used as tiny heating sources for hyperthermia and contrast agents for MRI applications with minimum dose.
Both Fe2O3@Ultra and γ'Fe4N@Ultra show well dispersed nanoparticles with diameters below 20 nm. Most of these nanoparticles have irregular shapes (page 5).
Figure 4(b) shows the hydrodynamic size distribution of -Fe4N@BM sample where the peak is around 100 nm, agreeing with the TEM image Figure 4(ii) added in the subset. The DLS result of the -Fe4N@BM show another peak at around 1000 nm, this finding suggests that the -Fe4N MNPs are aggregated into clusters.
See also Figure 4b showing a peak around 100 nm (+/- 10) in size distribution.
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Figure 4b
We can safely treat these sintered -Fe4N MNPs as 20 nm -Fe4N MNPs bundling together (S6).
In this work, OA is used as surfactant on -Fe4N nanoparticles, these lipophilic MNPs show very good dissolvability in polar liquids such as oil. In addition, it is reported that OA can form a dense protective monolayer that binds firmly to the MNP surfaces with enhanced colloidal stability. However, for biomedical applications, the lipophilic substances (i.e., OA) coated MNPs are not good candidates and thus the practical use of these MNPs are limited. In the future we can further functionalize OA-coated MNPs with trialkoxysilanes. Thus, the functionalized nanoparticles can be dispersed in various aqueous solutions such as human serum and plasma.63 Besides, the biocompatibility and colloidal stability of -Fe4N nanoparticles can be further enhanced by conjugating chemical compounds such as chitosan, polyethylene glycol (PEG), amino acids, citric acid, etc., so that the water solubility of MNPs can increase significantly (page 18).
Wu does not teach wherein the iron nitride nanoparticles in the suspension have a substantially unimodal size distribution.
Ohara teaches a magnetic particle-containing aqueous dispersion unit capable of producing homogeneous functionalities by easy modification and capable of producing a magnetic particle-containing medicine for diagnosis and treatment highly dispersed in an aqueous solution.
The surface of magnetic nanoparticles having a primary particle diameter of 10 to 100 nm is coated in the order of the first layer, the second layer, and the third layer, and the first layer is silicon oxide, and the second layer Is a silane coupling agent, amino acid or polysaccharide having a functional group selected from the group consisting of an amino group, a carboxyl group, a hydroxyl group, an azide, and an alkyne, and the third layer is the surface of the second layer (abstract).
The present invention has been made in view of the above-described conventional problems, and the particle surface of the magnetic fine particles is modified with a surface modification layer with an anionic, cationic or neutral polymer, and the surface is uniform. It is a technical object to provide a dispersed colloidal aqueous solution of magnetic fine particles having a uniform particle size (translation page 2).
Further, the present invention provides the composite magnetic fine particle powder according to the first or second aspect of the present invention, wherein the magnetic nanoparticles are at least one of metal iron, iron oxide, iron nitride, iron carbide, and iron boride. It is a fine particle powder (Invention 3).
In the composite magnetic fine particle powder according to the present invention, the surface of magnetic nanoparticles having a primary particle diameter of 10 to 100 nm is coated in the order of the first layer, the second layer, and the third layer. The first layer is silicon oxide. The second layer is a silane coupling agent, amino acid or polysaccharide having a functional group selected from the group consisting of an amino group, a carboxyalkyl group, a hydroxyl group, an azide, and an alkyne. The third layer is an amino acid having a functional group selected from the group consisting of a functional group of the second layer and an amide bond, an ester bond, an amino group that can be modified by a click reaction, a carboxyl group, a hydroxyl group, an azide, and an alkyne, Polysaccharides and imines.
The primary particle diameter of magnetic nanoparticles (average particle diameter of primary particles) is 10 nm to 100 nm. If the average particle diameter of the primary particles is less than 10 nm, it is not preferable because it is amorphous. Further, if the primary particle diameter exceeds 100 nm, it is not preferable in terms of magnetic aggregation. The primary particle size is preferably 12 to 90 nm, more preferably 15 to 80 nm (translation page 3).
The magnetic nanoparticles in the present invention are at least one selected from iron oxides such as magnetite (Fe3O4), maghemite (γ-Fe2O3), and wustite, metallic iron, iron nitride, iron carbide, and iron boride. It is. Each of the compounds may contain a different metal element. The metallic iron may be metallic iron or an alloy of iron and a different element (FeCo, FePt, etc.). Iron nitride, Fe 3-x N, Fe 4 N, and the like Fe 16 N 2, Co, may be substituted with a different element such as Ni. Iron carbide and iron boride may be substituted for each other. Moreover, you may have a surface oxidation layer (translation page 3).
Further, the obtained magnetic iron oxide fine particles can change the surface potential by a crosslinking reaction with polyethyleneimine having an amino group, and can also react with polyethylene glycol having a hydroxyl group and relatively low toxicity. It can be handled freely (translation page 5).
In addition, if the particle size of the magnetic particles is increased due to aggregation, a stable dispersion state cannot be maintained.
Further, in the pharmaceutical granulation step according to the use, the function of a ferromagnetic substance can be imparted to the granulated particles by adjusting the aggregate state of the fine particles.
The primary particle diameter of magnetic nanoparticles (average particle diameter of primary particles) is 10 nm to 100 nm. If the average particle diameter of the primary particles is less than 10 nm, it is not preferable because it is amorphous. Further, if the primary particle diameter exceeds 100 nm, it is not preferable in terms of magnetic aggregation. The primary particle size is preferably 12 to 90 nm, more preferably 15 to 80 nm.
After concentration with an evaporator, the supernatant is recovered with a centrifuge and the remaining aggregated particles are removed (translation page 5).
It would have been obvious to one of ordinary skill in the art at the time of the invention to remove the aggregated particles from the bimodal distribution of nanoparticles and aggregates in the dispersions of γ'-Fe4N, which have been wet-ball milled and comprise a surface active agent bound thereto, taught by Wu, when the teaching of Wu is taken in view of Ohara. Wu teaches particle suspensions having a peak around 100 nm (+/- 10) in size distribution corresponding to 20 nm particle bundles, and around 1000 nm due to aggregates, and teaches that with proper surface chemical modification and tuning on morphologies, γ'-Fe4N nanoparticles could be used as tiny heating sources for hyperthermia and contrast agents for MRI applications with minimum dose. Ohara teaches a magnetic particle-containing aqueous dispersion unit capable of producing homogeneous functionalities by easy modification and capable of producing a magnetic particle-containing medicine for diagnosis and treatment highly dispersed in an aqueous solution, but that if the primary particle diameter exceeds 100 nm, it is not preferable in terms of magnetic aggregation. One would have been motivated to remove the aggregates from Wu’s dispersion, with a reasonable expectation of success, because Ohara teaches that it is desirable to provide magnetic particles, including iron nitride, of uniform particle size (page 2); and that if the particle size of the magnetic particles is increased due to aggregation, a stable dispersion state cannot be maintained, and that aggregated particles can be removed via centrifugation.
Conclusion
No claims are allowed at this time.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
/LHS/
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618