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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 18, 2025 has been entered.
Response to Amendment and Status of Claims
Applicant’s amendments to the claims, filed June 18, 2025, are acknowledged. Claims 12, 16 and 21 are amended. Claim 19 is cancelled. Claim 25 is newly added.
Claims 1-4 and 6-8, and Claims 9-11, remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Inventions I and II, drawn to a magnetic body and to a curable composition, respectively, there being no allowable generic or linking claim. Applicant timely elected without traverse in the reply filed on July 21, 2023.
Claims 1-4, 6-14, 16, 18, 21-22 and 24-25 are pending, and Claims 12-14, 16, 18, 21-22 and 24-25 are currently being considered in this office action.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on July 14, 2025 and September 16, 2025 were filed after the mailing date of the Final Rejection on March 18, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 12, 14, 16, 18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Cao (previously cited, “Mesoporous Iron Oxide Nanoparticles Prepared by Polyacrylic Acid Etching and Their Application in Gene Delivery to Mesenchymal Stem Cells”) in view of Janjua (previously cited, US 20190366305 A1), Reddy (previously cited, “One-pot solvothermal synthesis and performance of mesoporous magnetic ferrite MFe2O4 nanospheres”), Cheng (CN 110605120 A, English Machine Translation provided), Enomura (previously cited, US 20100243947 A1) and Guardia Giros (previously cited and cited by Applicant in IDS filed July 31, 2023, US 20150064103 A1).
Regarding Claim 12, Claim 16 and Claim 22, Cao discloses a method for producing a magnetic body (Abstract), comprising:
mixing raw materials comprising a magnetic particle precursor and a polar organic solvent and heating to 200C to generate crystals (Pg. 927, Col. 1, Solvothermal Synthesis of s-IONPs, ferric chloride (raw material comprising a magnetic particle precursor), organic solvent (EG); EG is polar).
Cao fails to disclose wherein the raw material further comprises (Claim 12) water and (Claim 22) within a range of 1-30vol% relative to the polar organic solvent.
Janjua discloses wherein the solvent may be a mixture of polar organic solvents, and particularly ethylene glycol and water ([0089]; para. [0017], wherein solvent is combination of two solvents of EG and water, wherein water is 10-90%, including 30%). Janjua teaches wherein the polarity is tailored using the mixture of solvents to provide narrower particle distributions (para. [0131], wherein product B which uses a mixture of EG and water comprises a narrower size distribution of magnetic particles than those produced with EG alone in product A; Table 1; Fig. 7A-7B).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have (Claim 12) used water and further (Claim 22) in an amount of 10-30vol% of water, relative to the polar organic solvent ethylene glycol, as taught by Janjua, for the raw material of the invention disclosed by Cao. One would be motivated to do this in order to produce narrower particle size distributions.
Cao fails to disclose wherein the first step of mixing the raw materials prior to clustering (see Cao, 200C for solvothermal synthesis), is performed at an elevated temperature of 60-90C, and further by (Claim 16) (1-a) raising the temperature to the range of 60-90C and (1-b) maintaining the temperature for a period of time in the range of 30-120 minutes.
Reddy teaches wherein raw materials are mixed for 30 minutes at 50C in order to obtain a homogenous solution prior to heating to 160-200C and to generate crystals (Section 2.2, brown solution indicative of generating crystals; see also Results and Discussion, para. 2 and further Fig. 1, crystal grain nucleation from raw material mixture, and further growth of nucleated crystals in EG solution during solvothermal heating).
Cheng similarly teaches mixing raw materials at a temperature of 50-60C for 30-60 minutes in order to dissolve raw materials thoroughly prior to solvothermal heating at 180-240C (para. [0013]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have (Claim 12) performed a first step of heating the raw materials within the range of 50-60C, which reads on the claimed 60-90C, and further to have (Claim 16) raised and maintained the temperature of the raw materials to 50-60C and mixed for 30-60 minutes to generate crystals, as taught by Reddy and Cheng, for the invention disclosed by Cao, in order to ensure that the raw materials form a homogenous solution and are thoroughly dissolved prior to heating or solvothermal heating/clustering (see teaching above). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 2144.05.I. Further, Applicant has not provided criticality of the range, and it has been recognized that discovering a workable range involves only routine skill in the art, absent a showing of unexpected results. See MPEP 2144.05.I.
Additionally, one of ordinary skill in the art would appreciate that mixing the raw materials at 60C for 30-60 minutes would generate crystals as claimed because this feature is taught by Reddy (see above), and because the claimed raw materials and the taught mixing parameters are the same as claimed. When the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112.01.
Cao further discloses a second step of clustering the crystals by heating to 200C for 10 hours (Pg. 927, Col. 1, Solvothermal Synthesis of s-IONPs, IONPs collected; collection of IONPs reads on clustering). One of ordinary skill in the art would appreciate that to collect crystals after heating from a solution, the crystals would be clustered or aggregated by the reaction (see also Fig. 1 of Cao, wherein crystals comprise clustered/aggregated grains).
Cao fails to expressly disclose wherein the step of clustering comprises (2-a) raising the temperature of the crystals to a temperature within the range of 170-195C, and (2-b) maintaining the temperature of the crystals for a period of time for 20-80 hours.
However, regarding step (2-a), 200C is extremely close to the claimed value 195C, and it is the examiner's position that the amounts in question are so close that it is prima facie obvious that one skilled in the art would have expected them to have the same properties (Titanium Metals Corp. v. Banner, 227 USPQ 773. MPEP 2144.05.I).
Further, Reddy teaches wherein raw materials are heated in an autoclave for clustering (crystallization/growth) at 160-200C for 8-24 hours (Sect. 2.2, 160, 180 and 200C at 16hours and 160C for 8h and 24h). Reddy teaches wherein crystals are generated in the heated mixing of the first step (see Sect. 2.2, brown liquid generated indicative of forming crystals), and wherein the solvothermal process, which encompasses the solvothermal process of Cao, results in the clustering and aggregation of the crystals from the heated step to form particles (see Fig. 1 of Reddy).
Reddy teaches wherein the solvothermal temperature and time affects the size and magnitude of magnetic properties of the nanoparticles (Sect. 3, Results and discussion, para. 1). Further, Reddy specifically teaches wherein particle size decreases and particle distribution increases with decreasing solvothermal temperature, and suggests an optimal temperature of 180C (Pg. 39, Col. 2, para. 1), and wherein increasing reaction time increases particle size (Pg. 39, para. 4). Thus, Reddy teaches wherein both the solvothermal (crystallization/clustering) reaction temperature and reaction time are result-effective variables, the results being particle size (per time and temperature) and particle distribution (per temperature).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have raised the temperature of the crystals to a temperature within 160-200C, such as 180C, which reads on the claimed 170-195C, and to have maintained this temperature for 8-24 hours, which reads on the claimed 20-80hours, as taught by Reddy, for the invention disclosed by Cao, in order to successfully react the crystals while tailoring for particle size and distribution (see teachings above).
Further, Reddy demonstrates that the time and the temperature for crystal clustering is a result-effective variable, the result being particle size and particle size distribution (see above), and it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art absent a showing of criticality or unexpected results (see MPEP 2144.05.1; In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980)).
Additionally, the clustering solvothermal parameters taught by Reddy (for example 180C for 24 hours), are the same as claimed and one of ordinary skill in the art would appreciate that the crystals would behave in the claimed manner and therefore cluster as claimed. When the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112.01.
Cao further discloses a third step of mixing the clustered crystals with a primary surface treatment agent of PAA, so as to bond the primary surface treatment agent to a surface of the clustered crystals (Pg. 927, Col. 1, Preparation of m-IONPs Through Polyacrylic Acid Etching, PAA reads on surface treatment agent, see PAA-stabilized IONPs and wherein PEI is grafted via an interaction from the PAA bonded to IONP; see also Pg. 940, Col. 1, Discussion, “the surface of IONPs is protected densely by PAA as a result of strong chelation between the carboxyl groups and iron atoms”).
Cao discloses wherein the primary surface treatment agent comprises PAA, but does not disclose wherein the primary surface treatment comprises an alkyl based phosphoric acid-based compound or an alkylcarboxylic acid-based surface treatment agent.
Enomura teaches wherein the dispersant coated on a magnetic particle may include commercially available Disperbyk dispersants, which are alkyl phosphoric acid-based compounds (such as Disperbyk-180), acetic acid, which is an alkycarboylic acid-based surface treatment agent, phosphoric acids, PEI (polyethylene imine) and polyacrylic acid (PAA), and teaches wherein these dispersants may be used alone or in combination of two or more, and in order to provide excellent dispersability in solution (para. [0406]). Enomura therefore also demonstrates the art equivalence of using dispersants of PAA, PEI, phosphoric acids, acetic acid and commercially available alkyl phosphoric acid-based dispersants for the surface modification of magnetic nanoparticles, in addition to the combined use of such dispersants.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have included a primary surface treatment agent comprising at least one of phosphoric acids, acetic acid and commercially available alkyl phosphoric acid-based dispersants, as taught by Enomura, for the invention disclosed by Cao, in order to provide excellent and tailorable dispersability of the magnetite particles in solution (see teaching above). It would be obvious to one of ordinary skill in the art to use these surface treatments as the primary surface treatment agent, or in combination with the PAA and/or in addition to the PEI surface treatment agent disclosed by Cao, to further tailor the dispersability of the magnetite particles.
Therefore, Cao and Enomura disclose wherein the primary surface treatment agent comprises an alkyl based phosphoric acid-based compound or an alkylcarboxylic acid-based surface treatment agent, as claimed.
Cao further discloses wherein the third step comprises:
(3-a) mixing the clustered crystals with the primary surface treatment agent at an elevated temperature (Pg. 927, Col. 1, Preparation of m-IONPs Through Polyacrylic Acid Etching, crystals are mixed with a hot PAA solution (hot PAA solution reads on elevated temperature) and heated at 240C, 240C also reads on elevated temperature).
Cao discloses wherein the resultant m-IONPs (PAA treated particles) are collected and washed (Pg. 927, Col. 1, Preparation of m-IONPs Through Polyacrylic Acid Etching). One of ordinary skill in the art would appreciate that the particles would be cooled (see claimed step 3-b) prior to collecting and washing, as a matter of safe handling conditions and in order to store for later use. Therefore, one of ordinary skill in the art would appreciate that Cao discloses a cooling step as required by step (3-b).
Cao discloses applying a PEI layer to the PAA modified crystals, but does not disclose wherein this process occurs at an elevated temperature of 50-90C. Therefore, Cao fails to disclose, in the cooling step of (3-b), cooling from the elevated temperature to a temperature within the range of 50-90C, and (Claim 22) maintaining at this temperature for 30-120 minutes, prior to collection and washing.
Guardia Giros teaches wherein functionalization with ligands using ligand exchange occurs at temperatures below 120C, and at temperatures between 70-90C, and for a time of 60 minutes, in order to stabilize and complete the reaction while reducing the need for additional, room temperature purification steps (para. [0066]; [0083]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have cooled the primary surface agent treated nanocrystals obtained in step (3-a) to a temperature below 120C, preferably 70-90C (see step 3-b), and then at this temperature functionalized the primary surface agent treated nanocrystals with the PEI (and for example, further with an alkyl phosphoric acid based compound or alkylcarboxylic acid-based compound – see above teaching b Enomura), for a time of 60 minutes (see Claim 22 step 3-c), as taught by Guardia Giros, for the invention disclosed by Cao and Enomura. One would be motivated to do this in order to modify the surface through functionalization with PEI and the like without the need for the additional (in-between) collecting, washing, and redispersion steps, and to ensure stabilization and completion of the reaction during functionalization (see teaching above).
Cao discloses wherein the as-synthesized nanoparticles prior to surface treatment are uniform in size, and demonstrates images wherein the particle diameter sizes are substantially similarly after surface treatment (Fig. 1b and Fig. d; Pg. 937, Col. 2, Results, Para. 1). However, Cao fails to disclose wherein the particle diameter variation coefficient of the magnetic body is 5-30%.
Cao further fails to disclose an SAR value of 60 W/g or more under the claimed conditions (measured at a frequency of 310kHz).
Guardia Giros further teaches a high SAR (specific absorption rate) is desired in order to provide efficient hyperthermia treatment with minimum invasiveness to a patient, and in order to be safe for the human body and useable for drug delivery systems, which is further a concern of Cao (Guardia Giros, para. [0003]; para. [0084]: Cao, Pg. 936, Introduction). Guardia Giros also teaches wherein, like Cao, iron oxide nanoparticles are synthesized from Fe(III) chlorides and a solvothermal process ((para. [0041]-[0045], Fe3O4 from Fe(III) and Fe(II) chlorides).
Guardia Giros also teaches wherein a wide distribution of particle size negatively impacts hyperthermia performance and teaches obtaining nanoparticles with particle size distribution coefficients (granulometric distribution standard deviation) of less than 20%, preferably less than 15%, thereby producing SAR values greater than 60 W/g, including for frequencies of 310Hz (para. [0012]; para. [0042]; para. [0027]-[0031] and Fig. 8a-b; see also Fig. 17 (Table 3); 12.5+/-1nm, 19+/-3nm, 25+/-4nm, 38+/-9nm give variations of 8%, 16%, 16% and 24%, respectively).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have comprised a high SAR, such as 100 W/g or more at 310Hz, which reads on the claimed SAR of 60W/g at the claimed conditions, and a low particle size distribution coefficient, such as 15% or less, as taught by Guardia Giros, in order to comprise a drug delivery agent which is safe for the human body and one which may be efficiently hyperthermially released (see teachings above by Guardia Giros).
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 2144.05.I.
Regarding Claim 14, Cao discloses wherein the raw material further comprises a base, and the content of the base in the raw material is in a range of 0.4-2.0M (Pg. 927, Col. 1, Preparation of m-IONPs Through Polyacrylic Acid Etching, 40mmol of sodium acetate in 40ml of PEG solvent comprises a 1M content of base (sodium acetate)).
Regarding Claim 18, Reddy is silent towards the heating rate for raising the temperature of the raw material to 50C to form the homogenous solution (see Claim 16 above), as required by step (1-a).
However, it would be obvious to one of ordinary skill in the art to have achieved a heating rate within the claimed range because the claimed values are merely a workable range, and Applicant has not demonstrated criticality of the claimed range. One of ordinary skill in the art would be aware of the required heating rate to achieve homogenous solutions of the components disclosed by Cao and Reddy. One would also be aware of equipment cost and limitations to achieve certain heating rates. It has been recognized that discovering a workable range involves only routine skill in the art, absent a showing of unexpected results. See MPEP 2144.05.I.
Regarding Claim 21, Cao, Reddy and Cheng are silent towards heating rates for reaching the solvothermal reaction temperature.
Guardia Giros further teaches wherein the heating rate to reach the reflux temperature may be varied in order to tailor the nanoparticle size, and are preferably 1-7 C/min for obtaining monodisperse granulometric distributions in terms of shape and size (para. [0063]; see Fig. 4 and Fig .16 (Table 2), reducing the heating rate from 7 C/min to 2.5 C/min and 1.6 C/min increases the nanoparticle size from 22nm to 28nm and 31 nm, respectively). Guardia Giros there further teaches wherein heating rate is a result effective variable, the result being particle size and particle size/shape distribution.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a heating rate of 1-7C/min, which reads on the claimed 1.5-5 C/min, as taught by Guardia Giros, for the invention disclose by Cao, in order to tailor the nanoparticle size and to obtain a monodisperse granulometric distributions in terms of shape and size (see teaching above). Further, Guardia Giros demonstrates wherein heating rate is a result effective variable, the result being particle size and particle size/shape distribution, and it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art absent a showing of criticality or unexpected results (see MPEP 2144.05.1; In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980)).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Cao (previously cited, “Mesoporous Iron Oxide Nanoparticles Prepared by Polyacrylic Acid Etching and Their Application in Gene Delivery to Mesenchymal Stem Cells”) in view of Janjua (previously cited, US 20190366305 A1), Reddy (previously cited, “One-pot solvothermal synthesis and performance of mesoporous magnetic ferrite MFe2O4 nanospheres”), Cheng (CN 110605120 A, English Machine Translation provided), Enomura (previously cited, US 20100243947 A1) and Guardia Giros (previously cited and cited by Applicant in IDS filed July 31, 2023, US 20150064103 A1), as applied to Claim 12 above, in further view of Kim (previously cited and cited by Applicant in IDS filed July 31, 2023, US 20180254130 A1).
Regarding Claim 13, Cao discloses wherein the content of the magnetic particle precursor in the raw material is 0.5M, but fails to disclose a range of 0.025-0.125M (Pg. 937, Col. 1, Preparation of m-IONPs Through Polyacrylic Acid Etching, 20mmol of ferric chloride in 40ml of PEG solvent).
Kim teaches a similar process wherein an amount of 0.1M magnetic precursor (3.996mmol of ferric chloride in 40ml of PEG solvent, see para. [0045]), and teaches wherein the amount of iron precursor and the solvent are mixed in a molar ratio of preferably 1:40 to 1:200 ([0014]). Kim teaches wherein these parameters produce a higher yield of magnetic nanoparticles comprising a uniform size and particle size distribution with high aqueous solution dispersability (para. [0006]; para. [0029]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the amount of magnetic particle to be 0.1M, as taught by Kim, for the invention disclosed by Cao, in order to achieve a precursor to solvent molar ratio of 1:40 to 1:200, thereby producing a higher yield of magnetic nanoparticles comprising a uniform size and particle size distribution with high aqueous solution dispersability (see teaching by Kim above). A 0.1M ratio, as taught by Kim, would give a molar ratio of ferric chloride to EG solvent of approximately 1:180 (0.003996mol ferric chloride to 0.716mol EG).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Cao (previously cited, “Mesoporous Iron Oxide Nanoparticles Prepared by Polyacrylic Acid Etching and Their Application in Gene Delivery to Mesenchymal Stem Cells”) in view of Janjua (previously cited, US 20190366305 A1), Reddy (previously cited, “One-pot solvothermal synthesis and performance of mesoporous magnetic ferrite MFe2O4 nanospheres”), Cheng (CN 110605120 A, English Machine Translation provided), Enomura (previously cited, US 20100243947 A1) and Guardia Giros (previously cited and cited by Applicant in IDS filed July 31, 2023, US 20150064103 A1), as applied to Claim 12 above, in further view of Hong (previously cited, “Controlled synthesis of hollow magnetic Fe3O4nanospheres: Effect of the cooling rate”).
Regarding Claim 24, Cao and Guardia Giros fail to disclose a cooling rate for cooling from primary surface treatment agent modification (200C) to PEI layer functionalization (70-90C). However, it would be obvious to one of ordinary skill in the art to use natural cooling unless stated otherwise, and as a means to reduce cost and the need for cooling equipment. One of ordinary skill in the art would recognize natural cooling to comprise either furnace cooling or air cooling.
Hong teaches wherein furnace and air cooling rates are on the order of 1C/min when cooling from 200C to 90C (Fig. 1 of Hong).
Thus, it would be obvious to one of ordinary skill in the art that the cooling rate of reaching the functionalization temperatures for PEI layer formation taught by Guardia Giros (i.e., to reach 70-90C), comprise a cooling rate of 0.5-5C/min, as demonstrated by Hong, and as claimed. Further, applicant has not provided criticality of the range, and it has been recognized that discovering a workable range involves only routine skill in the art, absent a showing of unexpected results. See MPEP 2144.05.I.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Cao (previously cited, “Mesoporous Iron Oxide Nanoparticles Prepared by Polyacrylic Acid Etching and Their Application in Gene Delivery to Mesenchymal Stem Cells”) in view of Janjua (previously cited, US 20190366305 A1), Reddy (previously cited, “One-pot solvothermal synthesis and performance of mesoporous magnetic ferrite MFe2O4 nanospheres”), Cheng (CN 110605120 A, English Machine Translation provided), Enomura (previously cited, US 20100243947 A1) and Guardia Giros (previously cited and cited by Applicant in IDS filed July 31, 2023, US 20150064103 A1),, as applied to Claim 12 above, in further view of Chiaradia (“Incorporation of superparamagnetic nanoparticles into poly(urea-urethane) nanoparticles by step growth interfacial polymerization in miniemulsion”).
Regarding Claim 25, Cao fails to disclose wherein the method comprises a fourth step of mixing the magnetic particles surface-treated in the third step with a secondary surface treatment agent, wherein the secondary surface treatment is a polyurethane-based surface treatment agent, a polyurea-based surface treatment agent, a poly(urethan-urea)-based surface treatment agent and/or a polyester-based surface treatment agent.
Chiaradia teaches wherein a magnetic particle which has been coated and surface treated with a primary surface treatment agent (OA) is further encapsulated in a PUU (poly(urea-urethane) polymeric shell in order to protect the magnetic nanoparticles, improve stability against aggregation, maintain high magnetic response, and allow for further functionalization (Abstract; Pg. 597, Para. 1 Conclusions; see para. [0406] of Enomura, wherein oleic acid and PEI are art equivalent surface treatment agents for magnetic nanoparticles).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further included a fourth step of mixing the magnetic particles surface-treated in the third step (Fe3O4-PAA-PEI particles) with a secondary surface treatment of PUU, as taught by Chiaradia, for the invention disclosed by Cao, in order to protect the magnetic nanoparticles, improve stability against aggregation, maintain high magnetic response, and allow for further functionalization (see teachings by Chiaradia above).
Response to Arguments
Applicant’s arguments, filed June 18, 2026, with respect to Claim 12, and dependent claims thereof, rejected under 35 U.S.C. 103 over Cao in view of Janjua, Enomura and Guardia Giros, have been fully considered and are persuasive in view of Applicant’s amendments to the claims further limiting parameters of the first heating step, the particle distribution variation coefficient and the SAR value. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made over Cao in view of Janjua, Reddy, Cheng, Enomura and Guardia Giros, as detailed above.
Regarding Cao: Applicant argues that Cao does not teach or suggest clustering crystals, and further argues that Cao merely collects the crystals by centrifugation, washing and drying. Applicant argues that the application of heat of Cao is not a result of clustering.
This argument is not found persuasive.
One of ordinary skill in the art would appreciate that in order to collect crystals after heating from a solution, the crystals would be clustered or aggregated by the reaction and process (see also Fig. 1 of Cao, wherein crystals comprise clustered/aggregated grains). Further, Reddy teaches wherein crystals are generated in the heated mixing of the first step, and wherein the solvothermal process, which encompasses the solvothermal process of Cao, results in the clustering and aggregation of the crystals from the heated step to form particles (see rejection of Claim 12 above and Fig. 1 of Reddy). Additionally, the clustering parameters taught by Reddy are the same as claimed and one of ordinary skill in the art would appreciate that the crystals would behave in the claimed manner and therefore cluster.
Regarding Reddy:
Applicant argues that the solvothermal heating is for carrying out crystallization and is therefore for generating crystals and not for clustering.
This argument is not found persuasive.
Reddy teaches forming a brown solution by heated mixing of raw materials, and one of ordinary skill in the art would appreciate this solution color to be indicative of having generated crystals (Sect. 2.2). Additionally, Reddy discloses nucleation of grains (crystals) and wherein the formed crystals then aggregate (cluster) to form particles (Fig. 1; Sect. 3, results and discussion, para. 2), and therefore the solvothermal process is specifically taught to be a clustering process. Further, the clustering parameters and process limitations are met, and the clustering parameters are the same as claimed and one of ordinary skill in the art would appreciate the crystals to behave in the same manner as the claimed invention and therefore cluster (see rejection of Claim 12 above). Additionally, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Banaei (previously cited, “Synthesis and characterization of new modified silica coated magnetite nanoparticles with bisaldehyde as selective adsorbents of Ag(i) from aqueous samples”): teaches wherein the surface of magnetite particles may be modified with silica supported ligands in order to then functionalize the nanoparticle for removal of metal ions (Pg. 3, lines 18-23). Banaei teaches this involves mixing the synthesized magnetite particles with a surface treatment agent, and heating at 90C for 2 hours (Section 2.4.2).
Santra (previously cited “Drug/Dye-Loaded, Multifunctional Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Dual Optical/Magnetic Resonance Imaging”): teaches wherein ligand functionalization occurs after particle nucleation, in order to allow for the formation of stable, disperse and high crystalline superparamagnetic oxide nanocrystals with coatings (Pg. 1862, Results and Discussion, Para. 1).
Wu (“Solvothermal synthesis of cobalt ferrite nanoparticles loaded on multiwalled carbon nanotubes for magnetic resonance imaging and drug delivery”): teaches forming cobalt iron nanoparticles by a combination solvothermal co-precipitation method, wherein ferric chloride hexahydrate is mixed with DEG at 90C and stirred for 30 minutes, mixed with NaOH and stirred for 40 further minutes (co-precipitation), and then subjected to solvothermal reaction at 180-240C for 8 hours (Sect. 2.2, Preparation of MWCNT/CoFe2O4 hybrids).
Baker (US 20150306246 A): teaches wherein co-precipitation occurs from 0-100C, with crystal formation occurring instantaneously or occurring for up to 3 hours, and wherein a heating rate for such a reaction is 1-30C/hour (0.02-0.5 C/min) (para. [0039]). Baker further teaches a high SAR of 600 W/g in the frequency range of 100Hz-200KHz for applied field strengths of 10-1500Oe (para. [0010]; para. [0045]), and wherein a high SAR allows for drug release by hyperthermia reaction/thermal trigger (para. [0019]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE P SMITH whose telephone number is (303)297-4428. The examiner can normally be reached Monday - Friday 9:00-4:00 MT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Keith Walker can be reached on (571)-272-3458. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
CATHERINE P. SMITH
Patent Examiner
Art Unit 1735
/CATHERINE P SMITH/Examiner, Art Unit 1735
/KEITH WALKER/Supervisory Patent Examiner, Art Unit 1735