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 .
Response to Arguments
With respect to the rejection of Claims 1-2, 7, 9-11, 13-16, 18-20, 23, and 25 under 35 U.S.C. 102(a)(1) as being anticipated by Darr et al., as understood the traversal relies on amendments. Claim 1 has been amended to recite “wherein the initiator solution comprises a base”. Darr et al. does not disclose a base as part of the initiator solution. The rejections have been WITHDRAWN.
With respect to the rejection of Claim(s) 1, 9, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frenz et al., as understood the traversal relies on amendments. Claim 1 has been amended to recite “wherein the quenching agent is added to the reaction mixture 3 to 10 seconds after the initiation of the nanoparticle precipitation process.”. Frenz et al. does not specifically limit the quenching time. The rejections have been WITHDRAWN.
With respect to the rejection of Claims 3 and 5 under 35 U.S.C. 103 as being unpatentable over Frenz et al., as understood the traversal relies on amendments. Claim 1 has been amended to recite “wherein the quenching agent is added to the reaction mixture 3 to 10 seconds after the initiation of the nanoparticle precipitation process.”. Frenz et al. does not specifically limit the quenching time. The rejections have been WITHDRAWN.
With respect to the rejection of Claims 5 and 8 under 35 U.S.C. 103 as being unpatentable over Darr et al., as understood the traversal relies on amendments. Claim 1 has been amended to recite “wherein the initiator solution comprises a base”. Darr et al. does not disclose a base as part of the initiator solution. The rejections have been WITHDRAWN.
With respect to the rejection of Claim 17 under 35 U.S.C. 103 as being unpatentable over Darr et al. in view of Shaterabadi et al., as understood the traversal relies on amendments. Claim 1 has been amended to recite “wherein the quenching agent is added to the reaction mixture 3 to 10 seconds after the initiation of the nanoparticle precipitation process.”. Neither Darr et al. nor Shaterabadi et al. discloses a specific time to quench is between 3 to 10 seconds. The rejections have been WITHDRAWN.
Notwithstanding the foregoing, applicant’s amendments gave rise to the new rejections appearing below.
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) 1, 3, 5, 7, 9-11, 13-16, 18-20, 23, and 25-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009136300 A2 Frenz et al. in view of US 20160074823 Darr et al. Claim 1 requires “A method for synthesising metal oxide nanoparticles, the method comprising: mixing. to provide a reaction mixture, a precursor solution comprising metal ions with an initiator solution to initiate a nanoparticle precipitation process”. Frenz et al. discloses “For example, in the synthesis of iron oxide nanoparticles, the first reaction solution may contain a mixture of FeCl2 and FeCl3 salts and the second reaction mixture may comprise a mixture of ammonium hydroxide.” [0052]. The first reaction mixture is a precursor solution comprising metal ions and the second reaction solution is an initiator solution.
Claim 1 further requires “and quenching the precipitation process by adding a quenching agent to the reaction mixture so as to yield a dispersion comprising metal oxide nanoparticles.”. Frenz et al. discloses “For example, a newly formed encapsulated nanoparticle may then be injected into the same or a separate device for fusion with an additional set of droplets to quench or further modify the newly formed particles.” [0009].
Claim 1 further requires “wherein the initiator solution comprises a base”. Frenz et al. discloses “For example, in the synthesis of iron oxide nanoparticles, the first reaction solution may contain a mixture of FeCl2 and FeCl3 salts and the second reaction mixture may comprise a mixture of ammonium hydroxide.” [0052]. Ammonium hydroxide (NH4OH) is the initiator solution and a base.
Claim 1 further requires “wherein the quenching agent is added to the reaction mixture 3 to 10 seconds after the initiation of the nanoparticle precipitation process.”. Frenz et al. does not specifically limit the quench time. Darr et al. is similarly directed to the synthesis of iron nanoparticles “According to the present invention there is provided a co-current mixer for production of nanoparticles by precipitation” [0014]. Darr et al. similarly does not specifically limit the quench time, however they do disclose “A rapid quench is desirable, and the skilled man will be able to select by calculation and/or empirical experiment a suitable flow volume and inlet temperature, in order to achieve the size objective.” [0106]. It is understood that for a fixed distance (i.e. one particular reactor) controlling the flow volume and controlling the quench time are equivalent, the reaction quenches once the nanoparticles reach the quench zone which could be expressed either as a time of travel or a flow rate of solution. In other words Darr et al. discloses that quench time and particle size are a results effective variable and that one of ordinary skill in the art may vary quench time as needed by routine optimization to achieve the desired resulting size. This makes selecting a time, such as 3-10 seconds, obvious for one of ordinary skill in the art.
It would have been obvious to one of ordinary skill in the art to have combined the teachings of Frenz et al. with the teachings of Darr et al. for at least the reason that they both similarly relate to the synthesis of iron oxide nanoparticles from solution.
The motivation to have combined the method of Frenz et al. with the teaching from Darr et al. is that Frenz et al. does not provide guidance for size control or quench time. By referencing the teaching from Darr et al. that quench time can be used to control particle size one of ordinary skill in the art is afforded greater control over the final product.
Claim 3 requires “the metal oxide nanoparticles in the dispersion have an average diameter of less than 7 nm.”. Frenz et al. discloses “Particle size measurements by transmission electron microscopy (TEM) (Figure 10) show that the average particle diameter is smaller for the fast microfluidic compound mixing (4 +/- 1 nm) compared to bulk mixing (9 +/- 3 nm).” [Page 18, Paragraph 2]. It is worth noting that the method of forming the nanoparticles of Example 2 did not utilize a quenching agent as required by Claim 3 by virtue of being dependent on Claim 1. However, Frenz et al. discloses quenching as optional and therefore performing quenching is obvious and quenching would have only made the nanoparticles smaller (or about the same size) placing them further into the range presented by Claim 3.
Claim 5 requires “the quenching agent is added to the reaction mixture within about 3 to 7 seconds after the initiation of the precipitation process.”. Neither Frenz et al. nor Darr et al. specifically limit quenching time (see Claim 1), however Darr et al. motivates the one with ordinary skill in the art to optimize flow rate, and therefore necessarily quench time, in order to achieve a desired size of nanoparticle. Such routine optimization is expected to overlap with a quench time of 3-7 seconds.
Claim 7 requires “the quenching agent is added to the reaction mixture once nanoparticles comprising magnetic metal oxide phases have formed.”. Darr et al. discloses magnetic metal oxide phases quenched by citric acid solution “In one example nanoparticles of magnetic iron oxides (Fe3O4) were capped with citric acid” [0108].
Claim 9 requires “the metal oxide nanoparticles are magnetic.”. Frenz et al. discloses “EXAMPLE 2 Synthesis of magnetic iron oxide nanoparticles” [Page 16].
Claim 10 requires “the metal oxide nanoparticles are ferrite nanoparticles.”. Darr et al. discloses ferrite (Fe3O4) “In one example nanoparticles of magnetic iron oxides (Fe3O4) were capped with citric acid” [0108].
Claim 11 requires “the metal ions comprise iron ions”. Darr et al. discloses “The opposed inlets ( 31 ) received an aqueous solution of Fe3+ precursor” [0109].
Claim 13 requires “the quenching agent comprises at least one acid.”. Darr et al. discloses “Citric acid capping agent was fed as a water based solution via the third inlet” [0110].
Claim 14 requires “the at least one acid is a chelating agent.”. Darr et al. is silent to chelating agents, however uses citric acid (see Claim 13) which the present application specification discloses as an example chelating agent “examples include chelating agents such as carboxylic acids (e.g. citric acid)” [Page 13, Lines 17-18].
Claim 15 requires “the at least one acid comprises citric acid and/or hydrochloric acid.”. Darr et al. discloses “Citric acid capping agent was fed as a water based solution via the third inlet” [0110].
Claim 16 requires “adding the quenching agent reduces the pH of reaction mixture so as to inhibit growth of the metal oxide nanoparticles”. Darr et al. discloses “Citric acid capping agent was fed as a water based solution via the third inlet” [0110]. The citric acid would have lowered reaction pH by virtue of being an acid mixed with a neutral reaction solution.
Claim 18 requires “the dispersion comprising the metal nanoparticles is a colloidally stable dispersion.”. Darr et al. discloses “The coating is considered to be important in preventing agglomeration.” [0112]. It is understood that a nanoparticle dispersion which agglomerates is not colloidally stable but if agglomeration is prevented then the mixture is colloidally stable.
Claim 19 requires “the method is performed in a flow reactor.”. Darr et al discloses a flow reactor, see Figure 12 reproduced below:
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Claim 20 requires “the mixing of the precursor solution with the initiator solution occurs at a first junction of the flow reactor and the addition of the quenching agent to the reaction mixture occurs at a second junction of the flow reactor downstream from the first junction.”. From Figure 12 (above) it can be seen that mixing occurs at junction 34 and the quenching agent is added at junction 74, which is downstream.
Claim 23 requires “A product comprising metal oxide nanoparticles produced by the method of claim 1, wherein the product is an MRI contrast agent or a catalyst.”. Darr et al. is silent towards the use of the ferrite nanoparticles produced however a product and its properties are inseparable and intended use does not limit a product.
To the extent that the limitation “the product is an MRI contrast agent or a catalyst” is considered intended use, intended use is covered by MPEP 2111.02 which states “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim.”. In the present case no structure, other than having a high surface area to volume ratio (which is a common feature of all nanoparticles) is suggested which might serve to further limit a product.
Claim 25 requires “A flow reactor configured to perform the method of any one of claim 1.”. Darr et al. discloses a flow reactor (see Figure 12, above) and performing the method of Claim 1 (see Claim 1).
Claim 26 requires “the metal ions are iron ions”. Frenz et al. discloses “For example, in the synthesis of iron oxide nanoparticles, the first reaction solution may contain a mixture of FeCl2 and FeCl3 salts and the second reaction mixture may comprise a mixture of ammonium hydroxide.” [0052].
Claim 26 further requires “the base is sodium hydroxide”. Frenz et al. discloses ammonium hydroxide as the base, however one of ordinary skill in the art would recognize that sodium hydroxide would also similarly work as a base for coprecipitation. In other words replacing ammonium hydroxide with sodium hydroxide represents a simple substitution of one known element for another to yield predictable results.
Claim 26 further requires “the quenching agent comprises at least one acid and the acid is hydrochloric acid or citric acid.”. Frenz et al. discloses “As starting materials for theprecipitation of iron oxide nanoparticles FeCl2-4H2O (Sigma-Aldrich) and FeCl3-6H2O (Acros Organics) were used to form a first reaction solution; ammonium hydroxide solution (28% NH3 - Fluka) and hydrochloric acid (37% HCl- Acros Organics) of analytical grade were used form a second reaction solution.” [0057].
Claim(s) 17 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009136300 A2 Frenz et al. in view of US 20160074823 Darr et al. in further view of NPL - “High impact of in situ dextran coating on biocompatibility, stability and magnetic properties of iron oxide nanoparticles” Shaterabadi et al. Claim 17 requires “the precursor solution and/or the initiator solution comprises one or more stabilisers.”. Neither Frenz et al. nor Darr et al. disclose stabilizers.
Shaterabadi et al. discloses “Biocompatible ferrofluids based on dextran coated iron oxide nanoparticles were fabricated by conventional coprecipitation method. The experimental results show that the presence of dextran in reaction medium not only causes to the appearance of superparamagnetic behavior but also results in significant suppression in saturation magnetization of dextran coated samples.” [Abstract]. Specifically the dextran is added to the precursor solution “two different weight ratios of dextran to magnetite NPs (i.e. 1:1 and 2:1) were dissolved in reaction medium [aqueous FeCl2 and FeCl3 mixture] prior to adding sodium hydroxide.” [Page 948, Section 2.2].
It would have been obvious for one of ordinary skill in the art to have combined the method of Darr et al. with the dextran of Shaterabadi et al. because they both similarly relate to the problem of synthesizing iron oxide nanoparticles.
The motivation to combine the dextran of Shaterabadi et al. into the precursor solution of Darr et al. is that the nanoparticles would be biocompatible and be suitable for use inside of the body as, for example, an MRI contrast agent.
Claim 26 requires “the metal ions are iron ions”. Frenz et al. discloses “For example, in the synthesis of iron oxide nanoparticles, the first reaction solution may contain a mixture of FeCl2 and FeCl3 salts and the second reaction mixture may comprise a mixture of ammonium hydroxide.” [0052].
Claim 26 further requires “the base is sodium hydroxide”. Frenz et al. does not disclose sodium hydroxide. Shaterabadi et al. discloses “12 mL of 1M aqueous solution of sodium hydroxide (as a reducing agent) was then added to adjust solution pH to 12” [Page 948, Section 2.2].
Claim 26 further requires “the quenching agent comprises at least one acid and the acid is hydrochloric acid or citric acid.”. Frenz et al. discloses “As starting materials for the precipitation of iron oxide nanoparticles FeCl2-4H2O (Sigma-Aldrich) and FeCl3-6H2O (Acros Organics) were used to form a first reaction solution; ammonium hydroxide solution (28% NH3 - Fluka) and hydrochloric acid (37% HCl- Acros Organics) of analytical grade were used form a second reaction solution.” [0057].
Conclusion
Applicant's amendment necessitated the/any 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.
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/JOSHUA MAXWELL SPEER/
Examiner
Art Unit 1736
/DANIEL BERNS/Primary Examiner, Art Unit 1736