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 .
Detailed Action
Summary
This is a 2nd Non-Final Office action based on the 17/615425 RCE response filed 03/16/2026. This action was made Non-Final to add 112b rejection, which were not mentioned in the last office action.
Claims 1-9, 11-13, 18 & 25 have been cancelled.
Claims 10, 14-17, 19-24, 26-45 have fully been examined.
Response to Arguments
Applicant's arguments filed 03/16/2026 have been fully considered but they are not persuasive.
Amendments made 03/16/2026 were helpful, however--- the examiner noticed further 112 issues and objections with respect to claims upon further review, with respect to language that was in the claims prior to the last office action, so this instant rejection is made Non-Final. As the 112(b) issues are substantive, the examiner is sending out this office action instead of calling applicant, to give applicant and applicant’s representatives time to consider an appropriately amend the claims. If applicant’s representative would like to hold an examiner’s interview prior to filing their response, so the examiner can pre-review any claim amendments prior to filing the examiner would be happy to do this.
The prior objections and 112 (b) rejections were overcome by the instant amendments dated 03/16/2026, however further ones which were not noticed before are made as shown above.
It is likely that if applicant can clear up these issues that they will also overcome the prior art rejections. The prior art used is the best prior art found to date after multiple searches.
Applicant does not provide substantive arguments about the prior art other than to say they do not think that the prior art teaches of the claims amended as they are 03/16/2025. Applicant also argues that applicant remarks filed 11/06/2025 are incorporated by reference. The examiner notes that no remarks were filed 11/06/2026 and assumes that applicant meant the remarks that were filed 11/14/2025.
Arguments dated 11/14/2025 are short and do not provide much detail or discussion. For the time being, the examiner disagrees with these arguments due to the clarity issues with respect to the claims.
Applicant argued in arguments dated 11/14/2025 that the prior art does not teach of the claimed centrifugation with higher revolutions for a shorter period of time, “about 10 minutes.” The examiner maintains that “about 10 minutes,” can be interpreted broadly and that PAKDELs teaching of 90 minutes (Page 3993, column 1) of centrifugation can read on this. PAKDEL also teaches of using 8000rpm for centrifugation and the claims require, “about 10,000 rpm,” which can also be interpreted broadly. It would have been obvious to one of ordinary skill in the art to optimize the analysis and processing conditions used through routine experimentation. MPEP 2144.05.
What applicant focuses their arguments on in the arguments dated 11/14/2025--- is that they think the prior art does not teach of things which were amended into the claims on 11/14/2025, including the addition of a new claim 31. The examiner has shown in the below rejection how the prior art teaches of what is claimed in instant claim 31 and also of the linker which was amended into Claim 10 on 11/14/2025.
Applicant has not updated their arguments to reflect an opinion on what they think with respect to what the prior art currently teaches below, including both the linker claimed in Claim 10 and Claim 31.
All claims remain rejected.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10, 14-17, 19-24, 26-45 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to Claims 10 & 31, it is claimed that “precipitating the nanodot carriers,” is performed “after the mechanical processing,” however the “nanodot carriers,” are not even created in the claims until after both the mechanical processing AND the treating of the nanodots. While this is clear enough, it is confusing--- so requires correction.
With respect to Claims 10 & 31, it is confusing what is going on with the claimed “polar liquid,” and specifically if the “polar groups,” come that attach to the “imperfections,” come from the polar liquid or elsewhere.
Specifically, it is claimed that boron nitride nanodots are processed in polar liquid to create imperfections on the nanodots. It is also claimed that the nanodots are treated, “treating,” to provide “polar groups at the imperfections.” From this, is unclear if the claimed “processing,” and “treating,” are both done in the claimed “polar liquid,” or not. If not, what substance leads to “provide polar groups at the imperfections,” is unclear. Further--- if the same polar liquid is used for both the claimed “mechanically processing,” and “treating,” steps--- it is unclear how “mechanically processing,” and “treating,” are different from each other, from what is claimed--- if they are in fact different.
Even further, with respect to the “polar liquid,” in Claims 10 & 31--- it is claimed that precipitating the nanodot carriers happens by “centrifuging the nanodot carriers in the polar liquid.” Therefore, as claimed it seems that all of the “mechanically processing,” “treating,” and “precipitating….by centrifuging,” all occur in the “polar liquid.” Therefore- again, it is not exactly clear how the claimed steps are different from one another and further if the same polar liquid is being used or not in each step since the claims do not always refer back to “the” “polar liquid,” for proper antecedent basis. (Please check claims 10 & 31 to ensure proper antecedent basis.) Centrifuging, and mechanically processing can be interpreted to be the same thing. Is treating really an additional step since it seems like the particles are always in a polar liquid? Or--- are there other solution components or parameters added in these steps which make them different from one another? Correction is required.
Further with respect to Claim 10, lines- 9-10, and in Claim 31, lines 11-12 “after mechanically processing, treating, and precipitating,” should be “after the mechanically processing, treating, and precipitating,” to ensure proper antecedent basis.
Even further with respect to Claim 10, 3 lines from the bottom of the claim—“the polar group,” is confusing/unclear, since before this in the claim it was only referred to as “polar groups,” which is plural. So- when saying “the,” “polar group,” it is unclear if applicant means that the linker only needs to be provided at one of the polar groups of the polar groups, or all of them. Or- if instead, applicant meant that there is only one imperfection per nanodot or nanodot carrier.
Claims 14-17, 19-24, 26-30, & 32-45 are rejected by virtue of their dependency on Claims 10 & 31. Applicant should check the dependent claims for other instances related to the above points.
Claim Objections
Claim 30 is objected to because of the following informalities:
There should be a space between “about,” and “47%,” instead of it being claimed as “about47%,” as claimed. Applicant should check the claims to ensure there are no other such instances.
Appropriate correction is required.
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 non-obviousness.
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 10, 14-17, 21, & 23 are rejected under U.S.C. 103 as being obvious over QUNHONG in Functionalized hexagonal boron nitride nanomaterials: emerging properties and applications (as cited on IDS dated 11/30/2021) in view of PAKDEL in Nano boron nitride and and further in view of CHIU in US 20120282632.
With respect to Claim 10, QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1), obtainable via standard sonication-assisted liquid exfoliation and solvothermal processes.
Specifically, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered which creates, “imperfections,” as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” (Page 3995-3996). All of the groups on Pages 3995-3996 can be considered polar groups at imperfections. QUNHONG further teaches of processing in a polar liquid (water) (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG does not specifically use the word “imperfections,” so in case this is not clear to one of ordinary skill, PAKDEL is used to remedy this.
PAKDEL teaches of a review of boron nitride nanostructures, and specifically of a method for determining structural characteristics for monolayer, and multilayer structures (abstract). PAKDEL further teaches of using nanodots (Page 953, column 2, paragraph 2, line 8-10 & Page 939, paragraphs 1 & 2 & Page 940, paragraph 1), and even further that the nanomaterials can have topological defects and imperfections and defects (Page 938, 2.3, line 5 & column 2, paragraph 2, line 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to monitor or create structural imperfections as is done in PAKDEL in the method and composition of QUNHONG since topological defects and vacancies are inevitable, and due to the advantage this offers in knowing and influencing the properties of the nanomaterials since the imperfections influence the nanomaterial properties (Page 938, column 2, last paragraph).
QUNHONG teaches of covalently attaching groups to the BN nanostructure (Page 3992, column 2, 2nd from last paragraph) and also of attaching other substances such as aminos and amines and alkyls (Page 3995, column 1, 2nd from last paragraph, Page 3995, column 2, 3.3, Page 3996, column 1, paragraph 1). PADKEL teaches of what is shown above.
They do not teach of the use of the claimed linker.
CHIU teaches of a method of functionalizing polymer dots (abstract) which are nanoscale dots (paragraph 0007). CHIU more specifically teaches that the dot is covalently attached to the functional groups (paragraph 0103), which then facilitate bioconjugation. CHIU further teaches that the reactive functional groups on the dot can be carboxyl or hydroxyl of carbonyl (which has a first and second functional group) (paragraph 0107). CHIU also teaches that a linker can be used with the polymer dot to covalently bond together the molecules and that the linker molecules are molecules which have more than one functional group ( so a first and second functional group) (paragraph 0098). CHIU further teach of the dots/particles being fluorescent (paragraph 0085,0087, 0157). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to covalently bond the molecules together and use linker as is done in CHIU in the method of QUNHONG and PAKDEL due to the advantage using a covalent bond to nanodot or polymer offers for further functionalization and attachment of the dot to facilitate bioconjugation (CHIU, paragraph 0103).
With respect to Claims 14-15, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered to create, “imperfections,” as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11). With respect to Claim 14, QUNHONG teaches of sonicating (mechanically processing/agitating) (Page 3993, column 1, paragraph 1). Sonication can be considered agitation.
With respect to Claim 16, QUNHONG teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” and specifically this group that is added can be a hydroxyl group (Page 3995-3996 & Page 3992, column 2, 3.1). QUHONG teaches that acid treatment with H2 SO4 is used to help with this (Page 3993, column 1, line 18). PAKDEL also teaches of exfoliating with acid (Page 941, column 1, lines 3-4).
With respect to Claim 17, QUNHONG teaches of using DMF as a solvent (Page 3996, column 1, line 8).
With respect to Claim 21, QUNHONG teaches of using organic solvents such as chloroform, N, N-dimethylacetamide, THF, DMF, acetone, toluene, and ethanol (Page 3996, column 1, first paragraph).
With respect to Claim 23, QUNHONG teaches of using hexagonal boron nitride (abstract and title, Figure 3 description, and Page 3995, column 1, first paragraph).
Claims 19-20, 22, & 24, 26-30 are rejected under U.S.C. 103 as being obvious over QUNHONG in Functionalized hexagonal boron nitride nanomaterials: emerging properties and applications (as cited on IDS dated 11/30/2021) in view of PAKDEL in Nano boron nitride flatland and in further in view of CHIU in US 20120282632 and further in view of HUELSEMANN in US 20180017579.
With respect to Claim 19, QUNHONG teaches of the claims as shown above and further teaches of precipitating the hydroxylated BN materials (Page 3994, Figure 2 description). PAKDEL teaches of centrifugation (Page 940, column 1 paragraph 1). CHIU also teaches of the method as shown above. They do not teach of precipitation with centrifugation as claimed and the exchanging of polar liquid with water.
HUELSEMANN is used to remedy this and teaches of a method of making and modifying nanoparticles(nanodots) (paragraph 0049-0050). HUELSEMANN specifically teaches of making silica nanoparticles through the Stöber process. Ethanol, water and ammonia solution (polar solution since ethanol, water, and ammonia are all polar) are brought in contact with one another at a suitable ratio, depending on the desired size of the nanoparticle to be synthesized. Tetraethoxy orthosilicate (abbreviates as, TEOS) is added to this batch, and the Stöber process is carried out (adding to a batch/bringing into contact can be considered mechanically processing). The ratio of the solvents, catalysts and reactants to one another determines the size of the particles and is selected such that the nanoparticle has the size of the protein aggregate, such as an oligomer of the protein misfolding disease to be detected. As a result, the silica nanoparticle having the desired size of the aggregate and/or oligomer is present. HUELSEMANN further teaches that hydroxyl groups are present on the surface of the silica nanoparticle (hydroxyl groups are polar groups, and these can be considered “imperfections,” as claimed). HUELSEMANN teaches of centrifuging (mechanically processing) this solution (paragraph 0044).
HUELSEMANN also teaches of a carboxyl group(contains hydroxyl group)(polar imperfection) is applied to the particle surface by reacting the amino group with succinic acid anhydride(acid treatment). For this purpose, the particle pellet is dissolved under an argon atmosphere in 0.1 M succinic acid anhydride in DMF (dimethylformamide) sonified for 20 minutes, and subsequently stirred overnight under an argon atmosphere at room temperature. The next day, the DMF solution is replaced with ethanol by way of three centrifugation and washing steps (3000 g, at least 2 hours) with ethanol. The pellet must be sonified for at least 30 minutes after every centrifugation step so as to separate the particles again. [0113] In the case of 20 nm SiNP, 500 mg aminated SiNP (from step 3 A) in 50 mL of a 0.1 M succinic acid anhydride solution in DMF is stirred overnight (therefore, HUELSEMANN teaches of processing by stirring and sonication (which can be considered mechanical processing), and then following that by centrifugation in ethanol which is a polar liquid to separate/precipitate the particles (paragraph 0111-0119).
HUELSEMANN teaches that after centrifugation the particles are then washed in water (which can read as the polar solution being exchanged with water) (paragraph 0111-0119). See above reasons for combination
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to precipitate or centrifuge out the particles as is done in HUELSEMANN in the methods of PAKDEL and QUNHONG since this offers advantage of biofunctionalizing the particles (HUELSEMANN, paragraph 0110).
With respect to Claim 20, QUNHONG and PAKDEL teach of the claimed invention as shown above. HUELSEMANN teaches of dialyzing against ethanol (which means exchanging ethanol for water)(paragraph 0107), and then treating with acid (paragraphs 0111-0119). Also see Claim 19 rejection. See above reasons for combination.
With respect to Claims 22 & 24, QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1), obtainable via standard sonication-assisted liquid exfoliation and solvothermal processes.
Specifically, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered which creates, “imperfections,” /disruptions (which would give polarity imbalance) as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” (Page 3995-3996). All of the groups on Pages 3995-3996 can be considered polar groups at imperfections. QUNHONG further teaches of processing in a polar liquid (water) (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG does not specifically use the word “imperfections,” so in case this is not clear to one of ordinary skill, PAKDEL is used to remedy this.
PAKDEL teaches of a review of boron nitride nanostructures, and specifically of a method for determining structural characteristics for monolayer, and multilayer structures (abstract). PAKDEL further teaches of using nanodots (Page 953, column 2, paragraph 2, line 8-10 & Page 939, paragraphs 1 & 2 & Page 940, paragraph 1), and even further that the nanomaterials can have topological defects and imperfections and defects (Page 938, 2.3, line 5 & column 2, paragraph 2, line 1). PAKDEL further teaches of dispersing the nanomaterials is organic solvents (Page 940, column 2, second to last paragraph).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to monitor or create structural imperfections as is done in PAKDEL in the method and composition of QUNHONG since topological defects and vacancies are inevitable, and due to the advantage this offers in knowing and influencing the properties of the nanomaterials since the imperfections influence the nanomaterial properties (Page 938, column 2, last paragraph).
With respect to Claim 26, QUNHONG teaches of using hexagonal boron nitride (abstract and title, Figure 3 description, and Page 3995, column 1, first paragraph). PAKDEL teaches of the nanosheet and dots having a thickness which is 10 nm or less (less than 100 nm) (Page 940, column 2, 2nd from bottom paragraph, Page 943, column 1, paragraph 1).
With respect to Claim 27, QUNHONG teaches of the BN being layered structures (Page 3990, column 1, paragraph 1). PAKDEL also teach of using layered structures and including 10 layers (Page 947, column 2, paragraph 2). This can read on “about” 30 through broadest reasonable interpretation. PAKDEL also teaches of increasing the number of layers (Page 950, column 1, paragraph 1).
With respect to Claim 28, QUNHONG teaches of the BN being layered structures (Page 3990, column 1, paragraph 1) and further teaches of having 3 and 6 layers (Figure 5, description & Page 4000, column 2, paragraph 2).
With respect to Claim 29, QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1), obtainable via standard sonication-assisted liquid exfoliation and solvothermal processes.
Specifically, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered which creates, “imperfections,” as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” (Page 3995-3996). All of the groups on Pages 3995-3996 can be considered polar groups at imperfections. QUNHONG further teaches of processing in a polar liquid (water) (Page 3993, column 1, paragraph 1, lines 1-11). QUNHONG teaches that there are 5 polar groups (see Figure 1). It would have been obvious to one or ordinary skill in the art to optimize the amount of polar groups used through routine experimentation.
With respect to Claim 30, With respect to Claim 14, QUNHONG teaches of sonicating (mechanically processing/agitating) (Page 3993, column 1, paragraph 1). Sonication can be considered agitation. QUNHONG does not teach of sonicating for a time period, but PAKDEL is used to remedy this. PAKDEL teaches of sonicating for (8 hours, which includes 20-30 minute), or heat treating (heat is formed when centrifugation occurs, mixing and of centrifuging for 90 minutes (Page 3993, column 1). It would have been obvious to one of ordinary skill in the art to optimize the analysis and processing conditions used through routine experimentation. MPEP 2144.05.
Claims 31 & 35-45 are rejected under 31, U.S.C. 103 as being obvious over QUNHONG in Functionalized hexagonal boron nitride nanomaterials: emerging properties and applications (as cited on IDS dated 11/30/2021) in view of PAKDEL in Nano boron nitride flatland in further in view of HUELSEMANN in US 20180017579.
With respect to Claim 31, QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1), obtainable via standard sonication-assisted liquid exfoliation and solvothermal processes.
Specifically, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered which creates, “imperfections,” as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” (Page 3995-3996). All of the groups on Pages 3995-3996 can be considered polar groups at imperfections. QUNHONG further teaches of processing in a polar liquid (water) (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG does not specifically use the word “imperfections,” so in case this is not clear to one of ordinary skill, PAKDEL is used to remedy this.
PAKDEL teaches of a review of boron nitride nanostructures, and specifically of a method for determining structural characteristics for monolayer, and multilayer structures (abstract). PAKDEL further teaches of using nanodots (Page 953, column 2, paragraph 2, line 8-10 & Page 939, paragraphs 1 & 2 & Page 940, paragraph 1), and even further that the nanomaterials can have topological defects and imperfections and defects (Page 938, 2.3, line 5 & column 2, paragraph 2, line 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to monitor or create structural imperfections as is done in PAKDEL in the method and composition of QUNHONG since topological defects and vacancies are inevitable, and due to the advantage this offers in knowing and influencing the properties of the nanomaterials since the imperfections influence the nanomaterial properties (Page 938, column 2, last paragraph).
QUNHONG teaches of covalently attaching groups to the BN nanostructure (Page 3992, column 2, 2nd from last paragraph) and also of attaching other substances such as aminos and amines and alkyls (Page 3995, column 1, 2nd from last paragraph, Page 3995, column 2, 3.3, Page 3996, column 1, paragraph 1). PADKEL teaches of what is shown above.
They do not teach of the use of the claimed centrifugation or the claimed size of the particle.
HUELSEMANN is used to remedy this and teaches of a method of making and modifying nanoparticles(nanodots) (paragraph 0049-0050) which are under 100 nm (paragraph 0038, 0079-0080) (in thickness, width and length as is a particle). HUELSEMANN specifically teaches of making silica nanoparticles through the Stöber process. Ethanol, water and ammonia solution (polar solution since ethanol, water, and ammonia are all polar) are brought in contact with one another at a suitable ratio, depending on the desired size of the nanoparticle to be synthesized. Tetraethoxy orthosilicate (abbreviates as, TEOS) is added to this batch, and the Stöber process is carried out (adding to a batch/bringing into contact can be considered mechanically processing). The ratio of the solvents, catalysts and reactants to one another determines the size of the particles and is selected such that the nanoparticle has the size of the protein aggregate, such as an oligomer of the protein misfolding disease to be detected. As a result, the silica nanoparticle having the desired size of the aggregate and/or oligomer is present. HUELSEMANN further teaches that hydroxyl groups are present on the surface of the silica nanoparticle (hydroxyl groups are polar groups, and these can be considered “imperfections,” as claimed). HUELSEMANN teaches of centrifuging (mechanically processing) this solution (paragraph 0044).
HUELSEMANN also teaches of a carboxyl group(contains hydroxyl group)(polar imperfection) is applied to the particle surface by reacting the amino group with succinic acid anhydride(acid treatment). For this purpose, the particle pellet is dissolved under an argon atmosphere in 0.1 M succinic acid anhydride in DMF (dimethylformamide) sonified for 20 minutes, and subsequently stirred overnight under an argon atmosphere at room temperature. The next day, the DMF solution is replaced with ethanol by way of three centrifugation and washing steps (3000 g, at least 2 hours) with ethanol. The pellet must be sonified for at least 30 minutes after every centrifugation step so as to separate the particles again. [0113] In the case of 20 nm SiNP, 500 mg aminated SiNP (from step 3 A) in 50 mL of a 0.1 M succinic acid anhydride solution in DMF is stirred overnight (therefore, HUELSEMANN teaches of processing by stirring and sonication (which can be considered mechanical processing), and then following that by centrifugation in ethanol which is a polar liquid to separate/precipitate the particles (paragraph 0111-0119).
HUELSEMANN teaches that after centrifugation the particles are then washed in water (which can read as the polar solution being exchanged with water) (paragraph 0111-0119). See above reasons for combination
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to precipitate or centrifuge out the particles of the size as is done in HUELSEMANN in the methods of PAKDEL and QUNHONG since this offers advantage of bio-functionalizing the particles (HUELSEMANN, paragraph 0110).
With respect to Claim 35, QUNHONG teaches of using hexagonal boron nitride (abstract and title, Figure 3 description, and Page 3995, column 1, first paragraph). PAKDEL teaches of the nanosheet and dots having a thickness which is 10 nm or less (less than 100 nm) (Page 940, column 2, 2nd from bottom paragraph, Page 943, column 1, paragraph 1). HUELSEMANN is used to remedy this and teaches of a method of making and modifying nanoparticles(nanodots) (paragraph 0049-0050) which are under 100 nm (paragraph 0038, 0079-0080) (in thickness, width and length as is a particle).
With respect to Claim 36, QUNHONG teaches of the BN being layered structures (Page 3990, column 1, paragraph 1). QUNHONG further teaches of using hexagonal boron nitride (abstract and title, Figure 3 description, and Page 3995, column 1, first paragraph). PAKDEL also teach of using layered structures and including 10 layers (Page 947, column 2, paragraph 2). This can read on “about” 30 through broadest reasonable interpretation. PAKDEL also teaches of increasing the number of layers (Page 950, column 1, paragraph 1).
With respect to Claim 37, QUNHONG teaches of the BN being layered structures (Page 3990, column 1, paragraph 1) and further teaches of having 3 and 6 layers (Figure 5, description & Page 4000, column 2, paragraph 2). QUNHONG further teaches of using hexagonal boron nitride (abstract and title, Figure 3 description, and Page 3995, column 1, first paragraph).
With respect to Claims 38-39, QUNHONG teaches of using organic solvents such as chloroform, N, N-dimethylacetamide, THF, DMF, acetone, toluene, and ethanol (Page 3996, column 1, first paragraph).
With respect to Claim 40, QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1) and QUNHONG further teaches of the BN being layered structures (Page 3990, column 1, paragraph 1) and further teaches of having 3 and 6 layers (Figure 5, description & Page 4000, column 2, paragraph 2). QUNHONG further teaches of using hexagonal boron nitride (abstract and title, Figure 3 description, and Page 3995, column 1, first paragraph).
With respect to Claim 41, QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1), obtainable via standard sonication-assisted liquid exfoliation and solvothermal processes.
Specifically, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered which creates, “imperfections,” /disruptions (which would give polarity imbalance) as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” (Page 3995-3996). All of the groups on Pages 3995-3996 can be considered polar groups at imperfections. QUNHONG further teaches of processing in a polar liquid (water) (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG does not specifically use the word “imperfections,” so in case this is not clear to one of ordinary skill, PAKDEL is used to remedy this.
PAKDEL teaches of a review of boron nitride nanostructures, and specifically of a method for determining structural characteristics for monolayer, and multilayer structures (abstract). PAKDEL further teaches of using nanodots (Page 953, column 2, paragraph 2, line 8-10 & Page 939, paragraphs 1 & 2 & Page 940, paragraph 1), and even further that the nanomaterials can have topological defects and imperfections and defects (Page 938, 2.3, line 5 & column 2, paragraph 2, line 1). PAKDEL further teaches of dispersing the nanomaterials is organic solvents (Page 940, column 2, second to last paragraph).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to monitor or create structural imperfections as is done in PAKDEL in the method and composition of QUNHONG since topological defects and vacancies are inevitable, and due to the advantage this offers in knowing and influencing the properties of the nanomaterials since the imperfections influence the nanomaterial properties (Page 938, column 2, last paragraph).
With respect to Claim 42, With respect to Claim 14, QUNHONG teaches of sonicating (mechanically processing/agitating) (Page 3993, column 1, paragraph 1). Sonication can be considered agitation. QUNHONG does not teach of sonicating for a time period, but PAKDEL is used to remedy this. PAKDEL teaches of sonicating for (8 hours, which includes 20-30 minute), or heat treating (heat is formed when centrifugation occurs, mixing and of centrifuging for 90 minutes (Page 3993, column 1). It would have been obvious to one of ordinary skill in the art to optimize the analysis and processing conditions used through routine experimentation. MPEP 2144.05.
With respect to Claim 44, HUSSELMAN teaches of determining the size of the nanoparticles by electron microscopy (paragraph 0134).
With respect to Claims 43 & 45 QUNHONG teaches of a method for preparation (method of making) of edge-hydroxylated h-BN dots, which is a nanodot carrier and subsequent derivatization of their surface polar group (Page 3995-3996, Figure 3 description, Page 3995, column 1, paragraph 1), obtainable via standard sonication-assisted liquid exfoliation and solvothermal processes.
Specifically, QUNHONG teaches of mechanically processing boron nitride through sonication which includes hydrolysis induced exfoliation, cutting, and hydroxylation of the BN layers- this can be considered which creates, “imperfections,” as instantly claimed (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches that the surface polar group can be derivatized (this can be considered that “imperfections,” are treated to provide polar groups at the “imperfections,” (Page 3995-3996). All of the groups on Pages 3995-3996 can be considered polar groups at imperfections. QUNHONG further teaches of processing in a polar liquid (water) (Page 3993, column 1, paragraph 1, lines 1-11).
QUNHONG further teaches using heat treatment/reactions at high temperatures which can be between 60-180 degrees Celsius (Page 3992, column 2, last line, Figure 1) (this temperature would lead to evaporation of polar solvents like water).
Claims 32-34 are rejected under 31, U.S.C. 103 as being obvious over QUNHONG in Functionalized hexagonal boron nitride nanomaterials: emerging properties and applications (as cited on IDS dated 11/30/2021) in view of PAKDEL in Nano boron nitride flatland in further in view of HUELSEMANN in US 20180017579 and in further in view of CHIU in US 20120282632.
With respect to Claims 32-34, QUNHONG teaches of the claims as shown above, but QUNHONG does not specifically use the word “imperfections,” so in case this is not clear to one of ordinary skill, PAKDEL is used to remedy this.
PAKDEL teaches of a review of boron nitride nanostructures, and specifically of a method for determining structural characteristics for monolayer, and multilayer structures (abstract). PAKDEL further teaches of using nanodots (Page 953, column 2, paragraph 2, line 8-10 & Page 939, paragraphs 1 & 2 & Page 940, paragraph 1), and even further that the nanomaterials can have topological defects and imperfections and defects (Page 938, 2.3, line 5 & column 2, paragraph 2, line 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to monitor or create structural imperfections as is done in PAKDEL in the method and composition of QUNHONG since topological defects and vacancies are inevitable, and due to the advantage this offers in knowing and influencing the properties of the nanomaterials since the imperfections influence the nanomaterial properties (Page 938, column 2, last paragraph).
QUNHONG teaches of covalently attaching groups to the BN nanostructure (Page 3992, column 2, 2nd from last paragraph) and also of attaching other substances such as aminos and amines and alkyls (Page 3995, column 1, 2nd from last paragraph, Page 3995, column 2, 3.3, Page 3996, column 1, paragraph 1). PADKEL teaches of what is shown above. HUSSELMAN also teaches of the claimed invention as shown above.
They do not teach of the use of the claimed linker.
CHIU teaches of a method of functionalizing polymer dots (abstract) which are nanoscale dots (paragraph 0007). CHIU more specifically teaches that the dot is covalently attached to the functional groups (paragraph 0103), which then facilitate bioconjugation. CHIU further teaches that the reactive functional groups on the dot can be carboxyl or hydroxyl of carbonyl (which has a first and second functional group) (paragraph 0107). CHIU also teaches that a linker can be used with the polymer dot to covalently bond together the molecules and that the linker molecules are molecules which have more than one functional group (paragraph 0098). CHIU further teach of the dots/particles being fluorescent (paragraph 0085,0087, 0157). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of/to covalently bond the molecules together and use linker as is done in CHIU in the method of QUNHONG and PAKDEL and HUSSELMAN due to the advantage using a covalent bond to nanodot or polymer offers for further functionalization and attachment of the dot to facilitate bioconjugation (CHIU, paragraph 0103).
Conclusion
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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