Notice of Pre-AIA or AIA Status
The present application, filed on or after April 25, 2024, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention filed on 04/25/2024 in the matter of Application N° 18/704,561. Said documents are entered on the record. The Examiner further acknowledges the following: claims 16-25 represent all claims currently under consideration.
Claim Objections
Claims 23 and 24 objected to because of the following informalities: these claims depend from claim 17 and their limitations lack antecedent basis in claim 17. It is apparent that the intent was to have them depend from claim 22 and they have been examined as if that were the case. 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 nonobviousness.
Claims 16-25 are rejected under 35 U.S.C. 103 as being unpatentable over Senel et al. (Graphene quantum dots: Synthesis, characterization, cell viability, genotoxicity for biomedical applications Behiye Senel et al. 20 May 2019.), in view of Meierhofer et al. (Citric Acid Based Carbon Dots with Amine Type Stabilizers: pH Specific Luminescence and Quantum Yield Characteristics Florian Meierhofer et al. J. Phys. Chem. C 2020, 124, 8894-8904).
Senel et al. disclose wherein the emergence and use of new N-doped graphene quantum dots (GQDs) through the hydrothermal reaction of P-aminophenol with citric acid. The physico-chemical characteristics of the synthesized N-doped GQDS have been analyzed, along with their antibacterial, antioxidant, DNA binding, and cleavage properties. Studies on siRNA loading were conducted, and the impact on cells was assessed. The results of the microscopy showed that the N-doped GQDs were rapidly absorbed by the cell. The new N-doped GQDs containing siRNA have the potential to inhibit tumors in situ by breaking DNA and mRNA (See abstract).
Regarding claim 17, Senel et al. disclose wherein the N-GQDs zeta potential is -2.86 (mV) (See Table 3).
Regarding claim 18, Senel et al. disclose wherein the N-doped GQDs have a particle size of 10.9 (nm) (See Table 3).
Regarding claim 19, Senel et al. disclose wherein nitrogen-doped graphene quantum dots bound to a gene at ratios disclosed as a range. Although the prior art does not expressly disclose a binding ratio of 1:50. The ratio between the nitrogen-doped graphene quantum dots and the gene is a result-effective variable, and that an optimum ratio exhibiting desired effects could be derived by a person skilled in the art through routine and repeated experimentation. The numerical limitation of the binding ratio is not considered to involve any critical significance. Accordingly, it would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to select or optimize a binding ratio of 1:50 within the disclosed range, as such optimization would have involved no more than routine experimentation to achieve predictable results.
Regarding claim 20, Senel et al. teach the coupling of siRNA through electrostatic attraction between the negatively charged siRNA and positively charged Eudragit forming the GQDs (See page 848, 3.7.2 Binding studies with EpHA2 SiRNA of Eu-GQDs).
Regarding claim 21, Senel et al. disclose wherein studies on siRNA loading were carried out, and their impact on cells was assessed. The microscopy N-doped GQDs were rapidly absorbed into the cell, according to the results. Through DNA and mRNA breaking, the unique N-doped GQDs containing siRNA are a potential in situ tumor suppressor (See abstract).
However, Senel et al. do not teach wherein a method of preparing nitrogen-doped graphene quantum dots, comprising a mixed solution of citric acid and polyethylenimine to a hydrothermal reaction.
Regarding claims 22, and 25, Meierhofer et al. describe a process that uses a hydrothermal reaction between citric acid and polyethylenimine to create nitrogen-doped carbon dots (See abstract and page 8895, second paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the invention to incorporate the hydrothermal reaction between citric acid and polyethylenimine as taught by Meierhofer et al. into the method of preparing nitrogen-doped quantum dots into Senel et al.
Regarding claim 23, Meierhofer et al. teaches hydrothermal synthesis of nitrogen -doped carbon dots using citric acid and polyethylenimine. A hydrothermal reaction necessarily requires heating to elevated temperature under pressure. Microwave irradiation is a well-known, interchangeable heating technique for hydrothermal/solvothermal reactions. Selecting microwaves instead of conventional heating is routine optimization of a known process parameter, not a change in chemistry or function, MPEP2143/2144.
Meierhofer et al. disclose a hydrothermal process for synthesizing nitrogen-doped carbon dots via reaction of citric acid and polyethylenimine, which inherently requires heating the reaction mixture to elevated temperature under pressure (See abstract). Microwave irradiation is a well-known and commonly used alternative heat source for hydrothermal and solvothermal reactions, providing rapid and uniform temperature increase. A person of ordinary skill in the art would have recognize that microwave irradiation could be readily substituted for conventional heating to supply the thermal energy necessary for the hydrothermal reaction, motivated by predictable advantages such as reduced reaction time and improved heating efficiency. The selection of microwave irradiation therefore represents nothing more than the predictable use of a known heating technique to perform a known process, and constitutes a matter of routine optimization of a result- effective variable.
Regarding claim 24, Meierhofer et al. disclose carbon dot systems formed by a hydrothermal reaction between citric acid and polyethylenimine, and further teach that such systems exhibit high photoluminescence quantum yields (40% and 48%) at neutral pH, demonstrating that the reaction system is operable and effective for producing the desired photoluminescent carbon dots (See abstract).
The relative amounts of citric acid and polyethylenimine in the reaction mixture constitute a result-effective variable, as changes in precursor ratios are known to influence properties such as nitrogen content, surface functionality, and photoluminescence behavior. A person of ordinary skill in the art would have reasonably expected that adjusting the weight ratio of these known reactants would affect the optical properties of the resulting carbon dots. Accordingly, determining a suitable or optimal weight ratio, including a ratio falling within the claimed range of 1 to 10:1, would have been achieved through routine experimentation, such as systematically varying precursor ratios and measuring photoluminescence output, without requiring inventive skill. In the absence of evidence that the claimed numerical range is critical or produces unexpected results, the recited weight ratio represents nothing more than an optimization of a known process parameter, and therefore does not confer patentable distinction over the teachings of Meierhofer et al.
Conclusion
No claim is allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax, can be reached at telephone number (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY BARBER/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615