DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 1-10 are pending in this application.
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 .
Priority
This application is a 35 USC 111(a) having the filing date 29 Jan. 2024.
Information Disclosure Statement
An information disclosure statement (IDS) has not been filed with the instant application.
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 3, 8, and 10 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.
Instant claim 3 depends to claim 2 and requires that the particles are washed with ice-cold deionized water after resuspension; however, claim 2 requires already requires washing with ice cold water deionized water after resuspension.
Instant claim 8 recites the method of claim 9; however, claim 9 is directed to a theragnostic carbon quantum dot nanomedicine. Under the interpretation that claim 8 depends to claim 7, that claim already requires that the CQDs are dispersed in the coupling buffer through sonication for 10 min at high power. It is not clear that claim 8 would further limit claim 7.
Instant claim 10 recites weight amount and then further recites 500 mL and 10 mL which are volumes and not weight amounts.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lodi et al. (CN 116617411 A-English translation; published 22 Aug. 2023; see attached 892).
Regarding claims 9-10, Lodi et al. disclose a preparation of A. indica methanol extract. Fresh specimens of the neem tree were collected. 50 g of crushed dried neem lead powder is mixed with 500 mL of methanol, left to stand for 1 wk, the mixture is filtered, condensed using a rotary evaporator and freeze dried to obtain the methanol extract for further analysis. Lodi et al. teach that 0.57 g of L-cysteine was dissolved in 10 mL of deionized water and 1.5 g citric acid was added and mixed. The solution was sonicated for 10 min and then heated in a microwave for 4 min. After cooling the solution to room temperature, it was dissolved in 10 mL deionized water to obtain a brown solution. The solution was then centrifuged at 9000 rpm for 10 min to remove impurities. The CQD was extracted with ethyl acetate to obtain CQD nanomaterial which were stored in a refrigerator at 4oC for later use (examples 1).
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.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lodi et al. (CN 116617411 A-English translation; published 22 Aug. 2023; see attached 892).
Lodi et al. teach as discussed above. Lodi et al. teach thermal diagnosis carbon quantum dot nano compound for targeted drug delivery of acute myelogenous leukemia (see title).
Regarding claim 1 and 9-10, Lodi et al. teach a preparation of A. indica methanol extract. Fresh specimens of the neem tree were collected. 50 g of crushed dried neem lead powder is mixed with 500 mL of methanol, left to stand for 1 wk, the mixture is filtered, condensed using a rotary evaporator and freeze dried to obtain the methanol extract for further analysis ([0079]). Lodi et al. teach that 0.57 g of L-cysteine was dissolved in 10 mL of deionized water and 1.5 g citric acid was added and mixed. The solution was sonicated for 10 min and then heated in a microwave for 4 min. After cooling the solution to room temperature, it was dissolved in 10 mL deionized water to obtain a brown solution. The solution was then centrifuged at 9000 rpm for 10 min to remove impurities. The CQD was extracted with ethyl acetate to obtain CQD nanomaterial which were stored in a refrigerator at 4oC for later use (examples 1).
Regarding claims 2-3, Lodi et al. teach the preparation of phenolic conjugated CQDs (OH-CQDs). The method in this embodiment is to used 4.28 µg/µL of CQD nanomaterials and phytochemicals. The freeze-dried methanol extract of neem tree was suspended in the THF containing 50 mg/mL CDI and the particles were activated by mixing at room temperature for 2 h. The activated particles were washed with THF to remove excess CDI and byproducts then resuspended at a concentration of 10 mg/mL in cold coupling buffer (0.1 M sodium carbonate, pH 9.5) as washed with ice cold deionized water. Ribonucleic acid-containing amine was added at a volume of 1:1 between the methanol extract of neem tree and CQD and the mixture was stirred at 4oC for at least 18 h (example 3).
Regarding claim 4, Lodi et al. teach the synthesis of CD33-bound OH-CQDs by placing 10 mg of OH-CQDs in 10 mL of coupling buffer (50 mM sodium phosphate) and adjusting the pH to 8 with 1 M NaOH. 50 µL of rabbit polyclonal CD33 was dissolved in 10 mL of coupling buffer (0.1 M carbonate at pH 9.5). Mix the solutions thoroughly and add 10 mg of EDC (ECD to QCD is 1:1) to activate the carboxyl group of CQD while adjusting the pH to 6.4 with 1 M HCl. The reaction mixture was then incubated in the dark at 37oC for 2 h with continuous shaking at 100 rpm. Centrifuge at 12,000 rpm for 10 min at 40oC to remove any remaining unattached molecules then was three times with TBS (20 mL each time). The washed particles were suspended in 1xTBS buffer and stored at 20oC for later use (example 4).
Regarding claim 5, Lodi et al. teach the preparation of aldehyde-CQDs. The phytochemical extract in example 1 was oxidized to obtain an intermediate product containing aldehyde groups of methanol extract. The methanol extract of neem tree containing aldehyde group after oxidation treatment was suspended in buffer (0.05 M sodium carbonate and 0.1 M sodium citrate, pH=9.6) at a concentration of 1 mg/mL. Next, the amine functionalized CQD was added to the aldehyde containing oxidized neem methanol extract and dissolved in the above buffer solution at molar ratio of 1:4 between oxidized neem methanol extract with aldehyde groups and the CQD nanomaterial to obtain conjugated solution. Then, 10 µL of 1 M sodium hydroxide solution containing 5 M sodium cyanide borohydride was added to each mL of the conjugate solution and the solution was allowed to react on a vortex (rotator) mixer for 2 h. Unreacted sites were blocked by adding 10 µL of ethanolamine (pH = 9.6) per mL of conjugate solution and allowing it to react on a vortex mixer for 30 min. The particles were purified by dialysis for 15 min and stored at 4 oC for later use (example 5).
Regarding claim 6, Lodi et al. teach that 10 mg of aldehyde-CQDs was added to 10 mL of coupling buffer and 50 µL of CD33 was added to 10 mL of coupling buffer (50 mM sodium phosphate). The pH was adjusted to 8 with 1 M NaOH. The two solutions were mixed and then 10 mg of EDC (ratio 1:1) was added. The pH was adjusted to 6.4 with 1M HCl to activate the carboxyl groups. The reaction mixture was incubated in the dark at 37oC for 2 h with continuous shaking at 100 rpm. Then centrifuge at 12,000 rpm for 10 min at 4oC to remove any unattached molecules, followed by washing three times with TBS (20 mL each time). The washed particles were suspended in 1xTBS and stored at -20oC for later use (example 6).
Regarding claim 7, Lodi et al. teach that standard drug cytarabine was used to bind CQD using the glutaraldehyde method. First, excess glutaraldehyde was removed by aspirating the supernatant and washing CQD with coupling buffer: 100 mg CQD, was dispersed in 100 mL of coupling buffer (0.01 M pyridine HCl, pH 6, 0.1 M NaCl) by high power sonication for 10 min. The suspension was then centrifuged at 14,000 rpm for 40 min and the supernatant was removed after 10 min. After the second wash, the CQD was suspended in the coupling buffer (coupling buffer containing 5% glutaraldehyde; linking buffer), shaken at 100 rpm for 3 h at 25oC and then centrifuged at 14,000 rpm for 20 min. Then 10 mg of cytarabine was dissolved in 100 mL of coupling buffer (0.05 mL of carbonic acid, 0.1 mL of sodium citrate, pH 9.5) and 1 mL of was reserved as pre-coupling buffer. The remaining solution was combined with 100 mg of washed QCD. The mixture was shaken from start to finish at 25oC for 24 h and then centrifuged at 8000 rpm at 4oC to obtain the standard drug NFs. The identified conjugated CQDs were stored in 0.01 M Tris-Cl storage buffer at -20oC with a pH of 0.01 (example 7).
Lodi et al. do not expressly teach the method step of claim 1 that requires filtering with a filter following centrifuging the brown solution at 9000 rpm. Lodi et al. do not expressly disclose the step concentrations used at the step of claim 5 having a buffer with a concentration of 1 to 10 mg/mL at pH 8-10.
However, at [0022], Lodi et al. teach one embodiment that includes filtering with a filter after centrifuging at 9000 rpm for 10 min. At [0037]-[0038], Lodi et al. teach that the neem containing aldehyde groups was oxidized in buffer III at a concentration of 1-10 mg/mL, wherein the buffer III consisted of 0.05 M carbonate and 0.1 M sodium citrate, and the pH was 8-10; CQD nanomaterials were dissolved in buffer III at a molar ratio of 1:4.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the example 1 of Lodi et al. so that the after centrifuging the brown solution at 9000 rpm for 10 min to remove impurities the method includes filtering with a filter as taught by Lodi et al. because filtering with a filter would have been expected to advantageously separating impurities from the solution prior to extracting the CQD solution with ethyl acetate. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Lodi et al. so that at claim 5 the methanol extract of neem containing aldehyde groups was oxidized in a buffer at a concentration of 1 to 10 mg/mL wherein the buffer consisted of 0.05 M carbonate and 0.1 M sodium citrate and the pH was 8 to 10 as taught by Lodi et al. because it would have been expected to provide suitable conditions for preparing aldehyde CQDs.
Technical Background Material
Cui et al. (CN 110308126 A- English translation; published 8 Oct. 2019; see attached 892) and Ding et all. (CN 107936965 A-English translation; published 20 Apr. 2018; see attached 892) are being made of record; however, they are being used in a rejection because they are cumulative.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
Prosecution Insights