DETAILED ACTION
This office action is in response to applicant’s filing dated September 19, 2025.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 September 19, 2025 has been entered.
Status of Claims
Claims 1 and 2 is/are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed September 19, 2025. Acknowledgement is made of Applicant’s amendment of claim 1. Claims 3 and 4 were previously canceled.
Applicants elected with traverse Group II, drawn to a method for treating a subject with Parkinson’s disease with substance comprising a substance containing gold clusters (AuCs); wherein said substance comprises: AuCs; a ligand Y coating the AuCs externally, wherein the ligand Y is a thiol-containing compound as the elected invention and L-cysteine as the elected ligand Y species in the reply filed on November 22, 2022.
Claims 1 and 2 are presently under examination as they relate to the elected species:
L-cysteine
Priority
The present application is a divisional of 16/396,727 filed on April 28, 2019, which is a divisional of 16/129,896 filed on September 13, 2018, which is a continuation of PCT/CN2017/093671 filed on July 20, 2017, which claims benefit of foreign priority to CN2016106359125 filed on August 5, 2016.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Maintained Objections and/or Rejections
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1 and 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (US 2016/0015742 A1, published January 21, 2016, cited in the IDS filed April 5, 2021) in view of Antosova et al (Materials Science and Engineering C, 2012; 32:2529-2535, cited in the IDS filed April 5, 2021); Acres et al (J. Phys. Chem. C, 2014; 118:10481−10487, cited in a previous Office Action); and Arnold et al (WO 2014/070769 A1, cited in a previous Office Action).
Regarding claims 1, Yang teaches a method for treating a neurological disorder comprising administering an effective amount of metallic nanoparticles thereby treating the neurological disorder (claim 12) wherein the metallic nanoparticle is a gold nanoparticle or particle (claim 14) wherein the size of the nanoparticle is between 1 nm and 100 nm (claim 15) wherein the neurological disorder is Parkinson’s disease (claim 20). Yang teaches the size of metallic nanoparticles is preferably about 1 nm to about 5 nm [0041]. Yang does not explicitly teach the nanoparticles are coated with a ligand Y.
However, Antosova teaches biocompatible glutathione-covered gold nanoparticles (AuSG_7) with an average size of 3 nm depolymerize the amyloid aggregates and inhibit lysozyme aggregate formation (abstract) and the high disaggregating activity of AuSG_7 NPs suggests their usefulness as therapeutic agents against amyloid diseases in addition to their main use as carrier systems for the delivery of therapeutic moieties (page 2535, left, 1st paragraph). Antosova teaches misfolded proteins tend to agglomerate irreversibly into insoluble deposits (fibrillar assemblies) causing amyloidoses such as Parkinson’s disease (page 2529, left, 1st paragraph). Antosova further teaches that it is likely that the glutathione elements of AuSG_7 NPs act as peptide based inhibitors (so-called β-sheet breaker peptides) or chaperones (page 2534, left, 2nd paragraph).
Acres teaches gold nanoparticles functionalized with cysteine or glutathione (abstract).
Arnold teaches a method for treating Parkinson’s disease (claims 39 and 41) comprising administering a composition comprising glutathione (claim 1). Cysteine is a precursor to glutathione and cysteine can be used in place of glutathione (page 3, lines 15-20).
Since Yang teaches a method of treating Parkinson’s disease with a gold nanoparticle; since Antosova teaches that glutathione-covered gold nanoparticles depolymerize the amyloid aggregates and inhibit lysozyme aggregate and are useful as therapeutics for amyloid diseases such as Parkinson’s disease; since Acres establishes that gold nanoparticles functionalized with cysteine or glutathione were known in the art; and since Arnold teaches cysteine can be utilized in place of glutathione for the treatment of Parkinson’s disease, at the time of the invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute the gold particles taught by Yang with a cysteine-covered gold nanoparticle with an expectation of success, since the prior art establishes that glutathione-covered gold nanoparticles depolymerize the amyloid aggregates and inhibit lysozyme aggregate and are useful as therapeutics for amyloid diseases such as Parkinson’s disease, cysteine-covered and glutathione-covered gold nanoparticles were known in the art, and cysteine could be used in place of glutathione for the treatment of Parkinson’s disease.
Regarding the size of the gold particle of claims 1 and 2, Yang teaches particles are preferably about 1 nm to about 5 nm and Antosova teaches glutathione-covered gold nanoparticles with an average size of 3nm. MPEP 2144.05 states: 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). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Taken together, all this would result in the practice of the method of claims 1 and 2 with a reasonable expectation of success.
Response to Arguments
The Declaration of Taolei Sun under 37 CFR 1.132 filed September 19, 2025 is insufficient to overcome the rejection of record and is addressed in the response to arguments set forth below.
Applicant argues:
A Declaration by the inventor is enclosed herein to show that in the MPTP-lesioned PD mouse model experiments, L-cysteine/D-cysteine (Cys-AuCs), N-acetyl-L-cysteine (NAC-AuCs), and L-cysteine-L-arginine dipeptide (CR-AuCs) have demonstrated their therapeutic efficacy for treating Parkinson’s disease.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The Examiner notes that presently the instant claims are presently under examination as they relate to the elected species: L-cysteine (Cys-AuCs). MPEP 716.02(c) II. States:
"Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989) (Claims at issue were directed to a process of sterilizing a polyolefinic composition which contains an antioxidant with high-energy radiation. Although evidence was presented in appellant’s specification showing that particular antioxidants are effective, the Board concluded that these beneficial results would have been expected because one of the references taught a claimed antioxidant is very efficient and provides better results compared with other prior art antioxidants.).
In the instant case, as set forth above, Yang teaches a method of treating Parkinson’s disease with a gold nanoparticle. Thus, Yang establishes that it was known in the art that nanoparticles as small as 1 nm are useful for treating Parkinson’s disease. As set forth above, Antosova teaches that glutathione-covered gold nanoparticles depolymerize the amyloid aggregates and inhibit lysozyme aggregate and are useful as therapeutics for amyloid diseases such as Parkinson’s disease. As set forth above, Acres establishes that gold nanoparticles functionalized with cysteine or glutathione were known in the art. As set forth above, Arnold teaches cysteine can be utilized in place of glutathione for the treatment of Parkinson’s disease. Thus, it is not unexpected that cysteine-coated gold nanoparticles are useful for treating Parkinson’s disease in view of the teachings of the cited art.
MPEP 716.02(e) states:
An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). "A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). In the instant case, Antosova teaches glutathione-covered gold nanoparticles are useful as therapeutics for amyloid diseases such as Parkinson’s disease and the prior art establishes that cysteine is a precursor for glutathione and can be utilized in place of glutathione. Thus, glutathione-coated gold nanoparticles are considered to be the closest prior art.
Applicant argues:
As detailed in previous responses, Yang, Antosova, Acres, and Arnold do not teach or suggest the AuCs claimed in the present application, or provide any reasonable expectation of success in treatment of Parkinson’s disease with the claimed subject matters of the present application.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Arguments regarding Yang, Antosova, Acres, and Arnold have been previously addressed and will not be reiterated here.
Conclusion
Claims 1 and 2 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Rayna Rodriguez/Primary Examiner, Art Unit 1628