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 . Claims included in prosecution are claims 1, 3, & 7-9.
Previous Rejections
Applicants' arguments, filed Jan. 31, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103 (New)
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.
1. Claims 1, 3, and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (WO 2018/024111, Feb. 8, 2018) (hereinafter Sun) in view of Watanabe et al. (US 2006/0241038, Oct. 26, 2006) (hereinafter Watanabe) and further in view of Darweesh et al. (International Journal of Nanomedicine, Sep. 19, 2019:14 7643–7663) (hereinafter Darweesh) and Nosratabadi et al. (Nanomedicine: Nanotechnology, Biology, and Medicine, 12, 2016, 1961–1971) (hereinafter Nosratabadi) as evidenced by Karampoor et al. (Journal of Neuroimmunology, 301, 2016, 88–93) (hereinafter Karampoor).
Sun teaches a pharmaceutical use of a gold cluster and a substance containing the gold cluster and the preparation method and use thereof. The gold cluster and substance containing the gold cluster can inhibit the aggregation of beta amyloid protein (Aβ) alpha-synuclein (α-syn) and has excellent results (Abstract). The gold clusters generally have a plasma resonance peak at 520 ± 20 nm in the ultraviolet visible absorption spectrum (¶ [0007]). The gold cluster with medicinal activity includes a gold cluster and a ligand Y coated outside the gold cluster (satisfies AuC of claim 1) (¶ [0010]). The gold core diameter of the gold cluster is less than 3 nm, preferably 0.5-2.6 nm (satisfies diameter of claim 1 & 3) (¶ [0011]). The ligand Y includes, but is not limited to, one or more of L (D)-cysteine and derivatives thereof, cysteine containing oligopeptide and derivatives thereof, and other mercapto-containing compounds (¶ [0012]). The L (D)-cysteine and its derivatives are preferably L (D)-cysteine, N-isobutyryl-L (D)-cysteine (L (D)-NiBC) or N-acetyl-L (D)-cysteine (L (D)-NAC) (satisfies ligand of claim 1) (¶ [0013]). The cysteine-containing oligopeptide and the derivative thereof are preferably cysteine-containing dipeptide, cysteine-containing tripeptide or cysteine-containing tetrapeptide (¶ [0014]). The cysteine-containing dipeptide is preferably L-cysteine-L-arginine dipeptide (CR), L-arginine-L-cysteine dipeptide (RC), L-histidine-L-cysteine dipeptide (HC) or L-cysteine-L-histidine dipeptide (CH) (satisfies claim 7) (¶ [0015]). The cysteine-containing tripeptide is preferably glycine-L-cysteine-L-arginine tripeptide (GCR), L-proline-L-cysteine- L-arginine tripeptide (PCR), L-lysine-L-cysteine-L-proline tripeptide (KCP) or L-glutathione (GSH) (satisfies claim 8) (¶ [0016]). The cysteine-containing tetrapeptide is preferably glycine-L-serine-L-cysteine-L-arginine tetrapeptide (GSCR) or glycine-L-cysteine-L-serine-L-arginine tetrapeptide (GCSR) (satisfies claim 9) (¶ [0017]). The other mercapto-containing compounds are preferably 1-[(2S)-2-methyl-3-mercapto-1-oxopropyl ]-L-proline, mercaptoacetic acid, mercaptoethanol, thiophenol, D-3-mercaptovaline, N-(2-mercaptopropionyl)-glycine or dodecanethiol, and the like (¶ [0018]). In Example 3, a large amount of phosphate buffer was used to obtain a PBS buffer solution (satisfies excipient of claim 1) (¶ [0112]).
Sun differs from the instantly recited claims insofar as not disclosing wherein the pharmaceutical use of the composition is for the treatment of multiple sclerosis.
However, Watanabe discloses that beta amyloid protein based diseases include multiple sclerosis (¶ [0320]).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have used the composition of Sun in a method for the treatment of multiple sclerosis since Sun’s gold cluster has a pronounced effect in inhibiting the aggregation of beta amyloid protein, and multiple sclerosis is a beta amyloid protein based disease as taught by Watanabe.
The combined teachings of Sun and Watanabe do not disclose wherein the gold cluster reduces TNF-α, IL-17, & IFN-γ in a subject.
However, Darweesh conducted a review of the effects of gold nanoparticles on angiogenesis and the molecular mechanisms and biomedical applications associated with their effects (Abstract). Representative structural models of said nanoparticles consist of central
inner gold atoms “core” that determine the crystallinity of the structure; gold atoms on the outer surface of AuNPs structure, which usually have a different geometry than the
core atoms, that create the surface’s facets and edges that control the catalytic activity of the particle, and a protecting outer layer of organic ligands or surfactants which stabilize AuNPs and provide them with surface functionality. Depending on their size, these nanoparticles could form clusters (pg. 7647). Such AuNPs were found to decrease the production of TNF-α (pg. 7652), which is a controlling factor in angiogenesis (pg. 7644).
Angiogenesis plays a crucial role in the pathogenesis of multiple sclerosis (as evidenced by Karampoor, Abstract). Accordingly, it would have been obvious for one of ordinary skill in the art, when utilizing the cluster of Sun in view of Watanabe in a method for the treatment of multiple sclerosis to expect that said cluster would reduce the production of TNF-α, a controlling factor in angiogenesis, since such clusters are known to have this effect, as taught by Darweesh.
The combined teachings of Sun, Watanabe, and Darweesh do not disclose wherein the gold cluster reduces IL-17 & IFN-γ in a subject.
However, Nosratabadi discloses that multiple sclerosis (MS) is a neurodegenerative autoimmune disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the best experimental model for the study of the immunological and pathological mechanisms in human MS (Introduction). Part of the testing involved inducing EAE and treating with free form gold nanoparticles (free-GNP) (Study Design). The free-GNP had a sharp absorbance peak at 517 nm corresponding to the surface plasmon resonance (SPR) band of the spherical GNPs (Results). Treatment with free-GNP inhibited IFN-γ and IL-17A (Results). Both IFN-γ and IL-17A play a role in EAE (Discussion).
Accordingly, it would have been obvious for one of ordinary skill in the art, when utilizing the cluster of Sun in view of Watanabe and Darweesh in a method for the treatment of multiple sclerosis to expect that said cluster would reduce the production of IFN-γ and IL-17, which play a role in EAE, the best experimental model for the study of the immunological and pathological mechanisms in human MS, since nanoparticles which have an absorbance peak which overlaps with the clusters of Sun in view of Watanabe and Darweesh are known to inhibit such cytokines as taught by Nosratabadi.
Alternatively, assuming purely arguendo, that one of ordinary skill in the art would not have been led by the combined disclosures of Darweesh and Nosratabadi to the conclusion that the cluster of Sun in view of Watanabe would reduce TNF-α, IL-17, & IFN-γ in a subject, as discussed above, the method of Sun in view of Watanabe comprises substantially the same components and actives, where it comprises substantially the same, if not an identical, cluster, with substantially the same , if not identical, ligands, and substantially the same gold core, if not an identical, diameter as instantly claimed. Furthermore, the method of Sun in view of Watanabe treats substantially the same disease as instantly claimed. As such, one of ordinary skill in the art would reasonably conclude that the method of Sun in view of Watanabe and specifically the cluster of Sun in view of Watanabe would result in substantially the same properties, reducing TNF-α, IL-17, & IFN-γ in a subject, as the method/cluster of the instant claims.
Regarding the gold core diameter recited in instant claims 1 & 3 (i.e., less than 3 nm & 0.5-2.6 nm), in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(A). As discussed above, Sun’s gold core has a diameter of less than 3 nm, preferably 0.5-2.6 nm. Accordingly, because the gold core diameter recited in the instant claims overlap the values disclosed by Sun, the values disclosed by Sun meet the instantly recited limitations.
Response to Arguments
Applicant’s arguments with respect to claims 1, 3, and 7-9 have been considered but are moot because new rejections necessitated by Applicant’s amendment have been made.
Although Applicant’s arguments are moot because new rejections necessitated by Applicant’s amendment have been made, the Examiner will address those aspects of Applicant’s arguments insofar as they remain relevant to the new grounds of rejection.
Regarding Applicant’s argument that gold nanoparticles are structurally different from gold clusters, this is known from the Sun disclosure where Sun discloses motivation why one of ordinary skill in the art would choose to utilize a gold cluster as Sun has done (¶ [0006-0009]). Furthermore, as discussed above, Darweesh discloses that gold nanoparticles which consist of a central inner gold atom “core” could form clusters depending on their size. As such, one of ordinary skill in the art would have been motivated to formulate the method to utilize a cluster and would expect the gold nanoparticles and clusters to have the same effect when utilized for the same use.
Regarding Applicant’s argument with respect to “reference 136”, after reviewing said document, the Examiner found that while the average diameter of their nanoparticles may have been 25-50 nm, the particle size distribution plot showed that 21% of the particles had a particle size of 0-25 nm compared to 29% at 25-50 nm (Figure 1). As such, a significant portion of the nanoparticles used by the reference had a particle size that overlapped with the claimed size. Furthermore, in the discussion portion it is recited “However, in our work, the size of AuNPs is not uniform. Therefore, we cannot compare our results in terms of size of AuNPs”. As such, the reference itself recognizes that particle size does not appear to be the most appropriate measure for recognizing anti-inflammatory activity. Finally, the fact that documents cited in Darweesh’s reference section contain a citation which discuses larger sized particles does not negate the fact that Darweesh does unambiguously disclose that AuNPs were found to decrease the production of TNF-α which is a controlling factor in angiogenesis within the four corners of its disclosure.
Regarding Applicant’s argument with respect to “reference 18”, after reviewing said document, the Examiner found that this reference is drawn to inducing an immunological response with virus-like particles. As such, it is concerned with increasing the levels of cytokines, not decreasing them. In other words, this reference concludes that larger sized nanoparticles had the effect of sufficiently increasing the levels of cytokines while the smaller sized nanoparticles did not have the same effect of increasing levels of cytokines (Results and Discussion). As such, one could make the argument that one of ordinary skill in the art would reasonably expect smaller nanoparticles to have the opposite effect of decreasing the levels of pro inflammatory cytokines.
In light of the foregoing, the Examiner does not find Applicant’s arguments to be persuasive and the rejection is maintained.
Conclusion
Claims 1, 3, and 7-9 are rejected.
No claims are allowed.
Applicant's amendment necessitated the 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
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/A.A./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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