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 .
Election/Restrictions
Applicant’s election of group I and dihydrolipoic acids (DHLAs) in the reply filed on August 20, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
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.
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 – 3 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 2012/0100075) in view of Wang et al. (Biomaterials, 2019).
Chang et al. discloses fluorescent gold nanoclusters comprising a dihydrolipoic acid ligand (DHLA) on the surface with a particular diameter of 0.5 – 3 nm and fluorescence emission wavelength in the range of 400 – 1000 nm (whole document, e.g., abstract). The interaction between the DHLA and gold nanocluster generates the fluorescence (¶ [0012]). The disclosed size and fluorescence emission ranges overlap with those claimed and overlapping ranges are prima facie obvious (see MPEP 2144.05). The fluorescent gold nanoclusters can be used as bioprobes and/or applied in fluorescent biological label, clinical imaging as a contrast medium, clinical detection and clinical treatment (abstract). As shown in Figure 3 and discussed at ¶ [0051], biomolecules can be grafted onto the fluorescent gold nanoclusters.
The presence of at least a partial layer of α-glycerylphosphorylcholine (α-GPC) is not disclosed.
Wang et al. discloses that the surface chemistry of [the] nanoparticle largely determines the protein corona formation, which marks nanoparticles with biological identity, thereby determining their in vivo fate and biodistribution (p 1, col 2, ¶ 2). Zwitterionic polymers have been explored as antifouling surface chemistry but such polymers have limited solubility in organic polymers and poor dissolution even in some aqueous solutions due to the overwhelming network formation by the intermolecular charge relay (p 2, col 1, ¶ 1). Clustered zwitterionic moieties on the dendritic periphery not only provide more efficient sheltering effects than linear polymers but also minimize the incidence of intermolecular charge relay to dissolve readily in polar solvents and enable nanoparticle synthesis (p 2, col 1, ¶ 1). The zwitterionic Janus dendrimers (JDs) were prepared including one with glycerylphosphocholine (GPC; p 2, col 1, ¶ 4). Both the GPC and CB (carboxybetaine) coated surfaces significantly inhibited BSA (bovine serum albumin) adsorption and the GPC layer completely eliminated protein binding on the biosensor, indicating superior antifouling properties (p 5, col 1, ¶ 2). GPC mimics the component of the lipid bilayer plasma membrane and the GPC-JDs were more biocompatible, when compared with the CB-JDs, in the cell viability and hemolytic activity assays (p 5, col 2, ¶ 2). The GPC carrier was also able to transport the cargo inside the cells with higher efficiency and smoothly translocation from endosome/lysosome into the cytoplasm may also occur based on the cargo distribution beyond the endosome/lysosome compartments (p 5, col 2, ¶ 3). Nanocarriers with GPC antifouling surface can greatly prolong the in vivo pharmacokinetic profiles of protein cargo relative to PEGylated nanocarriers (¶ bridging p 8 and 9).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to add a GPC coating layer to the fluorescent nanoclusters comprising DHLA disclosed by Chang et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Wang et al. that such zwitterionic coatings provide antifouling properties to nanocarriers while also being biocompatible. The materials of Chang et al. have possible uses including as bioprobes and in clinical applications that render biocompatibility and lack of fouling important properties for the materials. A material with such properties can be provided by the use of GPC coating that mimics part of the lipid bilayer plasma membrane and applying them over the nanoclusters of Chang et al. will provide those properties to those fluorescent materials.
Claim(s) 1 – 3 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (US 2012/0100075) in view of Mackiewicz (US 2019/0015526).
Chang et al. is discussed above.
The presence of at least a partial layer of α-glycerylphosphorylcholine (α-GPC) is not disclosed.
Mackiewicz discloses nanoparticles that comprise a covalently coupled stability agent molecules the comprise covalently coupled stabilizing agent molecules that improve the stability of the nanoparticle composites and allow for tight packing of lipids and/or membranes (whole document, e.g., abstract). That nanoparticle can comprise one or more aggregation inhibitors such as L-α-glycerylphosphatidylcholine (¶¶ [0144] and [0153]). A plurality of one or more aggregation inhibitors can form a membrane around the core (¶ [0154]), reading on a layer encapsulating at a portion of the structure contained within.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a layer of the aggregation inhibitors L-α-glycerylphosphatidylcholine to the fluorescent gold nanoclusters with DHLA disclosed by Chang et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Mackiewicz discloses that L-α-glycerylphosphatidylcholine acts as an aggregation inhibitor for nanoparticles and the presence of such a layer will prevent any further aggregations of the gold nanoclusters disclosed by Chang et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 – 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 9,101,672 in view of Wang et al. (Biomaterials, 2019) or Mackiewicz (US 2019/0015526). The claims of US’672 recite a method in which gold nanoclusters coated with dihydrolipoic acid are contacted with cultured cells (claim 1). The gold nanoclusters can be about 0.1 to 20 nm in particle size (claim 1).
The presence of at least a partial layer of α-glycerylphosphorylcholine (α-GPC) is not disclosed.
Wang et al. and Mackiewicz are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a layer of glycerylphosphatidylcholine on the gold nanoclusters with DHLA claimed in US’672. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Wang et al. discloses this will result in a zwitterionic coatings provide antifouling properties to nanocarriers having such a coating while also being biocompatible while Mackiewicz discloses that L-α-glycerylphosphatidylcholine acts as an aggregation inhibitor for nanoparticles and the presence of such a layer will prevent any further aggregations of the gold nanoclusters. The overlapping size ranges for the cluster provide a prima facie case of obviousness (see MPEP 2144.05).
The fluorescent nature of the nanoclusters of US’672 are not recited in the claims. However, that behavior arises from the structure and the presence of DHLP on gold nanoclusters results in a fluorescent material with at least an overlapping fluorescence emission as evidenced by Wang et al. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618