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 without traverse of Group I, claims 1-15 and the species of functional component fluorophore/fluorescent dye rhodamine 6G; phenolic compound tannic acid; metal ion Zr4+; and plant VNP tobacco mosaic virus (TMV), in the reply filed on 6/10/26 is acknowledged.
Claims 15-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/10/26. After an extensive review of the art, the Examiner has expanded the search to include the metal ion Fe3+ and is including the medical drug cisplatin, the fluorescent dye thiazole orange, and plant VNPs TMV, CPMV and PVX and the phenolic compounds TA, EGCG and PDA.
Claim Status:
Claims 1-25 are pending.
Claims 16-25 are withdrawn.
Claims 1-15 are presented for examination on the merits as they read upon the elected subject matter.
Priority:
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Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 9/26/24 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 9 is objected to because of the following informalities: the word “die” is inappropriate. The fluorescent compounds named are dyes. Appropriate correction is required.
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 8 and 9 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.
Claim 8 recites the limitation “the medical drug” in line 1. There is no mention of a medical drug in claim 6. Thus, there is insufficient antecedent basis for this limitation in the claim. Correction is required.
Claim 9 recites the limitation "the at least one fluorescent die" in line 1. There is no mention of at least one fluorescent die[sic] in claim 1. Thus, there is insufficient antecedent basis for this limitation in the claim. Correction is required.
Claim Rejections - 35 USC § 102
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) 1-5 and 9-15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (ACSAppl.Mater. Interfaces 2022,14,13692−13702; published March 08, 2022; of record and different inventive entity).
Regarding claims 1-5 and 9-15, Wu et al. disclose methods of functionalizing plant viral nanoparticles via metal−phenolic networks (MPNs). Specifically, this method gives plant viruses, e.g., tobacco mosaic virus (TMV), cowpea mosaic virus, and potato virus X, additional functionalities including photothermal transduction, photoacoustic imaging, and fluorescent labeling via different components in MPN coating, i.e., complexes of tannic acid(TA), metal ions (e.g., Fe3+, Zr4+,or Gd3+), or fluorescent dyes (e.g., rhodamine 6G and thiazole orange) (Abstract). Wu et al. disclose: “choosing Fe3+−TA coating, the photothermal conversion efficiency was increased from0.8 to 33.2%, and the photoacoustic performance was significantly improved… bode well for using such materials in a variety of plant virus-based theranostic applications (Abstract; see also Figure 1 Schematic of the Synthesis of MPN Coating on Plant VNPs and Biomedical Applications and pages 13698-13699 Sections 4.4 Encapsulation of Plant VNPs with MPNs - 4.6 Dye attachment for Fluorescent labeling). Wu et al. explain: “In this work, we describe a simple and versatile strategy to modify VNPs using MPNs for multiple theranostic purposes including photoacoustic imaging (PAI), photothermal therapy (PTT), and fluorescent labeling (Scheme 1). Specifically, metal ions (e.g., Fe3+,Gd3+, and Zr4+) and tannic acid (TA) form MPN coatings with add-on fluorescence (i.e., by embedding fluorescent dyes into the MPN coatings) by exploiting the adherent nature of phenolic moieties” (Page 13693, left column last paragraph). Wu et al. teach a chemotherapeutic effect: “We finally evaluated the cytotoxicity of the TMV@Fe3+−TA and tested their photothermal cancer cell-killing capabilities.” (Page 13698, left column 2nd paragraph), thus being functionalized for both photothermal therapy and chemotherapy by killing cancer cells.
Thus, the same metal ions were selected and the same phenolic compound tannic acid formed a MPN with at least one functional group fluorophore with the same VNPs being encapsulated by the MPN coating with the same embedded fluorescent dyes. Claims 1-5 and 9-15 are anticipated by the reference.
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 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 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Delalande et al. (Nanoscale 2016;8:16221-16228; of record) and Venkataraman et al. (Front. Bioeng. Biotechnol. 2021; 9: Article 642794: 10 pages) and Zhang et al. (Molecules 2018, 23, 2311: 20 pages) and Lee et al. (Acc. Chem. Res. 2019, 52, 704−713) and Shah (CN111386123A; English language translation provided by the Examiner).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of an artisan in plant virus nanoparticles (VNPs) art and such an artisan possesses expertise at the intersection of virology, nanotechnology, and pharmacology. The artisan is familiar with the distinct architectures of various plant viruses—such as the icosahedral Cowpea mosaic virus (CPMV) or the rod-shaped Tobacco mosaic virus (TMV) and Potato virus X (PVX). They understand how to engineer, manipulate, and utilize virus structures and virus-like particles (VLPs) to safely and precisely transport therapeutic payloads.1 Accordingly, the ordinary artisan in this art will employ conventional knowledge in the art.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 3, 4 and 6, Delalande et al. teach methods of functionalizing a plant viral nanoparticles (VPN) comprising selecting brome mosaic virus (BMV), a Fe(III) metal ion and the phenolic compound tannic acid (TA) which construct a metal-organic network (MPN) nanohybrid structure from a solution of the selected metal and phenolic compound around the plant virus particle for therapeutic purposes (Abstract; Figures 1 and 4 where in Figure 4 the particle diameter is of the nanometer scale; Page 16223 Fe(m)-TA coating of BMV), thereby producing an MPN coating encapsulating the plant VPN. Delalande et al. teach biomedical application for timed drug delivery (Page 16222, right column 4th paragraph; 16227, top right column), inferring the addition of a drug, which is a therapeutic active ingredient.
Regarding claims 11-12 and 14, the Fe(III)-TA network of Delalande et al. implicitly functionalizes and enhances photothermal therapy and photoacoustic imaging because the instant specification teaches: “by choosing Fe3+-TA coating, the photothermal conversion efficiency was increased from 0.8% to 33.2%, and the photoacoustic performance was significantly improved” (Instant specification [4]).
Regarding claims 1-2, 6-8, 10 and 13, Venkataraman et al. teach plant virus nanoparticles as carriers for cancer therapy (Title; Abstract) where: “The most promising nano-scale systems have been adopted from naturally occurring plant viruses such as Tobacco mosaic virus (TMV), Cowpea mosaic virus (CPMV), Potato virus X (PVX)” (Page conclusion; page 2, left column 5th paragraph and right column 2nd paragraph; Figure 1); and: “The capacity for multifunctionality and multivalency makes plant nanoparticle platforms an ideal choice for theranostic applications…Plant nanoparticles are capable of precise molecular imaging to achieve accurate cancer diagnosis and therapy” (Page 4, left column last paragraph). Venkataraman et al. teach: “Plant virus VNPs have been used for targeted administration of platinum-based drugs against cancer. This is important as 50% of chemotherapy treatments involve the use of these platinum derived drugs. TMV has been demonstrated to efficiently deliver Cisplatin” (Page 5, left column last paragraph). Venkataraman et al. also teach the introduction of fluorescent dyes (Page 3, right column) and state: “plant VLPs can be developed to carry a wide array of contrast agents and fluorescent labels, as they can be modified with antibodies, peptides and aptamers to enable enhanced targeting to specific tissues and cells”; and: “which enable the monitoring of molecular and cellular processes in normal and diseased conditions in living subjects.” (Page 4, right column 2nd paragraph).
Regarding claims 1 and 2, Zhang et al. teach common plant viruses used to fabricate nanomaterials include brome mosaic virus, cowpea mosaic virus and tobacco mosaic virus (Abstract; Figure 1) as well as functionalization with fluorophores for application in drug delivery (Figure 2). Thus, the virus species are recognized in the art as functional equivalents of one another.
Regarding claim 4, Lee et al. teach tannic acid, epigallocatechin gallate and polydopamine as functional equivalents for metal-organic frameworks (Abstract; Figure 2; Page 707 Nature-derived Catechol/Gallol Families).
Regarding claim 9, Shah teaches the use of fluorescent reporter dyes for the purpose of tracking and detection and typically include a fluorophore of thiazole or rhodamine such as rhodamine 6G and thiazole orange (Page 19, last two paragraphs through page 21, first paragraph).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Delalande et al. is that Delalande et al. do not expressly teach embedding a functional component in the MPN coating where the functional components includes a fluorophore such as rhodamine 6G or thiazole orange for performing fluorescent labeling or at least one therapeutic agent such as a medical drug including cisplatin that is functionalized for performing theranostic function, photoacoustic imaging, photothermal therapy and chemotherapy. This deficiency in Delalande et al. is cured by the teachings of Venkataraman et al., Zhang et al. and Shah.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of Delalande et al. and embed a functional component in the MPN coating of Delalande et al. where the functional components includes a fluorophore such as rhodamine 6G or thiazole orange for performing fluorescent labeling or at least one therapeutic agent such as a medical drug including cisplatin that is functionalized for performing theranostic function, photoacoustic imaging, photothermal therapy and chemotherapy, as suggested by Venkataraman et al., Zhang et al. and Shah, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Delalande et al. suggest that the functionalized virus nanoparticle with Fe3+-TA is intended for drug delivery and the art of Venkataraman et al. teaches using the chemotherapeutic platinum-based drugs such as cisplatin because “plant nanoparticle platforms [are] an ideal choice for theranostic applications” (Venkataraman et al. page 4, left column last paragraph). The ordinary artisan is motivated to add a fluorophore such as rhodamine 6G or thiazole orange to monitor the delivery of the drug to cells as suggested by Venkataraman et al. and Shah. It is merely selection of known fluorophores taught in the art with a reasonable expectation of success. Accordingly, in view of the combined references it is obvious to functionalize VNPs with embedded functional components cisplatin and fluorophores in the MPN coating for performing photothermal therapy, chemotherapy, fluorescent labeling, photoacoustic imaging and theranostic function with a reasonable expectation of success.
2. The difference between the instant application and Delalande et al. is that Delalande et al. do not expressly teach wherein the plant VNP is selected from the group consisting of a tobacco mosaic virus (TMV), a cowpea mosaic virus (CPMV) and a potato virus X (PVX) or wherein the phenolic compound is selected from the group consisting of tannic acid (TA), epigallocatechin gallate (EGCG) and polydopamine (PDA). This deficiency in Delalande et al. is cured by the teachings of Venkataraman et al., Zhang et al. and Lee et al.
2. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of Delalande et al., wherein the plant VNP is selected from the group consisting of a tobacco mosaic virus (TMV), a cowpea mosaic virus (CPMV) and a potato virus X (PVX) or wherein the phenolic compound is selected from the group consisting of tannic acid (TA), epigallocatechin gallate (EGCG) and polydopamine (PDA)as suggested by Venkataraman et al., Zhang et al. and Lee et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because the art recognizes brome mosaic virus, tobacco mosaic virus, a cowpea mosaic virus and a potato virus X as commonly used plant viruses used to fabricate nanomaterials and thus functional equivalents as suggested by Zhang et al. and Venkataraman et al. Consequently, these plant viruses are interchangeable and known for the same function. “Where two known alternatives are interchangeable for a desired function, an express suggestion to substitute one for the other is not needed to render a substitution obvious." In re Fout 675 F.2d 297, 301 (CCPA 1982). Similarly in this art, TA, EGCG and PDA are recognized as polyphenolic compounds used in construction of metal-organic frameworks as taught by Lee et al. and thus interchangeable for a desired function. Accordingly, the claimed plant viral nanoparticle species and phenolic compounds TA, EGCG and PDA all obvious choices by the ordinary artisan in this art.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
1 See for example: Nkanga et al. (The Pharmacology of plant virus nanoparticles. Virology, 2021;556:39-61; Venkataraman et al. (Application of Plant Viruses in Biotechnology, Medicine, and Human Health, Viruses, 2021;13:21 pages); Venkataraman et al. (Plant Virus Nanoparticles for Anti-cancer Therapy. Front. Bioeng. Biotechnol., 14 December 2021; 10 pages); and Chung et al. (Advanced Drug Delivery Reviews 156 (2020) 214–235).
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