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 .
Application Status
Claims 1-2, 4, 6-7, 10-13, 15-21, 23, 27, and 30 are pending and examined on the merits herein.
Information Disclosure Statement
The information disclosure statement filed April 19, 2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statement filed January 27, 2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
The information disclosure statement filed July 23, 2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Drawings
The drawings are objected to because of the following informalities:
The label of the x-axis is cut off in figure 12D rendering the text illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
The term “about” is not defined in the instant specification and therefore shall be interpreted as +/- 10% of any value where the term is used.
Claim Objections
Claim 1 is objected to because of the following informalities:
The language “formed of” in line 1, it is unclear whether this language is intended to be a closed listing of included elements such as consisting of, or an open ended list of included elements such as comprising. For the purpose of compact prosecution “formed of” is being interpreted as comprising.
Appropriate 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sherwani (RSC Adv., 2015, 5: 39512-31; PTO-892).
Regarding claims 1-2, 4, 7, 10-12, and 30, Sherwani teaches a cisplatin loaded PLGA nanoparticle encapsulated by G4 PAMAM dendrimer that can further comprise liver cancer cell specific antibody and PLK-1 specific siRNA (Fig 1), further teaches that the nanoparticles are 241 nM and have a positive zeta potential (cationic) (table 2).
Regarding claim 13, Sherwani teaches that the nanoparticles were lyophilized after conjugation and stored at -20C until further use (page 39515, col 1, para 1).
Regarding claims 16 and 20-21, Sherwani teaches that administration of the PAMAM-siRNA-PLGA nanoparticles enhanced survival of mice with DEN-induced liver cancer (Fig 11).
Regarding claim 23, Sherwani teaches that PLK-1 is an important regulator of cell-cycle progression and that overexpression of PLK-1 has been shown to result in tumor development, so PLK-1 therefore represents an ideal target for cancer drug development that enhances sensitivity to cisplatin (page 39527, col 2, para 2).
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.
Claims 15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Sherwani (RSC Adv., 2015, 5: 39512-31; PTO-892) as applied to claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 above, and further in view of Wright (US 5,795,582; IDS entered 02/20/2023).
The teachings of Sherwani regarding claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 are detailed above.
Sherwani does not teach that the nanoparticles are effective as an adjuvant, or that the mammal is a human.
Regarding claim 15, Wright teaches a vaccine for Influenza comprising an effective amount of a composition formed of an Influenza antigen and a starburst dendrimer in a physiologically compatible carrier (claim 1), wherein said dendrimer comprises a poly(amidoamine) (PAMAM) dendrimer (claim 2), wherein said dendrimer is Generation 3-10 dendrimers (claim 3). Wright further teaches the use of PAMAM dendrimers as adjuvants for enhancing the immune response to a variety of antigens, which are particularly useful in vaccines because lower doses of the antigen can be used than in unadjuvanted vaccines (col 1, lines 4-9). Wright teaches a 71 fold improvement of titer after a single administration of adjuvanted vaccine versus non-adjuvanted and that it is clear that the dendrimers act as exceptional adjuvants, even on materials that are notoriously difficult to adjuvant (Example 1).
Regarding claim 17, Wright teaches that an object of the invention is to provide a method of immunizing humans against Influenza using a starburst dendrimer-adjuvanted vaccine (col 2, lines 45-47).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to use the PAMAM-siRNA-PLGA nanoparticles in a method to enhance immune response in cancer treatment as taught by Sherwani as an adjuvant for human treatment as taught by Wright. The ordinary artisan would have been motivated to do so because Wright teaches the same generation PAMAM dendrimer particles loaded with an antigen act as exceptional adjuvants, even on materials that are notoriously difficult to adjuvant. The ordinary artisan has a reasonable expectation of success to apply the knowledge of Wright that PAMAM dendrimers can be used as effective adjuvants in humans to the method of enhancing an immune response to cancer with PAMAM-siRNA-PLGA nanoparticles as taught by Sherwani.
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Sherwani (RSC Adv., 2015, 5: 39512-31; PTO-892) as applied to claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 above, and further in view of Kasala (Expert Opinion on Drug Delivery, 11(3), 379–392; PTO-892).
The teachings of Sherwani regarding claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 are detailed above.
Sherwani does not teach wherein the vector is a viral vector or the type of viral vector.
Regarding claims 18-19, Kasala teaches that adenovirus (Ad) is a promising candidate vector for cancer gene therapy because of its unique characteristics, which include efficient infection, high loading capacity and lack of insertional mutagenesis but it is hampered by host immune response and short half-life (abstract/ intro). Kasala further teaches that the fusion of bioengineering and biopharmaceutical technologies can provide solutions to the obstacles encountered during systemic delivery of Ads (abstract/expert opinion). Kasala further teaches that since cationic polymers contain several amine groups in their backbone, interaction between the positively charged cationic polymers and the negatively charged nucleic acid or Ad surface leads to the formation of nanocomplexes in aqueous solution and it is hypothesized that positively charged nanoparticles interact with the negatively charged cellular membrane, resulting in enhanced transgene expression in cells and efficient escape from endosomes via a ‘proton sponge effect’ which leads to several advantages including easy manipulation of molecular weight and conjugation of ligands, infectivity of the adenovirus is maintained while boosting transduction efficiency. Kasala further teaches that PAMAM has been shown to complex with adenovirus and can be ligand targeted to specific cells, demonstrating that non-covalent, charge-based coating of Ad vectors with ligand-equipped dendrimers is a viable strategy for efficient transduction of cells that are otherwise refractory to Ad infection (section 2.1.6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application that to substitute an adenovirus vector as taught by Kasala for the siRNA in the method to enhance immune response in cancer treatment with anti-PLK1-PAMAM-siRNA-PLGA nanoparticles as taught by Sherwani. The ordinary artisan would have been motivated to do so because Kasala teaches that adenovirus (Ad) is a promising candidate vector for cancer gene therapy because of its unique characteristics, which include efficient infection, high loading capacity and lack of insertional mutagenesis and that the combination of positive nanoparticles with the negatively charged adenovirus results in a system easy manipulation of molecular weight and conjugation of ligands, infectivity of the adenovirus is maintained while boosting transduction efficiency. Kasala further teaches that PAMAM has been shown to complex with adenovirus and can be ligand targeted to specific cells, demonstrating that non-covalent, charge-based coating of Ad vectors with ligand-equipped dendrimers is a viable strategy for efficient transduction of cells that are otherwise refractory to Ad infection. Sherwani teaches a cisplatin loaded PLGA nanoparticle encapsulated by G4 PAMAM dendrimer that can further comprise liver cancer cell specific antibody and PLK-1 specific siRNA, therefore a cancer targeted immunogen loaded PAMAM coated nanoparticle. The ordinary artisan has a reasonable expectation of success to substitute an adenovirus vector as taught by Kasala for the siRNA in the method of enhancing an immune response to cancer with a cancer Ab-PAMAM-siRNA-PLGA nanoparticles as taught by Sherwani in order to increase the efficiency of transduction, even in cells that are otherwise refractory to adenovirus infection.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Sherwani (RSC Adv., 2015, 5: 39512-31; PTO-892) as applied to claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 above, and further in view of Bratzler (US 2011/0293723 A1; PTO-892).
The teachings of Sherwani regarding claims 1-2, 4, 7, 10-13, 16, 20-21, 23, and 30 are detailed above.
Sherwani does not teach that the immunogen or vector is administered at a site that is different than the administration site for the nanoparticles.
Bratzler teaches a dosage form comprising: (1) a first population of synthetic nanocarriers that have one or more first antigens coupled to them, (2) one or more second antigens that are not coupled to the synthetic nanocarriers, and (3) a pharmaceutically acceptable excipient (claim 1), a method comprising: administering the dosage form of claim 1 to a subject (claim 55), wherein the subject has or is at risk of having cancer (claim 57). Bratzler further teaches that in embodiments antigens are not coadministered with the synthetic nanocarriers (para 0041) and further that the antigen and nanocarrier can be administered separately at a different time-point and/or at a different body location and/or by a different immunization route (para 0116). Bratzler further teaches that to the purpose of adding a second antigen is to provide broader immune protection against different strains of a given pathogen (para 0002) which can be broadened to be applied to cancer (para 0031) through targeting of cancer antigens (para 0065). Bratzler further teaches that the compositions and methods described herein can be used to induce, enhance, suppress, modulate, direct, or redirect an immune response to cancer (para 0131).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to substitute cancer antigens in multiple doses administered at separate sites as taught by Bratzler for the siRNA in the PAMAM-siRNA-PLGA nanoparticles used in a method to enhance immune response in cancer treatment as taught by Sherwani. The ordinary artisan would have been motivated to do so because Bratzler teaches that the administration of a second antigen at a separate administration site provides broader immune protection against multiple cancer antigens. The ordinary artisan has a reasonable expectation of success to apply the knowledge of Bratzler to broaden/ enhance the immune response by administering a second antigen at a separate site from the nanoparticle to the method of enhancing an immune response to cancer with PAMAM-siRNA-PLGA nanoparticles as taught by Sherwani.
Conclusion
No claims allowed.
Art not relied upon in this office action Intra (Journal of Drug Targeting, 2011, 19(6): 41; IDS entered 04/19/2023).
Regarding claims 1-2, 4, and 10-12, Intra teaches preparation of poly(D,L-lactide-co-glycolide)(PLGA) microparticles loaded with polyamidoamine (PAMAM)- plasmid DNA dendriplexes (abstract). Intra further teaches that particle size had an average range of 800-100nM and converts to a positive zeta potential when formulated with G3, G4, G5 or G6 PAMAM (Figure 4).
Regarding claim 13, Intra teaches that the PLGA-PAMAM-pDNA particles were washed and then lyophilized after preparation (page 371, col 1, last para- col 2 first para).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMBER K FAUST/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643