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 .
DETAILED ACTION
Applicant's response filed on 06/29/2026 is duly acknowledged.
Claims 15-22 and 28-39 were previously canceled.
Claims 1-14 and 23-27, as currently amended/presented, are pending in this application.
Claims 4-8 (non-elected species of group I), and claims 23-27 (non-elected Group II, without traverse) remain withdrawn.
Claims 1-3 and 9-14 (elected Group I with species “tumor cell”, without traverse; directed to “A silicified cell..”) have been examined on their merits in this action, hereinafter.
Priority
This application is a 371 of PCT/US2021/024776 (filed on 03/30/2021), which claims domestic benefit from a US provisional application 63/001,737 filed on 03/30/2020.
Claim Terms
It is noted that instant claim 1, as currently amended, recites the limitations “a nanoparticle comprising an exogenous polynucleotide encoding a bioactive agent loaded into the silicified cell or silicifiable compartment thereof,…”, wherein the limitations of “an exogenous polynucleotide encoding a bioactive agent” does not have a literal or direct support in the disclosure (or claims/drawings) of record. However, the specification summary (SPEC, p. 1; and Figures 6-7) of record states the following:
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Considering the above implicit support for a DNA plasmid, an siRNA, or an mRNA as a “bioactive agent”, the new matter rejection under 112(a) has not been made. The claims have been interpreted (for this office action hereinafter) to encompass a nanoparticle comprising such “a bioactive agent” (i.e. a DNA plasmid, an siRNA, or an mRNA) as meeting the limitations instant claim 1 as amended.
Claim Rejections - 35 USC § 112 - Withdrawn
In view of current amendments to claim 12, the 112(d) rejection as previously made by the examiner, has been withdrawn.
NOTE: 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 (i.e., changing from AIA to pre-AIA ) 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.
Claim Rejections - 35 USC § 103 – Made/Maintained
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.
1. Claims 1-3 and 9-14 (as currently amended/presented) are/remain rejected under 35 U.S.C. 103 as being unpatentable over Serda et al (hereinafter Serda et al 2019; WO 2019/055620 A1; FOR cited in applicant’s IDS dated 07/05/2023) taken with Serda et al (hereinafter Serda et al 2015; US 8,926,994 B2; previously of record).
Claim 1 (as presented) is directed to “A silicified cell comprising:
a silicified cell or silicifiable compartment thereof comprising a surface;
a nanoparticle comprising an exogenous polynucleotide encoding a bioactive agent loaded into the silicified cell or silicifiable compartment thereof, and
an immunomodulatory moiety bound to the surface.”
See also limitations of the dependent claims 2, 3 and 9-14, as currently amended or presented, and as pertinent to applicant’s elected species under examination: “tumor cell” (see dependent claims 2-3, in particular).
It is to be noted that the term “bioactive agent” has not been specifically defined by applicants on record (see SPEC, p. 1, “Summary”, and p. 6, last full paragraph).
Serda et al (March, 21st, 2019), while teaching silicified cell replicas, methods of making and using (see Title, Abstract, Summary, and claims), disclose silicified tumor cell comprising- a silicified cell comprising a surface (such as ID8-GFP- OVA ovarian cancer cells); a nanoparticle comprising a bioactive agent (such as mesoporous nanoparticles coated with an immunogenic lipid (ILM) loaded into the silicified cell; and an immunomodulatory moiety (such as lipopolysaccharide, LPS) bound to the surface (see page 12, lines 16-18, Figure 12a, for instance; and page 6, lines 3-6- that shows that cancer cell silicification and PAMP adsorption stimulates BMDC internalization of cancer cells); wherein the cell is a silicified ovarian ID8 tumor cell- LPS-ID8-GFP-OVA; wherein Serda et al 2019 also disclose the fact that instead of tumor cells, silicified microvesicles (MV) obtained from immunogenic cancer cells that are also capable of inducing an immune response, can be used (see page 13, line 24 to page 14, line 2; and page 15, lines 16-29, for instance); wherein the immunomodulatory moiety is bound to the surface via a cationic layer disposed on the surface with the use of aminosilane compounds APTES or EDABES (see Figure 14B; and page 6, lines 18-24; page 13, lines 15-22, for instance) that generate variable surface zeta potentials/charges; wherein the immunomodulatory moiety is bound to the surface via an anionic layer (see Figure 13; and page 6, lines 13-17, for instance); and wherein the immunomodulatory moiety (such as PAMP or DAMP, or LPS) is bound to the surface via siloxane (see page 29, claims 6-8, for instance).
However, a silicified cell comprising a nanoparticle comprising an exogenous polynucleotide encoding a “bioactive agent” loaded into the silicified cell (see amended claims 1 and 12) has not been specifically disclosed by Serda et al 2019, as discussed above.
Serda et al (2015), while teaching mesoporous silicon particles for the presentation of tumor antigens and adjuvant for anti-cancer immunity (see Title, Abstract, col. 1, lines 29-34; and Claims 1, 12), disclose “In one embodiment, the present invention provides cancer vaccines that utilize an array of tumor antigens conjugated to the Surface of nanoparticles (i.e., tumor mimetics). The tumor mimetics are co-loaded into a larger carrier particle in association with an expression vector, creating both a vehicle for tumor antigens and a source for cytokine production (i.e., multifunctional vector vaccines)” (see col. 2, lines 47-53, for instance); wherein the nanoparticles can comprise vaccine components including one or more diagnostic, imaging, and/or therapeutic compounds (see entire col. 3) that comprise “chemical targeting moiety includes at least one moiety selected from a the group consisting of a ligand, a dendrimer, an oligomer, an aptamer, a binding protein, an antibody, an antigen binding fragment thereof, a biomolecule, an siRNA, and any combination thereof” (see col. 3, lines 45-50); wherein siRNA (small interfering ribonucleic acid, siRNA, i.e. a polynucleotide encoding “a bioactive agent”) can be incorporated and/or encapsulated into nanoparticles “knocking down negative regulators of immune system” (i.e. encoding a bioactive agent in cells for the knock down effects; see Example 5, col. 35-36) as demonstrated in the mouse model and dendritic cells (see entire disclosure on col. 36). Thus, Serda et al 2015 disclose the nanoparticles (in the form of “mesoporous silicon multi-stage vehicles” MSV; see Abstract) comprising variety of therapeutic compounds and molecules including an exogenous polynucleotides encoding a bioactive agent (such as siRNA, CpG, aptamers, etc.; see also col. 16, last paragraph; col. 18, lines 35-37, for instance) that can modulate immune response in cancer cells such as for treatment of mammalian breast cancer.
Thus, give the detailed disclosure from Serda et al 2015 for the nanoparticles comprising polynucleotide encoding a bioactive agent such as siRNA, CpG, aptamers etc., that can regulate desired targets in cells (see teachings/suggestions from Serda et al 2015, above), an artisan of ordinary skill in the art would have been motivated to modify the silicified cells disclosed by Serda et al 2019 such that they incorporate suitable exogenous polynucleotides (such as a desired siRNA, CpG) encoding a bioactive agent into nanoparticles as taught by Serda et al 2015, in order to make silicified cells comprising nanoparticles that would be highly effective in modulating immune response and/or treating neoplastic tissues or cancers such as mammalian breast cancer, as already disclosed and exemplified by Serda et al 2015 (see Example 5, in particular). Since, the all the techniques for making such multi-stage delivery nanoparticle systems has already been taught by the disclosure from Serda et al 2015 (see Example 1), as well as Serda et al 2019 (see Figure 14, in particular), such modification of the silicified cell would have been obvious and/or fully contemplated by an artisan of ordinary skill in the art, unless evidence and/or data provided on record to the contrary (which is currently lacking on record; see SPEC, Example 2; Figures 6-7).
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
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.
1. Claims 1-3 and 9-14 (as currently amended) are/remain rejected on the ground of nonstatutory double patenting as being unpatentable over at least claim 1 of U.S. Patent No. 12,201,651 B2 (issued on Jan. 21, 2025 to same inventors and assignee; from US application 17/436,872). Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claim 1 of the ‘651 patent is also drawn to product comprising essentially the same “silicified cell” as reproduced hereinbelow:
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It is clear that the issued product is a species (at least for the limitation of the “cationic layer” disposed on “at least a portion of the silicified surface”) of the generic claims currently under examination (i.e. in a genus-species relationship with overlapping scope; as targeted delivery of various drugs or molecules loaded within silicified cells using mesoporous silica nanoparticles have been disclosed and/or fully contemplated by the issued patent ‘651; see 2nd and 4th paragraph of Summary; col. 4, 6th paragraph; col. 7, 3rd paragraph; col. 15, last paragraph), and therefore, an ODP rejection is still deemed proper, and is therefore made and/or maintained (see also the 103a rejection discussed above using the cited prior art references of Serda et al 2019 taken with Serda et al 2015).
Examiner’s Response to Applicant’s Arguments
Applicant’s arguments filed on 06/29/2026 (see REM, p. 6-8) with respect to claim(s) as currently amended on record, have been considered but are not found to be persuasive at least for the following reasons of record:
Regarding the 103(a) rejection of record, applicants mainly argue that “…it is not predictable from either Serda 2019 or Serda 2015 that the “exogenous polynucleotide encoding a bioactive agent loaded into the silicified cell” would still possess bioactivity after (a) being internalized by a living cell, then (b) the cell being silicified…” (see REM, p. 7). Applicant’s argument is duly noted and considered. However, Serda et al 2015 already disclose the art-known fact that- (1) “Hybrid particle vaccines are Superior to single particle vaccines because they accomplish multiple synergistic tasks that are needed to elicit effective immune responses. The use of porous microparticles (such as porous silicon) permits attachment of toll-like receptor ligand(s) (TLR-L) to the particle Surface and loading with both antigens and immune stimulating agents (for example, in the form of proteins, peptides, small molecules, RNA, DNA, and the like), either free or encapsulated in nanoparticles” (see Serda et al 2015, col. 9, lines 47-55); and (2) “Once internalized in cells, such microparticles are primarily contained within endosomes that eventually mature into acidic vesicles (see e.g., Ferrati et al., 2010). This acidification of endosomes is needed for antigen processing and presentation. It is within the acidic endosome that antigens are loaded into the cleft of major histocompatibility (MHC) molecules, which are then sent to the cell surface for presentation of antigen to other immune cells (T cells) in association the costimulatory molecules (e.g., CD80, CD86, CD40, and the like). Both expression of Surface co-stimulatory molecules and diversion of MHC to the cells surface are triggered by TLR activation” (see Serda et al 2015, col. 10, 3rd paragraph, for instance). Serda et al 2015 also disclose that “The introduction of nanoparticles to cancer vaccines provides a means of loading APC ex vivo and concurrently loading expression vectors for expression of cytokines to enhance APC maturation, migration, antigen processing, and surface expression of co-stimulatory molecules” (see Example 2, 3rd paragraph; and see also Example 3, col. 24, 3rd paragraph, for instance). They clearly disclose the fact that “Depending on the antigen incorporated in the nanoparticles, the vaccine can be used for cancer immunotherapy, transplantation immunology and autoimmune disease management” (see entire Example 5, disclosure on columns 35-36). Thus, they demonstrate the bioactivity of the polynucleotide encoded agents (such as desired siRNAs) delivered via nanoparticles that activate dendritic cells in order to effectuate immune response from the antigen presentation cells in vivo with a reasonable predictability, contrary to the arguments currently made by the applicants.
In addition, Serda et al 2019 have already demonstrated (see Figures 10-12, also see disclosure on p. 5-6, for instance) creating pathogen mimetic cancer cells through silicification and their internalization (via phagocytosis) by bone marrow derived dendritic cells (BMDCs) for activation and antigen presentation effects/results. They clearly disclose (see Serda et al 2019; entire disclosure on p. 18) that:
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Therefore, the arguments of unpredictability as currently made by applicants is duly noted and considered but is not deemed persuasive. For the same reasons, the argument that “the surface of the nanoparticles loaded into the silicified cell, as recited in claim 1, is not readily accessible to the target of the bioactive agent” (see REM, p. 7, 2nd paragraph) is duly noted, but is not deemed to be persuasive, as the cancer cell silicification (and PAMP adsorption, for instance) has already been shown to stimulate BMDC internalization of the cancer cells by Serda et al 2019 (see Figures 11-12, for instance).
Thus, the 103a rejection of record over the combined disclosure from the cited prior art references is still deemed proper and is therefore made and/or maintained.
Regarding the ODP rejection of record (see REM, p. 7), applicant states the following:
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As discussed above in the ODP rejection of record, since the issued claims are deemed as species of the generic claim in the instant application, in the absence of a Terminal Disclaimer from applicants, the ODP rejection is still deemed proper, and is therefore made/maintained.
Conclusion
NO claims are currently 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 SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
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