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 .
Amendments
Applicants’ amendments to the claims filed 8/25/2025 have been entered. Any objection\rejections from the previous office action filed 2/24/2025 not addressed below has been withdrawn.
Claim Rejections - 35 USC § 112
Claims 1-5,9,11-13,15-34,49 and 50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. In particular the new limitation in claim 1 for the amount of PEI being above 10%wt of PEI is considered new matter. While applicants do have support to claim 10-30% by wight of the nanoconstruct as recited in claim 10, they do not have support to claim all values above the upper limit of the range recited which is 30%. Claims 2-5,9,11-13,15-34,49 and 50 incorporate the new matter by dependency.
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 1-5,9,11-13,15-34,49 and 50 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. In particular, the new limitation in claim 1 that at least “10% by weight polyethylene imine” is bound to the surface is not clearly understood. Is the 10 by weight the total of the nanoconstruct or from the amount of PEI used to react with the nanoparticle? The limitation is unclear as the weight % is incomplete for not stating what the part to the whole encompasses, i.e. the nanoconstruct or the amount of PEI used. Claims 2-5,9,11-13,15-34,49 and 50 incorporate the indefinites by dependency.
Claim Rejections - 35 USC § 102
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.
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) 1,4,9-13,15-24,26-30,33-34 and 50 is/are rejected under 35 U.S.C. 102a1 as being anticipated by Bringley et al. (US 2006/0293396), cited IDS. This new rejection was necessitated by amendment.
Bringley discloses amine modified nanoparticulate carriers which include silica core and PEI-PEG shell nanoparticles with a size of 100 nm of less, within the claimed ranges, the examples used 20 wt% PEI of MW 2,000 and 10,000 g/mol, each within the claimed ranges, the nanoparticles caried a variety of cargo including targeting antibodies such as monoclonal antibodies and small organic fluorescent dyes bound to the nanoparticle. See entire disclosure, especially abstract, [0020]-[0025],[0028],[0031], [0035],[0038],[0052],[0063][0065]-[0066],[0082]-[0086] and claims. Regarding claims 11-12, the PEI was crosslinked, any crosslinking moiety is capable of being cleaved. See [0025],[0065]-[0068] and claim 5.
Claim Rejections - 35 USC § 103
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.
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) 1-5,9-13,15-34,49 and 50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al.” PEGylated polyethyleneimine grafted silica nanoparticles:
enhanced cellular uptake and efficient siRNA delivery” Anal Bioanal Chem (2011) 400:535–545 in view of Zink (US 2012/0207795), cited parent application, in view of Febvay “Targeted Cytosolic Delivery of Cell-Impermeable Compounds by
Nanoparticle-Mediated, Light-Triggered Endosome Disruption”, Nano Lett. 2010, 10, 2211–2219. This new rejection was necessitated by amendment.
Lee teaches PEGylated PEI (PEI25K-PEG5K) grafted silica nanoparticles for enhanced cellular uptake, the combustion analysis showed the PEI was at least 10 wt% but less than 25 wt % (10% N, 15% C, some C would be from PEG), from the figures the nanoparticles were ~50 nm. See entire disclosure, especially abstract and table 1. The PEI-PEG NP was labeled with RITC red dye, a small molecule. See page 542, 2nd col. and ¶ bridging page 543.
Lee is silent with respect to the nanoparticle containing a protein such as an antibody or chemokine, is silent with respect to mesoporous silica, cross-linking and PDI.
Zink teaches cationic coated mesoporous silica (MSP) nanoparticles for delivery of peptides including monoclonal antibodies and cytokines (meeting claims 21-25), bound electrostatically (meeting claim 15) with hydrodynamic diameter of ~70 and ~100 nm, particle size of less than 100 nm (data point is in range of claims 17-19), the cationic polymer including crosslinked PEI-PEG copolymer (MW 5-10 KDa per block, within range of claim 13), crosslinkers including cleavable moieties such as disulfide bonds to bind the protein to the surface of the nanoparticle. See entire disclosure, especially abstract, [0096], [0104]-[0105],[0126],[0128],[0167],[0266],[0280], [0302],[0308], [0326], table 1 and claims. The pores of the MSP allow small molecules, for example, therapeutic compound such as anticancer compounds to adhere or bind to the inside surface of the pores, and to be released from the silica body when used for therapeutic purposes. See [0096]. Regarding claim 27, the nanoparticles could further comprise small molecules including the chemotherapeutic agent doxorubicin. See claim 5. Regarding claims 29-30, Zink discloses use of targeting proteins and moieties. See [0108] and [0294]. Regarding claims 33-34, Zink discloses use of labels on the nanoparticles including fluorescent dyes such as rhodamine. See examples 1 and 3.
Since Lee and Zink are related in their teachings of PEI-PEG coated silica nanoparticles one of ordinary skill in the art would have a high expectation of success in electrostatically binding monoclonal antibodies or cytokines to the nanoparticle, crosslinking PEI-PEG and using MSP. Reason to substitute or add antibodies and cytokines by biodegradable crosslinking agents would be to target the nanoparticle to the target cell/tissue for payload delivery. Reason to substitute nonporous silica with mesoporous would be to increase encapsulation of therapeutics.
Febvay is used for its disclosure that control of MSP growth by increasing amounts of nonionic surfactant limits growth and results in NP with decreased average hydrodynamic size with excellent reproducibility and low polydispersity for PEI-PEG coated MSP. See entire disclosure, especially abstract, Fig 2, page 2213 rt col. Thus, Febvay is mainly used to show that there were methods to control PDI and hydrodynamic radius of PEI-PEG coated MSP such as those of Lee and were therefore well understood result effective parameters that one of ordinary skill could adjust through routine optimization. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal PDI as well as hydrodynamic radius needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of PDI would have been obvious at the time of applicant's invention. It is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426.
Thus the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Response to Amendment
The declaration under 37 CFR 1.132 filed 8/25/2025, which originally filed in parent case 15/429,971 is insufficient to overcome the rejection of the pending claims because: the affidavit is no longer relevant for the obviousness rejection in this action. Bringley is a 102 rejection and secondary considerations cannot overcome the reference. Regarding applicants argument of unexpected results, Evidence of secondary considerations, such as unexpected results or commercial success, is irrelevant to 35 U.S.C. 102 rejections and thus cannot overcome a rejection so based. In re Wiggins, 488 F.2d 538, 543, 179 USPQ 421, 425 (CCPA 1973). The obviousness rejection uses the primary reference Lee which is not addressed in the previously submitted declaration.
Response to Arguments
Applicant’s arguments with respect to the pending claim(s) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Note Zink is only used as a secondary reference to pick up some limitations not taught by the primary reference and is not bodily incorporated within.
Conclusion
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.
/JAMES W ROGERS/ Primary Examiner, Art Unit 1618