lissNotice 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
A second request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 5, 2026 has been entered.
Claims 1-3, 6-9, 11-18, 21, 22 and 24 are pending.
Claims 4, 5, 10, 19, 20 and 23 are cancelled.
Claims 12 and 24 are currently amended.
Claims 1-3, 6-9, 11, 18, 21 and 22 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 12-17 and 24 as filed on August 5, 2026 are under consideration.
Withdrawn Objections / Rejections
In view of the cancellation of claim 23, the previous rejection of claim 23 under 35 USC 103 further in view of Brisson is withdrawn.
In view of the amendment of claim 24, the previous rejection of claim 24 under 35 USC 112(b) is withdrawn and the previous rejection of claim 24 under 35 USC 103 in view of Karube is withdrawn.
Applicant’s arguments have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Objections
Claim 24 is objected to because of the following informalities:
“a substrate” is properly “the substrate” to reference the antecedent.
“a coating” is properly “the coating” to reference the antecedent.
“an amine group” is properly “the amine group” to reference the antecedent.
“a protein” is properly “the protein” to reference the antecedent.
Appropriate correction is required.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of 35 U.S.C. 112 (pre-AIA ). See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/837,223, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph for one or more claims of this application.
The prior-filed application does not disclose all of the cross-linkers of claim 12.
The earliest date available to claims 12-17 remains April 23, 2020 (see also page 5 of the Non-Final Rejection mailed February 12, 2025, pages 3-4 of the Non-Final Rejection mailed October 10, 2025, and pages 3-4 of the Final Rejection mailed May 5, 2026).
The prior-filed application discloses a sulfo-N-maleimidobutyryl-oxysuccinimide ester (e.g., claim 4) falling within the scope of the cross-linkers of claim 24. Claim 24 may be entitled to an effective date of April 23, 2019.
Response to Arguments: Priority
Applicant’s statement at page 6 of the Remarks that the provisional application discloses GMBS is acknowledged but not found persuasive because Applicant has not identified any passage of the provisional application disclosing GMBS per se. At most, the application discloses a sulfo-N-maleimidobutyryl-oxysuccinimide ester. For clarity of the written public record, GMBS as understood by those of skill in the art and sulfo-GMBS are different chemicals. See for example
Hemberger et al. (US 2005/0181985, e.g., paragraph [0029]) and Zander et al. (US 2005/0234230, e.g., Table 1):
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Notably, the instant claims, at narrowest (e.g., claim 24) recite N-[Symbol font/0x67]-maleimidobutyryloxy succinimide ester which is either GMBS per se as evidenced by Zander or which may be broadly and reasonably construed as encompassing a small genus of esters. Applicant has offered neither argument nor evidence substantiating the allegation that the instant claims are entitled to the date of the provisional application. Therefore, the Examiner maintains the pending claims are not fully supported by the prior-filed application.
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 of this title, 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.
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.
Claims 12-17 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Woeppel et al. “Enhancing surface immobilization of bioactive molecules via a silica nanoparticle based coating,” Journal of Materials Chemistry B 6:3058-3067, published April 6, 2018, IDS reference filed December 7, 2021 in view of Shakeri et al. “Biofunctionalization of glass- and paper-based microfluidic devices: a review,” Advanced Materials Interfaces 6:1900940, first published August 7, 2019, of record and Hansson et al. (US 4,671,410, published June 9, 1987, of record).
Woeppel teaches thiolated silica nanoparticle (TNP) surface coatings wherein the TNPs are linked to a substrate silanized with 3-glycidyloxypropyl trimethylsiloxane (GTS); said linked TNPs comprise surface thiol (-SH or sulfide) groups which can link to amine containing molecules inclusive of proteins inclusive of L1, a neuron-specific adhesion molecule, via an N-maleimidobutyryl-oxysuccinimide ester (GMBS) (TNP + GMBS = thioether bond as evidenced by page 16 of the instant specification) (abstract; Scheme 1, 3; page 3059, lhc, last full paragraph; page 3060, lhc, 1st full paragraph; page 3066, “Conclusions”):
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, as required by instant claims 14, 17, 24. Substrates include silicon and glass (Scheme 1; page 3059, paragraph bridging columns), as required by instant claim 15. Implanted neural electrodes are one example where surface modification has shown benefits (page 3059, lhc, 1st full paragraph), as required by instant claim 16. The coated substrates were dried (page 3061, lhc, “Surface characterization”). Woeppel further teaches TNPs were chosen due to their ability to be easily crosslinked to amine containing compounds, to attack epoxides, and to bind to each other through di-sulphide bonds (page 3061, rhc, “Nanoparticle fabrication”; Scheme 1, 2). Woeppel concludes TNPs were successfully immobilized onto glass and silicon substrates via silane chemistry (page 3066, “Conclusions”).
Regarding the consists essentially of transitional phrase as newly recited in instant claim 12, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355. Regarding the consisting of transitional phrase as newly recited in instant claim 24, the dried, coated substrates of Woeppel do not require an element excluded by the claims. See MPEP 2111.03.
Woeppel does not specifically teach a substrate comprising an amine group, the amine group linked to silica nanoparticles via a cross-linker selected from inter alia GMBS and does not specifically teach packaging as required by claims 12, 24.
Woeppel does not teach hermetically sealed packaging as required by claim 13.
These deficiencies are made up for in the teachings of Shakeri and Hansson.
Shakeri teaches biofunctionalization of glass achieved by silanization of the surface (title; abstract; section 2.1, “Silanization”). The most common silane coupling agents include 3-aminopropyltrimethoxysilane (APTMS) and 3-glycidyloxypropyl trimethoxysilane (GLYMO) (page 3, lhc, 1st full paragraph). GLYMO provides epoxy terminal groups on the surface while APTMS provides amino tail groups (substrate comprises an amine) which can bind to activated carboxylic groups (page 4, lhc, 2nd full paragraph; Figure 2(b,c)). Shakeri further teaches an embodiment wherein silanized glass was reacted with N-[Symbol font/0x67]-maleimidobutyryl-oxysuccinimide ester; in this embodiment the biofunctional agents remained stable for 6 months at room temperature (paragraph bridging pages 7 and 8; Figure 3).
Hansson teaches a package for sterile and contamination-free storage of artificial implants (title; abstract; claims). The package comprises a hermetically sealed outer casing; the outer cases prevents any possible impurities from reaching the implant (abstract; paragraph bridging columns 2 and 3), as required by instant claim 13. It is well known that the biocompatibility of an implant material is intimately associated with the surface properties of the material (column 1, lines 8-18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the GTS substrate silanization agent of Woeppel to comprise any silanization agent inclusive of APTMS as taught by Shakeri in order to introduce different functional groups onto the surface. There would be a reasonable expectation of success because Woeppel embraces silane chemistry for immobilizing TNPs onto glass and Shakeri evidences APTMS is an art recognized obvious variant of GTS for purposes of silanizing glass. The combined teachings of Woeppel in view of Shakeri therefore render obvious silanized substrates comprising amine groups. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to link the TNPs of Woeppel comprising surface thiol groups to the APTMS silanized substrate of Woeppel in view of Shakeri comprising amine groups via an N-maleimidobutyryl-oxysuccinimide ester (GMBS) as taught by Woeppel because Woeppel demonstrates GMBS links TNPs comprising surface thiol groups to amines.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to package the dried coated substrates of Woeppel in view of Shakeri within packaging comprising a hermetic seal as taught by Hansson in order to prevent any possible impurities from reaching the substrate because it is well known that the biocompatibility of an implant material is intimately associated with the surface properties of the material.
Regarding the wherein clause of claim 12 drawn to the activity of the protein during storage, because Woeppel in view Shakeri and Hansson render obvious hermetically sealed packing of dried protein-coated articles as instantly claimed, it necessarily follows that the packaged articles rendered obvious by Woeppel in view of Hansson are also characterized by the activity as claimed. In further support of this presumption, Shakeri teaches an embodiment wherein biofunctional agents remained stable for 6 months at room temperature when linked to silanized glass via a N-[Symbol font/0x67]-maleimidobutyryl-oxysuccinimide ester.
Claims 12-17 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Woeppel et al. “Enhancing surface immobilization of bioactive molecules via a silica nanoparticle based coating,” Journal of Materials Chemistry B 6:3058-3067, published April 6, 2018, IDS reference filed December 7, 2021 in view of Levicky et al. (US 2007/0072199, published March 29, 2007); Hemberger et al. (US 2005/0181985, published August 18, 2005) as evidenced by Shakeri et al. “Biofunctionalization of glass- and paper-based microfluidic devices: a review,” Advanced Materials Interfaces 6:1900940, first published August 7, 2019, of record; and in view of Hansson et al. (US 4,671,410, published June 9, 1987, of record).
Woeppel is applied herewith presuming an earlier effective filing date for claim 24 in the interest of compact prosecution
The teachings of Woeppel have been described supra. Woeppel further teaches sulfo-GMBS (page 3060, rhc, 1st full paragraph).
Woeppel does not specifically teach a substrate comprising an amine group, the amine group linked to silica nanoparticles via a cross-linker selected from inter alia GMBS and does not specifically teach packaging as required by claims 12, 24.
Woeppel does not teach hermetically sealed packaging as required by claim 13.
These deficiencies are made up for in the teachings of Levicky, Hemberger and Hansson.
Levicky teaches covalent methods for the immobilization of thiolated biomolecules on siliceous and metallic surfaces; siliceous materials include glass (title; abstract; claims; paragraph [0108]). The methods comprise silylating a siliceous substrate comprising a silanol surface with an aminosilane such as APTES (substrate comprises an amine),
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reacting the aminosilanized surface with a heterobifunctional linker such as sulfo-GMBS and reacting the maleimide surface with thiolated molecules (claims 1, 3-6; Figure 2, reproduced in part; paragraph [0223]).
Hemberger teaches linker molecules for connecting SH and NH functions include GMBS and sulfo-GMBS (paragraph [0029]).
The teachings of Hansson have been described supra.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the GTS substrate silanization agent of Woeppel to comprise any silanization agent inclusive of APTES (comprises an amine) as taught by Levicky because simple substitution of functionally equivalent elements yields predictable results, absent evidence to the contrary. See MPEP 2144.06 and 2144.07. There would be a reasonable expectation of success because Woeppel embraces silane chemistry for immobilizing TNPs onto glass. The combined teachings of Woeppel in view of Levicky therefore render obvious silanized substrates comprising amine groups. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to link the TNPs of Woeppel comprising surface thiol groups to the APTES silanized substrate of Woeppel in view of Levicky via a heterobifunctional linker such sulfo-GMBS as taught by Levicky or/and an N-maleimidobutyryl-oxysuccinimide ester (GMBS) as taught by Woeppel and by Hemberger because Woeppel demonstrates GMBS links TNPs comprising surface thiol groups to amines and because Hemberger evidences sulfo-GMBS is an art-recognized obvious variant of GMBS for purposes of linking a nitrogen to a sulfur.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to package the dried coated substrates of Woeppel in view of Levicky and Hemberger within packaging comprising a hermetic seal as taught by Hansson in order to prevent any possible impurities from reaching the substrate because it is well known that the biocompatibility of an implant material is intimately associated with the surface properties of the material.
Regarding the wherein clause drawn to the activity of the protein during storage, because Woeppel in view Levicky, Hemberger and Hansson render obvious hermetically sealed packing of dried protein-coated articles as instantly claimed comprising GMBS linkers as instantly claimed, it necessarily follows that the packaged articles rendered obvious by the combined teachings of the prior art are also characterized by the activity as claimed. In further support of this presumption, Shakeri teaches an embodiment wherein biofunctional agents remained stable for 6 months at room temperature when linked to silanized glass via a N-[Symbol font/0x67]-maleimidobutyryl-oxysuccinimide ester.
Response to Arguments: Claim Rejections - 35 USC § 103
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant’s statement at page 6 of the Remarks that the consisting of transitional phrase newly recited in instant claim 24 removes Shakeri is acknowledged but is unpersuasive because Shakeri renders obvious silane coupling agents.
Applicant’s statement at page 7 that the Office Action has not set forth a prima facie case of obviousness over claims 12-17 is unpersuasive. Applicant’s analysis that the Examiner does not understand how GMBS functions is unpersuasive. For clarity of the written public record, GMBS as understood by those of skill in the art and sulfo-GMBS are well-known, art-recognized linker molecules. See for example Hemberger et al. (US 2005/0181985, e.g., paragraph [0029]), Zander et al. (US 2005/0234230, e.g., Table 1), Levicky et al. (US 2007/0072199, e.g., Figure 15; paragraph [0223]), Biemans et al. (WO 2009/077438, e.g., Scheme 2), and Tanaka et al. Figure 2 as appended to the instant Office Action.
Applicant’s statements at pages 7-8 that the Examiner has failed to fully consider the prior-filed Declaration is incorrect and unpersuasive. The analysis in the Declaration does not render non-obvious the substitution of silane coupling agents.
Applicant’s statements at page 9 regarding the intermediate silica layer and unexpected advantages thereof remain unpersuasive because this structure is already known to the prior art in view of Woeppel.
Therefore, the rejections over Woeppel are properly maintained in modified form as necessitated by Applicant’s amendments.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hemberger et al. (US 2005/0181985) exemplifies linker molecules for connecting various functional groups inclusive of those for connecting SH and NH (e.g., paragraphs [0027]-[0039]):
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Zander et al. (US 2005/0234230) exemplifies crosslinking compounds inclusive of GMBS and sulfo-GMBS (Table 1, reproduced in part):
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where the “E” denotes the crosslinking compound to comprise an SH-reactive maleimido and an amine-reactive ester (Table in paragraph [0157]).
Levicky et al. (US 2007/0072199) teaches immobilization of molecules on siliceous and metallic surfaces by reacting an aminosilanized surface with a heterobifunctional linker inclusive of sulfo-GMBS; during reaction, an amine group attaches the ester to yield an amide linkage (title; abstract; claims, in particular 1, 6; Figures 2, 15; paragraph [0223]).
Biemans et al. (WO 2009/077438) teaches protein conjugates and exemplifies an embodiment of the reaction of the primary amino group of a first protein with a first bifunctional linker inclusive of GMBS (title; abstract; claims; Scheme 2):
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Chen et al. “Thermal stability, storage and release of proteins with tailored fit in silica,” Scientific Reports 7:46568, 2017 teaches proteins enclosed in silica render them stable (title; abstract).
Hernandez et al. “NanoKeepers: stimuli responsive nanocapsules for programmed specific targeting and drug delivery,” Chemical Communications 50:9489-9492, 2014 teaches silica nanocapsules modified with a sulfo-linker to facilitate coupling to amine-modified oligonucleotides (title; abstract; Figure 1).
Tanaka et al. “Oligonucleotide-arrayed TFT photosensor applicable for DNA chip technology,” Biotechnology and Bioengineering 95(1):22-28, 2006 teaches immobilization of thiolated oligonucleotide probes onto a titania coated photosensor using APTES and GMBS (title; abstract; Figure 2):
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISSA PROSSER whose telephone number is (571)272-5164. The examiner can normally be reached M - Th, 10 am - 6 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, DAVID BLANCHARD can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALISSA PROSSER/Examiner, Art Unit 1619
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
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