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 Request for Reconsideration dated January 7, 2026 is acknowledged.
Claims 1-3, 6-9, 11-18 and 21-24 are pending.
Claims 4, 5, 10, 19 and 20 are cancelled.
Claim 23 is currently amended.
Claim 24 is new.
Claims 1-3, 6-9, 11, 18, 21 and 22 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.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, 23 and 24 as filed on January 7, 2026 are under consideration.
This action is made FINAL.
Withdrawn Objections / Rejections
In view of the amendment of the claims, all previous claim rejections under 35 USC 112(b) are withdrawn.
Applicant’s arguments and the 132 Declaration of Xinyan Cui 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
New Grounds of Rejection Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
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.
Claim 24 is 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 24 recites the N-maleimidobutyryl-oxysuccinimide ester, however, claim 12 from which claim 24 depends recites two N-maleimidobutyryl-oxysuccinimide esters, the first linking the substrate to the nanoparticles and the second linking the protein to the nanoparticles. It is unclear whether the N-maleimidobutyryl-oxysuccinimide ester of claim 23 references the first, the second or both esters of claim 12.
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 or any of the cross-linkers of claim 23.
The earliest date available to claims 12-17 and 23 remains April 23, 2020 (see also page 5 of the Non-Final Rejection mailed February 12, 2025 and pages 3-4 of the Non-Final Rejection mailed October 10, 2025).
The prior-filed application discloses a sulfo-N-maleimidobutyryl-oxysuccinimide ester (e.g., claim 4) falling within the scope of the cross-linker 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 fully supports the kit of claim 12 is acknowledged but not found persuasive because Applicant has not identified support for all of the cross-linkers of claim 12. Therefore, the Examiner maintains claim 12 is not fully supported by the prior-filed application.
Maintained Grounds of Rejection / New Grounds of Rejection Necessitated by Amendment
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”):
PNG
media_image1.png
112
620
media_image1.png
Greyscale
, 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”).
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 claim 12.
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.
Claim 23 is 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) as applied to claims 12-17 and 24 above, and further in view of Brisson et al. (US 2009/0098574, published April 16, 2009, of record).
The teachings of Woeppel, Shakeri and Hansson have been described supra.
Although the kit of claim 23 does not require the cross-linker to be the N-maleimidoalkanoic-oxysuccinimide ester alternative of claim 12, Woeppel does not specifically teach the cross-linker is inter alia a 3-malimidocaproic acid N-hydroxysuccimide ester as required by claim 23.
This deficiency is made up for in the teachings of Brisson.
Brisson teaches nanoparticles functionalized with proteins (title; abstract; claims; Figure 1). Classical hetero-bifunctional coupling agents include inter alia N-[g-Maleimidobutyryloxy]succinimide ester (GMBS) or N-[e-maleimido-caproyloxy]succinimide ester (EMCS) (a 3-malimidocaproic acid N-hydroxysuccimide ester) (claim 21; paragraph [0052]), as required by instant claim 23.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute N-[e-maleimido-caproyloxy]succinimide ester (EMCS) (a 3-malimidocaproic acid N-hydroxysuccimide ester) as taught by Brisson for the GMBS linker of Woeppel because simple substitution of functionally equivalent elements yields predictable results, absent evidence to the contrary.
Claim 24 is 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 Karube et al. (JP H10267930 A, published October 9, 1998, as evidenced by the Google translation) 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) as applied to claims 12-17 above, and further in view of Brisson et al. (US 2009/0098574, published April 16, 2009, 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 does not specifically teach a substrate comprising an amine group, the amine group linked to silica nanoparticles via a GMBS cross-linker and does not specifically teach packaging as required by claim 24.
This deficiency is made up for in the teachings of Karube and Hansson.
Karube teaches a chip comprising a transparent substrate (1) such as glass, an organic silicon film (3) formed by using a silane coupling agent, and a physiologically active material (4) immobilized on the substrate (title; abstract; claims; Figure 1). Silane coupling agents include inter alia 3-aminopropyltrimethoxysilane (comprises an amine) (claims 8, 9; page 3, top half). The chip may further comprise a layer comprising a water-soluble bivalent reagent (6) such as N-succinimidyl 4-maleimidobutryic acid (GMBS) between said organic silicon film (3) and said active material (4) (claims 10, 11; Figure 4).
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 3-aminopropyltrimethoxysilane (comprises an amine) as taught by Karube 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 Karube 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 3-aminopropyltrimethoxysilane silanized substrate of Woeppel in view of Karube via a bivalent reagent (6) such as N-succinimidyl 4-maleimidobutryic acid (GMBS) as taught by Karube or/and 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 Karube 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 Karube 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 and 132 Declaration: 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 Shakeri is not prior art is not found persuasive because the instant claims are not entitled to the earliest priority date.
Applicant’s citation to the Declaration at pages 6-8 is acknowledged. The declaration at paragraph 4 states there is only 1 maleimide on GMBS. This is not found persuasive because in fact there are 2 maleimides on GMBS as evidenced by Sigma (copy provided):
PNG
media_image2.png
228
1054
media_image2.png
Greyscale
The instant claims do not require a sulfur ester as exemplified by the Declarant, however, the sulfur ester is taught by Woeppel (e.g., page 3060, rhc, 1st full paragraph). The declaration at paragraph 5 states the improved bound protein stability touted by Shakeri is due to the presence of trehalose. This is not found persuasive because the presence of trehalose is not precluded from the kit as instantly claimed. The declaration at paragraph 6 attributes the instantly claimed stability to nanoparticle modified substrate. This seems a reasonable conclusion given that it is axiomatic that function follows structure. However, the structure of a nanoparticle modified substrate is either known to the prior art (e.g., Woeppel) or is obvious in view of the combined teachings of the prior art. As set forth in the rejections, because the prior art renders obvious the combination of structural features claimed, it follows that the function or property claimed is necessarily present. See MPEP 2112 for information regarding rejections invoking inherency. The declaration at paragraph 7 references surprising stability, citing to the Examples within the instant specification. This line of argument remains unpersuasive because that which is unexpected can only be determined relative to the prior art. See MPEP 716. There is no evidence of record that the devices of Woeppel comprising nanoparticle modified substrates are unstable.
Therefore, there rejection over Woeppel is properly maintained and new grounds of rejection are set forth herein over new claim 24 in the interest of compact prosecution.
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.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALISSA PROSSER/
Examiner, Art Unit 1619
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
Prosecution Insights