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
Status of the Claims
Claims 1-9, 13-20, and 24-25 are pending. Claims 1-9 are the subject of this FINAL Office Action.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9 and 11) and the species of 3-aminopropyltriethoxysilane (aka APTES), succinic anhydride-modified base monomer and TiN in the reply filed on 03/16/2026 is acknowledged. Claims 13-20, and 24-25 are withdrawn.
Claim Interpretations
Claim 1 is still structured as a product-by-process, which means the claimed product dictates the scope of the claim. See MPEP §§ 2113 & 2173.05(p). For example, “wherein the bonding molecule is formed by reacting a silanized molecule with the surface of the chip.” The same applies to the processes recited in claims 3-6 and 9.
In sum claim 1 requires the following structure:
Chip (e.g. flat solid support) with TiN or TiW (“semiconductor chip” structurally undefined= any solid support);
Generic silane “bonding molecule” generically “linked” to chip; and
Generic hydroxyl-ester “functional molecular group” generically “linked” to generic silane “bonding molecule.”
As another example, claim 8 recites that the “functional molecule” “reacted” with the “silanized molecule” is a “of a succinic anhydride-modified base monomer.” In the context of a product, this means the resulting composition is:
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.
New Grounds of 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.
Claim(s) 1-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over FOSTER (20190161795), in view of PADMANABHAN (US 20050239112), TOKORO (US20100047579) and GOSHOO (US20100233429).
The prior art as a whole demonstrates that it would have been obvious to a skilled artisan in biological TiN electrode detection techniques at the time of filing to apply familiar silane attachment structures to the prior art nucleic acids to achieve familiar attachment results with a reasonable expectation of success.
As to claims 1-9, FOSTER teaches TiN working electrodes with attached biomolecules such as nucleic acids (Abstract). FOSTER explains the benefits of TiN chips:
Advances in micro-miniaturization within the semiconductor industry in recent years have enabled biotechnologists to begin packing traditionally bulky sensing tools into smaller and smaller form factors, onto so-called biochips. It would be desirable to develop techniques for biochips that make them more robust, efficient, and cost-effective.
[ . . . ]
In the present application, a non-faradaic electrochemical cell for nucleic acid sequencing that includes a titanium nitride (TiN) working electrode with increased electrochemical capacitance is disclosed. . . .
[ . . . ]
Building a non-faradaic electrochemical cell 1100 of a nanopore based sequencing chip with a spongy TiN working electrode has many advantages. Depending on the thickness of the TiN electrode (e.g., 500 angstroms to 3 microns thick), the specific surface area of the spongy TiN working electrode and its electrochemical capacaitance (e.g., 5 picofarads to 500 picofarads per square micron of base area) have a 10-1000 times improvement over that of a flat TiN working electrode with substantially identical dimensions (e.g., substantially identical thickness and base surface area). Since the spongy TiN working electrode allows electrolyte to diffuse through easily, the diameter/width of the spongy TiN working electrode may extend beyond the diameter/width of the well, such that the base surface area of the well and the working electrode can be optimized independently to provide the desired ratio between Cmembrane and Celectrochemical for improved system performance. Other advantages of using TiN include its low cost and ease of patterning and etching compared to other electrode materials, such as platinum.
(paras. 0002, 0048 & 0064). Although no specific biomolecule attachment technique is disclosed, yet silane and hydroxyl-ester attachments are routine in the art
For example, PADMANABHAN teaches a linker comprising 3-aminopropyltriethoxysilane (aka APTES; paras. 0040, 0043, 0045 & 0056) and succinic anhydride-modified base monomer (id.- nucleoside loaded to succinic anhydride treated 3-aminopropyltriethoxysilane). Scheme 1 shows
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This is the same structure as instant Figure 1:
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As explained above, claims 3-6 and 9 only describe the method of making the claimed linker, and fail to yield any distinguishable chemical characteristics of the linker from the prior art; and claim 11 only recites an intended use of the linker that fails to distinguish over prior art linkers.
TOKORO teaches a linker comprising 3-aminopropyltriethoxysilane (aka APTES; Example 21 @ para. 0110- “Silica coating was conducted in the same manner as in Example 15 except for using the coated, fine metal particles obtained in Example 20, to obtain silica-coated, fine metal particles. 0.1 g of the silica-coated, fine metal particles were mixed with 2 mL of an aqueous solution of 3-aminopropyltriethoxysilane (APS), and stirred for 1 hour. They were dried in the air to obtain amino-group-fixed magnetic beads (amino-group-coated magnetic beads). Using BioMag Plus Amine Particle Protein Coupling Kit available from Bang Laboratories, streptavidin was fixed to the amino-group-coated magnetic beads by the following procedure.”) and succinic anhydride-modified base monomer (Example 22- “An amino group was introduced by the same method as in Example 21, a carboxyl group was fixed using succinic anhydride, and streptavidin was fixed by activation with carbodiimide.”). The particles are TiN (paras. 0069-70).
As explained above, claims 3-6 and 9 only describe the method of making the claimed linker, and fail to yield any distinguishable chemical characteristics of the linker from the prior art; and claim 11 only recites an intended use of the linker that fails to distinguish over prior art linkers.
As further evidence that APTES/silane with succinic anhydride crosslinks were routine in the biomolecule attachment art, GOSHOO teaches exactly this point:
Alternatively, the silane coupling agent and the probe biomolecule may bond via cross linker. For example, a functional group such as amino group (—NH2) of lysine (Lys), carboxyl group (—COOH) of aspartic acid (Asp) and glutamic acid (Glu), phenolic group (—C6H4(OH)) of tyrosine (Tyr), imidazole group (—C3H3N2) of histidine (His), thiol group (—SH) of cysteine (Cys), etc., included in the protein such as a receptor, ligand, antagonist, antibody, antigen, etc., may be bonded to the amino group or the epoxy group of the silane coupling agent by the cross linker. In the case shown in FIG. 12, the amino group (—NH2) of the silane coupling agent and each amino group (—NH2) of the antibodies 95 a, 95 b, 95 c are bonded by a Disuccinimidyl suberate (DSS) that is the cross linker reacting to the amino groups (—NH2) at both terminals.
In addition, Bis[Sulfosuccinimidyl]suberate (BS3), Dimethyl suberimidate HCl DMS), Disuccinimidyl glutarate (DSG), Loman's Reagent, 3,3′-Dithiobis [sulfosuccinimidyl propionate] (DTSSP), and Ethylene glycol bis[succinimidylsuccinate] (EGS) that react to the amino groups at both terminals, and 1-Ethyl-3-[3-Dimethylaminopropyl]carbodiimide Hydrochloride (EDC) that react to the amino group and the carboxyl group can be used for the cross linker.
In addition, m-Maleimidobenzyl-N-hydroxysuccinimide ester (MBS), Succinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate (SMCC), Succinimidyl 4-[p-maleimidophenyl]-buthrate (SMPB), N-Succinimidyl 3-[2-pyridyldithio]propionate (SPDP), N-[γ-Maleimidobutyloxy]sulfosuccinimide ester (Sulfo-GMBS), Sulfosuccinimidyl 6-[3′ (2-pyridyldithio)-propionamide]hexanoate (Sulfo-LC-SPDP), m-Maleimidebenzoyl-N-hydroroxysulfo-succinimide ester (Sulfo-MBS), Sulfosuccinimidyl 4 [N-maleimidomethyl]-cyclohexane-1-carboxylate (Sulfo-SMCC), and Sulfosuccinimidy 4-[p-maleimidophenyl]-butyrate (Sulfo-SMPB) that react to the amino group and the thiol group can also be used as the cross linker
(paras. 0084-86). All that Applicants have done is combined a familiar biomolecule attachment technique with a familiar biomolecule chip surface to achieve familiar biomolecule attachment and detection results. Absent unexpected results, this is the epitome of obviousness.
In sum, it was obvious to apply familiar biomolecule attachment techniques to familiar TiN chips to achieve familiar results.
Prior Art
The following prior art teaches routine silanized chips with 3-aminopropyltriethoxysilane (APTES) and a succinic anhydride-modified APTES with added base monomer: EP 0173356 (para. 0004); US6423552 (Ex 1); US20030157538 (para. 0135).
The following prior art teaches routine silanized chips with 3-aminopropyltriethoxysilane (APTES) and a succinic anhydride treatment, then addition of a biological substance like a nucleotide: US9410953; WO 2007141811 A2; US20120202703; US 20140357529; US20170226571; US11203612; US20220390444.
The following prior art teaches routine attachment of succinic anhydride treated nucleosides to biochips: WO2001035100A2.
Conclusion
No claims are 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 Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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/AARON A PRIEST/Primary Examiner, Art Unit 1681
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