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 .
Claims 1, 4, 5, 7, 9-11, 13, 14, 16, 17, 19-23, 26, 28, 31, 33-36, 48, 51, and 84 are pending. Claims 1, 4, 5, 7, 9-11, 13, 14, 16, 17, 19-21, 48, and 51 are withdrawn. Claims 2, 3, 6, 8, 12, 15, 18, 24, 25, 27, 29-30, 32, 37-47, 49, 50, and 52-83 are cancelled. Claims 22, 23, 26, 28, 31, 33-36, and 84 are being prosecuted.
Claim Rejections - 35 USC § 103
2. 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.
3. Claim(s) 22, 23, 26, 28, 31, 33, 36 and 84 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shih et al (US 2010/0068490), in view of Morton et al (US 2017/0017872).
Shih et al teach a biosensor comprising:
a piezoelectric substrate (PMN-PT/Sn piezoelectric microcantilever sensor, par. 51) coated with a metal (PEMS with a nickel and titanium metal layer on one side, par. 51 and PEMS with a tin layer, par. 54);
an anchor substance (bi-functional molecule, par. 35) comprises a spacer (hydrolysable silanol groups, par. 36) and a binding component (organo-functional group, par. 35), wherein the spacer comprises a silane group which forms a covalent bond on the metal to bind the anchor substance directly to a surface of the metal (silanol group reacts with metals to form a covalent bond with the metal, par. 37; MTMS and MPS covalently bond with Ni, Sn, Ti or Cr metal surfaces, par. 45); and
a capture reagent, wherein the anchor substance is coupled with the capture reagent through the binding component (organo-functional group is the binding component and is activated to bind to an organic species, par. 38; the organic species is a protein, par. 48, including an antibody, par. 46-47).
With respect to claim 23, Shih et al. teach the binding component is an antibody binding protein (par. 46-47). With respect to claim 26, Shih et al. teach the binding component comprising an amine or carboxylic acid (bifunctional molecule has a residual group for protein conjugation that includes amine or carboxylic acid, par. 43).
With respect to claim 31, Shih et al. teach the anchor substance forming a layer on the surface of the piezoelectric substrate (the bi-functional molecule forms a layer, par. 34-42).
With respect to claim 33, Shih et al. teach the binding protein of the anchor substance is extended away from the surface of the piezoelectric substrate through the spacer (the antibody layer, 14, is illustrated as extending away from the piezoelectric substrate, 16, Fig. 15).
With respect to claim 36, Shih et al. teach the anchor substance binds to the surface of the piezoelectric substrate through a silane group (anchor binds to the metal coating on the piezoelectric substrate and is therefore considered bound to the piezoelectric substrate, par. 36-37 and 45).
Shih et al. teach a spacer that is 3-mercaptopropyl-trimethoxysilane (par. 45), but fail to teach a polymer spacer/linker, specifically a polyethylene glycol spacer/linker.
Morton et al. teach a biosensor comprising a piezoelectric substrate (par. 14) coated with a hydroxylated interface layer (par. 57) having an anchor substance comprising a spacer covalently attached via a silane group, wherein the spacer is either 3-mercaptopropyltrimethoxysilane or silane conjugated PEG (par. 62) (PEG is a polymer of repeating units of ethylene glycol) and an antibody capture reagent attached to the SAM (par. 64), in order to provide a SAM that binds to a locally patterned interface layer, but does not bind to other adjacent materials (par. 62).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to substitute the 3-mercaptopropyl- trimethoxysilane taught by Shih et al., with a silane conjugated PEG as taught by Morton et al. One having ordinary skill in the art would have been motivated to make such a change as a mere alternative and functionally equivalent spacer since the same expected insulation and attachment of antibody capture reagent would have been obtained. The use of alternative and functionally equivalent techniques would have been desirable to those of ordinary skill in the art based on the economics and availability of components.
4. Claim(s) 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shih et al (US 2010/0068490) and Morton et al (US 2017/0017872), as applied to claim 22, and further in view of Hashimoto et al (US 2004/0013794).
See above for the teachings of Shih et al and Morton et al.
Shih et al teach a piezoelectric substrate made from lead magnesium niobite- lead titanate (PMN-PT) and having a metal coating (par. 14 and 51), but fail to teach the piezoelectric material being one recited in claim 34.
Hashimoto et al. teach a piezoelectric material having a metal coating (par. 14), wherein the piezoelectric layer is either lead magnesium niobite titanate (PMN-PT) or lead zirconate titanate (PZT) (par. 24), in order to provide a piezoelectric material that functions as a sensor (par. 2).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to substitute for the PMN-PT piezoelectric material taught by Shih et al., a lead zirconate titanate as taught by Hashimoto et al. One having ordinary skill in the art would have been motivated to make such a change as a mere alternative and functionally equivalent detection technique and since the same expected piezoelectric function would have been obtained. The use of alternative and functionally equivalent techniques would have been desirable to those of ordinary skill in the art based on the economics and availability of components.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Shih and Hashimoto are similarly drawn to sensors comprising piezoelectric substrates with a metal layer.
5. Claim(s) 22, 23, 28, 31, 33-36, and 84 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rivas et al (US 2017/0117871) in view of Shih et al (US 2010/0068490).
Rivas et al. teach a biosensor component comprising:
a piezoelectric substrate coated with a hydroxylated interface layer (piezoelectric material overlaid with interface layer material, which may comprise a hydroxylated oxide surface, par. 17 and 50; hermeticity layer is optional, par. 13);
an anchor substance (organosilane, par. 45-46) wherein the anchor substance comprises a spacer and a binding component (organosilane, par. 55), the spacer comprises a silane group which forms a covalent bond on the hydroxylated layer to bind the anchor substance directly to a surface of the hydroxylated layer (hydroxylated oxide material layer, par. 50; organosilane SAMs promote surface bonding through silicon- oxygen bonds and therefore binds to the hydroxylated surface via a covalent bond with the silane group, par. 55), and
a capture reagent, wherein the anchor substance is coupled with the capture reagent through the binding component (functionalization material is specific binding material that couples to the SAM anchor substance, par. 45 and 57).
Rivas et al. fail to teach the hydroxylated interface layer being a metal.
Shih et al. teach a piezoelectric substrate comprising a layer comprising a natural oxide surface wherein the layer comprises a metal (par. 45 and 48) that bonds a spacer of an anchor substance directly to the metal surface via covalent bond with a silane group of the spacer (par. 45), in order to provide easy covalent immobilization of receptors for detection (par. 46).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to use as the hydroxylated oxide surface taught by Rivas et al., a metal with a natural oxide surface such as Ti, Ni, Sn and Cr as taught by Shih et al. because Rivas’s teaching that alternative materials incorporating hydroxylated oxide surfaces known in the art is generic with respect to the type of interface layer that can be incorporated into the biosensor. One would be motivated to use the appropriate interface layer for covalent silane attachment of a SAM.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Rivas and Shih are similarly drawn biosensors having a piezoelectric layer coated with a material having a hydroxylated oxide surface that forms a covalent bond with a silanol group of an anchor substance.
With respect to claim 23, Rivas et al. teach the binding component is an antibody (par. 57).
With respect to claim 28, Rivas et al. teach the spacer is polyethylene glycol (par. 55) (Polyethylene glycol is a polymer of repeating units of ethylene glycol).
With respect to claim 31, Rivas et aI. teach the anchor substance forms a self- assembled monolayer on the piezoelectric substrate (par. 50 and 55).
With respect to claim 33, Rivas et al. teach the binding protein of the anchor substance extends away from the surface of the piezoelectric substrate through the spacer (Fig. 7, binding protein is illustrated as extending away from the surface of the piezoelectric substrate).
With respect to claim 34, Rivas et al. teach the piezoelectric substrate is aluminum nitride or zinc oxide (par. 59).
With respect to claim 35, Rivas et al. teach the biosensor further comprising a housing (device included with walls and a cover that are considered a housing, par. 28 and 69, Fig. 7) and a fluidics chamber (52, Fig. 7; par. 69), wherein the surface of the piezoelectric material bearing the anchor substance forms a wall of the chamber (piezoelectric material, 22, coated with interface layer, 34, and anchor substance, 36, form the bottom wall of the chamber, 52 as illustrated in Fig. 7 and described at par. 69).
With respect to claim 36, Rivas et al. teach the anchor substance binds to the interface layer on the surface of the piezoelectric substrate through a silane group (bonding through silicon-oxygen bonds, par. 55).
Response to Arguments
6. Applicant's arguments filed 10/15/25 have been fully considered but they are not persuasive.
a.) In response to the 103 rejection over Shih in view of Morton, Applicants argue that Morton fails to remedy the deficiency in Shih because Morton teaches a “multi-layer acoustic reflector structure and is entirely silent regarding an acoustic wave biosensor component including an anchor substance comprising a spacer and a binding component, wherein the spacer comprises a polymer linker; and a capture reagent, wherein the anchor substance binds the metal coating of the piezoelectric substrate via a covalent bond with the polymer linker let alone a piezoelectric substrate comprising a metal coating. Applicants note that Morton discloses a piezoelectric material (22) overlain by several layers (Figure 3).
Applicant’s arguments have been considered but are not convincing. With respect to Shih, Shih teaches a piezoelectric substrate (16) with a metal coating (18) (Figure 15). The insulation layer (20) on the metal coating comprises a bi-functional molecule that has a silanol group on one end that can form a covalent bond with a metal surface and a hydrophobic group on the other end to couple a capture reagent (a protein or DNA) (paragraphs [0035] to [0043]). Shih teaches the basic structure of the biosensor recited in claim 22. But Shih fails to teach a polymer linker as the bi-functional molecule in insulation layer (22).
Instant claim 22 recites “a piezoelectric substrate comprising a metal coating”. First, given the broadest reasonable interpretation of this limitation and the open “comprising” language, there is no prohibition of additional layers of material being present between the piezoelectric substrate and the metal coating. Thus, the multi-layer structure shown in Figure 3B of Morton where there are multiple layers of material on the piezoelectric substrate is not precluded by the instant claims. Secondly, the interface layer (54) is optional (paragraph [0058]). The hermeticity layer (42) is also optional since Morton teaches that this layer “may be applied” in certain embodiments between the electrode and the optional interface layer (54) (paragraph [0059]). Thus, the electrode (28) supports the SAM layer (56) if there is no interface layer and no hermeticity layer (42). Figure 3B is a specific embodiment of Morton but is not the only embodiment.
b.) In response to the 103 rejection of Rivas in view of Shih, Applicants argue that nowhere does Shih describe or reasonably suggest at least a polymer linker and a capture reagent, wherein the anchor substance binds the metal coating of the piezoelectric substrate via a covalent bond with the polymer linker, as recited by independent claim 22.
Applicant’s argument has been considered but is not convincing. Shih teaches a piezoelectric substrate (16) with a metal coating (18) (Figure 15). The insulation layer (20) on the metal coating comprises a bi-functional molecule that has a silanol group on one end that can form a covalent bond with a metal surface and a hydrophobic group on the other end to couple a capture reagent (a protein or DNA) (paragraphs [0035] to [0043]).
c.) In response to the 103 rejection over Shih in view of Morton and Hashimoto, Applicant’s argue that Hashimoto describes "a method for manufacturing piezoelectric elements used for surface acoustic wave elements" which can include "adjusting the content of the metal particles dispersed in the solvent so as to obtain a metal layer having a desired thickness."
Applicant’s argument has been considered but is not convincing. Hashimoto was relied upon to teach an alternate piezoelectric material, lead zirconium titanate (PZT), to the lead magnesium niobite titanate (PMN-PT) of Shih. Hashimoto teaches that lead zirconium titanate (PZT) and lead magnesium niobite titanate (PMN-PT) are equivalent piezoelectric materials and would be obvious alternate materials in a piezoelectric substrate.
Conclusion
7. THIS ACTION IS MADE FINAL. 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.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L CHIN whose telephone number is (571)272-0815. The examiner can normally be reached Monday - Friday, 10:00am - 6:30pm.
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/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
2/20/2026