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 .
Election/Restrictions
Applicant’s election of Group I (claims 1-10) and the species of biotinylated anti-Tau antibody, in the reply filed on 2 October 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claim Objections
Claim1 is objected to because of the following informalities: Line 10 of the claim says “wherein the biotinylated probed in the …”. Thus, this should be “probe”. Appropriate correction is required.
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.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al., Sensors, 12:11239-11248, 2012; taken with Kim et al., Nature Communications, 11:119, 2020; and Biernat et al., EMBO, 11(4): 1593-1597, 1992; as evidenced by the RayBiotech, catalog brochure for anti-Tau antibody, biotinylated.
Regarding claim 1, the Kim prior art discloses a method comprising using a field-effect transistor (FET). Specifically, the authors create these transistor devices by contacting substrates with a biotinylated F8T2 polymer dissolved in the organic solvent p-xylene (0.04 wt.%) (pg. 11241, bullet 2.3). This teaches, “coating a chip with a first solution of biotin to form a biotin-coated chip”, as recited by the claim. Figure 2 of the reference depicts the standard FET structure with embedded source (S), drain (D), and gate (G) metalized contact terminals. The prior art further teaches, contacting this biotin-coated chip with an avidin solution (pg. 11241, bullet 2.3) and assessing the electric properties of the biotinylated F8T2 TFTs before and after exposure to solutions containing avidin (pg. 11242, bullet 2.4). The prior art teaches the concentration of avidin aqueous solution was 8 x 10-7 M (pg. 11243, bullet 3.2), which equates to 0.0000544 g/mL avidin (molecular weight 68,000 kDa).
Regarding claim 2, the Kim prior art teaches a field-effect transistor (FET) (Figure 2). As defined in the art, EGFET devices are FET structures in which the gate is connected to a separate sensing interface comprising a sensing film combined with a sensing layer and analyte solution. This is fulfilled by the biotinylation of the polymer surface (“sensing layer”) and treatment with the avidin solution, which form a biosensor. The Kim prior art discloses this biosensor demonstrates “a selective decrease in the conductivity of the transistor” and “Changes to the optical properties of this polymer…through the change of the UV-florescence color before and after treatment with avidin” (pg. 11246, at bullet 4). Therefore, the device of the Kim prior art provides two types of signal responses – conductance and optical property. This teaches the EGFET biosensor requirement of the instant claim.
Regarding the specific g/mL concentrations of instant claims 1-9, the Kim prior art fails to teach: the biotin in the first solution is in a first concentration ranging from 0.1 to 1 g/ml; the avidin in the second solution is in a second concentration ranging from 0.1 to 100 g/ml; and biotinylated probe in the third solution is in a third concentration ranging from 1 to 3 g/ml (claim 1); the biotin in the first solution is in the first concentration of 0.1 g/ml (claim 3); wherein the avidin in the second solution is in the second concentration of 30 g/ml (claim 4); wherein the biotinylated probed in the third solution is in third the concentration of 1 g/ml (claim 5); the biotin in the first solution is in the first concentration of 1 g/ml (claim 6); wherein the avidin in the second solution is in the second concentration of 100 g/ml (claim 7); wherein the biotinylated probed in the third solution is in the third concentration of 1 g/ml (claim 8); a ratio of the first concentration, the second concentration and the third concentration is 1:300:10 (claim 9).
The prior art differs from the claimed invention only with respect to concentration. The Court has stated that, generally, such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421.
MPEP 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because, for example, the specification discloses avidin over the range from 1 ng/mL to 30 µg/mL (Figure 5A). Therefore, the specification does not demonstrate that, for example, avidin at a concentration between 1 to 3 g/mL is critical for the invention.
Regarding Claim 10, the Kim (2012) prior art fully discloses use of their transistor device as a biosensor, and “make possible the real time monitoring of sensing materials in fluids” (pg. 11246, first paragraph). The Kim et al. prior art, however, fails to disclose the method further comprising “providing the avidin/biotin-coated chip with a third solution of a biotinylated probe to form the biochip, wherein the biotinylated probed in the third solution is in a third concentration ranging from 1 to 3 g/ml”.
These deficiencies are remedied by the Kim et al. Nature Communications, 2020 prior art taken with the Biernat prior art, as evidenced by the RayBiotech brochure that cites the Biernat reference.
The Kim (2020) prior art discloses methods comprising a multiplex sensing method for Alzheimer’s disease biomarkers. The reference teaches an array device “modified by different antibodies specific for t-tau, p-tau181, Aβ42, and Aβ40” (pg. 4, second column, section titled Multiplex sensing…”). Specifically, Kim et al. 2020 teach AD patients have higher levels of t-tau (Fig. 3C) and p-tau (Fig. 3D). It does not disclose contacting the array with the biotinylated anti-Tau antibody of instant claim 10, however, the Biernat reference discloses this antibody was commercially available in the art prior to filing, as evidenced by the RayBiotech brochure that cites Biernat.
A person having ordinary skill in the art, before the filing date of the application, would have been motivated to use the biotinylated anti-Tau antibody of the Biernat prior art in combination with the avidin/biotin coated chip element of the Kim (2012) prior art according to the known methods disclosed in the Kim et al. 2020 prior art. Motivation to use this specific antibody is explicit within the Biernat prior art wherein it states: “We consider AT8 superior to most other antibodies as a diagnostic tool: it recognizes all tau isoforms prepared from PHFs, but none of the isoforms from normal mammalian brain (human, porcine or bovine) in their mixed state of phosphorylation, nor any of the engineered tau constructs. However, all of these isoforms are recognized after phosphorylation with a kinase activity from brain. Thus the antibody is more specific for the Alzheimer state” (pg. 1596, Discussion, third paragraph). A person having ordinary skill would recognize this biotinylated antibody would strongly bind the avidin-coated biosensor disclosed in Kim 2012.
In KSR International Co. v. Teleflex, Inc., the Supreme Court has stated that combining prior art elements according to known methods to yield predictable results is prima facie obvious if the following rationale can be applied:
(1) the prior art includes each element claimed though not necessarily in the same reference.
(2) it was within the technical grasp of one of ordinary skill in the art to combine the elements as claimed by known methods, and that in combination, each element merely would have performed the same function as it did separately.
(3) one of ordinary skill in the art would have recognized that the results of such combination were predictable.
(KSR International Co. v. Teleflex, Inc. 127 S. Ct. 1727, 82 USPQ2d 1385, Supreme Court, April 30, 2007).
One of ordinary skill in the art would recognize the use of the Biernat antibody in combination with device of Kim (2012) according to the known methods disclosed in Kim (2020). Based on the guidance and direction within the prior art, such combination would have been well within the technical grasp of a skilled artisan. Since each of the elements in combination are merely performing the same function as they did separately, then one of ordinary skill in the art would have been able to predictably combine the elements , according to known methods, with a reasonable expectation of success.
Therefore, the invention as a whole is prima facie obvious, if not actually anticipated by the references.
Conclusion
No claim is allowed.
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/STACEY N MACFARLANE/ Examiner, Art Unit 1675
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