DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/1/25 has been entered.
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, 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, 3-4, 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Shah (US 2015/0122647) in view of Alarcon et al. (US 2007/0111196) and Sekisui Diagnostics (Glucose Oxidase L150), and further in view of Simpson et al. (US 2006/0257996).
As to claims 1 and 7, Shah teaches a stabilized medical device comprising a substrate that is at least partially electrically conductive ([0047] – base layer on which is formed a conductive layer); a stabilized enzyme layer disposed over at least a portion of a surface of the substrate ([0007] – enzyme disposed on a polymer selected for its ability to inhibit damage to glucose oxidase by ethylene oxide), the stabilized enzyme layer including: at least one biologically active sensing component ([0007] – glucose oxidase); the biologically active sensing component is configured to sense a level of glucose in a body of a patient ([0022]).
Shah does not necessarily teach that the one stabilizing component is non-covalently combined with the biologically active sensing component, wherein the sensing component has a activity level from about 25-1 million U/cm^3 following ethylene oxide sterilization of the biologically active sensing component, wherein a mass ratio of the stabilizing component to the biologically active sensing component in the stabilized enzyme layer is from about 10 to about 100, and the biologically active sensing component has a biological activity detection level after ethylene oxide sterilization that is within from about 45% to about 95% of a biological activity level before the ethylene oxide sterilization.
However, Shah does teach the use of various materials for the express purpose of inhibiting damage to the enzyme caused by ethylene oxide vapor during a sterilization process ([0009]). Alcoron teaches the sterilization of biosensors in which the stabilizing components are non-covalently immobilized with the enzymes ([0027]). While neither Shah nor Alcoron disclose the biological active level detection level following sterilization, a sales sheet by Sekisui Diagnostics listing out the properties of the glucose oxidase lists its activity as being between 14,500 – 22,000 U/ml (i.e. U/cm^3). Moreover, Alcoron discloses an example of the level of activity preserved with the use of trehalose (Fig. 4), which is far greater than the 99.8% loss in activity level required to get from 14,500 U/ml to 25 U/ml. Accordingly, it would have been obvious to modify Shah with Alcoron and Sekisui to utilize a stabilizing component that is expected to result in a biological activity detection level as recited, if not as an inherent property, then as a result of routine optimization to obtain a device which results in the biologically active sensing component retaining its ability within the recited range. Similarly, Alcoron teaches the use of using various concentrations of trehalose ([0062]). Accordingly, it would have been a matter of routine optimization to utilize a mass ratio within the recited ranges to find the optimum mass ratio which still optimally preserves its functionality within the recited percentile ranges as biologically active sensing components.
The above combination does not teach the substrate comprises electrically conductive ePTFE. Simpson teaches an analyte sensing device in which the substrate comprises ePTFE, which it discloses can be deposited with elastomeric carbon or other electrode material ([0237]). Accordingly, it would have been obvious to modify the above combination with Simpson to utilize a substate that is known to be usable in the measurement of analytes.
As to claims 3-4, it would have been a matter of routine optimization to arrive at the biological activity detection level of the recited ranges to preserve as much of its ability to function as biologically active sensing components.
As to claim 6, Alcoron teaches the use of using various concentrations of trehalose ([0062]). Accordingly, it would have been a matter of routine optimization to utilize a mass ratio within the recited ranges to find the optimum mass ratio which still optimally preserves its functionality as biologically active sensing components.
Response to Arguments
Applicant's arguments filed 4/30/25 have been fully considered but they are not persuasive.
Applicant has argued that the combination will result in neither an activity level of 25-1 million U/cm3, nor would routine optimization result in retention of ability within the recited range. This is not persuasive. As noted within the rejection, for the commercially available glucose oxidase (which has a listed activity level of at least 14,500) to have its activity level fall below 25 U/cm3, it would require a staggering loss of OVER 99.8% in its activity levels. Considering that the protective properties of trehalose for enzymes is well known, it would be unfathomable to even conceive that it would lose over 99.8% of its abilities and still be considered a protectant. Considering that the applicant recites neither the specific type of enzyme, its starting biological activity, a specific stabilizing component, any specifics as to how the incorporation is done structurally, and with ranges that go from 25-1,000,000 U/cm3 -for the activity level and mass ratios as wide as 0.1 to 10,000 simply indicates that the results could be easily derived from routine optimization, if not necessarily an inherent result. In fact, when considering applicant’s own disclosure, which notes that glucose oxidase that was sterilized without trehalose resulted in relative activity of 9.8 and 7.7%, such a reduction from 14,500 over its listed activity level would still place it within the recited range, meaning it would result in said range without even incorporating a stabilizing component at all. Moreover, contrary to applicant’s assertions that the retention of biological activity is “unexpected”, Alcaron already teaches that trehalose is protective against various different types of sterilizations, including irradiation, ultraviolet light, ethylene oxide treatment, superheated steam sterilization, as well as others ([0035]). It’s protective abilities are known elsewhere as well, including being protective against thermal inactivation (Sola-Penna et al.). Similarly, there are other art which teach the use of trehalose in being a protectant during ethylene oxide sterilization including Tautvydas (USP #6,187,555) – col. 7 lines 55-63 and Iwasaki et al. (US 2015/0064228) – [0008]). These results are not unexpected. Accordingly, it would be a routine optimization to obtain a device as recited. The rejections are maintained.
Response to Arguments
Applicant's arguments filed 6/12/25 have been fully considered but they are not persuasive.
Applicant has argued against the use of trehalose resulting in inherently resulting in the sensing component resulting in an activity level from about 25-1 million U/cm^3. As examiner noted, as the enzyme of Sekisui has a starting level of activity between 14,500-22,000 U/ml (i.e. U/cm^3), for it to remain at least above 25 U/cm^3 would mean that it can lose a whopping 99.8%+ percentage in its level of activity and STILL be within the claimed range. The examiner even noted that, going by applicant's own disclosure, doing absolutely NOTHING would still result in relative activity of 9.8% and 7.7% from its starting point, which would still be within the claimed range. In fact, it can even make the deterioration WORSE by more than a magnitude of 10 and STILL result in an activity level within the recited range. And as noted within the prior art combination AND additional references provided by the examiner, trehalose is well known to be a stabilizing molecule. Accordingly, any use of trehalose would thus necessarily and inherently still result in relative activity within the recited range. Furthermore, one of ordinary skill in the art would recognize the importance of maximizing the biological activity detection level post sterilization to retain device functionality, and would thereby be a matter of routine optimization to find a mass ratio which would result in the recited percentile ranges.
In addition, applicant has argued that routine optimization would have resulted in the claimed invention and notes that none of the references provide any guidance on such "optimization" and would not have arrived at the claimed invention absent impermissible degree of hindsight. This is not at all persuasive. Routine optimization within prior art conditions does not require that the references provide "guidance" on the optimization itself. If it did, it would simply be equivalent to teaching the limitations directly. In addition, applicant has failed to provide any showing of the criticality of the range. Of course, that would be rather difficult, as claims don't even recite one specific stabilizing compound, doesn't recite any specific biologically active sensing component at all, recites ratios that can be as wide as a factor of 5, and a loss of detection level of many degrees of differences. There is no demonstration of an "unexpectedly superior results" as asserted by the applicant.
In contrast, the examiner has provided further evidence why the claimed invention is neither obvious nor why the claimed ranges are unexpected, as trehalose has long been known for its protective abilities and its usage in a sterilization setting to stabilize against ethylene oxide sterilization is directly taught by the prior art combination. Getting to the wide ranges recited by the applicant, absent some sort of specific combination of recited stabilizing compound/sensing component/mass ratio to arrive at some actually unexpected specific number of biological activity detection level, is merely an optimization within routine prior art conditions.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTIAN JANG whose telephone number is (571)270-3820. The examiner can normally be reached Monday-Friday (7-3:30 EST).
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CHRISTIAN JANG
Primary Examiner
Art Unit 3791
/CHRISTIAN JANG/ Primary Examiner, Art Unit 3791 10/7/25