CTNF 18/104,599 CTNF 98022 Notice of Pre-AIA or AIA Status 07-03-fti AIA The present application is being examined under the pre-AIA first to invent provisions. 07-30-03-h AIA Claim Interpretation Claim 7 indicates an error in its dependency. For purposes of examination claim 7 will be interpreted as depending from claim 1 below. Claim 20 does not indicate which claim it was intended to depend from For purposes of examination claim 20 will be interpreted as depending from claim 1 below. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claims 7 and 20 are 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. As noted above, the dependencies for claims 7 and 20 are unclear and therefore indefinite. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-fti The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-fti The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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. 07-20-02-fti This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a). 07-21-fti 1. Claim s 1-3, 5-9, 12-14 and 17-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication No. 2009/0127589 to Rothberg et al. (cited by applicant) in view of U.S. Patent Application Publication No. 2005/0075482 to Tanaka et al. (cited by applicant) Rothberg et al. teaches an apparatus for measuring analytes using large scale ISFET arrays with a microwell array (Fig. 28 and paragraph 0239) and further teaches that the well comprises a solid support in the form of a bead, wherein the bead comprise a polyacrylamide (paragraph 0326). Rothberg et al. further teaches a passivation layer 72 that constitutes an ion-sensitive membrane that gives rise to the ion-sensitivity of the device [0008]. The ion-sensitive layer is above the floating gate structure 70 as shown in Fig. 1. It would have been obvious to one of ordinary skill in the art to provide an ion sensitive material layer above the plurality of ISFET sensors in Rothberg et al. so that the ion sensitive material layer forms the bottoms of the wells, thereby allowing ions in solutions in the wells can pass through the ion sensitive material and interact with the ISFET sensors. Rothberg et al. teaches that the well comprises a solid support in the form of a bead, wherein the bead comprise a polyacrylamide (paragraph 0326), but does not teach providing a conformal polymer matrix within the wells. Tanaka et al. teaches that forming polyacrylamide in a microwell array was well known in the art at the time of applicant’s invention. Tanaka teaches forming a polymer gel in an array of wells (i.e., containers) by pouring (i.e., applying) an aqueous liquid containing acrylamide monomer and an initiator into the wells and polymerizing the precursors to the wells to form polyacrylamide. As a result, the polymer matrix will conform to the wells. It would have been obvious to on of ordinary skill in the art to modify Rothberg et al. to provide acrylamide in the wells in the form of a conformal polymer matrix as taught by Tanaka et al. as an alternate manner of providing arylamide in the wells. I.) Regarding applicant’s claim 1, as noted above Rothberg et al. in view of Tanaka et al. teaches all the elements of claim 1. Therefore, Rothberg et al. in view of Tanaka et al. renders claim 1 obvious. II.) Regarding applicant’s claim 2 as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 2 depends. Claim 2 recites that the conformal polymer matrix includes a polyacrylamide matrix. As noted above Rothberg et al. teaches polyacrylamide beads and Tanaka et al. teaches mixing acrylamide and an initiator which would form a conformal polyacrylamide matrix in the wells. Therefore, Rothberg et al. in view of Tanaka et al. renders claim 2 obvious. III.) Regarding applicant’s claim 3, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 3 depends. Claim 3 recites that the polymer matrix is a cured-in-place polymer matrix. Claim 3 recites a product-by-process limitation that does not further limit the structure of the claimed invention. Regardless, Rothberg et al. in view of Tanaka et al. forms the polymer matrix in place in the wells. Therefore, Rothberg et al. in view of Tanaka et al. renders claim 3 obvious. IV.) Regarding applicant’s claim 5, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 5 depends. Claim 5 recites that well has a characteristic diameter in a range of 0.1 micrometers to 2 micrometers. Rothberg teaches that the well (i.e., the chamber) contains one bead per well (paragraph 0058) and bead to well size is in the range of 0.6-0.8 (paragraph 0327), wherein the bead diameter is about 1 to 10 um (paragraph 0326). One having ordinary skill in the art would recognize that the well diameter of 1.6 (assuming bead size of 1 um) Rothberg is within the range of 0.1 micrometers to 2 micrometers (paragraph 0752). Therefore, Rothberg et al. in view of Tanaka et al. renders claim 5 obvious. V.) Regarding applicant’s claim 6, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 6 depends. Claim 6 recites that the well has a thickness in the range of 0.01 micrometers to 10 micrometers. Regarding claim 3, Rothberg teaches that the well has a thickness of 4 um (paragraph 0263), which is in a range of 0.01 micrometers to 10 micrometers. Therefore, Rothberg et al. in view of Tanaka et al. renders claim 6 obvious. VI.) Regarding applicant’s claim 7, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 7 depends. Claim 7 recites that the conformal polymer matrix includes a polymer formed from a radically polymerizable monomer. Tanaka et al. teaches that the polymer precursors include a radically polymerizable monomer acrylamide (paragraph 0117). Therefore, Rothberg et al. in view of Tanaka et al. renders claim 7 obvious. VII.) Regarding applicant’s claim 8, as noted above Rothberg et al. in view of Tanaka et al. renders claim 7 obvious from which claim 8 depends. Claim 8 recites that the radically polymerizable monomer includes a vinyl-based monomer. Tanaka et al. teaches that radically polymerizable monomer includes a vinyl-based monomer (paragraph 0117). Therefore, Rothberg et al. in view of Tanaka et al. renders claim 8 obvious. VIII.) Regarding applicant’s claim 9, as noted above Rothberg et al. in view of Tanaka et al. renders claim 8 obvious from which claim 9 depends. Claim 9 recites that the vinyl-based monomer includes acrylamide, vinyl acetate, hydroxyalkylmethacrylate, variations or derivatives thereof or any combination thereof. Tanaka et al. teaches that the vinyl-based monomer includes acrylamide, hydroxyalkylmethacrylate (paragraph 0117). Therefore, Rothberg et al. in view of Tanaka et al. renders claim 9 obvious. IX.) Regarding applicant’s claim 12, as noted above Rothberg et al. in view of Tanaka et al. renders claim 7 obvious from which claim 12 depends. Claim 12 recites that the polymer is also formed with a crosslinker. Tanaka et al. teaches that the polymer can be formed with a crosslinker. [0074] Therefore, Rothberg et al. in view of Tanaka et al. renders claim 12 obvious. X.) Regarding applicant’s claim 13, as noted above Rothberg et al. in view of Tanaka et al. renders claim 12 obvious from which claim 13 depends. Claim 13 recites that the crosslinker is a bis-acrylamide. Tanaka et al. teaches that the polymer precursors include a bis-acrylamide crosslinker. [0117] Therefore, Rothberg et al. in view of Tanaka et al. renders claim 13 obvious. XI.) Regarding applicant’s claim 14, as noted above Rothberg et al. in view of Tanaka et al. renders claim 7 obvious from which claim 14 depends. Claim 14 recites that the polymer is further formed with a surface active additive. Tanaka et al. teaches that the polymer precursors include a multifunctional monomer which meets the limitation of surface active additive recited in generality. [0118] Therefore, Rothberg et al. in view of Tanaka et al. renders claim 14 obvious. XII.) Regarding applicant’s claim 17, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 17 depends. Claim 17 recites that the sensors of the sensor array comprise ion-sensitive field effect transistors. As noted above, Rothberg et al. teaches ISFET sensors. Therefore, Rothberg et al. in view of Tanaka et al renders claim 17 obvious. XIII.) Regarding applicant’s claim 18, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 18 depends. Claim 18 recites well array is housed within a flow cell. Rothberg et al. teaches providing the well array in a flow cell. (Fig. 8) Therefore, Rothberg et al. in view of Tanaka et al. renders claim 18 obvious. XIV.) Regarding applicant’s claim 19, as noted above Rothberg et al. in view of Tanaka et al. renders claim 18 obvious from which claim 19 depends. Claim 19 recites that the wells of the well array open to an interior of the flow cell. As noted above, Rothberg et al. teaches providing the well array in a flow cell which would require the wells of the well array to open to an interior of the flow cell (Fig. 8). Therefore, Rothberg et al. in view of Tanaka et al. renders claim 19 obvious. XV.) Regarding applicant’s claim 20, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 20 depends. Claim 20 recites that a well of the wells has a volume in a range of 0.05 fL to 10 pL. As noted above, Rothberg et al. teaches that the wells have diameters and thicknesses within applicant’s disclosed ranges. Therefore, the wells are interpreted as have volumes within the range applicant intended to recite in claim 20. Therefore, Rothberg et al. in view of Tanaka renders claim 20 obvious . 07-22-aia AIA 2. Claim s 4 and 15 are rejected under 35 USC 103 as being unpatentable over Rothberg et al. in view of Tanaka et al . as applied to claim s 1 and 7 above and further in view of U.S. Patent Application Publication No. 2003/0064507 to Gallagher et al. (cited by applicant) I.) Regarding applicant’s claim 4, as noted above Rothberg et al. in view of Tanaka et al. renders claim 1 obvious from which claim 4 depends. Claim 4 recites that the conformal polymer is conjugated to an oligonucleotide. Rothberg et al. in view of Tanaka et al. does not teach that the conformal polymer is conjugated to an oligonucleotide. Gallagher et al. teaches preparing polyacrylamide to bind oligonucleotide or nucleic acid or other ligands in three dimensional manner to thereby increasing the sensitivity of the target detection. It would have been obvious to one of ordinary skill in the art to modify Rothberg et al. in view of Tanaka et al. to conjugated the conformal polymer to an oligonucleotide as taught by Gallagher et al. to increase sensitivity of target detection. Therefore, Rothberg et al. in view of Tanaka et al. and Gallagher et al. renders claim 4 obvious. II.) Regarding applicant’s claim 15, as noted above Rothberg et al. in view of Tanaka et al. renders claim 7 obvious from which claim 15 depends. Claim 15 recites that the monomer includes an oligonucleotide functionalized acrylamide. Rothberg et al. in view of Tanaka et al. does not teach that monomer includes an oligonucleotide functionalized acrylamide. As noted above, Gallagher et al. teaches preparing polyacrylamide to bind oligonucleotide or nucleic acid or other ligands in three dimensional manner to thereby increasing the sensitivity of the target detection. It would have been obvious to one of ordinary skill in the art to modify Rothberg et al. in view of Tanaka et al. to include a monomer having an oligonucleotide functionalized acrylamide based on Gallagher et al. teaching that the use of oligonucleotide can increase sensitivity of target detection. Therefore, Rothberg et al. in view of Tanaka et al. and Gallagher et al. renders claim 15 obvious . 07-22-aia AIA 3. Claim 10 is rejected under 35 USC 103 as being unpatentable over Rothberg et al. in view of Tanaka et al . as applied to claim 9 above and further in view of U.S. Patent Application Publication No. 2013/0210991 to Fonnum et al . I.) Regarding applicant’s claim 10, as noted above Rothberg et al. in view of Tanaka et al. renders claim 9 obvious form which claim 10 depends. Claim 10 recites that the acrylamide includes hydroxyalkylacrylamide. Rothberg et al in view of Tanaka et al. does not teach that the acrylamide includes hydroxyalkylacrylamide. Fonnum et al. teaches polymerization of polyacrylamide and that the acrylamide can be hydroxyalkylmethacrylate or a hydroxyalkyl acrylamide. [0043] It would have been obvious to one of ordinary skill in the art to include hydroxyalkyl acrylamide in the acrylamide as taught by Fonnum et al. Therefore, Rothberg et al. in view of Tanaka et al. and Fonnum et al. renders claim 10 obvious. 4. Claims 11 and 16 are rejected under 35 USC 103 as being obvious over Rothberg et al. and Tanaka et al. as applied to claims 7 and 9 above and further in view of U.S. Patent Application Publication No. 2013/0116153 to Bowen et al. (cited by applicant) I.) Regarding applicant’s claim 11, as noted above Rothberg et al. in view of Tanaka et al. renders obvious claim 9 from which claim 11 depends. Claim 11 recites that the acrylamide includes a bromine functionalized acrylamide. Rothberg et al. in view of Tanaka et al. does not teach that the acrylamide includes a bromine functionalized acrylamide. Bowen et al. teaches that silane-free acrylamide polymer may be formed by polymerization of silane free acrylamide and N-(S bromoacetamidylpentyl) acrylamide (BRAPA). [0081] It would have been obvious to one of ordinary skill in the art to modify Rothberg et al. in view of Tanaka et al to include a bromine functionalized acrylamide as taught by Bowen et al. Therefore, Rothberg et al. in view of Tanaka et al. and Bowen et al renders claim 11 obvious. II.) Regarding applicant’s claim 16, as noted above Rothberg et al. in view of Tanaka et al. renders obvious claim 7 from which claim 16 depends. Claim 16 recites that the monomer includes N-(5- bromoacetamidylpentyl)acrylamide. Rothberg et al. in view of Tanaka et al. does not teach that the acrylamide includes a bromine functionalized acrylamide. Bowen et al. teaches that silane-free acrylamide polymer may be formed by polymerization of silane free acrylamide and N-(S bromoacetamidylpentyl) acrylamide (BRAPA). [0081] It would have been obvious to one of ordinary skill in the art to modify Rothberg et al. in view of Tanaka et al to include a bromine functionalized acrylamide as taught by Bowen et al. Therefore, Rothberg et al. in view of Tanaka et al. and Bowen et al renders claim 16 obvious. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL S. GZYBOWSKI whose telephone number is (571)270-3487. The examiner can normally be reached M-F 8:30-5:00. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /M.S.G./Examiner, Art Unit 1798 /CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798 Application/Control Number: 18/104,599 Page 2 Art Unit: 1798 Application/Control Number: 18/104,599 Page 3 Art Unit: 1798 Application/Control Number: 18/104,599 Page 4 Art Unit: 1798 Application/Control Number: 18/104,599 Page 5 Art Unit: 1798 Application/Control Number: 18/104,599 Page 6 Art Unit: 1798 Application/Control Number: 18/104,599 Page 7 Art Unit: 1798 Application/Control Number: 18/104,599 Page 8 Art Unit: 1798 Application/Control Number: 18/104,599 Page 9 Art Unit: 1798 Application/Control Number: 18/104,599 Page 10 Art Unit: 1798 Application/Control Number: 18/104,599 Page 11 Art Unit: 1798 Application/Control Number: 18/104,599 Page 12 Art Unit: 1798