CTFR 18/041,842 CTFR 99556 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. This action is in response to the amendment filed 02/17/2026, in which claims 1-4, 10 and 20 were amended, claims 5-9, 11 and 12 were previously presented and claims 13-19 were withdrawn due to a restriction election set forth in a previous Office Action. Claims 1-12 and 20 are currently pending. Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the reasons that follow. Any rejection and objections not reiterated in this action have been withdrawn. This action is FINAL. Claim Rejections - 35 USC § 102 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. 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. 07-15 AIA Claim 20 is rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Mason et al ( Nucleic Acids Research , Volume 16, Issue 14, 25 July 1988, Pages 6567–6583). This is a NEW Rejection, necessitated by the amendment filed on 02/17/2026 . Regarding claim 20, Mason teaches a plurality of genetically-modified Bacillus subtilis , wherein each genetically-modified Bacillus subtilis of the plurality comprises a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity (Page 6569, 1 st paragraph and last paragraph bridging Page 6570, 1 st paragraph). Response to Amendments - Claim Rejections - 35 USC § 102 The previous rejection of claim 20 under 35 U.S.C. 102(a)(1)/(a)(2) has been withdrawn in view of the amendments to the claims filed on 02/17/2026 . 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-aia AIA 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. 07-23-aia AIA 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. 07-21-aia AIA Claim s 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Bommarito et al (US 2019/0255208 A1) in view of Mason et al ( Nucleic Acids Research , Volume 16, Issue 14, 25 July 1988, Pages 6567–6583). This is a NEW Rejection, necessitated by the amendment filed on 02/17/2026 . Regarding claims 1 and 8, Bommarito teaches a microbial indicator device for liquid disinfection, comprising: a first housing comprising: a first cavity; a source of biological activity, wherein the source of biological activity is fluidically coupled to the first cavity via a portion of a first fluidic path (Claim 1). Bommarito teaches the microbial indictor device comprises a plurality of biological indictors (such as a species of test microorganisms) that are capable of producing biological activity such as microbial spores [0063]. Bommarito teaches the use of liquid nutrient medium which includes the enzyme substrate in order for visual indication that the spores, and thus microorgansims, are still present [0054 and 0058]. Bommarito teaches the user would activate the source of biological activity by breaking a frangible vial containing nutrient media allowing media to enter the chamber holding the indicator [0145]. Bommarito teaches β-Glucosidase catalyzes the breakdown of the β-glucosidic linkage in the fluorogenic substrate, β-4-methylumbelliferyl-beta-D-glucuronide, to release its component moieties glucose and the fluorescent compound 4-methylumbelliferone wherein this enzyme can then be measured as an increase in fluorescence over time from germinated spore suspensions [0073]. Bommarito teaches that depending on the effectiveness of the reprocessing system's disinfection cycle, a response would then be detected at a determined time point to establish if the cycle had passed or failed [0145]. Bommarito teaches the use of either Geobacillus or Bacillus microorganisms for the use as a biological indicator [0072]. Bommarito does not explicitly teach wherein the genetically-modified test microorganism comprises a functional fusion gene that encodes a non-naturally occurring chimeric protein, the chimeric protein comprising a first segment and a second segment that is contiguous with the first segment; wherein the first segment comprises at least a portion of a first polypeptide selected from the group consisting of a small acid-soluble spore protein, and a sporulation-associated GTP-binding protein; wherein the second segment comprises a second polypeptide having a detectable enzymatic activity. Mason teaches a plurality of genetically-modified Bacillus subtilis , wherein each genetically-modified Bacillus subtilis of the plurality comprises a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity (Page 6569, 1 st paragraph and last paragraph bridging Page 6570, 1 st paragraph). Mason teaches While different ssp-LacZ fusion mRNAs gave different rates of beta-galactosidase accumulation, for at least two of the ssp-LacZ fusions (sspA and sspE) gene dosage experiments indicated that the rates of bgalactosidase accumulation from these fusions were directly proportional to the level of LacZ mRNA over at least a 10-fold range (Page 6581, 2 nd Paragraph). Therefore, detection of LacZ (via Beta-galactosidase accumulation) shows the presence of the small acid-soluble spore protein. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bommarito to include the fusion gene that encodes a non-naturally occurring chimeric protein, wherein the first segment comprises at least a portion of a first polypeptide that is a small acid-soluble spore protein and the second segment comprises a second polypeptide having a detectable enzymatic activity as taught by Mason because Bommarito teaches it is within the ordinary skill in the art to use an article for assessing efficacy of a sterilization process comprising a housing having at least one wall that forms an opening into a compartment; a plurality of genetically-modified test microorganisms disposed in the housing, each genetically-modified test microorganism of the plurality comprising a spore-forming genetically-modified test microorganism; a liquid medium disposed in an openable container that is disposed in or attached to the housing; and an enzyme substrate capable of reacting with the detectable enzyme activity to form a detectable product, the enzyme substrate being disposed in the housing or in the openable container and Kim teaches the a plurality of genetically-modified Bacillus subtilis comprising a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity. One would have been motivated to make such a modification in order to receive the expected benefit of detection of the plurality of genetically modified Bacillus subtilis producing small acid-soluble spore protein using LacZ as taught by Mason. Regarding claims 2 and 3, Bommarito does not teach wherein the first polypeptide is selected from the group consisting of a small acid-soluble spore protein and a sporulation- associated GTP-binding protein or specifically, Bommarito does not teach wherein the first polypeptide is encoded by a gene selected from the group consisting of sspL, sspA, sspB, sspD, and sspE. Mason teaches a plurality of genetically-modified Bacillus subtilis , wherein each genetically-modified Bacillus subtilis of the plurality comprises a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity (Page 6569, 1 st paragraph and last paragraph bridging Page 6570, 1 st paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bommarito to include the fusion gene that encodes a non-naturally occurring chimeric protein, wherein the first segment comprises at least a portion of a first polypeptide that is a small acid-soluble spore protein and the second segment comprises a second polypeptide having a detectable enzymatic activity as taught by Mason because Bommarito teaches it is within the ordinary skill in the art to use an article for assessing efficacy of a sterilization process comprising a housing having at least one wall that forms an opening into a compartment; a plurality of genetically-modified test microorganisms disposed in the housing, each genetically-modified test microorganism of the plurality comprising a spore-forming genetically-modified test microorganism; a liquid medium disposed in an openable container that is disposed in or attached to the housing; and an enzyme substrate capable of reacting with the detectable enzyme activity to form a detectable product, the enzyme substrate being disposed in the housing or in the openable container and Kim teaches the a plurality of genetically-modified Bacillus subtilis comprising a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity. One would have been motivated to make such a modification in order to receive the expected benefit of detection of the plurality of genetically modified Bacillus subtilis producing small acid-soluble spore protein using LacZ as taught by Mason. Regarding claims 4 and 5, Bommarito does not teach wherein the second polypeptide has an enzyme activity selected from the group consisting of an esterase, a lipase, a glycosidase, an aminopeptidase, and a phosphatase, and a luciferase and specifically, Palmer does not teach wherein the second polypeptide has an enzyme activity selected from the group consisting of b-D-galactosidase; b-D-glucosidase; a-D-glucosidase; alkaline phosphatase; acid phosphatase; butyrate esterase; caprylate esterase; chloramphenicol acetytransferase; catechol-2,3-dioxygenase; myristate lipase; leucine aminopeptidase; valine aminopeptidase; chymotrypsin; phosphohydrolase; a-D-galactosidase; a-L-arabinofuranosidase; N-acetyl-b-glucosaminidase; b-D-cellobiosidase; alanine aminopeptidase; proline aminopeptidase; tyrosine aminopeptidase; phenylalanine aminopeptidase; b-D-glucuronidase, and fatty acid esterase. Mason teaches a plurality of genetically-modified Bacillus subtilis , wherein each genetically-modified Bacillus subtilis of the plurality comprises a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity (Page 6569, 1 st paragraph and last paragraph bridging Page 6570, 1 st paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bommarito to include the fusion gene that encodes a non-naturally occurring chimeric protein, wherein the first segment comprises at least a portion of a first polypeptide that is a small acid-soluble spore protein and the second segment comprises a second polypeptide having a detectable enzymatic activity as taught by Mason because Bommarito teaches it is within the ordinary skill in the art to use an article for assessing efficacy of a sterilization process comprising a housing having at least one wall that forms an opening into a compartment; a plurality of genetically-modified test microorganisms disposed in the housing, each genetically-modified test microorganism of the plurality comprising a spore-forming genetically-modified test microorganism; a liquid medium disposed in an openable container that is disposed in or attached to the housing; and an enzyme substrate capable of reacting with the detectable enzyme activity to form a detectable product, the enzyme substrate being disposed in the housing or in the openable container and Kim teaches the a plurality of genetically-modified Bacillus subtilis comprising a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity. One would have been motivated to make such a modification in order to receive the expected benefit of detection of the plurality of genetically modified Bacillus subtilis producing small acid-soluble spore protein using LacZ as taught by Mason. Regarding claims 6 and 7, Bommarito does not teach wherein the first segment comprises an N-terminal region of the first polypeptide and wherein the functional fusion gene includes at least one regulatory sequence that controls expression of the first polypeptide. Mason teaches a plurality of genetically-modified Bacillus subtilis , wherein each genetically-modified Bacillus subtilis of the plurality comprises a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity (Page 6569, 1 st paragraph and last paragraph bridging Page 6570, 1 st paragraph). Mason teaches the fragments of the sspA, B and E genes were cloned in plasmid pT7-1 which has a T7 RNA polymerase promoter just prior to the cloning sites (Page 6569, 1 st Paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bommarito to include the fusion gene that encodes a non-naturally occurring chimeric protein, wherein the first segment comprises an N-terminal region of the first polypeptide and wherein the functional fusion gene includes at least one regulatory sequence that controls expression of the first polypeptide as taught by Mason because Bommarito teaches it is within the ordinary skill in the art to use an article for assessing efficacy of a sterilization process comprising a housing having at least one wall that forms an opening into a compartment; a plurality of genetically-modified test microorganisms disposed in the housing, each genetically-modified test microorganism of the plurality comprising a spore-forming genetically-modified test microorganism; a liquid medium disposed in an openable container that is disposed in or attached to the housing; and an enzyme substrate capable of reacting with the detectable enzyme activity to form a detectable product, the enzyme substrate being disposed in the housing or in the openable container and Kim teaches the a plurality of genetically-modified Bacillus subtilis comprising a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity. One would have been motivated to make such a modification in order to receive the expected benefit of detection of the plurality of genetically modified Bacillus subtilis producing small acid-soluble spore protein using LacZ as taught by Mason. Regarding claim 9, Bommarito teaches the use of liquid nutrient medium which includes the enzyme substrate in order for visual indication that the spores, and thus microorgansims, are still present [0054 and 0058]. Regarding claim 10, Bommarito does not teach wherein the at least the portion of the first polypeptide that is normally found in spores comprises a section of the first polypeptide that constitutes not less than 1% of the amino acid residues of the first polypeptide. Mason teaches the cloned fragments all contained the amino-terminal part of the ssp gene coding sequence and 150 to 650 nucleotides of upstream sequence (Page 6569, 1 st paragraph). Therefore, the entire wild-type sspA, sspB and sspE sequence would be present. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bommarito to include the fusion gene that encodes a non-naturally occurring chimeric proteinwherein the at least the portion of the first polypeptide that is normally found in spores comprises a section of the first polypeptide that constitutes not less than 1% of the amino acid residues of the first polypeptide as taught by Mason because Bommarito teaches it is within the ordinary skill in the art to use an article for assessing efficacy of a sterilization process comprising a housing having at least one wall that forms an opening into a compartment; a plurality of genetically-modified test microorganisms disposed in the housing, each genetically-modified test microorganism of the plurality comprising a spore-forming genetically-modified test microorganism; a liquid medium disposed in an openable container that is disposed in or attached to the housing; and an enzyme substrate capable of reacting with the detectable enzyme activity to form a detectable product, the enzyme substrate being disposed in the housing or in the openable container and Kim teaches the a plurality of genetically-modified Bacillus subtilis comprising a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity. One would have been motivated to make such a modification in order to receive the expected benefit of detection of the plurality of genetically modified Bacillus subtilis producing small acid-soluble spore protein using LacZ as taught by Mason. Regarding claims 11 and 12, Bommarito does not teach wherein the fusion gene is disposed in the genetically-modified test microorganism in an extrachromosomal replicon and wherein the fusion gene is disposed in the genetically-modified test microorganism in a chromosomal replicon. Mason teaches the sspA, B and E-Lacz gene fusion derivatives were constructed into the plasmid pJF751, where their integration into the B. subtilis chromosome and the amplification of these fusions is determined by copy number (Page 6569, Paragraph 1). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bommarito to include the fusion gene that encodes a non-naturally occurring chimeric protein wherein the fusion gene is disposed in the genetically-modified test microorganism in an extrachromosomal replicon and wherein the fusion gene is disposed in the genetically-modified test microorganism in a chromosomal replicon as taught by Mason because Bommarito teaches it is within the ordinary skill in the art to use an article for assessing efficacy of a sterilization process comprising a housing having at least one wall that forms an opening into a compartment; a plurality of genetically-modified test microorganisms disposed in the housing, each genetically-modified test microorganism of the plurality comprising a spore-forming genetically-modified test microorganism; a liquid medium disposed in an openable container that is disposed in or attached to the housing; and an enzyme substrate capable of reacting with the detectable enzyme activity to form a detectable product, the enzyme substrate being disposed in the housing or in the openable container and Kim teaches the a plurality of genetically-modified Bacillus subtilis comprising a functional fusion gene comprising either the sspA, sspB or sspE gene fused to a LacZ gene and an enzyme substrate, such as MgCl2 and NaN3, for the detectable enzyme activity. One would have been motivated to make such a modification in order to receive the expected benefit of detection of the plurality of genetically modified Bacillus subtilis producing small acid-soluble spore protein using LacZ as taught by Mason. Response to Arguments - Claim Rejections - 35 USC § 103 The previous rejection of claims 1-12 under 35 U.S.C. 103 has been withdrawn in view of Applicant’s amendments to the claims filed on 02/17/2026. Conclusion 07-40 AIA 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 ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST. 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, JENNIFER A DUNSTON can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637 /CELINE X QIAN/Primary Examiner, Art Unit 1637 Application/Control Number: 18/041,842 Page 2 Art Unit: 1637 Application/Control Number: 18/041,842 Page 3 Art Unit: 1637 Application/Control Number: 18/041,842 Page 4 Art Unit: 1637 Application/Control Number: 18/041,842 Page 5 Art Unit: 1637 Application/Control Number: 18/041,842 Page 6 Art Unit: 1637 Application/Control Number: 18/041,842 Page 7 Art Unit: 1637 Application/Control Number: 18/041,842 Page 8 Art Unit: 1637 Application/Control Number: 18/041,842 Page 9 Art Unit: 1637 Application/Control Number: 18/041,842 Page 10 Art Unit: 1637 Application/Control Number: 18/041,842 Page 11 Art Unit: 1637 Application/Control Number: 18/041,842 Page 12 Art Unit: 1637 Application/Control Number: 18/041,842 Page 13 Art Unit: 1637 Application/Control Number: 18/041,842 Page 14 Art Unit: 1637
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