CTFR 17/918,108 CTFR 99612 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. Election/Restriction Applicant’s election without traverse of Group I: claims 41-50, drawn to a living biological system capable of modulatory properties in the reply filed on 08/07/2025 is acknowledged. Claims 51-60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/07/2025. 08-04 AIA Newly submitted claim 61 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 61 is drawn to Group II the nonelected invention, a method of visualizing optical properties of a living biological system . Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 61 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Priority Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional Application 63/008474, filed on 04/10/2020. 02-27 AIA Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/US2021/026920 , filed on 04/12/2021 . 12-151 AIA 26-51 12-51 Status of Claims Claims 41-50 are under examination. Claims 51-58, and 60-61 are withdrawn. Claims 1-40 and 59 are cancelled. Claim Rejections - 35 USC § 112 Rejection to claim 43 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph as failing to comply with the enablement requirement has been withdrawn in view of the applicant’s amendments filed 01/20/2026. Rejections maintained: 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. 07-15-03-aia AIA Claim s 41-44 and 48-50 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Gorodetsky et al. (US 2018/0052137 Al) . Regarding claim 41, Gorodetsky et al. teach a system which includes a living biological cell where reflectin proteins are introduced therefore the system is capable of modulatory optical properties (page 3, paragraph 0025). Gorodetsky et al. teach the reflectin can be introduced to various cell and organism types including human and non-human mammalian cells. Gorodetsky et al. teach introduction of a sequence for expressing a cephalopod reflectin biomolecule to a cell or organism where it would not be native or included in the genome (page 7, paragraph 77). Regarding claim 42, Gorodetsky et al. teach the sequence is for expressing a reflectin biomolecule. Gorodetsky et al. further teach the inclusion of a sequence motif identified as SEQ ID no:1 which is the same as SEQ ID no: 3 of the present application (page 2, paragraph 0012). Regarding claim 43, Gorodetsky et al. teach the protein variants encompass polypeptides that have a sequence identity of at least 60% to a known native PCCP polypeptide sequence (page 2, paragraph 0020). Gorodetsky et al. teach the sequence encoding the protein expressed is for reflectin-like protein A2 GenBank Accession Number ACZ577 65.1, which is SEQ ID no: 6 of the present application (pages 2-3, paragraph 0023). Regarding claim 44, Gorodetsky et al. teach the biological cell comprises a reflectin biomolecule that is expressed from the reflectin sequence (pages 2-3, paragraph 0020-0024). Regarding claim 48, Gorodetsky et al. teach the biological cell of claim 41. Gorodetsky et al. further teach the cell comprises a nucleic acid vector that comprises the sequence for expressing a reflectin biomolecule (pages 2-3, paragraphs 0023-0024). Regarding claim 49, Gorodetsky et al. teach a biological cell where the cell has been modified to include the sequence for expressing a reflectin biomolecule via a transformation vector (pages 2-3, paragraphs 0023-0024). Regarding claim 50, Gorodetsky et al. teach the cell of claim 41 where the cell could be various types including human or non-human mammals (page 7, paragraph 0076) . 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. 07-22-aia AIA Claim s 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Gorodetsky et al. (US 2018/0052137 Al) as applied to claim s 41 and 44 above, and further in view of Parker et al. (WO2014/085641 A1) . Gorodetsky et al. teach a system which includes a living biological cell where reflectin proteins are introduced therefore the system is capable of modulatory optical properties (page 3, paragraph 0025). Gorodetsky et al. teach the reflectin can be introduced to various cell and organism types including human and non-human mammalian cells. Gorodetsky et al. teach introduction of a sequence for expressing a cephalopod reflectin biomolecule to a cell or organism where it would not be native or included in the genome (page 7, paragraph 77). Gorodetsky et al. teach the biological cell comprises a reflectin biomolecule that is expressed from the reflectin sequence (pages 2-3, paragraph 0020-0024). Regarding claim 45, Gorodetsky et al. teach the living biological system where a transgenic biological cell comprises a reflectin biomolecule sequence for and expression of the subsequent protein. Gorodetsky et al. do not teach reflectin biomolecule is characterized by a tunable refractive index. Parker et al. teach the reflectin component is characterized by a tunable refractive index (page 2, lines 17-27). Parker et al. teach that light absorbance and reflection are critical for high performance photonic devices (page 1, lines 22-23). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Gorodetsky et al. for a system which includes a biological cell with expression of a reflectin biomolecule with the teachings of Parker et al. for the reflectin component that is controllable and can modulate the refractive index. Parker et al. provide motivation by teaching modulation of reflectin to provide enhanced coloration and reflectance (page 2, lines 22-24). One of skill in the art would have had a reasonable expectation of success at combining Gorodetsky et al. and Parker et al. because both teach the use of reflectin protein in a non-native environment. Regarding claim 46, Gorodetsky et al. teach the living biological system where a transgenic biological cell comprises a reflectin biomolecule sequence for and expression of the subsequent protein. Gorodetsky et al. do not teach the conformation of the expressed reflectin biomolecule or aggregation of the expressed reflectin biomolecule is controllable such that a refractive index of the biological cell is modulatory. Parker et al. teach the reflectin component is characterized by a tunable refractive index (page 2, lines 17-27). Parker et al. teach recombinant reflectin protein can aggregate to form nanospheres in ionic solutions. Parker et al teach reflectin carries a positive charge under neutral pH, it spontaneously forms hybrid nanostructures with the negatively charged fluorophore to create a pigment granule mimetic (page 9, lines 19-25). It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Gorodetsky et al. for a system comprising a cell with reflectin with the teachings of Parker et al. for modulation of reflectin protein for aggregation of reflectin which modulates the refractive index. Parker et al. provide motivation by teaching modulation of reflectin to provide enhanced coloration and reflectance (page 2, lines 22-24). One of skill in the art would have had a reasonable expectation of success at combining Gorodetsky et al. and Parker et al. because both teach the use of reflectin protein in a non-native environment. Regarding claim 47, Gorodetsky et al. teach the living biological system where a transgenic biological cell comprises a reflectin biomolecule sequence for and expression of the subsequent protein. Gorodetsky et al. do not teach the expressed reflectin biomolecule comprises a protein that is tagged with the reflectin biomolecule. Parker et al. teach pigment structures which include a reflectin protein, a crystalline protein, and a light absorbing material. Parker et al. teach the reflectin and crystalline protein as a fusion protein. Parker et al. teach a tethered network of pigment structures comprising a reflectin fusion protein, a crystalline fusion, and a light absorbing material (page 3, lines 9-30). The fusion protein comprising a crystalline protein and reflectin protein, reads on a reflectin biomolecule tagged with the reflectin protein. It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the teachings of Gorodetsky et al. for expression of a reflectin biomolecule with the teachings of Parker et al. for the reflectin protein fused to a crystalline protein. Parker et al. provide motivation by teaching that the tethered network of pigment structures mimic the optical properties of the pigment granules isolated from the brown chromatophores providing a fluorescent signal visible at various wavelengths (page 3, lines 28-30). One of skill in the art would have had a reasonable expectation of success at combining Gorodetsky et al. and Parker et al. because both teach the use of reflectin protein in a non-native environment . Response to Arguments 07-37 AIA Applicant's arguments filed 01/20/2026 have been fully considered but they are not persuasive. Applicant’s Arguments: Applicant argues Claim 41, recites the following that is not taught or rendered unpatentable by the combination of Gorodetsky et al. and Parker et al.: ° a transgenic biological cell comprising intracellular reflectin biomolecules; and ° an external stimulus in contact with the transgenic biological cell, ° the external stimulus affects conformation and aggregation of the intracellular reflectin biomolecules A skilled artisan reading Gorodetsky et al. and Parker et al. would not find any teaching or suggestion that an external stimulus in contact a transgenic biological cell comprising intracellular reflectin biomolecules, in which the external stimulus affects the conformation and aggregation of the intracellular reflectin biomolecules. Examples of external stimuli are recited within claim 61 (e.g., an electrical stimulus, a chloride salt, an aromatic compound, or an ionic compound). Accordingly, A skilled artisan would not find that Gorodetsky et al., Parker et al., or a combination thereof would have appreciation that intracellular reflectin biomolecules can be affected by external stimulation. Examiner’s Response: Gorodetsky et al. teach PCCP materials and devices such as proton emitters/absorbers or sensors may be used in intracellular implants or probes in living cells (page 7, paragraph 0078). Gorodetsky et al. teach PCCP sensors are used to measure proton fluxes in biological systems, for example in response to developmental events or external stimuli, e.g. the administration of active agents such as agonists or inhibitors of a specific process (page 7, paragraph 0078). The result of the stimulus is not an actionable step in the method and therefore cannot hold patentable weight. Claim 61 has been withdrawn as it depends on a method claim, the method claims were withdrawn as a result of a restriction and will not further be considered as the invention of this application. Conclusion 07-39 AIA 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Catherine L McCormick whose telephone number is (703)756-5659. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 pm. 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, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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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. /C.L.M./Examiner, Art Unit 1638 /Anna Skibinsky/ Primary Examiner, AU 1635 Application/Control Number: 17/918,108 Page 2 Art Unit: 1638 Application/Control Number: 17/918,108 Page 3 Art Unit: 1638 Application/Control Number: 17/918,108 Page 4 Art Unit: 1638 Application/Control Number: 17/918,108 Page 5 Art Unit: 1638 Application/Control Number: 17/918,108 Page 6 Art Unit: 1638 Application/Control Number: 17/918,108 Page 7 Art Unit: 1638 Application/Control Number: 17/918,108 Page 8 Art Unit: 1638 Application/Control Number: 17/918,108 Page 9 Art Unit: 1638 Application/Control Number: 17/918,108 Page 10 Art Unit: 1638 Application/Control Number: 17/918,108 Page 11 Art Unit: 1638
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