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 .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
Applicant's submission filed on 04/15/2026 has been entered. Claims 1-7, 10-12, and 14-23 are pending. Claims 1-3 and 20-23 are under consideration. Claims 4-7, 10-12, and 14-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Withdrawn Objections and/or Rejections
The rejection of claims 1-3 and 8-9 under 35 U.S.C. 102 (a)(1) as being anticipated by Touhara et al. (Proc. Natl. Acad. Sci. USA 96:4040-4045, 1999) is withdrawn in view of amended claims.
The rejection of claim 24 under 35 U.S.C. 103(a) as being unpatentable over Touhara et al. (Proc. Natl. Acad. Sci. USA 96:4040-4045, 1999) as applied to claims 1-3 and 8-9 above, and further in view of Oh et al. (Biosensors and Bioelectronics 53:18-25, 2014), Zhang et al. (Langmuir 23 (9):4728–4731, 2003), Shirokova et al. (J. Biol. Chem. 280(12):11807-11815, 2005), and Nache et al. (Scientific Reports Vol. 6, Article number 29378, pages 1-11, 2016) is made moot by cancellation of the claim.
Claim Rejections under 35 USC § 103(a)
(i). The following is a quotation of 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 though the invention is not identically disclosed or described as set forth in section 102 of this title, 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 negatived by the manner in which the invention was made.
(ii). Claims 1-3 and 23 are rejected under 35 U.S.C. 103(a) as being unpatentable over Oh et al. (Biosensors and Bioelectronics 53:18-25, 2014) in view of Touhara et al. (Proc. Natl. Acad. Sci. USA 96:4040-4045, 1999).
Oh et al. teach a method of odorant screening using a microwell cell array comprising a substrate, a PEGDA (hydrophilic) coating film on the substrate, wherein the PEGDA coating film has a plurality of through-holes, and a nucleic acid encoding for an olfactory receptor that is in contact with the substrate in the interior of the through-holes (see, e.g., Abstract; Figure 1). Oh et al. teach introducing a nucleic acid encoding an identified olfactory receptor into a plurality of HEK293-12CREs cells to transiently express the olfactory receptor in each well. The cells in each well transiently express one type of olfactory receptor and the olfactory receptors differ among the wells (see, e.g., page 23, left column, the 2nd paragraph; Fig. 4).
Specifically, HEK293-12CREs cells were reversely transfected with four different olfactory receptors, hOR3A1, hOR1A1, hOR1D2, and hOR1G1, which are known to specifically bind to helional, β-citronellol, bourgeonal, and geraniol, respectively. Each odorant (500 mM) with 100 mM IBMX and 1mM Shield-1 was added to the transfected HEK293-12CRE cells, and the odorant response was detected by fluorescence microscopy after one day incubation. The negative control was the transfected HEK293-12CRE cells that were not treated with odorant but only with the same concentrations of IBMX andShield-1. The negative control produced extremely low fluorescence, which was considered a negligible background signal. The response of the cells expressing each OR against its ligand. When the cells were stimulated with 500 mM helional, cells expressing hOR3A1 produced the highest fluorescence, whereas cells expressing other receptors showed relatively low fluorescence. Similarly, when the cells were stimulated with 500 mM β-citronellol, bourgeonal, or geraniol, respectively, the cells expressing each counterpart OR showed the highest fluorescence intensity (page 23, left column, the 2nd paragraph; Fig. 5).
Oh et al. do not explicitly teach measuring the amount of ions taken into each of the cells when the test substance is brought into contact with a plurality of eukaryotic cells expressing the olfactory receptor or when the same cells are depolarized.
Touhara et al. teach a method of measuring an increase in intracellular Ca2+ level in response to an odorant stimulation or HK (high KCl buffer), which depolarized the cells (Fig. 1 and legend to Fig. 1). Tissue-printed olfactory neurons comprising olfactory receptor MOR23 from mouse olfactory epithelium were subjected to fura-2 based Ca2+ imaging, and sequential applications of various odorants by use of the recording chamber (see Fig. 1) allowed identification of cells responding to certain odorant (Fig. 1). Touhara et al. also measured the odorant responses at a single cell level using MOR23 adenovirus-infected fluorescent cells isolated by the tissue printing method from the GFP-fluorescent epithelium (Figs. 2-5).
It would have been obvious for one skilled in the art to modify the method of Oh et al. to measure the amount of ions taken into each of the cells when the test substance is brought into contact with a plurality of eukaryotic cells expressing the olfactory receptor or when the same cells are depolarized with a reasonable expectation of success. One would have been motivated to do so because such a technique of measuring the amount of ions is well-known in the art and routinely practiced in the field of odorant screening method as taught by Touhara et al.
(iii). Claims 20-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Oh et al. (Biosensors and Bioelectronics 53:18-25, 2014) in view of Touhara et al. (Proc. Natl. Acad. Sci. USA 96:4040-4045, 1999) as applied to claims 1-3 and 23 above, and further in view of Shirokova et al. (J. Biol. Chem. 280(12):11807-11815, 2005), and Nache et al. (Scientific Reports Vol. 6, Article number 29378, pages 1-11, 2016).
Oh et al. and Touhara et al. in combination teach a method for calculating an activation degree of olfactory receptors by a test substance as applied to claims 1-3 and 23 above.
Oh et al. and Touhara et al. do not teach the limitations of claims 20-22.
Shirokova et al. teach HeLa cells expressing CNGA2 and Gαolf (GNAL) and the use of the cells for high-through screening (Abstract; page 11808, last paragraph of left column).
Nache et al. teach that olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b, which form a tetramer in CNG channels and are important for signaling in the olfactory system (see, e.g., Abstract, and Figure 1).
It would have been obvious for one skilled in the art to use HeLa cells expressing CNGA2, Gαolf (GNAL), CNGA4, and CNGB1b for odorant screening with a reasonable expectation of success. One would have been motivated to do so because eukaryotic cells, such as HeLa cells expressing CNGA2, Gαolf (GNAL), CNGA4, and CNGB1b may be used for high-through screening as taught by Shirokova et al. above.
(iii). Response to Applicant’s argument
Applicant argues that the claimed invention stipulates that the gene encoding the olfactory receptor is one type that is transiently expressed per well on the substrate and that a different olfactory receptor is transiently expressed per well, which is not taught or suggested by Touhara et al. Applicant argues that a system in which cells are infected with an adenovirus vector of Touhara et al. is unsuitable for arraying multiple types of receptors. Applicant argues that the purpose of Touhara is the identification and reconstitution of a single receptor, there is no incentive to one of ordinary skill in the art to analyze multiple types of receptors. Applicant’s argument has been fully considered but is not deemed to be persuasive for the reasons set forth in the rejection above.
Conclusion
No claims are allowed.
Advisory Information
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RUIXIANG LI/Primary Examiner, Art Unit 1674 July 25, 2026
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