The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received February 6, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 3, 6-8, 20-23, 29 are canceled. Claims 18-19, 24-25 are withdrawn. Claims 1-2, 4-5, 9-17, 26-28, to SEQ ID NO: 2, SEQ ID NO: 9, SEQ ID NO: 16, are under consideration.
Priority: This application is a CON of PCT/US2020/039005, filed June 22, 2020, which claims benefit of provisional application 62/864915, filed June 21, 2019.
The declaration under 37 CFR 1.130 filed February 6, 2026 is sufficient to overcome the rejection of claims 1-3, 13-16, 26 based upon Herbst et al. (2018 Biochemistry 57: 4726-4734; IDS 05.19.22).
Objections and Rejections
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.
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.
Claims 1-2, 4-5, 13-14, 16-17, 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Cornish (US 20100261167; IDS 05.19.22) in view of Golemis et al. (2008 Current Protocols in Molecular Biology 82:20.1.1-20.1.35) and Althoff et al. (US 20030203471). Cornish discloses systems for in vivo screening of compounds through the use of chemical inducers of protein dimerization (at least abstract, paragraph 0004). Cornish discloses the yeast three-hybrid system for detecting ligand-receptor interactions in vivo and that results demonstrate that the yeast three-hybrid system can be used to discover receptors for small ligands and to screen for new ligands to known receptors (at least paragraph 0013). Cornish discloses a cell-based assay comprising a yeast three-hybrid system comprising an engineered cell comprising nucleic acid molecules encoding a LexA-GR fusion protein and a DHFR-B42 fusion protein (at least paragraphs 0033-0037, also examples 1-3). Cornish discloses that design of the protein chimeras is based on the yeast two-hybrid assay because of its flexibility (at least paragraph 0156). Cornish discloses using the Brent two-hybrid system, which uses LexA as the DNA-binding domain and B42 as the transcription activation domain (at least paragraph 0156). Cornish discloses the compounds for binding to the receptor are selected from, in addition to dexamethasone, methotrexate, but also tetracycline (at least paragraphs 0055-0056). Cornish does not specifically teach a tetracycline receptor (TetR).
Golemis et al. disclose two-hybrid system variants include a LexA/TetR fusion protein (p. 29 Table 20.1.4).
Althoff et al. also disclose a three-hybrid system in an assay for screening (p. 1). Althoff et al. disclose the receptor domain can be selected from among a glucocorticoid receptor (i.e. GR) and tetracycline repressor (at least paragraph 0098). Althoff et al. disclose the pairing of tetracycline/tetracycline repressor (at least paragraph 0163).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the TetR of Golemis et al./Althoff et al. for the GR in the LexA fusion protein of Cornish to thereby arrive at the claimed engineered cell comprising nucleic acid molecules encoding a LexA-TetR fusion protein and a DHFR-B42 fusion protein (instant claim 1). The motivation to do so is given by the teachings of the prior art, where Cornish discloses compounds for binding to the three-hybrid system includes tetracycline and Golemis et al./Althoff et al., which disclose TetR is an alternative receptor to the GR of Cornish in a hybrid system. One of ordinary skill would have a reasonable expectation of success because LexA/TetR is a known hybrid system variant.
Regarding instant claim 2, Cornish discloses the engineered cell comprises a LacZ reporter gene under the control of LexA operators (at least paragraphs 0033-0037, 0156, examples 1-3).
Regarding instant claims 4-5, Cornish discloses the engineered cell is selected from among a yeast or bacteria (at least paragraphs 0086, 0157).
Regarding instant claims 13-14, Cornish discloses the reporter gene is LacZ (at least paragraphs 0033-0037, examples 1-3) or ura3 (at least paragraphs 0077, 0201, 0216, 0221).
Regarding instant claim 16, Cornish discloses dimerization of the first and second fusion protein induces expression of the reporter gene (at least paragraphs 0033-0037, 0156, examples 1-3).
Regarding instant claim 17, Cornish discloses the engineered cell comprises Dex-Mtx chemical inducer of dimerization for the LexA-GR fusion protein and DHFR-B42 fusion protein (at least paragraphs 0033-0037, 0145, examples 1-3). Althoff et al./Golemis et al. disclose TetR is an alternative receptor for GR in a LexA fusion protein (see above). Althoff et al. further disclose pairing of tetracycline and tetracycline repressor (at least paragraph 0163). Therefore, it would have been obvious to one of ordinary skill to arrive at a tetracycline-methotrexate chemical inducer of dimerization for the engineered cell comprising LexA-TetR fusion protein and DHFR-B42 fusion protein of Cornish in view of Golemis et al./Althoff et al. noted above.
Regarding instant claims 26-28, in In re Haller, 73 USPQ 403 (CCPA 1947), the Court held that an old compound, packaged and labeled to show its use, is not patentable. The packaging of a known compound and the application of an appropriate label thereto does not involve invention over the known compound. In this instance, the engineered cell comprising LexA-TetR fusion protein and DHFR-B42 fusion protein and a tetracycline-methotrexate chemical inducer of dimerization of Cornish in view of Golemis et al./Althoff et al. noted above can reasonably be incorporated into a kit for commercial purposes.
Claims 1-2, 4-5, 10-12, 13-14, 16-17, 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Cornish (US 20100261167; IDS 05.19.22) in view of Golemis et al. (2008 Current Protocols in Molecular Biology 82:20.1.1-20.1.35) and/or Althoff et al. (US 20030203471), and Golovko et al. (WO 0220811). The teachings of Cornish in view of Golemis et al./Althoff et al. over at least instant claims 1-2, 4-5, 13-14, 16-17, 26-28 are noted above.
Regarding instant claims 10-12, Golovko et al. disclose the nucleotide sequence encoding TetR (at least p. 17 lines 28-29, Fig. 29A, SEQ ID NO: 1), where SEQ ID NO: 1 of Golovko et al. has 99.8% sequence identity with instant SEQ ID NO: 9. Therefore, it would have been obvious to one of ordinary skill to incorporate the nucleotide sequence encoding TetR of Golovko et al. for the TetR in the engineered cell comprising LexA-TetR fusion protein and DHFR-B42 fusion protein of Cornish in view of Golemis et al./Althoff et al. noted above. One of ordinary skill would have a reasonable expectation of success because LexA/TetR is a known hybrid system variant.
Claims 1-2, 4-5, 9, 13-14, 16-17, 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Cornish (US 20100261167; IDS 05.19.22) in view of Golemis et al. (2008 Current Protocols in Molecular Biology 82:20.1.1-20.1.35) and/or Althoff et al. (US 20030203471), and Zhang et al. (2013 J Nat Prod 76: 1627-1636). The teachings of Cornish in view of Golemis et al./Althoff et al. over at least instant claims 1-2, 4-5, 13-14, 16-17, 26-28 are noted above.
Regarding instant claim 9, Zhang et al. disclose tetracycline are broad spectrum antibiotics and include tetracycline analogues doxycycline, 9-amino-doxycycline (at least p. 1627-1628). Therefore, it would have been obvious to one of ordinary skill that the TetR in the engineered cell comprising LexA-TetR fusion protein and DHFR-B42 fusion protein of Cornish in view of Golemis et al./Althoff et al. noted above can bind to a tetracycline analogue selected from doxycycline. One of ordinary skill would have a reasonable expectation of success because doxycycline is a tetracycline analogue and Cornish discloses compounds for binding to the receptor are selected from tetracycline, which reasonably includes tetracycline analogues.
Reply: In view of Applicants’ amendments/remarks and the declaration under 37 CFR 1.130 of Dr. Virginia Cornish filed February 6, 2026, the previous 102(a)(1) and 103 rejections over Herbst et al. have been withdrawn. In view of Applicants’ amendments/remarks, the previous 102(a)(1) rejection as being anticipated by Cornish has also been withdrawn. However, Cornish is maintained as a 103 reference in new 103 rejections in view of newly cited references Golemis et al. and Althoff et al. for the reasons noted above. Specifically, the deficiency of Cornish to not specifically teach a tetracycline receptor (TetR) is remedied by Golemis et al./Althoff et al. which disclose LexA/TetR is a known hybrid system variant.
Instant SEQ ID NOS: 2, 16 appear to be novel.
Claim 15 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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