DETAILED ACTION
Notice of Pre-AIA or AIA Status
Claims 1-4, 12, 20-33, and 42 are pending.
Claims 5-11, 13-19, 34-41, and 43-44 are cancelled.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-4, 12, and 20) in the Response filed on 06/30/2026 is acknowledged. Accordingly, claims 21-33 and 42 are withdrawn from consideration as directed to non-elected inventions.
Claim Interpretation
Claims 1 and 12 recite a synthetic transcriptional promoter comprising a core promoter, that is made up of a TATA box, an initiator element, an RNA polymerase II binding site, and a transcription start site. All of these are well-defined in the art, except for an RNA polymerase II binding site. As RNA pol II is recruited by general transcription factors (GTFs), there are not specific sequences described in the art that RNA pol II recognizes and binds directly. Therefore, “an RNA polymerase II binding site” is taken to be limited by its property (being able to be bound to RNA pol II), rather than its structure (a specific sequence). This property is rarely explicitly stated in the art, but can be inferred by the presence of motifs that bind general transcription factors (such as a TATA box) or by evidence of a core promoter’s overall ability to promote transcription. Though well-known, usage of the terms “initiator elements” and “transcription start sites” can vary in the art. For the purposes of examination, “an initiator element” is taken to mean a sequence around the transcription start site, typically derived from a consensus sequence and having the ability to promote transcription initiation. “A transcription start site” is taken to mean the position at which transcription is initiated. Frequently, an initiator element encompasses a transcription start site. Elements of core promoters are reviewed in Haberle et al. (Nat. Rev. Mol. Cell. Biol. (2018), 19: 621-637).
Claim Rejections - 35 USC § 102
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 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 –
(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.
Redden et al.
Claims 1-2 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Redden et al. (Nat. Comm. (2015), 6: 7810; of record).
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Redden Figure 5a (boxes = annotations)
Regarding claim 1, Redden discloses a method (Fig. 1c) for generating a synthetic transcriptional promoter that is functional in a eukaryotic cell comprising:
introducing an expression vector into a eukaryotic cell (p. 7, Methods, Strains and media, 3rd ¶: yeast transformations), wherein the expression vector comprises:
a synthetic transcriptional promoter (p. 5, Results, Minimal UAS elements…, 3rd ¶) comprising: first and second transcription factor binding sites that comprise an upstream enhancer element of 10 bp (p. 5, Results, Minimal UAS elements…: “minimal, constitutive 10-bp UAS elements”) where the nucleotide sequence of the second is different form the first (Fig. 5a: Synthetic UAS, annotated above); and a core promoter (Fig. 5a: Core) comprising a TATA box, a transcription start site, an initiator element, and an RNA pol II binding site (Fig. 1a; p. 2, Results, Creating a method for identifying minimal yeast promoters); and
a nucleotide sequence encoding a reporter polypeptide operably linked to the synthetic transcriptional promoter (p. 5, Results, Minimal UAS elements can create strong and short promoters, 3rd ¶; p. 2, Results, Core element designs: “linking these libraries to a fluorescent reporter protein (yECitrine)”); and
detecting expression of the reporter polypeptide which indicates that the synthetic transcriptional promoter is functional in the eukaryotic cell (Fig. 5b and legend).
In reference to core promoter elements, Redden does not explicitly state that the core promoter contains an initiator element nor an RNA pol II binding site, but the “transcription start site” Redden discloses encompasses both an initiator element and a transcription start site (“a transcription start site (TSS) with consensus sequence of A(Arich)5NYAWNN(Arich)6”). Additionally, the presence of elements (TATA box) known to bind GTFs, as well as evidence that the core promoter can support transcription initiation (Fig. 2a), indicates that it is able to be bound by RNA pol II and therefore meets the limitation of comprising an RNA pol II binding site.
Regarding claim 2, Redden discloses that the expression vector comprises 3 TFBS (Fig. 5a).
Regarding claim 4, Redden further discloses that the synthetic transcriptional promoter has a length of ~100-150bp (Fig. 5a).
Claim Rejections - 35 USC § 103
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Redden et al. and Roberts et al.
Claims 3, 12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Redden et al. in view of Roberts et al. (PGPub No: US 2023/0340460; effective filing date 12/23/2020).
Regarding claim 3, Redden discloses all limitations of claim 1, as discussed above. Additionally, Redden teaches that the fluorescence reporter method used has drawbacks, including “day-to-day absolute fluorescence variations” that are necessary to mitigate (p. 3-4, Results, Isolation of robust and minimal…) and that further candidate testing is needed after FACS (p. 7, Discussion: “constructs simply identified through FACS did not always function in a robust manner with respect to growth phase, homogenous expression and retransformation”).
Roberts discloses a method (Fig. 2) for promoter screening of an expression vector containing multiple TFBSs, a core promoter, a reporter polypeptide, and a nucleic acid barcode that identifies the combination of the TFBSs (p. 28, ¶[0419]). Roberts also discloses that the barcode is used “to facilitate the determination of the strength of said URE [unique regulatory element, such as a TFBS] with precision and accuracy” (p. 16, ¶[0170]) by normalizing the DNA barcode to transcribed mRNA barcode (p. 15, ¶[0157]). Additionally, Roberts discloses that reporter polypeptide screening results may differ from barcode screening results due to variables unique to mRNA vs. protein levels (p. 30, ¶[0434]). Therefore, Roberts provides motivation to incorporate the disclosed nucleic acid barcode into the expression vector of Redden because barcode sequencing and normalization provides an orthogonal method of promoter screening that can assist in mitigating the drawbacks to reporter polypeptide screening, which are acknowledged by Redden.
Furthermore, this addition of nucleic acid barcodes to the expression vector of Redden would have a reasonable expectation of success because the methods of Redden and Roberts have a high amount of overlap, including similarly designed eukaryotic vectors. Additionally, nucleic acid barcodes are well-known in the art and therefore robust methods of their incorporation and use are widely available.
Together, this indicates that it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the nucleic acid barcode of Roberts into the expression vector of Redden as an orthogonal or subsequent method to mitigate the drawbacks of the reporter polypeptide screening with a reasonable expectation of success.
Regarding claim 12, Redden discloses a library of expression vectors of the same design as that disclosed in relation to claim 1, but with one TFBS instead of at least two TFBSs (Fig. 1c; p. 5, Results, Minimal UAS elements…, 2nd ¶). Additionally, Redden discloses six minimal, constitutive 10-bp TFBS (Fig. 4b). Therefore the difference between Redden and the instant claim is that Redden did not disclose creation of a library of expression vectors comprising multiple TFBSs. However, Redden also discloses that the construct containing multiple TFBSs has stronger expression than the constructs containing only one (Fig. 5b). As the goal of Redden is to create a collection of short, strong, constitutive promoters (Abstract), it would therefore follow that screening a library of constructs containing multiple TFBSs would result in promoters of higher strength than those of the single TFBS library. Therefore, implicit in Redden is the motivation to create a library of expression vectors with at least two TFBSs.
Roberts discloses a library of expression vectors (p. 28, ¶[0419]) with TFBSs, a core promoter, and a reporter polypeptide. Each vector has a promoter construct created by randomly concatenating a pool of TFBSs (Fig. 8) that had sizes between 150 to 600 bp (p. 28, ¶[0422]), indicating that there were more than one TFBS present in each construct (Fig. 8). Based on the motivation of Redden, it would have been obvious to incorporate the random concatenation method of Roberts to the library of the expression vectors of Redden, resulting in a library of expression vectors with two or more TFBSs. Additionally, both Roberts and Redden demonstrate that this combination would have a reasonable expectation of success: Roberts by demonstrating that the concatenated TFBSs can be incorporated into an expression vector to generate a library, and Redden by showing that the disclosed expression vector can accommodate and function with more than one TFBS (Fig. 5b).
Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the concatenated TFBSs of Roberts into the expression vector of Redden, based on the motivation of producing a library with strong promoters, with a reasonable expectation of success.
Regarding claim 20, Roberts further discloses that the random concatenating method produced a library of 1.2 x 106 constructs. Additionally, the library of Redden would be able to accommodate a similar number of constructs, as the single TFBS library of Redden comprised 1.3 million members (Fig. 1c; p. 5, Results, Minimal UAS elements…, 2nd ¶).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexandra Olson whose telephone number is (571)272-7519. The examiner can normally be reached Monday-Friday 9-5pm.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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