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 .
Claim Objections
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4-23, and claim 25 are objected to under 37 CFR 1.75(c) and 112(d) as being in improper form. Multiple dependent claims must refer back to the claims they depend from in the alternative. Claims 4, 10, 20-22 do not refer back in the alternative. Furthermore, claims 5-9, 12-15, 23, and 25 are improper dependent claims because they depend from a multiple dependent claim. (see 37 CFR 1.75(c)). Additionally, claims 11, 16-19, and claim 25 are dependent claims that depend from an improper depend claim (aka they depend from a dependent claim which depends from a multiple depend claim) See MPEP § 608.01(n). Accordingly, the claims 4-23 will not been further treated on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 26-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 26 is indefinite because it refers back to the “cell” of claim 24 while claim 24 refers back to the expression vector of claim 1. Therefore, the dependent claim, claim 26 does not further limit the claim on which it depends, claim 24. Claim 26 merely introduces a new element to the claims but does not specify how the cell and expression vector are related. Therefore, it is unclear how claim 26 further limits claim 24.
Claim 27 is indefinite because it claims a method of regulating expression of multiple genes from a cell that contains the vector of claim 1. Claim 1 only contains one transcriptional unit, and thus only one nucleic acid sequence of interest. The additional genes are undefined.
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.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jun Ishii, et al. (2014). Jun Ishii, et al. (2014) discloses, “We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters.” (abstract). Furthermore, “The DNA fragment containing PADH1-MCS1-TADH1 and PTDH3-MCS2-TTDH3 was prepared by digesting pAT425 with XhoI/SacI and then inserted into the XhoI and SacI sites of pRS40x + 2 µm (x = 2, 4 and 6) yeast multi-copy vectors (Ishii et al., 2009), constructing pAT422, pAT424 and pAT426, respectively. The DNA fragment containing PADH1-MCS1-TADH1, PTDH3-MCS2-TTDH3 and PPGK1-MCS3-TPGK1 was prepared by digesting pATP425 with XhoI/SacI and then inserted into the XhoI and SacI sites of pRS40x + 2 µm (x = 2, 3, 4 and 6) yeast multi-copy vectors, generating pATP422, pATP423temp, pATP424 and pATP426, respectively.” (Materials and Methods section, 6th paragraph in the “plasmid constructs subsection”) (also refer to figure 1b). This is to say that there were several distinct expression cassettes inserted in to the backbone (pRS40x). 1 cassette contained the PADH1 promoter linked to a multiple cloning site (MCS). Sequence analysis revealed that the construction outlined here resulted in PADH1 being truncated by 60bp on the 5’ end and 257 bp on the 3’ end. (See additional material named “ADH1 promoter sequence”). Another cassette contained the PTDH3 promoter linked to a MCS. Sequence analysis revealed that the construction outlined here resulted in the PTDH3 promoter being truncated by 453bp on the 5’ end and 77bp on the 3’ end. (See additional material named “TDH3 promoter (aka GAP)”). Another cassette contained the PPGK1 promoter linked to a MCS. Sequence analysis revealed that the construction outlined here resulted in the PGK1 promoter being truncated by 371bp at the 5’ end and 1bp at the 3’ end. (See additional material named “PGK1 YCR012W”).
Furthermore, they disclose, “The DNA fragments encoding TagGFP2 genes were respectively prepared by digesting pBlue-G1, pBlue-G2 and pBlue-G3 with AvrII/FseI, SalI/NotI and XmaI/AscI and inserted into the AvrII/FseI, SalI/NotI and XmaI/AscI sites of pATP42x (x = 2–6) and pATP40x (x = 2 and 4– 6), creating pATP42x-G1, pATP42x-G2 and pATP42x-G3 (x = 2–6), and pATP40x-G1, pATP40x-G2 and pATP40xG3 (x = 2 and 4–6).” (Materials and Methods section, 6th paragraph in the “plasmid constructs subsection”). This is to say the researchers inserted GFP directly downstream of the PTDH3 promoter to create PATP42x-G2. Fig S3 (supplemental materials) provides a detailed map of pATP42x-G2. These disclosures anticipate claim 1 as the authors describe the creation of a plasmid that contains a nucleic acid sequence of interest (GFP) directly downstream, linked and controlled by a synthetic promoter (truncated PTDH3).
Next, the researchers performed the following cloning workflow. “The DNA fragment encoding the TagBFP gene was prepared by digesting pBlue-B1 with AvrII and FseI and inserted into the MCS linked to the PADH1 promoter of pATP422 and pATP402, constructing pATP422-B1 and pATP402-B1. The DNA fragment encoding the mKate2 gene was prepared by digesting pBlue-R2 with SalI and NotI and inserted into MCS linked to the PTDH3 promoter of pATP422-B1 and pATP402-B1, producing pATP422-B1R2 and pATP402-B1R2. The DNA fragment encoding the TagGFP2 gene was prepared by digesting pBlue-G3 with XmaI and AscI and inserted into the MCS linked to the PPGK1 promoter of pATP422-B1R2 and pATP402-B1R2, creating pATP422-B1R2G3 and pATP402-B1R2G3.” (Materials and Methods section, 11th paragraph in the “plasmid constructs subsection”). This is to say that researchers inserted BFP into the MCS of pATP422 and pATP402. This resulted in the creation of plasmids pATP422-B1 and pATP402-B1. Fig S3 (supplemental materials) provides a detailed map of pATP422-B1. Most importantly, the map details that BFP is inserted directly downstream of the PADH1 promoter in both pATP422-B1 and pATP-402-B1. They also inserted mKate2 into the same sites of pATP422-B1 and pATP402-B1, producing pATP422-B1R2 and pATP402-B1R2. Fig S3 (supplemental materials) provides a detailed map of pATP422-B1R1. Most importantly, pATP422-B1R2 still has BFP downstream of the PADH1 promoter, and now mKate2 has been inserted directly downstream of the PTDH3 promoter. Finally, GFP was inserted into the same sites of pATP422-B1R2 and pATP402-B1R2, creating pATP422-B1R2G3 and pATP402-B1R2G3. Fig S3 (supplemental materials) provides a detailed map pATP422-B1R2G3. Most importantly, pATP422-B1R2G3 still has BFP downstream of the PADH1 promoter, and mKate2 downstream of PTDG3, and finally, GFP directly downstream of PPGK1. (Materials and Methods section, 8th paragraph in the “plasmid constructs subsection”). These disclosures anticipate claim 2 and claim 3. pATP422-B1 was used to construct pATP422-B1R1. pATP422-B1 already had BFP inserted into the MCS linked to the PADH1 promoter. The modification of pATP422-B1 resulted in pATP422-B1R1. It was done by inserting mKate2 into the MCS linked to the PTDH3 promoter (claim 2). Additionally, pATP422-B1R1 was used to create pATP422-B1R2G3. pATP422-B1R2G3 was created by inserting GFP into the MCS linked to the PPGK1 promoter in pATP422-B1R1 (claim 3).
Claim 24 and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated M Gossen et al. (1992). M Gossen et al. (1992) discloses, “Multiple insertions of tetOs created a set of promoters that contained between 1 and 7tetO sequences upstream from position -81 of the tk promoter. A Xho I/Sal I fragment containing 7 tetOs fused head to tail was recovered from one of the constructs and transferred into the Xho I site upstream Of PhCMV*. Due to the asymmetry of the Xho I/Sal I fragment, two PhCMV*-tetO constructs were obtained that differ in the distance between the operators and position + 1 Of PhCMv, which is 95 bp for Phcmv*-1 and 76for PhCMvV*2. The plasmids containing these promoters are designated pUHC13-3 and pUHC134, respectively (Fig. lb). When HeLa cells were transiently transfected with these plasmids high levels of luciferase activity were monitored whenever the cells were transfected with pUHD15-1, which provided the coding sequence of tTA.” (Results paragraph 4). This anticipates claim 24 because it details the creation of a plasmid containing a synthetic promoter that drives transgene expression. Importantly, protein expression is validated and quantified in the HeLa cell line, a human cancer cell line. This indicates the expression vector is a mammalian vector. The disclosure also anticipates claim 27 because it details the creation of an expression plasmid with a synthetic promoter linked to, and controlling, the expression of a nucleotide sequence of interest (coding for luciferase). Importantly, this is a synthetic promoter because the insertion of multiple tetO sequences were arranged in a head-to-toe manner (unnatural). The tetO sequences were fused to a mammalian viral promoter (phCMV) and their distance from the transcription start site (76bp vs 95bp) was experimentally engineered.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Adam M Smith whose telephone number is (571)272-7517. The examiner can normally be reached Monday- Friday 10:30AM-5PM.
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/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638