DETAILED ACTION
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 .
Application Status
Applicant’s remarks and amendments to the claims and specification filed December 2, 2025 are acknowledged. Claims 1-2, 4, 19, and 21 were amended, and claims 83-84 were introduced. Claims 1-9, 11-26, 28-33, and 79-84 are pending.
Restriction/Election
Newly submitted claims 83-84 are directed to an invention that is related, but distinct, from the invention originally claimed. Original claims 1-9, 11-26, 28-33, and 79-82 (Group I) are directed to a nucleic acid construct, and yeast strain comprising the nucleic acid construct. Claims 83-84 (Group II) are directed to a “library of daughter-arresting program (DAP) yeast mutant strains produced by crossing the DAP yeast strain of claim 19 with a library of yeast mutants.” Group I lacks unity of invention with Group II, because even though these groups share the technical feature of the structural features of the DAP yeast strain of claim 19 (which would be inherited by the product-by-process library strains), these are not special technical features as they do not make a contribution over the prior art in view of Goldfarb, Janke, and Henderson (each of record). As described in paragraph 22 below, Goldfarb, Janke, and Henderson render obvious the structural features of the claimed DAP yeast strain, and therefore, the structural features which would be inherited in the process of producing the library strains of Group II. Groups I and II lack unity of invention a posteriori, accordingly. 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 Accordingly, claims 83-84 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Claims 1-9, 11-26, 28-33, and 79-82 are under consideration hereinafter, accordingly.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Withdrawn Rejections
Applicant’s remarks and amendments have been reviewed. The amendments to the claims are sufficient to overcome the § 112(b) rejections raised in the prior action. The aforementioned rejections are withdrawn, accordingly.
Applicant’s remarks and amendments have been thoroughly considered, but are not persuasive to place the claims in condition for allowance for the reasons that follow. Any rejection or objection not reiterated herein has been overcome by amendment.
Notice to Joint Inventors
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.
Claim Rejections - 35 USC § 103 – Goldfarb, Janke, and Henderson
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, 7-8, 11-16, 18-19, 24-25, and 28-33 are rejected under 35 U.S.C. 103 as being unpatentable over Goldfarb (Goldfarb, published 30 December 2004, US 2004/0265861 A1; of record) as evidenced by Witte (Witte et al., 6 July 2017, eLife, 2017;6:e26722; of record), in view of Janke (Janke et al., 2004, Yeast, 21:947-962; of record) and Henderson (Henderson et al., 2014, eLIFE, 2014;3:e03504; of record). The rejections that follow are maintained from the prior action with modification necessitated by Applicant’s amendments to the claims.
Regarding claim 1, Goldfarb teaches a nucleic acid construct for integration into a specific locus of a yeast cell genome (“DEAD cassette is a DNA construct (… integrated directly into the chromosomes) which contains two genes that both encode an essential protein, i.e., one that is required for growth and replication”, [0026]-[0029]). Regarding (a), Goldfarb teaches the nucleic acid construct comprises at each end, an integration sequence configured to effect integration into a yeast genome at the location of a endogenous gene encoding an essential protein (“the DEAD cassette can be inserted into the yeast genome such that the native essential gene is disrupted, and effectively replaced”, [0047], “The introduction by transformation of segments of DNA that share homology at both ends with sequences within the chromosome results in integration with high frequency at the preferred site”, [0052]-[0053]; “the two genetic elements of the DEAD cassette will be integrated into the chromosome(s) of the host strain, preferably at one locus (e.g., in tandem at the CDC6 locus)”, [0091]). Goldfarb teaches the endogenous gene encoding the essential protein may be, but is not limited to, for example, CDC6 or CDC42 (“proteins that can be used in accordance with the present invention include… CDC42 (Genbank Accessions X51906 and NC_001144”, [0036], “these strategies are not limited to the use of the CDC6 gene… CDC42… useful in formation of alternative DEAD cassettes”, [0092]). Witte teaches that CDC42 is required for cell division (pg. 1), and is associated with the plasma membrane (Fig. 10). Thus, Goldfarb teaches integration of the construct at an endogenous gene encoding an essential plasma membrane protein, i.e., CDC42.
Regarding (b), Goldfarb teaches the nucleic acid construct comprises two cassettes (“The two chimeric genes are different in that their transcription is directed by different promoters”, [0028]). Goldfarb teaches the first cassette (i) comprises a mother-specific promoter operably linked to an exogenous copy of the gene encoding the essential plasma membrane protein (“the other copy is driven by a promoter operable only in mother cells, such as an HO endonuclease promoter”, [0026]-[0029]). Goldfarb teaches the second cassette (ii) comprises a conditional promoter configured to control transcription of a second, exogenous copy of the gene encoding the essential plasma membrane protein (“One copy is driven by an inducible promoter that is responsive to growth medium conditions, such as a GAL promoter”, [0026]-[0029]).
Goldfarb teaches that the two cassettes of the nucleic acid construct are transcriptionally independent ([0028]), but Goldfarb does not expressly teach that the two cassettes are “oriented in opposite transcriptional directions” as recited in claim 1. MPEP 2131.02(III) states that “A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure.” The ordinarily skilled artisan would “at once envisage” the two possible arrangements of the cassettes’ transcriptional directions: opposite or same. Because the two species can be “at once envisage[d],” Goldfarb’s generic disclosure anticipates this claim limitation.
Goldfarb makes clear that expression from the endogenous gene encoding the essential plasma membrane protein must be controlled in order for the nucleic acid construct to function effectively in yeast cells ([0047], [0049]-[0050], [0052], [0091]). Accordingly, Goldfarb teaches that the second cassette (ii) of the nucleic acid construct contains an exogenous copy of the endogenous gene, controlled by a constitutive promoter, which when integrated into the yeast genome at the location of the endogenous copy, effectively replaces the endogenous gene.
Goldfarb does not teach that:
the integration sequences are configured to integrate the construct into the yeast genome between a sequence upstream of the start codon of the endogenous gene encoding the essential plasma membrane protein, and the start codon of the gene, and
that the second cassette (ii) is configured to control transcription of the endogenous gene upon integration into the yeast genome.
However, Janke teaches nucleic acid constructs configured to integrate upstream of the start codon of an endogenous gene and introduce a heterologous promoter as a means to control and modulate expression from the endogenous gene (pg. 957-958, “Promoter replacement and N-terminal tagging”; Table 1; Fig. 1C). Janke teaches that the heterologous promoter is operably linked to a reporter marker (“N-terminal tag”), such that upon integration the reporter marker is transcriptionally linked in-frame to the endogenous gene (pg. 958, left col.; Fig. 1C). Janke teaches that the integrated nucleic acid constructs can replace the endogenous (“internal”) promoter with an inducible promoter, e.g., GAL1 (pg. 958, left col.). Janke teaches that substitution of the endogenous promoter for a heterologous promoter, and reporter marker operably linked thereto, advantageously allows the skilled artisan “to interfere with transcriptional regulation and to conditionally deplete gene products, while the availability of N-terminal tags provides the possibility to label proteins…” (pg. 960, right col.).
Regarding I and II above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nucleic acid construct of Goldfarb as taught by Janke, such that the conditional promoter of the second cassette, upon integration, controls expression of and tags the endogenous copy of the essential plasma membrane protein. It would have amounted to applying well-known cassette construction techniques, to modify a known nucleic acid construct, to yield predictable results. A skilled artisan, recognizing that Janke’s design would allow tight control of endogenous gene expression necessary for the function of the construct, and offer the additional advantage of marking the endogenous gene, would have been motivated to modify the insertion sequences and second cassette taught by Goldfarb, such that upon integration, the second cassette controls expression of and marks the endogenous copy of the essential plasma membrane protein. The skilled artisan would have had a reasonable expectation that the nucleic acid construct could be prepared with a second cassette (ii) having a conditional promoter operably linked to a marker, and modified insertion sequences that allow for integration upstream of the first codon of the endogenous gene (so as to control expression from the endogenous gene), because methods of preparing constructs were routine in the art as evidenced by Goldfarb and Janke, and the sequence of the endogenous gene encoding the essential plasma membrane protein was known ([0036], [0053]), as evidenced by Goldfarb.
Goldfarb teaches that “The essential protein that is required for replication can be any yeast protein which, when knocked-out, degraded, or otherwise inhibited, results in death” ([0034]). However, neither Goldfarb nor Janke teach that the teach that the gene encoding the essential plasma membrane protein is PMA1.
Henderson teaches that PMA1 is an essential plasma membrane protein encoded by the gene PMA1, which is lethal when deleted (“In a screen to identify proteins asymmetrically retained in mother cells throughout aging, we identified the plasma membrane proton ATPase”, Pma1, pg. 2; “PMA1 is an essential gene and cannot be deleted”, pg. 4). Henderson also teaches that PMA1 is asymmetrically distributed in yeast mother and daughter cells; mother cells have much more PMA1 at the plasma membrane than nascent daughter cells, in which PMA1 is “largely absent” (Abstract; Fig. 2; Fig. 4D). Henderson demonstrates that as newborn daughter cells age into mother cells themselves, PMA1 expression increases (Fig. 2B; Fig. 4D). The sequence of the PMA1 gene was also known as evidenced by Henderson (“Strains,” pg. 7-8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the essential plasma membrane gene CDC42 taught by Goldfarb for PMA1 in view of Henderson. It would have amounted to a simple substitution of two known essential plasma membrane genes, by known means to yield predictable results. Because Goldfarb teaches that the essential protein can be any yeast protein which when knocked-out results in death, and Henderson teaches that PMA1 encodes such a protein, a skilled artisan would have had a reasonable expectation of success in substituting the two genes. Goldfarb teaches the nucleic acid construct improves efficiency of yeast aging studies, by ensuring that only mother cells produce daughter cells, and any resulting daughter cells are arrested (unable to grow or replicate due to lack of the essential gene) ([0008]-[0009], [0028]). Henderson teaches that PMA1 is an asymmetrically distributed yeast protein; mother cells express much more PMA1 than daughter cells, and daughter cells inherit very little, if any PMA1 from the mother cell. The skilled artisan, recognizing the utility of PMA1’s asymmetric distribution in the context of the nucleic acid construct taught by Goldfarb would have been motivated to substitute the two essential plasma membrane genes. Because little to no PMA1 protein would be inherited by nascent daughter cells from mother cells, the skilled artisan could ensure tight regulation over PMA1 expression (using the nucleic acid construct promoters) and daughter cell replicative capacity, and therefore, improve the ease of quantifying mother cell replicative lifespan.
Regarding claim 2, for the reasons described above, Goldfarb in view of Janke and Henderson renders obvious each limitation of claim 2.
Regarding claim 7, Goldfarb teaches that the nucleic acid construct comprises a selectable marker (“Successful integrations are identified by the incorporation of an antibiotic resistance or auxotrophic marker that can be selected for in the growth medium”, [0052]).
Regarding claim 8, Goldfarb teaches that kan is a selectable marker (“antibiotic resistance. By way of example, the KAN (kanamycin resistance) gene”, [0039]).
Regarding claim 11, the gene encoding the essential plasma membrane protein rendered obvious above is PMA1.
Regarding claims 12-13, Goldfarb teaches the conditional promoter is pGAL1 (“GAL1… preferred because of their tight regulation”, [0029]; “31… the promoter responsive to galactose presence is a GAL1”, pg. 17).
Regarding claims 14-15, Goldfarb teaches the mother-specific promoter is pHO (“The other copy is driven by a promoter operable only in mother cells), such as an HO endonuclease promoter”, [0028]; “30… the promoter operable in mother cells but not daughter cells is an HO promoter”, pg. 17).
Regarding claim 16, Goldfarb teaches a vector comprising the nucleic acid construct (“vectors… that contain the DNA construct”, [0013]; “35… An expression vector comprising the DNA construct”, pg. 17).
Regarding claim 18, Goldfarb teaches a yeast cell comprising the vector ([0047], [0052]; “41… wherein the host cell is a yeast”, pg. 17).
Regarding claim 19, the phrase “integrated into” indicates that the claimed yeast strain is a product-by-process. MPEP 2113(I) states that “product-by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.” The integration of the exogenous nucleic acid sequence requires the claimed yeast strain comprise the following structural elements: (b) a conditional promoter driving transcription of an endogenous copy of a gene encoding an essential plasma membrane protein, and adjacent thereto, (a) a mother-specific promoter driving transcription of a second copy of the gene encoding the essential plasma membrane protein, wherein (a) and (b) are oriented in opposite transcriptional directions, and wherein the gene encoding the essential plasma membrane protein is one of the recited genes. The distance between (a) and (b) is unspecified, i.e., they could be separated by many nucleotides within the nucleic acid sequence “comprising” (a) and (b), and therefore, be separated by many nucleotides within the yeast genome.
For the reasons described above, Goldfarb, Janke, and Henderson render obvious a daughter-arresting program (DAP) yeast strain, comprising a conditional promoter driving transcription of an endogenous copy of a gene encoding an essential plasma membrane protein, and adjacent thereto, a mother-specific promoter driving transcription of a second copy of the gene encoding the essential plasma membrane protein, wherein (a) and (b) are oriented in opposite transcriptional directions, and wherein the gene encoding the essential plasma membrane protein is PMA1.
Regarding claims 24-25, Goldfarb teaches that the nucleic acid construct comprises a selectable marker (“Successful integrations are identified by the incorporation of an antibiotic resistance or auxotrophic marker that can be selected for in the growth medium”, [0052]). Goldfarb teaches that kan is a selectable marker (“antibiotic resistance. By way of example, the KAN (kanamycin resistance) gene”, [0039]).
Regarding claim 28, the gene encoding the essential plasma membrane protein rendered obvious above is PMA1.
Regarding claims 29-30, Goldfarb teaches the conditional promoter is pGAL1 (“GAL1… preferred because of their tight regulation”, [0029]; “31… the promoter responsive to galactose presence is a GAL1”, pg. 17).
Regarding claims 31-32, Goldfarb teaches the mother-specific promoter is pHO (“The other copy is driven by a promoter operable only in mother cells), such as an HO endonuclease promoter”, [0028]; “30… the promoter operable in mother cells but not daughter cells is an HO promoter”, pg. 17).
Regarding claim 33, the phrase “an exogenous nucleic acid barcode sequence,” is interpreted as essentially any known nucleic acid sequence. As described in the preceding paragraphs, Goldfarb teaches many specific, known nucleic acid sequences, e.g., the HO promoter, the conditional promoter, the gene encoding the essential plasma membrane protein, or portions thereof. Thus, claim 33 is also obvious over Goldfarb, Janke, and Henderson.
Claims 9 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Goldfarb (Goldfarb, published 30 December 2004, US 2004/0265861 A1; of record) as evidenced by Witte (Witte et al., 6 July 2017, eLife, 2017;6:e26722; of record), in view of Janke (Janke et al., 2004, Yeast, 21:947-962; of record) and Henderson (Henderson et al., 2014, eLIFE, 2014;3:e03504; of record), as further evidenced by Farwick (Farwick et al., published 7 December 2017, WO 2017/207950 A1; of record). The rejections that follow are maintained from the prior action.
Regarding claims 9 and 26, Goldfarb does not teach that the selectable marker is hphNT1.
However, Janke teaches that that kanMX4 and hphNT1 are both selectable markers conferring antibiotic resistance (pg. 955, right col.) Janke teaches that hphNT1 cassettes are “as robust as the kanMX4 cassettes” (pg. 958, right col.). As evidenced by Farwick, kanMX4 and hphNT1 are art-recognized selectable markers for the same purpose ([0048]-[0053]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the selectable marker taught by Goldfarb, for hphNT1 in view of Janke. It would have amounted to a simple substitution of two known selectable marker genes, by known means to yield predictable results. A skilled artisan would have had a reasonable expectation of success in substituting the kan marker taught by Goldfarb, for hphNT1, because methods of constructing nucleic acid constructs comprising selectable markers was routine in the art as evidenced by Goldfarb and Janke. Janke and Farwick teach that kan and hphNT1 are functionally equivalent, art-recognized selectable markers conferring antibiotic resistance. Accordingly, “An express suggestion to substitute one equivalent component… for another is not necessary to render such substitution obvious.” See MPEP 2144.06(II).
Claim Rejections - 35 USC § 103 – Goldfarb, Janke, and Henderson, in view of Amen
Claims 3-6, 20-23, and 79-82 are rejected under 35 U.S.C. 103 as being unpatentable over Goldfarb (Goldfarb, published 30 December 2004, US 2004/0265861 A1; of record) as evidenced by Witte (Witte et al., 6 July 2017, eLife, 2017;6:e26722; of record), in view of Janke (Janke et al., 2004, Yeast, 21:947-962; of record) and Henderson (Henderson et al., 2014, eLIFE, 2014;3:e03504; of record) as applied to claims 1-2, 7-8, 11-16, 18-19, 24-25, and 28-33, and in further view of Amen (Amen et al., June 2017, Vol. 4, No. 6, p. 182-190; of record). The rejections that follow are maintained with modification, or new (claims 4, 21, and 79-82), as necessitated by Applicant’s amendments to the claims.
The teachings of Goldfarb, Janke, and Henderson are described above and applied as to claims 1-2, 7-8, 11-16, 18-19, 24-25, and 28-33 therein. Goldfarb, Janke, and Henderson render obvious a nucleic acid construct, and a yeast strain comprising the construct integrated upstream of the first codon of an endogenous PMA1 gene, wherein the construct comprises, oriented in opposite transcriptional directions, (i) a first cassette comprising a mother-specific promoter operably linked to an exogenous copy of the PMA1 gene, and (ii) a second cassette comprising a conditional promoter operably linked to a reporter marker, such that upon integration, the reporter marker is transcriptionally linked in-frame to the endogenous copy of PMA1.
In addition, Goldfarb teaches the nucleic acid construct attempts to overcome the tedious and time-intensive process of sorting and counting individual mother and daughter cells in yeast aging assays ([0009]). Goldfarb teaches that the nucleic acid construct “promises to speed lifespan analyses by orders of magnitude, particularly when optimized for automated screening of an entire yeast deletion library for genes that both increase and decrease yeast lifespan” ([0016]).
Janke also teaches nucleic acid constructs configured to integrate such that two endogenous proteins are transcriptionally linked in-frame to distinct fluorescent reporter markers (Fig. 1; Fig. 4; pg. 956). Janke teaches that GFP is a suitable fluorescent marker, which may be used in combination with dsRed, for example, to enable detection of the two distinctly-labelled proteins simultaneously (pg. 956, left col.; Fig. 4).
None of Goldfarb, Janke, or Henderson teach that the exogenous copy of the gene in the first cassette (i), and the endogenous copy of the gene in the second cassette (ii), are transcriptionally linked in-frame to a distinct fluorescent reporter marker, e.g., GFP, as encompassed by instant claims 3-6, 20-23, and 79-82.
However, Amen teaches nucleic acid constructs comprising two cassettes oriented in opposite transcriptional directions, in which each oppositely oriented distinct promoter is operably linked to a distinct fluorescent reporter marker, i.e., GFP and mCherry (Fig. 4, pg. 186-187). Amen teaches that integration of the nucleic acid construct can be “used for cell sorting (daughter/mother cells), studying aging, or screening yeast genome collections” (pg. 187).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have operably linked each promoter in the nucleic acid construct rendered obvious above, to two distinct fluorescent reporter markers, i.e., GFP and mCherry/dsRed, such that either the exogenous copy of the gene in the first cassette (i), or the endogenous copy of the gene in the second cassette (ii), are transcriptionally linked in-frame to the fluorescent reporter marker GFP. It would have amounted to a simple combination of known fluorescent reporter markers with a known nucleic acid construct, by known means to yield predictable results. A skilled artisan, seeking to improve the efficiency of mother/daughter cell sorting, and screening for aging-related genes, would have been motivated to transcriptionally link known fluorescent reporter markers to the exogenous and endogenous copy of the gene in the construct, because doing so would allow the skilled artisan to visually distinguish mother and daughter cells, and monitor expression of the endogenous and exogenous genes. A skilled artisan would have had a reasonable expectation of success because methods of preparing such constructs, and integrating them into specific yeast genome loci were routine in the art as evidenced by each of Goldfarb, Janke, and Amen.
Response to Remarks - 35 USC § 103
Applicant’s remarks regarding the § 103 rejections raised in the prior action have been reviewed. Applicant presents argument against the references individually. Applicant is reminded that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s arguments are addressed in order hereinafter as they apply to the combination of references cited in the prior action and above.
Applicant argues that “Goldfarb fails to describe or suggest part (b) of claim 1….” Applicant indicates that in contrast to the instant claims, which require that the second cassette of the construct comprise a conditional promoter designed to control transcription of the endogenous gene, Goldfarb describes that “deletion of the chromosomal copy of the essential gene is necessary (see Goldfarb at paragraph [0049]),” and means of “deleting the chromosomal copy of the essential gene… (see Goldfarb at paragraphs [0052]-[0053]).”
Examiner has reviewed the paragraphs of Goldfarb referenced by Applicant (i.e., paragraphs [0049], and [0052]-[0053]). Paragraph [0049] states that “it will be necessary to inactive, usually by deletion, the chromosomal copy of the essential gene employed in the DEAD transgenes” “[w]hen the DEAD cassette is meant to be maintained as an extrachromosomal plasmid.” Paragraphs [0052]-[0053] describe that “the DNA construct which forms the DEAD cassette can be… integrated directly into the host yeast genome,” and describe various exemplary means through which one can delete CDC6 (i.e., an essential gene described by Goldfarb) and insert sequences in yeast, e.g., using PCR. The skilled artisan would have interpreted these teachings, and others throughout Goldfarb (e.g., “When integration is desired, the DEAD cassette can be inserted into the yeast genome such that the native essential gene is disrupted, and effectively replaced by the DEAD transgenes,” [0047]), to mean that Goldfarb’s invention involves deletion of the endogenous gene, so that the only copies of the essential gene in the resultant yeast strain are under control of either a conditional promoter or a mother-specific promoter. A thorough review of Goldfarb failed to uncover any teachings which discourage modification of the constructs described therein through well-known cassette construction techniques known in the art. The skilled artisan would have been familiar with the teachings of Janke, and would have recognized that Janke’s cassette construction techniques would result in a construct and yeast strain with the same functions as that described by Goldfarb, i.e., wherein the only copies of the essential gene in the resultant yeast strain are under control of either a conditional promoter or a mother-specific promoter. There is no apparent deficiency in the combination of Goldfarb and Janke used to address the limitations of part (b) of the instant claims.
Applicant also states that Goldfarb does not teach the limitations of the instantly claimed yeast strains. Applicant’s remarks appear to copy the claim language, and do not appear to present any specific arguments to support the assertions of patentability over the combination of references used to render obvious the claims. These remarks will not be further addressed, accordingly.
Applicant states that “Janke also does not teach or suggest part (b) of claim 1.” Specifically, Applicant asserts that Janke does not teach or suggest a construct comprising two promoters oriented in opposite transcriptional directions. Examiner notes that Janke was not relied upon for this limitation. This limitation is covered by Goldfarb, for the reasons set forth in the prior action and above. There is no apparent deficiency in the teachings of the prior art or rationale with respect to this limitation.
Applicant also asserts that “Janke describes promoter replacement, the endogenous promoter is replaced with only a single promoter with different regulatory properties than the native promoter.” Examiner agrees with Applicant’s assessment that Janke describes promoter replacement, wherein an endogenous promoter is replaced with a promoter with different regulatory properties than the native promoter. Indeed, Examiner cites in the prior rejections and above, that “Janke teaches nucleic acid constructs configured to integrate upstream of the start codon of an endogenous gene and introduce a heterologous promoter as a means to control and modulate expression from the endogenous gene (pg. 957-958, “Promoter replacement and N-terminal tagging”; Table 1; Fig. 1C)… Janke teaches that the integrated nucleic acid constructs can replace the endogenous (“internal”) promoter with an inducible promoter, e.g., GAL1 (pg. 958, left col.). Janke teaches that substitution of the endogenous promoter for a heterologous promoter, and reporter marker operably linked thereto, advantageously allows the skilled artisan “to interfere with transcriptional regulation and to conditionally deplete gene products, while the availability of N-terminal tags provides the possibility to label proteins…” (pg. 960, right col.).”. There appears to be agreement about the teachings of Janke, and it is not clear how these remarks are intended to support the patentability of the instant claims over the combination of references above.
Applicant asserts that Henderson does not address the alleged deficiencies of Goldfarb and Janke. As Applicant indicates, Henderson is cited for separate teachings than Goldfarb and Janke. The rejections do not rely on Henderson for any teachings related to the alleged deficiencies of Goldfarb and Janke. Applicant’s remarks with respect to the alleged deficiencies of Goldfarb and Janke are addressed above. Taken together, Applicant’s remarks regarding the combination of Goldfarb, Janke, and Henderson are not found convincing to overcome the rejections, which are maintained above.
Applicant asserts that Farwick does not address the alleged deficiencies of Goldfarb, Janke, and Henderson. As Applicant indicates, Farwick is cited for separate teachings than Goldfarb, Janke, and Henderson. The rejections do not rely on Farwick for any teachings related to the alleged deficiencies of Goldfarb, Janke, and Henderson. Applicant’s remarks with respect to the alleged deficiencies of Goldfarb, Janke, and Henderson are addressed above.
Applicant also asserts that Amen does not “teach or suggest part (b) of claim 1” or “describe or suggest a construct that is integrated into a yeast genomic locus between a sequence upstream of the start codon of an endogenous gene encoding an essential plasma membrane protein and the start codon of the gene.” The limitations referred to by Applicant were addressed in the combination of Goldfarb, Janke, and Henderson; Amen is not relied on to teach these limitations. Applicant’s remarks with respect to the alleged deficiencies of Goldfarb, Janke, and Henderson are addressed above. Amen is relied upon to teach a construct comprising “two cassettes oriented in opposite transcriptional directions, in which each oppositely oriented distinct promoter is operably linked to a distinct fluorescent reporter marker, i.e., GFP and mCherry (Fig. 4, pg. 186-187),” which can be ““used for cell sorting (daughter/mother cells), studying aging, or screening yeast genome collections” (pg. 187).” The presence of specific working examples in Amen which differ in design from the instantly claimed invention would not be sufficient to discourage the skilled artisan from combining Amen with Goldfarb, Janke, and Henderson. A review of Amen failed to uncover any teachings which would have taught away from the instantly claimed invention. The skilled artisan would have been able to incorporate fluorescent reporter markers into the construct as claimed, and would have been motivated to do so, based on the teachings of art cited above.
Finally, Applicant asserts that new claims 83-84 are directed to non-obvious subject matter. These claims are withdrawn from consideration for the reasons described in paragraph 1 above, and have not been examined. Applicant’s remarks with respect to claims 83-84 are acknowledged, but are moot with respect to the claims under examination herein.
Allowable Subject Matter
A thorough search of the prior art did not uncover any teaching of SEQ ID NO: 1 or SEQ ID NO: 2 recited in instant claim 17. SEQ ID NO: 1 and SEQ ID NO: 2 align with portions of known vectors, and known portions of yeast genomes (see alignments of record). However, it is not apparent that the skilled artisan, guided by the teachings of Goldfarb, Janke, Henderson, or other relevant art reviewed during the search, would have arrived at the exact sequences of SEQ ID NO: 1 or SEQ ID NO: 2. Accordingly, SEQ ID NOs: 1 and 2 appear free of the prior art.
Conclusion
Claim 17 is allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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 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 JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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, JENNIFER A DUNSTON can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600