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
This action is written in response to applicant’s correspondence received on 01/28/2026. Claims 1-15, 20, 26, 33-34 are currently pending. Claims 20, 26 are withdrawn from prosecution as being drawn to nonelected subject matter. Accordingly, claims 1-15, 33-34 are examined herein. The restriction requirement mailed on 12.03.2025 is still deemed proper. Applicant's elected Group I, claims 1-15, 33-34 without traverse in the reply filed on 01/28/2026.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15, 33-34 in the reply filed on 01/28/2026 is acknowledged.
Claims 20, 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/28/2026.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in JP2020-039614 on 03/09/2020.
Drawings
The drawings are objected to because 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG.” In the current application, the view numbers for FIGs. 1-16 are preceded by the word "Fig." instead of the abbreviation "FIG.". Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10, 12-14, 33 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., law of nature, natural phenomenon, or product of nature) without significantly more. The inventor discloses and claims naturally occurring nucleic acid constructs. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Regarding claim 1, see the subject matter eligibility test below:
Step 1: Is the claim directed to a process, machine, manufacture, or composition of matter? Yes.
Claims 1-14, 33 recite “An artificial chromosome vector derived from a eukaryotic chromosome” and/or a “liposome”. Thus, the claimed invention is directed to a process, machine, manufacturer or composition of matter.
Step 2A,
Prong 1: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claims 1, No.
Claim 1 recites “An artificial chromosome vector derived from a eukaryotic chromosome”. The specification teaches that “… an ‘artificial chromosome vector’ is a vector that uses the replication mechanism of a eukaryotic chromosome, …, and can exist independently from the chromosomes of the host cells” (Page 11, ¶[0019], Lines 1-5). This definition encompasses a naturally occurring eukaryotic chromosome under the broadest reasonable interpretation (BRI), as eukaryotic chromosomes inherently use the replication mechanism of a eukaryotic chromosome. The further expansion on what “the replication mechanism of a eukaryotic chromosome” entails by the clause “which is capable of autonomous replication … … host cells” has no additional patentability weight to exclude naturally occurring eukaryotic chromosomes.
There are no markedly different characteristics in terms of structure between the claimed inventions in claims 1 and its closest natural counterparts, See MPEP § 2106.04(c)(II)(C)(2). The instant specification recites “… an ‘artificial chromosome vector’ is a vector … and can exist independently from the chromosomes of the host cells” (Page 11, ¶[0019], Lines 1-5). However, it lacks markedly different characteristics from nature because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Furthermore, the recitation “the vector comprising repetitive units of multiple ribosomal RNA genes (rDNA) and intergenic regions between the repetitive units…” encompass naturally occurring eukaryotic chromosomes such as chromosome XII (ChXII) of the budding yeast Saccharomyces Cerevisiae according to the instant specification (Page 1, ¶[0002]-¶[0003]; Page 11, ¶[0020], lines 4-8).
The instant specification attempts to define what is a barcode (BC) by reciting: “As used herein, a ‘barcode sequence’ is a nucleic acid for inserting a target gene into an artificial chromosome, and signifies a nucleic acid having a unique sequence for distinguishing among multiple target genes” in ¶[0031] (Page 14), however, the only disclosed structure for a barcode is “a nucleic acid”. The clause “for inserting a target gene … for distinguishing among multiple target genes” is intended use, thereby carries no patentability weight.
Lastly, Zhang et al. (Engineering the ribosomal DNA in a megabase synthetic chromosome. Science. 2017 Mar 10;355(6329):eaaf3981; Hereinafter, Zhang) teaches that “…the internal transcribed spacer (ITS) region, a ‘DNA barcode’ used widely in species identification” (Page 2 of 7, right column, 2nd ¶, lines 3-5), indicating that naturally occurring rDNA cluster sequences can be considered as “barcodes” under BRI, which also suggests that the naturally occurring IGS1 region sequences can also be considered “barcodes”.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 1, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 1 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 1 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
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Regarding claim 2, James et al. (Repetitive sequence variation and dynamics in the ribosomal DNA array of Saccharomyces cerevisiae as revealed by whole-genome resequencing. Genome Res. 2009 Apr;19(4):626-35; Hereinafter, James) teaches “ARS”, “5S”, “E-pro”, “RFB” (Page 630 Figure 2 by James; See below) of the S. cerevisiae ChXII. Kobayashi et al. (Recombination regulation by transcription-induced cohesin dissociation in rDNA repeats. Science. 2005 Sep 2;309(5740):1581-4; Hereinafter, Kobayashi’05) teaches “…cohesin association on both sides of E-pro, …” (Page 1581, right column, 2nd¶, lines 30-35). Since this is the intergenic region between 2 flanking rDNA repeats, these recited elements are inherently 5’ to one of the rDNA genes.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 2, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 2 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 2 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 3, Wang et al. (Transcriptional homogenization of rDNA repeats in the episome-based nucleolus induces genome-wide changes in the chromosomal distribution of condensin. Plasmid. 2008 Jan;59(1):45-53; Hereinafter, Wang) teaches condensin binding sites within the intergenic regions of rDNA array of the chromosome XII of S. Cerevisiae (Page 47, Fig. 1A, below, see arrows and marked rDNA array for the identified condensin binding sites within the intergenic region of rDNA).
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 3, No.
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There are no markedly different characteristics in terms of structure between the claimed inventions in claim 3 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 3 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 4, based on the teaching of Zhang et al. (Engineering the ribosomal DNA in a megabase synthetic chromosome. Science. 2017 Mar 10;355(6329):eaaf3981; Hereinafter, Zhang) that “…the internal transcribed spacer (ITS) region, a ‘DNA barcode’ used widely in species identification” (Page 2 of 7, right column, 2nd ¶, lines 3-5), therefore, it can be interpreted under BRI that the naturally occurring sequences between a 5S rDNA and an E-pro sequence of a eukaryotic chromosome that comprise an rDNA array can be considered a barcode.
James (2009, see citation above) teaches that the distance between an E-pro and its adjacent 5S rDNA is approximately 200nt (Page 630 Figure 2 by James; See below). However, James does not teach any restriction sites available in this sequence.
Genscript / WaybackMachine (restriction enzyme analysis in the GenScript Restriction Enzyme Map Analysis Tools www.genscript.com/tools/restriction-enzyme-map-analysis; First made public in 2017, see archival retrieval record of the 2017 Genscript website record WaybackMachine attached and listed in the PTO-892 form) teaches that the 200nt upstream sequence encompasses numerous restriction sites that could be selected to mark the “barcode” in the naturally occurring budding yeast ChXII rDNA IGS1 between the 5S rDNA and the E-pro (attached and listed in PTO-892 for as NPL_Genscript_WaybackMachineArchive_2017_Restriction Enzyme Map Analysis.pdf).
The source of the genomic data is the NCBI / Saccharomyces Genome Database (SGD; <www.yeastgenome.org>) and the related SGD ID is SGD:S000006479 updated on 02/14/2007. (Attached and listed as NPL_NCBI_SGD_2007_200nt upstream of 5S rDNA toward E-pro promoter.pdf in the PTO-892 form).
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 2, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 4 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 4 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 5, naturally occurring eukaryotic chromosomes further comprise a telomere sequence and a centromere sequence, because Cooper et al. (The Cell: A Molecular Approach. 2nd edition. Sunderland [MA]: Sinauer Associates; 2000. Chromosomes and Chromatin; Hereinafter, Cooper) teaches “…The telomere DNA sequences …” (Page 6, 2nd ¶, lines 1 & 9) and “Centromeric DNA sequences …” (Page 4, 4th ¶, line 1).
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 5, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 5 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 5 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 6, in addition to the presence of E-Pro bidirectional promoter sequence in the IGS1 sequence of S. Cerevisiae chromosome XII taught by Kobayashi’05 above, Bairwa et al. (Replication fork arrest and rDNA silencing are two independent and separable functions of the replication terminator protein Fob1 of Saccharomyces cerevisiae. J Biol Chem. 2010 Apr 23;285(17):12612-9; Hereinafter, Bairwa) teaches “Ter sites located in the intergenic spacer region of rDNA….” (Page 12612, Abstract, lines 1-4). Since that “replication terminator protein Fob1” binds the “Ter sites” (Figure 1A below) in IGS1 and “…promotes polar replication fork arrest” (Page 12612, Abstract, lines 1-4), these are inherently terminator sequences based on these interactions and outcomes.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 6, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 6 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 6 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 7, Kobayashi’11 (Regulation of ribosomal RNA gene copy number and its role in modulating genome integrity and evolutionary adaptability in yeast. Cell Mol Life Sci. 2011 Apr;68(8):1395-403; Hereinafter, Kobayashi’11) teaches that the replication fork barrier sequence (RFB binds the Fob1 terminator protein, hence RFB serves as the terminator sequence) is disposed on the 3’ side of the E-pro promoter sequence (See Fig. 1 below; Page 1396), and a target gene could be inserted between E-pro and the RFB terminator sequence.
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Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 7, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 7 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 7 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 8, Kobayashi’11 further teaches that “…approximately 150 copies of rDNA, located on chromosome XII” (Page 1396, left column, 1st¶, lines 7-8). Therefore, naturally occurring rDNA array-bearing chromosomes, such as the chromosome XII of the budding yeast can have minimum of 2 copies (otherwise wouldn’t count as “repeat”) up to 150 copies of rDNA.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 8, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 8 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 8 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claims 9-10, see example of the naturally occurring chromosome XII (12th) of the budding yeast (Page 1, ¶[0003]) taught by the instant specification.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claims 9-10, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claims 9-10 and their closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claims 9-10 refer to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 11, since Dultz et al. (Global reorganization of budding yeast chromosome conformation in different physiological conditions. J Cell Biol. 2016 Feb 1;212(3):321-34; Hereinafter, Dultz) teaches that “The budding yeast GAL locus on chromosome II (chr II) … consists of three genes, GAL7, GAL10, and GAL1, …” (Page 321, right column, lines 3-9). For a GAL promoter to enter the IGS1 region of the rDNA array on chromosome XII naturally, a transposition or a rare, complex double-strand break repair event involving homologous recombination between non-homologous regions (translocation) would be required. Therefore, the presence of an inducible GAL promoter in the IGS1 region of the rDNA repeats on a naturally occurring chromosome, such as ChXII of the budding yeast Saccharomyces Cerevisiae is unlikely to be found in nature.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 11, Yes.
There are markedly different characteristics in terms of structure between the claimed inventions in claim 11 and its closest natural counterpart, the S. cerevisiae ChXII, because it is NOT a product “derived” from the closest counterpart in nature with substantial alteration in any characteristics.
No, claims 11 does NOT refer to a judicial exception.
Regarding claim 12, there is no third alternative to “homologous or heterologous”.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 12, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 12 and its closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 12 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 13, there is no third alternative to “identical or different from each other”.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 13, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 13 and it’s closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 13 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 14, a naturally occurring eukaryotic cell naturally comprises a naturally occurring chromosome that claim 1 encompasses.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claims 14, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 14 amd their closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics.
Yes, claim 14 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes.
Regarding claim 33, van der Pol et al. (Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 2012 Jul;64(3):676-705. doi: 10.1124/pr.112.005983. Epub 2012 Jun 21; Hereinafter, van der Pol) teaches that “Both eukaryotic and prokaryotic cells release small, phospholipid-enclosed vesicles …” (Page 677, Abstract, lines 1-3) and that “Because vesicles may pass the blood-brain barrier, they can perhaps even be considered naturally occurring liposomes” (Page 677, Abstract, lines 22-25). Thus, both the element of “a liposome” and “the artificial chromosome vector according to claim 1” refer to naturally occurring structures.
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): Claim 33, No.
There are no markedly different characteristics in terms of structure between the claimed inventions in claim 33 and their closest natural counterpart, the S. cerevisiae ChXII, because it is merely a product “derived” from the closest counterpart in nature with no alteration in any characteristics. In addition, the specification does not teach any distinct difference between a naturally occurring liposome found in eukaryotic cells in nature and “a liposome”.
Yes, claim 33 refers to a judicial exception because the recited limitations encompass naturally occurring eukaryotic chromosomes and liposomes.
Step 2A,
Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? Claims 1-10, 12-14, 33, No.
Independent claim 1 recites “…wherein an intergenic region 1 (IGS1) of the intergenic regions comprises a barcode sequence for incorporating and distinguishing a target gene” when reciting the judicial exception, however, this element merely recites an intended use and fails to amount to a “particular treatment and prophylaxis”. See MPEP § 2106.04(d)(2).
Claims 2-10, 12-14, 33 that depend from claim 1 also fail to recite additional elements that amount to “particular treatment and prophylaxis”. And the recitation of “a liposome” in claim 33 does not remedy the failure to recite additional elements that amount to “particular treatment and prophylaxis”. See MPEP § 2106.04(d)(2).
Therefore, claims 1-10, 12-14, 33 do not include or recite additional elements that integrate the judicial exception into a practical application.
Step 2B: Does the claim recite additional elements that amount to significantly more? No.
Claims 1-10, 12-14, 33 do NOT recite any additional elements that are sufficient to amount to significantly more than the judicial exception.
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 12 and 15 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 12 recites the limitations “the inserted target gene” and “the host …”. There is insufficient antecedent basis for these limitations in the claim because neither claim 1 that claim 12 depends from nor claim 12 itself requires “a target gene” to have been inserted, nor do they require a “host” other than the “vector” itself. Therefore, the requirement that the target gene being homologous or heterologous to the host is ambiguous because the scope of the target gene depends upon a limitation that is outside the scope of the claim.
Claim 15 refers to plural barcode sequences, but claim 1 broadly encompasses just one barcode sequence. Therefore, it is not clear how many barcode sequences are required to be introduced. It is not clear whether it is sufficient to introduce just one barcode sequence or multiple barcode sequences.
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.
Claims 12-13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 12, the limitations that “a target gene has been inserted into a vector” and “a host” do not exist in claim 1 that claim 12 depends from, nor do they exist in claim 12 itself. Even if these limitations were required in either claim, there are only two possibilities for this inserted target gene, namely it is either homologous or heterologous to the host.
Regarding claim 13, for multiple target genes to be inserted into multiple barcode sequences within the artificial chromosome vector, these target genes can only be either identical or different, i.e. not identical, from each other, there could not be a third alternative.
Therefore, claims 12-13 fail to further limit the subject matter of claim 1 upon which they depend from.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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- 10, 12-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kobayashi’01 (Mol Cell Biol. 2001 Jan;21(1):136-47) as evidenced by Buck et al. (Nucleic Acids Res. 2016 Jul 27;44(13):6173-84) and Zhang (Science. 2017 Mar 10;355(6329):eaaf3981; see full citation in §101 rejection above). The rejection of claim 2 is further evidenced by James (Genome Res. 2009 Apr;19(4):626-35) and Kobayashi’05 (Science. 2005 Sep 2;309(5740):1581-4; Full citation above in §101 section). The rejection of claim 3 is further evidenced by Wang (Plasmid. 2008 Jan;59(1):45-53; See full citation in §101 above). The rejection of claim 4 is further evidenced by NCBI / SGD (2007), and Genscript / WaybackMachine (2017). The rejection of claim 5 is further evidenced by Cooper (The Cell: A Molecular Approach. 2nd edition. Sunderland [MA]: Sinauer Associates; 2000. Chromosomes and Chromatin). The rejection of claim 6 is further evidenced by Bairwa (J Biol Chem. 2010 Apr 23;285(17):12612-9; See full citation in §101 above). The rejection of claims 7-10 is further evidenced by Kobayashi’11 (Cell Mol Life Sci. 2011 Apr;68(8):1395-403; See full citation in §101 above).
Kobayashi’01 teaches:
an artificial chromosome vector in the TK201 yeast strain,
derived from a eukaryotic chromosome comprising repetitive units of multiple ribosomal RNA genes (rDNA) and intergenic regions between the repetitive units,
wherein an intergenic region 1 (IGS1) of the intergenic regions comprises a barcode sequence for incorporating and distinguishing a target gene.
The recitation “In the yeast Saccharomyces cerevisiae, approximately 150 rDNA tandem repeats are located on chromosome XII. … and two nontranscribed regions (NTS1 and NTS2)” (Page 136, first ¶, lines 4-8; Figure 1A) supports 1) and 2)
The recitation “…TAK201, which contained two copies of rDNA …” (Page 139, left column, 1st ¶, line 16) characterizes the key difference of the artificial chromosome vector TAK201 from the naturally occurring yeast ChXII.
Although Kobayashi’01 does not teach NTS1 is also known as IGS1. Buck (2016) confirms so by reciting “NTS1 and NTS2 are also observed in the literature as intergenic spacers IGS1 and IGS2, respectively.” (Page 6173, right column, 2nd ¶, lines 13-14).
Although Kobayashi’01 does not teach “wherein an intergenic region 1 (IGS1) of the intergenic regions comprises a barcode sequence for incorporating and distinguishing a target gene”. Zhang (2017) teaches that naturally occurring rDNA cluster sequences can be considered as “barcodes” under BRI, as discussed above in the “Markedly different characteristic analysis” section.
Regarding claim 2, Kobayashi’01’s teachings have been discussed above. Kobayashi’01 further teaches: an autonomous replicating sequence (ARS), a 5S rDNA sequence, and a replication fork barrier (RFB) sequence in that order from the 5’ side of the rDNA gene (see Figure 1A by Kobayashi’01; Page 136, first ¶, lines 4-8; Figure 1A).
However, neither Kobayashi’01, nor Buck, nor Zhang teaches “a cohesin binding site” or “a non-coding promoter (E-pro)” in that order from the 5’ side of the rDNA gene.
James (2009) and Kobayashi’05 (2005) teach the elements of “a cohesin binding site” and “a non-coding promoter (E-pro)” in that order from the 5’ side of the rDNA gene. The teachings of Kobayashi’05 have been discussed above in the 35 U.S.C. §101 subject matter analysis Step 2A Prong 1 section. However, since the artificial chromosome vector in yeast strain TAK201 disclosed by Kobayashi’01 was derived from naturally occurring budding yeast ChXII with 2 copies of rDNA genes and intact IGS1 and IGS2, the claimed elements are inherently incorporated in the artificial vector in TAK201.
Regarding claim 3, the teachings of Kobayashi’01 have been discussed above.
However, Kobayashi’01 does not teach that “the intergenic region further comprises a condensin binding site”.
Wang teaches that “the intergenic region further comprises a condensin binding site” and it has been discussed above in the 35 U.S.C. §101 subject matter analysis Step 2A Prong 1 section. However, since the artificial chromosome vector TAK201 disclosed by Kobayashi’01 derived from naturally occurring budding yeast ChXII with 2 copies of rDNA genes and intact IGS1 and IGS2, the claimed elements are inherently incorporated in TAK201.
Regarding claim 4, the teachings of Kobayashi’01 have been discussed above.
However, Kobayashi’01 does not teach that “each barcode sequence is inserted into a restriction enzyme site located between a 5S rDNA sequence and an E-pro sequence”.
The teachings of James, NCBI / SGD, and Genscript / WaybackMachine regarding the numerous restriction sites comprised in the approximately 200nt sequence between a 5S rDNA sequence and an E-pro sequences have been discussed above and in the 35 U.S.C. §101 subject matter analysis Step 2A Prong 1 section.
However, Kobayashi’01 only teaches using recombination as a method to generate a target gene insert in the IGS1 region by reciting “The fragment containing URA3 and the two flanking sequences was separated from the vector portion and then introduced into TAK201 by transformation for replacement of the pertinent segment with URA3” (Page 138, right column, 4th ¶, lines 16-19), and does not teach restriction enzyme site-based target gene insertion.
However, since the artificial chromosome vector comprised in the budding yeast strain TAK201 as disclosed by Kobayashi’01 was derived from naturally occurring budding yeast ChXII with 2 copies of rDNA genes and intact IGS1 and IGS2, the claimed elements, i.e. restriction enzyme sites, are inherently incorporated in the artificial chromosome vector in the strain TAK201.
Regarding claim 5, the teachings of Kobayashi’01 have been discussed above. However, Kobayashi’01 does not teach that the artificial chromosome vector TAK201 “further comprising a telomere sequence and a centromere sequence”.
Cooper (2000) teaches that telomeres and a centromere are specialized regions of a eukaryotic chromosome, and Cooper’s teaching has been discussed in the 35 U.S.C. §101 subject matter analysis Step 2A Prong 1 section.
However, since the artificial chromosome vector in the yeast strain TAK201 as disclosed by Kobayashi’01 was derived from naturally occurring budding yeast ChXII with 2 copies of rDNA genes and intact IGS1 and IGS2, the claimed elements are inherently incorporated in the artificial chromosome vector in the strain TAK201.
Regarding claim 6, the teachings of Kobayashi’01 have been discussed above. However, Kobayashi’01 does not teach that the artificial chromosome vector “wherein each barcode sequence comprises a promoter sequence and a terminator sequence for controlling expression of the target gene”.
The teaching of the presence of “E-pro” promoter by Kobayashi’05 (2005) has been discussed above. The teaching of the presence of terminator sequences “Ter sites” by Bairwa (2010) has been discussed in the 35 U.S.C. §101 subject matter analysis Step 2A Prong 1 section.
However, since the artificial chromosome vector in the yeast strain TAK201 disclosed by Kobayashi’01 was derived from naturally occurring budding yeast ChXII with 2 copies of rDNA genes and intact IGS1 and IGS2, the claimed elements are inherently incorporated in the artificial chromosome vector in the yeast strain TAK201. Since the “target gene” is not defined in the claims, nor in the specification, under BRI, the “target gene” is interpreted as any gene that E-pro and Ter sites control.
Regarding claim 7, the teachings of Kobayashi’01 have been discussed above. However, Kobayashi’01 does not teach that “the terminator sequence is disposed on the 3' side of each target gene and the promoter sequence is disposed on the 5' side”.
The teaching of the presence of “E-pro” promoter by Kobayashi’05 (2005) has been discussed above. The teaching of the terminator sequence on the 3’ side of the E-pro promoter sequence by Kobayashi’11 (2011) has been discussed in the 35 U.S.C. §101 subject matter analysis Step 2A Prong 1 section above (See Fig. 1 in Kobayashi’11 above; Page 1396), and a target gene could be inserted between E-pro and the RFB terminator sequence.
However, since the artificial chromosome vector in the yeast strain TAK201 disclosed by Kobayashi’01 was derived from naturally occurring budding yeast ChXII with 2 copies of rDNA genes and intact IGS1 and IGS2, the claimed elements are inherently incorporated in the artificial chromosome vector in the yeast strain TAK201. Since the “target gene” is not specifically defined in the claims, nor in the specification, under BRI, the “target gene” is interpreted as any gene that E-pro and Ter sites control.
Regarding claim 8, Kobayashi’11 further teaches that “…comprising approximately 150 copies of rDNA, located on chromosome XII” (Page 1396, left column, 1st¶, lines 7-8). Therefore, naturally occurring rDNA array-bearing chromosomes, such as the chromosome XII of the budding yeast can have minimum of 2 copies (otherwise wouldn’t count as “repeat”) up to 150 copies of rDNA. And the TAK201 taught by Kobayashi’01 contains 2 copies of rDNA repeats.
Regarding claim 9-10, Kobayashi’01 further teaches that the TAK201 artificial chromosome vector was derived from Saccharomyces cerevisiae, a budding yeast strain (see title of Kobayashi’01; Fig. 1legend, line 1, of Kobayashi’11 above).
Regarding claims 12-13, both fail to further limit claim 1, hence the above rejection still applies.
Regarding claim 14, Kobayashi’01 further teaches a yeast strain (a eukaryotic yeast cell) comprising an artificial chromosome vector with only 2 copies of the rDNA repeats, i.e. TAK201 (Page 139, left column, 1st ¶, line 16).
Regarding claim 15, Kobayashi’01 further teaches a method of manufacturing the artificial chromosome vector according to claim 1, the method comprising a step of inserting barcode sequences into IGS1. Based on the teachings of Zhang (2017) above, under BRI, any sequence can be interpreted as a “barcode”, therefore, the teaching by Kobayashi’01 that “The fragment containing URA3 and the two flanking sequences was separated from the vector portion and then introduced into TAK201 by transformation for replacement of the pertinent segment with URA3” (Page 138, right column, 4th ¶, lines 16-19) is a step of manufacturing the artificial chromosome vector.
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.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Kobayashi’01 (2001) as evidenced by Buck (2016), Zhang (2017), Kobayashi’05 (2005), and Bairwa (2010), as applied to claim 6 above, and further in view of Peng et al. (An Expanded Heterologous GAL Promoter Collection for Diauxie-Inducible Expression in Saccharomyces cerevisiae. ACS Synth Biol. 2018 Feb 16;7(2):748-751; Hereinafter, Peng).
The teachings of Kobayashi’01, Buck, Zhang, Kobayashi’05, and Bairwa have been discussed above.
However, none of Kobayashi’01, Buck, Zhang, Kobayashi’05, and Bairwa teaches that the artificial chromosome vector “wherein the promoter is a galactose inducible (GAL) promoter”.
Peng (2018) teaches that GAL promoters have been used to control gene expression in the budding yeast S. cerevisiae (Page 748, Abstract lines 1-3), which is known in the art, PHOSITAs have these GAL promoters as tools at disposal to meet diverse research objectives.
It would have been obvious to PHOSITAs before the effective filing date of the claimed invention to incorporate the teachings, strategies, and motivations taught by Peng to manipulate target gene expression and modify artificial chromosome vector in the yeast strain TAK201 taught by Kobayashi’01 according to known methods to perform simple substitution by replacing a non-inducible promoter with an GAL promoter, another known element, and yield predictable results in that inducible promoters provide greater control of the expression of the target genes.
Claims 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Kobayashi’01 (2001) as evidenced by Buck (2016) and Zhang (2017), as applied to claim 1 above, and further in view of Perkins (US2005/0181506A1) and Jeong (Adv. Funct. Mater.2020, 30, 1907182;).
The teachings of Kobayashi’01, Buck, and Zhang have been discussed above. However, none of Kobayashi’01, Buck, and Zhang teaches “an artificial cell comprising a liposome and the artificial chromosome vector according to claim 1”.
Perkins (2005) teaches that “the artificial chromosome is introduced into the … cell by … liposomes, …”. The claimed structure comprises “a liposome” and “the artificial chromosome” (Page 199, claim 80), which is inherently an artificial chromosome vector in a liposome. However, Perkins does not teach “an artificial cell”.
Jeong (January 2020) teaches “… supportive for creating artificial cells” (Page 1907180, left column, last 3 lines) and addresses the motivation of constructing an artificial cell using liposomes and genetic materials that encode membrane proteins by reciting “… in artificial cells to identify life phenomena and to reproduce actual cells” (Page 1907182, left column, 2nd¶, lines 5-8).
Regarding claim 33, an artificial cell comprising a liposome and an artificial chromosome vector is an obvious step for PHOSITAs motivated by the success of existing research based on artificial cells summarized by Jeong.
It would be obvious for a PHOSITA to make “an artificial cell” comprising the artificial chromosome vector according to claim 1 into a liposome based on the teachings of Kobayashi’01, Buck, Zhang, and Perkins, and following the teachings, strategies, and motivations taught by Jeong.
Regarding claim 34, the specification teaches “Examples of artificial cell membranes include liposomes and micelles. Liposomes are lipid bilayer vesicles, and can be prepared by known methods by a person skilled in the art” (Page 28, ¶[0085]).
It would have been obvious for PHOSITAs to apply known methods in the art and manufacture “an artificial cell”, the method comprising a step of introducing the artificial chromosome vector according to claim 1 into a liposome, based on the teachings, strategies, and motivation provided by Kobayashi’01, Buck, Zhang, Perkins, and Jeong, particularly when the target genes of interest involve membrane bound proteins and signaling networks related to such proteins that must be expressed on a cell membrane, and would have arrived at the claimed process invention admittedly known in the art.
Conclusion
No claims are allowable.
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/DELPHINUS DOU YI YU/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636