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 .
Election/Restrictions
Applicant’s election with traverse of Group I, claims 16-21, in the reply filed on November 26, 2025 is acknowledged. Claims 22-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Groups 2 through 4, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 11/26/2025.
Applicant’s traversal is not persuasive. The present application is being examined as a national stage application under 35 USC 372 guidelines, and therefore the determination of unity by the International Searching Authority is not binding to the USPTO (see MPEP 1893.03 (d)). The claims continue to be directed to distinct inventions including (i) a method of isolating a replication origin, (ii) nucleic acid compositions and vectors comprising the origin, (iii) a method of gene expression, and (iv) a computer program product. Accordingly, the restriction (10/7/2025) requirement is maintained.
Thus, claims 16-21 are under examination (2/16/2023).
Claim Status
Claims 16-21 are under examination (2/16/2023).
Priority
Claims 16-21 receive a priority date of 9/6/2021, the effective filing date of EP20305987.8.
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.
The Information Disclosure Statement filed 2/16/2023 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities (see MPEP § 608.01):
The use of the terms “Illustra” (p. 26), “Bioprime” (p. 26), “Illumina” (p. 26, 30), “Qiagen” (p. 30) which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The disclosure is further objected to because it contains an embedded hyperlink and/or other form of browser-executable code in reference to UCSC genome browser (p. 3), HMEC cells (p.25), ReMap origins (p. 30), and SNS-seq data (p. 35). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 16 is objected to because of the following informalities:
Claim 16, part (b) at line 1: “every 100 pb” should read “every 100 bp.”
Claim 16, part (c), line 19 “eukaryotic” should not be capitalized.
Claim 16, part (c), line 15: “500 pb up 6000 pb” should read “500 bp up to 6000 bp.”
Claim 19 is objected to because of the following informality:
Claim 19 at line 2: “first 500 pb” should read “first 500 bp.”
Claim 20 is objected to because of the following informality:
Claim 20 at line 2: “716pb” should read “716bp.”
Claim 21 is objected to because of the following informality:
Claim 21 is objected to under 35 USC 112(d) as being of improper dependent form because it recites “according to anyone of claims 16”, while claim 16 is a single claim. Correction is required to clarify proper dependency.
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 16-21 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 16 is rejected. Claim 16 recites the limitation "the 172" in step (c) at line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 is further rejected. Claim 16 recites the limitation "the variation" in step (c) at line 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 is further rejected. Claim 16 recites the limitation "the fragments" in step (c) at line 14. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 is further rejected. Claim 16 recites the limitation " the DNA of an Eukaryotic cell" in step (c) at line 19. There is insufficient antecedent basis for this limitation in the claim.
Claims 17-21 are included in this rejection due to their dependency on claim 16.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(g)(1) during the course of an interference conducted under section 135 or section 291, another inventor involved therein establishes, to the extent permitted in section 104, that before such person’s invention thereof the invention was made by such other inventor and not abandoned, suppressed, or concealed, or (2) before such person’s invention thereof, the invention was made in this country by another inventor who had not abandoned, suppressed, or concealed it. In determining priority of invention under this subsection, there shall be considered not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice, from a time prior to conception by the other.
A rejection on this statutory basis (35 U.S.C. 102(g) as in force on March 15, 2013) is appropriate in an application or patent that is examined under the first to file provisions of the AIA if it also contains or contained at any time (1) a claim to an invention having an effective filing date as defined in 35 U.S.C. 100(i) that is before March 16, 2013 or (2) a specific reference under 35 U.S.C. 120, 121, or 365(c) to any patent or application that contains or contained at any time such a claim.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 16-18 are rejected under 35 U.S.C. 102(a)(1) and 102 (a)(2) as being anticipated by Nadimpalli et al. (US PGPub 2003/0005483 A1; published 1/2/2003).
Regarding claims 16-17, Nadimpalli teaches isolated prolifera nucleic acids and their encoded proteins, including methods and compositions relating to altering prolifera levels in plants (i.e., invention further provides recombinant expression cassettes, host cells, transgenic plants, and antibody compositions) (Abstract). Nadimpalli incorporates in these teachings, an isolated nucleic acid comprising a member selected from the group consisting of (a) a polynucleotide having a specified sequence identity to a polynucleotide encoding a polypeptide of the present invention; (b) a polynucleotide which is complementary to the polynucleotide of (a); and, (c) a polynucleotide comprising a specified number of contiguous nucleotides from a polynucleotide of (a) or (b) where the isolated nucleic acid can be DNA (Paragraph 9, lines 1-5). Specifically, Nadimpalli teaches that replication control can be modified on a more local level, thereby allowing specific replication origins in some parts of the genome to be activated repeatedly providing a selective advantage for gene amplification and in Drosophila, chondrion genes have been shown to be selectively amplified by this process, where selectively expressing a prolifera polynucleotide of the present invention with the Origin Recognition Complex (ORC), at a set of replication origins of specific genes, copy number in cells can be controlled (Paragraph 86, lines 1-5).
Nadimpalli teaches that the previously shown method conditions are sequence-dependent and will be different in different circumstances and by controlling the stringency of the hybridization and/or washing conditions, target sequences can be identified which are 100% complementary to the probe (homologous probing) and can be adjusted to allow some mismatching in sequences so that lower degrees of similarity are detected (heterologous probing) where generally, a probe is less than about 1000 nucleotides in length, optionally approximately 500 nucleotides in length (Paragraph 61, lines 1-5).Nadimpalli also teaches that the previously explained method includes polynucleotides that can encode a polypeptide having a subsequence having at least 10, 15, 20, 25, 30, 35, 40, 45, or 50, contiguous amino acids from the prototype polypeptide and where further, the number of such subsequences encoded by a polynucleotide of the instant embodiment can be any integer selected from the group consisting of from 1 to 20, such as 2, 3, 4, or 5 and the subsequences can be separated by any integer of nucleotides from 1 to the number of nucleotides in the sequence such as at least 5, 10, 15, 25, 50, 100, or 200 nucleotides (Paragraph 118, lines 5-10). Nadimpalli also teaches that complementary bases associate through hydrogen bonding in double stranded nucleic acids where for example, the following base pairs are complementary: guanine and cytosine; adenine and thymine; and adenine and uracil (Paragraph 124, lines 1-5). Further, Nadimpalli teaches that as indicated in (g), above, the present invention provides isolated nucleic acids comprising polynucleotides which comprise at least 15 contiguous bases from the polynucleotides of sections (A) through (F) as discussed above where the length of the polynucleotide is given as an integer selected from the group consisting of from at least 15 to the length of the nucleic acid sequence from which the polynucleotide is a subsequence of, for example, polynucleotides of the present invention are inclusive of polynucleotides comprising at least 15, 20, 25, 30, 40, 50, 60, 75, or 100 contiguous nucleotides in length from the polynucleotides of interest and optionally, the number of such subsequences encoded by a polynucleotide of the instant embodiment can be any integer selected from the group consisting of from 1 to 20, such as 2, 3, 4, or 5, where the subsequences can be separated by any integer of nucleotides from 1 to the number of nucleotides in the sequence such as at least 5, 10, 15, 25, 50, 100, or 200 nucleotides (Paragraph 126, lines 1-10).
Nadimpalli teaches that for DNA-DNA hybrids, the content includes 41-61% of guanosine and cytosine nucleotides in the DNA, % form is the percentage of formamide in the hybridization solution, and L is the length of the hybrid in base pairs.
Nadimpalli teaches that in optional embodiments, the stringency allows for selective hybridization of sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, or 98% sequence identity over the length of the hybridized region where full-length enriched cDNA libraries can be normalized to increase the representation of rare sequences (Paragraph 130, lines 10-15). Further, Nadimpalli teaches the primers are complementary to a subsequence of the target nucleic acid which they amplify but may have a sequence identity ranging from about 85% to 99% relative to the polynucleotide sequence which they are designed to anneal to and those skilled in the art will appreciate, the sites to which the primer pairs will selectively hybridize are chosen such that a single contiguous nucleic acid can be formed under the desired nucleic acid amplification conditions where the primer length in nucleotides is selected from the group of integers consisting of from at least 15 to 50 and thus, the primers can be at least 15, 18, 20, 25, 30, 40, or 50 nucleotides in length where those of skill will recognize that a lengthened primer sequence can be employed to increase specificity of binding (i.e., annealing) to a target sequence (Paragraph 109, lines 1-10). Further, Nadimpalli teaches that a non-annealing sequence at the 5'end of a primer (a "tail") can be added, for example, to introduce a cloning site at the terminal ends of the amplicon (Paragraph 109, lines 1-10).
Nadimpalli teaches that the expression of isolated nucleic acids encoding a protein of the present invention will typically be achieved by operably linking, for example, the DNA or cDNA to a promoter (which is either constitutive or regulatable), followed by incorporation into an expression vector and the vectors can be suitable for replication and integration in either prokaryotes or eukaryotes where typical expression vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the DNA encoding a protein of the present invention (Paragraph 178, lines 1-10). Further, Nadimpalli teaches that to obtain high level expression of a cloned gene, it is desirable to construct expression vectors which contain, at the minimum, a strong promoter to direct transcription, a ribosome binding site for translational initiation, and a transcription/translation terminator and one of skill would recognize that modifications can be made to a protein of the present invention without diminishing its biological activity and some modifications may be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein and include, for example, a methionine added at the amino terminus to provide an initiation site, or additional amino acids (e.g., poly His) placed on either terminus to create conveniently located purification sequences (restriction sites or termination codons can also be introduced) (Paragraph 178, lines 10-20).
Nadimpalli also teaches that a variety of eukaryotic expression systems such as yeast, insect cell lines, plant and mammalian cells, are known to those of skill in the art (Paragraph 183, lines 1-5).
Regarding claim 18, Nadimpalli teaches that replication control can be modified on a more local level, thereby allowing specific replication origins in some parts of the genome to be activated repeatedly providing a selective advantage for gene amplification and in Drosophila, chondrion genes have been shown to be selectively amplified by this process, where selectively expressing a prolifera polynucleotide of the present invention with the Origin Recognition Complex (ORC), at a set of replication origins of specific genes, copy number in cells can be controlled (Paragraph 86, lines 1-5). Nadimpalli also teaches that the expression of isolated nucleic acids encoding a protein of the present invention will typically be achieved by operably linking, for example, the DNA or cDNA to a promoter (which is either constitutive or regulatable), followed by incorporation into an expression vector and the vectors can be suitable for replication and integration in either prokaryotes or eukaryotes where typical expression vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the DNA encoding a protein of the present invention (Paragraph 178, lines 1-10).
Thus, Nadimpalli teaches each and every limitation of claims 16-18, and therefore Nadimpalli anticipates claims 16-18.
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.
Claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Nadimpalli et al. (US PGPub 2003/0005483 A1; published 1/2/2003), as applied to claims 16-18 above, in view of Rhodes et al., (“G-quadruplexes and their regulatory roles in biology”, Nucleic Acids Research, 2015).
As shown above, Nadimpalli teaches an isolated nucleic acid comprising a member selected from the group consisting of (a) a polynucleotide having a specified sequence identity to a polynucleotide encoding a polypeptide of the present invention; (b) a polynucleotide which is complementary to the polynucleotide of (a); and, (c) a polynucleotide comprising a specified number of contiguous nucleotides from a polynucleotide of (a) or (b) where the isolated nucleic acid can be DNA (Paragraph 9, lines 1-5). Specifically, Nadimpalli teaches that replication control can be modified on a more local level, thereby allowing specific replication origins in some parts of the genome to be activated repeatedly providing a selective advantage for gene amplification and in Drosophila, chondrion genes have been shown to be selectively amplified by this process, where selectively expressing a prolifera polynucleotide of the present invention with the Origin Recognition Complex (ORC), at a set of replication origins of specific genes, copy number in cells can be controlled (Paragraph 86, lines 1-5).
Regarding claims 19-21, Nadimpalli teaches that the previously shown method conditions are sequence-dependent and will be different in different circumstances and by controlling the stringency of the hybridization and/or washing conditions, target sequences can be identified which are 100% complementary to the probe (homologous probing) and can be adjusted to allow some mismatching in sequences so that lower degrees of similarity are detected (heterologous probing) where generally, a probe is less than about 1000 nucleotides in length, optionally approximately 500 nucleotides in length (Paragraph 61, lines 1-5). Nadimpalli also teaches that the previously explained method includes polynucleotides that can encode a polypeptide having a subsequence having at least 10, 15, 20, 25, 30, 35, 40, 45, or 50, contiguous amino acids from the prototype polypeptide and where further, the number of such subsequences encoded by a polynucleotide of the instant embodiment can be any integer selected from the group consisting of from 1 to 20, such as 2, 3, 4, or 5 and the subsequences can be separated by any integer of nucleotides from 1 to the number of nucleotides in the sequence such as at least 5, 10, 15, 25, 50, 100, or 200 nucleotides (Paragraph 118, lines 5-10).
Nadimpalli teaches that typical expression vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the DNA encoding a protein of the present invention (Paragraph 178, lines 5-10). Further, Nadimpalli teaches that Further, Nadimpalli teaches the primers are complementary to a subsequence of the target nucleic acid which they amplify but may have a sequence identity ranging from about 85% to 99% relative to the polynucleotide sequence which they are designed to anneal to and those skilled in the art will appreciate, the sites to which the primer pairs will selectively hybridize are chosen such that a single contiguous nucleic acid can be formed under the desired nucleic acid amplification conditions (Paragraph 109, lines 1-10).
Nadimpalli does not teach or suggest the 500 bp window sequence containing tandemly G4 structures (12x) or the resultant fragment containing histone acetylation marks.
Rhodes teaches that DNA and RNA G-quadruplexes are in various cellular pathways including DNA replication, gene expression and telomere maintenance (Abstract). Rhodes also teaches that G-quadruplex structures are topologically very polymorphic and can arise from the intra- or inter- molecular folding of G-rich strands and intra-molecular folding requires the presence of four or more G-tracts in one strand, whereas inter-molecular folding can arise from two or four strands giving rise to parallel or antiparallel structures depending on the orientation of the strands in a G-quadruplex (Introduction: Paragraphs 1-2). Specifically, Rhodes teaches that a recent investigation on the role of the RNA helicase eIF4A, using ribosome footprinting to provide snapshots of translation across the transcriptome, has revealed that the hallmark of eIF4A dependent transcripts is a 12-nucleotide pG4 signature (CGG)4 that can form RNA G-quadruplex structures (Figure 5; G-quadruplexes in transcription and translation: Paragraphs 2-3).
Rhodes also teaches that, based on observations from replication studies in avian DT40 cells, it was concluded that transcriptional silencing occurred via G-quadruplex impeded DNA replication (Figure 5) affecting transcription through the inappropriate inheritance of epigenetic histone marks where, epigenetic instability can arise from a G-quadruplex located at a distance of up to 3500 base pairs from the transcription start-site and although these observations provide compelling evidence for the involvement of pG4s in the regulation of gene expression in vivo, whether the mechanism for transcriptional regulation is directly through G-quadruplex formation remains to be proven (G-quadruplexes in transcription and translation: Paragraphs 2-3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Nadimpalli, as applied to claims 16-18, in view of Rhodes. Nadimpalli teaches methods of identifying and isolating nucleic acid fragments associated with replication control, including selecting fragments based on sequence-dependent characteristics and defined fragment lengths influenced by sequence composition and specific genomic regions identification. Rhodes, however, teaches that G4 structures arise in G-rich nucleic acid regions are likewise implicated in DNA replication control within localized genomic regions, transcriptional regulation and chromatin-associated processes. Because Nadimpalli recognizes that replication control is sequence-dependent and Rhodes teaches that G-rich tandem G4 motifs affect replication and chromatin regulation, it would have been obvious to select or identify replication origin fragments containing tandem G-quadruplex-forming sequences or G-rich repeated elements as part of a method for isolating functional replication origins. The modification merely applies known sequence-structure relationships to the selection of replication-associated DNA fragments. Rhodes also teaches that G4 structures are associated with chromatin regulation and epigenetic effects, including interactions affecting histone modification and transcriptional silencing. Because replication origin activity and chromatin state are functionally linked, it would have been obvious to select or identify replication origin fragments containing polycomb binding sites or histone acetylation marks in order to further influence replication initiation and gene regulation, which reflects the predictable application of established principles in molecular biology.
Nadimpalli further teaches selection of nucleic acid fragments of defined lengths association with replication-related activity, including fragments less than about 1000 nucleotides. Selecting a specific core initiation origin sequence length within such a disclosed or suggested range constitutes routine optimization (see MPEP 2144.05) of a known result-effective variable, namely a fragment length sufficient to support replication initiation (i.e., 716 bp). In the absence of evidence demonstrating criticality of a particular length or unexpected results, choosing a specific value within a known range would have been obvious to one of ordinary skill in the art.
Therefore, a person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Nadimpalli and Rhodes because both references address sequence-dependent regulation of replication and chromatin processes, and the relationship between G-rich motifs, chromatin-associated marks, and replication activity was well understood at the time of the invention. The proposed combination involves the application of known techniques and known biological relationships and would have yielded predictable results without undue experimentation.
Conclusions
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ELIZABETH ROSE LAFAVE/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684