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 .
DETAILED ACTION
Claims 1-20, filed May 7, 2024, are currently pending in the instant application.
Therefore, claims 1-20 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application is a CON of US Patent Application 15970690, filed June 3, 2018 (now US11999948), which claims the benefit of US Provisional Patent Application 62501578, filed May 4, 2017.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 7, 2024 has been considered. An initialed copy of the IDS accompanies this Office Action.
Claim Objections/Rejections
Claim Objections
Claim 6 is objected to because of the following informalities: Claim 6 recites terms such as “kb”, where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “the duration” such as recited in claim 1, line 9. There is insufficient antecedent basis for the term “the duration” in the claim. The Examiner suggests that Applicant amend the claim to recite, for example, “conditions comprise a duration of the contacting.”
Claim 1 is indefinite for the recitation of the term “the concentration” such as recited in claim 1, lines 9-10. There is insufficient antecedent basis for the term “the concentration” in the claim.
Claim 13 is indefinite for the recitation of the term “immobilizing on a solid support” such as recited in claim 13, line 2 because claim 13 depends from instant claim 1, wherein claim 1 does not recite the presence of a solid support and, thus, the metes and bounds of the claim cannot be determined.
Claims 17-20 are indefinite because the claims appear to recite both a product and process in the same claim. The examiner cautions that according to the MPEP 2173.05(p)(II) states that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b). PXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990). ). For example, claim 17 recites the term: “a nucleic acid binding reagent comprising an affinity tag” in line 2; and “instructions for using the affinity tag” in line 3; while also reciting: “according to the method of claim 1” in line 4. Moreover, claim 20 recites “a solid support comprising a capture agent that binds to the affinity tag” in lines 1-2. Such claims may also be rejected under 35 U.S.C. 101 based on the theory that the claim is directed to neither a “process” nor a “machine,” but rather embraces or overlaps two different statutory classes of invention set forth in 35 U.S.C. 101 which is drafted so as to set forth the statutory classes of invention in the alternative only. Id. at 1551.
Claim 17 is indefinite for the recitation of the term “according to the method of claim 1” such as recited in claim 17, line 4 because independent claim 17 refers back to independent claim 1. It is noted that claim 17 does not incorporate by reference all the limitations recited in the previous independent claim. Unlike recited here, an independent claim is a stand-alone claim that contains all the limitations necessary to define an invention and, thus, the metes and bounds of the claim cannot be determined.
Claim 18 is indefinite for the recitation of the term “to nucleic acids of a nucleic acid sample of less than a desired length” such as recited in claim 18, lines 3-4 because claim 18 depends from instant claim 17, wherein claim 17 does not recite the presence of nucleic acids, a nucleic acid sample, or a nucleic acid sample of less than a desired length and, thus, the metes and bounds of the claim cannot be determined.
Claims 2-12 and 14-16 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
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 13 and 18 are rejected under 35 U.S.C. 112(d) 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.
Claim 13 recites (in part): “wherein the separating comprises immobilizing on a solid support the…the nucleic acid binding reagent” in lines 1-3 because claim 13 depends from claim 1, wherein claim 1 does not recite the presence of a solid support. Thus, claim 13 is an improper dependent claims 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.
Claim 18 recites (in part): “wherein the nucleic acid binding reagent comprises a nucleic acid, and wherein the kit…sample of less than a desired length” in lines 1-4 because claim 18 depends from claim 17, wherein claim 17 does not recite the presence of a nucleic acid, a nucleic acid sample, or a nucleic acid sample of less than a desired length. Thus, claim 18 is an improper dependent claims 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.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 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.
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Peter et al. (hereinafter “Peter”) (US Patent No. 10577644, issued March 3, 2020; effective filing date May 29, 2013) in view of Henn et. al. (hereinafter “Henn”) (US Patent Application Publication No. 20160040215; effective filing date March 14, 2013) as evidenced by Peter et al. (hereinafter “Peter”) (US Patent Application Publication 20130323725, published December 5, 2013); and Ach et al. (hereinafter “Ach”) (US Patent No. 8017328, issued September 13, 2011).
Regarding claims 1, 17 and 18, Peter teaches a method for fragmenting a genome is provided, wherein the method comprises: (a) combining a genomic sample containing genomic DNA with a plurality of Cas9-gRNA complexes, wherein the Cas9-gRNA complexes comprise a Cas9 protein and a set of at least 10 Cas9-associated guide RNAs that are complementary to different, pre-defined, sites in a genome, to produce a reaction mixture; and (b) incubating the reaction mixture to produce at least 5 fragments of the genomic DNA (interpreted as contacting; a DNA sample; and gDNA, claims 1, 14, 15 and 17) (Abstract, lines 1-9). Peter teaches that the sample used can contain total genomic DNA, which can be unamplified or amplified, e.g., genomic DNA that has been amplified by a whole genome amplification method, that can or may not be already fragmented by other means, e.g., fragmented into fragments that are over 10 kb, or over 50 kb in length (interpreted as nucleic acids >10kb, claims 1 and 6) (col 7, lines 19-24). Peter teaches that an NGS library that is ready for sequencing can be produced rapidly and without hybrid-selection approaches, including wherein biotinylated DNA "tags" such that these can be used to separate targeted integrants from the gDNA that is not part of the NGS library (interpreted as separating nucleic acids bound to the binding reagent from nucleic acids not bound to the binding reagent; and to produce a size-selected library, claim 1) (col 14, lines 27-32). Peter teaches an illustration in Figure 1, including randomly sheared long DNA fragments (>50kb) comprising 40kb target sequences; Cas9 binds and cleaves sequences flanking the 40kb targets; and cloning the 40kb fragments into fosmid vectors after optional size selection (interpreted as size-selection; and a size-selected library, claims 1 and 17) (col 1, lines 40-41; and Figure 1). Figure 1 is shown below:
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Peter teaches that the term "affinity tag," as used herein, refers to moiety that can be used to separate a molecule to which the affinity tag is attached from other molecules that do not contain the affinity tag, such that an "affinity tag" can bind to the "capture agent," where the affinity tag specifically binds to the capture agent, thereby facilitating the separation of the molecule to which the affinity tag is attached from other molecules that do not contain the affinity tag, wherein examples of affinity tags include biotin, digoxygenin, peptide tags, and protein tags (e.g., his-tags and the like) (interpreted as a binding reagent comprising an affinity tag; biotin and desthiobinotin; and separating molecules bound to the binding reagent from molecules that are not bound to the binding reagent, claims 1, 11, 12, 17 and 18) (col 3, lines 16-32). Peter teaches kits, wherein kits can include instructions (interpreted as kits with instructions, claim 17) (col 10, lines 57-59; and col 11, line 3). Peter teaches that the repeat sequences can be cleaved to any suitable size, e.g., to a size in the range of 13-200 bases and each repeat can be cleaved at multiple sites, wherein the repetitive sequences are cleaved into fragments that range in size from 20 bases to 1 kb, such that the smaller fragments (the repetitive sequences) can be separated from the larger fragments (containing the non-repetitive sequences) by any suitable method, including by size exclusion; and the longer fragments can be processed (e.g., cloned, amplified, sequenced, etc.), such that certain longer fragments can be selected by target enrichment prior to further analysis, wherein such methods are known in the art, for example, methods described in U.S. Pat. No. 8,017,328 and US patent application US20130323725, which are incorporated herein by reference (interpreted as separating fragments of different sizes including using affinity tags to bind fragments of a desired length, claim 1) (col 9, lines 29-43), wherein it is known in US patent application US20130323725 that the term “separating” refers to physical separation of two elements such as by size or affinity, etc.; as well as, degradation of one element, leaving the other intact; and that a target genomic fragment can be in the range of 1 kb in length to over 500 kb in length or more, e.g., 5 kb to 100 kb, for example as evidenced by Peter (US20130323725, paragraphs [0046]-[0047]); and where it is known that genomic regions of defined size can be isolated including large genomic regions (e.g., >50kb), genomic regions of interest can be targeted with a plurality of oligonucleotides to ensure efficient capture of a genomic region as evidenced by Ach (col 16, lines 13-18).
Regarding claims 2, 3 and 6, Peter teaches that the sites can be chosen to release fragments of a similar, defined, size, e.g., where at least 95% of the predicted fragments have a size that is within 20%, within 10% or within 5% of a chosen size, where the chosen size is in the range of 1 kb to 10 kb, or 10 kb to 100 kb, (interpreted as 60% or more of the nucleic acids less than (or more than) the desired size are not bound to the binding reagent; and a desired length of 10kb or greater, claims 2, 3 and 6) (col 7, lines 51-56).
Regarding claims 4 and 5, Peter teaches that the genomic sample comprises mammalian genomic DNA, wherein the genomic sample comprises human genomic DNA (interpreted as a sample that comprises DNA including gDNA, claims 4 and 5) (col 17, lines 10-13).
Regarding claim 7, Peter teaches that for a given SNP, a guide mRNA can be designed such that the unique sequence represented by the SNP is incorporated into the guide, wherein such a guide mRNA should program a Cas9 complex to cleave the SNP sequence but not the reference sequence (interpreted as a sample comprising mRNA, claim 7) (col 18, lines 9-14). Peter teaches that sheared fragments are then digested with a pool of Cas9 programmed with a guide mRNA library specific to from one to 100 unique pathogens, such that for each pathogen, pairs of sequences have been selected so that each pair is unique to a single pathogen of interest or to a family of pathogens, and is separated by 40 to 250 nucleotides.(interpreted as the sample comprises mRNA, claim 7) (col 19, lines 41-46).
Regarding claims 8 and 9, Peter teaches that the NGS library that is ready for sequencing can be produced rapidly and without hybrid-selection approaches, such as the use of biotinylated DNA “tags” such that these targeted integrants can be separated from the gDNA that is not part of the NGS library (interpreted as the binding agent comprises a nucleic acid, claim 8) (col 14, lines 27-33). Peter teaches hybridizing one or more fragments to one or more biotinylated oligonucleotides (interpreted as covalently linking the nucleic acids to the nucleic acid of the binding reagent, claim 9) (col 24, claim 20, lines 28-29).
Regarding claims 10-12 and 19, Peter teaches biotin affinity tags, wherein the term "biotin moiety" refers to an affinity agent that includes biotin or a biotin analog such as desthiobiotin, oxybiotin, 2'-iminobiotin, diaminobiotin, biotin sulfoxide, biocytin, etc., wherein biotin moieties bind to streptavidin with an affinity of at least 10-8M, such that biotin affinity agent can also include a linker, e.g., -LC-biotin, -LC-Biotin, -SLC-Biotin or -PEGn-Biotin where n is 3-12 (interpreting the binding reagents to be biotin and desthiobinotin, claims 10, 11, 12 and 19) (col 3, lines 23-32).
Regarding claims 13, 14 and 20, Peter teaches enrichment comprises hybridizing one or mor of the fragments to one or more biotinylated oligonucleotides; retrieving the hybridized fragments with magnetic streptavidin beads; and amplifying the fragments (interpreted as immobilizing on a solid support the nucleic acid and the nucleic acid binding reagent; and streptavidin as a capture agent, claims 13, 14 and 20) (col 24, claim 20, lines 26-32).
Regarding claims 15 and 16, Peter teaches that the fragments can be sequenced using nanopore sequencing (e.g. as described in Soni et al. 2007 Clin Chem 53: 1996-2001, or as described by Oxford Nanopore Technologies), such that nanopore sequencing is a single-molecule sequencing technology whereby a single molecule of DNA is sequenced directly as it passes through a nanopore (interpreted as nanopore-based sequencing, claim 16) (col 8, lines 56-62). Peter teaches that nanopore sequencing technology is disclosed in U.S. Pat. Nos. 5,795,782, 6,015,714, 6,627,067, 7,238,485 and 7,258,838 and U.S. Pat Appln Nos. 2006003171 and 20090029477 (col 9, lines 6-9). Peter teaches that the term "next-generation sequencing" refers to the so-called parallelized sequencing-by-synthesis or sequencing-by-ligation platforms currently employed by Illumina, Life Technologies, and Roche etc., wherein next-generation sequencing methods can also include nanopore sequencing methods or electronic-detection based methods such as Ion Torrent technology commercialized by Life Technologies (interpreted as nanopore-based sequencing, claim 16) (col 3, lines 58-65).
Peter does not specifically exemplify additional samples comprising RNA (claim 7, in part).
Regarding claim 7 (in part), Henn teaches the enrichment of microbes by affinity chromatography, such that with an appropriate affinity reagent including e.g. antibody, receptor, etc, specific microbes are selectively enriched from a microbial mixture as previously described (Accoceberry et al One Step Purification of Enterocytozoon bieneusi Spores from Human Stools by immunoaffinity expanded bed adsorption (EBA). J. of Clinical Microbiology, 39(5). 2001) (interpreted as separating nucleic acids) (paragraph [0297], Example 37, lines 1-11). Henn teaches that to enrich sequences of interest, an amount of greater than used for PCR is enriched for sequences of interest by contacting the sample with a solid phase comprising bound DNA oligonucleotides that selectively bind to sequences of interest via hybridization and thus enrich them, such that suitable solid phase materials include, by way of example and without limitation, polystyrene or magnetic beads, silicon chip surfaces, silica beads, or other suitable systems known to one skilled in the art, whereas a specific non-limiting example, short oligonucleotides (20-60 bp) are synthesized with biotin at the 5' or 3' ends and are bound to magnetic streptavidin beads (Life Sciences); alternatively, longer probes are developed by using the biotinylated oligonucleotides as PCR primers to amplify sequences of interest, purifying these longer probes, attaching them to the bead matrix and washing away the complementary strand not labeled with biotin under conditions that denature DNA but not the biotin streptavidin linkage (Holmberg et al., the biotin streptavidin interaction can be reversibly broken using water at elevated temperatures, Electrophoresis 26:501-510, 2005) (interpreted as biotin affinity moieties) (paragraph [0314]). Henn teaches that the enriched DNA sequences can then be sequenced by techniques described (see e.g. examples 3 and 4) or detected by qPCR-based techniques to quantify the amount of a particular DNA sequence present (paragraph [0316], lines 1-4).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of enriching bacterial nucleic acid sequences as exemplified by Henn, it would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to modify the method of using affinity tags to facilitate the separation of molecules that contain the affinity tag from molecules that do not contain the affinity tag as disclosed by Peter to include the method of characterizing and enriching bacterial compositions including through affinity chromatography and/or the use of nucleic acid aptamers specific for each bacterial strain as taught by Henn with a reasonable expectation of success in using affinity tags to separate, enrich, and/or purify target nucleic acid sequences having a defined size for removal and/or for further processing such as for cloning into a particular vector, NGS sequencing, and/or for characterizing a bacterial or therapeutic composition.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
Conclusion
Claims 1–20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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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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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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