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
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.
Status of the claims
Claims 1-5, 7-9, 12-13, 15, 17-18, 23, 26, 28-29 and 32-38 are pending and examined on merits in this office action.
Claim Rejections - 35 USC § 102
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 1-5, 7-9, 12-13, 15, 17-18, 28-29, 32-34, and 36-38 are rejected under 35 U.S.C. 102(a1) as being anticipated by Vlaminck et al. (WO2018/187521A2).
In regards to claims 1, 17, 18, 28 and 38, Vlaminck teaches a method of differentiating sample-intrinsic nucleic acids from contaminant nucleic acids (para [0011) "methods comprising the steps of (a) obtaining a sample of a subject at risk of a urinary tract or peritoneal infection ... (b) preparing a sequencing library from the sample, wherein the sequencing library comprises genomic DNAs present in the sample; (c) sequencing the DNAs in the sequencing library; and (d) detecting a non-host DNA in the library ... the non-host DNA is a non-human DNA"), the method comprising: providing a sample containing nucleic acids; tagging the nucleic acids [see instant specification, para [0010] and [0029]) "In some embodiments, the tagging comprises modifying one or more nucleotides of the nucleic acids in the sample. In some embodiments, the modifying comprises converting cytosine nucleotides into uracil nucleotides. In some embodiments, the converting cytosine nucleotides into uracil nucleotides is achieved by treating the nucleic acids with a bisulfite salt"] in or from the sample; subjecting the nucleic acids after tagging to nucleic acid sequencing; and differentiating sample intrinsic nucleic acids from contaminant nucleic acids based on tag and sequence analysis (para [0021) "methods comprising the steps of (a) obtaining a .sample of a subject ... (b) bisulfite treating [tagging, as cited by applicant] the sample; (c) preparing a sequencing library from the sample, wherein the sequencing library comprises genomic DNAs present in the sample; {d) sequencing the DNAs in the sequencing library; (e) analyzing the sequences for DNA methylation; and (d) detecting a non-host DNA in the library.").
In regards to claim 2, Vlaminck teaches a method of differentiating sample-intrinsic nucleic acids from contaminant nucleic acids, as discussed for claim 1. Vlaminck further teaches that the sample is obtained from a host and the sequence analysis comprises aligning the nucleic acid sequences to a host genome thereby identifying sequences from the host (para [0012] "aligning the DNA sequences ... to a human reference genome and removing sequences that align to the human reference genome, wherein the remaining sequences are the nonhuman DNA sequences.").
In regards to claim 3, Vlaminck teaches a method of differentiating sample-intrinsic nucleic acids from contaminant nucleic acids, as discussed for claims 1 and 2. Vlaminck further teaches that the tag and sequence analysis comprises: filtering the nucleic acid sequences into a preliminary group of tagged [bisulfite-treated) sequences (para [00150] "the inventors aligned sequenced reads from WGBS [whole genome bisulfite sequencing) samples that did not map to the human genome (assumed to be non-human)", para [00149] "it is possible to use standard sequencing to detect bacterial and viral DNA. However; as this type of DNA is not often cytosine-methylated, bisulfite treatment results in a decrease in base-pair complexity (from a 4 base pair system to a 3 base pair system). The inventors discovered that this decrease in base-pair complexity does not hinder the ability to detect pathogens.", para [00151) "These results demonstrated that pathogen detection can be accomplished using WGBS instead of standard sequencing, making WGBS a powerful tool for pathogen detection") and a preliminary group of untagged contaminants (i.e. not in a sample and thus not bisulfite treated) (para [0093] "To control for environmental and sample-to-sample contamination, a known-template control sample ... was included in every sample batch and sequenced ... The five most abundant genera detected across the 23 microbiome controls consisted of Propionibacterium (22.9%), Salmonella (10.9%), Pseudomonas (7.7%). polyomavirus (5.4%). and E.coli {5.2%). The mean representation of each genus in the control was used to filter out genera in samples identified as possible contaminants. Possible sources of contamination in these experiments include: environmental contamination during sample collection in the clinic, nucleic acid contamination in reagents used for DNA isolation and library preparation, sample-to-sample contamination", i.e. a preliminary group of non-bisulfate-treated sequences identified by comparison to a a known-template control sample).
In regards to claims 4, 5 and 9, Vlaminck teaches a method of differentiating sample-intrinsic nucleic acids from contaminant nucleic acids, as discussed for claim 1. Vlaminck further teaches that the sample is obtained from a host, and the tag and sequence analysis comprises: aligning the nucleic acid sequences to a host genome thereby identifying sequences from the host , and removing the host sequences (para [0012] "aligning the DNA sequences ... to a human reference genome and removing sequences that align to the human reference genome, wherein the remaining sequences are the non-human DNA sequences."); separating the remaining nucleic acid sequences into a preliminary group of tagged sequences (para [00150] "the inventors aligned sequenced reads from WGBS (whole genome bisulfite sequencing] samples that did not map to the human genome (assumed to be non-human)", para [00149] "it is possible to use standard sequencing to detect bacterial and viral DNA. However, as this type of DNA is not often cytosine-methylated, bisulfite treatment results in a decrease in base-pair complexity (from a 4 base pair system to a 3 base pair system). The inventors discovered that this decrease in base -pair complexity does not hinder the ability to detect pathogens.", para (00151] "These results demonstrated that pathogen detection can be accomplished using WGBS instead of standard sequencing, making WGBS a powerful tool for pathogen detection") and a preliminary group of untagged sequences(i.e. not in a sample and thus not bisulfite treated) (para (0093] "To control for environmental and sample-tosample contamination, a known-template control sample ... was included in every sample batch and sequenced ... The five most abundant genera detected across the 23 microbiome controls consisted of Propionibacterium (22.9%), Salmonella (10.9%), Pseudomonas (7.7%), polyomavirus (5.4%), and E. coli (5.2%). The mean representation of each genus in the control was used to filter out genera in samples identified as possible contaminants. Possible sources of contamination in these experiments include: environmental contamination during sample collection in the clinic, nucleic acid contamination in reagents used for DNA isolation and library preparation, sample-to-sample contamination", i.e. a preliminary group of non-bisulfate-treated sequences identified by comparison to a known-template control sample); aligning the preliminary group of tagged sequences and the preliminary group of untagged sequences to a database thereby determining the species origin of the preliminary group of untagged sequences (para [0012] "aligning the DNA sequences ... to a human reference genome and removing sequences that align to the human reference genome, wherein the remaining sequences are the non-human DNA sequences."); and identifying the tagged and untagged sequences of the same species origin as contaminant sequences (para [0093] "a known-template control sample ... was included in every sample batch and sequenced The five most abundant genera detected across the 23 microbiome controls consisted of Propionibacterium (22.9%), Salmonella (10.9%), Pseudomonas (7.7%), polyomavirus (5.4%), and E. coli (5.2%). The mean representation of each genus in the control was used to filter out genera in samples identified as possible contaminants").
In regards to claims 7-8 and 34, Vlaminck discloses extracting nucleic acid from sample ([0049], [0091], [00105], [00114], [00115] and [00141] and [0082]).
In regards to claims 12 and 13, Vlaminck teaches biological sample from patients (abstract), as for example, urine or plasma sample (para [0044]).
In regards to claim 15, Vlaminck teaches environmental sample (para [0093], [00104], [00116]).
In regards to claim 29, Vlaminck teaches tagging utilizing bisulfite and bisulfite reacts with unmethylated cytosines in DNA forming sulfonated cytosine, which thus includes attacking a compound to nucleic acid. Moreover, Vlaminck teaches taches tagging with biotin (para [0048], [0052], [0053]).
In regards to claims 32 and 33, the claims only defining the peptide and oligonucleotide recited in claim 29 but does not further limit tagging with the recited compounds and thus claims 32 and 33 are been rejected based on rejection of claim 29.
In regards to claim 35, Vlaminck teaches extraction CfDNA from UTI infention utilizing Qiagen Circulating Nucleic Acid Kit for cell-free nucleic acid extraction and Quagen circulating nucleic acid kit comprises proteinase K and buffer ACL and ATL, which lyses cell to release nucleic acid ([0091]-[0093], [00115] amd [00118]).
In regards to claim 36, Vlaminck teaches sample for detecting infection suspected to contain pathogenic microorganism (para [0059], [0060] and [00124]).
In regards to claim 37, Vlaminck teaches metagenomic sequencing (para [00125] and [00133]).
Claim Rejections - 35 USC § 103
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-5, 7-9, 12-13, 15, 17-18, 23, 26, 28-29, 32-34, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Vlaminck et al. (WO2018/187521A2) as applied to claims 1-5, 7-9, 12-13, 15, 17-18, 28-29, 32-34, and 36-38 above and further in view of He et al. (US 2018/0245128) and Helm et al (WO2020212512).
Vlaminck has been described above disclosing method of differentiating sample-intrinsic nucleic acid from contaminating nucleic acids comprising tagging sample nucleic acid wherein tagging comprises modifying sample one or more nucleotides of sample nucleic acid wherein one example of modifying is converting cytosine nucleotides to uracil nucleotides.
Vlaminck however, does not disclose modifying other nucleotides, as for example, adenosine or guanosine as claimed in claims 23 and 26.
He discloses modification of adenosine to inosine in sample nucleic acid (para [0012]). He teaches detection of modified adenosine and also teaches that adenosine deaminase ADAR) converts adenosine to inosines (para [0062]).
Helm et al discloses detection of nucleic acid modification using chemical deamination (Abstract). Helm teaches subjecting sample to deamination and teaches that Deamination converts adenosine (A) to inosine (I), guanosine (G) to xanthosine (X), and cytidine (C) to uridine (U) (page 5, lines 25-26).
Therefore, from the description in mind of He and Helm of the disclosure of various other nucleotide modification of nucleic acid and from the disclosure that the process of deamination can be carried out other nucleotide modifications of converting adenosine (A) to inosine (I), guanosine (G) to xanthosine (X), and cytidine (C) to uridine (U), it would be obvious to one of ordinary skilled in the art to easily envisage other nucleotide modifications, as for example, modification of adenosine to inosine or modification of guanosine to xanthosine as a method of tagging in the method of Vlaminck with the expectation of expanding tagging process with various other modification with a reasonable expectation of success. Since Vlaminck discloses nucleotide modification of cytosine to uracil as a tagging, the other types of nucleotide modification as tagging would be obvious to one of ordinary skilled in the art.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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