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
1. The Applicant’s response to the office action filed on October 21, 2025 is acknowledged.
Status of the Application
2. Claims 1-17 are pending under examination. New claims 18-20 are added. The Applicant’s arguments have been fully considered and found unpersuasive for the following reasons.
Claim Rejections - 35 USC § 103-Maintained
3. 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.
Claims 1-17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Aghvanyan et al. (US 2017/0089892) in view of Stapleton et al. (US 2016 /0152972).
Aghvanyan et al. teach a method of claim 1, analyzing an individual circulating membranous vesicle (single exosome) contained in a sample, wherein individual circulating membranous vesicle comprises at least three target molecules, wherein the target molecules comprise target polypeptide and DNA molecules (M13 phage DNA) (para 0220-0225, 0145-0150, 0335-0337);
wherein the method comprises measuring a signal corresponding to the presence or absence of at least two target molecules to produce a set of linked signals for the individual circulating membranous vesicle, wherein the linked signals correspond to the presence or absence the and one of the linked signals corresponds to the target protein or DNA in the sample (para 0221-0226, 0216, 0335-0337, 0177).
With reference to claims 2-11, Aghvanyan et al. teach that the fragments of genomic DNA comprise at least one modified nucleotide and the step of measuring a signal corresponding to modified nucleotide by using a barcoded affinity probe (unique proximity probe) comprising at least one affinity moiety (capture reagent or antibody) linked to barcoded oligonucleotide comprising at least one nucleotide and the affinity moiety is capable of binding to the modified nucleotide a barcoded affinity probe comprising at least one affinity moiety linked to barcoded oligonucleotide comprising at least one nucleotide and the affinity moiety is capable of binding to the target polypeptide (para 0006-0010,0189,para 0335-0337).
With reference to claims 12-17, 19-20, Aghvanyan et al. teach sample containing plurality of individual circulating microvesicles each comprising at least three or more target molecules and comprise at least 2, 3 or more target polypeptide target molecules (para 0220-0221).
However, Aghvanyan et al. did not teach detecting at least two linked signals of genomic target molecules.
Stapleton et al. teach a method of clams 1-17, 19-20, for analyzing genomic and peptide target molecules in a sample comprising at least three target molecules, wherein at least two target molecules are genomic DNA fragments, wherein the method comprises measuring two linked signals corresponding to the presence or absence of each target genomic DNA molecules by determining, amplifying barcode tagged nucleic acids and sequence reads of all or a portion of the nucleic acid fragments, wherein amplification comprises primers comprise modified nucleotides (para 0026-0040, 0004-0023, 0246-0248, 0068-0072).
It would have been prima facie obvious to one of the ordinary person skilled in the art before the effective filling date of the invention to modify the method as taught by Aghvanyan et al. with at least measuring a signal of a set of linked genomic target molecules comprising at least one linked signal for at least two genomic fragments as taught by Stapleton to improve the method for analyzing a sample. The ordinary person skilled in the art would have motivated to combine the references and have a
reasonable expectation of success that the combination would result in improving the sensitivity and accuracy of the method because Stapleton et al. explicitly taught measuring multiple genomic nucleic acid fragments in conjunction with encoded protein in a sample to detect genotype and phenotype information from nucleic acid aptamers, proteins (para 0247-0248) and such a modification of the method is considered to be obvious over the cited prior art.
Response Arguments:
With reference to the rejection of claims 1-17 under 35 USC 103 as being unpatentable over Aghvanyan et al. in view of Stapleton et al., the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. First, the amendment incorporating the limitations from the dependent claims, did not change the scope of the claims. Second, as discussed in the rejection, Aghvanyan et al. teach said limitations in the amended claim 1. With reference to the arguments drawn to no teaching of appending two fragments of genomic DNA to a barcode sequence to produce a set of linked fragments of genomic DNA and argue that Aghvanyan different method for different purpose. The arguments have been found unpersuasive. With reference to attacking references individually, the arguments were found unpersuasive. As noted in MPEP 2145-IV one cannot show nonobviousness by attacking references individually, where the rejection is based on a combination of references. Further, with reference to the arguments drawn to Aghvanyan et al. and Stapleton et al. teaching a different method for different purpose, the arguments were found unpersuasive because as noted in MPEP 2144-IV, The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).
As discussed in the rejection, Aghvanyan et al. teach detecting protein and genomic DNA fragments linked to antibody-probe conjugates (affinity probes) wherein detection antibodies specific for an analyte each comprises unique proximity probes (barcoded probes) which ligate to form circular target for rolling circle amplification (para 0336-0337). As discussed in the rejection, Stapleton et al. teach linking the genomic DNA fragments by appending barcodes to the fragments or tagging fragments with barcodes and detecting linked signals. With reference to the arguments drawn to Stapleton et al. teach additional step of fragmentation before the first adapter and not combinable with the disclosure of Aghvanyan, the arguments were found unpersuasive because the claims are in ‘comprising’ format and any unrecited elements are steps are within the scope of the claims and claims do not exclude said fragmentation. Further, the Applicant cited paragraph (para 0221) of Aghvanyan et al. teach disrupting exosomes and analyzing by PCR or sequencing, which can be combinable with the teaching of Stapleton et al., appending barcodes to genomic DNA and sequencing. As discussed in the rejection, it would be obvious to modify the method as taught by Aghvanyan et al. with the barcode tagged or linked genomic DNA to generate linked genomic DNA signals. For all the above the rejection of claims 1-17 has been maintained and restated to address the amendment.
Allowable Subject Matter
5. Claim 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681