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 .
Status of the claims
The amendment filed 06/22/26 is acknowledged and has been entered. Claims 5, 8, 14 and 19 have been amended. Claims 21-24 have been canceled. Claims 6-7, 9 and 13 were previously canceled. Accordingly, claims 1-5, 8, 10-12 and 14-20 are under examination.
Withdrawn Rejections
All rejections of claims not reiterated herein, have been withdrawn.
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.
Claim 8 is 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 8, line 2 is indefinite in reciting improper Markush language in reciting “the nanoparticles are selected from” because it appears to intend to limit the scope of the nanoparticles but improperly defines it as such. Perhaps, Applicant intends “the nanoparticles are selected from the group consisting of”.
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 1-5, 8, 10-12, 14-17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Kostarelos et al (WO 2018/046542) (submitted in the IDS filed 02/09/23) in view of Huang et al., (Nanotheranostics 2017, Vol 1, Issue 1, pages 80-102) (listed in the Notice of References Cited filed 12/22/25).
Kostarelos et al discloses a method of identifying a biomarker from a biofluid comprising administration of nanoparticles to a subject in a diseased state or incubating nanoparticles in a biofluid sample taken from a subject in a diseased state to allow a biomolecule corona to form on the surface of the nanoparticles; isolating the nanoparticles and surface-bound biomolecule corona; and analyzing the biomolecule corona to identify the biomarker (e.g. abstract, para’s 0001, 0007, 0009, 0023). Kostarelos et al discloses that the sample can be a plasma, urine, saliva or cerebrospinal and ocular fluids (e.g. para 0017). Kostarelos et al discloses that the biomarker can be nucleic acids such as different types of DNA (e.g. para 0020). Kostarelos et al discloses that the nanoparticles can be administered to the subject by intravenous injection (e.g. para 0032). Kostarelos et al discloses that the nanoparticles can be liposomes, gold nanoparticles and polymeric nanoparticles (e.g. para 0018). Kostarelos et al discloses that the method allows the benefit of removal of unbound and highly abundant biomolecules to allow identification of low abundant biomarkers (e.g. para 0011). Kostarelos et al discloses that the disease state can be cancer such as ovarian, lung or melanoma (e.g. para 0030). Kostarelos et al discloses that the analysis of the biomolecule corona in order to identify biomarkers can be carried out using any suitable technique capable of detecting the biomarker and in a particular embodiment of the invention, the biomolecule corona is analysed by gel electrophoresis, mass spectrometry, an immunoassay, UV-Vis, absorption, fluorescence spectroscopy, chromatography or NMR methodology. Conveniently, the biomolecule corona is analysed by mass spectrometry, which can allow qualitative and/or quantitative analysis of the biomolecule corona present on the nanoparticles (e.g. para’s 0024, 0090, 0117-0120). Kostarelos et al discloses that relative amounts compared to a control of the biomarker can be determined by mass spectrometry (e.g. para 0090). Kostarelos et al discloses that the methods also provide the ability to monitor changes in biomarkers in response to therapy such as administration of an anti-cancer compound (e.g. para 0026).
Kostarelos et al differs from the instant invention in failing to explicitly teach cell free nucleic acid (as recited in claims 1 and 11) and also fails to teach the nanoparticles are negatively charged (as recited in claim 10).
Huang et al teaches that dying tumor cells release small fragments (50 to 250 bp) of their DNA into the bloodstream and that these fragments, first found in cancer patients in 1977 are called cell-free ctDNA. Huang et al teaches that they carry genomic and epigenomic alterations identical to those of tumor tissues and discriminate from normal cell-free DNA. Huang et al teaches that ctDNA is broadly applicable, specific and sensitive biomarker that can be used for wide range of research and clinical purposes, including tumor genotyping, early cancer detection, patient prognosis, therapy evaluation, and minimal residual disease monitoring [citations]. Thus, ctDNA is becoming a new generation of biomarker for cancer assessment (page 89, column 1, paragraph 1). Huang et al. teaches that existing methods for ctDNA detection are restricted to genetic mutations. A dual genetic and epigenetic detection method for ctDNA was reported by Nguyen and Sim based on the LSPR sensing. The authors made peptide nucleic acid (PNA)-functionalized Au NPs to target two bio-signatures of ctDNA: mutations at two hot-spots E542K and E545K of the PIK3CA gene and methylation… Thus, hot-spot mutations and epigenetic changes on the ctDNA were detected in one-step by the nanoplasmonic biosensor, opening a new approach for detecting ctDNA biosignatures at high sensitivity and specificity (page 90, last paragraph of column 1 continued to first paragraph of column 2).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to analyze the Huang et al. cell-free DNA within the Kostarelos et al. methodologies because Huang et al. teaches that cell-free ctDNA “is broadly applicable, specific and sensitive biomarker that can be used for wide range of research and clinical purposes, including tumor genotyping, early cancer detection, patient prognosis, therapy evaluation, and minimal residual disease monitoring” (page 89, column 1, paragraph 1). Thus, one of ordinary skill would have been motivated to analyze the Huang et al. cell-free DNA within the methodologies rendered obvious by Kostarelos et al. in order to take advantage of the broadly applicable, specific, and sensitive biomarker teachings. The skilled artisan would have a reasonable expectation of success based on the disclosures Kostarelos et al., and further in view of Huang et al., as discussed in the preceding paragraphs.
Regarding claim 10, Huang et al. teaches "Au NP-based DNA assays were pioneered by Mirkin and colleagues who first developed a colorimetric method based on DNA-mediated Au NP assembly in 1997. They designed two oligonucleotide-functionalized Au NP probes with sequences complementary to different segments of the targeted polynucleotides. When the two oligonucleotide - Au NP conjugates bound to the target via hybridization… (page 89, column 2, last paragraph continued to page 90, column 1, first paragraph).
DNA oligonucleotides contain negatively charged phosphate backbones (see Huang et al. teaching "PNA is advantageous over DNA because it does not have electrostatic interference with the negatively charged phosphate backbone of target DNA" on page 90, column 2, paragraph 1).
Thus, these teachings read on claim 10 wherein the nanoparticles are negatively charged.
Although Kostarelos et al. is silent to the Huang et al. negatively charged nanoparticles and cell-free DNA, it would have been prima facie obvious to the skilled artisan. It is noted that Kostarelos et al. and Huang et al. are analogous disclosures to the instant nanoparticle-mediated detection field.
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to combine the analogous art. Huang et al. teaches that “oligonucleotide-functionalized Au NP probes” were able to bind to the target via hybridization (page 90, column 1, first paragraph). As discussed above, these nanoparticles are negatively charged as a result of the DNA oligonucleotide phosphate backbones. Thus, the skilled artisan would have been motivated to use the Huang et al. negatively charged nanoparticles within the methodologies rendered obvious by Kostarelos et al. in order to take advantage of nucleic acid target binding via hybridization. The skilled artisan would have a reasonable expectation of success based on the disclosures Kostarelos et al., and further in view of Huang et al., as discussed in the preceding paragraphs.
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Kostarelos et al in view of Huang et al as applied to claims 1-5, 8, 10, 12, 14-17 and 20 above, and further in view of Mortimer et al (US 2021/0115502).
See above for the teachings of Kostarelos et al and Huang et al.
Kostarelos et al and Huang et al differ from the instant invention in failing to teach determining a specific nucleic acid indicative of a disease.
Mortimer et al teaches that it is known and conventional in the art to analyze cell-free DNA to identify sequences having mutations which are associated with cancer (e.g. para’s 0002, 0007-0008, 0189-0191).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the identification of sequences such as taught by Mortimer et al into the modified method of Kostarelos et al because Mortimer et al shows that it is known and conventional in the art. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating the identification of sequences such as taught by Mortimer et al into the modified method of Kostarelos et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-5, 8, 10-12 and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11, 13-14, 16-17 and 19-21 of copending Application No. 18041131 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending 131' application directs to essentially same method of identifying cell free nucleic acid in a sample from a subject by incubating blood or serum samples with a plurality of nanoparticle to form corona biomolecule complex followed by analyzing the cell free DNA (cfDNA)(see claim 17 in 131' application). In additional, 131' application also uses intravenous injection of administering nanoparticles to the subject. Moreover, 131' application also teaches applying the detection method for diagnosis a or monitoring cancer progression or treament in a subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678
