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 .
Claims 1-11, 13-14, 16-17, 19-21, and 23-24 are pending and currently under examination. Claims 1-2, 6-9, 11, 14, 16-17, 20-21, and 23-24 are amended. Claims 12, 15, 18, 22, and 25 are cancelled.
Response to Amendment
The Amendment filed 4/22/26 has been entered. Claims 1-11, 13-14, 16-17, 19-21, and 23-24 are pending. Applicant’s amendments to claims 2, 6-9, 11, 14, 16-17 and 20-21 and specification have overcome the objections and 112(b) and 102 rejections previously set forth in the Non-Final Office Action mailed 10/22/25.
Response to Arguments
Applicant’s arguments, see pages 8-14, filed 4/22/26, with respect to the rejections of claims 1-11, 13-14, 16-17, 19-21, and 23-24 under 35 USC 101, 103, and nonstatutory double patenting have been fully considered are found unpersuasive, and the rejections documented in the Non-Final mailed 10/22/25 have been revised to address claim amendments filed 4/22/26 in this Final Office Action. More detailed responses to Applicant’s arguments are provided at the end of each maintained rejection.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-11, 13-14, 16-17, 19-21, and 23-24 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4 Monday, January 7, 2019).
This 101 rejection is revised/updated in response to claim amendments filed 4/22/26.
Step 1: The claims are directed to the statutory category of processes.
Step 2A, prong one: The claim recites a judicial exception.
Claim 1 recites “A method of identifying biomarkers … (c) analyzing… to identify”; claim 23 recites active step “(b) analyzing the biomolecule corona “; claim 24 recites “A method for monitoring… (b) analyzing the biomolecule corona”. These identifying, analyzing, and monitoring steps are abstract mental processes performed within the mind following data-gathering (see MPEP 2106.04(a)(2)(III)).
Claim 20 recites “wherein the specific nucleic acid is indicative of a disease”; claim 23 recites “disease-specific biomarkers…which is determinative of the presence of a disease”; and claim 24 recites “wherein the degree of cancer progression is determined based on the level of the cancer-specific biomarker(s)”. These natural correlations of biomarkers with diseases are laws of nature and natural phenomena, serving as examples of genotype and phenotype (see MPEP 2106.04(b)).
Step 2A, prong two: The judicial exception is not integrated into a practical application.
Claims 1-11, 13-14, 16-17, 19-21, and 23-24 recite extra-solution and data-gathering limitations for the judicial exceptions. Although claim 21 recites optional administration of an anti-cancer compound, this is not a particular treatment and prophylaxis (see MPEP 2106.04(d)(2)). The claims are not directed towards a particular compound (structure, composition), dosage, treatment course, or other specifics required for a particular treatment and prophylaxis.
Step 2B: The claim does not provide an inventive concept.
MPEP 2106.05(d)):
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377, 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
The claims are directed to well-understood, routine, and conventional activities in the life science arts recited at a high-level of generality. Additionally, multiomic analyses of nanoparticle-coronas are not inventive (see Kostarelos et al. (2018; WO 2018/046542 A1; FOR citation 1 in IDS filed on 2/9/23); and Huang et al. (2017; NPL citation U in PTO-892 filed 10/22/25; “Gold Nanoparticle Based Platforms for Circulating Cancer Marker Detection"; Nanotheranostics. 2017;1(1):80-102. doi: 10.7150/ntno.18216)).
For the reasons set forth above, claims 1-11, 13-14, 16-17, 19-21, and 23-24 are not directed to patent eligible subject matter.
Applicant’s Arguments and Response to Applicant’s Arguments
Applicant argues that the amended claims “apply natural relationships” through treatment (Remarks 4/22/26, page 8) and that the amended claims “now require something more than ‘an insignificant extra solution activity’ (i.e., [data-gathering methods]) to identify biomarkers from two or more distinct biomarker classes)” (Remarks 4/22/26, page 9).
The Examiner respectfully disagrees with these assertions. The claim 21 recitation of optional administration of an anti-cancer compound is not a particular treatment and prophylaxis (see MPEP 2106.04(d)(2)). The claims are not directed towards a particular compound (structure, composition), dosage, treatment course, or other specifics required for a particular treatment and prophylaxis.
Additionally, the amended claims 1 and 23-24 limitations of “performing one or more analytical measurements” constitute additional extra-solution and data-gathering activities that merely generate the data for the judicial exceptions. These activities do not contribute significantly more to the judicial exceptions (see MPEP 2106.05(g)).
Additionally, identification of “biomarkers from two or more distinct biomolecule classes” is not inventive (see Kostarelos et al. paragraphs 00017 and 00020 (2018; WO 2018/046542 A1; FOR citation 1 in IDS filed on 2/9/23); and Huang et al. page 98, paragraph 2 (2017; NPL citation U in PTO-892 filed 10/22/25; “Gold Nanoparticle Based Platforms for Circulating Cancer Marker Detection"; Nanotheranostics. 2017;1(1):80-102. doi: 10.7150/ntno.18216).
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, 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 1-11, 14, 16, 21, and 23-24 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Kostarelos et al. (2018; WO 2018/046542 A1; FOR citation 1 in IDS filed on 2/9/23).
This 103 rejection is revised/updated in response to claim amendments filed 4/22/26.
Relevant to claim 1, Kostarelos et al. teaches "In one aspect, the present invention relates to a method of identifying a biomarker from a biofluid, wherein the method comprises: a. administering a plurality of nanoparticles to a subject in a diseased state to allow a biomolecule corona to form on the surface of said nanoparticles or incubating a plurality of nanoparticles in a biofluid sample taken from a subject in a diseased state to allow a biomolecule corona to form on the surface of said nanoparticles; isolating the nanoparticles and surface-bound biomolecule corona; and c. analyzing the biomolecule corona to identify the said biomarker" (paragraph 0009).
Further relevant to claim 1, Kostarelos et al. teaches "In addition to the identification of a single biomarker, the methods also provide the ability to identify panels of biomarkers (multiplexing). This approach can lead to increased sensitivity and specificity of detection" (paragraph 00025).
Further relevant to claim 1, Kostarelos et al. paragraphs 00017, 00020, and 00025 teach that “the biomarker comprises at least one biomolecule (for example, a protein, peptide, fatty acid, lipid, amino acid, sugar, amide or nucleic acid)”; “The term ‘biomolecule’ in this context includes, but is not limited to, proteins, peptides, fatty acids, lipids, amino acids, amides, sugars and nucleic acids (such as for example different types of DNA or RNA)”; and “In addition to the identification of a single biomarker, the methods also provide the ability to identify panels of biomarkers (multiplexing). This approach can lead to increased sensitivity and specificity of detection.”
Further relevant to claim 1, Kostarelos et al. paragraph 00024 teaches “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.”
Relevant to claim 2, Kostarelos et al. teaches "Figure 1 shows the SDS-Page gel for protein recovered directly from plasma compared with the analysis conducted following either in vivo administration of nanoparticles in mice or after in vitro incubation with plasma taken from mice" (paragraph 00014)
Relevant to claim 3, Kostarelos et al. teaches "Conveniently, the route of administration of the nanoparticles is by intravenous injection" (paragraph 00032).
Relevant to claims 4-5, Kostarelos et al. teaches "… incubating a plurality of nanoparticles in a biofluid sample taken from a subject in a diseased state to allow a biomolecule corona to form on the surface of said nanoparticles…" (paragraph 0009).
Relevant to claims 6-7, Kostarelos et al. teaches "In a particular embodiment of the present invention, the biomarker comprises at least one biomolecule (for example, a protein, peptide, fatty acid, lipid, amino acid, sugar, amide or nucleic acid) and the biofluid is selected from plasma, urine, saliva, lacrimal, cerebrospinal and occular fluids" (paragraph 00017).
Relevant to claims 8-10, Kostarelos et al. teaches "Analysis of the biomolecule corona in order to identify biomarkers can be carried out using any suitable technique capable of detecting said biomarkers. 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" (paragraph 00024).
It is noted that page 12 of the instant specification provides broad definitions for genomics, proteomics, and lipidomics (“As used herein, ‘genomics’ is the analysis of genes and nucleic acids generally”; “As used herein, ‘proteomics’ is the analysis of proteins and elements of protein”; “As used herein, ‘lipidomics’ is the analysis of lipids and elements of lipids”).
Thus, the skilled artisan would find the Kostarelos et al. teaching of “any suitable technique capable of detecting” the biomarkers paired with the specific analysis techniques to obviously embrace the broad genomics, proteomics, and lipidomics analyses.
Relevant to claim 11, Kostarelos et al. teaches "In a particular embodiment, the nanoparticles are selected from liposomes, gold nanoparticles, polymeric nanoparticles, carbon nanotubes and graphene oxide nanoparticles" (paragraph 00018).
Relevant to claim 14, Kostarelos et al. teaches "Once the biomolecule corona has formed on said nanoparticles, said particles are isolated. Any isolation technique that is capable of preserving the surface-bound biomolecule corona is suitable. Conveniently, the nanoparticles with surface-bound biomolecule corona are isolated from the biofluid and purified to remove unbound and highly abundant biomolecules (for example albumin and/or immunoglobulins, which can constitute 90% of the plasma proteome) to allow identification of lower abundant biomarkers… Conveniently, the isolation is achieved by a method comprising size exclusion chromatography followed by ultrafiltration" (paragraph 00023).
Relevant to claim 16, Kostarelos et al. teaches "In yet a further aspect of this embodiment, the disease state is cancer, such as for example ovarian cancer, lung cancer or melenoma" (paragraph 00030).
Relevant to claim 21, Kostarelos et al. teaches "In addition to the identification of new biomarkers, the methods also provide the ability to monitor changes in biomarkers for example in response to therapy. In one particular embodiment the therapy administered to the subject prior to testing is a drug molecule, such as for example, an anti-cancer compound" (paragraph 00026).
Relevant to claim 23, Kostarelos et al. teaches "In another aspect, the present invention relates to a method of detecting a diseased state in a subject, wherein the method comprises: a. administering a plurality of nanoparticles to a subject to allow a biomolecule corona to form on the surface of the nanoparticles; b. isolating the nanoparticles and surface-bound biomolecule corona; and c. determining the total biomolecule content of the biomolecule corona, which is determinative of the presence of disease in said subject" (paragraph 00012).
Further relevant to claim 23, Kostarelos et al. paragraph 00024 teaches “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.”
Further relevant to claim 23, Kostarelos et al. paragraphs 00017, 00020, and 00025 teach that “the biomarker comprises at least one biomolecule (for example, a protein, peptide, fatty acid, lipid, amino acid, sugar, amide or nucleic acid)”; “The term ‘biomolecule’ in this context includes, but is not limited to, proteins, peptides, fatty acids, lipids, amino acids, amides, sugars and nucleic acids (such as for example different types of DNA or RNA)”; and “In addition to the identification of a single biomarker, the methods also provide the ability to identify panels of biomarkers (multiplexing). This approach can lead to increased sensitivity and specificity of detection.”
Relevant to claim 24, Kostarelos et al. teaches "In addition, inventors have also surprisingly found that particular methods of the invention can be employed to distinguish between healthy and disease states in a subject, for example the detection of the presence of a tumor or monitoring the growth and/or response to treatment of a tumor" (paragraph 0008).
Further relevant to claim 24, Kostarelos et al. paragraph 00024 teaches “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.”
Further relevant to claim 24, Kostarelos et al. paragraphs 00017, 00020, and 00025 teach that “the biomarker comprises at least one biomolecule (for example, a protein, peptide, fatty acid, lipid, amino acid, sugar, amide or nucleic acid)”; “The term ‘biomolecule’ in this context includes, but is not limited to, proteins, peptides, fatty acids, lipids, amino acids, amides, sugars and nucleic acids (such as for example different types of DNA or RNA)”; and “In addition to the identification of a single biomarker, the methods also provide the ability to identify panels of biomarkers (multiplexing). This approach can lead to increased sensitivity and specificity of detection.”
Further relevant to claim 24, Kostarelos et al. teaches "It will be understood that in order to identify a potential disease-specific biomarker, comparison against a suitable non-diseased control reference can be required" (paragraph 00010).
Further relevant to claim 24, Kostarelos et al. teaches "In yet a further aspect of this embodiment, the disease state is cancer, such as for example ovarian cancer, lung cancer or melenoma" (paragraph 00030).
Kostarelos et al. does not teach a specific embodiment having all the claimed elements. That being said, however, it must be remembered that "[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious." KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. AG. Pro, 425 U.S. 273, 282 (1976)). "[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious," the relevant question is "whether the improvement is more than the predictable use of prior art elements according to their established functions." (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR at 1741. The Court emphasized that "[a] person of ordinary skill is... a person of ordinary creativity, not an automaton." Id. At 1742.
Consistent with this reasoning, it would have been prima facie obvious to have selected various combinations of various disclosed elements — including analyses, nanoparticle compositions, cancer, and monitoring — for a method of identifying biomarkers, to arrive at compositions "yielding no more than one would expect from such an arrangement."
Applicant’s Arguments and Response to Applicant’s Arguments
Applicant argues that the Kostarelos et al. proteinaceous examples and disclosure would not enabled the skilled artisan to appreciate that “different classes of biomarkers, most suitably nucleic acids, proteins, and lipids, can all be measured from the same biofluid sample and the same biomolecule corona simultaneously” (Remarks 4/22/26, pages 10-11).
The Examiner respectfully disagrees with these assertions.
Applicant is reminded that the cited prior art reference must be read in its entirety, not
merely selective portions. As set forth in MPEP 2141.02:
Ascertaining the differences between the prior art and the claims at issue requires interpreting the claim language, and considering both the invention and the prior art references as a whole… A prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention… However, ‘the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….’ In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004) (emphasis added)
To that end, Kostarelos et al. paragraphs 00017 and 00020 teach that “the biomarker comprises at least one biomolecule (for example, a protein, peptide, fatty acid, lipid, amino acid, sugar, amide or nucleic acid)” and “The term ‘biomolecule’ in this context includes, but is not limited to, proteins, peptides, fatty acids, lipids, amino acids, amides, sugars and nucleic acids (such as for example different types of DNA or RNA).”
Additionally, the claims as written do not explicitly require the argued simultaneous identification of biomarkers from two or more distinct biomarker classes using the same biomolecule corona. The broadest reasonable interpretation of “a method of identifying biomarkers from two or more distinct biomolecule classes in a biofluid” via “contacting a plurality of nanoparticles with a biofluid to allow a biomolecule corona to form on the surface of said nanoparticles” includes the interpretation that the “plurality of nanoparticles” are separately able to identify distinct biomarker classes (i.e., nanoparticle 1 identifies nucleic acids, nanoparticle 2 identifies proteins, …). To this end, Kostarelos et al. paragraph 00025 teaches “In addition to the identification of a single biomarker, the methods also provide the ability to identify panels of biomarkers (multiplexing). This approach can lead to increased sensitivity and specificity of detection.”
Claims 13, 17, and 19-20 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Kostarelos et al. (2018; WO 2018/046542 A1; FOR citation 1 in IDS filed on 2/9/23), as applied to claims 1-11, 14, 16, 21, and 23-24 above, and further in view of Huang et al. (2017; NPL citation U in PTO-892 filed 10/22/25; “Gold Nanoparticle Based Platforms for Circulating Cancer Marker Detection"; Nanotheranostics. 2017;1(1):80-102. doi: 10.7150/ntno.18216).
The teachings of Kostarelos et al. are applied to instantly rejected claims 13, 17, and 19-20 as they were previously applied to claims 1-11, 14, 16, 21, and 23-24 as rendering obvious a method of identifying biomarkers.
Kostarelos et al. is silent to specifics regarding negatively charged nanoparticles (relevant to claim 13) and cell-free DNA (relevant to claims 17 and 19-20). However, these limitations were known in the prior art and taught by Huang et al.
Relevant to claim 13, 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 [citation]. 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).
Relevant to claims 17, 19, and 20, Huang et al. teaches "Dying tumor cells release small fragments (50 to 250 bp) of their DNA into the bloodstream [citation]. These fragments, first found in cancer patients in 1977 [citation], are called cell-free ctDNA. They carry genomic and epigenomic alterations identical to those of tumor tissues and discriminate from normal cell-free DNA [citation]. 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).
Further relevant to claims 17, 19, and 20, Huang et al. teaches "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 [citation]. 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).
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.
The skilled artisan would have been motivated 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.
Additionally, the skilled artisan would have been motivated 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, the skilled artisan 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.
Applicant’s Arguments and Response to Applicant’s Arguments
Applicant argues that the Huang et al. does not remedy the argued Kostarelos et al. deficiencies posed in above Arguments relevant to claim 1 (Remarks 4/22/26, pages 11-13).
The Examiner respectfully disagrees with this assertion.
As discussed in above Response to Applicant’s Arguments to rejection of claim 1, Kostarelos et al. discloses the instantly argued limitations of identification of biomarkers from two distinct biomarker classes.
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.
Claims 1, 11, 14, 16, and 21 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 11-12 of U.S. Patent No. 11,598,779 B2 (hereafter patent ‘779). Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
This nonstatutory double patenting rejection is revised/updated in response to claim amendments filed 4/22/26.
Instant claim 1 is drawn to A method of identifying biomarkers… with active steps that are coextensive with patent ‘779 claims 1 and 9 (reproduced below).
Instant claim 11 is drawn to nanoparticle compositions that are coextensive with patent ‘779 claims 2-3 (reproduced below).
Instant claim 14 is drawn to low abundant biomarkers that are coextensive with patent ‘779 claims 4-5 (reproduced below).
Instant claim 16 is drawn to cancers that is coextensive with patent ‘779 claims 11-12 (reproduced below).
Instant claim 21 is drawn to monitoring therapeutic response that is coextensive with patent ‘779 claims 6-8 (reproduced below).
Patent ‘779 claims
1. A method of discovering unique disease-specific biomarker not previously known to be associated with the disease, wherein the method comprises:
a. incubating a plurality of nanoparticles in a biofluid sample taken from a subject suffering from the disease and allowing a biomolecule corona to form on the surface of the nanoparticles;
b. isolating the nanoparticles and surface-bound biomolecule corona;
c. analyzing the isolated nanoparticles and surface-bound biomolecule corona by mass spectrometry and generating a mass spectrum;
d. comparing the mass spectrum with a mass spectrum generated from a biofluid sample from a subject not suffering from the disease, which serves as a suitable non-diseased control reference, and identifying differences; and
e. discovering a unique disease-specific biomarker not previously known to be associated with the disease based on the differences.
2. A method according to claim 1, wherein the nanoparticles are selected from liposomes, metallic nanoparticles, polymeric nanoparticles, fibre-shaped nanoparticles, and two dimensional nanoparticles.
3. A method according to claim 1, wherein the nanoparticles are liposomes.
4. A method according to claim 1, wherein the nanoparticles with surface-bound biomolecule corona are isolated from the biofluid and purified to remove unbound and highly abundant biomolecules to allow identification of low abundant biomarkers.
5. A method according to claim 4, wherein the nanoparticles with surface-bound biomolecule corona are isolated from the biofluid and purified to remove unbound and highly abundant biomolecules by a method comprising size exclusion chromatography followed by ultrafiltration.
6. A method according to claim 1, wherein a change in a biomarker in response to therapy is monitored.
7. A method according to claim 6, wherein the therapy administered to the subject prior to testing is a drug molecule.
8. A method according to claim 7, wherein the drug molecule is an anti-cancer compound.
9. A method according to claim 1, wherein the biomarker is a multiplex panel of disease-specific biomolecule biomarkers.
11. A method according to claim 1, wherein the said disease is cancer.
12. A method according to claim 11, wherein the disease is lung cancer, melanoma or ovarian cancer.
Applicant’s Arguments and Response to Applicant’s Arguments
Applicant argues that the ‘779 patent does not teach “identifying multiple biomarkers in two or more distinct biomarker classes” (Remarks 4/22/26, page 13). The Examiner respectfully disagrees and directs applicant to patent ‘779 claim 9 “multiplex panel of disease-specific biomolecule biomarkers” wherein the skilled artisan would recognize the obvious variants of biomarkers spanning more than one biomarker class within a multiplex panel.
Claims 1-7, 11, 13-14, 16-17, 19-21, and 23-24 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 10-12, 14-15, 18-21, and 23-24 of copending Application No. 18/041,141 (reference application; hereafter application ‘141). Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This nonstatutory double patenting rejection is revised/updated in response to claim amendments filed 4/22/26.
Instant claims 1, 7, and 17 are drawn to A method of identifying biomarkers… with active steps and cell-free DNA that are coextensive with application ‘141 claims 1 and 11.
Instant claim 2 is drawn to an administration that is coextensive with application ‘141 claim 2.
Instant claim 3 is drawn to an intravenous injection that is coextensive with application ‘141 claim 3.
Instant claim 4 is drawn to an incubation that is coextensive with application ‘141 claim 4.
Instant claims 5-6 are drawn to biofluid samples that are coextensive with application ‘141 claim 5.
Instant claim 11 is drawn to nanoparticle compositions that are coextensive with application ‘141 claim 8.
Instant claim 13 is drawn to negatively charged nanoparticles that are coextensive with application ‘141 claim 10.
Instant claim 14 is drawn to low abundant biomarkers that are coextensive with application ‘141 claim 12.
Instant claim 16 is drawn to cancers that are coextensive with application ‘141 claim 14.
Instant claim 19 is drawn to determination of amounts that are coextensive with application ‘141 claim 15.
Instant claim 20 is drawn to determination of nucleic acid sequences that are coextensive with application ‘141 claims 18-19.
Instant claim 21 is drawn to monitoring therapeutic responses that are coextensive with application ‘141 claim 20.
Instant claim 23 is drawn to detecting disease states that are coextensive with application ‘141 claim 21.
Instant claim 24 is drawn to monitoring cancer progressions that are coextensive with application ‘141 claims 23-24.
Although amended instant claims 1 and 23-24 include analysis via performing one or more analytical measurements selected from… that are absent from application ‘141 claims, these analytical measurements are recited at such a high level of generality that the skilled artisan would find them obvious and well-understood methods of measurements.
Applicant’s Arguments and Response to Applicant’s Arguments
Applicant argues that “the ‘141 application does not teach or suggest currently amended independent Claims 1, 23, or 24”. The Examiner respectfully disagrees, as the amended analytical measurements are recited at such a high level of generality that the skilled artisan would find them obvious and well-understood methods of measurements.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah J Kennedy whose telephone number is (571)272-1816. The examiner can normally be reached Monday - Friday 8a - 5p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH JANE KENNEDY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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