DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission of RCE and amendment filed on January 28, 2026 have been entered. The claims pending in this application are claims 1-28 and 30-33 wherein claims 3, 12, and 21-28 have been withdrawn due to the restriction requirement mailed on November 8, 2024 and applicant’s response filed on February 28, 2025. Since applicant has canceled selected species (3) (the majority nucleic acid species is a normal nucleic acid species, and the minority nucleic acid is tumor nucleic acid species, see claims 1, 2, 4-11, and 13-20), now the office is required to examine other species in claims 1 and 2. Since claims 3 and 12 are belong to non-selected species (1), in order to examine species (1), claims 3 and 12 must be rejoined with claims 1, 2, 4-11, and 13-20 for the examination. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on January 28, 2026. Claims 1-20 and 30-33 will be examined.
Claim Objections
Claim 8 or 17 is objected to because of the following informality: “contacting the sample nucleic acid with the agent” should be “said contacting the sample nucleic acid with an agent coupled to a solid support”.
Claim 8 or 17 is objected to because of the following informality: “in a chromosome or gene present in the histone-associated minority nucleic acid species” should be “in the histone-associated minority nucleic acid species”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Scope of Enablement
Note that the rejection is different from the rejection 35 U.S.C. 112(a) mailed on July 28, 2025.
Claims 1-20 and 30-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for contacting the biological sample with an agent coupled to a solid support, does not reasonably provide enablement for producing a separation product by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the methods recited in claims 1, 3-9, 19, 20, and 32 and analyzing the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a method for separating minority nucleic acid species from majority nucleic acid species in a biological sample comprising cell-free nucleic acid and histones and a method for analyzing a minority nucleic acid species from a biological sample comprising cell-free nucleic acid and histones. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 1, 3-9, 19, 20, and 32 encompass a method for separating minority nucleic acid species from majority nucleic acid species in a biological sample comprising cell-free nucleic acid and histones, wherein the cell-free nucleic acid comprises a minority nucleic acid species and a majority nucleic acid species, wherein (1) the majority nucleic acid species is a normal nucleic acid species, and the minority nucleic acid is an apoptotic nucleic acid species, or
(2) the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus, the method comprising, (a) contacting the biological sample with an agent coupled to a solid support, wherein the agent binds preferentially to one or more histones associated with the minority nucleic acid species than to other histones, wherein the one or more histones are selected from the group consisting of H1.1, H1.3, H1.5, H3.1, H3.2, and H3t, thereby the one or more histones and the minority nucleic acid associated therewith are attached to the solid support; and (b) separating the solid support, to which the minority nucleic acid species are attached, from the biological sample, thereby separating the minority nucleic acid species from the majority nucleic acid species in the biological sample and producing a separation product. Claims 2, 10-18, 30, 31, and 33 encompass a method for analyzing a minority nucleic acid species from a biological sample comprising cell-free nucleic acid and histones, wherein the cell-free nucleic acid comprises comprise a majority nucleic acid species and minority nucleic acid species, wherein (1) the majority nucleic acid species is a normal nucleic acid species, and the minority nucleic acid is an apoptotic nucleic acid species, or
(2) the majority nucleic acid are species is host nucleic acid species and the minority nucleic acid is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus, the method comprising: contacting the biological sample with an agent coupled to a solid support, wherein the agent binds preferentially to one or more histones associated with the minority nucleic acid species, thereby forming histone-associated minority nucleic acid species, wherein the one or more histones are selected from the group consisting of H1.1, H1.3, H1.5, H3.1, H3.2, and H3t, thereby the one or more histones and the histone-associated minority nucleic acid species are attached to the solid support, and analyzing the histone-associated minority nucleic acid species attached to the solid support.
Working Examples
The specification provides 3 examples (see pages 40-49 of US 2024/0401140 A1, which is US publication of this instant case). However, the specification provides no working example for producing a separation product by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the method recited in claims 1, 3-9, 19, 20, and 32 and analyzing the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus.
The Amount of Direction or Guidance Provided and The State of The Prior Art
Although the specification provides 3 examples (see pages 40-49 of US 2024/0401140 A1, which is US publication of this instant case), the specification provides no working example for producing a separation product by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the methods recited in claims 1, 3-9, 19, 20, and 32 and analyzing the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to produce a separation product by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the method recited in claims 1, 3-9, 19, 20, and 32 and analyze the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether a separation product can be produced by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the method recited in claims 1, 3-9, 19, 20, and 32 and the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones can be analyzed using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus.
Although the specification teaches that “[I]n one example, histone H3.1 can be highly enriched in fetal liver, compared to histone H3.1 levels in adult tissues including liver, kidney and heart. In adult tissue, the H3.3 variant can be more abundant than the H3.1 variant (see e.g., United States Patent Application Publication nos. 2007/0243549 and 2010/0240054). Thus, a first histone-associated nucleic acid species can be a nucleic acid associated with histone H3.3 and a second histone-associated nucleic acid species can be a nucleic acid associated with
histone H3.1. Because histone H3.1 can be enriched in fetal tissue, separating some or substantially all of the first histone-associated nucleic acid species (i.e. histone H3.3 associated nucleic acid) from the sample nucleic acid can deplete a proportion of maternal nucleic acid and generate a separation product enriched for fetal nucleic acid relative to fetal nucleic acid in the sample nucleic acid. In some instances, the conformational structure of fetal DNA in nucleosomes is such that histone H3.1 is more exposed in fetal DNA than in maternal DNA. Such a difference can also be exploited to target histone H3.1”, “[I]n another example, histone
H1a can be enriched in fetal retina, compared to histone H1a levels in adult retina, which can have relatively higher levels of histone H1 b and H1(0) (see Perkins and Young (1987) Jpn J Ophthalmol. 31(4):590-7). Thus, a first histone-associated nucleic acid species can be a nucleic acid associated with histone H1 b and/or H1(0) and a second histone-associated nucleic acid species can be a nucleic acid associated with histone H1a. Because histone H1a can be enriched in certain fetal tissue, separating some or substantially all of the first histone-associated nucleic acid species (i.e. histone H1 b and/or H1(0) associated nucleic acid) from the sample nucleic acid can deplete a proportion of maternal nucleic acid and generate a separation product enriched for fetal nucleic acid relative to fetal nucleic acid in the sample nucleic acid”, “[I]n some embodiments, a method comprises separating some or substantially all of a first histone-associated nucleic acid species from a second histone-associated nucleic acid species, thereby generating a separation product enriched for the second histone-associated nucleic acid species. In some embodiments, fetal nucleic acid in the separation product is enriched relative to fetal
nucleic acid in the sample nucleic acid. In certain instances, circulating cell free fetal DNA can be associated with microparticles and nucleosomes (e.g., histone bound) that are derived from
fetal tissue. In certain instances, circulating cell free maternal DNA can be associated with microparticles and nucleosomes (e.g., histone bound) that are derived from maternal tissue. Thus, in some embodiments, utilization of fetal source-specific binding agents (e.g., antibodies) to target fetal-derived microparticles and/or nucleosomes can enrich fetal DNA. In some embodiments, utilization of maternal source-specific binding agents (e.g., antibodies) to target maternal-derived microparticles and/or nucleosomes can enrich fetal DNA”, “[I]n some embodiments, antibodies to fetal-specific histones (e.g., H1.1, H1.3, H1.5), are used to enrich
fetal ccf DNA in certain positive selection approaches. In some embodiments, antibodies to maternal-specific histones (e.g., H1, H1.0), are used to enrich fetal ccf DNA in certain depletion-based entichment (i.e., negative selection) approaches. In some embodiments, antibodies to H1M histone (expressed in Xenopus embryos) and/or to H1 FOO (which are expressed in oocytes) are used to enrich fetal ccf DNA in certain positive selection approaches. These approaches can include any suitable separation method described herein or known in the art such as conventional immunoprecipitation and Chromatin ImmunoPrecipitation (CHIP) approaches, for example”, “[T]here are approximately eleven H1 variants, some of which may be specific (or show preferential binding) to fetal-derived ccf DNA. Additionally, various maternal versus
fetal differences in H3 histone subtype can be exploited to enrich for fetal fraction. For example, antibodies recognizing conformational exposure differences for histone H3.1 (e.g., differences between fetal and maternal H3.1) can be used for fetal DNA enrichment from plasma treated with such antibodies, in certain embodiments. For example, sequence variance (e.g., extra 10 amino acids at the c-terminus of fetal H3.1), and particular methylation of H3.1 in fetal versus maternal can be exploited for fetal DNA enrichment, in certain embodiments”, “[I]n this example, a process is described for enriching the amount of fetal derived DNA relative to total derived (maternal+fetal) DNA, also expressed as fetal fraction, in plasma samples. DNA prepared from plasma is often referred to as circulating cell-free DNA (ccf DNA), as described herein. Circulating cell-free DNA can exist in multiple states within whole blood. DNA can be naked, histone bound (i.e., nucleosomes containing DNA and histones), or encapsulated in a lipid bilayer as a microparticle (for example, in an apoptotic structure). Circulating cell free fetal DNA can be associated with microparticles and nucleosomes (e.g., histone bound) that are derived from fetal tissue. Circulating cell free maternal DNA can be associated with microparticles and nucleosomes (histone bound) that are derived from maternal tissue. Thus, utilization of fetal
source-specific antibodies to target fetal-derived microparticles and/or nucleosomes can enrich
fetal DNA. This example describes a process for specifically enriching for circulating cell free
fetal DNA associated nucleosomes (histone bound)”, “[N]ucleosome DNA typically is associated with an octamer of eight core histones: H2A (2), H2B (2), H3 (2), and H4 (2); and a linker histone H1. In maternal blood and cleared plasma, fetal ccf DNA may have a lower occupancy of H1 (i.e., a smaller percentage of the nucleosome DNA of fetal origin may have H1 bound, relative to the percentage of maternal ccf DNA having H1 bound). Without being limited by theory, the typical size distribution of fetal ccf DNA versus maternal ccf DNA is in accordance with this concept, since nucleosome DNA without H1 bound may be more susceptible to endonuclease digestion, thus resulting in shorter fragments”, “[U]se of an antibody to histone H1 (e.g., without particular specificity to H1 subtypes or sources) can serve as a suitable negative selection approach to enrich for fetal DNA. Treatment of plasma with such antibody in an immunoprecipitation (e.g., Chromatin ImmunoPrecipitation (CHIP)) protocol can deplete maternal ccf DNA from the sample, thus enhancing ccf DNA fetal fraction in the residual sample”, “[A]ntibodies to fetal-specific histones (e.g., H1.1, H1.3, H1.5), can enrich fetal ccf DNA when used in positive selection approaches. Antibodies to maternal-specific histones (e.g., H1.0), can enrich fetal ccf DNA when used in depletion-based entichment (i.e., negative selection) approaches. These approaches can include, conventional immunoprecipitation and Chromatin ImmunoPrecipitation (CHIP) approaches. Antibodies to H1M histone (expressed in Xenopus embryos) and to H1 FOO (which are expressed in oocytes) may offer some cross reactivity and selectivity to human fetal-derived chromatin DNA, and thus also may be used as a positive selection strategy”, “[T]here are approximately eleven H1 variants, some of which may be specific (or show preferential binding) to fetal-derived ccf DNA. Additionally, various maternal versus fetal differences in H3 histone subtype can be exploited to enrich for fetal
fraction. For example, antibodies recognizing conformational exposure differences for
histone H3.1 (e.g., differences between fetal and maternal H3.1) can be used for fetal DNA enrichment from plasma treated with such antibodies. For example, sequence variance (e.g., extra 10 amino acids at the c-terminus of fetal H3.1), and particular methylation of H3.1 in fetal versus maternal can be exploited for fetal DNA enrichment” (see paragraphs [0085], [0086], [0091], [0094], [0095], and [0249] to [0253] of US 2024/0401140 A1, which is US Publication of this instant case), the specification clearly indicates that antibodies to fetal-specific histones such as H1.1, H1.3 and H1.5 can be used to separate cell-free fetal DNA from cell-free maternal DNA in blood plasma. However, the scope of claims 1-20 and 30-33 are much broader than the scope of the specification since the specification does not teach to produce a separation product by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using antibodies specific for histones associated to apoptotic nucleic acid species and analyze the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones using antibodies specific for histones associated to nucleic acid species of a virus when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus. Although it is known that circulating tumor DNA can be isolated from blood plasma or serum by binding antibodies specific for histones H3.1 and/or H3.2 and/or H3.3 to circulating cell free nucleosome containing the circulating tumor DNA and the histones H3.1 and/or H3.2 and/or H3.3 (see US 2018/0024141 A1, paragraphs [0021] to [0040], [0067] to [0070], and [0072] to [0104], and claims 2-27), nowhere in the specification and prior arts show that a separation product can be produced by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using antibodies specific for histones associated to apoptotic nucleic acid species such as H1.1 or/and H1.3 or/and H1.5 or/and H3.1 or/and H3.2 or/and H3t and analyze the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones using antibodies specific for histones associated to nucleic acid species of a virus such as H1.1 or/and H1.3 or/and H1.5 or/and H3.1 or/and H3.2 or/and H3t when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus such that it is unpredictable how a separation product can be produced by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the method recited in claims 1, 3-9, 19, 20, and 32 and how the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones can be analyzed using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus. Furthermore, since it is known that blood plasma of a healthy human also contains cell free nucleosomes comprising H3.1 (see Figure 1 and paragraph [0023] of US 2023/0003735 A1), even though we assume that the nucleosomes in a biological sample such as a blood plasma can comprise H3.1 and apoptotic nucleic acid species, when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species, the nucleosomes comprising H3.1 and normal nucleic acid species and the nucleosomes comprising H3.1 and apoptotic nucleic acid species in the biological sample such as a blood plasma cannot be separated from each other using an agent coupled to a solid support such as H3.1 antibody such that the minority nucleic acid species cannot be separated from the majority nucleic acid species in the biological sample such as a blood plasma and a separation product cannot be produced as recited in claims 1, 3-9, 19, 20, and 32, and the majority nucleic acid species cannot be differentiated from the minority nucleic acid species and the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones such as a blood plasma cannot be analyzed using the methods as recited in claims 2, 10-18, 30, 31, and 33. In addition, since it is known that blood plasma of a healthy human also contains cell free nucleosomes comprising H3.1 (see Figure 1 and paragraph [0023] of US 2023/0003735 A1), even though we assume that the nucleosomes in a biological sample such as a blood plasma obtained from a user infected with a virus can comprise H3.1 and nucleic acid species of the virus, when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus, the nucleosomes comprising H3.1 and normal nucleic acid species and the nucleosomes comprising H3.1 and nucleic acid species from the virus in the biological sample such as a blood plasma obtained from a user infected with the virus cannot be separated from each other using an agent coupled to a solid support such as H3.1 antibody such that the minority nucleic acid species cannot be separated from the majority nucleic acid species in the biological sample such as a blood plasma obtained from a user infected with the virus and a separation product cannot be produced as recited in claims 1, 3-9, 19, 20, and 32, and the majority nucleic acid species cannot be differentiated from the minority nucleic acid species and the minority nucleic acid species attached to the solid support from a
biological sample comprising cell-free nucleic acid and histones cannot be analyzed using the methods as recited in claims 2, 10-18, 30, 31, and 33.
Second, since it is known that “[P]ost-translational modification (PTM) in histone proteins is a covalent modification which mainly consists of methylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation. PTMs have fundamental roles in chromatin structure and function. Histone modifications have also been known as epigenetic markers” (see abstract from Ramazi et al., J. Biosci., 45, 135, 2020), an assay using a binding agent such as an antibody for H1.1 or H1.3 or H1.5 or H3.1 or H3.2 or H3t which binds preferentially to a modified histone comprising one or more posttranslational modifications cannot be not used for analyzing a genetic variation of minority nucleic acid species of the histone-associated minority nucleic acid species in the attached to the solid support but is used for detecting the histones of the histone-associated minority nucleic acid species in the attached to the solid support. Thus, it is unpredictable how the presence or absence of a genetic variation in the histone-associated minority nucleic acid species can be detected using the assay of claim 10 as recited in claim 30.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether a separation product can be produced by separating the minority nucleic acid species from the majority nucleic acid species in the biological sample comprising cell-free nucleic acid and histones using the method recited in claims 1, 3-9, 19, 20, and 32 and the minority nucleic acid species attached to the solid support from a biological sample comprising cell-free nucleic acid and histones can be analyzed using the methods recited in claims 2, 10-18, 30, 31, and 33 when the majority nucleic acid species is a normal nucleic acid species and the minority nucleic acid is an apoptotic nucleic acid species or when the majority nucleic acid species is a host nucleic acid species, the minority nucleic acid species is a nucleic acid species of a virus, and the biological sample is obtained from a user infected with the virus.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
Applicant’s arguments with respect to claims 1, 2, 4-11, 13-20, and 30-33 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 PM.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
May 5, 2026
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