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 .
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.
Status of Claims
Claims 1-18 and 23-24 are pending. Claim 23 is drawn to the nonelected invention. Claims 1-18 and 24 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/13/2024 has been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-18) in the reply filed on 04/13/2026 is acknowledged. Applicant further elected the species of (1) plasma as the sample type and (2) cancer as the disease. Based on prior art search and compact prosecution, Group III (claim 24) is hereby rejoined. Thus, claims 1-18 and 24 are currently under examination.
Claim 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse.
In view of rejoining Group III (claim 24), applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
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.
Claims 5 and 18 are 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.
Regarding claim 5, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The interpretation for this claim is that the limitations following the phrase, such as, is not required by the claim.
Claim 18 appears to contain two duplicated claims or a typographical error. MPEP states that a claim must only contain a single sentence with one period punctation. Thus, claim 18 is unclear to the metes and bounds of what is contained in the claim.
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 1-18 and 24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: The instantly claimed invention is directed to a method of detecting a cell free chromatin fragment comprising a transcription factor and a DNA fragment in a body fluid sample obtained from a human or animal subject. Therefore, the instantly claimed invention falls into one of the four statutory categories. (Step 1: YES)
ELIGIBILITY STEP 2A; WHETHER A CALIM IS DIRECTED TO A JUDICIAL EXCEPTION. First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A Prong 1
Claim 1 recites the following steps which fall under the mental processes of abstract ideas and law of nature or natural phenomena:
Claim 1 is drawn to a method of detecting a cell free chromatin fragment of a transcription factor and a DNA fragment in a body fluid sample obtained from a human or animal subject and detecting or measuring the DNA fragment and using the presence or amount of the DNA fragment as an indicator for transcription factor in the sample.
First, these limitations contain abstract ideas of mental processes for the following reasons. In particular, the steps of detecting or measuring the DNA fragment associated with the transcription factor and using the presence or amount of the DNA as a measure of the amount (an indicator) for transcription factor in the sample can be practically performed in the mind assisted with pen and paper. The mental processes insofar as such comparison of information could take place wholly in the human mind, or by a human using pen and paper; for example, this could read on a human reading the marker levels off a chart and thinking about the marker levels with respect to the transcription factor in the sample (e.g., forming an observation/evaluation/judgment/opinion regarding DNA fragment and transcription in a sample). Similar concepts involving comparing information regarding a sample or test subject to a control or target data have been held to be an "abstract mental process", as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and determining the existence of alterations", the collecting and comparing of known information in Classen, the comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC. Therefore, these limitations recite a mental process.
Second, claims 1, 11, and 24 are drawn to the presence or amount of the DNA fragment as an indicator for a sample that may have cancer disease, which thereby reciting the laws of nature/ natural phenomena in a human or animal sample. The natural relationship to which the claims are directed (i.e., the naturally occurring correlation of the presence or amount of DNA in human or animal sample) exists in principle apart from any human action. Similar concepts have been held by the courts to constitute laws of nature/ natural phenomena, as in the identification of a correlation between the presence of a marker in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017); see also Univ. of Utah Research Found. v. Ambry Genetics Corp., 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)).
Dependent claims 9, 12, 14-15, and 17 further recite limitations directed to the law of nature and natural phenomena, as the claims further define the naturally produced cell-free chromatin fragments, tissue, body fluid samples and the naturally occurring diseases associated with the presence of DNA and transcription factor in the subject. (Step 2A, Prong 1: YES).
Step 2A: Prong 2:
The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the judicial exception. A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. Besides the abstract ideas and law of nature/natural phenomena, claims 1, 11 and 24 are drawn to contacting the body fluid sample with a binding agent which binds to the transcription factor (claims 1 and 11) and administering a treatment (claim 24).
Dependent claim 2 is drawn to isolating the transcription factor bound in step (i) from the remaining body fluid sample, prior to detection of the associated DNA fragment in step (ii). Claim 3 is drawn to step (ii) comprises sequencing the DNA fragment associated with the transcription factor. Claim 4 is drawn to extracting the DNA fragment associated with the transcription factor. Claim 5 is drawn to additionally comprises amplification of the extracted DNA fragment. Claim 6 is drawn to the DNA fragment associated with the transcription factor is detected and/or measured by real-time PCR. Claim 7 is drawn to removing cell free nucleosomes from the body fluid sample. Claim 8 is drawn to further comprising contacting the body fluid sample with a binding agent which binds to nucleosomes or a component thereof and removing the sample bound to the binding agent prior to step (ii). Claim 10 is drawn to the transcription factor bound by the binding agent in step (i) is washed with a buffer solution containing at least 1% concentration of detergent, prior to detection of the associated DNA fragment in step (ii). Claim 13 is drawn to sequencing the DNA associated with the transcription factor and using the presence of the transcription factor and the sequence of the associated DNA as a combined biomarker for determining a tissue affected by the disease in the subject. Claim 16 is drawn to the binding agent which binds to the transcription factor is an antibody or a fragment thereof. Claim 18 is drawn to the body fluid sample is a plasma sample which obtained by: (1) contacting a whole blood sample with a cross-linking agent; (2) contacting the cross-linked sample with a calcium ion chelating agent; and (3) isolating plasma from the sample.
When so evaluated, these steps constitute as insignificant extra solution activity, which are required for the judicial exception. The limitations as discussed above represent steps that are necessary to gather data information from/for the recited judicial exception and the steps are recited at a high level of generality. These steps of sequencing, extracting, amplification, real-time PCR, removing cell free nucleosomes from the sample, binding agent, washing, isolating plasma from the sample are directed to obtaining data information which are needed to carry out the judicial exceptions. These additional elements only interact with the judicial exception by providing data to be processed by the judicial exception. Thus, these limitations are not sufficient to integrate the judicial exceptions into a practical application (MPEP 2106.05(g)).
The additional element in claim 24 of administering a treatment if the subject is determined to have cancer does not integrate the judicial exceptions into a practical application because this step constitutes as mere instructions to apply the exception (see MPEP 2106.05(f)). The additional element of administering a treatment constitutes as mere instructions to apply the exception because of the generality of the application of the judicial exception. Further, these elements are not integrated into a practical application because by generically administering any treatment do not engage with the judicial exception in a manner which requires a specific treatment for the cancer and it is equivalent of merely adding the words “apply it” to the judicial exception. Therefore, administering a treatment does not apply or use the judicial exception in a meaningful way. Thus, none of the additional elements recited in the claims would integrate a judicial exception into a practical application, and the claims are directed the judicial exceptions (Step 2A, Prong 2: NO).
Step 2B:
In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05. The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
The additional limitations in claims 1, 11, and 24 are contacting the body fluid sample with a binding agent which binds to the transcription factor (claims 1 and 11) and administering a treatment (claim 24). The dependent claims further recite the additional elements of isolating the transcription factor or extracting the DNA fragment associated with the transcription factor (claims 2 and 4), amplification of DNA by PCR (claims 5-6 and 13), binding agent binds to nucleosomes and removing (claims 7-8), washing with buffer solution (claim 10), antibody (claim16), contacting blood sample with crosslinking agent, calcium ion chelating agent and isolating plasma from the sample (claim 18) and administering a treatment for lung cancer (claim 24).
The additional elements are well-understood, routine, and conventional. This position is supported by Sadeh et al. (WO2019175876A2, published 09/19/2019, hereinafter Sadeh, IDS submitted 02/13/2024, cite no. 12), Micallef et al. (WO2017162755A1, published 09/28/2017, hereinafter Micallef, IDS submitted 02/13/2024, cite no. 11), and Bock et al. (US20180237951A1, published 08/23/2018, hereinafter Bock, IDS submitted 02/13/2024, cite no. 1).
Sadeh teaches determining the origin of cell free DNA (cfDNA) for detecting death of a cell type or tissue in a subject (abstract). Sadeh teaches association of the DNA-associated protein with the genomic location is indicative of active transcription and the genomic location is within a tissue (see para. [0108]). Sadeh teaches the cfChIP protocol using antibody covalently bound to paramagnetic beads (see abstract and para. [0040]). Sadeh teaches determining a cellular state of a cell in a subject by sequencing cfDNA isolated by extracting proteins and modified proteins bound to that cfDNA (see paras. [006]-[007]). Sadeh teaches blood sample can be fractionated portion of peripheral blood, such as plasma sample and once the blood sample is obtained, total DNA can be extracted from the sample using standard techniques known to one skilled in the art (see para. [0119]). Sadeh teaches the sequencing comprises PCR amplification of the cfDNA (see paras. [092] and [0173]). Sadeh teaches identification of cancer-specific transcriptional programs can assist diagnosis and treatment choice (see para. [0235]). Sadeh teaches the blood samples were collected with EDTA added and blood was centrifuged for the supernatant to be used as plasma for ChIP (see para. [0170]).
Micallef teaches using said tissue specific transcription factor or cofactor adducts to identify the site of development of a cancer in a subject (abstract). Micallef teaches obtaining a biological fluid sample from the subject, contacting the sample with a first binding agent which binds to a transcription factor or cofactor and detecting or quantifying the binding (see pg. 9, lines 25-35). Micallef teaches ELISA results for circulating cell free nucleosomes levels and circulating DNA levels as measured by real time PCR (see pg. 4, lines 16-20). Micallef teaches the biological fluid sample from a subject includes whole blood, blood serum, and plasma (see pg. 25, lines 32-37). Micallef teaches the biotinylated antibody solution was washed 3 times with wash buffer (see pg. 32, lines 13-16). Micallef teaches ChIP method the cellular chromatin is cross-linked so that all the protein and nucleic acid components are covalently attached to each other and an antibody to the protein of interest is added (see pg. 6. Lines 5-15).
Bock teaches the addition of an agent binding to chromatin to a sample comprising a nucleic acid, isolating nucleic acid from chromatin, amplification of nucleic acid, sequencing of amplified nucleic acid and identifying molecular interactions (see abstract). Bock teaches formaldehyde for the crosslinking of DNA and the chromatin is then extracted from the cells (see para. [0085]). Bock teaches chromatin immunoprecipitation (ChIP), optionally followed by massive parallel sequencing (ChIP-seq) (see para. [0002]). Bock teaches ChIPmentation compared to standard ChIP-seq and library preparation by tagmentation of purified ChIP DNA (ChIP-tagmentation) and all three protocols start with fixing cells with formaldehyde, cell lysis, sonication of chromatin, and immunoprecipitation with a specific antibody bound to beads (see para. [0157]). Bock teaches blood cancer leukemia and fixing cells with formaldehyde or paraformaldehyde (see paras. [0038] and [0052]-[0053]). Bock teaches cells were fixed with paraformaldehyde and later incubated with SDS, NaCl, EDTA and Tris-HC1 (see paras. [0194] and [0204]). Bock teaches crosslinking fixatives-especially formaldehyde-tend to preserve the secondary structure of proteins and may protect significant amounts of tertiary structure as well (see para. [0112]).
The additional elements are well-understood, routine, and conventional. This position is supported by the recited references above. Therefore, taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. (Step 2B: NO)
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-17 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sadeh et al. (WO2019/175876A2, published 09/19/2019, IDS submitted 02/13/2024, cite no. 12).
With respect to claims 1 and 11, Sadeh teaches methods of determining the origin of cell free DNA (cfDNA), for detecting death of a cell type or tissue in a subject, for determining a cellular state of a cell as it died (see abstract). Sadeh teaches cell-free chromatin in plasma and contacting the body fluid sample with a binding agent which binds to the transcription factor (see abstract picture and para. [037]). Sadeh teaches the method of determination is providing a sample, wherein the sample comprises cfDNA; contacting the sample with at least one reagent that binds to a DNA-associated protein; isolating the reagent and any thereto bound proteins and cfDNA; sequencing the isolated cfDNA; and designating a cfDNA molecule comprising a DNA sequence of an informative genomic location as originating from a cell in a cellular state, originating from a tissue, originating from a tissue, originative form a cell type or a combination thereof, wherein association of the DNA-associated protein with the informative genomic location is indicative of the cellular state, tissue of origin, cell type or combination thereof in the cell that released the cfDNA (see para. [006]-[007]). Sadeh further teaches the DNA-associated protein binds DNA and is a sequence specific DNA binder and include a transcription factor (see para. [0079]). Sadeh teaches association of the DNA-associated protein with the genomic location is indicative of active transcription and the genomic location is within tissue (see para. [0108]).
With respect to claim 2, Sadeh teaches isolating the transcription factor bound in step (i) from the remaining body fluid sample, prior to detection of the associated DNA fragment in step (ii) (see abstract picture and para. [037]).
With respect to claim 3, Sadeh teaches the assay is chromatin immunoprecipitation followed by sequencing (ChIP-Seq) (see para. [037]).
With respect to claim 4, Sadeh teaches extracting and sequencing DNA from cf-nucleosomes carrying specific histone markers (see para. [0213] and abstract picture).
With respect to claims 5-6, Sadeh teaches the sequencing comprises PCR amplification of the cfDNA (see para. [092]). Sadeh teaches the eluted DNA were used for PCR amplification with Kapa hot-start polymerase (see para. [0173]).
With respect to claims 7-8, Sadeh teaches the antibody-beads complexes were added directly into the plasma and allowed to bind to cf-nucleosomes and following the removal of the beads, the plasma was stored as it was suitable for further rounds of cf-ChIP (see para. [0172]).
With respect to claim 9, Sadeh teaches the free chromatin fragment consists of the transcription factor and DNA fragment (see abstract picture).
With respect to claim 10, Sadeh teaches the DNA elution and cleanup steps the beads were incubated for 1 hour in chromatin elution buffer (Tris, EDTA, NaC1 and SDS) (see para. [0173]).
With respect to claim 11, see above.
With respect to claim 12, Sadeh teaches the assay is either used alone or in combination with existing biomarkers (see para. [055]).
With respect to claim 13, Sadeh teaches the assay is chromatin immunoprecipitation followed by sequencing (ChIP-Seq) (see para. [037]). Sadeh teaches methods of determining the origin of cell free DNA (cfDNA), for detecting death of a cell type or tissue in a subject, for determining a cellular state of a cell as it died (see abstract).
With respect to claim 14, Sadeh teaches the method of determination is providing a sample, wherein the sample comprises cfDNA; contacting the sample with at least one reagent that binds to a DNA-associated protein; isolating the reagent and any thereto bound proteins and cfDNA; sequencing the isolated cfDNA; and designating a cfDNA molecule comprising a DNA sequence of an informative genomic location as originating from a cell in a cellular state, originating from a tissue, originating from a tissue, originative form a cell type or a combination thereof, (see para. [006]-[007]). Sadeh teaches the cellular state is a disease state (see para. [014]).
With respect to claim 15, Sadeh teaches the disease state is cancer or inflammation (see para. [014]).
With respect to claim 16, Sadeh teaches the paramagnetic beads with covalent bound antibody (see abstract picture).
With respect to claim 17, Sadeh teaches body fluid is plasma (see abstract picture).
With respect to claim 24, Sadeh has been discussed above. Sadeh further teaches the method further comprises treating the subject with a suitable treatment based on the cellular state (see para. [031]). Fig. 3 shows cancer patients (also see para. [042]).
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.
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.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Sadeh et al. (WO2019/175876A2, published 09/19/2019, IDS submitted 02/13/2024, cite no. 12), as applied to claim 1 above, and further in view of Bock et al. (US2018/0237951A1, published 08/23/2018, IDS submitted 02/13/2024, cite no. 1).
Sadeh has been discussed above. Sadeh does teach the body fluid sample is a plasma sample (see abstract picture), EDTA was used (i.e., calcium ion chelating agent) and the blood was centrifuged wherein the supernatant was used as plasma for ChIP experiment and the plasma was stored (see para. [0170]). However, the reference fails to teach the contacting the blood sample with a cross-linking agent.
Bock teaches the addition of an agent binding to chromatin to a sample comprising a nucleic acid, isolating nucleic acid from chromatin, amplification of nucleic acid, sequencing of amplified nucleic acid and identifying molecular interactions (see abstract). Bock teaches formaldehyde for the crosslinking of DNA and the chromatin is then extracted from the cells (see para. [0085]). Bock teaches chromatin immunoprecipitation (ChIP), optionally followed by massive parallel sequencing (ChIP-seq) (see para. [0002]). Bock teaches ChIPmentation compared to standard ChIP-seq and library preparation by tagmentation of purified ChIP DNA (ChIP-tagmentation) and all three protocols start with fixing cells with formaldehyde, cell lysis, sonication of chromatin, and immunoprecipitation with a specific antibody bound to beads (see para. [0157]). Bock teaches blood cancer leukemia and fixing cells with formaldehyde or paraformaldehyde (see paras. [0038] and [0052]-[0053]). Bock teaches cells were fixed with paraformaldehyde and later incubated with SDS, NaCl, EDTA and Tris-HC1 (see paras. [0194] and [0204]). Bock teaches crosslinking fixatives-especially formaldehyde-tend to preserve the secondary structure of proteins and may protect significant amounts of tertiary structure as well (see para. [0112]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used the ChIP assay as taught by Sadeh with formaldehyde crosslinking as taught by Bock because Bock teaches formaldehyde crosslinks to DNA molecules before the chromatin is extracted from the cells and formaldehyde preserves the secondary structure of proteins and protects significant amounts of tertiary structure.
The person would have a reasonable expectation of success incorporating a crosslinking agent for chromatin extraction because it has been well understood by Bock to use formaldehyde to crosslink DNA for extracting chromatin in fluid samples.
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 1-3, 6, 9, 11-16 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 25-26 and 28-29 of copending Application No. 18/260011 (reference application).
With respect to claims 1 and 11, although the claims at issue are not identical, they are not patentably distinct from each other because the copending Application recites a method of detecting a cell free DNA chromatin fragment including all or a part of a transcription factor binding site sequenceAdditionally, claim 8 recites that wherein the DNA is analyzed for the presence of a transcription factor binding site and/or flanking sequence. Therefore, the analyzing step of the copending Application in claim 1 would be using the presence of DNA fragment as a measure of the amount of cell chromatin fragments comprising the transcription in the sample.
With respect to claims 2, 9, 13 and 16, copending claims 3-4 and 7 recite wherein the binding agent binds to a nucleosome core epitope, wherein the binding agent is all or a part of histone H1 moiety or a chromatin binding protein, and wherein the binding agent is attached to a solid support.
With respect to claims 3, 6 and 12, copending claims 9-10 recite the DNA is analyzed by PCR and wherein sequence pattern of the DNA as an indicator of the disease state of the subject.
With respect to claims 14-15, and 24, copending claims 25-26 recite a method of treating a disease in a subject in need thereof, wherein said method comprises the following steps:(i) contacting a body fluid sample obtained from the human or animal subject with a binding agent which binds to a nucleosome; (ii) detecting or measuring a DNA fragment not bound to the binding agent in step (i); (iii) using the presence, sequence, amount or fragmentation pattern of the DNA fragment as an indicator of the presence of the disease in the subject; and (iv) administering a treatment if the subject is determined to have the disease in step (iii) and the treatment is chemotherapy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-18 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 25-26 and 28-29 of copending Application No. 18/260011 in view of Bock et al. (US2018/0237951A1, published 08/23/2018, IDS submitted 02/13/2024, cite no. 1).
The copending Application 18/260011 recites a method of detecting a cell free DNA chromatin fragment including all or a part of a transcription factor binding site sequence
Bock has been discussed above. It would have been obvious to a person of ordinary skill in the art at the time of filing the claimed invention to have used the process of detecting cell free DNA chromatin fragment including transcription factor as recited in copending Application 18/260011 with the process of removing, extracting, isolating, and crosslinking blood sample as taught by Bock because Bock teaches extracting DNA chromatin and preserves the secondary structure of proteins and protects significant amounts of tertiary structure.
The person would have a reasonable expectation of success incorporating the process of Bock because it has been well understood by Bock to use extract DNA chromatin for sequencing and detection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAM P NGUYEN whose telephone number is (571)270-0287. The examiner can normally be reached Monday-Friday (8-4).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
Prosecution Insights