DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group I, Claims 1-2 and 4-9, drawn to a method for predicting the outcome or classifying the disease of a prostate carcinoma patient in the reply filed on 12/11/2025 is acknowledged. The traversal is on the ground(s) that “Applicant submits the special technical feature is not just the broad categories of components for isolating, enriching, sequencing and performing stats, but rather components that perform those broad categories in the method of claim 1. Thus, the special technical feature must comprise components for isolating, enriching, sequencing and performing stats wherein the components can "determining in a sample comprising a plurality of cell-free DNA (cfDNA) fragments the sequence coordinates of the start and/or stop of at least 100,000 cfDNA fragments by alignment to a reference sequence, determining in the reference sequence all nucleic acid motifs comprised of trinucleotides, tetranucleotides and pentanucleotides: within the range of 1 to 5 base pairs inwards but adjacent to each start and/or stop sequence coordinate determined in (i), and/or within a range of 1 to 5 base pairs outwards but adjacent to each start and/or stop sequence coordinate determined in (i), determining the frequency of: each sequence coordinate plus and/or minus 1 base pair determined in (i) in the plurality of cfDNA fragments comprised in the sample, each of the nucleic acid motifs determined in (ii) a) and b) in the plurality of cfDNA fragments comprised in the sample, calculating the ratio of each of the frequencies determined in (iii) a) and b) over a corresponding reference frequency, calculating a diagnostic score separately for each ratio determined in step (iv), said score being the respective weighted sum of all respective frequency ratios of step
(iv) calculating a combined diagnostic score from at least two or more of the diagnostic scores determined in (v) said score being the weighted sum of said two or more diagnostic scores determined in (v), and determining a classification of the sample by comparing the combined diagnostic score to a reference score." This special technical feature is not taught or suggested by Koumbaris.”.
This is not found persuasive because the special technical features does not make a contribution over the prior art in view of Koumbaris et al.as cited in the IDS) as recited in the Restriction Office Action (Pg. 3-4), mailed 11/13/2025. In this manner, the skilled person would arrive at the technical feature with a reasonable expectation of success.
The requirement is still deemed proper and is therefore made FINAL.
Claim 10 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group II, drawn to a kit, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/11/2025.
Claims Status
Claims 1, 2, 4-10 are pending.
Claim 10 are withdrawn.
Claim 3 is canceled.
Claims 1, 2, 4-9 are currently under examination.
Priority
This application is a national stage application under 35 U.S.C. §371 of International
Application No. PCT/EP2021/086255, filed on December 16, 2021, which claims the benefit of EP Patent Application No. 20215773.1, filed December 18, 2020.
Acknowledgment is made of applicant' s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of EP20215773.1 has been submitted of the record on 06/15/2023. Accordingly, the priority date of instant claims is determined to be 12/18/2020, the filing date of EP20215773.1.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract is more than 15 lines or 150 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 1-2 and 4-9 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.
Claim 1 is indefinite over the limitation “determined in (i)” (ln 10). It is unclear if the limitation is referring to the (i) that the limitation resides in or if the limitation is actually referring to step (a) of claim 1. Claims 2 and 4-9 depend on claim 1.
Claim 1 is indefinite over the limitation “determined in (i)” (ln 13). It is unclear if the limitation is referring to the (i) limitation that resides in step (b) or if the limitation is actually referring to step (a) of claim 1. Claims 2 and 4-9 depend on claim 1.
Claim 1 is indefinite over the limitation “determined in (i)” (ln 16). It is unclear if the limitation is referring to the (i) that the limitation resides in or step (a) and (b), if the limitation is actually referring to step (a) of claim 1. Claims 2 and 4-9 depend on claim 1.
Claim 1 is indefinite over the limitation “determined in (ii) a) and b)” (ln 18). It is unclear if the limitation is referring to the (ii) limitation that resides in step (a) and (b), as step (a) does not have a (ii) limitation, if the limitation is actually referring to step (b) of claim 1, or if the limitation is actually referring to step (b) i and ii. Claims 2 and 4-9 depend on claim 1.
Claim 1 is indefinite over the limitation “determined in (iii) a) and b)” (ln 20). It is unclear as to what the limitation is referring to as the claim does not have a (iii) limitation. Furthermore, it is unclear if limitation is actually referring to step (c) i and ii. Claims 2 and 4-9 depend on claim 1.
Claim 1 is indefinite over the limitation “determined in step (iv)” (ln 23) and “step iv” and (ln 24). It is unclear as to what the limitation is referring to as the claim does not have a step (iv) limitation. Furthermore, it is unclear if limitation is actually referring to step (d). Claims 2 and 4-9 depend on claim 1.
Claim 1 is indefinite over the limitation “determined in (v)” (ln 26 and ln 27). It is unclear as to what the limitation is referring to as the claim does not have a (v) limitation. Furthermore, it is unclear if limitation is actually referring to step (e). Claims 2 and 4-9 depend on claim 1.
Claim 2 is indefinite over the limitation “calculated in claim 4 step (v)” (ln 2). It is unclear as to what the limitation is referring to as claim 4 does not have a step (v) limitation. Furthermore, it is unclear if limitation is actually referring to claim 1 as claim 2 depend on claim 1 as the claim recites “the method of claim 1” (ln 1).
Claim 7 is indefinite over the limitation “wherein (step (i)” (ln 1). It is unclear as to what the limitation is referring to as claim 1 has steps (a-g).
Claim 8 is indefinite over the limitation “wherein (step (i)” (ln 1). It is unclear as to what the limitation is referring to as claim 1 has steps (a-g) and claim 6 does not refer to any additional enumerated steps.
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 1-2 and 4-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed towards abstract ideas of determining sequence coordinates by alignment, determining the frequency, determining a classification of the sample by comparing, mathematical relationship of calculating the ratio and diagnostic score and combined diagnostic score and routine and conventional methods of determining the sequence coordinates by alignment, determining motifs, and determining a classification of the sample, without significantly more. The claim(s) recite(s) abstract ideas and routine and conventional methods. This judicial exception is not integrated into a practical application because no additional elements integrate the judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are considered significantly more than the judicial exceptions.
Claim analysis
The instant claim 1 is directed towards: A method of classifying a sample as comprising cell-free tumor DNA, the method comprising the steps of: a. determining in a sample comprising a plurality of cell-free DNA (cfDNA) fragments the sequence coordinates of the start and/or stop of at least 100,000 cfDNA fragments by alignment to a reference sequence, b. determining in the reference sequence all nucleic acid motifs comprised of trinucleotides, tetranucleotides and pentanucleotides: i. within the range of 1 to 5 base pairs inwards but adjacent to each start and/or stop sequence coordinate determined in (i), and/or ii. within a range of 1 to 5 base pairs outwards but adjacent to each start and/or stop sequence coordinate determined in (i), c. determining the frequency of: i. each sequence coordinate plus and/or minus 1 base pair determined in (i) in the plurality of cfDNA fragments comprised in the sample, ii. each of the nucleic acid motifs determined in (ii) a) and b) in the plurality of cfDNA fragments comprised in the sample, d. calculating the ratio of each of the frequencies determined in (iii) a) and b) over a corresponding reference frequency, e. calculating a diagnostic score separately for each ratio determined in step (iv), said score being the respective weighted sum of all respective frequency ratios of step (iv) f. calculating a combined diagnostic score from at least two or more of the diagnostic scores determined in (v) said score being the weighted sum of said two or more diagnostic scores determined in (v), and g. determining a classification of the sample by comparing the combined diagnostic score to a reference score, wherein the sample is classified as comprising tumor cfDNA, if the combined diagnostic score value is higher than the mean of the reference score by at least one standard deviation of the reference score, wherein the reference score is calculated from one or more reference values.
The determining sequence coordinates by alignment, determining motifs, determining the frequency, determining a classification of the sample by comparing are considered abstract ideas and routine and conventional methods, without significantly more as demonstrated by the 35 USC § 103 rejections stated below. (See MPEP 2106.04 (a)(2) Part II-III; 2106.05(d))
The calculating the ratio, a diagnostic score and a combined diagnostic score are considered to abstract ideas containing a mathematical relationship. (See MPEP 2106.04 (a)(2) Part IV)
Dependent claims set forth further limitations about the diagnostic score, amount of cfDNA, reference samples, sequence determination, and enrichment of cfDNA fragments, sample classification.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case, the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract ideas.
With regard to claim 1, the claim recites “A method of classifying a sample as comprising cell-free tumor DNA, the method comprising the steps of: a. determining in a sample comprising a plurality of cell-free DNA (cfDNA) fragments the sequence coordinates of the start and/or stop of at least 100,000 cfDNA fragments by alignment to a reference sequence, b. determining in the reference sequence all nucleic acid motifs comprised of trinucleotides, tetranucleotides and pentanucleotides: i. within the range of 1 to 5 base pairs inwards but adjacent to each start and/or stop sequence coordinate determined in (i), and/or ii. within a range of 1 to 5 base pairs outwards but adjacent to each start and/or stop sequence coordinate determined in (i), c. determining the frequency of: i. each sequence coordinate plus and/or minus 1 base pair determined in (i) in the plurality of cfDNA fragments comprised in the sample, ii. each of the nucleic acid motifs determined in (ii) a) and b) in the plurality of cfDNA fragments comprised in the sample, d. calculating the ratio of each of the frequencies determined in (iii) a) and b) over a corresponding reference frequency, e. calculating a diagnostic score separately for each ratio determined in step (iv), said score being the respective weighted sum of all respective frequency ratios of step (iv) f. calculating a combined diagnostic score from at least two or more of the diagnostic scores determined in (v) said score being the weighted sum of said two or more diagnostic scores determined in (v), and g. determining a classification of the sample by comparing the combined diagnostic score to a reference score, wherein the sample is classified as comprising tumor cfDNA, if the combined diagnostic score value is higher than the mean of the reference score by at least one standard deviation of the reference score, wherein the reference score is calculated from one or more reference values.” The determining sequence coordinates by alignment, determining motifs, determining the frequency, determining a classification of the sample by comparing are considered abstract ideas. (See MPEP 2106.04 (a)(2) Part II-III) The calculating the ratio, a diagnostic score and a combined diagnostic score are considered to abstract ideas containing a mathematical relationship. (See MPEP 2106.04 (a)(2) Part IV)
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? No, there are no additional steps that integrate the claims into a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, there are no additional elements that are significantly more than the judicial exceptions.
Regarding claim 1, the claim requires the routine and conventional active steps of determining sequence coordinates by alignment, determining motifs, determining the frequency, determining a classification of the sample by comparing similar to that of Namsaraev et al. (“Namsaraev”; Patent App. Pub. WO 2018081130 A1, May 3, 2018).
Namsaraev discloses “Methods are provided to improve the positive predictive value for cancer detection using cell-free nucleic acid samples. Various embodiments are directed to applications (e.g., diagnostic applications) of the analysis of the fragmentation patterns and size of cell-free DNA, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, including viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).” (Abstract).
Thus, the claim does not provide additional steps which are significantly more.
Dependent claims require diagnostic score, amount of cfDNA, reference samples, sequence determination, and enrichment of cfDNA fragments, sample classification which are all routine and conventional based on Namsaraev et al. (“Namsaraev”; Patent App. Pub. WO 2018081130 A1, May 3, 2018).
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 1-2 and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Namsaraev et al. (“Namsaraev”; Patent App. Pub. WO 2018081130 A1, May 3, 2018).
Namsaraev discloses “Methods are provided to improve the positive predictive value for cancer detection using cell-free nucleic acid samples. Various embodiments are directed to applications (e.g., diagnostic applications) of the analysis of the fragmentation patterns and size of cell-free DNA, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, including viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).” (Abstract).
Regarding claim 1 step (a), Namsaraev teaches a method comprising “analyzing the first plurality of cell-free nucleic acid molecules or the plurality of cell-free nucleic acid molecules comprises receiving, at the computer system, the plurality of sequence reads; and aligning, by the computer system, the plurality of sequence reads to the reference genome to determine genomic positions for the plurality of sequence reads.” (Para. 9). Namsaraev teaches a method comprising “As a high number of sequencing reads, in the order of hundreds of thousands to millions or even possibly hundreds of millions or billions (e.g., 100,000, 1,000,000 (1M), 10M, 100M, 1000M, or more reads), are generated from each sample in each run, the resultant sequenced reads can form a representative profile of the mix of nucleic acid species in the original specimen” (Para. 216). Thus, Namsaraev teaches a method comprising step (a) determining in a sample comprising a plurality of cell-free DNA (cfDNA) fragments the sequence coordinates of the start and/or stop of at least 100,000 cfDNA fragments by alignment to a reference sequence
Regarding claim 1 step (b), Namsaraev teaches a method comprising “"informative DNA fragment" can correspond to a DNA fragment bearing or carrying …a particular ending-motif (e.g., a number of nucleotides at each end of the DNA fragment having a particular sequence) …confirm the presence of the informative ends” (Para. 453; Para.155). “a particular ending-motif (e.g., a number of nucleotides at each end of the DNA fragment having a particular sequence” reads on “nucleic acid motifs comprised of trinucleotides, tetranucleotides and pentanucleotides i. within the range of 1 to 5 base pairs inwards but adjacent to each start and/or stop sequence coordinate determined in (i), and/or ii. within a range of 1 to 5 base pairs outwards but adjacent to each start and/or stop sequence coordinate determined in (i)” Thus, Namsaraev teaches a method comprising step (b) determining in the reference sequence all nucleic acid motifs comprised of trinucleotides, tetranucleotides and pentanucleotides: i. within the range of 1 to 5 base pairs inwards but adjacent to each start and/or stop sequence coordinate determined in (i), and/or ii. within a range of 1 to 5 base pairs outwards but adjacent to each start and/or stop sequence coordinate determined in (i).
Regarding claim 1 step (c), Namsaraev teaches a method comprising “Various statistical values of a size distribution of nucleic acid fragments can be determined. For example, an average, mode, median, or mean of a size distribution can be used. Other statistical values can be used, e.g., a cumulative frequency for a given size or various ratios of amount of nucleic acid fragments of different sizes. A cumulative frequency can correspond to a proportion (e.g., a percentage) of DNA fragments that are of a given size or smaller, or larger than a given size.” (Para.437). Thus, Namsaraev teaches a method comprising step (c) determining the frequency of: i. each sequence coordinate plus and/or minus 1 base pair determined in (i) in the plurality of cfDNA fragments comprised in the sample, ii. each of the nucleic acid motifs determined in (ii) a) and b) in the plurality of cfDNA fragments comprised in the sample.
Regarding claim 1 step (d-g), Namsaraev teaches a method comprising “the statistical value can be a ratio of: (1) a first amount the plurality of nucleic acid molecules in the biological sample from the reference genome that are within a first size range; and (2) a second amount the plurality of nucleic acid molecules in the biological sample from the reference genome that are within a second size range that is difference than the first size range.” (Para. 448). Namsaraev teaches a method comprising “A size-based z-score can be calculated using the mean and SD values of AF of control subjects” (Para. 441) Namsaraev teaches a method comprising “A weighted sum can be determined for each of a plurality of bases” (Para. 535). Namsaraev teaches a method comprising “an end ratio (e.g., a ratio of a first amount of nucleic acid molecules ending on a first set of genomic positions to a second amount of nucleic acid molecules ending on a second set of genomic positions) can be used to determine a classification of a proportional contribution of a tissue type. In some embodiments, a combination of metrics (e.g., at least two of an end ratio, copy number, and nucleic acid fragment size) may be used to detect a condition (e.g., a tumor) in a subject.” (Para.496) Thus, Namsaraev teaches a method comprising step (d). calculating the ratio of each of the frequencies determined in (iii) a) and b) over a corresponding reference frequency; Step (e) calculating a diagnostic score separately for each ratio determined in step (iv), said score being the respective weighted sum of all respective frequency ratios of step (iv); step (f) calculating a combined diagnostic score from at least two or more of the diagnostic scores determined in (v) said score being the weighted sum of said two or more diagnostic scores determined in (v); and step (g) determining a classification of the sample by comparing the combined diagnostic score to a reference score, wherein the sample is classified as comprising tumor cfDNA, if the combined diagnostic score value is higher than the mean of the reference score by at least one standard deviation of the reference score, wherein the reference score is calculated from one or more reference values.
The teachings of Namsaraev are documented above in the rejection of claim 1 under 35 U.S.C. 103. Claims 2, 4-7 and 9 depend on claim 1. Claim 8 depend on claim 6, which depends on claim 1.
Regarding claim 2, Namsaraev teaches a method wherein “In some embodiments, a combination of metrics (e.g., at least two of an end ratio, copy number, and nucleic acid fragment size) may be used to detect a condition (e.g., a tumor) in a subject” (Para.496). Thus, Namsaraev teaches a method wherein the combined diagnostic score is calculated from all of the diagnostic scores calculated in claim 4 step (v).
Regarding claim 4, Namsaraev teaches a method wherein “a high number of sequencing reads, in the order of hundreds of thousands to millions or even possibly hundreds of millions or billions (e.g., 100,000, 1,000,000 (1M), 10M, 100M, 1000M, or more reads), are generated from each sample in each run” (Para. 216). Thus, Namsaraev teaches a method wherein the minimum amount of cfDNA fragments comprised within a sample to be analyzed is between 100 thousand to 500 thousand, 500 thousand to 1 million,1 million to 2 million, 2 million to 5 million, or 5 million to 10 million, or 10 million to 20 million, or 20 million to 50 million, or 50 million to 500 million.
Regarding claim 5, Namsaraev teaches a method wherein “In some embodiments, the method comprises generating a comparison, and generating a comparison comprises calculating a first value of a first parameter providing a statistical measure of a size profile of DNA fragments in the second biological sample. In some embodiments, the method comprises generating a comparison, and generating a comparison comprises comparing the first value to at least one second calibration value.” (Para. 16). Namsaraev also teaches a method wherein “"classification" can refer to an amount of tumor tissue in the subject and/or sample, a size of the tumor in the subject and/or sample, a stage of the tumor in the subject, a tumor load in the subject and/or sample, and presence of tumor metastasis in the subject. The classification can be binary (e.g., positive or negative) or have more levels of classification (e.g., a scale from 1 to 10” (Para. 162). “The classification can …have more levels of classification (e.g., a scale from 1 to 10” reads on “sample can be classified as low if the combined diagnostic score is between 2 and 4 standard deviations of the reference scores, as moderate if the combined score is between 4 and 6.5 standard deviations of the reference scores and high if the combined score is more than 6.5 standard deviations of the reference scores”. Thus, Namsaraev teaches a method wherein the amount of tumor cfDNA in the sample can be classified as low if the combined diagnostic score is between 2 and 4 standard deviations of the reference scores, as moderate if the combined score is between 4 and 6.5 standard deviations of the reference scores and high if the combined score is more than 6.5 standard deviations of the reference scores.
Regarding claim 6, Namsaraev teaches a method wherein “… "reference," "reference sample… can be used to describe a sample from a subject that does not have a particular condition, or is otherwise healthy. In an example, a method as disclosed herein can be performed on a subject having a tumor, where the reference sample is a sample taken from a healthy tissue of the subject.” (Para.137). “a subject that does not have a particular condition, or is otherwise healthy” reads on “cancer free patients” Thus, Namsaraev teaches a method wherein the reference samples can be samples from cancer free patients, or from non- relapsed patients, or from successfully treated cancer patients.
Regarding claim 7, Namsaraev teaches a method wherein “sequencing on the cell-free nucleic acid molecules to generate sequence reads. In some embodiments, the method comprises determining an amount of the sequence reads that align to a reference genome” (Para. 15). Thus, Namsaraev teaches a method wherein step (i) comprises the determination of the nucleic acid sequence of at least a portion of the plurality of cfDNA fragments in the sample prior to the alignment to a reference sequence.
Regarding claim 8, Namsaraev teaches a method wherein “sequencing after target enrichment” (Para. 452). Thus, Namsaraev teaches a method wherein step (i) further comprises the enrichment of cfDNA fragments prior to the determination of the nucleic acid sequence of cfDNA fragments.
Regarding claim 9, Namsaraev teaches a method wherein “In some embodiments, the pathology is selected from the group consisting of bladder cancer, bone cancer, a brain tumor, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gastrointestinal cancer, hematopoietic malignancy, leukemia, liver cancer, lung cancer, lymphoma, myeloma, nasal cancer, nasopharyngeal cancer, oral cancer, oropharyngeal cancer, ovarian cancer, prostate cancer, sarcoma, stomach cancer, and thyroid cancer” (Para. 8). Thus, Namsaraev teaches a method wherein the sample is classified as comprising tumor cfDNA originating from a tumor selected from the group of blood cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer, breast cancer, gastric cancer, glioblastoma, colorectal cancer, head and neck cancer, a solid tumor, a benign tumor, a malignant tumors, an advanced stage of cancer, a metastasis or a precancerous tissue.
Therefore, the invention as recited in claims 1-2 and 4-9 is prima facie obvious over the prior art Namsaraev et al. One of ordinary skill in the art would have had a reasonable expectation of success given the lack of novelty. It would have been obvious to classify a sample comprising cell-free tumor DNA according to the limitations of the instant application claims 1-2 and 4-9 based on Namsaraev et al. (Patent App. Pub. No. WO 2018081130 A1).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/267617, Filed on Dec. 19, 2021). Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed invention is made obvious over the claims of copending Application No. 18/267617.
The claims of copending Application No. 18/267617 are drawn to:
“Method of classifying a sample as comprising cell-free tumor DNA, the method comprising the steps of:(i) determining in a sample comprising a plurality of cell-free DNA (cfDNA) fragments the sequence coordinates of the start and/or stop, and of the start and/or stop plus and/or minus 1 base pair, of at least 100,000 cfDNA fragments by alignment to a reference sequence, (ii) determining the frequency of each coordinate determined in (i) in the plurality of cfDNA fragments comprised in the sample, (iii) calculating the ratio of the frequency of each coordinate determined in (ii) over a corresponding reference frequency, (iv) calculating a diagnostic score from all ratios determined in (iii) said score being the weighted sum of all frequency ratios determined in (iii), and (v) determining a classification of the sample by comparing the diagnostic score to a reference score, wherein the sample is classified as comprising tumor cfDNA, if the diagnostic score value is higher than the mean of the reference score by at least one standard deviation of the reference score, wherein the reference score is calculated from one or more reference values.”
Therefore, the invention as recited in claims 1 is prima facie obvious over the copending Application No. 18/267617. One of ordinary skill in the art would have had a reasonable expectation of success given the lack of novelty. It would have been obvious to use a method of classifying a sample as comprising cell-free tumor DNA according to the limitations recited in claim 1 of the instant application based on 1 of copending Application No. 18/267617.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are in condition for allowance.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682