DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Remarks
This action is in response to the amendments filed 06/16/2025.
Claims 1, 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-67 are pending.
Response to Arguments
Applicant’s arguments, see pages 6-8, filed 06/16/2025, with respect to the rejection of claims 1, 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-66 under 35 U.S.C. 103 have been fully considered and are persuasive. Independent claim 1 has been amended to specify performing a “wherein the one or more biomarkers comprise one or more genes selected from Tables 4, 6-8, 10 and 13”. Applicant argues that the cited references do not teach or suggest, alone or in combination, the amended limitation. Examiner agrees. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made, as explained in the office action below.
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.
Claims 1, 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-67 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 claims a generic “lung condition” but the specification only focuses on lung cancer. The trained algorithm provides details related to training sets to identify lung cancer and not any other condition. Therefore, there are not a representative number of species in the disclosure to cover the entire genus of “lung condition” as claimed. See MPEP 2163(II)(A)(3)(a)(ii), specifically: “The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)…”.
Examiner suggests amending the limitation “lung condition” to “lung cancer”. Claims 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-67 are rejected based on their dependency on claim 1.
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, 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-67 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea without significantly more. The claims recite a method for screening a subject for a lung condition comprising analyzing health or medical data using a trained machine learning algorithm, identifying the subject as having an increased risk of developing a lung condition based on the analysis, assaying tissue to identify presence or absence of biomarkers, and once the biomarkers have been identified, assaying other epithelial tissue at a second point in time. To determine whether a claim satisfies the criteria for subject matter eligibility, the claim is evaluated according to a stepwise process as described in MPEP 2106(III) and 2106.03-2106.04. The instant claims are evaluated according to such analysis.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Claim 1 is directed towards a method, and thus meet the requirements for step 1.
Step 2A (Prong 1): Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Claim 1 recites a method for screening a subject for a lung condition comprising analyzing health or medical data using a trained machine learning algorithm, identifying the subject as having a first risk of developing a lung condition based on the analysis, obtaining and assaying a tissue sample to identify presence or absence of biomarkers to determine a second risk of the subject developing a lung condition, and if the second risk is less than the first risk, performing an assay on other epithelial tissue at a second point in time, or if the second risk is greater than or equal to the first risk, providing a recommendation of interventive therapy of imaging analysis. The limitation of a method for screening a subject for a lung condition, as drafted in claim 1, under its broadest reasonable interpretation, covers performance of the limitation in the mind or using pen and paper, but for the recitation of a trained machine learning algorithm. Further, the broadest reasonable interpretation of the claim could simply end in providing an output recommendation (the first part of step d) is not required if the condition is not met. Outputting a recommendation is insignificant, extra-solution activity of data reporting/output.
For example, in the context of this claim, a clinician can look at a data printout of genes and note a risk of lung cancer if the patient has a gene known to be associated with lung cancer. See example A in MPEP 2106.04(d)(2): “For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a).” Additionally, the relationship of genes to lung cancer is a natural correlation, see MPEP 2106.04(d)(2): “For example, consider a claim that recites a natural correlation (law of nature) between blood glucose levels over 250 mg/dl and the risk of developing ketoacidosis (a life-threatening medical condition).”
If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental Processes” grouping of abstract ideas. Therefore, claim 1 recites an abstract idea of a mental process.
Step 2A (Prong 2): Does the claim recite additional elements that integrate the judicial exception into a practical application?
The additional elements of a trained machine learning algorithm and obtaining and assaying epithelial tissue are recited at a high level of generality (i.e. a generic trained machine learning algorithm which is a computer implementation of the abstract idea, and data gathering to collect information about the epithelial tissue) such that they amount to no more than mere instructions to apply the exception using generic computer components. See MPEP 2106.06(b) and MPEP 2106.04(a)(2)(III)(C).
Accordingly, the additional elements do not integrate the abstract idea into a practical application.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
The additional elements are not enough to qualify as significantly more than the abstract idea. As discussed above with respect to the integration of the abstract idea into a practical application, the additional element of using a trained machine learning algorithm amounts to no more than mere instructions to apply the exception using generic computer components. Mere instructions to apply an exception using a generic computer component cannot provide an inventive concept. The additional element of obtaining and assaying epithelial tissue is simply a data gathering step. Furthermore, the additional elements do not amount to more than generically linking the use of a judicial exception to a particular technological environment or field of use (see MPEP 2106.05(h)). Therefore, the claims are not patent eligible.
Claims 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-67 depend on claim 1 and recite the same abstract idea as claim 1 from which they depend. Further, these claims only contain recitations that further limit the abstract idea (that is, the claims only recite limitations that further limit the mental proves). For example, the additional limitations recited in claims 5 and 6 (i.e. specifying what the lung condition could be) are simply steps that describe what the gathered data could be. The additional elements individually do not amount to significantly more than the judicial exception explained above (the abstract idea). Looking at the limitations as a whole adds nothing that is not already present when looking at the elements taken individually. There is no indication that the combination of elements improves any technology or includes a particular solution to a computer-based problem or a particular way to achieve a computer-based outcome.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5-7, 9-12, 14, 17, 23, 26, 27, 30-32, and 61-66 are rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. (US Patent Application Publication 2015/0337385 – of record), hereinafter Harris, further in view of Whitney et al. (International Publication WO 2016/011068 – of record), hereinafter Whitney, further in view of Cohen et al. (International Publication WO 2016/094330 – of record), hereinafter Cohen, further in view of Twine et al. (Twine NA, et al. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease. PLoS One. 2011 Jan 21;6(1):e16266. doi: 10.1371/journal.pone.0016266. PMID: 21283692; PMCID: PMC3025006. – of record), hereinafter Twine, and further in view of Brody et al. (US Patent Application Publication 2009/0061454).
Regarding claim 1, Harris teaches a method for screening a subject for a lung condition (e.g. Abstract), comprising:
(a) computer analyzing health or medical data of said subject for a presence of one or more risk factors for developing said lung condition, and based at least on said computer analyzing, identifying said subject as having an increased risk of developing said lung condition (e.g. Pars. [0010]-[0013]: subject is identified as at risk for developing lung cancer based on the comparison of the classifier with the reference and the levels of biomarkers BRCA1, HIF1A, DLC1, XPO1, and miR-21 with the reference values; Par. [0034]: tissue samples are assayed to determine biomarker levels);
(b) subsequent to (a), obtaining a tissue sample of said subject at a first point in time (e.g. Par. [0018]: obtaining tissue sample from the lung);
(c) assaying tissue from said tissue sample to identify a presence or absence of one or more biomarkers associated with a risk of developing said lung condition in said first sample (e.g. Pars. [0010]-[0013]: subject is identified as at risk for developing lung cancer based on the comparison of the classifier with the reference and the levels of biomarkers BRCA1, HIF1A, DLC1, XPO1, and miR-21 with the reference values; Par. [0034]: tissue samples are assayed to determine biomarker levels); and
(d) performing an assay to detect gene expression on other epithelial tissue from a second sample of said subject obtained at a second point in time (e.g. Par. [0027]: if the subject is determined to be at risk of developing lung cancer, further screening/imaging/CT scans are required which occurs at a second time after a first sample is analyzed; Par. [0034]: tissue samples are assayed to determine biomarker levels; Par. [0051]; Par. [0147]: multiple samples can be used).
However, Harris does not teach the tissue being epithelial tissue, using a trained machine learning algorithm, wherein said subject has not been identified as having a lung nodule in a lung region by an electronic imaging scan, wherein said subject has not been diagnosed for said lung condition, wherein the trained machine learning algorithm has been trained to identify one or more features associated with said one or more risk factors, specifically identifying said subject as having a low risk of developing said lung condition based on said presence or absence of said one or more biomarkers, wherein the second point in time is at least 24 hours from said first point in time, and specifically identifying the subject as having a first risk of developing said lung condition based on the computer analysis, identifying said subject as having a second risk of developing said lung condition based on the assay, wherein (i) if said second risk is less than said first risk performing an assay, or (ii) if said second risk is greater than or equal to said first risk, providing an output recommending an interventive therapy or imaging analysis, and specifically wherein the assay is a whole-transcriptome ribonucleic (RNA) sequencing assay, and wherein the one or more biomarkers comprise one or more genes selected from Tables 4, 6-8, 10, and 13.
Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known to use epithelial tissue as the biological sample in order to determine expression levels (e.g. Par. [0025]: biological sample from respiratory epithelium is used; Par. [0026]), and using a trained machine learning algorithm, wherein the trained machine learning algorithm has been trained to identify one or more features associated with said one or more risk factors (e.g. Pars. [0089]-[0090]: a trained classifier is used to classify lung cancer using expression levels of biomarkers).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris to include the tissue being epithelial tissue and a trained machine learning algorithm as taught by Whitney, because doing so would result in determining the expression levels to detect lung cancer.
However, Harris in view of Whitney fail to teach wherein said subject has not been identified as having a lung nodule in a lung region by an electronic imaging scan, wherein said subject has not been diagnosed for said lung condition, specifically identifying said subject as having a low risk of developing said lung condition based on said presence or absence of said one or more biomarkers, wherein the second point in time is at least 24 hours from said first point in time, and specifically identifying the subject as having a first risk of developing said lung condition based on the computer analysis, identifying said subject as having a second risk of developing said lung condition based on the assay, wherein (i) if said second risk is less than said first risk performing an assay, or (ii) if said second risk is greater than or equal to said first risk, providing an output recommending an interventive therapy or imaging analysis, and specifically wherein the assay is a whole-transcriptome ribonucleic (RNA) sequencing assay, and wherein the one or more biomarkers comprise one or more genes selected from Tables 4, 6-8, 10, and 13.
Harris teaches the system being used to diagnose a subject at risk of developing lung cancer (e.g. Pars. [0010]-[0013]), but does not specifically teach the subject has not been identified as having a lung nodule in a lung region by an electronic imaging scan, wherein said subject has not been diagnosed for said lung condition.
Cohen, in a similar field of endeavor, teaches methods and systems for predicting the likelihood or risk of having cancer. Cohen teaches it is known for the subject to not have been identified as having a lung nodule in a lung region by an electronic imaging scan, wherein said subject has not been diagnosed for said lung condition (e.g. Par. [0024]: imaging of the patient occurs only after risk calculation of occurrence of lung cancer is determined; Par. [0058]: asymptomatic patients are patients that have not previously been diagnosed with cancer risk; Pars. [0101]-[0103]: describing method of determining cancer risk in asymptomatic patients), specifically identifying said subject as having a low risk of developing said lung condition based on said presence or absence of said one or more biomarkers (e.g. Par. [0017]: measuring biomarkers to determine disease likelihood; Par. [0024]), identifying the subject as having a first risk of developing said lung condition based on computer analysis and identifying said subject as having a second risk of developing said lung condition based on the assay (e.g. pars. [0018]-[0019]; par. [0103]; par. [0153]; pars. [0193]-[0195]), wherein if said second risk is greater than or equal to said first risk, providing an output recommending an interventive therapy or imaging analysis (e.g. par. [0181]: if the risk score is higher, the physician can recommend follow up testing such as CT scanning), wherein the second sample is taken at least 24 hours from the first sample (e.g. Par. [0193]: time of biomarker determination can be 3 months, 6 months, and 1 year).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney to include the subject has not been identified as having a lung nodule in a lung region by an electronic imaging scan, wherein said subject has not been diagnosed for said lung condition, specifically identifying said subject as having a low risk of developing said lung condition based on said presence or absence of said one or more biomarkers, and identifying first and second risks of developing the lung condition and providing a recommended output, wherein the second sample is taken at least 24 hours after the first sample as taught by Cohen, because doing so would improve determination of cancer risk in patients in order to provide appropriate preventative action.
However, Harris in view of Whitney and Cohen fail to specifically disclose wherein the assay is a whole-transcriptome ribonucleic (RNA) sequencing assay, and wherein the one or more biomarkers comprise one or more genes selected from Tables 4, 6-8, 10, and 13.
Twine, in a similar field of endeavor, is directed towards whole transcriptome analysis for Alzheimer’s disease. Twin discloses it is known to use a whole-transcriptome ribonucleic (RNA) sequencing assay in order to identify levels of gene expression (e.g. page 10, left column, section titled Discussion: a whole transcriptome sequencing technique was used, “Using a whole transcriptome sequencing technique (RNA-Seq), we were able to identify the levels of differentially expressed genes and establish genes with alternative promoter usage and splicing patterns that changed in association with neurodegeneration.”).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney and Cohen to include the whole transcriptome sequencing as taught by Twine as this is a known technique that for identifying levels of gene expression (e.g. Twine, page 10, left column, section titled Discussion).
However, Harris in view of Whitney, Cohen, and Twine fails to disclose wherein the one or more biomarkers comprise one or more genes selected from Tables 4, 6-8, 10, and 13.
Brody, in a similar field of endeavor, is directed towards diagnosis and prognosis of lung cancer using gene expression analysis. Brody discloses using biomarkers UBE1L, P4HB, CCT4, EIF4A1, and DUSP3, which are listed under Table 4 of the instant specification (e.g. Table 1; Par. [0104]: table 1 shows genes that were identified as distinguishing smokers with and without cancer).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, and Twine to include the genes as identified by Brody, because Brody teaches that these genes are known to indicate smokers with and without cancer.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 5, Harris further teaches wherein said lung condition is lung cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or any combination thereof (e.g. Abstract; Par. [0005]: biomarkers for early stage lung adenocarcinoma detection).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 6, Harris further teaches wherein said lung condition is a lung cancer, and wherein said lung cancer comprises: a non-small cell lung cancer; an adenocarcinoma; a squamous cell carcinoma; a large cell carcinoma; a small cell lung cancer; or any combination thereof (e.g. Par. [0005]: adenocarcinoma; Par. [0031]: non-small cell lung cancer).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 7, Harris fails to teach wherein said first sample or said second sample is obtained by a bronchoscopy, bronchial brushing, or nasal brushing. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known to use bronchial brushing to obtain the sample (e.g. Par. [0025]).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include obtaining the sample by bronchia brushing as taught by Whitney, because doing so would allow the user to obtain the necessary biological sample.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 9, Harris fails to teach wherein said first sample or said second sample comprises a mucous epithelial tissue, a nasal epithelial tissue, a lung epithelial tissue, or any combination thereof. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known for the biological sample to comprise nasal or lung epithelial tissue (e.g. Par. [0025]: “The respiratory epithelium can be of the mouth, nose, pharynx, trachea, bronchi, bronchioles, or alveoli.”).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include the biological sample comprising nasal or lung epithelial tissue as taught by Whitney, because doing so would result in obtaining the necessary biological sample.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 10, Harris fails to teach wherein said first sample or said second sample comprises epithelial tissue obtained along an airway of said subject. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known for the biological sample to comprise epithelial tissue obtained along an airway of the subject (e.g. Par. [0025]; Par. [0034]: epithelial cells obtained from airway samples can be used).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include the biological sample comprising epithelial tissue obtained along an airway of the subject as taught by Whitney, because doing so would allow the user to obtain the necessary biological sample.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 11, Harris fails to teach wherein a portion of said first sample or said second sample is subjected to cytological testing that identifies said first sample or said second sample as ambiguous or suspicious. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known for the sample to be subjected to cytological testing that identifies the sample as suspicious (e.g. Par. [00215]: “Patients were diagnosed as having primary lung cancer based on cytopathology obtained at bronchoscopy”).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include subjecting the sample to cytological testing that identifies the sample as suspicious as taught by Whitney, because it is a known method of diagnosing lung cancer.
Claim 11 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 12, Harris further teaches upon identifying said first sample or said second sample as ambiguous or suspicious, performing (d) on a second portion of said first sample or second sample, which second portion comprises said epithelial tissue (e.g. Par. [0027]: if the subject is determined to be at risk of developing lung cancer, further screening/imaging is required; Par. [0051]; Par. [0147]: multiple samples can be used).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 14, Harris fails to teach wherein said second sample is a different sample type from said first sample. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known for the second sample to be a different sample type from the first sample (e.g. Par. [0025]: multiple sample types can be taken).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include the second sample to be a different sample type from the first sample as taught by Whitney, because doing so would result in obtaining the biological sample.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 17, Harris further teaches wherein (c) comprises comparing said presence or absence of said one or more biomarkers to a reference set of one or more biomarkers (e.g. Pars. [0010]-[0013]: subject is identified as at risk for developing lung cancer based on the comparison of the classifier with the reference and the levels of biomarkers BRCA1, HIF1A, DLC1, XPO1, and miR-21 with the reference values).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 23, Harris further teaches wherein said one or more risk factors comprise: smoking; exposure to environmental smoke; exposure to radon; exposure to air pollution; exposure to radiation; exposure to an industrial substance; inherited or environmentally-acquired gene mutations; a subject's age; a subject having a secondary health condition; or any combination thereof (e.g. Page 27, Par. [0180], lines 21-23: “…clinically relevant risk factors such as age, smoking and stage.”).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 26, Harris further teaches wherein said one or more biomarkers comprise one or more of: a gene or fragment thereof; a sequence variant; a fusion; a mitochondrial transcript; an epigenetic modification; a copy number variation; a loss of heterozygosity (LOH); or any combination thereof (e.g. Abstract: four genes are used).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 27, Harris further teaches wherein said presence or absence of said one or more biomarkers comprises a level of expression (e.g. Par. [0129]: levels of certain biomarkers are detected).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 30, Harris fails to teach wherein said trained machine learning algorithm is trained by a training set comprising epithelial cells obtained from an airway of an individual. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known to train the machine learning algorithm with a training set comprising epithelial cells obtained from an airway of an individual (e.g. Par. [0034]: epithelial cells obtained from airway samples can be used; Par. [0090]: classifier is trained on a dataset comprising information about biological samples).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include training the machine learning algorithm with a training set comprising epithelial cells obtained from an airway of an individual as taught by Whitney, because doing so would aid in the detection of lung cancer.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 31, Harris fails to teach wherein said trained machine learning algorithm is trained by a training set comprising samples benign for said lung condition and samples malignant for said lung condition. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known for the training set to comprise samples both benign and malignant for lung cancer in order to increase the confidence of classification (e.g. Par. [0090]: the training set includes data for both subjects having lung cancer and not having lung cancer).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include the training set to comprise samples both benign and malignant for lung cancer as taught by Whitney, because doing so would result in increased confidence of classification.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 32, Harris fails to teach wherein said trained machine learning algorithm is trained by a training set comprising samples obtained from subjects having one or more risk factors. Whitney, in a similar field of endeavor, teaches methods for evaluating lung cancer status. Whitney teaches it is known for the training set to comprise samples obtained from subjects having a risk factor of smoking (e.g. Par. [0090]: the population can include subjects who are smokers or former smokers) in order to accurately classify lung cancer.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody with the training set comprising samples obtained from subjects having one or more risk factors as taught by Whitney, because doing so would result in accurate classification of lung cancer.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 61, Harris further teaches wherein performing said assay to detect gene expression or genetic aberrations comprises detecting a gene expression level (e.g. Par. [0129]: levels of certain biomarkers are detected).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 62, Harris further teaches wherein performing said assay to detect gene expression or genetic aberrations comprises a sequencing assay (e.g. Par. [0122]).
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 63, Harris fails to teach wherein said second point in time is at least 1 month from said first point in time. Cohen, in a similar field of endeavor, teaches methods and systems for predicting the likelihood or risk of having cancer. Cohen discloses that the second point in time for sample collection is at least 1 month from said first point in time (e.g. Par. [0193]: time of biomarker determination can be 3 months, 6 months, and 1 year).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include the second point in time for sample collection being at least 1 month from said first point in time as taught by Cohen, because doing so would allow monitoring the progression of the disease in a patient.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 64, Harris fails to teach wherein said second point in time is at least 1 year from said first point in time. Cohen, in a similar field of endeavor, teaches methods and systems for predicting the likelihood or risk of having cancer. Cohen discloses that the second point in time for sample collection is at least 1 year from said first point in time (e.g. Par. [0193]: time of biomarker determination can be 3 months, 6 months, and 1 year).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include the second point in time for sample collection being at least 1 year from said first point in time as taught by Cohen, because doing so would allow monitoring the progression of the disease in a patient.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 65, Harris fails to teach wherein said second risk is less than said first risk. Cohen, in a similar field of endeavor, teaches methods and systems for predicting the likelihood or risk of having cancer. Cohen discloses wherein said second risk is less than said first risk (e.g. Par. [0193]: classifying patient as low risk if biomarker velocity decreases).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include identifying and comparing a first and second risk of developing a condition as taught by Cohen to result in earlier identification and treatment of cancer.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 66, Harris fails to teach wherein said second risk is greater than or equal to said first risk. Cohen, in a similar field of endeavor, teaches methods and systems for predicting the likelihood or risk of having cancer. Cohen discloses wherein said second risk is greater than or equal to said first risk (e.g. Par. [0193]: classifying patient as high risk if biomarker velocity increases).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include identifying and comparing a first and second risk of developing a condition as taught by Cohen in order to result in earlier identification and treatment of cancer.
Claim 67 is rejected under 35 U.S.C. 103 as being unpatentable over Harris et al. (US Patent Application Publication 2015/0337385 – of record), hereinafter Harris, further in view of Whitney et al. (International Publication WO 2016/011068 – of record), hereinafter Whitney, further in view of Cohen et al. (International Publication WO 2016/094330 – of record), hereinafter Cohen, further in view of Twine et al. (Twine NA, et al. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease. PLoS One. 2011 Jan 21;6(1):e16266. doi: 10.1371/journal.pone.0016266. PMID: 21283692; PMCID: PMC3025006. – of record), hereinafter Twine, and further in view of Brody et al. (US Patent Application Publication 2009/0061454), hereinafter Brody, as applied to claim 1 above, and further in view of Halvardson et al. (Halvardson J, et al. Exome RNA sequencing reveals rare and novel alternative transcripts. Nucleic Acids Res. 2013 Jan 7;41(1):e6. doi: 10.1093/nar/gks816. Epub 2012 Aug 31. PMID: 22941640; PMCID: PMC3592422. – of record), hereinafter Halvardson.
Claim 1 is obvious over Harris, Whitney, Cohen, Twine, and Brody, as indicated above. Regarding claim 67, Harris fails to disclose wherein said whole-transcriptome RNA sequencing assay comprises exome-enriched RNA sequencing. Halvardson is directed towards whole exome enrichment of RNA. Halvardson discloses using exome enriched RNA sequencing in order to identify transcripts present at low levels (e.g. Abstract: exome enrichment was used prior to RNA sequencing in order to identify transcripts present at low levels).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Harris in view of Whitney, Cohen, Twine, and Brody to include using exome enriched RNA sequencing as taught by Halvardson as this is a known technique that provides the results of identifying transcripts present at low levels (e.g. Halvardson, abstract).
Conclusion
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/SHREYA ANJARIA/Examiner, Art Unit 3796
/ALLEN PORTER/Primary Examiner, Art Unit 3796