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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 18 September 2025 has been entered.
Application Status
This action is written in response to applicant’s correspondence received 18 September 2025. Claims 1, 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, 185-195 are currently pending. Accordingly, claims 1, 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, 185-195 are examined herein.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Objections
Claim 1 objected to because of the following informalities: MPEP 608.01(m) states, “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.” In the instant case, the claim contains periods in lines 15-16 within the phrases “(b).” and “a drug treatment.”. Appropriate correction is required.
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, 9, 11, 17, 22, 26, 29, 37, 39, 45, and 185-195 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Step 1: Is the Claim to a Process, Machine, Manufacture, or Composition of Matter? YES.
Regarding claims 1 and 193-194, the claims recite methods for processing or analyzing a body sample of a subject comprising the following active method steps: “(a) analyzing said body sample to yield a data set […]”, “(b) computer processing said data set from (a) […]”, “(c) electronically outputting a report […]”, and “(d) providing a clinical intervention for said subject […] wherein said clinical intervention comprises: a drug treatment, intensive glycemic control, and high blood pressure control […]”.
Step 2A, Prong 1: Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES.
Regarding step (b), “[…] computer processing said data set from (a) to determine a presence, an absence, an elevated risk, or a decreased risk of said kidney disease or disorder in said subject at an accuracy of at least about 80%, as determined by a percentage of independent test subjects that are correctly identified or classified as either having or not having the kidney disease or disorder […]”, the method step is drawn to the mental process of determining a presence of kidney disease from computer processed data, as taught by MPEP 2106.04(a). As taught by MPEP 2106, “an abstract idea does not become nonabstract by limiting the invention to a particular field of use or technological environment, such as the Internet [or] a computer.” Accordingly, the limitation requiring that the dataset is processed via a computer does not rectify the abstract determining step.
Step 2A, Prong 2: Does the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
This judicial exception is not integrated into a practical application because the additional elements present in the method (i.e., method steps (a) and (c)-(d)) do not add significantly more to the abstract idea as both limitations are drawn to insignificant extra-solution activities.
Regarding method step (a), the additional element does not integrate the product of nature into a practical application because the method step of “analyzing said bodily sample to yield a data set comprising a set of levels of gene expression products in said bodily sample, which set of levels of gene expression products correspond to a set of genes associated with a kidney disease or disorder” is drawn to the insignificant extra-solution activity of mere data gathering (see MPEP 2106.05(g)). As the claim currently reads, the method step of “analyzing said bodily sample to yield a data set comprising a set of levels of gene expression products in said bodily sample, which set of levels of gene expression products correspond to a set of genes associated with a kidney disease or disorder” is drawn to the analysis of gene expression products (i.e., the gathering of data) utilized in order to determine if a subject is at risk for kidney disease in method step (b). Thus, as taught in MPEP 2106.05(g), the limitation regarding the analysis of the gene expression products has an insignificant relationship to the judicial exception.
Regarding method step (c), the additional element does not integrate the product of nature into a practical application because the method step of “electronically outputting a report that identifies said presence, said absence, said elevated risk or said decreased risk of said kidney disease or disorder in said subject determined in (b)” is drawn to the insignificant extra-solution activity of selecting a particular data source or type to be manipulated (see MPEP 2106.05(g)). As the claim currently reads, the method step of “electronically outputting a report that identifies said presence, said absence, said elevated risk or said decreased risk of said kidney disease or disorder in said subject determined in (b)” is drawn to the generation of a report (i.e., the manipulation of data) derived from the abstract determination step present in method step (b). Thus, as taught in MPEP 2106.05(g), the limitation regarding the preparation of a report has an insignificant relationship to the judicial exception.
Regarding method step (d), the additional element does not integrate the product of nature into a practical application because the method step of “providing a clinical intervention for said subject based at least in part on said presence or said elevated risk of said kidney disease or disorder determined in (b), wherein said clinical intervention comprises: a drug treatment, intensive glycemic control, and high blood pressure control” is not a particular treatment as required by MPEP 2106.04(d)(2). The claim limitation of “a drug treatment” broadly encompasses any drug at any dosage. MPEP 2106.04(d)(2), analogously to the instantly claimed invention, teaches that “a claim that recites [an] abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application.” Because the instantly claimed “drug treatment” is not particular and encompasses any drug at any dosage, as described in MPEP 2106.04(d)(2), the treatment step does not integrate the mental analysis step into a practical application.
Step 2B: Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements present in method steps (a) and (c)-(d) are well known and routine in the art.
Davicioni (PG Pub No. US 2016/0032395 A1) is drawn to an invention concerned with methods, systems and kits for the diagnosis, prognosis and determination of cancer progression of a cancer in a subject (Abstract). Davicioni teaches that the method may comprise (a) assaying (i.e., analyzing) an expression level of a set of genes in a sample from the subject for a plurality of targets associated with kidney cancer (i.e., a kidney disease), wherein the plurality of targets comprises one or more target genes selected from Table 1 ([0005]). Davicioni teaches that (c) the expression levels can be analyzed via a classifier (i.e., a computer processing system) with an accuracy of at least 80% ([0096]). Davicioni teaches the use of a device that can comprise means for characterizing the expression level of a target sequence of the invention ([0187]). Davicioni teaches that the device may correlate the expression levels of the target sequences being studied with a prognosis of disease outcome and output a disease status or prognosis (i.e., a report that identifies the presence, absence, elevated risk, or decreased risk of kidney disease) ([0191]-[0192]). Davicioni teaches that following the diagnosis of kidney cancer in a subject, (d) a treatment modality selected from chemotherapy (i.e., a drug treatment) may be administered to the patient ([0307]).
Thus, the additional elements of method steps (a) and (c)-(d) do not, alone or in combination, contribute to an inventive concept under Step 2B of the 35 USC § 101 eligibility flow chart because both additional elements are well known and routine in the art. Therefore, claim 1 is rejected under 35 USC § 101.
Regarding claims 5, 9, 11, 17, 22, 26, 29, 39, 45, and 185-192, and 195, the claims are also rejected under 35 USC § 101 as they are dependent on claim 1 and do not additionally recite either a markedly different characteristic, a practical application, or significantly more.
Regarding claim 37, the claim recites different clinical interventions. However, the claimed clinical interventions are not specific treatments as required by MPEP 2106.04(d)(2) and have insignificant relationships to diabetic nephropathy. For example, the claimed clinical interventions of lowering high cholesterol and fostering bone health don’t require a particular treatment. Further, there are examples of the broadly claimed clinical interventions that have insignificant relationships, as defined in MPEP 2106.04(d)(2), to diabetic nephropathy such as lifestyle changes (i.e., a term that encompasses lifestyle changes that are not limited to becoming healthier as it relates to diabetic nephropathy), tobacco cessation (i.e., a term that encompasses doing nothing if the subject did not use tobacco), and diet control (i.e., a term that does not necessarily require healthy eating as it relates to diabetic nephropathy). Thus, the clinical interventions recited in claim 37 are not particular treatments nor do they have significant relationships to diabetic nephropathy. Accordingly, the claim is rejected under 35 USC 101 as the claim does not additionally recite either a markedly different characteristic, a practical application, or significantly more.
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, 9, 11, 17, 22, 26, 29, 37, 39, 45, and 185-195 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.
Regarding claim 1, the claim is broadly drawn towards a method of determining the presence of diabetic nephropathy with at least 80% accuracy via the analysis of 6 genes if the subject is male and 5 genes if the subject is female. Accordingly, the claims are interpreted as claiming a method of diagnosis that is at least 80% accurate and only requires the analysis of 6 genes if the subject is male and 5 genes if the subject is female. The instant specification does not provide support for the broadly claimed gene sets being able to determine the presence of diabetic nephropathy with at least 80% accuracy and the prior art provides evidence that the determination of the presence of diabetic nephropathy via the analysis of genes is unpredictable.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would leave one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP 2163. A claimed genus may be satisfied through sufficient descriptions of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with known or disclosed correlation between function and structure. MPEP 2163(3)a(II). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
As the claims currently recite, as described above, the claim is directed towards a method of determining the presence of diabetic nephropathy that is at least 80% accurate and only requires the analysis of 6 genes if the subject is male and 5 genes if the subject is female. While claiming a genus of structures (i.e., specific genes) by a function (i.e., a method of diagnosing the presence of a diabetic nephropathy with at least 80% accuracy) is not prohibited, there must be a sufficient structure-function relationship described in the specification such that the claimed genus was represented by a representative number of species or the teachings of the specification, or, the prior art can be used to support a well-known structure-function relationship.
In the instant case, the instant specification does not provide support that the broadly claimed genes alone are able to perform the claimed function. Further, the prior art demonstrates that the ability for diabetic nephropathy to be diagnosed through the analysis of sets of genes is unpredictable.
Working Examples
With regard to working examples, the specification provides little evidence on the possession of a sufficient number of species which are encompassed by the entirety of the claimed genus.
MPEP 2163 teaches that “for some arts, there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed [emphasis added].”
In the instant case, the specification teaches the use of 10 different sets of genes that can be analyzed in female subjects and 9 different sets of gens that can be analyzed in male subjects in order to determine the presence of a kidney disease with at least 80% accuracy ([0196]-[0199]; see Tables 3-6). However, the required genes present in the sets of genes that could perform the claimed function in the specification in both males and females are much larger and more specific than the instantly claimed set of genes. For females, the disclosed sets of genes that could perform the claimed function included 38, 53, 55, 59, 65, 76, 81, 89, 110, and 132, individual genes ([0196]-[0197]; see Tables 3-4). For males, the discloses set of genes that could perform the claimed function included 50, 60, 70, 74, 88, 94, 106, and 134 individual genes ([0198]-[0199]; see Tables 5-6). Thus, when taken as a whole, the set of genes present in the specification is not representative of the claimed genus as a while because the claimed genus broadly encompasses a method that can performed the claimed function only through the analysis of only 6 genes if the subject is male and only 5 genes if the subject is female. Further, MPEP 2163 teaches that “[…] an adequate description of a genus may not support claims to a subgenus or species within the genus […]”. Therefore, the instantly claimed and broader subgenus of genes present in claim 1 is not adequately described in the specification as being able to determine the presence of diabetic nephropathy with at least 80% accuracy, as claimed.
Thus, the instant specification does not provide written description for the entirety of the claimed method comprising the analysis of 6 genes if the subject is male and 5 genes if the subject is female (see Claim 1).
Prior Art
Regarding the state of the prior art, the prior art demonstrates that the structure of the genes that can be utilized to determine the presence of diabetic nephropathy can vary widely and the successful use of the genes to determine the presence of diabetic nephropathy in a subject is unpredictable and requires experimentation.
Tang (Renal Failure 37.3 (2015): 363-371) is drawn towards a review study concerned with gene and protein markers of diabetic nephropathy (i.e., “DN”) (Abstract). Tang teaches that while there are some studies pointing to specific sets of candidate genes that could be utilized in genetic linkage studies, “there has been no consistent and reproducible identification of genetic loci or candidate genes for DN risk or protection” (pg. 364).
Thus, the prior art shows that prior to the effective filing date of the claimed invention it was not predictable that a broad set of genes could be utilized to determine the presence of diabetic nephropathy with an accuracy of at least 80%. Rather, the prior art shows that a candidate set of genes that could be utilized to determine the presence of diabetic nephropathy is very specific and not predictable. Further, the prior art explicitly states that there has been no consistent and reproducible identification of genetic loci or candidate genes for the determination of diabetic nephropathy DN risk in a subject.
Conclusion
The specification does not identify a representative number of species of the broadly claimed set of genes that possess the claimed function of determining the presence of diabetic nephropathy in a subject with an accuracy of at least 80%. Further, the prior art shows that prior to the effective filing date of the claimed invention that determining genes associated with the presence of diabetic nephropathy was unpredictable and highly specific. Therefore, a person of ordinary skill in the art would not have concluded that Applicant was in possession of the invention as claimed. Thus, claim 1 is rejected under 35 U.S.C. 112(a).
Regarding claims 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, and 185-192, as the claims are ultimately dependent on claim 1 and do not rectify the 35 USC 112(a) rejection above, the claims are also rejected under 35 USC 112(a).
Regarding claim 193, the claim is drawn towards a method of determining the presence of a kidney disease with at least 80% accuracy via the analysis of “male-specific” and “female-specific” genes (see Claim 193). The pertinent analysis of the claim is discussed above as applied to claim 1 because the claim is even broader than instant claim 1 because the claim does not claim any male-specific genes or female-specific genes. Therefore, as applied above to claim 1, the claim is rejected under 35 USC 112(a).
Regarding claim 194, the claim is drawn towards a method of determining the presence of a kidney disease with at least 80% accuracy via the analysis of 10 genes if the subject is male and 8 genes if the subject is female (see Claim 194). The pertinent analysis of the claim is discussed above as applied to claim 1 because the claim broadly claims a set of genes that is not supported in the specification to be able to determine the presence of a kidney disease with at least 80% accuracy. Further, as discussed above as applied to claim 1, the prior art teaches that determining the presence of a kidney disease via the analysis of a set of genes is unpredictable. Therefore, as applied above to claim 1, the claim is rejected under 35 USC 112(a).
Regarding claims 195, as the claim is ultimately dependent on claim 194 and does not rectify the 35 USC 112(a) rejection above, the claim is also rejected under 35 USC 112(a).
Claims 1, 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, 185-192, and 194-195 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.
Regarding claims 1 and 194, the claims recites a method that can determine the presence of diabetic nephropathy with at least 80% accuracy via the analysis of 6 genes if the subject is male and 5 genes if the subject is female (see Claim 1) or the analysis of 10 genes if the subject is male and 8 genes if the subject is female (see Claim 194). However, as discussed above in the written description rejection of claims 1, 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, and 185-195, the specification as originally filed does not provide support for the claimed set of genes performing the claimed functions. The claimed set of genes is much broader than, and is not limited to, the specific sets of genes that were capable of performing the claimed function described in the specification.
Further, the currently pending Remarks, filed 18 September 2025, do not identify a specific paragraph from which the newly amended set of genes has support in the specification as being able to perform the claimed function.
Thus, the claims are rejected under 35 USC 112(a) for introducing new matter because the claim language was not original and the scope of the claim goes beyond what the specification describes.
Regarding claims 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, 185-192, and 195, as the claims are ultimately dependent on claims 1 and 194 and do not rectify the new matter rejection above, the claims are also rejected under 35 USC 112(a).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 192 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 192, the claim further limits the report to specific clinical indications. However, the contents of the claimed report are nonfunctional descriptive material that are not given patentable weight. Therefore, the dependent claim specifying the contents of the reports of claim 1 fails to further limit the subject matter of claim 1.
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.
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.
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.
Claim(s) 193 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConnell (PG Pub No. CA 2,881,748; published 20 February 2013) in view of Huang (Applied Intelligence 48 (2018): 594-607) as applied to claims 1, 22, 26, 29, 39, 45, and 191-192 above, and further in view of Huang (Applied Intelligence 48 (2018): 594-607) and Davicioni (PG Pub No. US 2016/0032395 A1).
Regarding claim 193, McConnell is drawn to an invention concerned with analyzing kidney disease biomarkers (Abstract). McConnell teaches that (a) the invention provides methods for the diagnosis and treatment of renal dysfunction (i.e., a kidney disease or disorder) by analyzing the expression of FABP1 (i.e., a bodily sample can yield a data set comprising a set of levels of gene expression products that can correspond to a set of genes associated with a kidney disease) (pg. 4-5). McConnell teaches the use of (b) both a multinominal logistic regression model and an artificial neural network (i.e., trained machine learning algorithms that computer process the gene expression products to determine the presence of said kidney disease) that were able to predict disease state at a level of 86.2% and 84%, respectively (pg. 28-29). McConnell teaches that (c) the algorithms are able to report if the subject had the renal dysfunction or not (i.e., the algorithms can electronically output a report that identified a presence of increased risk of kidney disease) (pg. 28-29). McConnell teaches that (d) the invention may be utilized to determine the efficacy of a treatment (i.e., clinical intervention selected from a drug treatment) for the kidney disease following administration of the drug treatment to a patient (pg. 6-7, 34; see Claim 7). McConnell teaches that the renal disease may be diabetic nephropathy (pg. 9). McConnell further teaches that detecting FABP1 expression levels in urine was routine in the art and indicative of the deterioration of renal function (pg. 4). McConnell also teaches that there is an importance to measure clinical parameters for chronic kidney disease in urine (pg. 5). McConnell teaches that different markers (i.e., FABP1, creatinine, cystatin C, AST, and y-GT) that are influenced by gender (i.e., a set of gene expression products from different male-specific or female-specific genes based on a gender of said subject) can be measured and inputted into the machine learning algorithms (pg. 28-29). McConnell teaches that the machine learning algorithms were trained on both subjects that had the kidney disease (i.e., a first set of bodily samples) and healthy volunteers (i.e., a second set of bodily samples from subjects that did not have a kidney disease), such that FABP1 was identified to be elevated in serum from subjects that had the kidney disease (pg. 28). McConnell teaches that the machine learning algorithms were able to successfully identify different stages of the kidney disease (i.e., by utilizing at least a third set of bodily samples from subjects having other types of kidney diseases that is different from the first set of bodily samples) via the expression levels of FABP1 (pg. 28-29).
McConnell does not teach or suggest that (a) comprises reverse transcribing RNA obtained from said bodily fluids to yield cDNA and sequencing at least a portion of said cDNA molecules to yield a data set (Claim 193). McConnell in view of Huang does not teach or suggest that (a) comprises selectively enriching and amplifying at least a portion of said cDNA molecules for a set of genomic loci associated with said kidney disease (Claim 193). McConnell in view of Huang does not teach or suggest that (a) comprises aligning at least a portion of said sequencing reads to a human reference genome, generating counts of gene transcripts, and normalizing said counts (Claim 193). McConnell does not teach or suggest the use of a recursive feature algorithm (Claim 193).
However, one of ordinary skill in the art would have considered the teachings of Huang and Davicioni as both references are common fields of endeavor pertaining to the study and diagnosis of kidney disease.
Huang is drawn to a study concerned with feature clustering based support vector machine recursive feature elimination (i.e., RFE) for gene selection (pg. 594). Huang teaches that the RFE algorithm can be trained to detect prostate cancer on two training datasets: prostate tumor samples (i.e., a training sample from subjects suffering from a disease) and non-tumor prostate samples (i.e., a second training sample from subjects that do not have a diseases) (pg. 600). Huang teaches that the RFE algorithm can be run on multiple gene expression profiles from different subjects (i.e., expression profiles that are different from either the first or second training sets) in order to determine if the subject has cancer or not (pg. 602). Huang teaches that the RFE algorithm can be trained on different types of cancer (i.e., Huang is interpreted as teaching that the RFE algorithm can be trained on a first and a second set of genes that differentially distinguishes between cancer) (pg. 600-604). Huang teaches that RFE achieves a better performance and a lower computational complexity than other compared methods (pg. 595).
Davicioni is drawn to an invention concerned with methods, systems and kits for the diagnosis, prognosis and determination of cancer progression of a cancer in a subject (Abstract). Davicioni teaches that the method may comprise assaying (i.e., analyzing) an expression level in a sample from the subject for a plurality of targets associated with kidney cancer (i.e., a kidney disease), wherein the plurality of targets comprises one or more targets selected from Table 1 ([0005]). Davicioni teaches that the sample may comprise urine ([0170]). Davicioni teaches that the expression levels can be analyzed via a classifier (i.e., a computer processing system) with an accuracy of at least 80% ([0096]). Davicioni teaches that following sample collection and nucleic acid expression the mRNA target polynucleotides of interest (i.e., mRNA obtained or derived from genes associated with kidney cancer) can be reverse transcribed in order to selectively create cDNA prior to detection (i.e., prior to yielding the data set via sequence reads) ([0196]). Davicioni teaches that the expression patterns can be determined and compared to (i.e., aligned to) one or more reference profiles (i.e., Davicioni teaches that at least a portion of a sequencing read can be aligned to a reference genome) ([0314]). Davicioni teaches that the expression patterns can be normalized (i.e., Davicioni is interpreted as teaching that counts of gene transcripts can be normalized) ([0225], [0314]). Davicioni teaches that the gene expression analysis method may be utilized in patients that do not exhibit evidence of a disease ([0215]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the trained machine learning algorithm of McConnell for a recursive feature elimination algorithm, as described in Huang, and the gene expression products of McConnell in view of Huang for cDNA that was reverse transcribed from RNA present in a bodily sample indicative of kidney disease, selectively enriching and amplifying at least a portion of said cDNA molecules for a set of genomic loci associated with said kidney disease, and aligning at least a portion of said sequencing reads to a human reference genome, generating counts of gene transcripts, and normalizing said counts, as described by Davicioni. A person of ordinary skill in the art would have been motivated to do so in order to utilize an algorithm that achieves a better performance than other algorithms and utilize an expression dataset that can detect the presence of a disease in patients who do not exhibit evidence of the disease. A person of ordinary skill in the art would have had a reasonable expectation of success because both McConnell and Huang tech the use of algorithms can be used to analyze gene expression products and Davicioni teach that gene expression products can be determined via the use of cDNA molecules that can be reverse transcribed, selectively enriched and amplified, and aligned to a reference genome.
Closest Prior Art
Regarding claims 1, 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, 185-192, and 194-195, the closest prior art is McConnell.
The teachings of McConnell are discussed above as applied to claim 193.
However, neither McConnell nor the prior art teaches that said set of genes comprises at least one gene selected from the group consisting of: SNORA61, PAPPA2, IGFBP7, ADAMDEC1, TMOD1, GPT, and further comprises SNORA80E, SNORA49, SNORA48, SPRR2D, and SERPINB4, if said subject is male; and HBB, HBA2, UPK3A, and UPK2, if said subject is female (see Claim 1). Further, neither McConnell nor the prior art teaches that the said first set of genes comprises: GPT, and further comprises: SNORAS80E, SNORA49, SNORA48, SPRR2D, and SERPINB4, if said subject is male; and HBB, HBA2, UPK3A, and UPK2, if said subject is female; and wherein said second set of genes comprises: KLK8 and PTPRQ, and further comprises: NEFH and SNORA44, if said subject is male; and UPK3A, if said subject is female (see Claim 194).
Therefore, claims 1, 5, 9, 11, 17, 22, 26, 29, 37, 39, 45, 185-192, and 194-195 are free of the prior art.
Response to Arguments
Regarding claim 193, Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Applicant alleges that McConnell as relied upon explicitly teaches away from a urine-based analysis featured in claim 193. Applicant alleges that McConnell that the teaching away is evidenced by the following passages in McConnell: “there is scientific literature to suggest that the findings of urinary FABP1 have not been consistent across different research groups" (pg. 5) and "the use of serum FABP 1 as not being an effective biomarker for kidney disease as the source of FABP1 can also originate from liver tissue damage" (pg. 5). Applicant alleges that McConnell states that the methodology prefers a sample isolated from a serum sample.
This argument is not found persuasive because McConnell further teaches that detecting FABP1 expression levels in urine was routine in the art and indicative of the deterioration of renal function (pg. 4). McConnell also teaches that there is an importance to measure clinical parameters for chronic kidney disease in urine (pg. 5). The second passage cited to by Applicant is the discussion of FABP1 present in serum FABP1 and not urine. Further, the preference of McConnell for a serum sample the comprises FABP1 gene expression products is not an explicit teaching away from FABP1 gene expression products measured in urine. As discussed above, McConnell teaches that measuring gene expression products from urine was known in the art to be routine and of importance when determining the presence of chronic kidney disease.
Applicant alleges that Huang teaches methods for prostate cancer detection and these address different technical problems than the kidney disease detection approach recited in claim 193.
This argument is not found persuasive because both McConnell and Huang teach the use of algorithms that can identify the presence of a disease via the analysis of gene expression products. The teachings of Huang that were relied upon in the action are specifically address towards the teachings of Huang that demonstrate that recursive feature algorithms can be utilized to analyze different gene expression profiles form different subjects in order to determine the presence of a disease, analogously to the algorithms of McConnel which were used to analyze different gene expression profiles form different subjects in order to determine the presence of a choric kidney disease. Thus, both McConnell and Huang address the same technical problem of detecting the presence of a disease via the analysis of gene expression products through the use of an algorithm.
Applicant alleges that Davicioni as cited by the Office does not teach the specific combination of (1) urine sample analysis, (2) diabetic nephropathy detection, (3) recursive feature elimination algorithms, and (4) the specific training methodology featured in claim 193.
This argument is not found persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It is the combination of McConnell, Huang, and Davicioni that allow one of ordinary skill in the art to arrive at the claimed invention.
Conclusion
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636