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 .
Applicant’s response of 07/10/2026, including amendments to the specification and replacement drawings, has been received and entered into the application file.
Claims 55-58, 71, and 78-79 were amended in the claim set filed 07/10/2026.
Claims 73 and 74 were canceled in the claim set filed 07/10/2026.
Claims 1-15, 31, 43-48, 54-58, 70-72, 75-80 are pending, of which claims 1-15, 31, 43-48, and 54 were previously withdrawn.
Accordingly, claims 55-58, 70-72, and 75-80 are pending and under consideration.
Election/Restrictions
Applicant’s previous election without traverse of Group IV (claims 55-58) in the reply filed on 11/04/2025 is acknowledged.
Claims 1-15, 31, 43-48, and 54 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/04/2025.
New claims 70-80 were added in the reply filed on 11/04/2025. Claims 73 and 74 were cancelled in the reply filed 07/10/2026. Accordingly, claims 55-58, 70-72, and 75-80 are pending and under consideration.
Information Disclosure Statement
Receipt of an information disclosure statement on 07/10/2026 is acknowledged. The signed and initialed PTO-1449 has been mailed with this action.
Prior Grounds of Objection/Rejection
RE: Drawings
►The drawings were previously objected to for various informalities.
The replacement drawings received 07/10/2026 have obviated the basis of the objections of record. The objections of record are hereby withdrawn.
RE: Specification
►The disclosure was previously objected to for various informalities.
The amendments to the instant specification received on 07/10/2026 have obviated the basis of the objections of record. The objections of record are hereby withdrawn.
RE: Claim Objections
►Claims 55, 56, 58, and 77-79 were previously objected to for various informalities.
The amendments to the instant claim set have obviated the basis of most, but not all, objections of record. Those objections not repeated below are hereby withdrawn.
RE: Claim Rejections - 35 USC § 112(a)
►Claims 55-58 and 70-80 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for preparing a personalized yeast model for determining whether a subject is at risk of a disease, said method comprising identifying a gene encoding ornithine transcarbamylase (OTC) in two alleles from the genomic DNA, does not reasonably provide enablement for preparing a personalized yeast model for determining whether a subject is at risk of a disease, said method comprising identifying a gene encoding ornithine transcarbamylase (OTC) in at least two alleles (i.e. more than two alleles) from the genomic DNA. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The amendments to the instant claim set have obviated the basis of the rejection of record. The rejection of record is hereby withdrawn.
RE: Claim Rejections - 35 USC § 112(b)
►Claims 56, 57, 71, 73, and 74 were previously 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.
The cancellation of claims 73 and 74 renders the rejection thereof moot.
The amendments to the instant claim set have obviated the basis of the rejection of record. The rejection of record is hereby withdrawn.
RE: Claim Rejections - 35 USC § 103
►Claims 55, 70-72, and 77 were previously rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022) in view of Sun et al., 2016 (hereinafter Sun), Liu et al., 2017 (hereinafter Liu), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025), and Wilnai et al., 2018 (hereinafter Wilnai), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas), Paulson, 2017 (hereinafter Paulson), and Singh, 2013 (hereinafter Singh).
►Claims 56, 79, and 80 were previously rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022) in view of Sun et al., 2016 (hereinafter Sun), Liu et al., 2017 (hereinafter Liu), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025), and Wilnai et al., 2018 (hereinafter Wilnai), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas), Paulson, 2017 (hereinafter Paulson), and Singh, 2013 (hereinafter Singh) as applied to claim 55 above, and further in view of Wadsworth Center Prenatal Genetics Referrals, 2019 (hereinafter Wadsworth).
►Claims 57, 58, 73, and 74 were previously rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022) in view of Sun et al., 2016 (hereinafter Sun), Liu et al., 2017 (hereinafter Liu), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025), and Wilnai et al., 2018 (hereinafter Wilnai), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas), Paulson, 2017 (hereinafter Paulson), and Singh, 2013 (hereinafter Singh) as applied to claim 55 above, and further in view of Wadsworth Center Prenatal Genetics Referrals, 2019 (hereinafter Wadsworth) and Trevisson et al., 2009 (hereinafter Trevisson; as cited in the IDS filed 11/04/2022).
►Claims 75, 76, and 78 were previously rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022) in view of Sun et al., 2016 (hereinafter Sun), Liu et al., 2017 (hereinafter Liu), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025), and Wilnai et al., 2018 (hereinafter Wilnai), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas), Paulson, 2017 (hereinafter Paulson), and Singh, 2013 (hereinafter Singh) as applied to claim 55 above, and further in view of Magesh and Doss, 2014 (hereinafter Magesh).
The cancellation of claims 73 and 74 renders the rejection thereof moot.
Applicant has traversed the rejections of record, asserting that the Examiner has not provided the requisite teaching, suggestion, or motivation of why a skilled artisan would have selected these references and then combined and modified them to arrive at the pending claims with the requisite expectation of success. Specifically, Applicant asserts that Hamza discloses the use of Saccharomyces cerevisiae as a platform for testing human genetic variants-not for generating personalized clinical recommendations for a subject. Similarly, Sun and Liu also teach or disclose population-scale variant classification rather than an individualized clinical workflow, subject-specific data generation, or personalized recommendation delivery as presented in the instant claims. Applicant further asserts that Kingsmore is directed to an entirely different objective, which is the use of rapid whole-genome sequencing and bioinformatic analyses for the diagnosis of genetic disorders. Therefore, Applicants asserts that there would have been no reason to modify the processes of Hamza, Liu, and Sun in view of Kingsmore because Kingsmore is directed to an entirely different objective.
In response, this is not found persuasive. First, it is noted that KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http://www.uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
The combination of prior art cited in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007): “Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.”
Therefore, the claimed invention, as a whole, is prima facie obvious.
Additionally, regarding the selection of art, the MPEP sets forth that a person of ordinary skill in the art is also a person of ordinary creativity (MPEP § 2141.03). A person of ordinary skill in the art also has access to the prior art and may pick and choose references that may or may not be informative as a person of ordinary creativity as well. Regarding Applicant’s arguments concerning population-scale assays versus individualized clinical workflows, the Examiner notes that while Sun and Liu do disclose population-scale variant classification, Sun explicitly discloses that the improved identification of germline or somatic pathogenic mutations taught therein can enable disease risk assessment for individual patients (page 670, column 1, paragraph 1). Sun further discloses that the results taught therein support the use of surrogate genetics to identify and characterize pathogenic variants (page 977, column 1, paragraph 5), wherein said pathogenic variants may be used to assess disease risk for individual patients, as set forth above. As set forth above, a person of ordinary skill in the art is also a person of ordinary creativity (MPEP § 2141.03) and would therefore be motivated based on the disclosure of Sun to apply the methods taught therein to disease risk assessment for individual patients, as set forth in the non-final rejection dated 01/12/2026.
While the Examiner acknowledges that the prior art does not specifically teach and individualized clinical workflow, the steps of the individualized clinical workflow, as instantly claimed, were all known in the art prior to the effective filing date of the instant application. Furthermore, as a person of ordinary creativity, a person of ordinary skill in the art would reasonably predict that the population level methods taught in the art would also be applicable to assayed individuals, as all such methodologies rely on yeast-human complementation.
Regarding Applicant’s arguments concerning Kingsmore, the Examiner notes that Kingsmore is also drawn to diagnostic workflows. Thus, one of ordinary skill in the art researching diagnostic workflows would be motivated to search the literature for diagnostic workflows, including those of Kingsmore, which discloses the utility of genome sequencing in diagnosing patients and using the information obtained therefrom to present management options to the subject. The sequencing of Kingsmore is not incompatible with the methods taught in Hamza, Sun, and Liu. In fact, Hamza explicitly discloses that next generation sequencing (such as that taught in Kingsmore) facilitates screening of rare disease variants using the methods taught therein (page 1273, column 1, paragraph 1).
As set forth in the non-final rejection dated 01/12/2026, one of ordinary skill in the art would have been motivated to combine the cited art in order to receive the expected benefit of identifying OTC deficiency mutations with significantly higher precision and specificity than current computational methods, thereby facilitating treatment (including prenatal treatment) to offer better outcomes for affected patients.
The rejection of record is hereby maintained, as set forth in detail below.
RE: Double Patenting
Claims 55, 70-78, and 80 were previously provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-13 of copending Application No. 17/047,667 (corresponds to US 2021/0155971 A1; as cited in the IDS filed 11/04/2022) in view of Sun et al., 2016 (hereinafter Sun), Wilnai et al., 2018 (hereinafter Wilnai), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025), and Magesh and Doss, 2014 (hereinafter Magesh).
The cancellation of claims 73 and 74 renders the rejection thereof moot.
Applicant has traversed the rejection of record, asserting that the amended claims are patentably distinct from the claims of the reference application, as none of the claims of the reference application recite the features recited in the amended claims.
In response, this is found not found persuasive. Although the claims at issue are not identical, they are not patentably distinct from each other, as the methods claimed in the instant and copending applications require identical steps albeit for querying different genes.
The rejection of record is hereby maintained, as set forth in detail below.
New/Maintained Grounds of Objection/Rejection
Claim Objections
Claim 55 is objected to because of the following informalities:
As previously set forth, a colon separating lines two and three (i.e. following “the method comprising”) is required. It would be remedial to amend the instant claim language to include the requisite colon, thereby comporting with standard grammatical and/or linguistic conventions.
Appropriate correction is required.
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.
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 55, 70-72, and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022; of record) in view of Sun et al., 2016 (hereinafter Sun; of record), Liu et al., 2017 (hereinafter Liu; of record), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025; of record), and Wilnai et al., 2018 (hereinafter Wilnai; of record), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas; of record), Paulson, 2017 (hereinafter Paulson; of record), and Singh, 2013 (hereinafter Singh; of record).
With regard to amended claim 55, which recites “a method of preparing a personalized yeast model for determining whether a subject is at risk of a disease, the method comprising [:]
a) obtaining genomic DNA from a first subject;
b) identifying a gene encoding ornithine transcarbamylase (OTC) in up to two alleles from the genomic DNA;
c) inserting the gene into a construct, wherein the construct is a linear DNA;
d) providing a test cell, wherein the test cell has a homologous gene of the gene encoding OTC, wherein the homologous gene has been knocked out of the test cell;
e) introducing the construct into the test cell;
f) evaluating the test cell for cell growth in a media, wherein the media lacks an amino acid, wherein the test cell growth is compared to a control cell that has the homologous gene, wherein when test cell growth is comparable to that of the control cell[,] it indicates that the gene encodes a functional OTC protein, and wherein when the test cell growth is slow as compared to the control cell, it indicates that the gene encodes a non-functional OTC protein or OTC protein with decreased function and indicates the disease;
g) generating data for a look-up table;
h) generating one or more personalized disease amelioration recommendations for the first subject; and
i) presenting the one or more personalized disease amelioration recommendations to the first subject for disease management,” both Hamza and Sun disclose the utility of testing human genes for complementation with yeast genes in order to assess genetic variants, as set forth below. Hamza discloses that model organisms such as yeast can be utilized to test human genetic variants by assaying human-yeast gene complementation pairs for growth defects (abstract). These assays include inserting a queried gene of interest into an expression vector, transforming said expression vector into a corresponding haploid-convertible heterozygous diploid knockout yeast strain (homologs are disclosed at tables S2, S3, and S5), growing the transformants in media lacking leucine, and monitoring cell growth of both mutant and wild-type yeast by measuring optical density every 30 minutes over a period of 48 hours to calculate area under the curve (AUC) value, which is a measure of cell growth (page 1265, column 2, paragraphs 1 and 2). Hamza specifically discloses that mutant alleles that result in a nonfunctional protein reduce strain fitness (page 1273, column 1, paragraph 1), wherein strain fitness is defined as the AUC (i.e. growth) of the mutant curves relative to the AUC of the wild-type allele (page 1265, column 2, paragraph 2). Thus, the disclosure of Hamza reads on steps (c)-(f) of instant claim 55, with the exception of the linear DNA construct of step (c). This deficiency is cured by Liu, which discloses that transformation of a linear DNA construct into yeast is a robust and well-established methodology (page 8, paragraph 3).
Similarly, Sun discloses that yeast-based functional complementation assays may be used to measure the impact of human disease mutations with significantly higher precision and specificity than current computational methods (abstract). Per Sun, these methods are particularly relevant to improving carrier screening and pre-implantation embryonic screening (page 670, column 1, paragraph 1). As depicted in Figure 1, Sun discloses that complementation relationships between human and yeast genes are identified by assessing whether a human gene provided in a yeast expression plasmid rescues phenotypic defects of a loss-of-function in its cognate yeast gene, said loss-of-function being generated by heterozygous diploid knockout (page 971, column 1, paragraph 3-column 2, paragraph 2; page 677, column 2, paragraphs 2 and 3), thereby facilitating the identification and characterization of deleterious pathogenic variants (page 677, column 1, paragraph 5). This rescue of the null mutant may be monitored by evaluating differences in cell growth in liquid media or on solid media (Figure 2; page 678, column 1, paragraphs 2 and 3). Sun further discloses that the data obtained from the experimentation disclosed therein may be used to provide a look-up table for functionality of human variants and to identify potential therapeutics for the queried disease mechanism/gene (page 676, column 2, paragraph 4), as in steps (g) and (h) of instant claim 55.
Regarding steps (a) and (i) of instant claim 55, Kingsmore discloses detection of nucleotide sequence variants in patients for purposes of diagnosing genetic diseases (abstract), albeit by different methodology than the human-yeast complementation assays disclosed in Hamza and Sun. The disclosure of Kingsmore establishes that diagnosis of genetic diseases in patients required extraction of genomic DNA from said patients (paragraph [0140]), as recited at step (a) of instant claim 55. Furthermore, Kingsmore discloses that all patients provided informed written consent for participating in diagnosis and treatment of genetic disease (paragraphs [0053] and [0056]). Thus, it is considered that Kingsmore discloses that for purposes of diagnosing and treating a genetic disease, the patient’s genomic DNA must be isolated in order to be studied, and the data obtained therefrom may be used to inform treatment options, as in steps (a) and (i) of instant claim 55.
Regarding step (b) of instant claim 55, Wilnai discloses that mutations in the ornithine transcarbamylase (OTC) gene cause OTC deficiency, which is a severe X-linked condition that can be diagnosed prenatally and presents particularly severely in hemizygous males (abstract; page 297, column 2, paragraph 1; page 298, column 1, paragraph 2). Bukaveckas teaches that humans are diploid organisms, wherein each cell carries two copies of each gene and thus carries two alleles of each gene (page 354, column 1, paragraph 3). Per Wilnai, a prenatal diagnosis of urea cycle defects such as OTC deficiency is essential to initiating appropriate therapy as soon as possible to offer a better outcome (page 299, column 1, paragraphs 5-6). Thus, Wilnai motivates assaying the OTC gene (of which humans have two alleles) to diagnose OTC deficiency, as in step (b) of instant claim 55.
Furthermore, as set forth above, Sun discloses that the improved identification of germline or somatic pathogenic mutations taught therein can enable disease risk assessment for individual patients (page 670, column 1, paragraph 1). Furthermore, Hamza explicitly discloses that next generation sequencing (such as that taught in Kingsmore) facilitates screening of rare disease variants using the methods taught therein (page 1273, column 1, paragraph 1).
With regard to claim 70, which recites “the personalized yeast model [of the method of claim 55] is for determining prenatal risk of the disease,” as set forth above, Sun discloses that yeast-based functional complementation assays may be used to measure the impact of human disease mutations with significantly higher precision and specificity than current computational methods, and that these assays are particularly relevant to improving carrier screening and pre-implantation embryonic screening (abstract; page 670, column 1, paragraph 1). Pre-implantation embryonic screening is performed following in vitro fertilization to select embryos generated from the process for implantation (taught in Paulson). Thus, it is considered the pre-implantation embryonic screening is used to determine prenatal disease risk. As set forth above, Wilnai discloses that early, prenatal diagnosis of OTC deficiency is essential to initiating appropriate therapy as soon as possible to offer a better outcome (page 299, column 1, paragraphs 5-6). Thus, it is considered that Sun and Wilnai collectively disclose and/or motivate each and every additional limitation of instant claim 70, as set forth in greater detail below.
With regard to amended claim 71, which recites “the method of claim 55, wherein cell growth is measured by optical density of a liquid culture, or a number of pixels of a colony of cells growing on solid media,” as set forth above, both Hamza and Sun disclose evaluating cell growth in liquid media (via optical density or absorbance at 600 nm) or on solid media (Hamza: Figures S1-S4 and page 1265, column 2, paragraph 2; Sun: Figure 2). Thus, both Hamza and Sun disclose each and every additional limitation of instant claim 71.
With regard to claim 72, which recites “the method of claim 5, wherein the evaluating step comprises measuring cell growth for 0.5, 2, 4, 6, 8, 10, 12, 24, 36, 72, 96, or 120 hours or any number of hours in between a range defined by any two aforementioned values,” as set forth above, both Hamza and Sun disclose evaluating cell growth in liquid media (via optical density or absorbance at 600 nm) or on solid media (Hamza: Figures S1-S4 and page 1265, column 2, paragraph 2; Sun: Figure 2) over periods of time including 48 hours (Hamza: page 1265, column 2, paragraph 2) and 25 hours (Sun: Figure 2), which falls within the range defined by 24 and 36 hours, as in instant claim 72. Thus, both Hamza and Sun disclose each and every additional limitation of instant claim 72.
With regard to amended claim 77, which recites “a t-test is performed between the test cell and control cell to determine a significant growth difference, wherein a p-value of < 0.0001 indicates a significant growth difference between the test cell and control cell,” as set forth above, Hamza discloses that mutant alleles that result in a nonfunctional protein reduce strain fitness (page 1273, column 1, paragraph 1), wherein strain fitness is defined as the AUC (i.e. growth) of the mutant curves relative to the AUC of the wild-type allele (page 1265, column 2, paragraph 2). Significant differences in growth are disclosed to have been determined using a t-test (page 1265, column 2, paragraph 2). While Hamza is silent as to the significance threshold for p-values calculated from said t-test, these thresholds are generally standard in the field, as evidenced by Singh, which discloses that a p-value of less than 0.0001 is an extremely low p-value with clinical relevance, as its low value indicates that the queried results are not accidental and can be used as strong evidence against the null hypothesis (table of page 3; page 3, paragraph 8). Thus, Hamza, as evidenced by Singh, discloses each and every additional limitation of instant claim 77.
Hamza specifically discloses mutant alleles that result in a nonfunctional protein reduce strain fitness (page 1273, column 1, paragraph 1), wherein strain fitness is defined as the AUC (i.e. growth) of the mutant curves relative to the AUC of the wild-type allele (page 1265, column 2, paragraph 2).
Given that Hamza discloses that model organisms such as yeast can be utilized to test human genetic variants by comparing growth of human-yeast gene complementation pairs (generated by inserting a human gene into a yeast cell in which the corresponding gene has been knocked out) to wild-type growth using a t-test (with a p-value significance threshold of 0.0001, as taught by Singh); that Sun similarly discloses that yeast-based functional complementation assays may be used to measure the impact of human disease mutations for carrier screening and pre-implantation screening (which is used to determine prenatal disease risk per Paulson) with significantly higher precision and specificity than current computational methods and to generate a look-up table for functionality of human gene variants and to identify potential therapeutics for the queried disease mechanism/gene; that Kingsmore discloses that for purposes of diagnosing and treating a genetic disease, the patient’s genomic DNA must be isolated in order to be studied, and the data obtained therefrom may be used to inform treatment options; and that Wilnai discloses that mutations in the ornithine transcarbamylase (OTC) gene (of which humans have two alleles per Bukaveckas) cause OTC deficiency, which is a severe X-linked condition that can be diagnosed prenatally and presents particularly severely in hemizygous males, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to diagnose and treat genetic diseases (as disclosed in Kingsmore) using the methodology disclosed by Hamza and Sun to detect mutations in the OTC gene to predictably determine carrier status or prenatal risk of developing OTC deficiency due to a mutated, non-functional OTC gene. One would have been motivated to make such a modification in order to receive the expected benefit of identifying OTC deficiency mutations with significantly higher precision and specificity than current computational methods, thereby facilitating treatment (including prenatal treatment) to offer better outcomes for individual affected patients.
Claims 56, 79, and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022; of record) in view of Sun et al., 2016 (hereinafter Sun; of record), Liu et al., 2017 (hereinafter Liu; of record), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025; of record), and Wilnai et al., 2018 (hereinafter Wilnai; of record), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas; of record), Paulson, 2017 (hereinafter Paulson; of record), and Singh, 2013 (hereinafter Singh; of record) as applied to claim 55 above, and further in view of Wadsworth Center Prenatal Genetics Referrals, 2019 (hereinafter Wadsworth; of record).
The combined disclosures of Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh are described above and applied as before. However, these disclosures do not teach the second subject of instant claim 56, the prenatal testing of instant claim 70, or the subjects of instant claims 79 and 80.
With regard to amended claim 56, which recites “the method of claim 55…further comprises: a) obtaining a second genomic DNA from a second subject, wherein the second set of two alleles corresponds to a second gene encoding OTC, wherein the second gene encoding OTC is placed in a second construct; b) introducing the second construct into a second test cell, evaluating the second test cell for cell growth in a media, wherein the media lacks an amino acid, wherein the test cell growth is compared to a control cell that has the homologous gene, wherein when second test cell growth is comparable to that of the control cell, it indicates that the gene encodes a functional OTC protein and wherein the test cell growth is slow as compared to the control cell, it indicates that the gene encodes a non-functional OTC protein or OTC protein with decreased function,” as set forth above, both Hamza and Sun disclose human-yeast complementation assays in which the ability of a human gene to rescue a null mutant of the corresponding yeast homolog is determined by introducing a construct carrying said human gene into a haploid yeast strain in which the corresponding homolog is knocked out and subsequently monitoring growth of mutant and control cells (see sections cited above regarding instant claim 55). Sun discloses that yeast-based functional complementation assays may be used to measure the impact of human disease mutations with significantly higher precision and specificity than current computational methods, and that these assays are particularly relevant to improving carrier screening and pre-implantation embryonic screening (abstract; page 670, column 1, paragraph 1). Additionally, as set forth above, Wilnai discloses that mutations in the ornithine transcarbamylase (OTC) gene (of which humans have two alleles per Bukaveckas (page 354, column 1, paragraph 3)) cause OTC deficiency, which is a severe X-linked condition that presents particularly severely in hemizygous males and can be diagnosed prenatally to improve treatment outcomes (abstract; page 297, column 2, paragraph 1; page 298, column 1, paragraph 2; page 299, column 1, paragraphs 5-6). While none of the cited art discloses testing a second subject, this deficiency is cured by Wadsworth.
Wadsworth discloses that carrier screening can be performed at any time before or during pregnancy, wherein genetic testing is performed in one or both parents in order to determine risk for a child conceived to be affected with recessive or x-linked genetic conditions (table 1 on page 2). As set forth above, Wilnai discloses that OTC deficiency is a severe X-linked condition (abstract). Accordingly, in view of the disclosure of Wadsworth, carrier testing for OTC deficiency would be indicated in one or both parents (i.e. first and second subjects) in order to determine risk for their child to be affected with OTC deficiency, as it is a severe X-linked condition. As set forth above, the method collectively disclosed by Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, and Singh comprises introducing the queried gene into a construct that is then transformed into a knockout yeast test cell and evaluating growth of the test and control cells, as instantly claimed. Furthermore, as set forth above regarding instant claim 70, the disclosure of Sun explicitly teaches that human-yeast gene complementation testing is well-suited to carrier screening (as disclosed in Wadsworth) and pre-implantation embryonic screening (abstract; page 670, column 1, paragraph 1). Thus, it is considered that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, Singh, and Wadsworth collectively disclose the method of claim 56.
With regard to amended claim 79, which recites “either the first subject [of the method of claim 56] is a female and the second subject is a male, or the first subject is a male and the second subject is a female,” as set forth above, Wadsworth discloses that carrier screening of both parents can be performed at any time before or during pregnancy to determine the risk for a child conceived to be affected with recessive or x-linked genetic conditions (table 1 on page 2), such as OTC deficiency (Wilnai: abstract). Given that carrier screening is indicated in both parents to determine the risk of their child inheriting an x-linked genetic condition, and that genetically, one parent must be male and one parent must be female, it is considered that the two subjects of the method of instant claim 56 must be male and female, as instantly claimed. Thus, it is considered that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, Singh, and Wadsworth collectively disclose the subject matter of claim 79.
With regard to claim 80, which recites “when the subject [of the method of claim 79] is female, the subject is pregnant,” as set forth above, Wadsworth discloses that carrier screening of both parents can be performed at any time before or during pregnancy to determine the risk for a child conceived to be affected with recessive or x-linked genetic conditions (table 1 on page 2), such as OTC deficiency (Wilnai: abstract). Given that carrier screening is indicated at any time before or during pregnancy, it is considered that such screening is indicated in pregnant female subjects, as instantly claimed. Thus, it is considered that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, Singh, and Wadsworth collectively disclose the subject matter of claim 80.
Given that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh collectively disclose a method of preparing a personalized yeast model for determining a subject at risk of a disease as recited at instant claim 55, wherein Sun explicitly discloses that human-yeast gene complementation testing is well-suited to carrier screening and pre-implantation embryonic screening, and that Wadsworth discloses that carrier screening can be performed in one or both parents at any time before or during pregnancy in order to determine risk for a child conceived to be affected with x-linked genetic conditions (such as OTC deficiency, as disclosed in Wilnai), it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method collectively disclosed by Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh to perform carrier screening in both parents, before or during pregnancy, to predictably determine the risk of a child conceived by said couple being affected with an x-linked genetic condition such as OTC deficiency. One would have been motivated to make such a modification in order to receive the expected benefit of precisely and specifically identifying disease risk via carrier screening performed with human-yeast gene complementation (as disclosed in Sun).
Claims 57 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022; of record) in view of Sun et al., 2016 (hereinafter Sun; of record), Liu et al., 2017 (hereinafter Liu; of record), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025; of record), and Wilnai et al., 2018 (hereinafter Wilnai; of record), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas; of record), Paulson, 2017 (hereinafter Paulson; of record), and Singh, 2013 (hereinafter Singh; of record) as applied to claim 55 above, and further in view of Wadsworth Center Prenatal Genetics Referrals, 2019 (hereinafter Wadsworth; of record) and Trevisson et al., 2009 (hereinafter Trevisson; as cited in the IDS filed 11/04/2022; of record).
The combined disclosures of Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh are described above and applied as before. However, these disclosures do not teach the cell mating of instant claim 57 or the media of instant claim 58.
With regard to amended claim 57, which recites “the method of claim 55 further compris[es] obtaining a second genomic DNA from a second subject and identifying a second gene(s) of interest encoding OTC in up to two alleles from the genomic DNA, inserting at least one of the second gene(s) of interest encoding OTC into a second construct, introducing the second construct into a second test cell, and mating the second cell with the test cell to produce a progeny cell,” as set forth above regarding instant claim 56, Wadsworth discloses that carrier screening can be performed at any time before or during pregnancy, wherein genetic testing is performed in one or both parents in order to determine risk for a child conceived to be affected with x-linked genetic conditions (table 1 on page 2), such as OTC deficiency (Wilnai: abstract). Given that Sun discloses that human-yeast complementation assays are highly accurate and particularly useful for carrier screening (abstract; page 670, column 1, paragraph 1), it is considered that it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the claimed invention to utilize the method collectively disclosed by Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh to perform carrier screening in both parents (i.e. two subjects), before or during pregnancy, to predictably determine the risk of a child conceived by said couple being affected with an x-linked genetic condition such as OTC deficiency, as set forth in greater detail above regarding instant claim 70. However, the cited art set forth above is silent as to the production of a progeny cell by mating two test cells.
This deficiency is cured by Trevisson. Trevisson discloses yeast-based functional complementation assays to assess the pathogenicity of mutations in argininosuccinate lyase (ASL) that cause argininosuccinic aciduria, which is a urea cycle defect (abstract). It is noted that OTC deficiency is also a urea cycle defect (Wilnai: abstract) and that Trevisson discloses that the methods taught therein may be easily adapted for the analysis of mutations in other genes involved in urea cycle disorders (abstract). The methods of Trevisson 2009 producing transformant yeast by transforming haploid yeast cells lacking the yeast homolog of the human ASL gene with constructs comprising human and yeast ASL or ARG4 sequences and monitoring the ability of cells to grow on media lacking arginine (page 28928, column 1, paragraphs 2 and 3). Furthermore, Trevisson further discloses mating said transformants to produce diploid, “compound heterozygous” yeast to monitor their growth on media lacking arginine as a readout for intragenic complementation (abstract; page 28928, column 2, paragraphs 3 and 4; Figures 4 and 5). Thus, it is considered that Trevisson discloses each and every additional limitation of instant claim 57 not addressed above.
With regard to amended claim 58, which recites “the method of claim 57 further compris[es] evaluating the progeny cell for cell growth in a media, wherein the media lacks arginine, wherein the test cell growth is compared to a control cell that has the homologous gene, wherein when progeny cell growth is comparable to that of the control cell[,] it indicates that the gene encodes a functional OTC protein, and wherein when the progeny cell growth is slow as compared to the control cell[,] it indicates that the gene encodes a non-functional OTC protein or OTC protein with decreased function and indicates the disease,” as set forth above, Trevisson discloses mating yeast transformants and monitoring their growth on media lacking arginine, wherein growth on media lacking arginine is indicative of functional complementation (page 28928, column 2, paragraph 1; page 28928, column 2, paragraph 3). Furthermore, Wilnai discloses that administration of arginine to subjects with OTC deficiency is therapeutic, as the biochemical hallmarks of OTCD include low levels of arginine, the administration of which activates alternative pathways of nitrogen elimination (abstract; page 298, column 1, paragraphs 1 and 3). Thus, one of ordinary skill in the art would reasonably expect that media lacking arginine would not be able to rescue the growth of cells modeling OTC deficiency. Accordingly, it is considered that Trevisson, in view of Wilnai, discloses each and every additional limitation of instant claim 58.
Given that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh collectively disclose a method of preparing a personalized yeast model for determining a subject at risk of a disease as recited at instant claim 55, that Wilnai specifically discloses that OTC deficiency is a urea cycle defect that can be treated (in part) by administering arginine to compensate for low levels of arginine in affected subjects and activate alternative pathways of nitrogen elimination, and that Trevisson discloses production of diploid, “compound heterozygous” yeast to assay growth on media lacking arginine as a readout for intragenic complementation of another gene implicated in a urea cycle defect, wherein lack of growth of test cells as compared to control cells indicates the disease state and retention of growth of test cells as compared to control cells indicates lack of the disease state, it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the claimed invention to mate the haploid yeast produced from subjects 1 and 2 (i.e. the parents) using the method collectively disclosed by Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh to generate a diploid, “compound heterozygous” yeast to assay growth on media lacking arginine as a readout for intragenic complementation (as in Trevisson) to predictably detect intragenic complementation, wherein growth on media lacking arginine is indicative of functional complementation (as disclosed in Trevisson). One would have been motivated to make such a modification in order to receive the expected benefit of precisely and specifically identifying disease risk of a child produced by subjects 1 and 2 (i.e. the parents) via screening performed with human-yeast gene complementation (as disclosed in Sun).
Claims 75, 76, and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Hamza et al., 2015 (hereinafter Hamza; as cited in the IDS filed 11/04/2022; of record) in view of Sun et al., 2016 (hereinafter Sun; of record), Liu et al., 2017 (hereinafter Liu; of record), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025; of record), and Wilnai et al., 2018 (hereinafter Wilnai; of record), as evidenced by Bukaveckas et al., 2004 (hereinafter Bukaveckas; of record), Paulson, 2017 (hereinafter Paulson; of record), and Singh, 2013 (hereinafter Singh; of record) as applied to claim 55 above, and further in view of Magesh and Doss, 2014 (hereinafter Magesh; of record).
The combined disclosures of Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh are described above and applied as before. However, these disclosures do not teach the single-nucleotide polymorphism of instant claims 75 and 76 or the specific OTC mutation of instant claim 78.
With regard to claim 75, which recites “the gene [of the method of claim 55] is further analyzed for a single-nucleotide polymorphism,” as set forth above, it is considered that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh collectively disclose the method of instant claim 55. Additionally, Kingsmore discloses that single-nucleotide polymorphisms (SNPs) are useful in calling variants during sequencing (paragraph [0036]) and can in fact indicate known disease variants (paragraph [0127]). Furthermore, Magesh discloses that the variants of the OTC gene are known to comprise mutations that are deleterious SNPs causing OTC deficiency (abstract). Thus, it is considered that Kingsmore and Magesh disclose each and every additional limitation of instant claim 75.
With regard to claim 76, which recites “the single-nucleotide polymorphism [of the method of claim 75] is identified as being associated with loss of function or decreased function of OTC protein encoded by the gene,” as set forth above, Magesh discloses that the variants of the OTC gene are known to comprise mutations that are deleterious SNPs causing OTC deficiency (abstract). Thus, it is considered that Magesh discloses each and every additional limitation of instant claim 76.
With regard to amended claim 78, which recites “the gene [of the method of claim 55] encodes OTC with an amino acid mutation otc-R141Q,” as set forth above, Magesh discloses that the variants of the OTC gene are known to comprise mutations that are deleterious SNPs causing OTC deficiency (abstract). One such disease-causing SNP is disclosed to be the R141Q mutation, in which Q (glutamine) is substituted for R (arginine), thereby altering OTC protein structure and decreasing its stability (Tables 1, 2, and 5). Thus, it is considered that Magesh discloses each and every additional limitation of instant claim 78.
Given that Hamza, Sun, Liu, Kingsmore, Wilnai, Bukaveckas, Paulson, and Singh collectively disclose a method of preparing a personalized yeast model for determining a subject at risk of a disease as recited at instant claim 55, that Kingsmore explicitly discloses detecting SNPs as part of a workflow for diagnosing genetic diseases, and that Magesh discloses that the R141Q mutation in the OTC gene is a disease-causing SNP that alters OTC protein structure and decreases its stability, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to further analyze the OTC gene of the subject of the method of claim 55 to predictably determine whether said OTC gene comprises disease-causing SNPs such as the R141Q mutation. One would have been motivated to make such a modification in order to receive the expected benefit of assessing the queried subject for deleterious SNPs such as the R141Q mutation in the OTC gene.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 55, 70-72, and 75-78, and 80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 7, 8, and 11-13 of copending Application No. 17/047,667 (corresponds to US 2021/0155971 A1; as cited in the IDS filed 11/04/2022; of record) in view of Sun et al., 2016 (hereinafter Sun; of record), Wilnai et al., 2018 (hereinafter Wilnai; of record), US 2017/00617070 A1 (hereinafter Kingsmore; as cited in the IDS filed 11/04/2025; of record), and Magesh and Doss, 2014 (hereinafter Magesh; of record).
Copending claim 1 recites a method of screening a subject for a disease associated with an amino acid deficiency, said method comprising obtaining genomic DNA from the subject, identifying a gene of interest from the genomic DNA (wherein the subject is determined to have a variant of the gene of interest), inserting the variant of the gene of interest into a linear DNA construct that is introduced into a test cell (limited to a yeast cell at copending claim 3) wherein the homologous gene of the variant gene of interest has been knocked out of the test cell, and evaluating the test cell for cell growth via a yeast cell assay in a media lacking an amino acid. Copending claim 1 further recites that when test cell growth is lower than that of a control cell (limited to a yeast cell at copending claim 3) comprising the homologous gene knocked out in the test cell, it is indicative that the gene variant encodes a non-functional protein or protein with decreased function. Copending claim 1 further recites that the quantified growth of the test cell is compared with quantified growth information recorded in a look-up table of other variants, thereby identifying the subject as having the disease when quantified growth of the test cell with the variant in the yeast cell assay is comparable to or lower than the predicted threshold. Copending claim 1 further limits the gene of interest assessed via the method of copending claim 1 to a gene encoding PSAT.
The limitations recited at copending claims 1 and 3 collectively read on each and every limitation recited at instant claim 55, with the exception of the gene of interest being OTC (and the associated disease being OTC deficiency), generating data for a look-up table, generating personalized disease amelioration recommendations, and presenting said recommendations to the subject. However, these deficiencies are cured by various secondary references. Wilnai discloses that mutations in the OTC gene cause OTC deficiency, which is a severe X-linked condition that can be diagnosed prenatally and presents particularly severely in hemizygous males (abstract; page 297, column 2, paragraph 1; page 298, column 1, paragraph 2). Per Wilnai, a prenatal diagnosis of urea cycle defects such as OTC deficiency is essential to initiating appropriate therapy as soon as possible to offer a better outcome (page 299, column 1, paragraphs 5-6). Thus, while copending claim 6 limits the gene of interest to a gene encoding 3-PGDH, PSAT1, or PSPH, the disclosure of Wilnai motivates utilizing the same method for assaying the OTC gene to diagnose OTC deficiency, as in instant claim 55.
Additionally, Sun discloses that data obtained from human-yeast complementation assays may be used to generate a look-up table of human disease variants before they have even been observed in the clinic (page 676, column 2, paragraph 4). Furthermore, Kingsmore discloses that all patients provided informed written consent for participating in diagnosis and treatment of genetic disease (paragraphs [0053] and [0056]). Thus, it is considered that Kingsmore discloses that for purposes of diagnosing and treating a genetic disease, the data obtained from testing for such diseases (i.e. by the methods of the instant and copending applications) may be used to inform patients of treatment options for their specific genetic disease.
Copending claim 2 limits the subject to be screened by the method of claim 1 to a fetus, a neonate, juvenile, or adult, while copending claim 5 limits the subject to be screened by the method of claim 1 to a pregnant person.
The limitations recited at copending claims 2 and 5 are not patentably distinct from the limitations recited at instant claims 70 and 80, which respectively recite that the claimed method is used to determine prenatal risk of disease, and that the tested subject is a pregnant female. Regarding the claimed determination of prenatal risk of disease, assessing a fetus via the methods of the instant and copending applications would necessarily have the effect of determining prenatal risk of disease. Additionally, a subject that is a pregnant adult reads on all limitations of copending claims 2 and 5, as well as of instant claim 80.
Copending claim 7 recites that measuring the area of the spot of the test cell growing on solid media comprises determining a number of pixels of the area, which is identical to the limitations recited at instant claim 71 regarding measurement of growth on solid media.
Copending claim 8 recites that evaluation of cell growth comprises measuring cell growth for 0.5, 2, 4, 6, 8, 10, 12, 24, 36, 72, 96, or 120 hours or any number of hours in between a range defined by any two of the aforementioned values, which is identical to the limitations recited at instant claim 72.
Copending claims 11 and 12 recite that the variant of the gene of interest of the method claimed therein is further analyzed for a single-nucleotide polymorphism, said single-nucleotide polymorphism being limited to being associated with the non-functional protein or protein with decreased function. These limitations are identical to the limitations recited at instant claims 75 and 76, with the exception of the gene of interest of the instant application (OTC). However, as set forth above, Wilnai motivates utilizing the methods of both the instant and copending applications for assaying the OTC gene to diagnose OTC deficiency. Additionally, Magesh discloses that the variants of the OTC gene are known to comprise mutations that are deleterious SNPs causing OTC deficiency (abstract). One such disease-causing SNP is disclosed to be the R141Q mutation, in which Q (glutamine) is substituted for R (arginine), thereby altering OTC protein structure and decreasing its stability (Tables 1, 2, and 5). This mutation is recited at instant claim 78.
Copending claim 13 recites that quantified growth of the test cell and of the control cell is compared using a t-test, wherein a t-test with a p-value of < 0.0001 indicates a significant growth difference between the quantified growth of the test cell and of the control cell, which is identical to the limitations recited at instant claim 77.
Thus, the copending application discloses a method of assessing gene variants of a gene of interest in subjects such as fetuses and pregnant subjects using yeast cells, wherein the methodology of the copending application reads on each and every limitation of the instantly claimed methodology, with the exception of the queried gene of interest, the generation of a look-up table, and informing the subject of their personalized treatment plan, all of which are addressed by various secondary references, as set forth above. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to select OTC as the gene of interest (as motivated by Wilnai) to be assessed for variants and incorporated into a genetic variant look-up table (as disclosed in Sun) in order to inform patients of treatment options for their specific genetic disease (as disclosed in Kingsmore) to predictably detect and assess variant OTC sequences and provide appropriate treatment as early as possible (as disclosed in Wilnai and set forth above). One would have been motivated to make such a modification in order to receive the expected benefit of detecting and assessing variant OTC sequences and providing appropriate treatment as early as possible.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAH E ALLEN/ Examiner, Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637
Prosecution Insights