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 .
Status of Claims
This action is in reply to the application filed on 16 July 2025.
Claims 1-15 are currently pending and have been examined.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 12/01/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The drawings are objected to because Figures 2, 4, and 21 are improper as they are blurry or contain fuzzy photographs 37 CFR 1.84(b)(1)) and because the text is not legible (37 CFR 1.84(l)), but the concepts could practicably be depicted in a line drawing (37 CFR 1.84(b)(1)). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Step 1
The claim(s) recite(s) subject matter within a statutory category as a process (claims 1-15).
INDEPENDENT CLAIMS
Step 2A Prong 1
Claim 1 recites steps of
a) Obtaining genetic instruments for therapeutic targets of the drug;
b) Identifying genes (or alleles, or variants thereof) associated with the genetic instruments obtained from step a);
c) Obtaining effect sizes of genetic instruments for targets associated with the unrelated disease;
d) Identifying genes (or alleles, or variants thereof) associated with the genetic instruments obtained from step c);
e) Harmonising the genes obtained from step b) and the genes identified from step d);
f) Identifying overlapping genes in the harmonised genes obtained in step e); and
g) Performing two-sample Mendelian randomization using the overlapping genes identified in step e), wherein the results obtained from the two-sample Mendelian randomization identify the causal relationship, if present;
wherein the drug is a specific drug of a group of structurally or functionally related drugs.
These steps for identifying a causal relationship, as drafted, under the broadest reasonable interpretation, includes performance of the limitations in the mind. That is, nothing in the claim element precludes the italicized portions from practically being performed in the mind through the evaluation and determination of a causal relationship between a drug and an unrelated disease. This could be analogized to collecting information, analyzing it, and displaying certain results of the collection and analysis. Additionally, the claimed steps map out a methodology that mirrors cognitive steps a geneticist or bioinformatician perform to conduct drug target Mendelian randomization (MR). If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitations in the mind but for the recitation of generic computer components, then it falls within the “Mental Process” grouping of abstract ideas. Accordingly, the claim recites an abstract idea.
Step 2A Prong 2
This judicial exception is not integrated into a practical application. In particular, the additional elements, non-italicized portions identified above for claim 1, do not integrate the abstract idea into a practical application, other than the abstract idea per se, because the additional elements amount to no more than limitations which:
add insignificant extra-solution activity to the abstract idea (such as recitation of Obtaining genetic instruments for therapeutic targets of the drug; and, Obtaining effect sizes of genetic instruments for targets associated with the unrelated disease amounts to mere data gathering since it does not add meaningful limitations to the obtaining actions performed, see MPEP 2106.05(g))
Each of the above additional elements therefore only amounts to add insignificant extra-solution activity to the abstract idea. There is no indication that the combination of elements improves the functioning of a computer or improves any other technology. These elements are therefore not sufficient to integrate the abstract idea into a practical application. Therefore, the above claims, as a whole, are directed to an abstract idea.
Step 2B
The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to discussion of integration of the abstract idea into a practical application, the additional elements amount to no more than add insignificant extra-solution activity to the abstract idea. Additionally, the additional limitations, other than the abstract idea per se, amount to no more than limitations which:
amount to elements that have been recognized as well-understood, routine, and conventional activity in particular fields such as recitation of Obtaining genetic instruments for therapeutic targets of the drug; and, Obtaining effect sizes of genetic instruments for targets associated with the unrelated disease, e.g., receiving or transmitting data over a network, Symantec, MPEP 2106.05(d)(II)(i).
Looking at the limitations as an ordered combination adds nothing that is not already present when looking at the elements taken individually. There is no indication that the combination of elements improves the functioning of a computer or improves any other technology. Their collective functions merely provide generic computer implementation.
DEPENDENT CLAIMS
Step 2A Prong 1
Dependent claims recite additional subject matter which further narrows or defines the abstract idea embodied in the claims (such as claims 2-15 reciting particular aspects for identifying a causal relationship such as
[Claim 2] wherein the genetic instruments from step a) are obtained using at least two different methods;
[Claim 3] wherein genetic instruments shown to be statistically significant in both of the at least two different methods are selected;
[Claim 4] wherein the method further comprises a step of validating the genetic instruments;
[Claim 5] wherein the at least two different methods are GTEx instruments and GWAS instruments;
[Claim 6] wherein the genetic instruments of step a) are selected from the group consisting of single nucleotide polymorphisms (SNPs), gene expression, and protein expression;
[Claim 7] wherein the genetic instruments have a weak linkage disequilibrium with each other;
[Claim 8] wherein the therapeutic target of the drug of step a) is a drug target gene or a protein affected by the drug;
[Claim 9] wherein the drug target gene is identified using protein-protein-interaction (PPI)-based gene identification;
[Claim 10] wherein the target associated with the unrelated disease is selected from the group consisting of a gene, a protein, a mutant gene, a mutant protein, a dysregulated gene, or a dysregulated a protein;
[Claim 11] wherein the genetic instruments of step c) are obtained from a database selected from the group consisting of the GWAS Catalogue, Integrative Epidemiology Unit (IEU) Open GWAS, FinnGen Consortium, the Breast Cancer Association Consortium, and combinations thereof;
[Claim 12] wherein the harmonisation of step e) comprises aligning the direction of alleles identified in step b) with an exposure dataset and aligning the direction of alleles identified in step d) with an outcome dataset;
[Claim 13] wherein the genetic instruments of step a) are obtained from DrugBank;
[Claim 14] wherein the method further comprises a step of validating the results obtained in step g);
[Claim 15] wherein the step of validation is selected from the group consisting of in vitro assays, in vivo assays, and in silico assays;
these italicized portions covers performance of the limitations in the mind. These identified limitations merely describe types of data and determinations that can be performed by humans.
Step 2A Prong 2
Dependent claim 2 recites additional subject matter which amount to limitations consistent with the additional elements in the independent claims (the additional limitations add insignificant extra-solution activity to the abstract idea (such as recitation of claim 2 (wherein the genetic instruments from step a) are obtained using at least two different methods) amounts to mere data gathering since it does not add meaningful limitations to the acquiring action performed, see MPEP 2106.05(g)). Accordingly, these additional elements do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea.
Step 2B
Dependent claim 2 recites additional subject matter which amount to elements that have been recognized as well-understood, routine, and conventional activity in particular fields such as recitation of receiving the reference image set amounts; e.g., receiving or transmitting data over a network, Symantec, MPEP 2106.05(d)(II)(i). There is no indication that these additional elements improve the functioning of a computer or improves any other technology. Their collective functions merely provide generic computer implementation.
Therefore, in consideration of all the facts, the present invention is not a patent-eligible invention under USC 101. Additionally, it is evident that the present claims monopolize the scientific method of discovering how specific drugs interact with unrelated diseases, restricting further innovation in this area without offering a specific, technical improvement to how the computer actually operates; “monopolization of those tools through the grant of a patent might tend to impede innovation more than it would tend to promote it.” Alice Corp., 573 U.S. at 216, 110 USPQ2d at 1980 (quoting Myriad, 569 U.S. at 589, 106 USPQ2d at 1978 and Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012)).
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148
USPQ 459 (1966), that are applied 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.
Claims 1-4, 6-8, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Reid et al. (US20170286594A1) in view of Sheng et al. (Evaluating the Causal Effects of Gestational Diabetes Mellitus, Heart Disease, and High Body Mass Index on Maternal Alzheimer’s Disease and Dementia: Multivariable Mendelian Randomization).
Regarding claim 1, Reid discloses a) Obtaining genetic instruments for therapeutic targets of the drug ([0103] “In one aspect, the genetic variant data are obtained from genomic sequencing of the subjects for whom genetic variant and phenotype data are contained in the system.”)
b) Identifying genes (or alleles, or variants thereof) associated with the genetic instruments obtained from step a) ([0159] “Allelic association tests examine the association between one allele of the variant and the phenotype”)
c) Obtaining effect sizes of genetic instruments for targets associated with the unrelated disease ([0418] “In case/control analyses, heterozygosity for PI*Z was associated with alcoholic and non-alcoholic liver disease (odds ratio [OR] 2.41, p=0.001; OR 1.24, p=0.04, respectively), COPD (OR 1.27, p=0.008), and emphysema (OR 1.41, p=0.02).”)
d) Identifying genes (or alleles, or variants thereof) associated with the genetic instruments obtained from step c) ([0157] “For example, the effect size of a statistical association can be measured as the ratio of the odds of the presence of the phenotype(s) of interest in subjects who have 1 or 2 copies of the variant allele of interest”)
f) Identifying overlapping genes in the harmonised genes obtained in step e) ([0185] “The user can be provided a total number of carriers having duplications, deletions, or any CNVs overlapping the query gene, followed by a table listing all super-loci that overlap the query gene. […] a list of genes overlapping the locus (including the query gene)”)
wherein the drug is a specific drug of a group of structurally or functionally related drugs ([0328] “a set of 11 genes whose products are the targets of lipid lowering drugs”)
Reid does not explicitly disclose however Sheng teaches e) Harmonising the genes obtained from step b) and the genes identified from step d ([pg. 4] “After extracting the data, 52 SNPs met the requirements and were incorporated into the subsequent harmonizing procedure to complete the two-sample MR analysis”)
and g) Performing two-sample Mendelian randomization using the overlapping genes identified in step e), wherein the results obtained from the two-sample Mendelian randomization identify the causal relationship, if present ([pg. 4] “First, we used two-sample MR analysis to assess the significance level of the causal effect of each exposure factor”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid e) Harmonising the genes obtained from step b) and the genes identified from step d; and, g) Performing two-sample Mendelian randomization using the overlapping genes identified in step e), wherein the results obtained from the two-sample Mendelian randomization identify the causal relationship, if present as taught by Sheng since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Regarding claim 2, Reid discloses wherein the genetic instruments from step a) are obtained using at least two different methods ([0103] “In one aspect, the genetic variant data are obtained from genomic sequencing of the subjects for whom genetic variant and phenotype data are contained in the system. In another aspect, the genetic variant data are obtained from exome (for example, whole exome) sequencing of the subjects for whom genetic variant and phenotype data are contained in the system.”)
Regarding claim 3, Reid discloses wherein genetic instruments shown to be statistically significant in both of the at least two different methods are selected ([0166] “The data analysis component 208 can generate and store a visualization, for example, a Manhattan plot, that shows variants along the x-axis and significance along the y-axis.” [0210] “In another embodiment, the PHEHATTAN style plot is a dynamic plot. A PHEHATTAN style Plot depicts the significance of the association between a gene or a genetic variant and a one or more phenotypes.”)
Regarding claim 4, Reid discloses wherein the method further comprises a step of validating the genetic instruments ([0220] “The results interface 308 enables a user to validate data that may not seem to fit. As the results interface 308 operates on computed results, the need for R-scripts and flat files is avoided.”)
Regarding claim 6, Reid discloses wherein the genetic instruments of step a) are selected from the group consisting of single nucleotide polymorphisms (SNPs), gene expression, and protein expression ([0136] “The variant identification component 210 can identify (e.g., call) one or more variants […] The sequence itself may or may not contain SNP”)
Regarding claim 7, Reid does not explicitly disclose however Sheng teaches wherein the genetic instruments have a weak linkage disequilibrium with each other ([pg. 4] “no linkage disequilibrium (LD) with other SNPs to ensure that we obtained genetically independent SNPs (Lawlor et al., 2008).”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid the genetic instruments have a weak linkage disequilibrium with each other as taught by Sheng since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Regarding claim 8, Reid discloses wherein the therapeutic target of the drug of step a) is a drug target gene or a protein affected by the drug ([0315] “Genetic variants in human populations may illuminate new therapeutic targets.” [0316] “Of these drug target genes, 6/9 harbored pLoF variants that were at least nominally associated with lipid phenotypes recapitulating clinical effects of the therapeutic agent.”)
Regarding claim 10, Reid discloses wherein the target associated with the unrelated disease is selected from the group consisting of a gene, a protein, a mutant gene, a mutant protein, a dysregulated gene, or a dysregulated a protein ([0181] “Among currently approved therapeutics […] PCSK9 (n=49 heterozygotes), which encodes the target of alirocumab, evolocumab, and bococizumab and reduced LDL-C levels”)
Regarding claim 11, Reid does not explicitly disclose however Sheng teaches wherein the genetic instruments of step c) are obtained from a database selected from the group consisting of the GWAS Catalogue, Integrative Epidemiology Unit (IEU) Open GWAS, FinnGen Consortium, the Breast Cancer Association Consortium, and combinations thereof ([pg. 4] “We identified SNPs strongly related (p < 5e−8) to a high BMI (BMI≥ 30kg/m2) from GWAS data of European ancestry that were published in 2015 (Locke et al., 2015) and screened these SNPs using a moderate linkage disequilibrium (LD) criterion (r2 = 0.05, kb = 1000).”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid the genetic instruments of step c) are obtained from a database selected from the group consisting of the GWAS Catalogue, Integrative Epidemiology Unit (IEU) Open GWAS, FinnGen Consortium, the Breast Cancer Association Consortium, and combinations thereof as taught by Sheng since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Regarding claim 12, Reid does not explicitly disclose however Sheng teaches wherein the harmonisation of step e) comprises aligning the direction of alleles identified in step b) with an exposure dataset and aligning the direction of alleles identified in step d) with an outcome dataset ([pg. 5] “First, we identified two SNPs strongly associated with GDM (p = 5e−8, Supplementary Data S1), and the maternal AD/dementia-related information was independently extracted (r2 = 0.05, kb = 1000, Supplementary Data S2). By harmonizing these SNPs, we could calculate their causal effects on GDM and maternal dementia.”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid the harmonisation of step e) comprises aligning the direction of alleles identified in step b) with an exposure dataset and aligning the direction of alleles identified in step d) with an outcome dataset as taught by Sheng since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Claims 5 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Reid et al. (US20170286594A1) in view of Sheng et al. (Evaluating the Causal Effects of Gestational Diabetes Mellitus, Heart Disease, and High Body Mass Index on Maternal Alzheimer’s Disease and Dementia: Multivariable Mendelian Randomization) and further in view of He et al. (Non-steroidal anti-inflammatory drug target gene associations with major depressive disorders: a Mendelian randomisation study integrating GWAS, eQTL and mQTL Data).
Regarding claim 5, Reid discloses wherein the at least two different methods are […] and GWAS instruments ([0209] “In one embodiment, the results interface 308 can display results from a GWAS statistical analysis.”)
Reid in view Sheng does not explicitly disclose however He teaches […] GTEx instruments […] ([pg. 97] “To explore the biological mechanisms of significant genes using analytical strategies, the GTEx Portal (https://gtexportal.org/home/) was used to identify target gene expression levels in 13 brain regions and whole blood samples.”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid and evaluating the causal effects system of Sheng GTEx instruments as taught by He since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Regarding claim 13, Reid in view Sheng does not explicitly disclose however He teaches wherein the genetic instruments of step a) are obtained from DrugBank ([pg. 96] “Genes whose protein products were targeted by any of NSAIDs active ingredients were identified using DrugBank.”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid and evaluating the causal effects system of Sheng the genetic instruments of step a) are obtained from DrugBank as taught by He since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Regarding claim 14, Reid in view Sheng does not explicitly disclose however He teaches wherein the method further comprises a step of validating the results obtained in step g) ([pg. 96] “We also used whole blood mQTL data from the UKHLS study (n=1193; European heritage) to validate our results.”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid and evaluating the causal effects system of Sheng a step of validating the results obtained in step g) as taught by He since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Regarding claim 15, Reid in view Sheng does not explicitly disclose however He teaches wherein the step of validation is selected from the group consisting of in vitro assays, in vivo assays, and in silico assays ([pg. 100] “Importantly, these NEU1 roles in macrophages are confirmed by several in vitro studies.”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid and evaluating the causal effects system of Sheng the step of validation is selected from the group consisting of in vitro assays, in vivo assays, and in silico assays as taught by He since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Reid et al. (US20170286594) in view of Sheng et al. (Evaluating the Causal Effects of Gestational Diabetes Mellitus, Heart Disease, and High Body Mass Index on Maternal Alzheimer’s Disease and Dementia: Multivariable Mendelian Randomization) and further in view of Safari-Alighiarloo et al. (Protein-protein interaction networks (PPI) and complex diseases).
Regarding claim 9, Reid in view Sheng does not explicitly disclose however Safari-Alighiarloo teaches wherein the drug target gene is identified using protein-protein-interaction (PPI)-based gene identification ([pg. 21-22] “It is noticeable that PPI networks can be used to explore the differences between healthy and diseased states (68, 69). […] Protein interaction studies play a major role in the prediction of genotype phenotype associations. Disease networks can improve drug design by determining key nodes as potential drug targets. If, for example, the target is a hub (a highly connected protein)”)
Therefore, it would have been obvious to one of ordinary still in the art to include in the genetic variant-phenotype analysis system of Reid and evaluating the causal effects system of Sheng the drug target gene is identified using protein-protein-interaction (PPI)-based gene identification as taught by Safari-Alighiarloo since the claimed invention is merely a combination of old elements, and in the combination each element merely would have performed the same function as it did separately, and one of ordinary skill in the art would have recognized that the results of the combination were predictable.
Prior Art Cited but Not Relied Upon
Pu, Y., Liu, J., Bennett, A. N., & Chan, K. H. K. (2025). Identifying Therapeutic Targets for Allergic Asthma through Atopic Dermatitis-Associated Genetic Mechanisms. Journal of Allergy and Clinical Immunology: Global, 100568.
This reference is relevant because is discloses the applicant’s claimed invention.
Conclusion
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/WINSTON R FURTADO/Primary Examiner, Art Unit 3687
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