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 filed 12/4/2025 has been fully considered. The following rejections
and/or objections are either reiterated or newly applied.
Status of Claims
Claims 9, 12-14, 19-23, 25-29, 31-32, and 34-48 canceled.
Claims 1-8, 10-11, 15-18 and 24 withdrawn.
Claims 49-56 newly added.
Claims 30, 33, and 49-56 pending and examined on the merits.
Priority
The instant application claims the benefit of priority to U.S. Provisional Application No. 62/843,095 filed on May 03, 2019. The instant application is a national stage entry of PCT/US2020/030998 filed on May 01, 2020. Thus, the effective filing date of the claims is May 03, 2019.
Withdrawn Rejections and Response to Arguments
35 USC § 112
The rejection of claims 30 and 33 under 35 USC 112(b) in the non-final action filed 6/4/2025 withdrawn in view of Applicant's claim amendments filed on 12/4/2025. Examiner notes there are newly added rejections under 35 USC 112(b) in view of Applicant's claim amendments filed on 12/4/2025.
35 USC § 101
Applicant asserts that claims 30 and 33 are no longer directed to non-statutory subject matter due to current amendments (Remarks 12/4/2025 Pages 1-2). Examiner notes the judicial exceptions and additional elements detailed in the below section "Claim Rejections - 35 USC 101" necessitated by Applicant's most recent claim amendments filed 12/4/2025. Therefore, the rejection of claims 30 and 33 under 35 USC 101 is maintained.
35 USC § 102
The rejection of claims 30 and 33 under 35 USC 102(a)(2) in view of Spurlock et al. (WO-2019071121) withdrawn in view of Applicant's claim amendments filed on 12/4/2025. However, a rejection of these claims under 35 USC 102(a)(2) is newly applied in view of Applicant's claim amendments filed on 12/4/2025 (see section "Claim Rejections - 35 USC § 102" below).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 30, 33, and 49-56 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 30 recites "A method for detecting one or a plurality of nucleic acid or protein biomarkers from different human chromosomes correlated with Alzheimer's disease or an Alzheimer's disease comorbidity susceptibility" in lines 1-3. It is not clear what "different human chromosomes" are correlated with AD, or AD comorbidity or susceptibility, or why different chromosomes are specifically called out in this limitation (is Applicant concerned with a biomarker from each human chromosome, or are they only looking for one biomarker per human chromosome, or does this not matter for their invention?). Additionally, it is not clear from the limitation what is considered an AD "comorbidity susceptibility". Are all possible comorbid medical conditions known, is any detected change in a single biomarker enough to identify AD and AD comorbidity? Likewise, is it know what makes an individual more susceptible to AD than another? What are the qualities of susceptibility? To further prosecution, the limitation is interpreted as "A method for detecting one or a plurality of nucleic acid or protein biomarkers associated with Alzheimer's disease".
Claim 30 also recites " reprogramming the one or the plurality of cell samples to produce one or a plurality of induced pluripotent stem cell samples" in lines 6-7. It is not clear what steps are being performed in order to produce iPSC samples, and the specification does not further illuminate the matter. Furthermore, the preceding procuring step is directed towards any cell type, and the disclosure does not provide a description for how to reprogram all cell types. Therefore, to further prosecution, the cell type for reprogramming is interpreted as encompassing claim 49 "the at least one cell sample reprogrammed to the induced pluripotent stem cell is a fibroblast derived from skin or blood cells from humans", and the method for reprogramming encompasses any cell reprogramming method available to one of ordinary skill in the art.
Claim 30 also recites "treating the one or the plurality of induced pluripotent stem cell samples to obtain one or more patient specific neural organoids" in lines 8-9. It is not clear what steps are being performed in order to treat the iPSCs to obtain a neural organoid, and the disclosure does not further specifically illuminate the matter beyond a superficial description in para.0058 and an incorporation by reference. Claims are required to particularly point out the invention, of which specific treatment steps are a part, e.g. variables in these protocols include growth factors, media, substrates, particular feeding schedules, proliferation time, etc.
Claim 30 also recites "using algorithmic techniques to detect changes in nucleic acid or protein biomarker expression" in lines 11-12. It is unclear, in several different ways, how changes are to be detected in biomarker expression. First, there is no assaying step, so it is not clear what kind of data is being received for applying to the "algorithmic techniques", or where that data may be derived. Second, there is no preceding step of procuring samples from different groups in order to be compared, as step (e) further goes on to claim comparing biomarker expression of the AD organoid to a non-AD organoid (i.e. if only one sample is being taken for generating expression data, there is nothing in the claim for it to be compared against). Third, the cell sample(s) collected in step (a) and processed through (d) are not patient that do or do not have AD, or a comorbidity, or a susceptibility; they are simple "human". Forth, there is no output of any results following application of the "algorithmic technique" (i.e. no significance calculation, true/false positive negative analysis, likelihood of AD or comorbidity susceptibility etc).
Claim 33 recites "the data analytic techniques" in line 1. There is insufficient antecedent basis for “the data analytic techniques”. To further prosecution, the limitation is interpreted as “the algorithmic techniques".
Regarding claims 50-52 and 55; claim 50 recites "the genes identified in Table 1, Table 2, Table 5, or Table 7", claim 51 recites "a plurality of biomarkers identified in Table 1, Table 2, Table 5 or Table 7 or variants thereof", claim 52 recites "one or a plurality of biomarkers comprising a nucleic acid encoding human genes identified in Table 1", and claim 55 recites "one or a plurality of Alzheimer's disease biomarkers as identified in Table 1 and Table 7". Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Additionally, there are only gene names in these tables. Gene names alone are not enough to particularly point out and distinctly claim a specific biomarker or set of biomarkers, as simply reciting a common name of a gene is not enough to describe all biomarkers one could generate from that gene. The tables do not describe a particular gene sequence, or particular variant, or particular protein sequence.
Claim 51 rejected as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends. Claim 51 recites "the measured biomarkers comprise a plurality of biomarkers identified in Table 1, Table 2, Table 5 or Table 7 or variants thereof", which does not further limit claim 50 because measuring the genes of the listed tables is required (although not explicitly claimed) for identifying the fibroblast derived skin or blood cells.
Claim 52 recites "a combination of biomarkers is detected, the combination comprising a nucleic acid encoding human A2M, APP variants, and one or a plurality of biomarkers comprising a nucleic acid encoding human genes identified in Table 1" in lines 1-3. It is not clear whether the APP variants being detected are also only nucleic acid encoding variants, or if they may also be protein variants. To further prosecution, the limitation is interpreted as "a combination of biomarkers is detected, the combination selected from a group consisting of nucleic acid encoding human A2M, any variant of nucleic acid encoding human APP, and one or a plurality of biomarkers comprising a nucleic acid encoding human gene identified in Table 1".
Claim 53 recites "the neural organoid biological sample" in line 1. There is insufficient antecedent basis for “the neural organoid biological sample”. To further prosecution, the limitation is interpreted as “the patient specific neural organoid biological sample".
Claim 53 also recites "the neural organoid biological sample is collected after about one hour up to about 12 weeks post inducement" in lines 1-2. It is not clear whether only a portion of the patient specific neural organoid is collected, or if the entire organoid is collected at each time point past inducement. To further prosecution, the limitation is interpreted as "a portion of the patient specific neural organoid biological sample is collected after about one hour up to about 12 weeks post inducement".
Claim 54 recites "the neural organoid sample" in line 1. There is insufficient antecedent basis for “the neural organoid sample”. To further prosecution, the limitation is interpreted as “the patient specific neural organoid biological sample".
Claim 55 recites "the neural organoid" in line 1. There is insufficient antecedent basis for “the neural organoid”. To further prosecution, the limitation is interpreted as “the patient specific neural organoid".
Claim 55 also recites "the neural organoid contains microglia, and one or a plurality of Alzheimer's disease biomarkers as identified in Table 1 and Table 7" in lines 1-2. It is not clear how microglia are being identified in the patient specific neural organoid as there are no details in the treatment step for differentiation, or any "microglia" specific gene list being compared against (i.e. are microglia an inherent quality of the differentiation?).
Claim 56 recites "the method is used to identify causes or accelerators of Alzheimer's disease, detect environmental factors that cause or exacerbate Alzheimer's disease, identify nutritional factors or supplements for treating Alzheimer's disease, or as predictive toxicology for factors including infectious agents, that cause or exacerbate Alzheimer's disease" in lines 1-4. It is not clear how any step in claim 30 is used to identify: causes of AD; accelerators of AD; detect environmental factors that cause AD; detect environmental factors that exacerbate AD; identify nutritional factors for treating AD; identify supplements for treating AD; predict any toxicology for factors that cause AD; predict any toxicology for infections agents that cause AD; predict toxicology for any factor that exacerbates AD; or predict toxicology for any infectious agent that exacerbates AD. Each of these intended uses of claim 30 require significantly different steps, information, processes, and analyses well beyond what is provided.
All other claims depend from independent claim 30, therefore are also rejected under 35 USC 112(b).
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.
Claims 51-52 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.
Claim 51 rejected as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends. Claim 51 recites "the measured biomarkers comprise a plurality of biomarkers identified in Table 1, Table 2, Table 5 or Table 7 or variants thereof", which does not further limit claim 50 because measuring the genes of the listed tables is required (although not explicitly claimed) for identifying the fibroblast derived skin or blood cells.
Claim 52 depends from claim 51, therefore is interpreted as depending from claim 50.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 30, 33, and 49-56 rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of a mental process, a mathematical concept, organizing human activity, or a law of nature or natural phenomenon without significantly more. In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 30: “using algorithmic techniques to detect changes in nucleic acid or protein biomarker expression” provides an evaluation (detecting changes in biomarker expression requires evaluation of expression data) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“the expression levels are compared to the same nucleic acid or protein biomarker expression from a patient specific neural organoid” provides a comparison (comparing expression levels between disease/control samples) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 52: “a combination of biomarkers is detected” provides an evaluation (detecting a combination of biomarkers requires evaluation of expression data) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 56: “the method is used to identify causes or accelerators of Alzheimer's disease, detect environmental factors that cause or exacerbate Alzheimer's disease, identify nutritional factors or supplements for treating Alzheimer's disease, or as predictive toxicology for factors including infectious agents, that cause or exacerbate Alzheimer's disease” provides an evaluation (identifying/detecting causes of disease requires evaluation of relevant data) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
These recitations are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or are mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. As such, claims 30, 33, and 49-56 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exceptions listed above are not integrated into a practical application because the claims do not recite an additional element or elements that reflects an improvement to technology. Specifically, the claims recite the following additional elements:
Claim 30: “a) procuring one or a plurality of cell samples from a human, comprising one or a plurality of cell types; b) reprogramming the one or the plurality of cell samples to produce one or a plurality of induced pluripotent stem cell samples; c) treating the one or the plurality of induced pluripotent stem cell samples to obtain one or more patient specific neural organoids; [and] d) collecting a biological sample from the patient specific neural organoid” provides insignificant extra-solution activities (procuring, reprogramming, treating, and collecting cell samples is a pre-solution activity involving sample gathering and manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 53: “the neural organoid biological sample is collected after about one hour up to about 12 weeks post inducement” provides insignificant extra-solution activities (collecting a sample after a certain period of time is a pre-solution activity involving sample gathering and manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 54: “the neural organoid sample is procured from structures of the neural organoid that mimic structures developed in utero at about 5 weeks” provides insignificant extra-solution activities (collecting a sample from specific locations is a pre-solution activity involving sample gathering and manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
The steps for procuring, reprogramming, treating, and collecting cell samples are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application because they are pre- and post-solution activities involving sample gathering and manipulation steps (see MPEP 2106.04(d)(2)). Therefore, claims 30, 33, and 49-56 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application, or equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. The limitations for procuring, reprogramming, treating, and collecting cell samples are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application. Furthermore, no inventive concept is claimed by these limitations as they are well-understood, routine, and conventional. Specifically, beyond the obviously conventional steps of procuring and collecting samples, the steps of reprogramming and treating cells are well-understood, routine, and conventional as evidenced by Zhao and Patel: page 1 col 1 paragraph 1 "Although tremendous effort has been put into deriving such immune compatible cells, success was limited until very recently when induced pluripotent stem (iPS) cells were obtained by transducing embryonic and adult fibroblasts with defined transcription factors [Takahashi and Yamanaka, 2006]. In this review, we will summarize the landmark discoveries of iPS cell derivation, then discuss the potential problems and challenges faced by this field. Finally, we will provide an overview of the mechanisms that maintain pluripotency and discuss the potential mechanisms of reprogramming" (Zhao et al., "From fibroblasts to iPS cells: induced pluripotency by defined factors." Journal of cellular biochemistry 105.4 (2008): 949-955); and Page 6 col 2 last paragraph "Transcription factors Oct4, Sox2, c-myc and klf4 have been routinely used to reprogram fibroblasts. These factors are sufficient to convert fibroblasts to iPS cells which have similar characteristics to ES cells" (Patel et al., "Advances in reprogramming somatic cells to induced pluripotent stem cells." Stem Cell Reviews and Reports 6.3 (2010): 367-380).
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 30, 33, and 49-56 are not patent eligible.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 30, 33, and 49-56 rejected under 35 U.S.C. 102(a)(2) as being anticipated by Quadrato et al. (WO-2017117547).
Regarding claim 30, Quadrato teaches a method for detecting one or a plurality of nucleic acid or protein biomarkers from different human chromosomes correlated with Alzheimer's disease or an Alzheimer's disease comorbidity susceptibility (Page 27 line 18 "As used herein, "neuro disorder" or "neuro disease" refer to neurodegenerative disorders, neuropsychiatric disorders and/or neurodevelopmental disorders. "Neuro disease" also refers to neurological, neuropsychological, neuropsychiatric, neurodegenerative, or neuropsychopharmacological diseases. Neuro disorders may be any disease affecting neuronal network connectivity, synaptic function and activity. "Neurodegenerative disorder" refers to a disease condition involving neural loss mediated or characterized at least partially by at least one of deterioration of neural stem cells and/or progenitor cells. Non-limiting examples of neurodegenerative disorders include" and page 40 line 33 "the method can include detecting the positive expression ( e.g. the presence) of a marker for neural tissue or cells. In some embodiments, the marker can be detected using a reagent. A reagent for a marker can be, for example, an antibody against the marker or primers for a RTPCR or PCR reaction, e.g., a semi-quantitative or quantitative RT-PCR or PCR Reaction").
Quadrato also teaches procuring one or a plurality of cell samples from a human, comprising one or a plurality of cell types (Page 29 line 8 "The term "tissue" refers to a group or layer of specialized cells which together perform certain special functions. The term "tissue-specific" refers to a source of cells from a specific tissue").
Quadrato also teaches reprogramming the one or the plurality of cell samples to produce one or a plurality of induced pluripotent stem cell samples (Page 13 line 3 "Reprogrammed pluripotent cells (e.g., IPS cells as that term is defined herein) also have the characteristic of the capacity of extended passaging without loss of growth potential, relative to primary cell parents, which generally have capacity for only a limited number of divisions in culture" and page 33 line 32 "The stem cells may be themselves (for example, without substantially any undifferentiated cells being present) or may be used in the presence of differentiated cells. In certain examples, the stem cells may be cultured in the presence of suitable nutrients and optionally other cells such that the stem cells can grow and optionally differentiate").
Quadrato also teaches treating the one or the plurality of induced pluripotent stem cell samples to obtain one or more patient specific neural organoids; and collecting a biological sample from the patient specific neural organoid (Page 3 line 22 "The invention also provides methods for screening of molecular, cellular and network-level defects associated with diseases, including complex mental diseases, through use of patient-derived induced pluripotent stem cells. Brain organoids generated from patient cells can be screened for defects in cellular composition, as well as for spontaneous network activity").
Quadrato also teaches using algorithmic techniques to detect changes in nucleic acid or protein biomarker expression from one or more human chromosomes, of the patient specific neural organoid from a patient having Alzheimer's disease or an Alzheimer's disease comorbidity susceptibility: wherein the expression levels are compared to the same nucleic acid or protein biomarker expression from a patient specific neural organoid, from a patient that does not have Alzheimer's disease or an Alzheimer's disease comorbidity (Page 72 line 24 Drop-seq single cell sequencing Section "A first round of clustering with the Louvain modularity-based community detection algorithm (Modularity Optimizer package implemented in Java) utilized a resolution of 0.01 to generate a total of 10 first-round clusters. Each of these clusters was again subjected to gene selection and PCA. These PCs were evaluated for statistically significant gene expression signals using the Jackstraw method (Chung and Storey, 2014; Macosko et al 2015)", and comparison between healthy/control groups (as well as between different time points) is well-understood, routine, and conventional experimental design choice that confers no technical improvement over prior art).
Regarding claim 33, Quadrato teaches the data analytic techniques include one or more of the following algorithmic techniques; artificial intelligence, machine and deep learning as predictive analytics tools for identifying biomarkers for diagnostic, therapeutic target and drug development process for disease (Page 75 line 14 "All descriptive statistics and statistical tests were performed in MATLAB R environment (version 8.3, R2014a, The Math Works, Inc.), using the Statistics Toolbox (version 9.0, R2014a, The Math Works, Inc.)" contain machine-learning algorithms, primarily under the methods of classification, regression, and clustering).
Regarding claim 49, Quadrato teaches the at least one cell sample reprogrammed to the induced pluripotent stem cell is a fibroblast derived from skin or blood cells from humans (Page 34 line 22 "the stem cells can be isolated from tissue including solid tissue. In some embodiments, the tissue is skin, fat tissue (e.g. adipose tissue), muscle tissue, heart or cardiac tissue. In other embodiments, the tissue is for example but not limited to, umbilical cord blood, placenta, bone marrow, or chondral").
Regarding claim 50, Quadrato teaches the fibroblast derived skin or blood cells from humans is identified with the genes identified in Table 1, Table 2, Table 5, or Table 7 (Page 40 line 32 "In some embodiments, such cells or tissue can be identified by selective gene expression markers", and it is noted that any known gene may be used as an expression marker and will be detectable in WGS data).
Regarding claims 51 and 52, Quadrato teaches the measured biomarkers comprise a plurality of biomarkers identified in Table 1, Table 2, Table 5 or Table 7 or variants thereof; and a combination of biomarkers is detected, the combination comprising a nucleic acid encoding human A2M, APP variants and one or a plurality of biomarkers comprising a nucleic acid encoding human genes identified in Table 1 (Page 63 line 28 "we examined cells in the retina cluster that expressed the transcription factor CRX, a known marker of both 30 developing and mature photoreceptors (developing and mature photoreceptors can be easily differentiated at the molecular level)", as CRX is in table 1, and gene expression via single-cell sequencing (using in Quadrato) will easily detect all possible known variants of human genes).
Regarding claims 53 and 54, Quadrato teaches the neural organoid biological sample is collected after about one hour up to about 12 weeks post inducement; and the neural organoid sample is procured from structures of the neural organoid that mimic structures developed in utero at about 5 weeks (Page 64 line 23 "we followed the expression of synaptic markers over time in culture. The pre-synaptic marker synapsin 1 (SYN1) was absent at 1 month but began to be expressed at 3 mo, persisting for at least 9 month in culture (FIG. 3E and data not shown)", and it is noted that this time period overlaps this 5 week limitation and the structures depend on the organoid used).
Regarding claim 55, Quadrato teaches the neural organoid contains microglia, and one or a plurality of Alzheimer's disease biomarkers as identified in Table 1 and Table 7 (Page 85 claim 40 "A three dimensional neural tissue composition comprising a cerebral organoid and at least one cell type selected from the group consisting of microglia, oligodendrocytes, endothelial cells, cells of the immune system and stromal cells").
Regarding claim 56, Quadrato teaches the method is used to identify causes or accelerators of Alzheimer's disease, detect environmental factors that cause or exacerbate Alzheimer's disease, identify nutritional factors or supplements for treating Alzheimer's disease, or as predictive toxicology for factors including infectious agents, that cause or exacerbate Alzheimer's disease (Page 52 line 27 "the iPS cells and/or neural tissue derived from neuropsychiatric patients are used to screen for agents ( e.g., agents which are able to modulate genes contributing to a neurospychiatric phenotype)" and 53 line 17 "the invention provides a method of screening test agents to identify treatment agents for a neuro disease or diseases affecting neuronal network connectivity, synaptic function and/or synaptic activity").
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 30, 33, and 49-56 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of US-20240369538 in view of Quadrato et al. (WO-2017117547). Although the claims at issue are not identical, they are not patentably distinct from each other because both involve procuring cells from a patient, reprogramming them to produce IPSC samples, treating IPSC samples to obtain a patient-specific organoid, collecting an organoid sample, and detecting changes in biomarker expression.
While US-20240369538 does not explicitly teach using machine learning algorithms to compare diseased/healthy samples, it would have been obvious to one of ordinary skill in the art to modify these methods, with those taught by Quadrato as described above for claim 1 of the instant application, in order to evaluate statistically significant gene expression signals (Page 72 line 24 Drop-seq single cell sequencing Section "A first round of clustering with the Louvain modularity-based community detection algorithm (Modularity Optimizer package implemented in Java) utilized a resolution of 0.01 to generate a total of 10 first-round clusters. Each of these clusters was again subjected to gene selection and PCA. These PCs were evaluated for statistically significant gene expression signals using the Jackstraw method (Chung and Storey, 2014; Macosko et al 2015)", and comparison between healthy/control groups (as well as between different time points) is well-understood, routine, and conventional experimental design choice). One skilled in the art would have a reasonable expectation of success because the method of Quadrato is also concerned with analyzing gene expression data of neural organoids.
Claims 30, 33, and 49-56 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of US-20210163886 in view of Quadrato et al. (WO-2017117547). Although the claims at issue are not identical, they are not patentably distinct from each other because both involve procuring cells from a patient, reprogramming them to produce IPSC samples, treating IPSC samples to obtain a patient-specific organoid, collecting an organoid sample, and detecting changes in biomarker expression.
While US-20210163886 does not explicitly teach using machine learning algorithms to compare diseased/healthy samples, it would have been obvious to one of ordinary skill in the art to modify these methods, with those taught by Quadrato as described above for claim 1 of the instant application, in order to evaluate statistically significant gene expression signals (Page 72 line 24 Drop-seq single cell sequencing Section "A first round of clustering with the Louvain modularity-based community detection algorithm (Modularity Optimizer package implemented in Java) utilized a resolution of 0.01 to generate a total of 10 first-round clusters. Each of these clusters was again subjected to gene selection and PCA. These PCs were evaluated for statistically significant gene expression signals using the Jackstraw method (Chung and Storey, 2014; Macosko et al 2015)", and comparison between healthy/control groups (as well as between different time points) is well-understood, routine, and conventional experimental design choice). One skilled in the art would have a reasonable expectation of success because the method of Quadrato is also concerned with analyzing gene expression data of neural organoids.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 TH REE-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 finaI action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert A. Player whose telephone number is (571)272-6350. The examiner can normally be reached Mon-Fri, 8am-5pm.
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, Larry D. Riggs can be reached on 571-270-3062. 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.
/R.A.P./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686