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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application US 62/408,045 filed 13 October 2016 was claimed. However, the concept “glioblastoma”, “astrocytes” and glioblastoma treatment; the master regulator genes “BASP1, “NKX6.2”, “MYCN”, “ASCL1”; and the perturbagen classes (RNAi, siRNA, shRNA, small molecule) (all concepts, genes and perturbagens above are recited in claims 6, 28, 35 and 38-42) are mentioned only in the 1/20/2026 version of amended specification and Drawings.
Paragraph [0090] expressly says the inventors applied the operations to identify core master regulators described in U.S. Provisional Application No. 62/506,413 filed May 15, 2017. Because May 15, 2017 is after the asserted Oct. 13, 2016 priority date, any claim limitation that relies on that later provisional may not receive the Oct. 13, 2016 effective filing date unless it is also supported in the Oct. 13, 2016 provisional.
Therefore, the current claims 6, 28, 35 and 38-42 are given this priority date: 1/20/2026. Since claims 6 and 28 are the only two independent claims in this application and dependent claims 7-9, 12, 29-31, 34, and 37 inherit the claims 6 and 28 limitations, claims 6-9, 12, 28-31, 34-35, and 37-42 are all given the priority date of 1/20/2026.
Status of the Claims
Claims 1–5, 10-11, 13–27, 32-33 and 36 are canceled.
Claims 6-9, 12, 28-31, 34-35, and 37-42 are pending and are examined on the merits.
Claim Objections
Claim 29 is objected to because of the following informalities: “wherein wherein” has a duplication.
Claims 35 and 40 both recite: “a RNA-interference agent”, which should be “an RNA-interference agent.”
Appropriate correction is required.
Withdrawn Rejections/Objections
The rejection of claims 6-10, 12, 21-25, 27-32 and 34-37 under 35 U.S.C. 112(a) in the Office action posted 02/19/2026 is withdrawn in view of specification amendments and persuasive arguments (Remarks: page 12, 1st para through page 19, 3rd para) both filed 2/15/2026. However, a new 112(a) rejection is applied.
The rejection of claims 6-10, 12, 21-25, 27-32 and 34-37 under 35 U.S.C. 112(b) in the Office action posted 02/19/2026 is withdrawn in claim amendments filed 2/15/2026.
The rejection of claims 6, 12, 27-28 and 34-37 under 35 U.S.C. 103 in the Office action posted 02/19/2026 is withdrawn in claim amendments filed 2/15/2026.
Regarding the 35 U.S.C. 102/103
The claims are free of art because close art, identified in the search as well as cited in the previous Office Action, does not teach treat glioblastoma with two or more target genes. The concept is captured in claims 6 and 28 as the following claim limitations:
treating the patient with the combination of perturbagens targeting the two
or more master regulators,
wherein the two or more master regulators are selected from the group consisting of BASP1, NKX6.2, MYCN, and ASCL1, and
wherein the combination of perturbagens targeting the two or more master regulators inhibits at least one of BASP1, NKX6.2, MYCN, and ASCL1.
This combination is not obvious.
The claims hence are art free. In this regard, Applicant’s Remarks of 5/15/2026 (page 16, 4th para through page 18, 4th para) support the withdrawn of the art rejections.
Claim Rejections - 35 USC § 112—Second Paragraph
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 6-9, 12, 28-31, 34-35, and 37-42 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.
Claims 6 and 28 recite (step (h)) selecting a “subset of highest importance scores,” but do not state how many are selected unless “two or more” is the only bound. The phrase may be broad but likely definite if understood as top-ranked nodes; however, the specific selection threshold could be challenged. In fact the Fig. 10 in the Drawings does not support a strict top-ranking of node selection. Fig. 10 suggests a combined top-ranking with expert-knowledge in master regulator selection. Claims hence are indefinite regarding how the nodes are selected.
Claim 6, Step (I) (line 4 of claim 1) recites “a combination of perturbagens that are determined by:” Step (I) (a) to (h) does not result in determining a combination of perturbagens. Claim 6 Step (II) recites treating the patient with “the combination of perturbagens.” However it is not clear how Step (I) (a) to (h) integrate into Step (II) of treating with the combination of perturbagens. The method as whole is unclear because the relationship between steps (I) and (II) are unclear. It is unclear how steps (a) to (h) are drawn to determining a combination of perturbagens. Claim 28 recites similar limitations which should also be clarified.
Claim 28 is a method of treating a patient comprising providing non-transitory media with instructions and treating the patient. Literally, the targets selected at step (II) has no direct relation to the “master regulators” determined recited in step (I) (h) (by the process recited in the non-transitory media with instructions). Because the selection in step (I) is based on “a subset of highest importance scores” and the selection in step (II) is from a list of four. of step (I) results in determining two or more master regulators based on the process of step (I). Step (II) appears to be an independent step where two or more master regulators are selected from the group. It is unclear how the step of determining master regulators in (h) is related to selecting master regulators in step (II). The connection between the determined master regulators and subsequent step of selecting master regulators is unclear. Steps (I) and (II) appear to be two unrelated methods. It is unclear why master regulators are selected in step (II) if master regulators were already determined in step (I).
Claim Rejections - 35 USC § 101
The instant rejection is maintained from the previous Office Action filed 10/22/2025 and modified in view of Applicant’s amendments filed 1/20/2026.
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 6-9, 12, 28-31, 34-35, and 37-42 are rejected under 35 USC § 101 because the claimed inventions are directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 6-9, 12, 35 and 38-39 are to a “method” with functional steps, so a process.
Claims 28–31, 34, 37 and 40-42 are to another “method”, so another process.
Each of these fall within one of the categories of statutory subject matter.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s)
Receiving, by one or more processors from a data filtering software via a computational processing pipeline, an initial dataset that describes a gene expression network, wherein the gene expression network comprises a regulatory network that is generated based on gene expression data.
--Receiving data from a data filtering software is interpreted as a process affected by human judgement and decision-making; To represent the gene expression data in the way of a regulatory network reads on a natural correlation between the gene expression data and the regulatory network, such a natural correlation is achieved in human mind; further, to represent the gene expression data in a graphic regulatory network reads on a data re-organization, which can be achieved in human mind. Therefore this step equates to an abstract idea of mental processes
Extracting, by the one or more processors, one or more subnetworks of the gene expression network.
--Extracting some data out of the existing data reads on data manipulation based on judgement. Therefore this step equates to an abstract idea of mental processes.
Determining, by the one or more processors, an individual score for each node in the one or more subnetworks;
--Under a broadest reasonable interpretation (BRI), this step is conducted by calculating a score for a node based on topology in the sub-network graph. Therefore this step equates to an abstract idea of mathematical concepts.
Determining, by the one or more processors, a neighborhood score for each node in the one or more subnetworks;
--Under a BRI, this step is conducted by calculating a score for a node based on topology in the sub-network graph. Therefore this step equates to an abstract idea of mathematical concepts.
Generating, by the one or more processors, a combined node score for each node in the one or more subnetworks based at least in part on a combination of the individual score and the neighborhood score.
--Under a BRI, this step is conducted by adding up the two scores acquired in the previous two steps. Therefore this step equates to an abstract idea of mathematical concepts.
Determining, by the one or more processors and based at least in part on one or more performance predictions that are generated by a machine learning model that is trained based at least in part on one or more differential expression datasets, a given parameter set from a plurality of parameter sets that comprises at least the one or more input parameters;
--Under a BRI, the “machine learning model” can be a linear regression model. Hence the “given parameter” is acquired by calculating. Therefore this step equates to an abstract idea of mathematical concepts.
Determining, by the one or more processors, a set of one or more importance scores for a set of one or more nodes in the one or more subnetworks based at least in part on the parameter set and the combined node score;
--Under a BRI, this step is conducted by mathematical calculations. Therefore this step equates to an abstract idea of mathematical concepts.
Determining, by the one or more processors, the two or more master regulators based at least in part on one or more genes that are selected based at least in part on the importance score.
--Under a BRI, this step is conducted by comparing the individual “importance score” to a threshold which is a mathematical operation. Therefore this step equates to an abstract idea of mathematical concepts.
Hence, the claims do recite elements that, individually and in combination, constitute abstract ideas. Dependent claims, such as claims 7-9, 22-24 and 29-31 recite mathematical equations explicitly; claims 10, 12, 25, 27, 32 and 34 recite mathematical operations to calculate different scores. These claims are all directed to abstract ideas of mathematical concepts. The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)).
Step 2A Prong Two: Consideration of Practical Application
The claims result in a treatment for the glioblastoma patients using perturbagens targeting two or more master regulators. However, the claims do not integrate the abstract idea into a practical application, because the judicial exceptions (the data analytical processes that leads to the identification of master regulators) is unrelated to the treatment of glioblastoma. The analysis steps (a) to (h) leads to determining at least two master regulators based on genes with highest importance score , while the treatment step (II) is drawn to targeting two or more master regulators selected from a group of four genes. The identified master regulators in the analytical steps are not necessarily the same as the two or more genes selected from BASP1, NKX6.2, MYCN and ASCL1 for patient treatment.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
“One or more processors" (claim 6).
"A system comprising memory and one or more processors communicatively coupled to the memory, the one or more processors configured to" (claim 21).
"One or more non-transitory computer-readable storage media including instructions" (claim 28).
--These limitations do not improve the functions of the computer or integrate the abstract idea into a practical application. The limitations are drawn to a generic computer that performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, as described in MPEP 2106.05(f)
Claims 6, 21 and 28 all recite:
“Treating the patient with the combination of perturbagens targeting two or more master regulators
wherein the two or more master regulators are selected from the group consisting of BASP1, NKX6.2, MYCN, and ASCL1, and
wherein the combination of perturbagens targeting the two or more master regulators inhibits at least one of BASP1, NKX6.2, MYCN, and ASCL1.”
No other additional elements are recited in dependent claims.
Treating glioblastoma patients using perturbagens and small molecules are known. For example, Cohen et al. ("Localized RNAi therapeutics of chemo-resistant grade IV glioma using hyaluronan-grafted lipid-based nanoparticles." ACS nano 9.2 (2015): 1581-1591. Previously cited) disclosed (page 1581, Title and Section “Abstract”) treating glioblastoma patients using RNAi.
Nara et al. ("Silencing of MYCN by RNA interference induces growth inhibition, apoptotic activity and cell differentiation in a neuroblastoma cell line with MYCN amplification." International journal of oncology 30.5 (2007): 1189-1196. Previously cited) disclosed (page 1189, Title and Section “Abstract”) treating glioblastoma cells using RNAi and hyaluronan-grafted lipid-based nanoparticles (which reads on a small molecule) to treat glioblastoma.
Berthold et al. ("Neuroblastoma: current drug therapy recommendations as part of the total treatment approach." Drugs 59.6 (2000): 1261-1277. Previously cited) disclosed (page 1267, Table V) 13 drugs used in glioblastoma therapy.
Ng et al. ("A small interference RNA screen revealed proteasome inhibition as strategy for glioblastoma therapy." Clin Neurosurg 56 (2009): 107-118. Previously cited). demonstrated (page 110, Figure 19.1) that siRNA targeting the PSMA1 gene (a RNA-interference agent targeting PSMA1) sensitize the U87MG cells (a known glioblastoma cell line) to TMZ (a small molecule) treatment, which indicate the combination therapy of siRNA targeting the PSMA1 gene and a small molecule (TMZ) is effective against the U87MG glioblastoma cells.
Targeting the master regulators (such as MYCN) is also known. However, the data and process steps by which the master regulators are identified is generic and unrelated to glioblastoma. Therefore the claim does not integrate abstract ideas into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information.
Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Applicant’s Arguments
In the Remarks filed 5/15/2026, Applicant argues (page14, last para through page 15, 2nd para) that “none of Cohen, Ng, Nara, or Berthold, either alone or in combination, teach or suggest ‘[a]combination of perturbagens targeting two or more master regulators [that] inhibits at least one of BASP1, NKX6.2, MYCN, and ASCL1,’ as recited in amended claims 6 and 28” (page 16, 2nd para).
In response, Applicant’s arguments are not responsive. Applicant seems to argue a particular treatment with specific medicine (page 14, 3rd para). Even with a particular treatment with specific medicine, they have to pertain to the JEs of data analysis in order to integrate the claims into a practical application at Step 2A/Prong two. At Step 2B, the treatment step is conventional, because Berthold, Nara, Ng and Cohen, from year 2000, to year 2007, to year 2009, to year 2015, had been practicing treating glioblastoma targeting specific genes, such as MYCN, using the RNA interference technology.
In the Remarks, Applicant argues (page15, 3rd las) that “the amended claims recite a particular disease (glioblastoma), a particular set of master regulators (BASP1, NKX6.2, MYCN, and ASCL1), and a particular treatment (a combination of perturbagens targeting two or more master regulators that inhibits at least one of BASP1, NKX6.2, MYCN, and ASCL1, and integrates the abstract idea into a practical application).”
In response, Applicant’s arguments are not responsive. First, a “perturbagen” is “any chemical or biological agent—such as a small molecule, peptide, or genetic reagent like CRISPR—used to treat cells and disrupt normal intracellular processes” (definition provided by wiki), which is not a particular treatment. Second, the judicial exception (i.e. abstract idea) of data analysis should be integrated into a practical application at Step 2A/Prong two. As discussed in the above 101 analysis, the analytical steps (a) to (h) (in both claims 6 and 28) lead to the determining two master regulators based on the identification of two or more genes with the highest importance scores. However, the treatment step is based on treating with “the combination of perturbagens” targeting master regulators selected from the groups consisting of BASPI, NKX6.2, MYCN, ASCL1. The identified master regulators in the analytical steps (a) to (h) are not necessarily the same as the two or more genes selected from BASP1, NKX6.2, MYCN and ASCL1 for patient treatment. There is an unclear connection between step (I) and step (II), as set forth above under 35 USC 112(b), and therefore, the abstract idea is not integrated into a practical application.
For the above reasons, the 101 rejection is maintained.
Conclusion
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 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.
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/GL/
Patent Examiner
Art Unit 1686
/Anna Skibinsky/
Primary Examiner, AU 1635
Prosecution Insights