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 the Claims
The claim set received 25 August 2025 has been entered into the application.
Claims 43-47 are new.
Claims 1-22 are previously cancelled.
Claims 40-42 are cancelled.
Claim(s) 23-39 and 43-47 are pending.
Priority
Acknowledgment is made of applicant’s claim to priority to U.S. Provisional Application No. 62/016,078 filed on 27 April 2020.
Drawings
The objection to the drawings in the Office Action mailed 28 January 2025 is withdrawn in view of the replacement drawings filed 28 July 2025 and 25 August 2025.
The drawings were received on 28 July 2025 and 25 August 2025. These drawings are accepted.
Specification
The amendments to the specification regarding the replacement drawing sheet received 25 August 2025 have been entered into the application.
The objection to the specification because unique uncorrected joint p-value of claim 33 in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The amendment filed 22 December 2023 and 25 August 2025 are objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
The added material not supported is “member” of claims 23, 27-31, 33, and 37-39. (filed 22 December 2023).
The added material not support is “pathway-specific unique uncorrected joint p-value unique” of claim 33. (filed 25 August 2025).
Applicant is required to cancel the new matter in the reply to this Office Action.
Response to Arguments
Applicant’s arguments filed 25 August 2025, have been fully considered but the objection is maintained.
It is noted that the Applicant was not responsive with respect to canceling the new matter from the claims. Therefore, the objection to the specification is maintained. It is noted that amending uncorrected joint p-value to recite unique pathway specific uncorrected joint p-value does not obviate the objection because the specification only supports combining the first and second probabilities and does not support a “pathway specific uncorrected joint p-value” as described in the 35 U.S.C § 112(a) new matter rejection below.
Claim Rejections - 35 USC § 112
35 U.S.C § 112(a)
The instant rejection is maintained for reason for record in the Office Action mailed 28 January 2025 and modified in view of the amendments filed 25 August 2025.
The rejection of claim 40-42 under 35 U.S.C § 112(a) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The rejection of claim 33 “unique uncorrected joint p-value” under 35 U.S.C § 112(a) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 23-39 and 43-46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a New Matter rejection based on the new introduced claims filed 22 December 2023 and 25 August 2025. With respect to the new matter introduced on 22 December 2023, the Applicant has not cancelled or amended the new matter from the claims.
Claims 23, 28, and 37 require identifying a member by selecting the member from a group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype. The limitation “member” is required to determine the targeted drug treatment and determining probabilities which is further used for treating the subject with a targeted drug treatment and/or administering the targeted drug treatment. However, the specification does not encompass literal or figurative support for limitation “member”. In addition, the original claim set received 27 April 2021 does not appear contain the limitation “member”. The due to lack of written description for identifying a “member,” the specification also does not provide guidance as to how the “member” is utilized to determine the targeted treatment configured to reverse expression of the set of biomolecules. The claims appear to depend on the data of the member to identify a targeted drug treatment and to treat a subject with the identified targeted drug treatment, but do not provide guidance as to what data of the “member” is utilized and incorporated in the claims. The amended limitation “member” is new matter.
With respect to claims 28, 33 and 37, the claim utilizes the limitation “unique pathway-specific uncorrected joint p-value”. The specification does not provide literal or figurative support and guidance as to what encompasses “unique pathway-specific uncorrected joint p-value” or “unique pathway-specific uncorrected joint p-value for multiple comparisons”. The specification provides guidance for using a “a unique pathway-specific uncorrected combined p-value”, but does not provide guidance for using “a unique pathway-specific uncorrected joint p-value”. The amended limitation “unique pathway-specific uncorrected joint p-value” is new matter.
It is recommended that the applicant amend the claims to recite unique pathway-specific uncorrected “combined” p-value to provide language consist with the specification. It is further recommended to amend the claims 23, 33, and 37 identifying a member step to recite “identifying a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator, wherein the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator are selected from a group consisting of biological pathways, biological mechanisms, biological processes, biochemical functions, and upstream regulators perturbed by the set of biomolecules affected by the phenotype” to provide clarity and language and limitations consistent with the specification.
Claims 24-36, 38-39, and 43-46 are rejected because the base claims from which they depend are rejected and the claims fail to provide limitation to overcome the deficiencies of the base claims.
All new matter is required to be cancelled or amended in the reply to this action.
Response to Arguments
Applicant’s arguments filed 25 August 2025, have been fully considered but the rejection is maintained. However, upon further consideration, a new ground(s) of rejection is made in view of the amendments filed 25 August 2025.
It is noted that the Applicant did not cancel or amend the new matter “member” from the claims as required above.
The Applicant states “The rejection under 35 U.S.C. § l 12(a) alleging that the term "member" lacks written description support is misplaced. The term "member" does not introduce new matter, nor does it require explicit support in the specification. In the context of the claims, "member" is simply a generic linguistic term used to refer to individual parts of a list (e.g., a "Markush group"), which is a common and accepted usage in U.S. patent law. It does not represent a separate or novel concept that demands specific written description support.” [remarks, page 12]. The Applicant states “Furthermore, the disputed portion of the claim is structured as a conventional Markush group, which inherently defines a closed set of alternatives. The claim explicitly recites the Markush group as consisting of: (1) a biological pathway, (2) a biological mechanism, (3) a biological process, (4) a biochemical function, and (5) an upstream regulator perturbed by the set of biomolecules affected by the phenotype. By definition, the individual parts of the Markush group are the "members" of the group. Therefore, the term "member" is nothing more than a shorthand reference to an individual element of the Markush group, which does not require separate or explicit written description support in the specification. A person of ordinary skill in the art would immediately understand that the term "member" refers to any one of the enumerated elements of the group. The specification provides written support for the individual parts of the group, including biological pathways, mechanisms, processes, functions, and regulators. As such, the Markush group structure inherently provides support for the term "member," making the rejection unwarranted. With respect to connecting up the claimed group members with the specification as originally filed, and based upon the advanced knowledge of one skilled in the life sciences and bioinformatics, Applicant respectfully submits that the members of the grouping of Claim 23 ("a member selected from the group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator") are supported by reference to the specification as follows, taking each group member in turn.” [remarks, page 13-14]. The Applicant points to the specification paragraphs [0017, 0055, 0076, 0016, 0049, 0060, 0079-0080, 0083, 0037, 0052-0053, 0035-0036] for guidance with respect to the term “member” [remarks, pages 13-14].
In response, the term “member” is considered an integral part of the selection of the group. Here, the member, under Broadest Reasonable Interpretation (BRI), can be interpreted as any member or sub-section of a pathway (which pathway), mechanism (which mechanism), biological process (which biological process), a biochemical function (which biochemical function), and an upstream regulator (which gene) is perturbed by a set of molecules. Although the member is selected from a group, the member is new matter because it does not define or specify what the member of the group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype is used for determining a targeted drug treatment that is subsequently administered. As such, “member” is new matter because the specification does not provide a definition for what is to encompass the member from each member of the Markush group. Although the limitations are part of a Markush group, it doesn’t preclude the limitation from containing new matter as the “member” is not defined or specified in such way that one of ordinary skill in the art would recognize as to what member from the pathways, processes, mechanisms, biological functions, or upstream regulators are being identified to which a targeted treatment can be determined and administered. Therefore, support for the ”member” is required because one of ordinary skill in the art would not be able to treat a patient with a targeted treatment based on any member (i.e., process, function, pathway, gene) in order to treat a patient with coronavirus. It is noted that the claim language is written such that a “member” can encompass any pathway from biological pathway, any mechanism from a biological mechanism, any process from biological processes, any function from a biochemical function, and any upstream regulator (i.e., gene, poly A tail, stop codon), for example.
It is noted that on pages 13-14 of the remarks that the Applicant has provided support from the specification regarding the group of claims 23 and 37 but the Applicant did not point out what specific data is used for selecting a member. The Applicant does not provide support for the limitation “member”. For example, claim 23 recites identifying a member selected from a group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype, but the specification, claims and arguments do not provide as to what data or attributes the member is to comprise from the groups for determining a target treatment for treatment of a phenotype associated with a corona virus. The argument is not persuasive because, in view of the specification and the claims, there is no support for the limitation “member” encompassing a data selected from a group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype. It is recommended to amend the claims as noted in the 35 U.S.C § 112(a) above. The argument is not further persuasive because the Applicant has not provided what data is utilized for limiting the limitation “member” and what data is utilized for identifying the member for administering a targeted drug treatment. Therefore, the rejection regarding “identifying a “member” selected” is maintained because the Applicant has not cancelled or amended the limitation to provide clarity with respect to what data or other attributes the “member” is to comprise.
The Applicant states “that the rejection under 35 U.S.C. § l 12(a) alleging that the limitation "unique uncorrected joint p-value" lacks written description support is improper. The specification provides support for this limitation in paragraph 14, which states: In one aspect, the method further includes combining the first probability value (pORA) and the second probability value (pACC) so as to determine a unique pathway-specific uncorrected p-value for each of the one or more biological pathways.” [remarks, page 14]. The Applicant points to specification Paragraph 14 describes how the first and second probability values are combined to create a "unique pathway-specific uncorrected p-value." The addition of the word "joint" in the claims is merely for clarity purposes, as it accurately reflects the combination of the two probability values into a single p-value. A person of ordinary skill in the art would readily understand that the term "joint" in this context refers to the p-value resulting from the combination of the two distinct probabilities. To further clarify the claim language” The Applicant states claims have been amended such that each instance of "unique uncorrected joint p-value" to read "pathway-specific unique uncorrected joint p-value." This amendment aligns the claim language with the terminology used in the specification.” [remarks, page 14].
In response, the argument is not persuasive because the "pathway-specific unique uncorrected joint p-value” is not supported by the specification. Here, it is acknowledged that the Applicant may be their own lexicographer. It is noted that an applicant is entitled to be their own lexicographer and may rebut the presumption that claim terms are to be given their ordinary and customary meaning by clearly setting forth a definition of the term that is different from its ordinary and customary meaning(s) in the specification at the relevant time. However, it is important to note that any special meaning assigned to a term “must be sufficiently clear in the specification that any departure from common usage would be so understood by a person of experience in the field of the invention.” Multiform Desiccants Inc. v. Medzam Ltd., 133 F.3d 1473, 1477, 45 USPQ2d 1429, 1432 (Fed. Cir. 1998). See MPEP 2111.01 (IV)(A). Here, providing a joint probability is not supported in the specification because as noted by the Applicant [remarks, page 14], the term “joint” is used to clarify the combined first and second values. Here, the specification discloses “the method further includes combining the first probability value (pORA) and the second probability value (pACC) so as to determine a unique pathway-specific uncorrected p-value for each of the one or more biological pathways.”. The term “joint” with respect to encompassing a “pathway-specific unique uncorrected joint p-value” is not disclosed throughout the specification such that it describes a statistical joint probability “pathway-specific unique uncorrected joint p-value” sufficiently clear so that one of ordinary skill in the art can mathematical differentiate between the formula for calcualting “pathway-specific unique uncorrected joint p-value” compared to combining probability values to determine a targeted treatment. However, combining the results of first probability value (pORA) and the second probability value (pACC) so as to determine a unique pathway-specific uncorrected p-value is not the same as a mathematical/statistical formula “pathway-specific unique uncorrected joint p-value” which suggests the “pathway-specific unique uncorrected joint p-value” is a specific formula for calculating a “pathway-specific unique uncorrected joint p-value”, not merely combining data (i.e., combining the first probability value (pORA) and the second probability value (pACC)) to determine a result “pathway-specific unique uncorrected joint p-value”. Furthermore, it is known in the art that “joint” and “combine” entail different meanings in the art of statistics with respect to probabilities. For example, “joint probability" is a specific term for the probability of two or more events occurring simultaneously, while "combined" is a more general term that can refer to combining probabilities in different ways, such as with "or" (union) or "and" (intersection). The key distinction is that "joint" probability specifically refers to the intersection of events ("and"), not their union ("or"). Therefore, the argument is not persuasive, and it is recommended to amend the claims as recommended by the Examiner to obviate the rejection.
35 U.S.C § 112(b)
The instant rejection is maintained for reason for record in the Office Action mailed 28 January 2025 and modified in view of the amendments filed 25 August 2025.
The rejection of claim 40-42 under 35 U.S.C § 112(a) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The rejection of claim 33 under 35 U.S.C § 112(a) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
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 23-39 and 43-46 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.
With respect to claims 23, 33, and 37, the metes and bounds of the limitation “member” is indefinite because the specification nor the claims provide a limiting definition for the term. One of ordinary skill in the art would not be apprised to know what the “member” is and what data encompasses the “member”. It is further indefinite because it is unclear if the member is a member from the group consisting biological pathway (chemokine signaling pathway), a biological mechanism (methylprednisolone mechanism of action), a biological process, a biochemical function, and an upstream regulator (a specific gene) or if the member is the biological pathway or a biological mechanism or a biological process or a biochemical function, or an upstream regulator, for example. One of ordinary skill in the art would not be apprised to know if the “member” is a gene, protein, or other molecule to which will be utilized to determine the targeted drug treatment and determine the pORA and pACC. It is further unclear what data of the “member” is used to determine the targeted drug treatment and determine the pORA and pACC. Here, the metes and bounds of the term “member” render the claims indefinite because it is not clear if the “member” is an entire biological pathway, biological mechanism, biological process, biochemical function, or upstream regulator or if the member is a sub section of a pathway (i.e., chemokine signaling pathway [Spec 0017]), mechanism (i.e., mechanism through which methylprednisolone act [Spec 0016] which mechanism), process (does not claim a specific process), function (i.e., metabolomics or catalysis [0049 and 0052]), or regulator (i.e., downstream gene and the arrow with the negative sign) which does not claim an upstream regulator. It is recommended to amend the claims to clarify if the member is one of the five members of the group such as biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator or if the member is a subgroup or category of biological pathway (i.e., chemokine signaling pathway), a biological mechanism (i.e., methylprednisolone mechanism of action), a biological process, a biochemical function, and an upstream regulator (e.g., a specific gene) that is affected by a perturbation.
Claims 24-36, 38-39, and 43-46 are rejected because the base claims from which they depend fail to provide limitations to overcome the deficiencies of the base claims.
Response to Arguments
Applicant’s arguments filed 25 August 2025, have been fully considered and the rejection has been maintained. However, upon further consideration, a new ground(s) of rejection is made in view of the amendments filed 25 August 2025.
The Applicant states “claims 23 and 37 were amended to clarify that the "member" is one of the five members of the group consisting of (1) a biological pathway, (2) a biological mechanism, (3) a biological process, (4) a biochemical function, and (5) an upstream regulator perturbed by the set of biomolecules affected by the phenotype.” [remarks, page 15].
With respect to the rejection under 112(b), the Applicant did not address the limitation “member”. Therefore, the rejection regarding “member” is maintained.
Claim Rejections - 35 USC § 101
The instant rejection is maintained for reason for record in the Office Action mailed 28 January 2025 and modified in view of the amendments filed 25 August 2025. It is noted the amendments received 25 August 2025 are necessitated by new ground(s) of rejection.
The rejection of claim 40-42 under 35 U.S.C § 101 in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
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 23-39 and 43-46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Following the flowchart from MPEP 2106.
Step I - Process, Machine, Manufacture or Composition
Claims 23-39 and 43-46 are directed towards a method, so a process.
Claim 47 is drawn to method of treatment, so a process. However, the claim is drawn to statutory matter and is therefore not rejected.
2A Prong I - Identification of an Abstract Idea
Claim 23 recites:
Comparing a plurality of sets of biomolecules from the phenotype to a plurality of sets of biomolecules from a control.
This step can be performed in the human mind by observing and judging biomolecules of a phenotype and a control and is therefore an abstract idea.
Identifying a set of biomolecules of the sets of biomolecules from the phenotype that is affected by the phenotype, each biomolecule having a differential expression between the phenotype and the control.
This step can be performed in the human mind by observing and evaluating differential expression data between a set of biomolecules and controls and is therefore an abstract idea.
Identifying a member, wherein the member is selected from a group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype.
This step can be performed in the human mind by observing and evaluating a perturbation to identify a member and is therefore an abstract idea.
Determining the targeted drug treatment configured to reverse the differential expression of the set of biomolecules based upon the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator.
This step can be performed in the human by observing and evaluating data based on the selected member and is therefore an abstract idea.
Claim 37 recite:
Identifying a set of biomolecules affected by the phenotype, each biomolecule having a differential expression between the phenotype and a control.
This step can be performed in the human mind by observing and evaluating a set of biomolecules and a control and is therefore an abstract idea.
Identifying a member wherein the member is selected from a group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype.
This step can be performed in the human mind by observing and evaluating a perturbed biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator to select a member to identify and is therefore an abstract idea.
Determining a first probability including a first probability value of p over representation (pORA) representing a probability of observing an actual number of biomolecules affected by the phenotype in the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype just by chance.
This step can be performed in the human mind by following instructions to determine first probability value of p over representation (pORA) representing an observed number of biomolecules perturbed by the phenotype and is therefore an abstract idea. The step encompasses determining a value of p over representation (pORA) representing a probability of observing an actual number of biomolecules affected by the phenotype in the member selected from the group which encompasses performing mathematical/statistical computations to determine a probability and is therefore a further abstract idea.
Determining a second probability including a second probability value (pACC) representing the probability of observing a measured total perturbation accumulation in the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype just by chance.
This step can be performed in the human mind by following instructions to determine a second probability and is therefore an abstract idea. This step encompasses determining a second probability value (pACC) representing the probability of observing a measured total perturbation accumulation in the member selected which encompasses performing mathematical/statistical computations to determine a probability and is therefore a further abstract idea.
Combining the first probability value (pORA) and the second probability value (pACC) so as to determine a unique pathway specific uncorrected joint p-value for the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype just by chance.
This step can be performed in the human mind by organizing and combining data from the pORA and the pACC to determine an unique pathway specific uncorrected joint p-value for the member selected from the group and is therefore an abstract idea. The step encompasses combining the data of the pORA and pACC to determine an unique pathway-specific uncorrected joint p-value for the member which encompasses performing mathematical/statistical computations to determine a probability and is therefore a further abstract idea.
Correcting the unique pathway-specific uncorrected joint p-value for multiple comparisons based on a number of members selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype using a False Discovery Rate (FDR) or Bonferroni correction method.
This step can be performed in the human mind following instructions to correct the uncorrected joint p-value for multiple comparisons based on a number of members selected from the group using a False Discovery Rate (FDR) or Bonferroni correction method and is therefore an abstract idea. The step encompasses correcting the uncorrected joint p-value using statistical operations such as using a False Discovery Rate (FDR) or Bonferroni correction method to correct data which encompasses performing mathematical/statistical computations to determine a probability and is therefore a further abstract idea.
Determining the targeted drug treatment configured to reverse the differential expression of the biomolecule based upon the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator and selecting the targeted drug treatment when the corrected joint p-value is less than predetermined threshold and reverses the differential expression of two of the biomolecules.
This step can be performed in the human mind by observing, comparing, and evaluating a targeted drug treatment based on the member selected from a group and is therefore an abstract idea. This step can be performed in the human mind by observing and comparing the corrected joint p-value to select a targeted drug treatment and is therefore a further abstract idea.
Claims 24-25, 26-31, 33, 35-36, and 38-39 are further drawn to limitations that describe the abstract ideas of claims 23 and 37 and are therefore also abstract ideas.
2A Prong II - Consideration of Practical Application
Claims 23
Claim 23 does not recite any additional elements to which integrate the recited judicial exception into a practical application because administering of the targeted drug treatment (i.e., targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof) is not integrated with the judicial exception. For example, claim 23 recites comparing biomolecules of the phenotype to a control set of biomolecules, identifying a set of biomolecules, identifying a member from a group of biological pathways, biological processes, biochemical functions, and upstream regulator perturbed by the set of biomolecules, determining a targeted drug treatment configured to reverse differential expression of the set of biomolecules based on the member selected from a group, and administering the targeted drug treatment. With respect to the particular treatment(s), the treatments are not integrated into a practical application because the treatments do not have more than a nominal or insignificant relationship to the exception(s). For example, the is a disconnect between the treatments and what is being treated. Here, claim 23 recites a subject having corona virus, but the claimed steps do not connect and/or provide a correlation between set of biomolecules to a biological pathway, biological processes, biological mechanism, biochemical functions, and an upstream regulator and the targeted treatments with respect to a corona virus infection. To exemplify, it is known in the art that diclofenac, dexamethasone, and prednisolone [Wiles, disclosure 0800] are utilized as anti-inflammatories. Esters are used for their anti-inflammatory properties [disclosure 0829-0830] while myochrysine is utilized in the art for treating rheumatoid arthritis (RA) [Wiles, disclosure 0813]. However, the claims do not correlate any sets of biomolecules and identified members to a determined targeted drug treatment in order to treat phenotypes induced by corona virus infection. Furthermore, there is not a significant or more than nominal relationship between a set of biomolecules and the treatment step. For example, the set of biomolecules can be any biomolecules, the member can be any biological pathway, process, or mechanism, any biochemical function, and any upstream regulator that can be treated using said targeted drug treatments. Thus, in context of claim 23, the administration step is not significantly related to the recited correlation of set of biomolecules and the members to the targeted drug treatments to reverse differential gene expression. As described by the MPEP 2106.04(d)(2)(a), that in order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. Here, the treatments are not particular as to treating a particular disease and the phenotype (i.e., treating a pathway from a corona virus infection that induces inflammation (i.e., cytokine-cytokine pathway or chemokine pathway)) to affect a type of change in a biological pathway, process, mechanism, biochemical function, and/or an upstream regulator such that the targeted drug treatment agonizes or antagonizes reverse differential gene expression. Although claim 23 recites a subject with corona virus, there is no natural law correlation between subject’s physiological response (i.e., set of biomolecules, members) perturbed by a corona virus and which differentially expressed genes are to be reversed. Claim 23 and the dependent claims do not connect which differentially expressed genes are reversed by using the target drug treatment. For example, claim 23 recites a member can be an upstream regulator(s), but the claims do not connect/correlate differential gene expression of any particular gene regulator(s) such that the gene (i.e., upstream regulator) regulation is reversed (i.e., affected) using the targeted drug treatments.
Alternatively, since it is known that diclofenac, dexamethasone, and prednisolone [Wiles, disclosure 0800] are utilized as anti-inflammatories, esters are used for their anti-inflammatory properties [disclosure 0829-0830] while myochrysine is utilized in the art for treating rheumatoid arthritis (RA) [Wiles, disclosure 0813], there is no correlation of treating the symptoms (i.e., inflammation from fevers, headaches, fatigue (i.e., phenotype)) of corona virus with the treatments in order to reverse differential expression of genes related to the phenotypes (i.e., symptoms of infection).
Therefore, the administration of the targeted drug treatments and the targeted drug treatments of claims 23 and 43-44 do not integrate the recited judicial exception into a practical application because the claims do not recite limitations that have more than a nominal or insignificant relationship to the exception(s). See MPEP 2106.04(d)(2)(b).
Claim 37
Claim 37 recites identifying a set of biomolecules. Claim 37 recite identifying a member selected from a group. Claim 37 recites determining a targeted drug treatment. Claim 37 recites determining a first probability (pORA) and a second probability (pACC). Claim 37 recites combining the pORA and the pACC to determine an uncorrected joint p-value for the selected member. Claims 37 recites correcting the uncorrected joint p-value. Claim 37 recites determining the targeted drug treatment when the corrected joint p-value is less than a threshold. Claims 37 recites administering the targeted treatments (i.e., targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof) while claims 45-46 recite dosages and schedules for the administration of the myochrysine and diclofenac.
Claims 37 and 45-46 do not recite any additional elements to which integrate the recited judicial exception into a practical application because administering of the targeted drug treatment (i.e., targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof) is not integrated with the judicial exception. For example, claim 37 recites comparing biomolecules of the phenotype to a control set of biomolecules, identifying a set of biomolecules, identifying a member from a group of biological pathways, biological processes, biochemical functions, and upstream regulator perturbed by the set of biomolecules, determining a first probability (pORA) and a second probability (pACC), combining the pORA and the pACC to determine an uncorrected joint p-value for the selected member, correcting the uncorrected joint p-value, determining the targeted drug treatment when the corrected joint p-value is less than a threshold, and administering the targeted drug treatment, but the treatments are not integrated into a practical application because the treatments do not have more than a nominal or insignificant relationship to the exception(s). For example, there is a disconnect and/or no correlation between the treatments and what is being treated. Here, claim 37 recites a subject having corona virus, but the claimed step does not connect and/or provide a correlation between set of biomolecules of a biological pathway, biological processes, biological mechanism, biochemical functions, and an upstream regulator and the targeted treatments. To exemplify, it is known in the art that diclofenac, dexamethasone, and prednisolone [Wiles, disclosure 0800] are utilized as anti-inflammatories. Esters are used for their anti-inflammatory properties [disclosure 0829-0830] while myochrysine is utilized in the art for treating rheumatoid arthritis (RA) [Wiles, disclosure 0813]. However, the claims do not correlate any sets of biomolecules and identified members (i.e., pathway, processes, mechanism, biochemical function, and upstream regulator) to a determined targeted drug treatment in order to treat symptoms induced by corona virus infection, such as inflammation. Furthermore, there is not a significant or more than nominal relationship between a set of biomolecules and the treatment step. For example, the set of biomolecules can be any biomolecules, the member can be any biological pathway, process, or mechanism, any biochemical function, and any upstream regulator that can be treated using said targeted drug treatments. Thus, in context of claim 37, the administration step is not significantly related to the recited correlation of set of biomolecules and the members to the targeted drug treatments to reverse differential gene expression. Additionally, there is a further disconnection between a subject infected with corona virus and the targeted treatments. For example, as described by the MPEP 2106.04(d)(2)(a), that in order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. Here, the treatments are not particular as to treating a particular disease and inducing a change in phenotype. Although claim 37 recites a subject with corona virus, there is no natural law correlation between subject’s physiological response (i.e., set of biomolecules, members) perturbed by a corona virus and between reversing differentially expressed genes using the target treatments to effect or change the disease or condition (i.e., phenotypes induced by a corona virus). Claim 37 and it associated dependent claims do not connect/correlate which differentially expressed genes are reversed using the target drug treatment. For example, claim 37 recites a member can be an upstream regulator(s), but the claims do not connect any particular upstream regulator gene (i.e., expressed gene) to any particular disease or condition that can be treated by a targeted drug to reverse differentially gene expression of said upstream regulator.
Alternatively, since it is known that diclofenac, dexamethasone, and prednisolone [Wiles, disclosure 0800] are utilized as anti-inflammatories, esters are used for their anti-inflammatory properties [disclosure 0829-0830] while myochrysine is utilized in the art for treating rheumatoid arthritis (RA) [Wiles, disclosure 0813], there is no correlation of treating the phenotype of corona virus with the targeted drug treatments in order to reverse differential gene expression of a specific phenotype.
Therefore, the administration of the targeted drug treatments and the targeted drug treatments of claims 37 and 45-46 do not integrate the recited judicial exception into a practical application because the claims do not recite limitations that have more than a nominal or insignificant relationship to the exception(s). See MPEP 2106.04(d)(2)(b).
Claim 32 recites the phenotype is associated with a coronavirus and administering a targeted treatment to treat the coronavirus. Claim 32 does not recite an additional element to which integrates the recited judicial exception claim 23 into a practical application because the administering of a treatment or prophylaxis limitations must have more than a nominal or insignificant relationship to the exception(s). The claim limitation must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. Thus, this administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Therefore, the administration step does not integrate the mental analysis step into a practical application. See MPEP 2106.04(d)(2).
Claim 34 recites administering the targeted drug treatment to the subject includes administering a therapeutically effective amount of a first composition to the subject and administering a therapeutically effective amount of a second composition different from the first composition to the subject. Claim 34 does not recite an additional element to which integrates the recited judicial exception of claim 23 into a practical application because the claim limitation must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. Thus, this administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Therefore, the administration step does not integrate the mental analysis step into a practical application. See MPEP 2106.04(d)(2).
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.
2B Analysis: Consideration of Practical Application
The claimed method also recited “additional elements” that are not limitations drawn to abstract ideas.
The recited additional element of using a targeted drug treatment (i.e., the targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof) of claims 23, 32, 34, 37, and 43-46 does not amount to more than the judicial exception because administering targeted drug treatments are well-known, routine, and conventional. To provide evidence of conventionality, Wiles et al. (Wiles) discloses using prednisolone [page 295 left col para 0800], dexamethasone [page 295 left col para 0800], diclofenac [page 295 left col para 0800], myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347]. Wiles discloses that the compounds can be to treat respiratory disease [page 23 left 0257]. Wiles discloses the compounds of the invention can be used to treat acute respiratory distress syndrome, adult respiratory distress syndrome [page 291 left col top para 0767]. Wiles discloses the drug of the invention can be used viral infection more generally, for example selected from Flaviviridae, Retroviruses, Coronaviridae, Poxviridae, Adenoviridae, Herpesviridae, Caliciviridae, Reoviridae, Picomaviridae, Togaviridae, Orthomyxoviridae, Rhabdoviridae, or Hepadnaviridae [page 289 right col para 0762] (Patent Pub: US 2020/0071301 Patent Pub Date: 05 March 2020).
To provide further evidence of conventionality, Wiles et al. (Wiles (2017)) discloses using prednisolone [col 65 lines 50-55], dexamethasone [col 65 lines 50-55], diclofenac [col 65 lines 60-65], myochrysine [col 67 lines 54-60], and ester [abstract]. Wiles (2017) discloses using the drugs for treating respiratory disease [col 13 lines 15-25] (US Patent: 9,732,103, Patent Date: 15 August 2017).
The recited additional element of administering a targeted treatment of claims 23, 34, 37, and 43-46 does not amount to more than the judicial exception because administering drug treatments are well-known, routine, and conventional.
The recited additional element of administering of claim 32 does not amount to more than the recited judicial exception because treating a subject with a coronavirus by administering drug treatments is well-known, routine, and conventional to perform the acts of administering a treatment. To exemplify conventionality of treating coronavirus with treatments, Zhou et al. (Zhou) teaches network-based drug repurposing for novel coronaviruses [title and abstract]. Zhou teaches a discovered subnetwork highlighting network-predicted drug-HCoV associations connecting 135 drugs and HCoVs [page 7 figure 4]. Zhou teaches a discovered drug-protein-HCoV network and 16 candidate repurposable drugs [page 8-9 fig 5] (Cell discovery, 2020-03, Vol.6 (1), p.14, Article 14).
In conclusion, when viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant’s arguments filed 25 August 2025, have been fully considered but the rejection is maintained. However, upon further consideration, a new ground(s) of rejection is made in view of the amendments filed 25 August 2025.
The Applicant states “the preceding rejections are no longer applicable to the subject claims and are therefore novel and nonobvious.” The Applicant states “In the Office Action dated June 22, 2023, on page 15, former Claims 14 and 15 were specifically identified as reciting patent-eligible subject matter. The use of diclofenac and myochrysine as treatments for coronavirus is not conventional and thus supports subject matter eligibility under MPEP § 2106.05(d).” [remarks, page 15].
In response and with respect to the Applicants argument regarding that using myochrysine and diclofenac to treat a corona virus are novel and nonobvious, the argument is not persuasive because the MPEP states “Although the courts often evaluate considerations such as the conventionality of an additional element in the eligibility analysis, the search for an inventive concept should not be confused with a novelty or non-obviousness determination. See Mayo, 566 U.S. at 91, 101 USPQ2d at 1973. As made clear by the courts, the "‘novelty’ of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claim falls within the § 101 categories of possibly patentable subject matter." Intellectual Ventures I v. Symantec Corp.,” The MPEP further states “the search for a § 101 inventive concept is thus distinct from demonstrating § 102 novelty."). In addition, the search for an inventive concept is different from an obviousness analysis under 35 U.S.C § 103”. ("The inventive concept inquiry requires more than recognizing that each claim element, by itself, was known in the art. . . . [A]n inventive concept can be found in the non-conventional and non-generic arrangement of known, conventional pieces."). Specifically, lack of novelty under 35 U.S.C § 102 or obviousness under 35 U.S.C § 103 of a claimed invention does not necessarily indicate that additional elements are well-understood, routine, conventional elements. Because they are separate and distinct requirements from eligibility, patentability of the claimed invention under 35 U.S.C § 102 and 103 with respect to the prior art is neither required for, nor a guarantee of, patent eligibility under 35 U.S.C § 101. The distinction between eligibility (under 35 U.S.C § 101) and patentability over the art (under 35 U.S.C § 102 or 103) is further discussed in MPEP § 2106.05 (d). See MPEP 2106.05(I).
Furthermore, the 35 U.S.C § 101 rejection was not obviated because the judicial exception in not integrated with the particular treatments. With respect to the conventionality of using diclofenac and myochrysine, the argument is not persuasive because as noted Step 2B of the 35 U.S.C § 101 rejection, it is conventional to use diclofenac and myochrysine to treat respiratory diseases or conditions (i.e., treating a coronaviridea infection). Therefore, the 35 U.S.C § 101 rejection is maintained.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 23-27, 30-31, and 40 under 35 U.S.C. 102(a)(1) as being anticipated by Ahsan et al. (Current Protocols in Bioinformatics, 2017-03, Vol.57 (1), p.7.15.1-7.15.30) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 47 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wiles et al. (Patent Pub: US 2020/0071301; Patent Pub Date: 05 March 2020).
Claim 47 recites method of treatment of a subject infected with a corona virus with a targeted drug treatment. Claim 47 recites administering the targeted drug treatment, wherein the targeted drug treatment includes a composition comprising a compound selected from a group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof.
Wiles et al. (Wiles) disclose “In one embodiment, a method for the treatment of such a disorder is provided that includes the administration of an effective amount of a compound of Formula I, Formula II, Formula III, Formula IV, or Formula V or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition, as described in more detail below.” [disclosure page 5 left col para 0039].
Wiles discloses using prednisolone [page 295 left col para 0800], dexamethasone [page 295 left col para 0800], diclofenac [page 295 left col para 0800], myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347]. Wiles discloses that the compounds can be to treat respiratory disease [page 23 left 0257]. Wiles discloses the compounds of the invention can be used to treat acute respiratory distress syndrome, adult respiratory distress syndrome [page 291 left col top para 0767]. Wiles discloses the drug of the invention can be used viral infection more generally, for example selected from Flaviviridae, Retroviruses, Coronaviridae, Poxviridae, Adenoviridae, Herpesviridae, Caliciviridae, Reoviridae, Picomaviridae, Togaviridae, Orthomyxoviridae, Rhabdoviridae, or Hepadnaviridae [page 289 right col para 0762].
Claim Rejections - 35 USC § 103
The instant rejection is maintained for reason for record in the Office Action mailed 28 January 2025 and modified in view of the amendments filed 25 August 2025. It is noted the amendments received 25 August 2025 are necessitated by new ground(s) of rejection.
The rejection of claim(s) 23-27, 28, 30-31, 33-34, and 40 under 35 U.S.C. 103 as being unpatentable over Ahsan et al., as set forth above for claims 23-27, 30-31 and 40 and in view of Kohly et al. (Frontiers in immunology, 2018-06, Vol.9, p.1300) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The rejection of claim 29 under 35 U.S.C. 103 as being unpatentable over Ahsan in view of Kohly, as applied to claims 23-27, 28, 30-31, 33-34 and 40 above, and in further view of Wagner et al. (Molecular Systems Biology, 2015-03, Vol.11 (3), p.791-n/a) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The rejection of claims 32 and 35-36 under 35 U.S.C. 103 as being unpatentable over Ahsan in view of Kohly, as applied to claims 23-27, 28, 30-31, 33-34 and 40 above, and in further view of Zhou et al. (Cell discovery, 2020-03, Vol.6 (1), p.14, Article 14) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
The claim(s) 37-39 and 41-42 under 35 U.S.C. 103 as being unpatentable over Ahsan in view of Kohly et al. (Frontiers in immunology, 2018-06, Vol.9, p.1300) in the Office Action mailed 28 January 2025 is withdrawn in view amendments received 25 August 2025.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 23-27, 30-32, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Ahsan et al. (Current Protocols in Bioinformatics, 2017-03, Vol.57 (1), p.7.15.1-7.15.30; Cited in the Office Action mailed 28 January 2025) in view of Wiles et al. (Patent Pub: US 2020/0071301 Patent Pub Date: 05 March 2020).
Claim 23 recites comparing biomolecules from a phenotype (disease) with a set of biomolecules [Specification page 16 [0051]] from a control set of biomolecules. Claim 23 recites identifying a set of biomolecules that is affected by a phenotype. Claims 23 recites identifying a member selected from a group consisting biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype that has been perturbed by the biomolecules. Claim 23 recites determining a targeted drug treatment configured to reverse differential expression of the biomolecule based on the member selected from the group. Claims 23 recites administering the targeted drug treatment, wherein the targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof.
Ahsan et al. (Ahsan) teaches using the publicly available dataset GSE47363. This data set was used to study the impact of miR-542-3p in osteosarcoma (USOS) cell. Ahsan teaches the sample data is a classic example of a control vs treated where the “control” is defined by expression of a mock control to U2OS cells and “treated” was defined by the treating the same cells with a mimic of miR-542-3p. Ahsan teaches the goal of the study was to understand the effect of miRNA has on gene expression throughout these cells. [page 7.15.7-7.15.8 “Files’], as in claim 23 comparing biomolecules from a phenotype (disease) with a set of biomolecules [Specification page 16 [0051]] from a control set of biomolecules. Here, the teachings of Ahsan are analogous because the dataset of Ahsan teaches using differential expression data U2OS cells as a control and U2OS cells treated with a mimic of miR-542-3p which further teaches a visual representation of comparing the differentially expressed gene targets.
Ahsan teaches that microRNA analysis that provides a summary view of the significant microRNA’s predicted based on the differentially gene in a data set [page 7.15.15 figure 7.15.8]. Here, the teachings of Ahsan are analogous because it provides the identity of targeted differentially expressed genes such as THRC and LPP, for example [page 17.15.15 fig 7.15.8], as in claim 23 identifying a set of biomolecules that is affected by a phenotype step.
Ahsan teaches a panel that shows a small part of the MAPK signaling pathway using KEGG. The pathway shows the location of various gene or gene products, what gene interacts with the other genes, type of each interaction (activation, repression, phosphorylation), the direction of the signal propagation, and potentially other things [page 7.15.4 fig 7.15.1]. Ahsan teaches identifying differentially expressed genes for the selected miRNA is provided (top center) along with a boxplot showing the differentially expressed genes regulated by the specified miRNA [page 7.15.5 figure 7.15.8] which teaches identified members of the gene set. Ahsan teaches the limitation because the figure 7.15.1 teaches taste transduction pathway (biological pathway). Ahsan teaches a mechanism acting on the apical and basal interaction (biological mechanism). Ahsan teaches using gene ontology terms and (biological processes). Ahsan teaches calcium signaling pathway and cAMP processing to PKA to inhibit KCN (biochemical function). Ahsan teaches using Total Perturbation” for a given gene is the combination of the measured log fold change for that gene plus the cumulative effect of all signals coming to that gene from all its upstream regulators (upstream regulator) [page 7.15.17 last para], as in claim 23 identifying a member selected from a group consisting of biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype that has been perturbed by the biomolecules.
Ahsan teaches that iPathwayGuide (iPG) analyzes a list of differentially expressed genes and identifies the signaling pathways and Gene Ontology (GO) terms that are significant between the two phenotypes. In addition, iPG also identifies the diseases and drugs that are associated with any of the pathways involved, as well as the putative mechanisms that would explain all measured gene expression changes throughout the system [page 7.15.2], as in claim 23 determining a targeted drug treatment configured to reverse differential expression of the biomolecule based on the member selected from the group. Here, the limitations of Ahsan are analogous because it teaches that iPG identifies a disease and associated drug.
Dependent claims 24-27 and 30-31
Ahsan teaches that gene expression alone can measured gene expression alone, iPG can also infer activity of microRNAs (miRNAs) that may explain the differences between the two phenotypes [page 7.15.2, lines 11-12], as in claim 24.
Ahsan teaches that there are two types of differential expression data sets in that can be analyzed in iPG: datasets that involve two experimental conditions that form a contrast (Basic Protocol) and datasets derived from the comparison of two or more experimental conditions [page 7.15.5 par. 3]. Ahsan teaches the interpretation of the gene expression differences between two conditions e.g., control versus treated or healthy vs cancer [page 7.15.5 par. 3]. Ahsan teaches using the publicly available dataset GSE47363. This data set was used to study the impact of miR-542-3p in osteosarcoma (USOS) cell. The sample data is a classic example of a control vs treated where the “control” is defined by expression of a mock control to U2OS cells and “treated” was defined by the treating the same cells with a mimic of miR-542-3p. Here, the teachings of Ahsan are analogous because the dataset encompasses teaches an affected dataset while the treated cell of the dataset were treated with a mimic of miR-542-3p [page 7.15.8], as in claim 25.
Ahsan teaches an over-enrichment analysis to determine whether there is an enrichment in differentially expression genes linked to phenotype: over-representation approach [page 7.15.2, par. 2], as in claim 26.
Ahsan teaches a panel that shows a small part of the MAPK signaling pathway using KEGG. The pathway shows the location of various gene or gene products, what gene interacts with the other genes, type of each interaction (activation, repression, phosphorylation), the direction of the signal propagation, and potentially other things [page 7.15.4 fig 7.15.1]. Ahsan teaches identifying differentially expressed genes for the selected miRNA is provided (top center) along with a boxplot showing the differentially expressed genes regulated by the specified miRNA [page 7.15.5 figure 7.15.8] which teaches identified members of the gene set. Ahsan teaches the limitation because the figure 7.15.1 teaches taste transduction pathway (biological pathway). Ahsan teaches a mechanism acting on the apical and basal interaction (biological mechanism). Ahsan teaches using gene ontology terms and (biological processes). Ahsan teaches calcium signaling pathway and cAMP processing to PKA to inhibit KCN (biochemical function). Ahsan teaches using Total Perturbation” for a given gene is the combination of the measured log fold change for that gene plus the cumulative effect of all signals coming to that gene from all its upstream regulators (upstream regulator). Here, the teachings of Kohly are analogous because Ahsan teaches the importance of adding pathway data to a general gene dataset containing only simple gene set without pathway information. This suggests using data other than a gene set such as using the biochemical function or biological mechanism data of 7.15.1, for example, as in claim 27.
Ahsan teaches iPathwayGuide calculates whether each signal between any two genes on the pathway is consistent with the phenomena described by the pathway, i.e., coherent, and then identifies those situations in which there are chains of such coherent steps that are longer than a minimum length set by the user (e.g., 3 or 4). Ahsan teaches these long chains of coherent perturbation propagation can be considered putative mechanisms and are reported to the user [page 7.15.4], as in claim 30. Here, the teachings of Ahsan are analogous because Ahsan teaches the coherence is described as whether A represses gene B and gene A is downregulated while gene B is up-regulated, this particular step is consistent with the expected behavior. Therefore, the perturbations of the genes A and B are said to be coherent which links two or more biomolecules affect each other function.
Ahsan teaches using iPathwayGuide to provide to identify putative mechanism. Ahsan teaches that iPathwayGuide requires a minimum of six samples in each phenotype group is recommended, although results will be greatly improved with more samples. Ahsan teaches iPG requires the following information for each gene, an identifier, a relative log fold change value between the given conditions, and the corresponding p-value [page 7.15.5], as in claim 31
Ahsan does not teach a subject with corona virus of claim 23. Ahsan does not teach wherein the targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof of claim 23. Ahsan does not teach claims 32 and 43-44.
Wiles
Wiles et al. (Wiles) disclose “In one embodiment, a method for the treatment of such a disorder is provided that includes the administration of an effective amount of a compound of Formula I, Formula II, Formula III, Formula IV, or Formula V or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition, as described in more detail below.” [disclosure page 5 left col para 0039]. Wiles et al. (Wiles) discloses using prednisolone [page 295 left col para 0800], dexamethasone [page 295 left col para 0800], diclofenac [page 295 left col para 0800], myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347]. Wiles discloses that the compounds can be to treat respiratory disease [page 23 left 0257]. Wiles discloses the compounds of the invention can be used to treat acute respiratory distress syndrome, adult respiratory distress syndrome [page 291 left col top para 0767]. Wiles discloses the drug of the invention can be used viral infection more generally, for example selected from Flaviviridae, Retroviruses, Coronaviridae, Poxviridae, Adenoviridae, Herpesviridae, Caliciviridae, Reoviridae, Picomaviridae, Togaviridae, Orthomyxoviridae, Rhabdoviridae, or Hepadnaviridae [page 289 right col para 0762], as in claim 23 a subject with corona virus and administering a targeted drug treatment, wherein the targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof of claim 23. Here, it is obvious that drug treatments like prednisolone inherently reverse differential gene expression to control inflammation, for example.
Dependent claims 32 and 43-44.
Wiles et al. (Wiles) discloses using prednisolone [page 295 left col para 0800], dexamethasone [page 295 left col para 0800], diclofenac [page 295 left col para 0800], myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347]. Wiles discloses that the compounds can be to treat respiratory disease [page 23 left 0257]. Wiles discloses the compounds of the invention can be used to treat acute respiratory distress syndrome, adult respiratory distress syndrome [page 291 left col top para 0767]. Wiles discloses the drug of the invention can be used viral infection more generally, for example selected from Flaviviridae, Retroviruses, Coronaviridae, Poxviridae, Adenoviridae, Herpesviridae, Caliciviridae, Reoviridae, Picomaviridae, Togaviridae, Orthomyxoviridae, Rhabdoviridae, or Hepadnaviridae [page 289 right col para 0762], as in claim 32.
Wiles discloses “In certain embodiments the pharmaceutical composition is in a dosage form that contains from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of the active compound and optionally from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of an additional active agent in a unit dosage form. Examples are dosage forms with at least about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600,
650, 700, 750, 800, 900, 1000, 1100, 1200, 1250, 1300, 1400, 1500, or 1600 mg of active compound, or its salt or prodrug. In one embodiment, the dosage form has at least about 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 200 mg, 400 mg, 500 mg, 600 mg, 1000 mg, 1200 mg, or 1600 mg of active compound, or its salt. The amount of active compound in the dosage form is calculated without reference to the salt. The dosage form can be administered, for example, once a day (q.d.), twice a day (b.i.d.), three times a day (t.i.d.), four times a day ( q.i.d.), once every other day (Q2d), once every third day (Q3d), as needed, or any dosage schedule that provides treatment of a disorder described herein.” [disclosure page 282 left col para 0713]. Wiles et al. (Wiles) discloses using diclofenac [page 295 left col para 0800] and myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347], as in claims 43-44. Here, the claims are rendered obvious because Wiles discloses the pharmaceutical compositions can contain multiple dosages ranging from 0.5mg to 1600 mg a day (q.d). It is obvious that the compositions can contain diclofenac and myochrysine. It is further obvious to adjust a medication regime for taking medication during time periods such as everyday or weekly because Wiles discloses “any dosage schedule that provides treatment of a disorder described herein.” [disclosure page 282 left col para 0713].
It would have been obvious to one of ordinary skill in the art by the effective filing data of the claimed invention to modify Ahsan in view of Wiles because Wiles discloses using compounds such as diclofenac, prednisolone, dexamethasone [disclosure page 295 left col para 0800] for treating respiratory disease [page 23 left col para 0260] or conoraviridea [disclosure page 289 right col para 0762]. One of ordinary skill in the art would be motivated to combine Ahsan in view of Wiles because Wiles discloses using compounds formulas that can be used for treating or preventing respiratory disease [page 23 left col para 0260]. Here, there is a reasonable expectation of success to combine Ahsan in view of Wiles because Wiles discloses drug treatments that can be used to treat coronoviridea family viruses [disclosure page 289 right col para 0762]. As such, combining the teachings of Ahsan with the drug treatments of Wiles would yield a predictable method for identifying a targeted drug treatment for a person infected with a respiratory disease or condition (i.e., corona virus infection) and treating the subject with the medication.
Claim(s) 28 and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ahsan in view of Wiles, as applied to claims 23-27, 30-32, and 43-44, and in further view of Kohly et al. (Frontiers in immunology, 2018-06, Vol.9, p.1300; Cited in the Office Action mailed 28 January 2025).
Ahsan in view of Wiles teaches claims 23-27, 30-32, and 43-44.
Ahsan in view of Wiles teaches a method identifying a targeted drug treatment and treating a subject with a respiratory condition (i.e., infected with corona virus) by administering a targeted drug therapy.
Ahsan in view of Wiles does not teaches claims 28 and 33-34.
Claim 28
With respect to claim 28, the claim is rendered obvious because Ahsan teaches x axis measures the p-value obtained using the classical over-representation or enrichment analysis (pORA) [page 7.15.16]. Ahsan teaches (pORA) represents the probability of obtaining just by chance a number of differentially expressed genes greater than or equal to the one observed on the given pathway in the actual data [7.15.16 pathways], as in claim 28 determining a first probability of p over-representation (pORA) representing a probability of observing an actual number of biomolecules affected by the phenotype in the member.
Ahsan teaches the y axis represents the p-value obtained from total perturbation accumulation (pAcc) in the pathway. Ahsan teaches pAcc is calculated based on the amount of perturbation, which is defined by the propagation of the measured expression changes across the pathway topology [7.15.16 pathways], as in claim 28 determining a second probability including a second probability value (pACC) representing the probability of observing a measured total perturbation accumulation in the member.
However, Ahsan does not teach claim 28 combining the first probability value (pORA) and the second probability value (pACC) so as to determine an uncorrected joint p-value for the member and does not teach claim 28 correcting the uncorrected joint p-value for multiple comparisons based on a number of members. Ahsan does not teach claims 33-34.
Kohly et al. (Kohly) teach combining pORA and pAcc is done to produce a unique global p value using Fisher’s method [page 6 right col], as in claim 28 combining the first probability value (pORA) and the second probability value (pACC) so as to determine an uncorrected joint p-value for the member. Kohly teaches combining pORA and pAcc is done to produce a unique global p value using Fisher’s method, which is then corrected for multiple comparisons using the false discovery rate method [page 6 right col], as in claim 28 correcting the uncorrected joint p-value for multiple comparisons based on a number of members.
With respect to claim 33, the claim is obvious because as evidenced by Ahsan in view of Kohly above, it encompasses the same limitations as claims 23 and 28 which are rejected.
Kohly teaches evaluate the direct role of RvE1 impacting bone cells, primary calvarial mouse osteoblasts were stimulated with interleukin (IL)-6 (10 ng/ml) and IL-6 receptor (10 ng/ml) and simultaneously incubated with or without RvE1 (100 nM) [abstract], as in claim 34. Here, treatments of interleukin (IL)-6 (10 ng/ml) and IL-6 receptor (10 ng/ml) could be the first composition and the RvE1 (100 nM) could be the second composition, for example. Here, the teachings of Kohly provide different therapeutic compositions while including a composition using two different treatment compositions.
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify the method of Ahsan in view Wiles, and in further view of Kohly because Kohly teaches using RNA-seq and transcriptomic analysis pipeline analysis that revealed RvE1 significantly downregulates osteoclast differentiation mediated by differential regulation of NFκB and PI3K–AKT pathways. One of ordinary skill in the art would recognize that Ahsan in view Wiles, and in further view of Kohly because Kohly are in similar fields of endeavor. One of ordinary skill in the art would be motivated to combine Ahsan in view Wiles, and in further view of Kohly because Kohly teaches using iPathwayGuide to find a significant perturbation in the osteoclast differentiation pathway after stimulation of osteoblasts with IL-6 [page 6 fig 4]. There is a reasonable expectation of success combining Ahsan in view Wiles, and in further view of Kohly because Kohly teach methods for evaluating differential gene expression. Here, Ahsan and Kohly account for pORA and pACC, with respect to overrepresented genes, but Kohly teaches combining the pORA and pACC into a single value to construct a global p-value using the Fischer’s method that is then further corrected for multiple comparisons using the false discovery rate method. Therefore, combining the methods of Ahsan in view Wiles, and in further view of Kohly would yield a predictable method for identifying a targeted drug treatment for a subject infected with a corona virus and administering the target drug to a subject.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Ahsan in view of in view of Wiles in view of Kohly, as applied to claims 28 and 33-34 above, and in further view of Wagner et al. (Molecular Systems Biology, 2015-03, Vol.11 (3), p.791-n/a; Cited in the Office Action mailed 28 January 2025).
Ahsan in view of Wiles in view of Kohly teaches claims 28 and 33-34.
Ahsan in view of Wiles in view of Kohly teaches a method identifying a targeted drug treatment and treating a subject with a respiratory condition (i.e., infected with corona virus) by administering a targeted drug therapy.
Ahsan in view of Wiles does not teach claim 29.
With respect to claim 29, the claim is obvious because Wagner teaches deviations from the baseline gene expression and deviations from the baseline physiology are correlated across different experimental groups and treatment regimens [page 8 figure 4]. Wagner teaches post-treatment deviation from the baseline omic state (e.g., in gene expression) is correlated with a deviation from the baseline physiology with p-values of less than 2x10 -10. Wagner teaches first identified the genes that were most differentially expressed between the HFD and LFD groups [page 2 right col].
With further respect to claim 29, the claim is further obvious because Ahsan further teaches determining the targeted drug step as evidenced above. Here, the teachings are analogous because, as evidenced above, Ahsan teaches results from iPG allow users to efficiently generate hypotheses, identify biomarkers, elucidate molecular mechanisms, discover drug targets, and measure therapeutic response via the given comparison of two or more conditions [page 7.15.2 top paragraph] which makes obvious determining a targeted drug treatment because Ahsan teaches iPG can discover drug targets to which can be targeted by drugs. Ahsan teaches measuring therapeutics which makes obvious administering therapeutics because administering a drug is a key step for measuring therapeutic between two or more conditions.
It would have been obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Ahsan in view Wiles in of view of Kohly, and in further view of Wagner because Wagner teaches methods for analyzing treatments that reverse gene expression in dyslipidemia [title]. One of ordinary skill in the art would be motivated to combine Ahsan in view Wiles in view of Kohly, and in further view of Wagner because Wagner because Wagner provides lists of treatments and uses geneset enrichment analysis (GSEA) to detect pathways that are enriched in genes that are either upregulated or downregulated in each treatment group compared with the HFD-16-week group [Supplementary GSEA analysis page 5]. Although Wagner does not teach using iPathwayGuide as Ahsan and Kohly, one of ordinary skill in the art would expect a reasonable success in combining Ahsan in view Wiles in of view of Kohly, and in further view of Wagner because Wagner provides a pathway analysis using GSEA enrichment analysis to determine if a treatment reverses gene expression. Here, the combination of Ahsan in view Wiles in of view of Kohly, and in further view of Wagner would yield predictable a method using ipathway analysis that can be utilized to facilitate determining targeted drug treatments.
Claims 35-36 are is rejected under 35 U.S.C. 103 as being unpatentable over Ahsan in view Wiles, as applied to claims 23-27, 30-32, and 43-44 above, and in further view of Zhou et al. (Cell discovery, 2020-03, Vol.6 (1), p.14, Article 14; Cited in the Office Action mailed 28 January 2025).
Ahsan in view of Wiles teaches claims 23-27, 30-32, and 43-44.
Ahsan in view of Wiles in view of Kohly teaches a method identifying a targeted drug treatment and treating a subject with a respiratory condition (i.e., infected with corona virus) by administering a targeted drug therapy.
Ahsan in view of Wiles does not teaches claim 35-36.
With respect to claim 35, the claim is obvious because Ahsan teaches that quantitative characterization and interpretation of the gene expression differences between two conditions, e.g., control versus treated, healthy versus cancer, drug A versus drug B, etc. [page 7.15.5]. Zhou teaches Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%) [abstract]. Therefore, it would be obvious to use a dataset to compare phenotypes that would encompass cells that do and do not present the desired phenotype.
With respect to claim 36, the claim is obvious because Zhou teaches comparing different coronaviruses to determine which drugs can be repurposed to treat a coronavirus. Ahsan teaches that quantitative characterization and interpretation of the gene expression differences between two conditions, e.g., control versus treated, healthy versus cancer, drug A versus drug B, etc. [page 7.15.5]. Zhou teaches Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%) [abstract]. Therefore, it would be obvious to use a dataset encompassing two conditions such as cells with a virus and cells without the virus.
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Ahsan in view Wiles, and in further view of Zhou because Zhou teaches performing enrichment analysis to determine treatments to repurpose for treating a coronavirus. One of ordinary skill in the art would recognize that Ahsan, Wiles, and Zhou are related to similar field of endeavor. One of ordinary skill would be motivated to combine Ahsan in view Wiles, and in further view of Zhou because Zhou teaches analyzing coronavirus pathways and networks to determine treatments regarding coronaviruses. One of ordinary skill in the art would expect a reasonable success combining Ahsan in view Wiles, and in further view of Zhou because Zhou teaches network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2 [abstract]. This there is a further expectation of success that using Ahsan in view Wiles, and in further view of Zhou because combining the prior art elements according to known methods, such as using GSEA, would yield a predictable method for identifying targeted drug treatments that can reverse differential gene expression and administering the targeted drug treatments.
Claim(s) 37-39 and 45-46 are rejected under 35 U.S.C. 103 as being unpatentable over Ahsan in view of Wiles in view of Kohly in view of Wagner.
Claims 37 recites a method for identifying a targeted drug treatment for treatment of a phenotype in a subject infected with a corona virus and treating the subject with the targeted drug treatment. Claims 37 recites identifying a set of biomolecules affected by the phenotype, each biomolecule having a differential expression between the phenotype and a control.
Claims 37 recites identifying a member, wherein the member is selected from a group consisting of a biological pathway, a biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype.
Claims 37 recites determining a first probability including a first probability value of p over-representation (pORA) representing a probability of observing an actual number of biomolecules affected by the phenotype in the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype just by chance.
Claims 37 recites determining a second probability including a second probability value (pACC) representing the probability of observing a measured total perturbation accumulation in the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype just by chance.
Claims 37 recites combining the first probability value (pORA) and the second probability value (pACC) so as to determine a a unique pathway-specific uncorrected joint p-value for the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype just by chance.
Claims 37 recites correcting the unique pathway-specific uncorrected joint p-value for multiple comparisons based on a number of members, wherein the members are selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator perturbed by the set of biomolecules affected by the phenotype using a False Discovery Rate (FDR) or Bonferroni correction method.
Claims 37 recites determining the targeted drug treatment configured to reverse the differential expression of the biomolecule based upon the member selected from the group consisting of the biological pathway, the biological mechanism, the biological process, the biochemical function, and the upstream regulator and selecting the targeted drug treatment when the corrected joint p-value is less than a predetermined threshold and reverses the differential expression of two of the biomolecules; and administering the targeted drug treatment to the subject.
Claim 37 recites administering the targeted drug treatment to the subject, wherein the targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof.
Claim 37
Ahsan teaches that microRNA analysis that provides a summary view of the significant microRNA’s predicted based on the differentially gene in a data set [page 7.15.15 figure 7.15.8]. Here, the teachings of Ahsan are analogous because it provides the identity of targeted differentially expressed genes such as THRC and LPP, for example [page 17.15.15 fig 7.15.8], as in claim 37 identifying a set of biomolecules that is affected by a phenotype step.
Ahsan teaches a panel that shows a small part of the MAPK signaling pathway using KEGG. The pathway shows the location of various gene or gene products, what gene interacts with the other genes, type of each interaction (activation, repression, phosphorylation), the direction of the signal propagation, and potentially other things [page 7.15.4 fig 7.15.1]. Ahsan teaches identifying differentially expressed genes for the selected miRNA is provided (top center) along with a boxplot showing the differentially expressed genes regulated by the specified miRNA [page 7.15.5 figure 7.15.8] which teaches identified members of the gene set. Ahsan teaches the limitation because the figure 7.15.1 teaches taste transduction pathway (biological pathway). Ahsan teaches a mechanism acting on the apical and basal interaction (biological mechanism). Ahsan teaches using gene ontology terms and (biological processes). Ahsan teaches calcium signaling pathway and cAMP processing to PKA to inhibit KCN (biochemical function). Ahsan teaches using Total Perturbation” for a given gene is the combination of the measured log fold change for that gene plus the cumulative effect of all signals coming to that gene from all its upstream regulators (upstream regulator) [page 7.15.17 last para], as in claim 37 identifying a member selected from a group consisting of biological mechanism, a biological process, a biochemical function, and an upstream regulator perturbed by the set of biomolecules affected by the phenotype that has been perturbed by the biomolecules.
Ahsan teaches x axis measures the p-value obtained using the classical over-representation or enrichment analysis (pORA) [page 7.15.16]. Ahsan teaches (pORA) represents the probability of obtaining just by chance a number of differentially expressed genes greater than or equal to the one observed on the given pathway in the actual data [7.15.16 pathways], as in claim 37 determining a first probability of p over-representation (pORA) representing a probability of observing an actual number of biomolecules affected by the phenotype in the member.
Ahsan teaches the y axis represents the p-value obtained from total perturbation accumulation (pAcc) in the pathway. Ahsan teaches pAcc is calculated based on the amount of perturbation, which is defined by the propagation of the measured expression changes across the pathway topology [7.15.16 pathways], as in claim 37 determining a second probability including a second probability value (pACC) representing the probability of observing a measured total perturbation accumulation in the member.
Ahsan teaches that iPathwayGuide (iPG) analyzes a list of differentially expressed genes and identifies the signaling pathways and Gene Ontology (GO) terms that are significant between the two phenotypes. In addition, iPG also identifies the diseases and drugs that are associated with any of the pathways involved, as well as the putative mechanisms that would explain all measured gene expression changes throughout the system [page 7.15.2], as in claim 23 determining a targeted drug treatment configured to reverse differential expression of the biomolecule based on the member selected from the group. Here, the limitations of Ahsan are analogous because it teaches that iPG identifies a disease and associated drug.
Dependent claims 38-39
Ahsan teaches iPathwayGuide calculates whether each signal between any two genes on the pathway is consistent with the phenomena described by the pathway, i.e., coherent, and then identifies those situations in which there are chains of such coherent steps that are longer than a minimum length set by the user (e.g., 3 or 4). Ahsan teaches these long chains of coherent perturbation propagation can be considered putative mechanisms and are reported to the user [page 7.15.4], as in claim 38. Here, the teachings of Ahsan are analogous because Ahsan teaches the coherence is described as whether A represses gene B and gene A is downregulated while gene B is up-regulated, this particular step is consistent with the expected behavior. Therefore, the perturbations of the genes A and B are said to be coherent which links two or more biomolecules affect each other function.
Ahsan teaches using iPathwayGuide to provide to identify putative mechanism. Ahsan teaches that iPathwayGuide requires a minimum of six samples in each phenotype group is recommended, although results will be greatly improved with more samples. Ahsan teaches iPG requires the following information for each gene, an identifier, a relative log fold change value between the given conditions, and the corresponding p-value [page 7.15.5], as in claim 39.
However, Ahsan does not teach claim 37 a subject infected with a corona virus. Ahsan does not teach claim 37 combining the first probability value (pORA) and the second probability value (pACC) so as to determine an uncorrected joint p-value for the member. Ahsan does not teach claim 37 correcting the uncorrected joint p-value for multiple comparisons based on a number of members. Ahsan does not teach claim 37 the biochemical function, and the upstream regulator and selecting the targeted drug treatment when the corrected joint p-value is less than a predetermined threshold and reverses the differential expression of two of the biomolecules, and administering the targeted drug treatment to the subject. Ahsan does not teach claim administering step. Ahsan does not teach claims 45-46.
Kohly et al. (Kohly) teach combining pORA and pAcc is done to produce a unique global p value using Fisher’s method [page 6 right col], as in claim 37 combining the first probability value (pORA) and the second probability value (pACC) so as to determine an uncorrected joint p-value for the member.
Kohly teaches combining pORA and pAcc is done to produce a unique global p value using Fisher’s method, which is then corrected for multiple comparisons using the false discovery rate method [page 6 right col], as in claim 37 correcting the uncorrected joint p-value for multiple comparisons based on a number of members.
Wiles et al. (Wiles) disclose “In one embodiment, a method for the treatment of such a disorder is provided that includes the administration of an effective amount of a compound of Formula I, Formula II, Formula III, Formula IV, or Formula V or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition, as described in more detail below.” [disclosure page 5 left col para 0039]. Wiles et al. (Wiles) discloses using prednisolone [page 295 left col para 0800], dexamethasone [page 295 left col para 0800], diclofenac [page 295 left col para 0800], myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347]. Wiles discloses that the compounds can be to treat respiratory disease [page 23 left 0257]. Wiles discloses the compounds of the invention can be used to treat acute respiratory distress syndrome, adult respiratory distress syndrome [page 291 left col top para 0767]. Wiles discloses the drug of the invention can be used viral infection more generally, for example selected from Flaviviridae, Retroviruses, Coronaviridae, Poxviridae, Adenoviridae, Herpesviridae, Caliciviridae, Reoviridae, Picomaviridae, Togaviridae, Orthomyxoviridae, Rhabdoviridae, or Hepadnaviridae [page 289 right col para 0762], as in claim 37 a subject with corona virus and claim 37 administering a targeted drug treatment, wherein the targeted drug treatment includes a composition comprising a compound selected from the group consisting of prednisolone, dexamethasone, diclofenac, myochrysine, esters thereof, derivatives thereof, salts thereof, and combinations thereof. Here, it is obvious that drug treatments like prednisolone inherently reverse differential gene expression to control inflammation, for example.
With respect to claim 37 the biochemical function, and the upstream regulator and selecting the targeted drug treatment when the corrected joint p-value is less than a predetermined threshold and reverses the differential expression of two of the biomolecules, the claimed limitation is obvious because Wagner teaches deviations from the baseline gene expression and deviations from the baseline physiology are correlated across different experimental groups and treatment regimens [page 8 figure 4]. Wagner teaches post-treatment deviation from the baseline omic state (e.g., in gene expression) is correlated with a deviation from the baseline physiology with p-values of less than 2x10 -10. Wagner teaches first identified the genes that were most differentially expressed between the HFD and LFD groups [page 2 right col]. With further respect to claim 37 the biochemical function, and the upstream regulator and selecting the targeted drug treatment when the corrected joint p-value is less than a predetermined threshold and reverses the differential expression of two of the biomolecules, the claimed limitation is further obvious because Ahsan further teaches determining the targeted drug step as evidenced above. Here, the teachings are analogous because, as evidenced above, Ahsan teaches results from iPG allow users to efficiently generate hypotheses, identify biomarkers, elucidate molecular mechanisms, discover drug targets, and measure therapeutic response via the given comparison of two or more conditions [page 7.15.2 top paragraph] which makes obvious determining a targeted drug treatment because Ahsan teaches iPG can discover drug targets to which can be targeted by drugs. Ahsan teaches measuring therapeutics which makes obvious administering therapeutics because administering a drug is a key step for measuring therapeutic between two or more conditions.
Dependent claims 45-46
Wiles discloses “In certain embodiments the pharmaceutical composition is in a dosage form that contains from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of the active compound and optionally from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of an additional active agent in a unit dosage form. Examples are dosage forms with at least about 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 10, 15, 20, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 900, 1000, 1100, 1200, 1250, 1300, 1400, 1500, or 1600 mg of active compound, or its salt or prodrug. In one embodiment, the dosage form has at least about 1 mg, 5 mg, 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 200 mg, 400 mg, 500 mg, 600 mg, 1000 mg, 1200 mg, or 1600 mg of active compound, or its salt. The amount of active compound in the dosage form is calculated without reference to the salt. The dosage form can be administered, for example, once a day (q.d.), twice a day (b.i.d.), three times a day (t.i.d.), four times a day ( q.i.d.), once every other day (Q2d), once every third day (Q3d), as needed, or any dosage schedule that provides treatment of a disorder described herein.” [disclosure page 282 left col para 0713]. Wiles et al. (Wiles) discloses using diclofenac [page 295 left col para 0800] and myochrysine [page 297 right col para 0813], and esters [page 29 left col 0338-0347], as in claims 45-46. Here, the claims are rendered obvious because Wiles discloses the pharmaceutical compositions can contain multiple dosages ranging from 0.5mg to 1600 mg a day (q.d). It is obvious that the compositions can contain diclofenac and myochrysine. It is further obvious to adjust a medication regime for taking medication during time periods such as everyday or weekly because Wiles discloses “any dosage schedule that provides treatment of a disorder described herein.” [disclosure page 282 left col para 0713].
It would have been obvious to one of ordinary skill in the art by the effective filing data of the claimed invention to modify Ahsan in view of Wiles because Wiles discloses using compounds such as diclofenac, prednisolone, dexamethasone [disclosure page 295 left col para 0800] for treating respiratory disease [page 23 left col para 0260] or conoraviridea [disclosure page 289 right col para 0762]. One of ordinary skill in the art would be motivated to combine Ahsan in view of Wiles because Wiles discloses using compounds formulas that can be used for treating or preventing respiratory disease [page 23 left col para 0260]. Here, there is a reasonable expectation of success to combine Ahsan in view of Wiles because Wiles discloses drug treatments that can be used to treat coronoviridea family viruses [disclosure page 289 right col para 0762]. As such, combining the teachings of Ahsan with the drug treatments of Wiles would yield a predictable method for identifying a targeted drug treatment for a person infected with a respiratory disease or condition (i.e., corona virus infection) and treating the subject with the medication.
It would be obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify the method of Ahsan in view Wiles in view of Kohly because Kohly teaches using RNA-seq and transcriptomic analysis pipeline analysis that revealed RvE1 significantly downregulates osteoclast differentiation mediated by differential regulation of NFκB and PI3K–AKT pathways. One of ordinary skill in the art would recognize that Ahsan in view Wiles in view of Kohly because Kohly are in similar fields of endeavor. One of ordinary skill in the art would be motivated to combine Ahsan in view Wiles in view of Kohly because Kohly teaches using iPathwayGuide to find a significant perturbation in the osteoclast differentiation pathway after stimulation of osteoblasts with IL-6 [page 6 fig 4]. There is a reasonable expectation of success combining Ahsan in view Wiles in view of Kohly because Kohly teach methods for evaluating differential gene expression. Here, Ahsan and Kohly account for pORA and pACC, with respect to overrepresented genes, but Kohly teaches combining the pORA and pACC into a single value to construct a global p-value using the Fischer’s method that is then further corrected for multiple comparisons using the false discovery rate method. Therefore, combining the methods of Ahsan in view Wiles in view of Kohly because Kohly would yield predictable a method for identifying a targeted drug treatment for a subject infected with a corona virus and administering the target drug to a subject.
It would have been obvious to one of ordinary skill in the art by the effective filing date of the claimed invention to modify Ahsan in view Wiles in of view of Kohly in view of Wagner because Wagner teaches methods for analyzing treatments that reverse gene expression in dyslipidemia [title]. One of ordinary skill in the art would be motivated to combine Ahsan in view Wiles in of view of Kohly in view of Wagner because Wagner teaches lists of treatments and uses geneset enrichment analysis (GSEA) to detect pathways that are enriched in genes that are either upregulated or downregulated in each treatment group compared with the HFD-16-week group [Supplementary GSEA analysis page 5]. Although Wagner does not teach using iPathwayGuide as Ahsan and Kohly, one of ordinary skill in the art would expect a reasonable success in combining Ahsan in view Wiles in of view of Kohly in view of Wagner because Wagner provides a pathway analysis using GSEA enrichment analysis to determine if a treatment reverses gene expression. Here, the combination of Ahsan in view Wiles in of view of Kohly in view of Wagner would yield predictable a method using ipathway analysis that can be utilized to facilitate determining targeted drug treatments.
Response to Arguments
Applicant’s arguments filed 25 August 2025, have been fully considered and are not persuasive. However, upon further consideration, a new ground(s) of rejection is made in view of the amendments filed 25 August 2025. Here, Ahsan, Wiles, Kohly, Wagner, and Zhou address the amendments received 25 August 2025.
Conclusion
Claims 23-39 and 43-47 are rejected.
No claims are allowed.
Finality
This 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.
Inquires
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH C PULLIAM whose telephone number is (571)272-8696. The examiner can normally be reached 0730-1700 M-F.
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, Karlheinz Skowronek can be reached at (571) 272-9047. 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.
/J.C.P./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
Prosecution Insights