DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. This action is in response to the amendment filed on 09 April 2026. Applicant's arguments and amendments to the claims have been fully considered but do not place the application in condition for allowance. All rejections not reiterated herein are hereby withdrawn. In particular, the previous rejection of claims 1-5, 10, 23, 25, 26 and 28 on the basis that that the claims contain an improper Markush grouping of alternatives has been obviated by the amendments to the claims. The previous rejection of claims 1-5, 10, 23, 25, 26 and 28 under 35 U.S.C. 112(b) and the previous rejection of claims 23, 25 and 26 under 35 U.S.C. 112(d) have been obviated by the amendments to the claims.
Claim Status
3. Claims 1-5, 25, 26, and 28 are pending and have been examined herein.
Maintained / Modified Claim Rejections - 35 USC § 101
4. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 25, 26, and 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature / natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant' s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” which discusses the Alice/Mayo two-part test for evaluating subject matter eligibility.
Regarding Step 1 of the subject matter eligibility test set forth at MPEP 2106III, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite the correlation between the level of isoforms of the Elavl2 gene and pre-symptomatic ALS. That is, the claims recite “identifying the subject as having pre-symptomatic ALS when the ΔΨ score is a positive value” wherein the ΔΨ score is a score based on the level of isoforms of the ELavl2 gene. As in Mayo Collaborative Services v. Prometheus, the recited relationship is a natural phenomenon that exists apart from any human action. See also Cleveland Clinic Foundation v. True Health Diagnostic, LLC, 2018-1218 (Fed Cir. 2019) which states that “The re-phrasing of the claims does not make them less directed to a natural law.”
The claims also recite the judicial exception of an abstract idea and particularly mental processes.
MPEP 2106.04(a) states that the enumerated groupings of abstract ideas include:
“1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);…
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).”
The claims require performing the steps of “calculating” a psi score; “comparing” a psi score to that of a control and “identifying” a subject as having pre-symptomatic ALS if the absolute value of the ΔΨ score is a positive value.
Neither the specification nor the claims set forth a limiting definition for “calculating,” "comparing" or “identifying” and the claims do not set forth how these steps are accomplished. The broadest reasonable interpretation of the “comparing” step is that this step may be accomplished by critical thinking processes. Such “comparing” thereby encompasses only an abstract idea / process. Similarly, “identifying” may also be accomplished by critical thinking processes. “Identifying” may also be accomplished verbally. Such verbal communication is also abstract, having no particular concrete or tangible form.
The calculating step may also be accomplished by critical thinking processes or with the aid of pen and paper or a generic computer. Such calculating is considered to be an abstract idea. Note that the use of pen and paper or a generic computer or software program to implement an abstract idea does not itself impart patent eligibility.
As stated in MPEP 2106.04(a)(2) III “The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation” and that “Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer.”
The claims also recite the judicial exception of a mathematical concept of the formula that is used to calculate the psi score and delta psi score. See MPEP 2106.04(a)(2):
“A claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the “mathematical concepts” grouping. A mathematical calculation is a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. There is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word “calculating” in order to be considered a mathematical calculation. For example, a step of “determining” a variable or number using mathematical methods or “performing” a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation.”
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). The additionally recited step of detecting levels of two or more isoforms of ELavl2 in a biological sample from a subject is part of the data gathering process necessary to observe the judicial exception. This step does not practically apply the judicial exception.
Further, the claims have been amended to recite “administering to the subject identified as having pre-symptomatic ALS an effective amount of an ALS therapeutic agent,” including agents that are any peptide, protein, nucleic acid or small molecule or any antibody (claim 28). These treatments are recited at a high degree of generality.
The specification does not provide a limiting definition for what constitutes an “ALS therapeutic agent.” The specification (para [0020] and [0101]) states: “(i)n some embodiments, treatment comprises administering an effective amount of a known ALS therapeutic agent, such as Riluzole (Rilutek, Sanofi-Aventis), to a subject identified as having ALS.” This constitutes an example of a known ALS therapeutic agent but is not a limiting definition for an “ALS therapeutic.”
Note also that the claims are drawn to methods “for identifying a subject as having pre-symptomatic amyotrophic lateral sclerosis (ALS).” The claims do not require any particular outcome of the administering step.
As broadly recited, the claims encompass administering any known or currently unknown agent, including any protein, peptide or antibody, that could be administered to a patient having ALS, including agents that don’t affect the symptoms or outcome of ALS. Accordingly, the administering step is merely an “apply it” limitation and is not a practical application of the judicial exception.
Regarding specific treatments, see MPEP 2106.04(d)(2):
When determining whether a claim applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, the following factors are relevant.
a. The Particularity Or Generality Of The Treatment Or Prophylaxis
The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application….
b. Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)
The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). For example, consider a claim that recites a natural correlation (law of nature) between blood glucose levels over 250 mg/dl and the risk of developing ketoacidosis (a life-threatening medical condition). The claim also recites "treating a patient having a blood glucose level over 250 mg/dl with insulin". Insulin acts to lower blood glucose levels, and administering insulin to a patient will reduce the patient’s blood glucose level, thereby lowering the risk that the patient will develop ketoacidosis. Thus, in the context of this claim, the administration step is significantly related to the recited correlation between high blood glucose levels and the risk of ketoacidosis. Because insulin is also a "particular" treatment, this administration step integrates the law of nature into a practical application. Alternatively, consider a claim that recites the same law of nature and also recites "treating a patient having a blood glucose level over 250 mg/dl with aspirin." Aspirin is not known in the art as a treatment for ketoacidosis or diabetes, although some patients with diabetes may be on aspirin therapy for other medical reasons (e.g., to control pain or inflammation, or to prevent blood clots). In the context of this claim and the recited correlation between high blood glucose levels and the risk of ketoacidosis, administration of aspirin has at best a nominal connection to the law of nature, because aspirin does not treat or prevent ketoacidosis. This step therefore does not apply or use the exception in any meaningful way. Thus, this step of administering aspirin does not integrate the law of nature into a practical application.(Emphasis added).
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The additionally recited step in claim 1 of detecting the level of isoforms of Elavl2 in a biological sample obtained from a subject is recited at a high degree of generality, covering any method of detecting nucleic acids. Methods of detecting and quantifying nucleic acids, including methods of RNA sequencing (RNA-seq; see claim 14) were well-known, routine and conventional in the prior art. This finding is supported by the teachings in the specification at para [0059] and [0119-0120] (note that paragraph numbering herein is with respect to the published application), which disclose that methods of RNA sequencing, including next generation sequencing, were well-known in the prior art. This finding is also supported by the teachings of Akerman et al (WO 2019/226804; cited in the IDS) which teaches well-known RNA-seq platforms for detecting alternative splicing of RNA transcripts (e.g., para [075] and [0162]); the teachings of Katz et al (Nature Methods. 2010. 7(12): 1009-1015; cited in the IDS) which teaches methods of RNA sequencing to identify RNA isoforms present in a mixture of isoforms (e.g., abstract and p. 2); and the teachings of Prudencio et al (Nature Neuroscience. 2015. 18: 1175; cited in the IDS) which teaches the use of RNA-seq to screen for alternative splicing transcripts in brain tissue of subjects having ALS (e.g., p. 1175, col. 2 to p. 1176 col. 1).
See also MPEP 2106.05(d) II which states that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Note that while the claims recite detecting isoforms of a particular gene (i.e., the Elavl2 gene), the identity of the gene is part of the judicial exception and not something in addition to the recited judicial exceptions. The claims do not require using a particular non-conventional reagent, such as a particular, non-conventional probe or primer consisting of or comprising a specific nucleotide sequence so as to add something ‘significantly more’ to the recited judicial exceptions.
Further, to the extent that a computer may be intended to be used to accomplish the calculating step, MPEP 2106.05(a) states that ”Limitations that the courts have found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include: i. Adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, e.g., a limitation indicating that a particular function such as creating and maintaining electronic records is performed by a computer, as discussed in Alice Corp., 134 S. Ct. at 2360, 110 USPQ2d at 1984 (see MPEP § 2106.05(f))”
In Mayo v. Prometheus, the Supreme Court stated: "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377, 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.Response to Remarks:
The response states:
“independent claim 1 has been amended to recite an active step of "administering to the subject identified as having pre-symptomatic ALS an effective amount of an ALS therapeutic agent". Support for this amendment is found, for example, from page 38, line 1 to page 42, line 8 of the application as originally filed. The amended claims integrate the alleged judicial exceptions into a practical application because they recite administration to effect a particular treatment or prophylaxis for a disease or medical condition (i.e., pre-symptomatic ALS) in a particular patient population (i.e., subjects having a positive delta psi (AP) score for Elavl2).”
These arguments and the amendment to claim 1 have been fully considered but do not obviate the rejection. While the claims do recite a particular patient population, the claims do not recite administering a particular treatment or prophylaxis to effect a particular disease or medical condition. The claims as amended recite administering to the subject identified as having pre-symptomatic ALS an effective amount of an “ALS therapeutic agent,” including agents that are any peptide, protein, nucleic acid or small molecule (claim 26), or any antibody (claim 28). The “ALS therapeutic agent” is recited at a high degree of generality and is not considered to be a specific treatment. The specification does not provide a limiting definition for what constitutes an “ALS therapeutic agent” but rather provides an example of an ALS therapeutic agent. That is, the specification (para [0020] and [0101]) states: “(i)n some embodiments, treatment comprises administering an effective amount of a known ALS therapeutic agent, such as Riluzole (Rilutek, Sanofi-Aventis), to a subject identified as having ALS.” The cited teachings at p. 38 list known and currently unknown/unspecified “therapeutic agents” per se. However, the claims are not limited to methods that include a step of administering particular known therapeutic agents for alleviating / reducing one or more symptoms of ALS (as disclosed at para [0020]: “treatment comprises administering an effective amount of a therapeutic agent, such as baclofen, diazepam, phenytoin, trihexyphenidyl and/or amitriptyline, which reduces one or more symptoms of ALS”). As broadly recited, the claims encompass administering any agent that could be administered to a patient having ALS, including agents that don’t affect the symptoms or outcome of ALS.
Note also that the claims are drawn to methods “for identifying a subject as having pre-symptomatic amyotrophic lateral sclerosis (ALS).” The claims are not drawn to a method of treating pre-symptomatic ALS and do not require any particular outcome of the administering step.
Accordingly, the administering step is considered to be merely an “apply it” limitation and is not a practical application of the recited judicial exception(s).
The rejection is maintained for the reasons set forth above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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