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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 19 February 2026 has been entered. 3. Applicant's arguments and amendments to the claims presented in the reply of 19 February 2026 have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
Claim Status
4. Claims 16-20, 29 and 32-36 are pending and have been examined herein.
Claim Objections
5. Claim 20 is objected to because of the following informalities:
Claim 20 recites “the at least one drug used for treating acute myeloid leukemia,” whereas the claim should recite “the at least one anti-AML drug,” so as to ensure clear antecedent basis for the phrase.
Appropriate correction is required.
Modified / Maintained Claim Rejections - 35 USC § 101
6. 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 16-20, 29 and 32-36 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 gene expression of SEQ ID NO: 1-23 and the prognosis of the outcome for an individual with AML, as well as the likelihood that the individual with be responsive to a DNA repair pathway inhibitor. 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 step of “prognosing” an individual based on calculated scores, as compared to a reference value. Claim 18 also recites a step of “classifying” the individual based on the presence of an NPM1 or FLT3-ITD mutation. The broadest reasonable interpretation of the prognosing steps is that these steps may be performed by critical thinking processes wherein one reaches a conclusion regarding the prognosis or classification of a subject based on the comparison of the calculated score to the reference value. Such “prognosing” and “classifying” thereby encompasses processes that may be performed mentally and thus is an abstract idea. The “prognosing” and “classifying” steps may also be accomplished verbally. Such verbal communication is also abstract, having no particular concrete or tangible form.
The claims also necessarily require performing a step of "comparing" step since the prognosis or classification is based on detecting a higher or lower score relative to a reference value. Neither the specification nor the claims set forth a limiting definition for "comparing" and the claims do not set forth how comparing is 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.
The claims also require performing a calculating step. As broadly recited, the calculating step may be performed mentally, or with the use of pen and paper, or using a generic computer.
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.”
Accordingly, the broadly recited calculating step does not constitute something more than an abstract idea.
Dependent claim 18 recites “determining the mutational status of both the NPM1 gene and FLT3 gene.” The claims do not set forth how the mutational status is determined and do not require assaying a sample to determine the mutation status of the NPM1 and FLT3 genes. As broadly recited, the mutational status can be determined by reading information in a database or report regarding the mutation status of the NPM1 and FLT3 genes in a biological sample previously obtained from the subject.
The claims also recite the judicial exception of a mathematical concept of the formula that is used to calculate the SCOREPATH.
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 measuring gene expression in a biological sample obtained from an individual is part of the data gathering process necessary to observe the judicial exception. These steps do not practically apply the judicial exception.
The claims include a step of administering a composition comprising a DNA repair pathway inhibitor to those individuals who are prognosed as likely to respond to a DNA repair pathway inhibitor in step c) of claim 16. That is, claim 16 at step d) recites:
“d) treating the individual prognosed to be likely to respond to a DNA repair pathway inhibitor in step c) by administering to the individual a composition comprising at least one DNA repair pathway inhibitor”
Only those individuals with the scores set forth in i, iii, v, vii, ix and xi are characterized as likely to respond to the DNA repair pathway inhibitor and are administered the composition comprising the DNA repair pathway inhibitor.
The claims include methods wherein the individual is not prognosed as being likely to respond to a DNA repair pathway inhibitor - i.e., those individuals with the scores set forth in ii, iv, vi, viii, x, and xii. The claims do not require administering the DNA repair pathway inhibitor to these individuals.
Thus, the claims include the embodiment wherein the individual is not “prognosed to be likely to respond to a DNA repair pathway inhibitor in step c)” and no administering step is performed at d). In these embodiments encompassed by the claims in which the administering step does not occur, the claims do not recite a practical application of the judicial exception.
Dependent claim 17 recites that the individual is further prognosed as xiv, xv or xvi, but does not recite that any of these individuals are prognosed as likely to respond to a DNA repair pathway inhibitor.
Dependent claim 18 recites that the individual is classified as a low risk group (in i or ii) or a median or high risk group (in iii), but does not recite how these classifications affect the prognosis of the individual as likely to respond to a DNA repair pathway inhibitor.
Also, the preamble of the claims recites that “the individual has [a] poor outcome after previous treatment with at least one anti-AML drug.” This limitation defines the individual and is not an active process in the claim that practically applies the recited judicial exceptions. This limitation is part of the judicial exception in that this defines the individual in which the correlation between the expression levels of SEQ ID NO: 1-23 and OYS and/or responsiveness to a DNA repair inhibitor occurs. Further, this is extra-solution activity and not a practical application of the judicial exception.
Applicant’s attention is directed to M.P.E.P. § 2106.04(d)(2)(c), which states:
“The treatment or prophylaxis limitation must impose meaningful limits on the judicial exception, and cannot be extra-solution activity or a field-of-use. For example, consider a claim that recites (a) administering rabies and feline leukemia vaccines to a first group of domestic cats in accordance with different vaccination schedules, and (b) analyzing information about the vaccination schedules and whether the cats later developed chronic immune-mediated disorders to determine a lowest-risk vaccination schedule. Step (b) falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). While step (a) administers vaccines to the cats, this administration is performed in order to gather data for the mental analysis step, and is a necessary precursor for all uses of the recited exception. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.”
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 something 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 step of measuring gene expression is recited at a high degree of generality and methods of measuring gene expression were well-known, routine and conventional in the prior art. This finding is evidenced by the teachings in the specification which states, for example:
“The expression level of the genes is measured by well-known protocol in the art. These methods are for instance, DNA-CHIPs containing probesets of said 23 genes, so that an expression level can be determined for each of said 23 genes. Other methods can be used, such that quantitative PCR strategy” (p. 5, lines 6-9).
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); …
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;…
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 measuring the expression level of particular genes, the identity of the genes 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 Applicant may assert that a computer is to be used to calculate the SCOREPATH, 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 that, in response to the statement in the rejection that the claims include methods that do not require the administering step at d) and do not recite a practical application of the judicial exception, “Applicant removes the prognostic steps where individual is "not prognosed to be likely to respond to a DNA repair pathway inhibitor", as mentioned in the above section.”
However, as amended, the claims still encompass methods in which no administering step occurs at d) since step d) is limited to administering the DNA repair pathway inhibitor to only “the individual prognosed to be likely to respond to a DNA repair pathway inhibitor in step c).” Step c) is not limited to prognosing the individual as likely to respond to s DNA repair pathway inhibitor. Rather, claim 16 at step c) includes the following embodiments:
“ii. if all the scores ScorePATH1 to ScorePATH5 are lower than or equal to their respective reference value Refi to Refs, then the individual is likely to have a good outcome with an OYS higher than 50%”
“iv. if the score ScorePATH1 is lower than or equal to its respective reference value Refi, then the individual is likely to have a good outcome with an OYS higher than 55%”
“vi. if the score ScorePATH2 is lower than or equal to its respective reference value Ref2, then the individual is likely to have a good outcome with an OYS higher than 60%”
“viii. if the score ScorePATH3 is lower than or equal to its respective reference value Ref3, then the individual is likely to have a good outcome with an OYS higher than 70%”
“x. if the score ScorePATH4 is lower than or equal to its respective reference value Ref4, then the individual is likely to have a good outcome with an OYS higher than 50%”
“xii. if the score ScorePATH5 is lower than or equal to its respective reference value Refs, then the individual is likely to have a good outcome with an OYS higher than 80%.”
No prognosis that the individual is likely to respond to a DNA repair pathway inhibitor occurs at the embodiments of ii), vi), viii), x) and xii). In these embodiments encompassed by the claims, only step a) of measuring and the abstract / judicial exception steps of b) calculating and c) prognosing occur. In these embodiments encompassed by the claims, no step d) of administering the composition comprising a DNA repair pathway inhibitor step occurs. Thereby, the claims include the embodiment in which the only non-patent-ineligible step is the measuring step. The measuring step is a data gathering step and is not a practical application of the judicial exceptions. Further, the measuring step is recited at a high degree of generality and was well-known, routine and conventional in the prior art. The measuring step does not amount to something significantly more than the recited judicial exceptions.
Note also that claim 17 includes further prognosing the individual as having an OYS higher than 80% or between 60-80%. In these embodiments, if consistent with claim 16, the individual would not be treated with a DNA repair pathway inhibitor. Claim 17 also further prognosis an individual as having an OYS below 30%, but does not recite that the individual is prognosed as likely to respond to a DNA repair pathway inhibitor.
The response argues that claim 16 has been amended to recite that the individual “"has a poor outcome after previous treatment with at least one anti-AML drug." It is stated that this limitation imposes “a meaningful limitation on the claimed method that restricts its application to patients who have responded poorly to prior anti-AML therapy.”
These arguments and the amendment to the claims have been fully considered but do not obviate the rejection. While this recitation does limit the identity of the individual, the identity of the individual as being one that has a poor outcome after previously being treated with an anti-AML drug is part of the judicial exception in that this recitation defines the individual in which the correlation between the expression levels of SEQ ID NO: 1-23 and OYS and/or responsiveness to a DNA repair inhibitor occurs. The limitation that the individual has a poor outcome after previously having been administered an anti-AML drug is extra-solution activity and is not a practical application of the recited judicial exceptions.
Applicant’s attention is directed to M.P.E.P. § 2106.04(d)(2)(c), which states:
“The treatment or prophylaxis limitation must impose meaningful limits on the judicial exception, and cannot be extra-solution activity or a field-of-use. For example, consider a claim that recites (a) administering rabies and feline leukemia vaccines to a first group of domestic cats in accordance with different vaccination schedules, and (b) analyzing information about the vaccination schedules and whether the cats later developed chronic immune-mediated disorders to determine a lowest-risk vaccination schedule. Step (b) falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). While step (a) administers vaccines to the cats, this administration is performed in order to gather data for the mental analysis step, and is a necessary precursor for all uses of the recited exception. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.”
The rejection is maintained for the reasons set forth above.
New Claim Rejections - 35 USC § 112(b) - Indefiniteness
7. 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 16-20, 29 and 32-36 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.
A. Claims 16-20, 29 and 32-36 are indefinite over the recitations of “k defines Base Excision Repair pathway,” “k defines Fanconi pathway,” “k defines Homologous Recombination Repair pathway,” “k defines Mismatch Repair pathway,” and “k defines Nucleotide Excision Repair pathway.” These phrases are not clearly defined in the specification and it is not clear as to what is intended to be meant by these phrases.
It is noted that the specification at para [0056] (with respect to the published application) teaches:
“Each gene of each of the 5 groups of genes is assigned with a substitute SEQ ID NO according to the DNA repair pathway group they belong to (letter A for the BER pathway group, letter B for the FANC pathway group, letter C for the HRR pathway group, letter D for the MMR pathway group and letter E for the NER pathway group).”
However, this teaching in the specification does not clarify the relationship between k and the recited pathways in the phrases “k defines…pathway” and does not clarify what constitutes “Kn” and “k1” in the recited formula.
B. Claims 17 and 18 are indefinite over the recitations of “low risk,” “median risk” and “high-risk” because the claims do not indicate what the risk is associated with - e.g., a risk of a poor outcome, or a risk of a poor one year survival (OYS) or a risk of not being responsive to a DNA repair pathway inhibitor.
C. Claim 29 is indefinite over the recitation of “and possibly for which some resistance occurs” because it is not clear as to whether the claim requires this limitation or does not require this limitation. That is, it is unclear as to whether the at least one drug for treating acute myeloid leukemia is limited to a drug that the individual (or AML) may have resistance to or if the at least one drug may be any drug that treats acute myeloid leukemia. See MPEP § 2173.05(d).
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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