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
Claim set received 17 October 2025 has been entered into the application.
Claims 1-7 are pending.
Priority
This Application is a 371 of PCT/EP2021/060092 filed 19 April 2021.
Restriction/Species Election
The Applicant traversed the election/restriction mailed 20 August 2025 in the response filed 17 October 2025. However, the election/restriction requirement in the Office Action 20 August 2025 is withdrawn. Therefore, claims 1-7 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11 May 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The drawings were received on 20 October 2022. These drawings are accepted.
Specification
The amendments to the specification received 20 October 2022 have been entered into the application.
The specification received 20 October 2022 and 08 May 2023 has been entered into the application.
Claim Objections
Claim 3 is objected to because of the following informalities: “wherein the number of said specific reference genes used to calculate said score and selected from the genes listed in Table 2 with an identical nucleic acid sequence to at least one of said target nucleic acid sequences from said sample is from the range of 50-1396.” The claim should be amended to recite “wherein the number of said specific reference genes used to calculate said score selected from the genes listed in Table 2 with an identical nucleic acid sequence to at least one of said target nucleic acid sequences from said sample is from the range of 50-1396”. Appropriate correction is required to address the grammatical correctness of the claim.
Claim 4 is objected to because of the following informalities: “wherein said nucleic acid analysis comprises the sequential use of one or more techniques selected from the group of reverse transcription, microarray analysis, DNA sequencing, Next Generation Sequencing, NanoString Hyb & Seq NGS analysis, nCounter-analysis, nanopore sequencing, third-generation sequencing, Sanger sequencing, digital or droplet PCR analysis, quantitative real-time PCR analysis, PCR amplification, RNA sequencing, DNA sequencing, Whole Genome Sequencing, Whole Exome Sequencing, Single Cell Sequencing, Targeted Sequencing, spatial sequencing, ATAC-Seq and ChIP-Seq.” The claim should be amended to recite “Wherein said nucleic acid analysis comprises the sequential use of one or more techniques selected from the group of reverse transcription, microarray analysis, DNA sequencing, Next Generation Sequencing, NanoString Hyb & Seq NGS analysis, nCounter-analysis, nanopore sequencing, third-generation sequencing, Sanger sequencing, digital or droplet PCR analysis, quantitative real-time PCR analysis, PCR amplification, RNA sequencing, DNA sequencing, Whole Genome Sequencing, Whole Exome Sequencing, Single Cell Sequencing, Targeted Sequencing, spatial sequencing, ATAC-Seq, or ChIP-Seq.”. Appropriate correction is required to address the grammatical correctness of the claim.
Claim 5 recites “wherein said patient is a human patient, an animal or a cell culture of a patient-derived sample of a human patient, of an animal or an animal model, of a sample from an "organ-on-a-chip".” The claim should be amended to recite “wherein said patient is a human patient, an animal or a cell culture of a patient-derived sample of a human patient, an animal or an animal model, a sample from an "organ-on-a-chip" model, a sample from a microphysiological system, or a cell line or an organoid.” Appropriate correction is required to address the grammatical correctness of the claim.
Claim 6 recites “wherein the sample is selected from the group consisting of an organ, a tissue, a biopsy, a liquid biopsy, a blood sample, a patient derived xenograft sample, of a sample from an "organ-on-a chip" model, of a sample from a microphysiological system, of a cell line or a cell culture of a patient-derived sample of a human patient, an animal or an animal model, a cell line or an organoid.” The claims should be amended to recite “wherein the sample is selected from the group consisting of an organ, a tissue, a biopsy, a liquid biopsy, a blood sample, a patient derived xenograft sample, a sample from an "organ-on-a chip" model, a sample from a microphysiological system, a cell line or a cell culture of a patient-derived sample of a human patient, an animal or an animal model, a cell line, or an organoid.” Appropriate correction is required to address the grammatical correctness of the claim.
Claim Rejections - 35 USC § 112
35 USC § 112(b)
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 1-7 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.
Antecedent Basis
Claims 1 and 7 step (d) recite the limitation "the logHR" in line 3. There is insufficient antecedent basis for this limitation in the claim. It is recommended to amend the claim to recite “weighted by a logHR value” to provide antecedent basis for the term because that is what is listed in Table 2.
Claims 2-6 are rejected because they fail to provide limitations to overcome the deficiencies of the base claim(s).
Indefiniteness
Claims 1 and 7 step (b) recites “…reference gene selected from the group of reference genes listed in Table 2”. The claimed steps recite using table 2 in place of required genes which renders the claims indefinite. Here, the MPEP 2173.05(s) provides that “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).” It is recommended to amend the claim to recite which genes are to be utilized.
Claim 3 is rejected because it depends on claim 1 and also recites using Table 2 instead of using the gene names.
Claims 1 and 7 step (c) recite normalizing of the target nucleic acid sequence abundancies against a reference dataset and standardization. The term “standardization” renders the claim indefinite because the term is not clear and is vague as to what “standardization” is. The metes and bounds are not clear. For example, it is not clear if the term is referencing a standardized value for normalizing sequence abundancies or standardization methods. For clarity, it is recommended to amended the claim to address the clarity issues or, for example, amend the claim to recite normalizing and standardizing of the target nucleic acid sequence abundancies against a reference dataset. Similar language is provided in the specification [page 2 summary of invention lines 19-21].
Claims 1 and 7 are further rendered indefinite because claims 1 and 7 steps (d) recite “…weighted by the logHR value…listed in Table 2”. Here, claims 1 and 7 steps (d) recite that the target nucleic acid is weighted by the logHR value of a corresponding reference gene in Table 2, however, Table 2 [Spec pages 25-68] only discloses a weighted_logHR, not a log_HR. As such, it is not clear if Table 2 lists values that have already been weighted and/or if those are the values used to perform the weighting as recited in step (d). It is recommended to amend the claims to clarify which value (i.e., weighted_logHR or logHR) is being used for weighting the abundancy.
Claims 2-6 are rejected because they fail to provide limitations to overcome the deficiencies of the base claim(s).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step I - Process, Machine, Manufacture or Composition
Claims 1-6 are drawn to a method, so a process.
Claim 7 is drawn to a method, so a process.
Step 2A Prong I - Identification of an Abstract Idea
Claim 1 recites a method for predicting the outcome or classifying prostate carcinoma in a patient while claim 7 is drawn to a method for use in the treatment of prostate. Here, claims 1 and 7 recite similar limitations and are therefore examined similarly.
Claims 1 and 7 recite:
b) analyzing the plurality of nucleic acids, thereby determining the abundancy of at least 50 different target nucleic acid sequences
This step can be performed in the human mind by observing, judging, and evaluating information (i.e., nucleic acid data) to determine an abundancy of target nucleic acids and is therefore an abstract idea.
wherein each of the at least 50 different target nucleic acid sequences is identical to the nucleic acid sequence of a corresponding specific transcript or isoform of a reference gene selected from the group of reference genes listed in Table 2
This step describes the target nucleic acid data as a transcript or isoform of a reference gene that is identical to a reference listed in table 2.
c) normalizing of the target nucleic acid sequence abundancies against a reference dataset and standardization
This step can be performed in the human mind by organizing data (i.e., abundancies, dataset, standardization) to normalize sequence data and is therefore an abstract idea. This step encompasses performing mathematical computations for normalizing sequence data abundancies with reference data and standardization which reads on abstract ideas. For example, normalizing sequence data encompasses the mathematical concepts of scaling, division, and log transformations to correct data (i.e., sequencing depth and compositional bias).
d) weighting the abundancy of the at least one or more different target nucleic acid using a corresponding reference value
This step can be performed in the human mind by organizing information (i.e., corresponding reference value) to weight the abundancies of different target nucleic acids and is therefore an abstract idea. This step encompasses performing mathematical/statistical computations for weighting abundancies using corresponding values which reads on abstract ideas. For example, weighting data encompasses scaling and normalizing methods, statistical distributions (i.e., negative binomial), and weighted calculations (i.e., weighted geometrics means).
wherein said abundancy of the target nucleic acids is weighted by the logHR value of a corresponding reference gene listed in Table 2
This step can be performed in the human mind by organizing data (i.e., logHR values) for performing weighting methods using the abundancy of the target nucleic acids and is therefore an abstract idea. This step encompasses using mathematical variables (i.e., logHR value) for quantitatively weighting the abundancy of target nucleic acids to the logHR of the references genes which reads on abstract ideas.
wherein the nucleic acid sequence of said reference gene, or of a transcript or isoform thereof, is identical to the nucleic acid sequence of one or more of said target nucleic acid sequences from said sample
This step describes the reference gene and the transcript/isoform of the reference gene as identical to the sample target nucleic acid sequences.
e) calculating a score value
This step can be performed in the human mind by organizing data to calculate a score value and is therefore an abstract idea. This step encompasses performing calculations to calculate a score value which reads on abstract ideas.
wherein, if the score value is above a threshold value of 0, the patient is classified as having a high risk of death of disease and/or biochemical recurrence and/or if the score value is below a threshold value of 0, the patient is classified as having a low risk of death of disease and/or biochemical recurrence.
This step can be performed in the human mind by observing, comparing, and evaluating whether the score value is above a threshold of 0 to classify a patient as having a high risk of death from a disease or biochemical recurrence and is therefore an abstract idea. This step can further be performed in the human mind by observing, comparing, and evaluating whether the score value is below a threshold of 0 to classify a patient as having a low risk of death from a disease or biochemical recurrence and is therefore an abstract idea. This step encompasses using the mathematical concepts of equalities and inequalities for comparing data (i.e., score value) to thresholds which reads on abstract ideas.
Claim 7 recites
wherein the outcome or classification of the disease of a prostate carcinoma patient from whom said sample was derived is predicted based on said score value.
This step can be performed in the human mind by observing and evaluating data (i.e., score) to predict the outcome or classification of a disease of a patient and is therefore an abstract idea.
wherein, if the score value is above a threshold value of 0, the patient is classified as having a high risk of death of disease and/or biochemical recurrence and/or if the score value is below a threshold value of 0, the patient is classified as having a low risk of death of disease and/or biochemical recurrence
This step can be performed in the human mind by observing, comparing, and evaluating whether the score value is above a threshold of 0 to classify a patient as having a high risk of death from a disease or biochemical recurrence and is therefore an abstract idea. This step can further be performed in the human mind by observing, comparing, and evaluating whether the score value is below a threshold of 0 to classify a patient as having a low risk of death from a disease or biochemical recurrence and is therefore an abstract idea. This step encompasses using the mathematical concepts of equalities and inequalities for comparing data (i.e., score value) to thresholds which reads on abstract ideas.
Claims 2-3 and 5 are further drawn to limitations that describe the abstract ideas of claim 1 and are therefore also abstract ideas.
Step 2A Prong Two - Consideration of Practical Application
Claims 1 and 7 do not contain any additional elements which integrate the recited judicial exception into a practical application.
Here, in the instant case, the claims merely set forth a method of nucleic acid sequence data analysis for calculating a score value for determining whether a patient is classified as having a high risk of death of a disease and/or biochemical recurrence of the disease and/or as having a low risk of death of a disease and/or biochemical recurrence of the disease. Such a result only produces information and does not provide for a practical application in the physical-realm of physical things and acts, i.e., the claims do not utilize the data generated by the judicial exception to affect any type of change. See MPEP 2106.04(a)(2)(A)(iv). Therefore, the claims do not utilize the obtained sequence data and the calculated score value and the abstract ideas to construct a practical application such as treating a subject, transformation of matter, or improving upon an existing technology.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Step 2B - Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea.
The recited additional element of the obtaining nucleic acids of claims 1 and 7 step (a) does not add significantly more than the recited judicial exception because obtaining nucleic acids sources that are subsequently utilized as a source of nucleic acids is deemed a well-known and conventional extra-solution activity. See MPEP 2106.05(d)(II)(i-iii, v, vii) and 2106.05(g).
The recited additional element of using different nucleic acid sequencing methods of claim 4 does not add significantly more than the recited judicial exception because using sequencing methods to obtain sequencing data that is subsequently evaluated by the abstract ideas is deemed a well-known and conventional extra-solution activity. See MPEP 2106.05(d)(II)(i-iii, v, vii) and 2106.05(g). It is noted the specification [page 15 last paragraph] states the sequencing technologies/methods of claim 4 are known to those of ordinary skill in the art.
The recited additional element of samples of claim 6 does not add significantly more than the recited judicial exception because using samples as source nucleic acid data that is subsequently evaluated by the abstract ideas is deemed a well-known and conventional. To provide evidence of conventionality of using “organ-on-chip“, Wu et al. (Wu) review different organ-on-chips such as liver tumor on a chip [page 5 fig 1], lung on a chip [page 6 fig 2], heart on a chip [9 fig 4], combining multi-organs plates [page 12 fig 6], and reviews using 2D and 3D cell cultures [13 fig 7]. (Biomedical engineering online, 2020-02, Vol.19 (1), p.9-19, Article 9). To provide evidence of conventionality of using xenograft samples, Rossello et al. (Rossello) teaches next-generation sequencing analysis of cancer xenograft models [title]. Rossello teaches using next generation sequencing of exome and whole-genome sequencing for sequencing small-cell lung cancer (SCLC). Rossello also teaches using RNA-seq on the xenograft samples [page 2 left col materials and methods and right col RNA-Seq] (PloS one, 2013-09, Vol.8 (9), p.e74432).
In conclusion and 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.
Conclusion
Claims 1-7 are rejected.
No claims are allowed.
Finality
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this action.
Inquiries
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
/Anna Skibinsky/
Primary Examiner, AU 1635