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 .
Election/Restrictions
Applicant's election with traverse of the invention of Group 1 (claims 1-3, methods for selecting reference genes), and the particular target gene that is c-Met, in the reply filed on 08/14/2025 is acknowledged. The traversal is on the ground(s) that there would be no burden on the examiner to search all of the claimed inventions. This is not found persuasive because the instant application is a 371 national stage application, and therefore the relevant issue is unity of invention, not search burden; the Examiner maintains that the common technical feature of the different inventions is not a special technical feature in view of the prior art. None the less it is noted that the different inventions require non-coextensive searches and analysis, where the search for the general methods of reference gene criteria evaluation of the elected invention is different than the search required for a composition directed to any particular set of genes.
It is noted that in light of the Examiner’s search an analysis of the elected subject matter, the species election as it was applied to the different target genes of claim 3 is withdrawn.
The requirement, as it was applied to the different inventions of Groups 1-4 (p.3 of the Requirement of 05/15/2025) and the species elections related to the inventions of Groups 2-4 (p.4 of the Requirement of 05/15/2025) is still deemed proper and is therefore made FINAL.
Claims 4-19 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/14/2025.
Objection to the Drawings
Color Drawings with no Granted Petition
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. See the drawings provided as Figures 2, 6, 7, 8, 10 and 11, which contain color shading. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112 - Indefiniteness
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 1-3 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-3 are unclear over the use of the phrase “target gene” in the claims. The term “target gene” is used in the specification to indicate a gene of interest for which a copy number in a sample is determined. The use of “target gene” in the phrase “obtaining variation information in a target gene”, as recited in step (b) of claim 1 is unclear because a “normalizing gene candidate group” is a group of genes that may be used as reference genes in normalizing a detected copy number of a “target gene”, but a “normalizing gene candidate group” does not itself include a “target gene”. Such a definition of “target gene” is evidenced by claim 3 which recites “the target gene is”, and supplies a listing of genes where the copy number of the gene may be diagnostic of a pathology, whereas the “normalizing gene group” as set forth in claim 2 provides genes suitable of copy number normalization.
Claims 1-3 are unclear the limitations “obtaining variation information in a target gene in the candidate group and determining whether or not pathogenic variation is present”, as recited in step (b) of claim 1, and “calculating a variation rate of the pathogenic variation and selecting the target gene having a variation rate of less than 0.001”, as recited in step (c) of claim 1. It is unclear what is required to determine whether or not pathogenic variation is present; it is unclear if the claims are intended to require that some mutation is, or is not, in fact present in a sample from some particular subject. And it is unclear what is required to determine any variation rate because it is unclear what total population is intended to be required to determine any rate. For example, where claim 2 indicates that HBB is a suitable gene for the normalizing gene candidate group, it appears that the HBB gene (encoding the beta-globin protein) in fact has mutations of pathogenic significance, and that the mutations are found at different rates in different populations, as noted in Carlice-dos-Reis (2017); the reference further indicates that there are conflicting reports when comparing predictors of pathogenicity to determine the clinical significance of any mutation. In this regard the specification (p.11) provides only:
The pathogenic variation is a phenomenon in which the original pathogenicity is changed, and the determination of the pathogenic variation is performed by determining whether clinical information (Clin. Sig.) of each gene provided by for example, Ensembl (http://ensembl.org) corresponds to ‘pathogenic’, ‘likely pathogenic’, or ‘likely benign to pathogenic’. When the variation corresponding thereto has a frequency (gmaf-freq) of 0.01 or more, it is determined as the pathogenic variation.
So, it remains unclear where any variation may be “present” to make such a determination, or what frequencies from any particular populations are required to determine that a variation rate is less than 0.001.
Claims 1-3 are unclear over the recitation of criteria as set forth in step (d) of claim 1. The lack of any conjunction (e.g.: and; or) between the criteria set forth as (i) and (ii) makes it unclear if the exclusion requires both criteria to be met, or if meeting either criterion is suitable for exclusion. Additionally, it is unclear where the criteria are required to be met (e.g.: what sample source) in order for a gene to be excluded. For example, it is unclear if the presence of any truncation mutation in any sample is sufficient to exclude the gene from the group, or if some particular sample is to be considered. For example, claim 2 indicates that HPRT1 is a gene in a normalizing gene group, but Fu et al (2012) teaches that there are missense and truncating mutations in the gene. And claim 2 indicates that TFRC is a gene in a normalizing gene group, but Racz et al (1999) teaches that the gene is amplified in cancer.
Claims 1-3 are unclear over recitation of the limitation “selecting 3 to 6 normalizing genes from the normalizing gene group selected in steps (b) to (d)”, as recited in step (e) of claim 1, because steps (b) and (d) are not steps of “selecting”. Step (b) is related to determining whether or not a variation is present, and step (d) is directed to “excluding” (not selecting) genes. The phrase is further unclear because the relevant “selecting” step, as recited in step (c) is set forth as “selecting the target gene” (i.e.: a singular gene), and thus it is unclear how the required plurality of “3 to 6” genes is selected.
Claims 1-3 are unclear over recitation of the phrase “the target gene to detect the copy number variation” because there is no antecedent basis for any “target gene to detect the copy number variation”
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 1-3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e.: abstract ideas including mathematical concepts and mental processes) without significantly more.
The claim(s) are directed to methods of gene selection, and recite steps of selecting and excluding genes from a group, which are mental processes that are an evaluation of, or providing a judgment about, the suitability of a gene (e.g.: MPEP 2106.04(a)(2)(III). The claims recite obtaining in in formation and making a determination based on the information, which is a step of making an observation, that is a mental process (e.g.: MPEP 2106.04(a)(2)(III). The claims include “calculating a variation rate”, which is properly considered an abstract idea falling within the "mathematical concepts" grouping (e.g.: MPEP 2106.04(a)(I)(C). Where the claims recite “obtaining variation information” (step (b) of claim 1), it is noted that MPEP 2106.04(a)(2)(III)(A) provides that examples of mental processes include collecting and comparing known information.
This judicial exception is not integrated into a practical application because there are no practical steps related to the selected normalizing genes. The claims end with the selection of genes, and do not require that any tangible process is performed with any selected genes (see MPEP 210.04(d)).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no steps that are required in the addition to the noted mental process and mathematical calculations.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683