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 .
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.
Current Status of 17-271,981
This Office Action is responsive to the arguments and amendments received 5 November 2025.
Claims 9, 17, 39, 55-59, and 61-64 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group I, being claims 1-5, 9-12, 17, 20, 22, 33, 36 and 38-40 in the reply filed on 18 March 2024 is acknowledged.
The elected group has been determined to read on claims 9, 17, 39, 55-59, and 61-64. No claims are currently withdrawn due to the restriction requirement.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/US2019/048818 (filed 29 August 2019) and US 62-724,337 (filed 29 August 2018) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to Amendments
The objections to the claims, present in the previous rejection, are hereby withdrawn due to Applicant’s amendments, but new objections are presented herein.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments, but new rejections are presented herein.
The 35 U.S.C. 101 rejections to the claims, present in the previous office action, are hereby withdrawn, but new rejections are presented herein.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are withdrawn herein, but new rejections are presented herein.
Claim Objections
Claim 9 is objected to because of the following informalities: The word “and” should be placed after section “a)” of claim 9 to conform with standard English grammar. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: Each occurrence of the word “level” within claims 9, 17, 57-58, and 63-64 should be replaced by the word “levels” to match the plurality of the genes named therein. All articles should be corrected to match the plural “levels”. Claims 39 should continue to contain only the word “level”, not “levels”. Appropriate correction is required.
Claim 17 is objected to because of the following informalities: The comma in the phrase “MGMT, and GRASP1” in section b)(i) is grammatically incorrect. Applicant may choose to remove this comma. Appropriate correction is required.
Claim 39 is objected to because of the following informalities: The conjunction within the list of genes in section “(A)” of claim 39 should be “or”, not “and” due to the singularity of the “expression level”. Appropriate correction is required.
Claim 59 is objected to because of the following informalities: Each occurrence of the word “levels” within claim 59 should be replaced by the word “level” to match the singularity of the word “level” at the beginning of the claim. The phrase “plurality of” in section “(B)” should be deleted for the same reason. Appropriate correction is required.
Claim 59 is objected to because of the following informalities: The conjunction within the list of genes in sections “(A)” and “(B)” of claim 59 should be “or”, not “and” due to the singularity of the “expression level”. Appropriate correction is required.
Claim 59 is objected to because of the following informalities: Claim 59, section “(A)” now contains the phrase “a mean of of the”. One of the words “of” in the quoted phrase should be deleted. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 9, 17, 39, 55-59, and 61-64 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.
Claims 9 and 17 each recite GRASP1, which is not present in the original specification or the original claims. This matter is inherited by claims 39, 55-59, and 62-64. Applicant may choose to amend each of these claims to recite GPRASP1 instead of GRASP1.
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 17, 59, and 61-64 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.
Claim 17 requires both: “centering and scaling” of the gene/gene product expression levels in section “a)” (which would logically include a reference value) and measurement relative to a reference level in section “a)”. It is unclear to the reader if the artisan is required to compare the measured value to a reference value once or twice. This renders claims 17, 59, and 61-64 indefinite. Applicant may choose to delete the phrase “relative to a reference level,” in section “a)” of claim 17.
Claim 17 recites “a sample”. The reader is led down the path of inferring that the sample is related to the glioblastoma tumor established above in the claim. However, the claim fails to define what the sample is or where it comes from. As currently written, it is unclear to the reader if the sample of section “a)” refers to a sample from the subject with the glioblastoma tumor or to a sample from another source. This renders claims 17, 59, and 61-64 indefinite. Applicant may choose to replace the phrase “in a sample, wherein” with the phrase “in a glioblastoma tumor sample from the subject, wherein”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 63 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 63 recites “one or more of MGMT, GPRASP1…” in two locations. The use of “one or more of” attempts to expand the scope of the parent claim. The parent claim, claim 17, requires the measurement of the levels of all of the genes within that list. Applicant may choose to delete both occurrences of the phrase “one or more of”.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Interpretation
Instant claim 9 recites “A treatment regimen for use in a method”. Because of this preamble, the Examiner is interpreting this claim to be limited only by the limitations of the treatment regimens therein (method steps b)(i), b(ii), or b(iii)), and not the measuring recited in step a).
Response to Arguments
Applicant's arguments received 5 November 2025 have been fully considered, but they are not persuasive.
Applicant argues that neither OKADA nor WILLEMS discloses MGMT and GPRASP1 collectively as a “gene signature for identifying subjects that would benefit from an alkylating chemotherapy”. Applicant argues that the data within the instant examples “demonstrated an increased benefit from chemotherapy compared to assessing levels of MGMT alone”. Applicant argues that the Examiner’s other cited references also do not disclose the measurement of all of the expression levels of the instantly claimed genes.
OKADA teaches the treatment of subjects having glioblastoma and having low MGMT expression therein with temozolomide (an alkylating chemotherapy). The teachings of OKADA do not discuss GPRASP1. One of ordinary skill in the art would have understood the teachings of OKADA to be applicable to all patients having glioblastoma with a low expression of MGMT therein, regardless of any GPRASP1 expression. Applicant’s arguments do not directly address the obviousness of treating all patients with glioblastoma and low MGMT expression using temozolomide. Applicant argues that the selection of a subpopulation of glioblastoma + low MGMT patients, being those patients also having decreased GPRASP1 expression, shows a greater benefit from temozolomide within that subpopulation. But Applicant has not explained to the Examiner why, before the instant effective filing date, one of ordinary skill in the art would not have applied the teachings of OKADA to that subpopulation.
If a particular drug was known to be useful when applied to a specific patient population, and the patient population is then subdivided, application of the same drug to any of these subpopulations would have been obvious. However, if it can be shown that there were significant teachings against applying the drug to the subpopulation, or if it could be shown that the subpopulation is sufficiently small that it was not commonly treated with the drug before or was never treated with the drug before, these facts could argue against obviousness. The Examiner has not found any prior art that would argue against obviousness in this manner. Applicant is invited to provide such prior art.
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 17, 59, and 61-64 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The method of instant claim 17 requires a step of measuring the expression levels of several genes and requires particular therapies to be applied if specific expression profiles are present within the tumor sample. Because there are many expression profiles that are not mentioned within the claim (for example CHGA and MAPK8 being decreased), claim 17 seems to implicitly state that if any non-enumerated expression profile is determined to be present, only the expression level measuring step will be performed. Those embodiments of claim 17 are directed to measurement of naturally occurring concentrations, without adding significantly more. This judicial exception is not integrated into a practical application, because no other actions are required by these embodiments of the claim. The measurement of all expression levels within a cell or population of cells was well-known within the literature before the instant effective filing date. ZHAO (Previously cited by the Examiner, Zhao, S.; Fung-Leung, W.; Bittner, A.; et al. “Comparison of RNA-Seq and Microarray in Transcriptome Profiling of Activated T Cells” PLOS ONE | January 2014 | Volume 9 | Issue 1 | e78644) compares the benefits of RNA-Seq and microarray technology in transcriptome profiling (abstract), and transcriptome profiling is a method of determining the expression of all RNA transcripts within a cell or cell population. See MPEP 2106.05.
The following is an excerpt from MPEP 2106.05(d): In Mayo, the claims at issue recited naturally occurring correlations (the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that a drug dosage will be ineffective or induce harmful side effects) along with additional elements including telling a doctor to measure thiopurine metabolite levels in the blood using any known process. 566 U.S. at 77-79, 101 USPQ2d at 1967-68. The Court found this additional step of measuring metabolite levels to be well-understood, routine, conventional activity already engaged in by the scientific community because scientists “routinely measured metabolites as part of their investigations into the relationships between metabolite levels and efficacy and toxicity of thiopurine compounds.” 566 U.S. at 79, 101 USPQ2d at 1968. Even when considered in combination with the other additional elements, the step of measuring metabolite levels did not amount to an inventive concept, and thus the claims in Mayo were not eligible. 566 U.S. at 79-80, 101 USPQ2d at 1968-69.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 9, 39, and 55-58 are rejected under 35 U.S.C. 103 as being unpatentable over:
OKADA (Okada, M.; Sato, A.; Shibuya, K.; et al. “JNK contributes to temozolomide resistance of stem-like glioblastoma cells via regulation of MGMT expression” INTERNATIONAL JOURNAL OF ONCOLOGY 44: 591-599, 2014).
As explained above, the Examiner is interpreting this claim to be limited only by the limitations of the treatment regimens therein (steps b)(i), b(ii), or b(iii)), and not the measuring recited in step a).
OKADA teaches, in the Discussion section, that temozolomide resistance is caused by increased expression of MGMT. OKADA also teaches that glioblastoma cells with relatively low expression of MGMT are “widely known” to be sensitive to treatment with temozolomide specifically due to the low MGMT expression (2nd paragraph Pg. 598). OKADA teaches that the expression of MGMT was determined by RT-PCR (Materials and Methods section and Fig. 3). OKADA teaches that the findings therein “will be” applied to clinical studies, which would include human patients, in the future. Temozolomide is defined as an alkylating chemotherapy in instant claims 55 and 61.
The teachings of OKADA teach the alkylating chemotherapy treatment option of instant claim 9 (in section b)(i)), with the exception of the GPRASP1 limitation. OKADA does not provide any teachings regarding GPRASP1. One of ordinary skill in the art would have read the method of treating glioblastoma of OKADA and would have understood this to be applicable to all patients having glioblastoma with a low expression of MGMT therein, regardless of any GPRASP1 expression.
If a particular drug was known to be useful when applied to a specific patient population, and the patient population is then subdivided, application of the same drug to any of these subpopulations would have been obvious. However, if it can be shown that there were significant teachings against applying the drug to the subpopulation, or if it could be shown that the subpopulation is sufficiently small that it was not commonly treated with the drug before or was never treated with the drug before, these facts could argue against obviousness. The Examiner has not found any prior art that would argue against obviousness in this manner. Applicant is invited to provide such prior art.
Regarding claim 56: Instant claim 56 further specifies the type of radiation therapy, but does not require its use.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625