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 .
Election/Restrictions
Applicant’s election without traverse of Group I+, claims 1-4, 18, 19, 42-53, & 68, and the species election of the combination of C1orf226, TMEM92, LINC00482, MMP9, CD163, has-miR-3918, AK5, MICU3, CD200, and has-miR-760 in claims 1-4, 42, 43, & 68, of chemotherapy in claim 45, and of whole blood in claim 48 in the reply filed on 01/29/2026 is acknowledged. Group II+, claim 158, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 1-4, 18, 19, 42-53, & 68 is set forth herein and claim 158 is withdrawn from consideration.
Information Disclosure Statement
The listing of references in the specification in pg. 53-60 & 75-81 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.
Claim Rejections - 35 USC § 112
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 1-4, 18, 19, 42-53, & 68 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.
Regarding claim 1, the claim recites the limitation “the expression level of one or more biomarkers” in lines 2-3 of the claim and there is insufficient antecedent basis for this limitation in the claim. In addition, the recitation of “a miRNA biomarker listed in FIG. 3C or 12B, and a gene biomarker listed in FIG. 3D, 4C, or 12B” in lines 4-5 of the claim are indefinite. As stated in MPEP 2173.05(s), the claims should be complete to themselves and reference to a figure in the specification renders the claim incomplete. Claims which recite figures are only permitted in exceptional circumstances where there is no practical way to define the invention in words or where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.
Regarding claim 3, the recitations of “hsa-miR-3918” and “hsa-miR-760” in lines 2-3 of the claim is unclear if recitations of biomarkers of “hsa-miR-3918” and “hsa-miR-760” are the same biomarkers of “miR-3918” and “miR-760” as recited in claims 1 & 2, from which claim 3 depends from, or if they encompass more or different qualities than the previously recited biomarkers of “miR-3918” and “miR-760”.
Regarding claim 4, the recitations of “hsa-miR-3918” and “hsa-miR-760” in line 2 of the claim is unclear if recitations of biomarkers of “hsa-miR-3918” and “hsa-miR-760” are the same biomarkers of “miR-3918” and “miR-760” as recited in claims 1 & 2, from which claim 4 depends from, or if they encompass more or different qualities than the previously recited biomarkers of “miR-3918” and “miR-760”.
Regarding claim 18, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. What is the range? Is there a particular range of expression levels in a subject identified as having GBM? How does within the range of expression levels in samples of a subject compare to within the range of expression levels in samples of subjects identified as high risk? It is unclear how the metric of “within the range of expression levels” would be determined.
Regarding claim 19, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. What is the range? Is there a particular range of expression levels in a subject identified as having GBM? How does within the range of expression levels in samples of a subject compare to within the range of expression levels in samples of subjects identified as high risk? It is unclear how the metric of “within the range of expression levels” would be determined.
Regarding claim 42, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. What is the range? Is there a particular range of expression levels in a subject identified as having GBM? How does within the range of expression levels in samples of a subject compare to within the range of expression levels in samples of subjects identified as high risk? It is unclear how the metric of “within the range of expression levels” would be determined.
Regarding claim 43, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. What is the range? Is there a particular range of expression levels in a subject identified as having GBM? How does within the range of expression levels in samples of a subject compare to within the range of expression levels in samples of subjects identified as high risk? It is unclear how the metric of “within the range of expression levels” would be determined.
Regarding claim 68, the claim recites the limitation “the expression level of one or more biomarkers” in lines 1-2 of the claim and there is insufficient antecedent basis for this limitation in the claim. In addition, the recitation of “a miRNA biomarker listed in FIG. 3C or 12B, and a gene biomarker listed in FIG. 3D, 4C, or 12B” in lines 4-5 of the claim are indefinite. As stated in MPEP 2173.05(s), the claims should be complete to themselves and reference to a figure in the specification renders the claim incomplete. Claims which recite figures are only permitted in exceptional circumstances where there is no practical way to define the invention in words or where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.
Claims 2, 44, 48, & 50-53 are rejected due to their dependence on claim 1 and claims 45-47 & 49 are rejected due to their dependence on claim 18.
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 1-4, 18, 19, 42-45, & 48-53 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to [methods/products] and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method for treating a subject with GBM. The claimed invention also recites treating the subject for GBM after the expression level of one or more biomarkers has been determined in a sample of the subject which is a recitation of an abstract idea because it encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of treating the subject for GBM after the expression level of one or more biomarkers has been determined in a sample from the subject, however, this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the step of obtaining a sample is considered insignificant post solution activity. The steps of expression level of one or more biomarkers has been determined are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[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.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than an abstract idea and any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
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.
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.
Claim(s) 1-4, 18, 19, 42-44, 48-53, & 68 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maachani (Maachani et al.; OncoTarget, Vol. 7, pages 52912-52927, May 2015), in view of Dong (Dong et al.; International Journal of Oncology, Vol. 45, pages 746-756, April 2014), as cited on the IDS dated 09/06/2023.
Regarding claim 1, Maachani teaches treatment of glioblastoma (GBM) samples comprising measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array, in which the Affymetrix HuEx-1_0-st-v2 array comprises oligonucleotides that measure the expression of genes including MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 (the expression level of one or more biomarkers of MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 has been determined in a sample from the subject) (pg. 52913 column 1 2nd full paragraph lines 14-22; pg. 52917 paragraph bridging column 1 & 2 lines 5-11; pg. 52923 paragraph bridging column 1 & 2 lines 1-40; pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Maachani does not teach the expression level of miR-3918 or miR-760 has been determined in a sample from the subject.
Dong teaches that miRNAs are frequently dysregulated in GBM patients and analysis of miRNAs in the serum of patients with GBM through microarray analysis to determine differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array in which this miRNA PCR array comprises targets for miR-3918 and miR-760 (the expression level of one or more biomarkers of miR-3918 and miR-760 has been determined in a sample from the subject) (abstract lines 1-10; pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6; pg. 747 column 1 1st full paragraph lines 1-7; pg. 747 column 1 2nd full paragraph lines 1-10). In addition, Dong teaches that analysis of miRNA profiles in the blood may serve as a new biomarker for glioma diagnosis with high specificity and sensitivity (abstract lines 19-22).
Maachani and Dong are considered to be analogous to the claimed invention because they are all in the same field of measuring the expression levels of biomarkers in GBM samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array in Maachani to incorporate the measurement of differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array as taught in Dong because Dong teaches that doing so would provide a method to analyze miRNA profiles in blood to serve as a new biomarker for glioma diagnosis with high specificity and sensitivity.
Regarding claim 2, Maachani teaches measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array, in which the Affymetrix HuEx-1_0-st-v2 array comprises oligonucleotides that measure the expression of genes including MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 (biomarkers comprises one or more of MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 has been determined in a sample from the subject) (pg. 52913 column 1 2nd full paragraph lines 14-22; pg. 52917 paragraph bridging column 1 & 2 lines 5-11; pg. 52923 paragraph bridging column 1 & 2 lines 1-40; pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Dong teaches that miRNAs are frequently dysregulated in GBM patients and analysis of miRNAs in the serum of patients with GBM through microarray analysis to determine differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array in which this miRNA PCR array comprises targets for miR-3918 and miR-760 (biomarkers comprises one or more of miR-3918 and miR-760 has been determined in a sample from the subject) (abstract lines 1-10; pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6; pg. 747 column 1 1st full paragraph lines 1-7; pg. 747 column 1 2nd full paragraph lines 1-10).
Regarding claim 3, Maachani teaches measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array, in which the Affymetrix HuEx-1_0-st-v2 array comprises oligonucleotides that measure the expression of genes including MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 (biomarkers comprises one or more of MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 has been determined in a sample from the subject) (pg. 52913 column 1 2nd full paragraph lines 14-22; pg. 52917 paragraph bridging column 1 & 2 lines 5-11; pg. 52923 paragraph bridging column 1 & 2 lines 1-40; pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Dong teaches that miRNAs are frequently dysregulated in GBM patients and analysis of miRNAs in the serum of patients with GBM through microarray analysis to determine differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array in which this miRNA PCR array comprises targets for hsa-miR-3918 and hsa-miR-760 (biomarkers comprises one or more of hsa-miR-3918 and hsa-miR-760 has been determined in a sample from the subject) (abstract lines 1-10; pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6; pg. 747 column 1 1st full paragraph lines 1-7; pg. 747 column 1 2nd full paragraph lines 1-10).
Regarding claim 4, Maachani teaches measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array, in which the Affymetrix HuEx-1_0-st-v2 array comprises oligonucleotides that measure the expression of genes including MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 (biomarkers comprises one or more of MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 has been determined in a sample from the subject) (pg. 52913 column 1 2nd full paragraph lines 14-22; pg. 52917 paragraph bridging column 1 & 2 lines 5-11; pg. 52923 paragraph bridging column 1 & 2 lines 1-40; pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Dong teaches that miRNAs are frequently dysregulated in GBM patients and analysis of miRNAs in the serum of patients with GBM through microarray analysis to determine differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array in which this miRNA PCR array comprises targets for hsa-miR-3918 and hsa-miR-760 (biomarkers comprises one or more of hsa-miR-3918 and hsa-miR-760 has been determined in a sample from the subject) (abstract lines 1-10; pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6; pg. 747 column 1 1st full paragraph lines 1-7; pg. 747 column 1 2nd full paragraph lines 1-10).
Regarding claim 18, it is noted, as discussed above, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk).
Maachani teaches analyzing differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array (determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Regarding claim 19, it is noted, as discussed above, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk).
Maachani teaches analyzing differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array (determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Regarding claim 42, it is noted, as discussed above, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk).
Maachani teaches analyzing differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array (determining differential expression levels in samples with GBM compared to control comprising MMP9, TMEM92, C1orf226, CD163, and LINC00482 (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Dong teaches determining differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array (determining differential expression levels in samples with GBM compared to control comprising miR-3918 (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 747 column 1 1st full paragraph lines 1-7).
Regarding claim 43, it is noted, as discussed above, the recitation of “within the range of expression levels in samples of subject identified as having GBM or identified as high risk” in lines 4-5 of the claim is unclear what “within the range of expression levels” would encompass. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to encompass determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk).
Maachani teaches analyzing differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array (determining differential expression levels in samples with GBM compared to control comprising AK5, CD200, and MICU3 (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Dong teaches determining differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array (determining differential expression levels in samples with GBM compared to control comprising miR-760 (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 747 column 1 1st full paragraph lines 1-7).
Regarding claim 44, Maachani teaches treatment of glioblastoma (GBM) samples comprising measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array (subject is treated for GBM) (pg. 52913 column 1 2nd full paragraph lines 14-22; pg. 52917 paragraph bridging column 1 & 2 lines 5-11; pg. 52923 paragraph bridging column 1 & 2 lines 1-40; pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Regarding claim 48, Dong teaches the sample comprises a blood sample from GBM patients and healthy controls (sample from the subject comprises a whole blood sample) (pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6).
Regarding claim 49, it is noted that claim 18, from which claim 49 depends from, recites determining expression levels of one or more biomarkers in the sample determined to be increased compared to levels of expression in samples from subjects identified as not having GBM, subjects identified as low risk, or normal tissues or within the range of expression levels in samples of subjects identified as having GBM or identified as high risk. Therefore, claim 18 and dependent claim 49 do not require the use of normal tissues.
Maachani teaches analyzing differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array (determining differential expression levels in samples with GBM compared to control (determining expression level of biomarkers in the sample within range of expression levels in samples of subjects identified as having GBM or identified as high risk)) (pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Regarding claim 50, Dong teaches the sample comprises a blood sample from GBM patients and healthy controls in which RNA is extracted from the sample (sample from the subject comprises nucleic acids) (pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6).
Regarding claim 51, Dong teaches the sample comprises a blood sample from GBM patients and healthy controls in which RNA is extracted from the sample (sample from the subject comprises a fractionated blood sample comprising nucleic acids) (pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6).
Regarding claim 52, Maachani teaches the subject is a human GBM patient (subject is a human subject) (pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Dong teaches the sample comprises a blood sample from GBM patients and healthy controls (sample comprises a human sample) (pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6).
Regarding claim 53, the sample comprises a blood sample from GBM patients and healthy controls without GBM (sample from subjects identified as not having GBM comprises samples from subjects without GBM) (pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6).
Regarding claim 68, Maachani teaches treatment of glioblastoma (GBM) samples comprising measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array, in which the Affymetrix HuEx-1_0-st-v2 array comprises oligonucleotides that measure the expression of genes including MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 (the expression level of one or more biomarkers of MMP9, TMEM92, C1orf226, CD163, LINC00482, AK5, CD200, and MICU3 has been determined in a sample from the subject) (pg. 52913 column 1 2nd full paragraph lines 14-22; pg. 52917 paragraph bridging column 1 & 2 lines 5-11; pg. 52923 paragraph bridging column 1 & 2 lines 1-40; pg. 52924 paragraph bridging column 1 & 2 lines 1-10).
Maachani does not teach the expression level of miR-3918 or miR-760 has been determined in a sample from the subject.
Dong teaches that miRNAs are frequently dysregulated in GBM patients and analysis of miRNAs in the serum of patients with GBM through microarray analysis to determine differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array in which this miRNA PCR array comprises targets for miR-3918 and miR-760 (the expression level of one or more biomarkers of miR-3918 and miR-760 has been determined in a sample from the subject) (abstract lines 1-10; pg. 746-747 paragraph bridging pg. 746 & 747 lines 1-6; pg. 747 column 1 1st full paragraph lines 1-7; pg. 747 column 1 2nd full paragraph lines 1-10). In addition, Dong teaches that analysis of miRNA profiles in the blood may serve as a new biomarker for glioma diagnosis with high specificity and sensitivity (abstract lines 19-22).
Maachani and Dong are considered to be analogous to the claimed invention because they are all in the same field of measuring the expression levels of biomarkers in GBM samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring the differential expression of biomarkers in GBM patients with the Affymetrix HuEx-1_0-st-v2 array in Maachani to incorporate the measurement of differentially expressed miRNAs in serum between the GBM and normal controls with the Human panelI+II v3 miRCURY LNATM Universal RT miRNA PCR array as taught in Dong because Dong teaches that doing so would provide a method to analyze miRNA profiles in blood to serve as a new biomarker for glioma diagnosis with high specificity and sensitivity.
Claim(s) 45-47 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maachani (Maachani et al.; OncoTarget, Vol. 7, pages 52912-52927, May 2015) and Dong (Dong et al.; International Journal of Oncology, Vol. 45, pages 746-756, April 2014), as cited on the IDS dated 09/06/2023, as applied to claims 1-4, 18, 19, 42-44, 48, 50-53, & 68 above, and further in view of Wang (Wang et al.; EBioMedicine, Vol. 37, pages 68-77, October 2018), as cited on the IDS dated 09/06/2023, as evidenced by Kanzawa (Kanzawa et al.; British Journal of Cancer, Vol. 89, pages 922-929, 2003).
The teachings of Maachani and Dong with respect to claims 1 & 18 are discussed above.
Regarding claims 45-47, Maachani and Dong does not teach that the treatment comprises treatment with the chemotherapy temozolomide.
Wang teaches measuring expression of biomarkers with a microarray in GBM patients and then treating GBM cell lines with temozolomide (treatment for GBM comprises treatment with chemotherapy temozolomide), in which temozolomide can be administered orally as evidenced by Kanzawa (pg. 922 column 1 1st full paragraph lines 1-5 of Kanzawa) (abstract background lines 1-3; abstract methods lines 1-5; pg. 69-70 paragraph bridging pg. 69 & 70 lines 1-8; pg. 74-75 paragraph bridging pg. 74 & 75 lines 1-8). In addition, that this method provides new insights to early diagnosis and the prognosis for GBM patients and provides potential GM therapeutic targets to treat GBM (abstract interpretation lines 1-3).
Maachani, Dong, and Wang are considered to be analogous to the claimed invention because they are all in the same field of measuring the expression levels of biomarkers in GBM samples. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treatment of glioblastoma (GBM) samples comprising measuring differential expression of biomarkers with an array in Maachani to incorporate the treatment of GBM with the chemotherapy temozolomide as taught in Wang because Wang teaches that doing so would provide provides new insights to early diagnosis and the prognosis for GBM patients and provides potential GM therapeutic targets to treat GBM.
Conclusion
Claims 1-4, 18, 19, 42-53, & 68 are rejected.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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