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 .
The examiner reviewing this application in the USPTO have changed. All new correspondence should be directed to examiner Bailey Buchanan, Art Unit 1682.
Election/Restrictions
Applicant's election with traverse of the claims of Group in the reply filed on 07/27/2026 is acknowledged. The traversal is on the ground(s) that the restriction between Groups I and II as the methods of Group I and II both require detecting expression level of the same plurality of biomarkers in a sample obtained from a subject from the same sub-population of subjects and, accordingly, examination of the claims encompassed by Groups I and II can be performed without serious burden This is found persuasive and Group II, claims 33-35, 37-40, 42, 44, 97, & 99, is rejoined with Group I, claims 1, 10, 12, 14-16, 77, & 79. Group III, claim 51, is withdrawn from consideration pursuant to 37 CFR 1/142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant’s election without traverse of the species election of fibromyalgia for (a), Table 6 for (b), and all of the biomarkers recited in Table 6 for (c) in the reply filed 07/27/2026 is acknowledged. The species of the plurality of biomarkers from Table 6 is rejoined with wherein the plurality is two biomarkers from Table 6 and the species of fibromyalgia is rejoined with chronic fatigue. The cancellation of claims 10, 12, 14, 16, 38, 40, 42, 44, 77, 79, 97, & 99 in the reply filed on 07/27/2026 without prejudice or disclaimer is acknowledged.
A first office action on the merits of claims 1, 15, 33-35, 37, & 39 is set forth herein and claim 51 is withdrawn from consideration.
Priority
5. The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/489,881, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The provisional application, 63/489,881, does not have support of all of the limitations in claims 1, 15, 33-35, 37, & 39 of the instant application. The provisional application, 63/489,881, does not provide support for Table 6. Accordingly, claims 1, 15, 33-35, 37, & 39 are not entitled to the benefit of the prior applications. Therefore, claims 1, 15, 33-35, 37, & 39 are given a priority date of filing 03/13/2024.
Information Disclosure Statement
The listing of references in throughout the specification and at pages 175-180 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.
Improper Markush Rejection
Claims 1, 15, 33-35, 37, & 39 are rejected on the basis that it contains an improper Markush grouping of alternatives. See Jn re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (Le., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements when the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. See MPEP § 2117 which provides guidance on the analysis of a proper Markush group.
Regarding claims 1, 15, 33, 34, & 39, the Markush group in question is any plurality of biomarkers from Table 6, alternatively recited gene from the structurally and functionally different genes in claims 1, 15, 33, 34, & 39.
Regarding “single structural similarity”, the MPEP at 2117 IIA states that a recognized physical, chemical, or an art recognized class is a class where there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. It is specifically stated that “Thus a Markush grouping is ordinarily proper if all the members for the group belong to a recognized class (whether physical, chemical, or art recognized) and are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed invention, and it is clear from their very nature or from the prior art that all members possess this property (emphasis added)”. Therefore, in analysis of whether a claim contains an improper Markush grouping, the MPEP states: A Markush claim contains an “improper Markush grouping” if either (emphasis added): (1) the members of the Markush group do not share a ‘single structural similarity’ or (2) the members do not share a common use.”
In the instant case, the genes do not share any common structural element that is essential to the asserted utility of being associated with a disease the results from an immune deficiency selected from fibromyalgia, chronic fatigue, etc. The different genes are from different parts of the human genome and are composed of different nucleic acid sequences in distinct genetic contexts and the proteins encoded by the genes do not share any particular biological activity or active domain that is essential to being associated with a disease that results with an immune deficiency selected from fibromyalgia, chronic fatigue, etc. Thus when considering the different genes recited in the alternative, as recited in the rejected claims, there does not appear to be any common structure related to the function of the genes in the claims.
For example: The gene encoding A4GNT is located on chromosome 3 and encodes a protein involved in transfer of N-acetylglucosamine to branched O-glycans and is involved with the Golgi apparatus membrane. Diseases associated with A4GNT include stomach inflammation and increased tumor growth/size. The gene encoding TEC is located on chromosome 4 and encodes for a signal transducer in immune regulation, hematopoiesis, and growth pathways. Diseases associated with TEC include transient erythroblastophenia of childhood and soft tissue sarcoma. The gene encoding IGSF3 is located on chromosome 1 and encodes for immunoglobulin-like membrane protein. Diseases associated with IGSF3 include familial congenital nasolacrimal duct obstruction and lacrimal duct effect. The gene encoding RPL15 is located on chromosome 3 and encodes for a large ribosomal subunit that participates in translation. Diseases associated with RPL15 include Fanconi anemia and protein deficiency anemia. The gene encoding ZNF532 is located on chromosome 18 and encodes for DNA-binding activity and regulation of DNA-templated transcription. Diseases associated with ZNF532 include midline carcinoma and thrombocytosis.
Therefore it is clear that when considering the different genes there does not appear to be any common structure related to the function of the genes individually, or any particular combination of the genes, let alone an association with a disease that results with an immune deficiency selected from fibromyalgia, chronic fatigue, etc. Furthermore, the recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different genes. The only structural similarity present is that all the genes are made up of nucleotides. However, comprising nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with a disease that results with an immune deficiency selected from fibromyalgia, chronic fatigue, etc.
Following this analysis, the claims 1, 15, 33, 34, & 39 are rejected as containing improper Markush grouping and claims 35 & 37 are rejected due to their dependence on claim 33.
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 15, 33-35, 37, & 39 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 15, the recitation of “at least 90%, at least 95% or at least 99% of the biomarkers” in lines 4-5 of the claim is unclear if at least 95% and at least 99% are part of the same group selection or if this is the result of a typographical error and should read “at least 90%, at least 95%, or at least 99% of the biomarkers”.
Regarding claim 33, the recitation of “a probiotic, a post-biotic and a standard of care for the disease” in lines 20-21 of the claim is unclear if a post-biotic and a standard of care for the disease are part of the same treatment selection or if this is the result of a typographical error and should read “a probiotic, a post-biotic, and a standard of care for the disease”.
Regarding claim 34, the recitation of “comparing the nucleic acid levels of the plurality of biomarkers from Table 6 to the nucleic acid expression levels of the plurality of biomarkers from Table 6 in at least one sample training set(s)” in liens 2-4 of the claim is unclear what sets of nucleic acid levels are being compared. Are the levels of the biomarkers from Table 6 being compared also with the biomarkers of Table 6? In addition, the recitations of “from a reference the disease” in line 6 of the claim and of “from a reference non-disease” in line 8 of the claim is unclear and it is suggested to amend the recitations to “from a reference of the disease” or “from a disease reference” in line 6 of the claim and “from a reference of a non-disease” or “from a non-disease reference” in line 8 of the claim. In addition, the recitation of “classifying the subject as having the disease that results from an immune deficiency based on the results of the comparing step” in lines 9-10 of the claim is unclear what the relationship is between a disease that results from an immune deficiency and results of a comparing step? What results of comparisons classify the subject as having the disease that results from an immune deficiency versus results of comparisons that do not?
Regarding claim 35, the recitation of “systemic lupus erythematosus (SLE), Sjogren Syndrome and multiple sclerosis” in lines 4-5 of the claim is unclear if a Sjogren Syndrome and multiple sclerosis are part of the same disease selection or if this is the result of a typographical error and should read “systemic lupus erythematosus (SLE), Sjogren Syndrome, and multiple sclerosis”.
Claim 37 is rejected due to its dependence on claim 34 and claim 39 is rejected due to its dependence on claim 33.
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 33-35, 37, & 39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and 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 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 of treating a disease that results from an immune deficiency selected from fibromyalgia (FM) comprising measuring a nucleic acid expression level of a plurality of biomarkers in a sample obtained from a subject suspected of suffering from a disease consisting of FM wherein the nucleic acid expression level of the plurality of biomarkers indicates that the subject has a disease selected from FM and administering a treatment for the disease. This recitation is a natural correlation between expression level of a plurality of biomarkers and indication that a subject has a disease selected from FM. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “comparing the nucleic acid expression levels of the plurality of biomarkers from Table 6 to the nucleic acid expression levels of the plurality of biomarkers from Table 6” 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 measuring a nucleic acid expression level of a plurality of biomarkers and administering a treatment for the disease, 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.
Although the claims recite “administering a treatment for the disease that results from an immune deficiency” to the patient, this step is conditional as it is based on the indication that a subject has the disease from the nucleic acid expression level of a plurality of biomarkers. Accordingly, these generally recited elements are considered nothing more than instructions to apply the law of nature because no particular conditions are required by the step of detecting gene expression. As such, the “administering” step is merely a generalized “treat” limitation with no particularity that integrates the judicial exception into a practical application. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294.
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 steps of measuring gene expression level of a plurality of biomarkers 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 the determination that a natural correlation/phenomena exists. 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 § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 & 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mohapatra (Mohapatra et al.; Scientific Reports, Vol. 14, pages 1-16, February 17th, 2024).
Regarding claim 1, Mohapatra teaches a method of measuring gene expression levels in patients with fibromyalgia (subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from fibromyalgia) comprising measuring the expression of 1,720 differentially expressed genes (measuring the nucleic acid expression level of a plurality of biomarkers) and analyzing with Qiagen Ingenuity Pathway Analysis and Gene Set Enrichment Analysis in which the 1,720 differentially expressed measured genes of supplemental table 1 are the same as the 1,720 genes listed in Table 6 of the instant application (measuring a nucleic acid expression level of a plurality of biomarkers from Table 6) (abstract lines 1-15; pg. 2-3 paragraph bridging lines 1-13; pg. 3 3rd full paragraph lines 1-10; Supplemental Table 1).
Regarding claim 15, Mohapatra teaches the 1,720 differentially expressed measured genes of supplemental table 1 are the same as the 1,720 genes listed in Table 6 of the instant application (the plurality of biomarkers selected from Table 6 comprises at least 99% of the biomarkers from Table 6) (abstract lines 1-15; pg. 2-3 paragraph bridging lines 1-13; pg. 3 3rd full paragraph lines 1-10; Supplemental Table 1).
Claim(s) 1 & 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Syenina (Syenina et al.; PLOS Biology, Vol. 20, pages 1-23, May 2022).
Regarding claim 1, it is noted, as discussed above the species of wherein the plurality of biomarkers from Table 6 is rejoined with wherein the plurality is two biomarkers from Table 6 and the species of fibromyalgia is rejoined with chronic fatigue.
Syenina teaches a method of measuring nucleic acid expression level of a plurality of biomarkers with the Affymetrix Human Gene Chip 2.0 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene Chip 2.0 ST array (measuring a nucleic acid expression level of a plurality (two) of biomarkers from Table 6), in a sample obtained from patients with chronic fatigue post COVID-19 vaccination (sample obtained from the subject wherein the subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from chronic fatigue) (abstract lines 1-17; pg. 2 3rd full paragraph lines 1-10; pg. 16 3rd full paragraph lines 1-13).
Regarding claim 15, Syenina teaches a method of measuring nucleic acid expression level of a plurality of biomarkers with the Affymetrix Human Gene Chip 2.0 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene Chip 2.0 ST array (wherein the plurality of biomarkers selected from Table 6 comprises at least 10% of the biomarkers from Table 6) (abstract lines 1-17; pg. 2 3rd full paragraph lines 1-10; pg. 16 3rd full paragraph lines 1-13).
Claim(s) 1 & 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jones (Jones et al.; Clin. Exp Rheumatol., Vol. 34, pages 89-98, June 2016).
Regarding claim 1, it is noted, as discussed above the species of wherein the plurality of biomarkers from Table 6 is rejoined with wherein the plurality is two biomarkers from Table 6.
Jones teaches a method of measuring nucleic acid expression level in fibromyalgia patients and healthy controls with the Affymetrix Human Gene 1.1 ST Peg array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene 1.1 ST Peg array (measuring a nucleic acid expression level of a plurality (two) of biomarkers from Table 6) in samples obtained from patients with fibromyalgia and healthy controls (sample obtained from the subject wherein the subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from fibromyalgia) (abstract methods lines 1-3; abstract results lines 1-9; pg. 3-4 paragraph bridging pg. 3 & 4 lines 1-5; pg. 4 1st full paragraph lines 1-10).
Regarding claim 15, Jones teaches a method of measuring nucleic acid expression level in fibromyalgia patients and healthy controls with the Affymetrix Human Gene 1.1 ST Peg array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene 1.1 ST Peg array (wherein the plurality of biomarkers selected from Table 6 comprises at least 10% of the biomarkers from Table 6) (abstract methods lines 1-3; abstract results lines 1-9; pg. 3-4 paragraph bridging pg. 3 & 4 lines 1-5; pg. 4 1st full paragraph lines 1-10).
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) 33-35, 37, & 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mohapatra (Mohapatra et al.; Scientific Reports, Vol. 14, pages 1-16, February 17th, 2024), in view of Gillis (United States Patent Application Publication US 2021/0236616 A1, August 2021), as cited in the IDS dated 07/10/2024.
Regarding claim 33, Mohapatra teaches a method of measuring gene expression levels in patients with fibromyalgia (subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from fibromyalgia) comprising measuring the expression of 1,720 differentially expressed genes (measuring the nucleic acid expression level of a plurality of biomarkers) and analyzing with Qiagen Ingenuity Pathway Analysis and Gene Set Enrichment Analysis in which the 1,720 differentially expressed measured genes of supplemental table 1 are the same as the 1,720 genes listed in Table 6 of the instant application (measuring a nucleic acid expression level of a plurality of biomarkers from Table 6) (abstract lines 1-15; pg. 2-3 paragraph bridging lines 1-13; pg. 3 3rd full paragraph lines 1-10; Supplemental Table 1). Mohapatra also teaches that this method will lead to the development of accurate diagnostic markers and effective therapeutic options for fibromyalgia (abstract lines 14-15).
Mohapatra does not teach administering a treatment that modulates the immune system, a vaccine, a nutritional supplement, a pre-biotic, a probiotic, a post-biotic, or a standard of care for fibromyalgia.
Gillis teaches a method for detecting altered expression of biomarkers in fibromyalgia and for treatment of fibromyalgia comprising administering a therapeutically effective amount of a vaccine to the subject (administering a treatment for the disease that results from an immune deficiency (fibromyalgia) selected from a group consisting of a vaccine) (paragraph [0009] lines 1-5; paragraph [0026] lines 1-24). Gillis also teaches that this treatment method can induce epigenetic changes that can provide the individual with life-long immunity against re-occurrence of fibromyalgia (paragraph [0025] lines 1-8).
Mohapatra and Gillis are considered to be analogous to the claimed invention because they are all in the same field of detecting expression of biomarkers and treatment of fibromyalgia. 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 gene expression levels in patients with fibromyalgia comprising measuring the expression of 1,720 differentially expressed genes to determine therapeutic options in Mohapatra to incorporate the treatment of fibromyalgia with a vaccine as taught in Gillis because Gillis teaches that doing so would provide a treatment that can induce epigenetic changes that can provide the individual with life-long immunity against re-occurrence of fibromyalgia.
Regarding claim 34, Mohapatra teaches comparing the nucleic acid expression levels of the 1,720 measured genes in supplemental table 1, in which supplemental table 1 is the same as instant Table 6, in fibromyalgia and control cases (comparing the nucleic acid expression levels of a plurality of biomarkers from Table 6 in at least one sample training set comprising data from a reference of the disease and from a reference from the non-disease (control) to classify subject as having fibromyalgia) (pg. 3 2nd full paragraph lines 1-5; pg. 3 4th full paragraph lines 1-10; pg. 3 5th full paragraph lines 1-3; supplemental table 1).
Regarding claim 35, Mohapatra teaches comparing the nucleic acid expression levels of the 1,720 measured genes in supplemental table 1 in fibromyalgia and control cases in which the control cases are samples comprising individuals without fibromyalgia (the disease that results from an immune deficiency is fibromyalgia and wherein the non-FM sample is obtained from an individual not known to have FM) (pg. 3 2nd full paragraph lines 1-5; pg. 3 4th full paragraph lines 1-10; pg. 3 5th full paragraph lines 1-3; Table 1).
Regarding claim 37, Mohapatra teaches cluster analysis of the differentially expressed genes comprising use of the software ‘R’ and using the algorithm of the transcripts per million between the fibromyalgia and control cases (comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample obtained from the subject and at least one training set and classifying the sample as having fibromyalgia based on the results of the statistical algorithm) (pg. 3 4th full paragraph lines 1-10; pg. 3 5th full paragraph lines 1-3).
Regarding claim 39, Mohapatra teaches the 1,720 differentially expressed measured genes of supplemental table 1 are the same as the 1,720 genes listed in Table 6 of the instant application (the plurality of biomarkers selected from Table 6 comprises at least 99% of the biomarkers from Table 6) (abstract lines 1-15; pg. 2-3 paragraph bridging lines 1-13; pg. 3 3rd full paragraph lines 1-10; Supplemental Table 1).
Claim(s) 33-35, 37, & 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Syenina (Syenina et al.; PLOS Biology, Vol. 20, pages 1-23, May 2022), in view of Rimes (Rimes & Chalder; Occupational Medicine, Vol. 55, pages 32-39, January 2005).
Regarding claim 33, it is noted, as discussed above the species of wherein the plurality of biomarkers from Table 6 is rejoined with wherein the plurality is two biomarkers from Table 6 and the species of fibromyalgia is rejoined with chronic fatigue.
Syenina teaches a method of measuring nucleic acid expression level of a plurality of biomarkers with the Affymetrix Human Gene Chip 2.0 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene Chip 2.0 ST array (measuring a nucleic acid expression level of a plurality (two) of biomarkers from Table 6), in a sample obtained from patients with chronic fatigue post COVID-19 vaccination (sample obtained from the subject wherein the subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from chronic fatigue) to minimize and treat the adverse events of chronic fatigue post COVID-19 vaccination (abstract lines 1-17; pg. 2 3rd full paragraph lines 1-10; pg. 16 3rd full paragraph lines 1-13).
Syenina does not teach administering a treatment that modulates the immune system, a vaccine, a nutritional supplement, a pre-biotic, a probiotic, a post-biotic, or a standard of care for fibromyalgia.
Rimes teaches methods for treating patients with chronic fatigue comprising treatment of chronic fatigue with a variety of different methods comprising cognitive behavior therapy (standard of care) and corticosteroids (treatment that modulates the immune system) (administering a treatment fort the disease that results from an immune deficiency (chronic fatigue) selected from a group consisting of a treatment that modulates the immune system and a standard of care for the disease) (abstract aims lines 1-2; abstract results lines 1-6; pg. 32-33 paragraph bridging pg. 32 & 33 lines 1-23; pg. 32 column 2 2nd full paragraph lines 1-11). Rimes also teaches that these methods for treatment of chronic fatigue play an important role in reducing symptoms in patients with chronic fatigue and improving their function and ability to return to work (abstract conclusions lines 1-4).
Syenina and Rimes are considered to be analogous to the claimed invention because they are all in the same field of analysis and treatment of chronic fatigue. 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 nucleic acid expression level of a plurality of biomarkers with the Affymetrix Human Gene Chip 2.0 ST array in patients with chronic fatigue to minimize and treat the adverse events of chronic fatigue post COVID-19 vaccination in Syenina to incorporate the treatment of chronic fatigue with standard of care of cognitive behavior therapy or immune modulating treatment of corticosteroids as taught in Rimes because Rimes teaches that doing so would play an important role in reducing symptoms in patients with chronic fatigue and improving their function and ability to return to work.
Regarding claim 34, Syenina teaches comparing the nucleic acid expression levels of the genes measured with the Affymetrix Human Gene Chip 2.0 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene Chip 2.0 ST array, in patients with chronic fatigue post vaccination and healthy control cases from pre-vaccination that had mild fatigue or no fatigue (comparing the nucleic acid expression levels of a plurality (two) of biomarkers from Table 6 in at least one sample training set comprising data from a reference of the disease and from a reference from the non-disease (control) to classify subject as having chronic fatigue) (pg. 16 3rd full paragraph lines 1-13).
Regarding claim 35, Syenina teaches a method of measuring nucleic acid expression level of a plurality of biomarkers with the Affymetrix Human Gene Chip 2.0 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene Chip 2.0 ST array (measuring a nucleic acid expression level of a plurality (two) of biomarkers from Table 6), in a sample obtained from patients with chronic fatigue post COVID-19 vaccination (sample obtained from the subject wherein the subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from chronic fatigue) to minimize and treat the adverse events of chronic fatigue post COVID-19 vaccination (abstract lines 1-17; pg. 2 3rd full paragraph lines 1-10; pg. 16 3rd full paragraph lines 1-13).
Regarding claim 37, Syenina teaches cluster analysis of the measuring gene expression using Python algorithm to compare between patients with chronic fatigue post vaccination and healthy control cases from pre-vaccination that had mild fatigue or no fatigue (comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample obtained from the subject and at least one training set and classifying the sample as having chronic fatigue based on the results of the statistical algorithm) (pg. 16 3rd full paragraph lines 1-13).
Regarding claim 39, Syenina teaches a method of measuring nucleic acid expression level of a plurality of biomarkers with the Affymetrix Human Gene Chip 2.0 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene Chip 2.0 ST array (wherein the plurality of biomarkers selected from Table 6 comprises at least 10% of the biomarkers from Table 6) (abstract lines 1-17; pg. 2 3rd full paragraph lines 1-10; pg. 16 3rd full paragraph lines 1-13).
Claim(s) 33-35, 37, & 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jones (Jones et al.; Clin. Exp Rheumatol., Vol. 34, pages 89-98, June 2016), in view of Gillis (United States Patent Application Publication US 2021/0236616 A1, August 2021), as cited in the IDS dated 07/10/2024.
Regarding claim 33, it is noted, as discussed above the species of wherein the plurality of biomarkers from Table 6 is rejoined with wherein the plurality is two biomarkers from Table 6.
Jones teaches a method of measuring nucleic acid expression level in fibromyalgia patients and healthy controls with the Affymetrix Human Gene 1.1 ST Peg array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene 1.1 ST Peg array (measuring a nucleic acid expression level of a plurality (two) of biomarkers from Table 6) in samples obtained from patients with fibromyalgia and healthy controls (sample obtained from the subject wherein the subject suffers from or is suspected of suffering from a disease that results from an immune deficiency selected from fibromyalgia) (abstract methods lines 1-3; abstract results lines 1-9; pg. 3-4 paragraph bridging pg. 3 & 4 lines 1-5; pg. 4 1st full paragraph lines 1-10).
Jones does not teach administering a treatment that modulates the immune system, a vaccine, a nutritional supplement, a pre-biotic, a probiotic, a post-biotic, or a standard of care for fibromyalgia.
Gillis teaches a method for detecting altered expression of biomarkers in fibromyalgia and for treatment of fibromyalgia comprising administering a therapeutically effective amount of a vaccine to the subject (administering a treatment for the disease that results from an immune deficiency (fibromyalgia) selected from a group consisting of a vaccine) (paragraph [0009] lines 1-5; paragraph [0026] lines 1-24). Gillis also teaches that this treatment method can induce epigenetic changes that can provide the individual with life-long immunity against re-occurrence of fibromyalgia (paragraph [0025] lines 1-8).
Jones and Gillis are considered to be analogous to the claimed invention because they are all in the same field of detecting expression of biomarkers and treatment of fibromyalgia. 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 gene expression levels in patients with fibromyalgia comprising measuring nucleic acid expression level in fibromyalgia patients and healthy controls with the Affymetrix Human Gene 1.1 ST Peg array to determine tailor treatment options in Jones to incorporate the treatment of fibromyalgia with a vaccine as taught in Gillis because Gillis teaches that doing so would provide a treatment that can induce epigenetic changes that can provide the individual with life-long immunity against re-occurrence of fibromyalgia.
Regarding claim 34, Jones teaches comparing the nucleic acid expression levels of the genes measured with the Affymetrix Human Gene 1.1 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene 1.1 ST Peg array, in patients with fibromyalgia and healthy control cases (comparing the nucleic acid expression levels of a plurality (two) of biomarkers from Table 6 in at least one sample training set comprising data from a reference of the disease and from a reference from the non-disease (control) to classify subject as having fibromyalgia) (pg. 5-6 paragraph bridging pg. 5 & 6 lines 1-15).
Regarding claim 35, Jones teaches comparing the nucleic acid expression levels of the genes measured with the Affymetrix Human Gene 1.1 ST array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene 1.1 ST Peg array, in patients with fibromyalgia and healthy control cases (the disease that results from an immune deficiency is fibromyalgia and wherein the non-FM sample is obtained from an individual not known to have FM) (pg. 5-6 paragraph bridging pg. 5 & 6 lines 1-15).
Regarding claim 37, Jones teaches the comparison step comprises an internal training cohort data sets that are trained with a SVM classifier model and use of ANOVA on the corresponding training group to determine significant genes (comparing step comprises applying a statistical algorithm which comprises determining a correlation between the expression data obtained from the sample obtained from the subject and at least one training set and classifying the sample as having fibromyalgia based on the results of the statistical algorithm) (pg. 5-6 paragraph bridging pg. 5 & 6 lines 1-15).
Regarding claim 39, Jones teaches a method of measuring nucleic acid expression level in fibromyalgia patients and healthy controls with the Affymetrix Human Gene 1.1 ST Peg array, in which a plurality (two or more) of biomarkers in Table 6 are measured with the Affymetrix Human Gene 1.1 ST Peg array (wherein the plurality of biomarkers selected from Table 6 comprises at least 10% of the biomarkers from Table 6) (abstract methods lines 1-3; abstract results lines 1-9; pg. 3-4 paragraph bridging pg. 3 & 4 lines 1-5; pg. 4 1st full paragraph lines 1-10).
Conclusion
Claims 1, 15, 33-35, 37, & 39 are rejected.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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