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 .
This Office Action is in reply to Applicants’ correspondence of 4/20/2026. Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put this application in condition for allowance. New grounds of rejection, necessitated by amendments, are presented in this Office Action. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action. This Action is FINAL.
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Newly submitted claims 31 and 32 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the claims contain species of genes that were not originally presented as part of the methods claims that were originally elected. As originally presented, the claims did not include a step of measuring gene expression levels of a gene selected from a group consisting of RPS11, NCOR2, LY6D, RACK1, EMP1, MYADM, SERPINE1, TRIM29, ZC2HC1A, EGLN1, PHC3, KRIT1, and COMMD8. These species are independent or distinct because the different elements (i.e., each different
gene, or different subcombinations thereof) are structurally distinct and require different reagents (e.g., primers, probes, antibodies) for their detection and analysis. In addition, they are functionally distinct in that they are each involved in vastly different biological processes and so a reference pertaining to one element may not be expected to be a reference pertaining to any other different element.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 31 and 32 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Status
Claims 11, 13, and 20-36 are pending.
Claims 31-32 are withdrawn (see explanation above).
Claims 11, 13, 20-30, and 33-36 are being examined on the merits.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: “administering treatment to a subject with endometriosis” and “adjusting the treatment for endometriosis for the subject” are limitations in the present claims which do not find support in the disclosure (as covered in the 112a rejection below).
Please note that the above claim limitations have been rejected under 112a as “new matter” added to the claims (see below). Applicant is cautioned against amending the specification in a way that may introduce new matter into the disclosure.
Claim Objections
Claims 23-30 and 34-36 are objected to because of the following informalities:
Claims 23-30 and 34-36 read “The method of claim” in the preamble and should read “The method [[of]]according to claim” to maintain consistent claim format with all previously existing claims.
Appropriate correction is required.
New Claim Rejections - 35 USC § 112a – New Matter
Necessitated by Amendments
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.
Claims 20-21, 24-26, 28, 30, and 33-36 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. This is a new matter rejection.
Claims 20 and 25 contain the limitation “administering to the subject a treatment for endometriosis” and “administering a treatment for endometriosis to the subject”, respectively. However, administering a treatment to a subject that has endometriosis is not in the disclosure as filed (prior claim sets or RU document). The specification mentions “monitoring the effectiveness of endometriosis treatment (both hormonal and surgical)” (paragraph [0078]), but does not mention anywhere that the method comprises administering a treatment to an individual. Merely monitoring an effectiveness of a treatment is not equivocal to administering specific types of treatment to a patient that has been diagnosed based on said the defined method of diagnosing endometriosis. Therefore “administering a treatment” does not find adequate written description in the disclosure and constitutes an addition of new matter.
Claims 21, 24, 26, 28, and 30, depend from claim 20, inherit this deficiency, and are rejected on the same basis.
Claim 33 recites “adjusting the treatment for endometriosis for the subject”. However, adjusting a treatment is not in the disclosure as filed (prior claim sets or RU document). The specification mentions “monitoring the effectiveness of endometriosis treatment (both hormonal and surgical)” (paragraph [0078]), but does not mention anywhere that the method subsequently comprises adjusting a treatment to the subject. Further, the disclosure does not indicate what adjusting would entail (increase of treatment, decrease of treatment, cessation of treatment, change of treatment, etc.). Therefore “adjusting the treatment” does not find adequate written description in the disclosure and constitutes an addition of new matter.
Claims 34-36 depend from claim 33, inherit this deficiency, and are rejected on the same basis.
Claim Rejections - 35 USC § 112b – Indefiniteness
Withdrawn: The rejection of claims 11, 13, and 20-23 under 35 U.S.C. 112(b) as detailed in the Office Action of 1/26/2026 is withdrawn in light of Applicant’s amendments to the claims.
New (Necessitated by Amendments):
Claims 11, 13, 22-23, 25, 27-29, and 33-36 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 11 recites the limitation “generating a gene signature value at least in part based on a combination of expression levels measured in (c)”. It is unclear what the scope of the limitation “at least in part based on” encompasses. According to the examples in the specification, the gene signature value is calculated using only the combination of gene expression levels that are measured as in step (c). It is unclear what else could be used for the generation of the gene signature value, especially given that the language “at least in part” cannot be found in the disclosure. Clarification is required.
Claims 13, 22-23, 25, 27, and 29 depend from claim 11, inherit this deficiency, and are rejected on the same basis.
Claims 27 and 28 recite the limitation “wherein the given device comprises a sequencing device or a quantitative polymerase chain reaction device”. However, it is unclear how the device could be a qPCR machine, given that the claims from which these claims depend (claims 11 and 20, respectively) require the generation of at least 1 million uniquely mapped sequencing reads. Therefore, the scope of the claim is indefinite.
Claim 33 recites “adjusting the treatment for endometriosis for the subject”. However, it is unclear what “adjusting the treatment” means or how this relates to the result of the gene signature value being above the threshold value. Adjusting the treatment could be increasing the treatment, decreasing the treatment, changing the treatment, or stopping the treatment, and it is unclear how any of these relate to the determination that that patient’s gene signature value exceeds a threshold. The specification does not provide any examples of what “adjusting” may mean or how treatment may be modulated based on a second determination of a gene signature value over a threshold. Clarification is required.
Claims 34-36 depend from claim 33, inherit this deficiency, and are rejected on the same basis.
New Claim Rejections - 35 USC § 112d
Necessitated by Amendments
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.
Claims 27 and 28 are 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. As noted in the 112b rejection of claims 27 and 28 above, the claims recite the limitation “wherein the given device comprises a sequencing device or a quantitative polymerase chain reaction device”. However, it is unclear how the device could be a qPCR machine, given that the claims from which these claims depend (claims 11 and 20, respectively) require the generation of at least 1 million uniquely mapped sequencing reads. Therefore, these claims are rejected under 112d as they fail to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
Withdrawn: The rejection of claims 11, 13, and 20-23 under 35 U.S.C. 101 as detailed in the Office Action of 1/26/2026 is withdrawn in light of Applicant’s amendments to the claims.
New (Necessitated by Amendments): Claims 11, 13, 20-24, 27-30, and 33-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (e.g.: a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claim(s) is/are directed to a judicial exception encompassing abstract ideas and natural phenomena. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception as set forth below. The judicial exception is not integrated into a practical application of the judicial exception.
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S._, (2010) (slip op., at 5). “Phenomena 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).
Additionally, the unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Inti, 134 S. Ct. 2347, 2354 (2014).
The following inquiries are used to determine whether a claim is drawn to patent- eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes - the claims are directed to methods.
Step 2A, prong 1. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes — Where the claims are directed to “defining a threshold value…wherein the defining comprises calculating and minimizing Type I error rate and Type II error rate” and generating/calculating a gene signature value using gene expression levels using a generic device and diagnosing endometriosis by comparing a determined value to a threshold, the claims are directed to an abstract idea (mathematical processes – i.e, mathematical calculations, mathematical formulas, and mathematical relationships). Where the claims are directed to the association of the expression levels of a set of genes and a diagnosis of endometriosis the claim is directed to a natural phenomenon (a gene-expression:phenotype relationship).
Step 2A, prong 2. Does the claim integrate the judicial exception into a practical application? No - The judicial exception(s) to which the claims are directed are not integrated into a practical application because there are no required particular practical steps recited with specificity related to the endometriosis diagnosis, such as applying a particular endometriosis treatment to the subject. Additionally, claim 33 does not require that a treatment be administered at all. As noted in the 112b rejection above, the “adjusting a treatment” is indefinite in that there is no definition in the specification as to what “adjusting” entails, and thus could be cessation of treatment (therefore, no treatment is administered and there is no practical application of a particular step).
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No - The claims recite only routine steps related to measuring gene expression. It is known in the art to measure gene expression in relation endometriosis, as evidenced by the GEO data set GSE135485, published on October 1, 2019, which is a data set of expression profiling via high throughput sequencing in endometrial samples (GSE135485, 2019).
Additionally, it is noted that the specification indicates that the practical step of using a device to measure gene expression would be known to experts in the field. For example, the specification provides (page 14, lines 3-7), that experts in the field would understand how the methodology of determining gene expression would vary depending on the device used and the configuration that would be needed for said device.
Other additional elements include “obtaining…a sample from the subject by a minimally invasive collection procedure” and “generating at least 1 million uniquely mapped sequence reads”. However, these steps of data gathering are well understood, routine and conventional. Obtaining a sample through a minimally invasive means, such as through a blood sample, is known in the art and is recognized as desirable over invasive sample collection procedures such as laparoscopy, as taught by May et al. (Introduction, paragraph 1 and Table 1; Human Reproduction Update, 2011; cited on IDS of 8/17/2022). Generating at least 1 million uniquely mapped sequence reads when measuring gene expression is also well understood and routine in the art, as evidenced by the instant specification indicating that sequencing was performed with commercial platforms and that previous studies on the subject of quality of RNAseq have identified 3.5 million as an internal quality control threshold (Suntsova et al., Scientific Data, 2019). Additionally, Wang et al. teaches that RNAseq routinely generates millions of reads that are uniquely mapped to the genome of the organism in question to provide adequate coverage of whole transcriptomes (Challenges for RNA-Seq - Coverage versus cost; Nature Reviews, 2009; cited on IDS of 8/17/2022).
So even where a practical step of the claim may require measuring gene expression using samples obtained through minimally invasive means and at least 1 million uniquely mapped reads, or calculating and minimizing Type I and Type II error rates using conventional methods that have been practiced in the art, in University of Utah Res. Foundation v. Ambry Genetics Corp. (Fed Cir, 2014), the Court addressed claims that recite known methodological steps for collecting data (specifically genetic information) to be used in the application of a judicial exception, and held that:
Having determined that the comparison steps of claims 7 and 8 are abstract ideas, we move to the second step of Alice and ask whether the particular mechanism for the comparisons added by claims 7 or 8 renders the claims patent-eligible. For this step, Alice dictates that we ask whether the remaining elements, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to “transform the nature of the claim’ into a patent-eligible application.” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297). There must be a further inventive concept to take the claim into the realm of patent-eligibility. Id. at 2355. The second paragraph of claim 7 describes the way in which the sequences are compared: they are compared by 1) hybridizing a BRCA gene probe and 2) detecting the presence of a hybridization product. Similarly, claim 8 requires 1) amplification of the BRCA1 gene and 2) sequencing of the amplified nucleic acids. The non-patent-ineligible elements of claims 7 and 8 do not add “enough” to make the claims as a whole patent- eligible.
Additionally, In University of Utah Research v. Ambry Genetics the courts stated, "Recently in Alice the Supreme Court reiterated its two-step test to determine patent eligibility for any claims that allegedly encompass abstract ideas. First, "we determine whether the claims at issue are directed to [a] patent-ineligible concept. If so, we then ask, ‘what else is there in the claims before us?" Id. at 2355 (quoting Mayo, 132 S. Ct. at 1296-97) (citations and punctuation omitted). That is, we next ask whether the remaining elements, either in isolation or combination with the other non-patent- ineligible elements, are sufficient to " ‘transform the nature of the claim’ into a patent- eligible application." Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further "inventive concept" to take the claim into the realm of patent eligibility."
For these reasons the claims are rejected under 35 USC 101 as directed to subject matter that is not significantly more than a judicial exception.
Response to Remarks
Applicant traverses the rejection of claims 11, 13, and 20-23 under 35 USC 101 on pages 9-15 of the Remarks of 4/20/2026. Applicant's arguments have been fully considered but they are not deemed persuasive for the following reasons.
Applicant argues on page 11 of Remarks that the claims (such as claim 11) “recites several operations that cannot be performed in the human mind”. However, these “tangible operations” (obtaining a sample, measuring expression levels by generating at least 1 million uniquely mapped sequence reads) are not the judicial exceptions in question, and rather are extra-solution activity/additional elements that do not amount to significantly more (see the new 101 claim rejection above that details why these particular examples do not amount to significantly but are rather well-understood, routine, and conventional). The claims still recite judicial exceptions and thus the analysis proceeds to step 2A, prong two (does the claim integrate the recited judicial exceptions into a practical application).
Applicant argues on page 12 of Remarks that the “claimed methods represent a concrete improvement and inventive concept over the prior art” by “requiring that the sample be obtained through a minimally invasive collection procedure” and “specify[ing] a particular unconventional configuration of a specific device and particular method of using the data from the device” using “at least 1 million uniquely mapped sequence reads”. However, as noted above, these steps are data-gathering steps and are well-understood, routine and conventional in the art. Moreover, the claims do not require a “specific device”, the claims require “a given device” (claim 11) or “a device” (claim 20), both of which are generic for some type of device that can perform sequencing on a sample and can output a value. Applicant argues that “the independent claims do not claim a mere association between expression levels and a diagnosis…they specify a particular unconventional arrangement of steps involving a specific five-gene panel”. However, as noted above, the expression of genes is itself a natural phenomenon, as is the association between gene expression and a phenotype.
Applicant argues on page 13 of Remarks that “amended claim 20 and claim 33 recites “meaningful limitations” that use or interact with the judicial exception to integrated it into a practical application of “effecting[ing] a particular treatment…for a…medical condition.”. However, the recitation of “administering a treatment” in claim 20 is not a particular treatment. As stated in MPEP 2106.04(d)(2),
“Examples of "treatment" and prophylaxis" limitations encompass limitations that treat or prevent a disease or medical condition, including, e.g., acupuncture, administration of medication, dialysis, organ transplants, phototherapy, physiotherapy, radiation therapy, surgery, and the like.”
A specific type of treatment or prophylaxis must be provided to be considered “particular”:
“The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way” MPEP 2106.04(d)(2).
Thus, the administration step does not integrate the mental analysis step into a practical application.” And as noted above, claim 33 does not require that a treatment be administered, as “adjusting a treatment” could be interpreted to mean that no treatment is administered and additionally does not provide any particularities with regard to the what the treatment is.
Applicant argues on page 14-15 that “the claims as a whole represent novel and non-obvious methods that amount to significantly more than any alleged judicial exception”. However, as noted in the 101 rejection above and in the previous paragraphs in Response to Remarks, this argument is not persuasive. The data gathering steps that exist around the recited judicial exceptions (mathematical processes, natural phenomena) do not amount to significantly more.
For these reasons, the 101 rejection against claims 11, 13, 20-24, 27-30, and 33-36 is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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