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 of Group I (claims 1-8 and 16) and species a) measuring the activation of inflammasome pathway in the reply filed on 12/12/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The restriction requirement is made Final.
Claims 1-14 and 16-18 are currently pending.
Claims 9-14 and 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/12/2025.
Claims 3-5 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected specie, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/12/2025.
Claims 1-2, 6-8 and 16 have been examined on their merits.
Claim Objections
Claim 2 is objected to because of the following informalities:
Regarding claim 2, the asterisks in step d are improper form and should be removed.
Appropriate correction is required.
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 2, 7 and 8 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 2, reciting the limitation “the activation of inflammasome pathway” in line 4 renders the claim indefinite because there is insufficient antecedent basis for this limitation in the claim.
Regarding claim 7, the phrase "such that" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 7 also recites the limitation "the peptidic hormones" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 8, reciting the limitation “wherein the activation of inflammasome pathway” in lines 1-2 renders the claim indefinite because there is insufficient antecedent basis for this limitation in the claim as it is dependent upon claim 1 which does not recite an inflammasome pathway.
For examination purposes claim 8 will be interpreted as if it were dependent upon claim 7 which does recite an inflammasome pathway.
Appropriate correction is required.
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 1-2, 6-8 and 16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (natural phenomenon and an abstract idea) without significantly more.
The United States Patent and Trademark Office (USPTO) issued a revised guidance for evaluating subject matter eligibility, referred to as "2019 Revised Patent Subject Matter Eligibility Guidance", which became effective on January 7, 2019 (see 84 Fed. Reg. 50).
In the instant application, claims 1-2, 6-8 and 16 recite a natural phenomenon and an abstract idea.
This judicial exception is not integrated into a practical application, and the claims do not include additional elements that are sufficient to amount to significantly more than said judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP 2106:
Step (1). Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A). Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 - Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Prong 2 - If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application?
Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP 2106.05(a)
• Applying or using a judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition. See Vanda Memo
• Applying the judicial exception with, or by use of, a particular machine. See MPEP 2106.05(b)
• Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP 2106.05(c)
• Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP 2106.05(e) and Vanda Memo.
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A),
• Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
• Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis on View of the Interim Guidance
In regards to claim 1, regarding step 1, claim 1 is drawn to a method for determining if a compound is an endocrine disruptor by a) contacting a compound with a human endocrine cell culture, b) measuring in the culture medium an expression level of a set of four hormones including progesterone and a polypeptidic hormone, c) comparing the measured expression levels of the hormones with a control, measuring an expression level/activity of a P2X7 membrane receptor protein in a contacted cell and comparing to a control and e) making conclusions based on the measured expression level of the hormones compared to the measured expression or activity level of P2X7 membrane receptor protein.
Therefore, the answer to Step 1 is “yes” since the claims are directed to a process, which is a statutory category.
Regarding step 2A prong 1, The claims include steps for comparing and concluding which involve mental processes (natural phenomenon and abstract idea).
Therefore, the answer to Step 2A prong 1 is “yes”, since the claim is drawn to a mental process (natural phenomenon).
Regarding step 2A prong 2, while claim 1 recites additional method steps that do not require mental steps, such as contacting and measuring (steps a, b, d) these are deemed to be data gathering steps that are routine in the art of toxicology.
Fedorova et al. (Circulation: Cardiovascular Genetics, 2015) teaches the use of human endocrine placental cells (JEG-3) cultured in minimal essential nutrients and a serum of 2.5% for the measurement of set of four hormones including progesterone and a polypeptidic hormone (pages 738-739).
Similarly, Dawid et al. (Journal of Physiology and Pharmacology, 2019) teaches methods for the measurement of at least four hormones including progesterone and hCG (polypeptidic hormone) in a human endocrine placental cell culture (figure 6).
Therefore, these limitations are simply appending well-understood, routine, conventional activities previously known to the industry.
Therefore, as whole, the claim is drawn to a mental process, and the additional method steps, are a means to perform this mental process. As a result, the claim does not recite additional elements that integrate the judicial exception into a practical application
Therefore, the answer to Step 2A prong 2 is “no” since the claims do not recite additional elements that integrate the judicial exception into a practical application.
Regarding step 2B, while the method utilizes method steps of contacting and measuring, these steps are recited at a high level of generality which is evidence that the applicant is relying on measurement steps that are routine and conventional in the art (see MPEP 2106.05(d).
Again, Fedorova et al. (Circulation: Cardiovascular Genetics, 2015) teaches the use of human endocrine placental cells (JEG-3) cultured in minimal essential nutrients and a serum of 2.5% for the measurement of set of four hormones including progesterone and a polypeptidic hormone (pages 738-739).
Similarly, Dawid et al. (Journal of Physiology and Pharmacology, 2019) teaches methods for the measurement of at least four hormones including progesterone and hCG (polypeptidic hormone) in a human endocrine placental cell culture (figure 6).
Therefore, these limitations are simply appending well-understood, routine, conventional activities previously known to the industry.
The dependent claims do not remedy this determine because they recite either inherent properties or method steps pertaining to method steps that are well-known in the art as discussed below.
Therefore, the answer to step 2B is “no” since the additional limitations are ancillary to the judicial exception and routine in the art.
In regards to claim 2, the method of claim 1 further comprises an additional measurement of the activation of inflammasome pathway in the human endocrine placental cell culture and comparing this measurement to a control and a step for a conclusion (a mental process and thus a judicial exception).
Perez-Albaladejo et al. (Society of Toxicology 2019-from IDS filed 09/28/2023) teach the measurement of the activation of inflammasome pathway in the human endocrine placental cell culture and comparing this measurement to a control (page 337, column 2).
Therefore, these limitations are simply appending well-understood, routine, conventional activities previously known to the industry.
Regarding claim 6, this claim merely includes the property that a difference of =/- 15% between the measured and the control values is significant which would be an inherent property of the claimed method.
Regarding claims 7 and 16, these claims appear to refer to the peptidic hormone type including hCG or one of its derivatives.
Dawid et al. (Journal of Physiology and Pharmacology, 2019) teaches methods for the measurement of at least four hormones including progesterone and beta hCG (polypeptidic hormone) in a human endocrine placental cell culture (figure 6).
Therefore, these limitations are simply appending well-understood, routine, conventional activities previously known to the industry.
Regarding claim 8, this claim indicates that the measurement of the inflammasome pathway is measured by evaluating caspase-1 or IL-1beta.
Premyslova et al. (Placenta 2006-from IDS filed 09/28/2023) teach the measurement of IL-1beta in a human placental endocrine cell culture (Title, abstract, page 583).
Therefore, these limitations are simply appending well-understood, routine, conventional activities previously known to the industry.
Hence, claims 1-2, 6-8 and 16 do not qualify as eligible subject matter under 35 U.S.C. §101.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 6-7, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wakx et al (Toxicology in Vitro, 2016-from IDS filed 09/28/2023) in view of Dawid et al (Journal of Physiology and Pharmacology 2019).
Regarding claims 1, 7 and 16, Wakx disclose a method to identify an endocrine disruptor using JEG-3 cells (human endocrine placental cell cultures) and PX27 expression/activity as a biomarker (abstract, page 78 sections 2.14-2.16). Cells were cultured with 2.5% FCS (serum) in minimal essential medium (page 77 section 2.5, page 81 Figure 4).
Wakx do not additionally evaluate the expression levels of a set of four hormones including progesterone and polypeptidic hormone, such as human gonadotrophin (hCG).
Dawid teach a method of measuring a set of at least four hormones in a human endocrine placental cell culture (JEG-3 cell line) to evaluate the effect of apelin as recent studies have indicated a link between apelin and placenta function (abstract, pages 895-896). Apelin is a hormone known to be associated with certain complications of pregnancy (page 895). Evaluating the effect of this endocrine disruptor on human endocrine placental cells is disclosed as measuring a four hormone set including progesterone, estradiol, hCG and human placental lactogen (abstract, page 895), specifically βhCG (page 897, table 1).
One of ordinary skill in the art would have been motivated to include the measurement of a four hormone set, including progesterone and βhCG, along with controls and comparisons in the method of Wakx because Dawid indicate that these hormones can provide information regarding the effect that an endocrine disruptor can have on human placental cells. One of ordinary skill in the art would have had a reasonable expectation of success because both Wakx and Dawid are testing endocrine disruptors on JEG-3 placental cells.
Regarding claim 6, the limitation of “wherein there is a significant difference when the measured and the control values differ by +/- 15%” is deemed to be an inherent property of the method of claim 1 and thus inherently present in the method of Wakx when modified as described above by the teaching of Dawid.
Therefore, the combined teachings of Wakx et al and Dawid et al render obvious Applicant’s invention as claimed.
Claim(s) 2 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Wakx et al (Toxicology in Vitro, 2016-from IDS filed 09/28/2023) in view of Dawid et al (Journal of Physiology and Pharmacology 2019) as applied to claims 1, 6-7 and 16 above, and further in view of Shirasuna et al (Frontiers in Endocrinology 2020-from IDS filed 01/09/2026).
Regarding claims 2 and 8, the combined teachings of Wakx and Dawid render obvious Applicant’s invention as described above, but do not specifically include a further step for measuring the activation of inflammasome pathway, such as measuring IL-1β expression or secretion.
Shirasuna teach that interleukin (IL)-1β is a pivotal inflammatory cytokine that is produced by placental cells when the placenta is exposed to inflammasomes (abstract, page 1, page 8 conclusion). IL-1β secretion is regulated by caspase-1 activation by many inflammasomes (page 3). IL-1β expression or secretion is disclosed as being linked to inflammation and immune cell activation in preeclampsia (PE) (page 4) suggesting measuring IL-1β for evaluating the placenta health.
One of ordinary skill in the art would have been motivated to further include a measuring step for IL-1β expression or secretion and caspase-1 activity in the human placental cells of Wakx because Shirasuna teach and suggest that this allows for the evaluation of placenta cell health. One of ordinary skill in the art would have had a reasonable expectation of success because Wakx and Shirasuna are both concerned with evaluating the health of placental cells.
Therefore, the combined teachings of Wakx et al, Dawid et al and Shirasuna et al render obvious Applicant’s invention as claimed.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Fry et al., “Developing novel in vitro methods for the risk assessment of developmental and placental toxicants in the environment”, Toxicol Appl Pharmacol. 2019, Vol. 378, pp. 1-28.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631