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 with traverse of the species of MUC16, THY1 and GPX8 along with Group I (claims 1, 2, 4-7, 12, 14-16, 21-23, 25-27, 33-35, 40 and 42-44) in the reply filed on 12/11/2025 is acknowledged. The search was expanded to include IGF2. In addition, the instant specification incorporates WO2012/062325 by reference (see paragraph [0128]), and this document discloses measuring KRT5, KRT17 and KRT18. The traversal is on the ground that searching additional species will not unduly burden the office. This is not found persuasive because this case is a national stage application submitted under 35 U.S.C. 371, in which burden is not considered. As noted at p. 3 of the Restriction requirement mailed 10/23/2025, hereby incorporated, the prior art of Wienhues-Thelen (US20160146836—of record) and Alcaraz-Asensio et al. (US2016017433—of record) both teach detecting biomarkers recited in claim 1. The requirement is still deemed proper and is therefore made FINAL.
Claims 41 and 45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/23/2025.
Claims 1, 2, 4-7, 12, 14-16, 21-23, 25-27, 33-35, 40 and 42-44 are under examination.
Effective Filing Date
Applicant’s claim for the domestic benefit of prior-filed applications under 35 U.S.C. 119(e) and 365(c) is acknowledged. No foreign priority claims are made. Under the AIA , the effective filing date of a claimed invention is the earlier of:
The actual filing date of the application;
OR
The filing date to which the application is entitled to a right of foreign priority or domestic benefit as to such claimed invention.
Regarding the claiming domestic benefit of prior-filed applications, see MPEP 211.05. Based on the information given by Applicants and an inspection of the prior applications, the examiner has concluded that the subject matter defined in the instant claims is supported by the disclosure in PCT/US2021/036562 and provisional application serial no. 63/037,212. The effective filing date of claims of the instant application is deemed to be 06/10/2020.
Claim Interpretation
Claims 1, 2, 4-7, 12, 14-16 and 21 recite an “assay”, which can refer either to a product of manufacture or a method/process. In the context of claim 1, which recites the active steps of obtaining a blood sample and determining on or more biomarkers in amnion or chorion cells in the blood sample, the “assay” is interpreted as a method or process.
Further, the broadest reasonable interpretation of “determining the presence of one or more biomarkers…in amnion and/or chorion cells in the blood sample” in claim 1 encompasses detecting the biomarker(s) in a portion of maternal blood. This is consistent with the instant specification, for example, at paragraph [0063] and with instant claim 6.
Although Applicant elected three biomarker species, the claims recite “one or more biomarkers”, thus the broadest reasonable interpretation of the claims encompasses detecting a single biomarker.
Claim 22 recites “determining the presence of amnion and/or chorion cells in the blood sample” in part (b). The specification defines this step at paragraph [0063]:
In one embodiment, the presence of amnion and/or chorion cells is determined by detection of one or more specific amnion and/or chorion cell markers. In another embodiment, the one or more amnion and/or chorion cell markers are detected at the protein level. This may be accomplished by contacting the blood sample or a fraction thereof isolated from a pregnant woman with a ligand directed to the amnion and/or chorion cell markers. In another embodiment, the one or more amnion and/or chorion cell markers are detected at the RNA level. This may be accomplished by contacting the blood sample or a fraction thereof isolated from a pregnant woman with a hybridization probe comprising nucleotides complementary to a gene encoding the amnion and/or chorion cell markers.
Therefore, step (b) in claim 22 is interpreted as encompassing detecting amnion/chorion cell markers at either the protein or nucleic acid level in order determine the presence of amnion and/or chorion cells. This interpretation is supported by dependent claim 23, which recites “wherein the presence of amnion and/or chorion cells is determined by at least one of: detecting one or more specific amnion and/or chorion cell markers” in the alternative.
Claim Objections
Claims 7, 15 and 33 are objected to because of the following informalities.
(i) Claim 7 contains an extra space and comma (,) in line 1.
(ii) Claim 15 (lines 6-9) recites “wherein an amount of amnion and/or chorion cells in the blood sample or fraction thereof is higher than the amount in a control is indicative of preterm premature rupture of the membranes and pre-term birth or an associated clinical condition…”, which is grammatically awkward. The clause could be amended to recites something like “wherein a higher
(iii) Claim 33 contains an extra space and comma (,) in line 3.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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, 4-6, 12, 14, 21, 23, 25, 33, 40, 42 and 44 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 2 recites the limitation “wherein the presence of amnion and/or chorion cells” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim because claim 1, from which claim 2 depends, recites “determining the presence of amnion and/or chorion cell markers”.
Claim 4 is indefinite because it depends from claim 3, which was canceled. Since claim 4 depends from a canceled claim, the metes and bounds of that claim cannot be determined. The claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant (see MPEP 2171). Claims 5 and 6 are hereby included since claim 5 depends from claim 4 and claim 6 depends from claim 4 in the alternative.
Regarding claims 12, 21, 33, 40 and 44, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. See MPEP § 2173.05(d).
Claim 14 recites the limitation “wherein the clinical condition associated with pre-term birth…” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim because claim 1, from which claim 14 depends, does not recite anything regarding pre-term birth. Note that this issue could be addressed by amending claim 14 to depend from claim 2.
Claim 21 depends from claim 1 and recites “a treatment is provided to the pregnant woman for minimizing the risk of preterm birth or ameliorating the consequences of pre-term birth”. The passive voice wording is unclear because it can be interpreted as meaning a treatment is made available but not necessarily actively administered. The metes and bounds of the claim are not known because it is not clear if the treatment was actually administered, and if so, at what timepoint, namely prior to determining the presence of the biomarkers or as a result of the measurement. The claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant (see MPEP 2171). Claim 40, which depends from claim 22 and is worded similarly as claim 21, has the same issue.
Claim 23 depends from claim 22 and recites “wherein the presence of amnion and/or chorion cells is determined by…differentially expressed in amnion and/or chorion cells compared to a blood sample or a fraction thereof isolated from the pregnant woman” in the alternative. The clause appears to state that the presence of amnion/chorion cells determined by their differential expression compared to a blood sample taken from the pregnant woman, which is confusing. It is not clear how one could determine amnion/chorion cell presence by comparing their “expression” to that of a blood sample, since the maternal blood sample, by necessity, must contain all of the amnion/chorion cells being measured. It appears that the clause should state something like “differentially expressed amnion and/or chorion cell markers in amnion and/or chorion cells compared to said markers in a blood sample or fraction thereof isolated from the pregnant woman”. See paragraphs [0014] and [0049] of the instant specification: “the specific amnion and/or chorion cell markers are [may be] differentially expressed in amnion and/or chorion cells compared to a blood sample or a fraction thereof isolated from a pregnant woman”. See also instant claim 25, which states: “the log2 fold difference between the expression of the amnion and/or chorion cell marker in amnion and/or chorion cells compared with the expression in a blood sample or fraction thereof is at least 5, at least 10, or at least 15”, thereby suggesting it is the markers that are differentially expressed compared to the blood sample and not the cells per se.
Claim 25 is indefinite because it depends from claim 24, which was canceled. Since claim 25 depends from a canceled claim, the metes and bounds of that claim cannot be determined. The claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant (see MPEP 2171).
Claim 42 recites “the method comprising the steps of” in line 3 followed by a list of steps, (a)-(e). The body of the claim is unclear because “comprising the steps of” suggests that all steps (a)-(e) should be performed, but there is an “and” only between steps (a) and (b), thus it is not clear whether only claims (a) and (b) are required. Note that this issue could be addressed by placing the “and” between steps (d) and (e).
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 2, 4-6, 14-16, 22, 23, 25-27, 33-35, 40 and 42-44 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims recite methods for detecting the presence of amnion/chorion cell markers in order to determine if there is an increased risk of pre-term birth or other associated clinical condition or preeclampsia. Thus, the claims are drawn to the statutory category of a process. See Step 1 in the Revised Guidelines.
The first step in determining whether a claim recites patent eligible subject matter is to consider whether the claims recite an abstract idea, law of nature or a natural phenomenon. See Prong One of Step 2A in the Revised Guidelines. The claims recite the following:
Claims
Judicial Exception
4-5
Amnion/chorion cell marker(s) are differentially expressed in amnion/ chorion cells compared to a blood sample/fraction thereof, wherein a comparative log2 fold difference is at least 5, at least 10, or at least 15.
6
The presence of amnion/chorion cell marker(s) indicates of pre-term birth or an associated clinical condition.
15-16
Comparing the amount of amnion/chorion cells to a control; wherein a higher amount in the blood sample/fraction thereof compared to control indicates preterm premature rupture of the membranes and pre-term birth or an associated clinical condition.
*22-23, 25
Determining preterm premature rupture of the membranes/pre-term birth or an associated clinical condition wherein the presence of amnion/chorion cells indicates pre-term birth or an associated clinical condition, wherein the presence of amnion/chorion cells is determined by detecting one or more specific amnion/chorion cell markers; or differentially expressed [markers?] in amnion and/or chorion cells compared to a blood sample/fraction thereof isolated from the pregnant woman, wherein the log2 fold difference between the expression of the amnion and/or chorion cell marker in amnion and/or chorion cells compared with the expression in a blood sample or fraction thereof is at least 5, at least 10, or at least 15.
26-27, 33
The presence of an amnion/chorion cell marker indicates pre-term birth or an associated clinical condition, wherein said markers are listed in claim 27, and measuring further epithelial/mesenchymal markers recited in claim 33.
34-35, 40
Comparing the amount of amnion/chorion cells to a pregnant control, wherein a higher amount of amnion/chorion cells in the blood sample or fraction thereof compared to control indicates pre-term birth or an associated clinical condition.
*42-44
Comparing a gene expression profile of the isolated amnion/chorion cells to a pregnant control, wherein the gene expression profile is indicative of pre-term birth or an associated clinical condition.
*Claims 22 and 42 are independent claims
The steps outlined above encompass the mental step of comparing amnion/chorion cell markers and amnion/chorion cells to control in order to arrive at a decision about whether the pregnant woman has or is at risk for pre-term birth or an associated clinical condition. The judicial exception is the correlation between amnion/chorion cell markers and/or amnion/chorion cells and the diagnosis or risk of pre-term birth or an associated clinical condition.
Claim 2 depends from claim 1 and although claim 1 does not recite a judicial exception, claim 2 introduces, in the alternative, a diagnostic step: “the presence of amnion and/or chorion cells is…indicative of pre-term birth, an associated clinical condition, an increased risk of pre-term birth or an increased risk of an associated clinical condition of the pregnant woman, or preeclampsia”. The indication of pre-term birth or its associated conditions requires the comparison to a control value and a decision about increased risk. Similarly, claim 14 depends from claim 1, but introduces a judicial exception, namely the correlation between detecting amnion/chorion cell markers and a clinical condition associated with pre-term birth. The mental step of comparing biomarker levels is similar to comparing information regarding a sample or test subject to a control or target data (see Univ. of Utah Research Found, v. Ambry Genetics Corp., 113 USPQ2d 1241 (Fed. Cir. 2014), or diagnosing an abnormal condition by performing clinical tests and thinking about the results (see In re Grams, 12 USPQ2d 1824 (Fed. Cir. 1989). The answer to Prong One of Step 2A is yes.
The second step in determining patent-eligibility of claimed subject matter is to consider whether the claims recite additional elements that integrate the judicial exception into a practical application. The claims encompass providing blood samples, contacting samples with ligands directed to or hybridization probes complementary to amnion/chorion cell markers, determining the amount of amnion/chorion cells in a blood sample and providing a treatment to the pregnant woman for minimizing the risk of preterm birth or ameliorating the consequences of pre-term birth.
Regarding sample collection and measuring cell markers or amnion/chorion cells, such is merely the necessary data gathering required in order to perform the mental analysis steps of comparison and diagnosis. While some of the claims recite particular biomarkers, the discovery of the relationship between biomarkers and a particular condition is not sufficient to integrate the judicial exception into a practical application. See MPEP 2106.04(l), which states:
The Supreme Court’s cited rationale for considering even “just discovered” judicial exceptions as exceptions stems from the concern that “without this exception, there would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and thereby ‘inhibit future innovation premised upon them.’” Myriad, 569 U.S. at 589, 106 USPQ2d at 1978-79 (quoting Mayo, 566 U.S. at 86, 101 USPQ2d at 1971). See also Myriad,
569 U.S. at 591, 106 USPQ2d at 1979 (“Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry.”). The Federal Circuit has also applied this principle, for example, when holding a concept of using advertising as an exchange or currency to be an abstract idea, despite the patentee’s arguments that the concept was “new”. Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709, 714-15, 112 USPQ2d 1750, 1753-54 (Fed. Cir. 2014). Cf. Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151, 120 USPQ2d 1473, 1483 (Fed. Cir. 2016) (“a new abstract idea is still an abstract idea”) (emphasis in original).
Further, in explaining Prong Two of Step 2A, MPEP 2104.04(II)(A)(2) states patent “eligibility ‘cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea’” itself.
Regarding claim 40, which recites “a treatment is provided to the pregnant woman for minimizing the risk of preterm birth, such as hospitalizing the individual”, this is not a particular treatment. First, as noted above in the rejection under 35 USC 112(b), it is not clear that any treatment is administered; rather the broadest reasonable interpretation encompasses merely making treatment available or known. Further, neither “a treatment” nor “hospitalizing the individual” represent a particular treatment, but rather is an instruction to apply the exception in a generic way and does not integrate the judicial exception into a practical application. The answer to Prong Two of Step 2A is no.
The final step in determining whether the claims recite patent eligible subject matter is to consider whether the claims recite additional elements that amount to significantly more than the judicial exception. The instant specification discloses that methods of detecting the markers are well known in the art (for example, see, paragraphs [0076]; [0102]; [0106]-[0107]). See also paragraph [0155] of the specification:
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims.
In addition, see Boniface et al. (WO2018/02171—on IDS filed 12/09/2022), who disclose that IGF2 levels are differentially expressed in preterm labor vs. controls as measured by antibody-based assays nucleotide-based assays and that suitable samples include blood (see paragraphs [0033] and [00101]; [00142]; [00161]; claims 4 and 5). For a claim reciting a judicial exception to be eligible, the additional elements in the claim must “transform the nature of the claim” either at Prong Two or in Step 2B. In the instant case, the additional elements are simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (see MPEP 2106.05(d)). Thus, the claims are not patent eligible.
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
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.
Claims 1, 6, 7, 14, 21, 22, 26, 27 and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boniface et al. (WO2018/027171—on IDS filed 12/09/2022). As noted above under “Claim Interpretation”, the step of “determining the presence of one or more biomarkers…in amnion and/or chorion cells in the blood sample” in claim 1 is interpreted as detecting the biomarker(s) in a portion of maternal blood. Furthermore, the step of “determining the presence of amnion and/or chorion cells in the blood sample” in claim 22 is interpreted as encompassing detecting amnion/chorion cell markers at either the protein or nucleic acid level in order determine the presence of amnion and/or chorion cells (see “Claim Interpretation”). Boniface et al. disclose that IGF2 levels are differentially expressed in preterm labor vs. controls (see paragraphs [00142]; [00161]; claims 4 and 5). Boniface et al. teach that suitable samples include blood and that biomarkers can be measured by antibody-based assays nucleotide-based assays (see paragraphs [0033] and [00101]). Boniface et al. teach that their methods allow for the “early identification of risk for preterm birth”, which would enable early treatments (see paragraphs [0008]; [0021]; [00103]). Therefore, Boniface et al. teach the limitations of claims 1, 6, 7, 14 and 21. Further, since Boniface et al. disclose detecting IGF2 levels, an amnion/chorion cell marker, by contacting a blood sample with an antibody or nucleotide probe, they also teach the limitations of claims 22, 26, 27 and 40.
Claims 1, 7 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eckelt et al. (WO2012/062325—on IDS filed 12/09/2022). Eckelt et al. disclose detecting KRT5, KRT17 and KRT18 in maternal blood samples (see p. 11, Table 1; p. 13, Table 3; lines 14-18). In addition, Eckelt et al. teach contacting the maternal blood sample with either hybridization probe comprising at least 10 contiguous nucleotides complementary to either the genes encoding KRT5, KRT17 and/or KRT18 or a ligand capable of cross-reacting to the KRT5, KRT17 and/or KRT18 proteins as well as epithelial markers CK1-CK8, CK10 and CK13-CK19 and/or human vimentin (see p. 15, whole page through p. 16, line 15; p. 23, lines 25-29).
Although Eckelt et al. are silent with respect to amnion or chorion cells, they teach the same method as recited in instant claims 1, 7 and 12, thus measuring amnion and/or chorion cells is inherent to the methods disclosed therein.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Boniface et al. (WO2016/205723) teach determining preterm birth probability comprising detecting various biomarkers, including IGF2, in blood (see claims 7-13). Murtha (US 2016/003837—on IDS filed 12/09/2022) teach progesterone receptor membrane component 1 (PRMC1) expression, which is normally highly expressed in fetal membranes, was significantly reduced in chorion cells from patients with premature rupture of membranes (PPROM) compared to term or preterm no labor (see paragraphs [0142]-[0144]). Since PRMC1 expression is reduced in chorion cells associated with PPROM compared to control, one having ordinary skill in the art would not expect that higher PRMC1 levels are associated with PPROM.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675