DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group III, claims 1-26 in the reply filed on 05/26/2026 is acknowledged. Additionally, Applicant elected the following species: a serum sample (claim 14), increase the frequency of maternal and fetal monitoring (claim 16), MBI over 24 (claim 22), and P1GF (claim 23) telephonically on 07/08/2026. Claim 27 has been withdrawn from consideration due to this group/claim not being elected to by Applicant.
Priority
The instant application filed on 06/06/2024 is a 371 of PCT/EP2022/085007 filed on 12/08/2022 which claims priority to EP21213234.4 filed on 12/08/2021. EP21213234.4 finds support for the instantly claimed invention; therefore, the effective filing date of the instant application is 12/08/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/06/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 11 objected to because of the following informalities: claim 11 recites “occurring from begin of 20th week”; however, this should read “occurring from the beginning of the 20th week”. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: PP13 and ADAM12 are recited multiple times within the list of biomarkers. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b), Indefiniteness
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.
Claim 23 is rejected under 35 U.S.C. 112(b) 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 23 recites the following abbreviations: hCG, BNP, ANP, CRP, IL6, IL11, MR-proADM-VEGF, PAPP-A, P1GF, PP-13, ADAM-12, GDF15, pp13, uE3, CT-proET1, sTNF1a1, RBP4, ICAM, FSTL3, MMP9, TIMP1, PCT, SHGB, GBP1, IGFALS, and PAI1/PAI2. However, these abbreviations are indefinite because they are not defined in the instant specification and the abbreviations can stand for multiple things. Additionally, claim 23 recites “heme (bilirubin, biliverdin, carbon monoxide, ferritin)”; however, it is unclear if what is recited in parenthesis is part of the instantly claimed invention, or a preferred embodiment. For the purposes of applying prior art, the Examiner has interpreted what is recited in parenthesis to be a preferred embodiment and not part of the instantly claimed invention.
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 1-26 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revied Patent Subject Matter Eligibility Guidance).
Broadest reasonable interpretation (BRI) of base claim 25: the broadest scope of claim 25 is drawn to a mental step of evaluating or determining the level of soluble fms-like tyrosine kinase-1 (sFlt-1) in a sample. Therefore, this claim is drawn to a mental step or abstract principle of evaluating sFlt-1 levels.
STEP 1: Is the claim directed to a process, machine, manufacture, or a composition of matter?
YES, the claims are directed to a process (method).
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES, the claims are considered to be an “abstract idea” (i.e., “determining” and “comparing”). Per MPEP 2106.04(a), an abstract idea can be a “mental process – concepts performed in the human mind (including an observation, evaluation, judgement, opinion)”. These claims pertain to an abstract idea or method of determining the level of sFlt-1 in a sample. Determining is not defined in the specification as a measurement step and thus the broadest reasonable interpretation includes looking at data and reading the level, i.e. determining. Further, the dependent claims recite comparing to a reference level which is also considered a mental process.
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the additional elements or a combination of elements in the claims does not impose a meaningful limit on the judicial exception. The additional element in independent claim 25 recites an isolation step which is a mere data gathering step to make the correlation/determination. The additional elements recited, such as treating the subject for preeclampsia, as recited in claim 26, is recited at such a high level of generality (for instance, a specific drug or dosages is not specified) that it is at best mere instructions to apply the exception.
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to an abstract idea without significantly more. Note the claims must be interpreted under the BRI standard when evaluating for a marked difference. Under BRI, the claims broadly read on a mental method for determining and comparing levels of sFlt-1 and PlGF in a sample, and a mental method for determining and/or comparing maternal age, body mass index, uterine artery doppler measurement, and mean arterial pressure. There is no indication that the claimed invention has any differences from a mental process. Per MPEP 2106.04(a)(2)(III)(A), “claims do recite a mental process when they contain limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgements, and opinions”, wherein “a claim to “collecting information, analyzing it, and displaying certain results of the collection and analysis,” wherein the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USOQ2d 1739, 1741-42 (Fed Cir. 2016)”. Therefore, collecting and comparing data, as it pertains to sFlt-1 levels, P1GF levels, maternal age, body mass index, uterine artery doppler measurement, and mean arterial pressure can practically be performed in the human mind since they are recited at a high level of generality.
Furthermore, collecting and comparing data (i.e., determining) is routine and conventional within the art (see, e.g., MPEP 2106.05(d)(II)). For example, Karumanchi (WO 2004/008946; Date of Publication: January 29, 2004 – cited in the IDS filed on 06/06/2024) teaches “the invention provides a method of diagnosing a subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, the method involves measuring the level of sFlt-1, NEGF, or PIGF polypeptide in a sample from the subject” (see, e.g., Karumanchi, pg. 5, lines 17-20). Moreover, Karumanchi teaches that the subject can be a pregnant human (see, e.g., Karumanchi, pg. 7, lines 26-28). Additionally, Karumanchi teaches measuring sFlt-1 levels in pre-eclamptic pregnant women and comparing these levels to normotensive pregnant woman (see, e.g., Karumanchi, Example 1). Karumanchi teaches determining circulating concentrations of PlGF and sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Therefore, it is routine and conventional within the art to collect data for sFlt-1 and P1GF levels and compare these levels between pregnant women with preeclampsia and normotensive pregnant women in order determine if these are biomarkers for risk of developing preeclampsia during pregnancy. Determining the level of biomarker(s) in a patient and comparing these levels between patients is a well-understood, routine, and conventional laboratory technique, and the combination of these data gathering steps is conventional, as evidenced by Karumanchi.
Therefore, the claims, as whole are considered an abstract idea (i.e., mental process) which are directed to judicially recognized exceptions without amounting to significantly more than what can practically be performed in the human mind, and are not eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112(a), Written Description
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.
Claims 1-26 are rejected under 35 U.S.C. 112(a) 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.
Independent claim 25 includes a “soluble fms-like tyrosine kinase-1 (sFlt-1) or fragment(s) thereof”. Dependent claims 2, 7-8, 10, 15, and 24 includes “placental growth factor (P1GF) for fragment(s) thereof”. The instant specification defines sFlt-1 as “soluble Flt-1 (sFlt-1)" (soluble fms-like tyrosine kinase 1, also known as sVEGF-R1) refers to the soluble form of the Flt-1 receptor, that is homologous to the protein defined by GenBank accession number U01134 or UniProt P17948 or entry name VGFR1_HUMAN and that has sFlt-1 biological activity. The biological activity of an sFlt-1 polypeptide may be assayed using any standard method, for example, by assaying sFlt-1 binding to VEGF. sFlt-1 lacks the transmembrane domain and the cytoplasmic tyrosine kinase domain of the Flt-1 receptor. sFlt-1 can bind to VEGF and PIGF bind with high affinity, but it cannot induce proliferation or angiogenesis and is therefore functionally different from the Flt-1 and KDR receptors. sFlt-1 was initially purified from human umbilical endothelial cells and later shown to be produced by trophoblast cells in vivo. As used herein, sFlt-1 includes any sFlt-1 family member or isoform” (see, e.g., instant specification, pg. 19, lines 23-33). The instant specification defines fragment as “a portion of a polypeptide or nucleic acid molecule. This portion contains, preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 813 or more nucleotides or 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 186, 200, 250, 271 amino acids or more. Preferred fragments have sFlt-1 biological activity” (see, e.g., instant specification, pg. 22, lines 28-33). The Examiner has interpreted these phrases to mean that there is no necessary core structure and/or sequence needed for the polypeptide or fragment to exhibit sFlt-1 and/or P1GF activity. As such, the scope of the claimed polypeptide or fragment(s) encompasses a large array of polypeptides without any necessary core structure and/or sequence that would be needed in order for the polypeptides to exhibit the claimed function of sFlt-1 and/or P1GF activity.
The instant specification does not provide written description and guidance on sFlt-1 and P1GF fragments. Moreover, the instant specification states “Preferred fragments have sFlt-1 biological activity” (see, e.g., instant specification, pg. 22, lines 28-33); therefore, it is not required, but preferred, that sFlt-1 fragments have biological activity. Therefore, sFlt-1 fragments can constitute a large array of polypeptides with and without biological activity; however, the instant specification does not provide written description and guidance on how these fragments can be identified and what fragments read upon the instantly claimed invention in order for one of ordinary skill in the art to avoid infringement. Moreover, Applicant does not provide a representative number of species for the fragments in order to show possession. Therefore, based on this, Applicant does not have possession of sFlt-1 and P1GF fragments.
Claim Rejections - 35 USC § 102, Anticipation
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 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, 8-16, 18, 22-23, and 25-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Karumanchi (WO 2004/008946; Date of Publication: January 29, 2004 – cited in the IDS filed on 06/06/2024).
Karumanchi’s general disclosure relates to methods for diagnosing pre-eclampsia and eclampsia, as well as methods for treating pre-eclampsia and eclampsia using compounds that increase VEGF and PlGF levels or compounds that decrease sFlt-1 levels (see, e.g., Karumanchi, abstract).
Regarding claim 25 pertaining to a method for determining a level of sFlt-1 in a pregnant subject, Karumanchi teaches “the invention provides a method of diagnosing a subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, the method involves measuring the level of sFlt-1, NEGF, or PIGF polypeptide in a sample from the subject” (see, e.g., Karumanchi, pg. 5, lines 17-20). Moreover, Karumanchi teaches that the subject can be a pregnant human (see, e.g., Karumanchi, pg. 7, lines 26-28). Additionally, Karumanchi teaches measuring sFlt-1 levels in pre-eclamptic pregnant women and comparing these levels to normotensive pregnant woman (see, e.g., Karumanchi, Example 1). Karumanchi teaches determining circulating concentrations of PlGF and sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Furthermore, Karumanchi teaches measuring sFlt-1 levels from subjects at a gestational age of 8-12 weeks (see, e.g., Karumanchi, Figures 5A and 5C); therefore, one of ordinary skill in the art would understand that samples are isolated before the end of the 12th week of gestation.
Regarding claim 1 pertaining to sFlt-1 levels being indicative of early onset preeclampsia and treatment, Karumanchi teaches determining circulating concentrations of PlGF and/or sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Additionally, Karumanchi teaches that sFlt-1 levels are increased in pregnant women with pre-eclampsia (see, e.g., Karumanchi, Example 1). Furthermore, levels of sFlt-1 would inherently be indicative of early onset preeclampsia occurring before the end of the 33rd week of gestation. Moreover, Karumanchi teaches the method of determining sFlt-1 levels in the subject, which inherently would be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation. Furthermore, Karumanchi teaches administration of antibodies against sFlt-1 for the treatment or prevention of pre-eclampsia or eclampsia (see, e.g., Karumanchi, pg. 75, lines 20-30).
Regarding claim 2 pertaining to determining PlGF levels, Karumanchi teaches determining circulating concentrations of PlGF and/or sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Furthermore, the combination of sFlt-1 and P1GF levels would inherently be indicative of early onset preeclampsia occurring before the end of the 33rd week of gestation. Moreover, Karumanchi teaches that PlGF serum levels are lower in patients with pre-eclampsia as compared to normal control patients, while sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Additionally, Karumanchi teaches “In a related aspect, the invention provides a method of diagnosing a subject as having, or having a propensity to develop, pre-eclampsia or eclampsia, by determining the levels of at least two of sFlt-1, NEGF, or PIGF polypeptide in a sample from a subject and calculating the relationship between the levels of sFlt-1 NEGF, or PIGF using a metric, where an alteration in the subject sample relative to a reference diagnoses pre-eclampsia or eclampsia in a subject. In one embodiment, the metric is a pre-eclampsia anti-angiogenic index (PAAI): [sFlt- 1/VEGF + PIGF], where the PAAI is used as an indicator of anti-angiogenic activity. In one embodiment, a PAAI greater than 20 is indicative of pre- eclampsia or eclampsia. In another embodiment, the levels of sFlt-1, NEGF, or PIGF polypeptide is determined by an immunological assay, such as an ELISA. In various embodiments of the above aspects, the sample is a bodily fluid, such as serum or urine. In one embodiment, a level of sFlt-1 greater than 2 ng/ml is indicative of pre-eclampsia or eclampsia” (see, e.g., Karumanchi, pg. 5, lines 21-31 & pg. 6, lines 1-3). Moreover, Karumanchi teaches that “At 8-20 weeks, after adjustment for gestational age, body mass index, and sFlt-1, case patients with PIGF in the lowest quartile of the distribution of control values had almost a 12-fold increased risk of pre-eclampsia at <34 weeks (Odds Ratio [OR] 11.7, p<0.05) compared to cases with PIGF in the three higher quartiles (Table 3). The risk for pre-eclampsia at <34 weeks in the lowest quartile, as compared to the highest quartile was increased almost 16-fold” (see, e.g., Karumanchi, Table 3). Moreover, Karumanchi teaches the method of determining PlGF and sFlt-1 levels in the subject, which inherently would be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation.
Regarding claims 3-4 pertaining to the gestational age of the subject, Karumanchi teaches measuring sFlt-1 levels from subjects at a gestational age of 8-12 weeks (see, e.g., Karumanchi, Figures 5A and 5C); therefore, one of ordinary skill in the art would understand that samples are isolated before the end of the 12th week of gestation.
Regarding claim 5 pertaining to body mass index and sFlt-1 being indicative of preeclampsia, Karumanchi teaches that case patients with mild or severe pre-eclampsia had a higher body mass index and higher baseline blood pressure (see, e.g., Karumanchi, Table 2 & Example 7). Furthermore, Karumanchi teaches that sFlt-1 levels are increased in pregnant women with pre-eclampsia (see, e.g., Karumanchi, Example 1). Therefore, the combination of BMI and sFlt-1 levels would inherently be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation because higher BMI and higher sFlt-1 levels are indicative of pre-eclampsia in pregnant women. Additionally, Karumanchi teaches “an increase in the level of sFlt-1 nucleic acid or polypeptide relative to a reference is a diagnostic indicator of pre-eclampsia or eclampsia” and BMI levels are increased in pregnant subjects with pre-eclampsia; therefore, based on Karumanchi’s teachings, BMI and sFlt-1 levels would inherently be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation. Moreover, Karumanchi teaches the method of determining BMI and sFlt-1 levels in the subject, which inherently would be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation.
Regarding claim 6 pertaining to mean arterial pressure, Karumanchi teaches measuring mean arterial pressure in pregnant and nonpregnant rats treated with control, sFlt-1, or sFil-IFc protein (see, e.g., Karumanchi, Example 4, Table 1). Karumanchi teaches that sFlt-1 increases mean arterial pressure compared to control rats, which increases the risk of pre-eclampsia (see, e.g., Karumanchi, Example 4). Furthermore, Karumanchi teaches that sFlt-1 levels are increased in pregnant women with pre-eclampsia (see, e.g., Karumanchi, Example 1). Therefore, based on Karumachi’s teachings, the combination of sFlt-1 levels and MAP levels in a subject would inherently be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation because increased sFlt-1 and increase MAP increases the risk of pre-eclampsia. Moreover, Karumanchi teaches the method of determining MAP and sFlt-1 levels in the subject, which inherently would be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation.
Regarding claim 8 pertaining to sFlt-1, PlGF, maternal age, BMI, and MAP, Karumanchi teaches determining circulating concentrations of PlGF and/or sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Karumanchi teaches that PlGF serum levels are lower in patients with pre-eclampsia as compared to normal control patients, while sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Karumanchi teaches maternal age for case subjects is 20.8 ± 4.5, and maternal age for control subjects is 20.2 ± 3.6 (see, e.g., Karumanchi, Table 2). Karumanchi teaches that the case subjects have a BMI of 27.3 ± 6.8, and the control subjects have a BMI of 25.1 ± 6.1 (see, e.g., Karumanchi, Table 2). Karumanchi teaches measuring mean arterial pressure in pregnant and nonpregnant rats treated with control, sFlt-1, or sFil-IFc protein (see, e.g., Karumanchi, Example 4, Table 1). Karumanchi teaches that sFlt-1 increases mean arterial pressure compared to control rats, which increases the risk of pre-eclampsia (see, e.g., Karumanchi, Example 4). Furthermore, Karumanchi teaches that PlGF serum levels are lower in patients with pre-eclampsia as compared to normal control patients, while sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Karumanchi teaches that case patients with mild or severe pre-eclampsia had a higher body mass index and higher baseline blood pressure (see, e.g., Karumanchi, Table 2 & Example 7). Therefore, based on the teachings of Karumanchi, sFlt-1, PlGF, maternal age, BMI, and MAP are all determinants for determining the likelihood of pre-eclampsia. Moreover, Karumanchi teaches the methods of determining sFlt-1, PlGF, maternal age, BMI, and MAP in the subject, which inherently would be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation. Furthermore, the Examiner has interpreted “optional” to not be required as part of the instantly claimed invention.
Regarding claim 9 pertaining to sFlt-1 levels, Karumanchi teaches “we performed Northern blots to analyze the placental sFlt-1 mRNA levels (Figure 1A) and ELISA assays to measure serum protein levels of sFlt-1 (Figure IB) in pre-eclamptic pregnant women as compared with normotensive pregnant women” (see, e.g., Karumanchi, Example 1). Furthermore, Karumanchi teaches that sFlt-1 levels in control and case subjects are the same at 8-12 weeks (see, e.g., Karumanchi,, Figure 5); therefore, since the sFlt-1 case level is equal to the reference level, this would be inherently indicative of a high risk of early onset pre-eclampsia and treating said subject. Moreover, Karumanchi teaches that sFlt-1 levels fluctuate during pregnancy and gestational age in case subjects, compared to control subjects (see, e.g., Karumanchi, Example 7); therefore, one of ordinary skill in the art would understand that the gestational age by which the samples are obtained and sFlt-1 levels are determined would affect interpretation of the data for whether the samples indicate early onset pre-eclampsia.
Regarding claim 10 pertaining to PlGF levels, Karumanchi teaches measuring PlGF levels in case and control patents (see, e.g., Karumanchi, Figure 6). Furthermore, Karumanchi teaches that PlGF levels in control and case subjects are the same at 8-12 weeks (see, e.g., Karumanchi,, Figure 6); therefore, since the PlGF case level is equal to the reference level, this would be inherently indicative of a high risk of early onset pre-eclampsia and treating said subject. Moreover, Karumanchi teaches that P1GF levels fluctuate during pregnancy and gestational age in case subjects, compared to control subjects (see, e.g., Karumanchi, Example 7); therefore, one of ordinary skill in the art would understand that the gestational age by which the samples are obtained and P1GF levels are determined would affect interpretation of the data for whether the samples indicate early onset pre-eclampsia.
Regarding claim 11 pertaining to the sFlt-1 level and early onset pre-eclampsia, Karumanchi teaches determining circulating concentrations of PlGF and/or sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Additionally, Karumanchi teaches that sFlt-1 levels are increased in pregnant women with pre-eclampsia (see, e.g., Karumanchi, Example 1). Furthermore, levels of sFlt-1 would inherently be indicative of early onset preeclampsia occurring from the beginning of the 20th week of gestation and end of the 33rd week of gestation. Moreover, Karumanchi teaches the same method of determining sFlt-1 levels in the subject, which inherently would be indicative of early onset preeclampsia occurring from the beginning of the 20th week of gestation and end of the 33rd week of gestation.
Regarding claim 12 pertaining to the sFlt-1 level and intra-uterine fetal death, Karumanchi teaches determining circulating concentrations of PlGF and/or sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Additionally, Karumanchi teaches that sFlt-1 levels are increased in pregnant women with pre-eclampsia (see, e.g., Karumanchi, Example 1). Therefore, Karumanchi teaches the same method of determining the level of sFlt-1, which would inherently be indicative of the occurrence of intra-uterine fetal death.
Regarding claim 13 pertaining to the maternal age, Karumanchi teaches maternal age for case subjects is 20.8 ± 4.5, and maternal age for control subjects is 20.2 ± 3.6 (see, e.g., Karumanchi, Table 2).
Regarding claim 14 pertaining to the sample, Karumanchi teaches that the sample is a serum sample (see, e.g., Karumanchi, Examples 1-2 & 7).
Regarding claim 15 pertaining to the level of sFlt-1 and initiating treatment, Karumanchi teaches “ In one example, if a subject is determined to have a serum sFlt-1 protein level of 10 ng/mL and a serum level of free PIGF of 100 pg/mL, then NEGF can be administered until the serum PIGF level rises to approximately 400 pg/mL. In this embodiment, the levels of sFlt-1, PIGF, and VEGF, or any and all of these, are measured repeatedly as a method of not only diagnosing disease but monitoring the treatment and management of the pre-eclampsia and eclampsia” (see, e.g., Karumanchi, pg. 49, lines 25-31). Moreover, Karumanchi teaches that “levels of sFlt-1 are markedly elevated in placental tissue samples from pregnant women suffering from pre-eclampsia” and that “compounds that increase NEGF and PIGF levels are administered to a subject to treat or prevent pre- eclampsia or eclampsia by countering the effects of elevated sFlt-1” (see, e.g., Karumanchi, pg. 3, lines 6-8). Furthermore, decreasing the risk of developing, delaying the onset or reducing the severity of pre-eclampsia, balancing angiogenetic/anti-angiogenetic process, and lowering blood pressure are all considered inherent due to the treatment. Karumanchi teaches treatment of subjects with NEGF and PlGF based on sFlt-1 levels, which would inherently result in decreasing the risk of developing, delaying the onset or reducing the severity of pre-eclampsia, balancing angiogenetic/anti-angiogenetic process, and lowering blood pressure,
Regarding claim 16 pertaining to increasing the frequency of maternal and fetal monitoring, Karumanchi teaches “The disease state or treatment of a subject having pre-eclampsia, eclampsia, or a propensity to develop such a condition can be monitored using the methods and compositions of the invention. In one embodiment, the expression of an sFlt-1, VEGF, or PIGF polypeptide present in a bodily fluid, such as urine, plasma, amniotic fluid, or CSF, is monitored. Such monitoring may be useful, for example, in assessing the efficacy of a particular drug in a subject or in assessing disease progression. Therapeutics that decrease the expression of an sFlt-1 nucleic acid molecule or polypeptide or that increase the expression of a VEGF or PIGF nucleic acid molecule or polypeptide are taken as particularly useful in the invention” (see, e.g., Karumanchi, pg. 77, lines 5-14). Moreover, Karumanchi teaches “A mild form of pre-eclampsia can be treated with bed rest and frequent monitoring” (see, e.g., Karumanchi, pg. 1, lines 23-24). Therefore, Karumanchi teaches monitoring of the condition to assess disease progression.
Regarding claim 18 pertaining to the subject, Karumanchi teaches that the subject is nulliparous (see, e.g., Karumanchi, Example 7).
Regarding claim 22 pertaining to risk factors, Karumanchi teaches that the case subjects have a BMI of 27.3 ± 6.8, and the control subjects have a BMI of 25.1 ± 6.1 (see, e.g., Karumanchi, Table 2).
Regarding claim 23 pertaining to determining the level of PlGF, Karumanchi teaches measuring PlGF levels in serum samples from patients with pre-eclampsia compared to normal patients (see, e.g., Karumanchi, Example 1 & Figure 6).
Regarding claim 26 pertaining to treating the subject, Karumanchi teaches “levels of sFlt-1 are markedly elevated in placental tissue samples from pregnant women suffering from pre-eclampsia” and that “compounds that increase NEGF and PIGF levels are administered to a subject to treat or prevent pre- eclampsia or eclampsia by countering the effects of elevated sFlt-1” (see, e.g., Karumanchi, pg. 3, lines 6-8). Recitation of “to decrease the risk of developing, delay the time point of the onset and/or reduce the severity of preeclampsia” is considered inherent. Karumanchi teaches administering compounds that increase NEGF and PlGF levels to treat or prevent pre- eclampsia or eclampsia which would inherently result in decreasing the risk of developing, delaying the time point of the onset and/or reducing the severity of preeclampsia.
Claim Rejections - 35 USC § 103, Obviousness
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.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Karumanchi as applied to claims 1-6, 8-16, 18, 22-23, and 25-26 above, and further in view of Crispi (Predictive value of angiogenic factors and uterine artery Doppler for early- versus late-onset pre-eclampsia and intrauterine growth restriction; 2007).
The teachings of Karumanchi are discussed above.
Regarding claim 7 pertaining to sFlt-1, maternal age, and BMI, Karumanchi teaches determining circulating concentrations of PlGF and/or sFlt-1 during the first trimester to identify pregnant woman at risk for developing pre-eclampsia (see, e.g., Karumanchi, Table 3). Karumanchi teaches that sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Karumanchi teaches maternal age for case subjects is 20.8 ± 4.5, and maternal age for control subjects is 20.2 ± 3.6 (see, e.g., Karumanchi, Table 2 Karumanchi teaches that the case subjects have a BMI of 27.3 ± 6.8, and the control subjects have a BMI of 25.1 ± 6.1 (see, e.g., Karumanchi, Table 2). Karumanchi teaches that case patients with mild or severe pre-eclampsia had a higher body mass index and higher baseline blood pressure (see, e.g., Karumanchi, Table 2 & Example 7). Karumanchi teaches that sFlt-1 increases mean arterial pressure compared to control rats, which increases the risk of pre-eclampsia (see, e.g., Karumanchi, Example 4). Therefore, based on the teachings of Karumanchi, sFlt-1, maternal age, and BMI are all determinants for determining the likelihood of pre-eclampsia. Moreover, Karumanchi teaches the methods of determining sFlt-1, maternal age, and BMI in the subject, which inherently would be indicative of early onset pre-eclampsia occurring before the end of the 33rd week of gestation. Furthermore, the Examiner has interpreted “optional” to not be required as part of the instantly claimed invention.
However, Karumanchi does not teach: determining a uterine artery doppler measurement (claim 7).
Crispi’s general disclosure relates to investigating “potential differences in the prediction of early- vs. late-onset pre-eclampsia and/or intrauterine growth restriction (PE/IUGR) by second-trimester uterine artery Doppler examination, and measurement of maternal serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt1)” (see, e.g., Crispi, abstract). Furthermore, Crispi teaches that the best test for predicting pre-eclampsia or intrauterine growth restriction at 20-24 weeks of gestation is uterine artery doppler examination (see, e.g., Cripsi, Introduction, pg. 303).
Regarding claim 7 pertaining to uterine artery doppler measurement, Crispi teaches performing uterine artery doppler measurements on pregnant subjects, as well as measuring maternal serum PlGF and sFlt-1 concentrations (see, e.g., Crispi, “Methods – Study population”, pg. 304). Moreover, Crispi teaches that uterine artery doppler measurements were performed at 24 week of gestation by transabdominal ultrasound imaging (see, e.g., Crispi, “Methods - Uterine artery Doppler evaluation”, pg. 304). Furthermore, Crispi teaches that the uterine artery mean PI was significantly higher in the subjects with early onset PE/IUGR and late onset PE/IUGR, comparted to controls (see, e.g., Crispi, Figure 1 & Table 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine sFlt-1, maternal age, and BMI in pregnant and control subjects, as taught by Karumanchi, as well as perform uterine artery doppler measurements, as taught by Crispi. One would have been motivated to do so because Crispi teaches that the best test for predicting pre-eclampsia or intrauterine growth restriction at 20-24 weeks of gestation is uterine artery doppler examination (see, e.g., Cripsi, Introduction, pg. 303). Moreover, Crispi teaches that “PlGF measurement maybe a useful second-trimester screening test for early-onset PE/IUGR, alone or in combination with sFlt1 or uterine artery Doppler examination” (see, e.g., Crispi, Discussion, pgs. 305 & 307). Moreover, Karumanchi teaches that sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Karumanchi teaches that case patients with mild or severe pre-eclampsia had a higher body mass index and higher baseline blood pressure (see, e.g., Karumanchi, Table 2 & Example 7). Therefore, based on the teachings of Karumanchi and Crispi, it would be obvious to determine or measure sFlt-1, maternal age, BMI, and uterine artery doppler measurement in order to assess a subject’s risk of pre-eclampsia. One would have expected success because Karumanchi and Crispi both teach risk assessment of pre-eclampsia in pregnant subjects by measuring sFlt-1 and P1GF levels.
Claims 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Karumanchi as applied to claims 1-6, 8-16, 18, 22-23, and 25-26 above, and further in view of Poon (Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history; 2017).
The teachings of Karumanchi are discussed above.
However, Karumanchi does not teach: wherein the treatment comprises administration of acetylsalicylic acid (claim 17); or wherein the subject had one or more former pregnancies (claim 19).
Poon’s general disclosure relates to determining “whether there are differences in the effect of aspirin on the incidence of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial in subgroups defined according to maternal characteristics and medical and obstetrical history” (see, e.g., Poon, “Objective”, pg. 585.e1).
Regarding claim 17 pertaining to administration of acetylsalicylic acid, Poon teaches administration of aspirin to pregnant women from 11 to 14 until 36 weeks’ gestation (see, e.g., Poon, Background, pg. 585.e1). Moreover, Poon teaches “aspirin administration from 11 to 14 until 36 weeks’ gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004)” (see, e.g., Poon, Background, pg. 585.e1).
Regarding claim 19 pertaining to the subject having one or more former pregnancies, Poon teaches assessment of multiparous subjects with and without pre-eclampsia (see, e.g., Poon, Figure 1). Moreover, Poon teaches that administration of aspirin decreases multiparous pregnancies with pre-eclampsia (see, e.g., Poon, Figure 1).
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure sFlt-1 levels in a pregnant subject suspected to be at risk of pre-eclampsia, as taught by Karumanchi, wherein the pregnant subject is being administered acetylsalicylic acid, as taught by Poon. One would have been motivated to do so because Poon teaches “aspirin administration from 11 to 14 until 36 weeks’ gestation was associated with a significant reduction in the incidence of preterm preeclampsia (odds ratio 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004)” (see, e.g., Poon, Background, pg. 585.e1). Moreover, Karumanchi teaches that sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Therefore, based on the teaching of Karumanchi and Poon, it would have been obvious to administer acetylsalicylic acid to a pregnant woman at risk of pre-eclampsia in order to determine if acetylsalicylic acid decreases sFlt-1 levels, which are increased in patients with pre-eclampsia compared to control patients. It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure sFlt-1 levels in a pregnant subject suspected to be at risk of pre-eclampsia, as taught by Karumanchi, wherein the pregnant subject has had one or more former pregnancies, as taught by Poon. One would have been motivated to do so because Poon teaches that administration of aspirin decreases multiparous pregnancies with pre-eclampsia (see, e.g., Poon, Figure 1). Moreover, Karumanchi teaches sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Therefore, based on the teachings of Karumanchi and Poon, it would have been obvious to assess sFlt-1 levels in a subject with one or more former pregnancies because multiparous subjects have an increased risk of pre-eclampsia, and pre-eclampsia is associated with increased sFlt-1 levels. One would have expected success because Karumanchi and Poon both teach risks and treatment of pre-eclampsia.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Karumanchi as applied to claims 1-6, 8-16, 18, 22-23, and 25-26 above, and further in view of Boniface (US 2014/0287947; Date of Publication: September 25, 2014).
The teachings of Karumanchi are discussed above.
However, Karumanchi does not teach: wherein the subject has a multiple pregnancy (claim 20).
Boniface’s general disclosure relates to “the discovery that certain proteins and peptides in biological samples obtained from a pregnant female are differentially expressed in pregnant females that have an increased risk of developing in the future or presently suffering from preeclampsia relative to matched controls. The present disclosure is further based, in part, on the unexpected discovery that panels combining one or more of these proteins and peptides can be utilized in methods of determining the probability for preeclampsia in a pregnant female with relatively high sensitivity and specificity. These proteins and peptides disclosed herein serve as biomarkers for classifying test samples, predicting a probability of preeclampsia, monitoring of progress of preeclampsia in a pregnant female, either individually or in a panel of biomarkers” (see, e.g., Boniface, abstract).
Regarding claim 20 pertaining to the subject having multiple pregnancy, Boniface teaches “the methods of determining probability for preeclampsia in a pregnant female further encompass detecting a measurable feature for one or more risk indicia associated with preeclampsia”, wherein one of these risk indicia is multiple pregnancy (see, e.g., Boniface, [0047]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure sFlt-1 levels in a pregnant subject suspected to be at risk of pre-eclampsia, as taught by Karumanchi, wherein the pregnant subject has a multiple pregnancy, as taught by Boniface. One would have been motivated to do so because Boniface teaches that multiple pregnancy is a risk factor for pre-eclampsia in pregnant subjects (see, e.g., Boniface, [0047]). Moreover, Karumanchi teaches assessing risk of pre-eclampsia in pregnant subjects, wherein sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Therefore, based on the teachings of Karumanchi and Boniface, it would have been obvious to assess sFlt-1 levels in a pregnant subject, wherein the pregnant subject has a multiple pregnancy, since a multiple pregnancy is a risk factor for pre-eclampsia and high sFlt-1 levels are associated with pre-eclampsia. One would have expected success because Karumanchi and Boniface both teach assessment of risk factors associated in pregnant subjects with pre-eclampsia.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Karumanchi as applied to claims 1-6, 8-16, 18, 22-23, and 25-26 above, and further in view of Van Trappen (Pre-eclampsia and chromosomal abnormalities; 1998).
The teachings of Karumanchi are discussed above.
However, Karumanchi does not teach: wherein the suspect is suspected of carrying a fetus with a chromosomal abnormality (claim 21).
Van Trappen’s general disclosure relates to the relationship between pre-eclampsia and chromosomal abnormalities through case reports (see, e.g., Van Trappen, Introduction & Case Reports). Moreover, Van Trappen discloses an association between trisomy 13 and pre-eclampsia (see, e.g., Van Trappen, Introduction).
Regarding claim 21 pertaining to the subject being suspected for carrying a fetus with a chromosomal abnormality, Van Trappen teaches the association between fetal trisomy 13 and maternal pre-eclampsia due to aberrant expression of genes on chromosome 13, wherein “trisomy 13 is a rare event (approximately one in 10,000 live births) with an estimated incidence rate of 2-3 per 10,000 births in pre-eclampsia patients, two to three times higher than in normal pregnancies” (see, e.g., Van Trappen, Introduction). Moreover, Van Trappen teaches a pregnant patient with pre-eclampsia giving birth to a baby with a 69XXX triploidy (see, e.g., Van Trappen, Case A) .
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure sFlt-1 levels in a pregnant subject suspected to be at risk of pre-eclampsia, as taught by Karumanchi, wherein the pregnant subject is suspected of carrying a fetus with a chromosomal abnormality, as taught by Van Trappen. One would have been motivated to do so because Van Trappen teaches the association between fetal trisomy 13 and maternal pre-eclampsia due to aberrant expression of genes on chromosome 13, wherein “trisomy 13 is a rare event (approximately one in 10,000 live births) with an estimated incidence rate of 2-3 per 10,000 births in pre-eclampsia patients, two to three times higher than in normal pregnancies” (see, e.g., Van Trappen, Introduction). Moreover, Karumanchi teaches assessing risk of pre-eclampsia in pregnant subjects, wherein sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Therefore, based on the teachings of Karumanchi and Van Trappen, it would have been obvious to assess sFlt-1 levels in a pregnant subject, wherein the pregnant subject is suspected of carrying a fetus with a chromosomal abnormality, since pre-eclampsia being a risk factor for incidence of chromosomal abnormalities. One would have expected success because Karumanchi and Van Trappen both teach assessment of risk factors associated in pregnant subjects with pre-eclampsia.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Karumanchi as applied to claims 1-6, 8-16, 18, 22-23, and 25-26 above, and further in view of Hund (US 2015/0338415; Date of Publication: November 26, 2015).
The teachings of Karumanchi are discussed above.
Regarding claim 24 pertaining to detection reagents for sFlt-1 and P1GF, Karumanchi teaches “Enzyme- linked immunosorbent assays (ELISA) for human sFlt-1, free PIGF, and free NEGF were performed according to the manufacturer's instructions, using kits purchased from R&D Systems (Minneapolis, MΝ). Aliquots of serum samples which had been stored at -70°C, were thawed to room temperature, diluted with BSA/Tris-buffered saline, and incubated for 2 hours in a 96-well plate pre-coated with a capture antibody directed against sFlt-1, PIGF, or NEGF. The wells were then washed three times, incubated 20 minutes with a substrate solution containing hydrogen peroxide and tetramethylbenzidine, and the reaction quenched with 2N sulfuric acid. Optical density was determined at 450 nm (wavelength correction 550 nm). All assays were performed in duplicate. Protein concentrations were calculated using a standard curve derived from known concentrations of the respective recombinant proteins. If the difference between duplicates exceeded 25%, the assay was repeated and initial results discarded. The assays had sensitivities of 5, 7, and 5 pg/ml for sFlt 1, PIGF, and VEGF, respectively, with inter- and intra-assay coefficients of variation of 7.6% and 3.3% for sFlt 1, 11.2% and 5.4% for PIGF, and 7.3% and 5.4% for VEGF” (see, e.g., Karumanchi, Example 7). Furthermore, Karumanchi teaches that PlGF serum levels are lower in patients with pre-eclampsia as compared to normal control patients, while sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Karumanchi teaches that sFlt-1 increases mean arterial pressure compared to control rats, which increases the risk of pre-eclampsia (see, e.g., Karumanchi, Example 4). Karumanchi teaches that case patients with mild or severe pre-eclampsia had a higher body mass index and higher baseline blood pressure (see, e.g., Karumanchi, Table 2 & Example 7).
However, Karumanchi does not teach: a computer readable medium and/or computer software in the form of computer executable code, configured to: i. compare a determined level of sFlt-1 or fragment(s) thereof and a determined level of P1GF or fragment(s) thereof, to one or more reference levels, preferably corresponding to a population average and/or median for a healthy population, and ii. compare maternal age, body mass index, MAP and/or a uterine artery doppler measurement of the subject, to one or more reference levels, corresponding to a population average and/or median for a healthy population (claim 24).
Hund’s general disclosure relates to a method for diagnosing whether a pregnant subject is not at risk for preeclampsia within a short window of time comprising a) determining the amount of at least one angiogenesis biomarker selected from the group consisting of sFlt-1, Endoglin and PlGF in a sample of said subject, and b) comparing the amount with a reference, whereby a subject being not at risk for developing preeclampsia within a short period of time is diagnosed if the amount is identical or decreased compared to the reference in the cases of sFlt-1 and Endoglin and identical or increased in the case of PlGF, wherein said reference allows for making the diagnosis with a negative predictive value of at least about 98%” (see, e.g., Hund, abstract).
Regarding claim 24 pertaining to the computer readable medium, Hund teaches diagnosing whether a subject is at risk for pre-eclampsia by “a) determining the amount of at least one angiogenesis biomarker selected from the group consisting of sFlt-1, Endoglin and PlGF in a sample of said subject; and [0015] b) comparing the amount with a reference” (see, e.g., Hund, [0014]-[0015]). Moreover, Hund teaches that “ Preferably, step (a), and/or (b) may in total or in part be assisted by automation, e.g., by a suitable robotic and sensory equipment for the determination in step (a), a computer-implemented calculation algorithm on a data processing device and/or comparison and/or diagnosis algorithm on a data processing device in step (b)” (see, e.g., Hund, [0016]). Furthermore, Hund teaches “ The comparison referred to in step (b) of the method of the present invention may be carried out manually or computer assisted. The value of the amount and the reference can be, e.g., compared to each other and the said comparison can be automatically carried out by a computer program executing an algorithm for the comparison. The computer program carrying out the said evaluation will provide the desired assessment in a suitable output format. Preferably, the evaluation unit of the device of the invention or the computing device of the system of the invention can be used for carrying out the said comparison” (see, e.g., Hund, [0054]). Additionally, Hund teaches “ Computer-readable media may be any available media that can be accessed by the computing device and includes both volatile and non-volatile media. Further, computer readable-media may be one or both of removable and non-removable media” (see, e.g., Hund, [0075]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to assess sFlt-1, PlGF, material age, BMI, and MAP in pregnant subjects at risk of pre-eclampsia, as taught by Karumanchi, wherein these levels and risk factors are assessed and compared using a computer readable medium, as taught by Hund. One would have been motivated to do so because Hund teaches that using a computer readable medium or code to compare amounts of sFlt-1 and PlGF with a reference would allow for automation since comparison and assessment would automatically be carried out by a computer program executing an algorithm for comparison (see, e.g., Hund, [0054]). Moreover, Karumanchi teaches that PlGF serum levels are lower in patients with pre-eclampsia as compared to normal control patients, while sFlt-1 levels are higher in patients with pre-eclampsia as compared to normal control patients (see, e.g., Karumanchi, Example 1). Karumanchi teaches that sFlt-1 increases mean arterial pressure compared to control rats, which increases the risk of pre-eclampsia (see, e.g., Karumanchi, Example 4). Karumanchi teaches that case patients with mild or severe pre-eclampsia had a higher body mass index and higher baseline blood pressure (see, e.g., Karumanchi, Table 2 & Example 7). Therefore, these are risk factors that can be used alongside the executable code to determine one’s risk of pre-eclampsia. Therefore, based on the teachings of Karumanchi and Hund, it would have been obvious to compare sFlt-1 and PlGF levels, along with maternal age, BMI, and MAP, in order to determine one’s risk of pre-eclampsia in an automated format. One would have expected success because Karumanchi and Hund both teach risk assessment of pre-eclampsia in pregnant subjects by measuring sFlt-1 and P1GF levels.
Conclusion
Claims 1-26 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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, Sharmila Landau can be reached at (571) 272-0614. 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.
/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
Prosecution Insights