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 19-27), drawn to a method of determining the likelihood of a pregnant subject undergoing delivery within about 7 days by contacting a sample with a reagent to a biomarker, to form a complex, and measuring the complex formed to determine the amount of the biomarker in the sample, in the reply filed 07/30/2026 is acknowledged. Hence, claims 1-18 and 28-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Status of the Claims
Claims 1-35 are pending. Claims 1-18 and 28-35 are withdrawn. Claims 19-27 are examined herein in view of the restriction.
Priority
The present application, filed 12/26/2023, is a 371 of PCT/CA2022/050888, filed 06/03/2022, which claims benefit of U.S. Provisional Patent Application 63/216,682, filed 06/30/2021. The benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 06/30/2021.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 07/30/2026 are acknowledged and have been considered.
Claim Objections
Claim 19 is objected to because of the following informalities: The abbreviation “hFM” is used without being fully set forth or defined in the claim. The specification indicates that “hFM” refers to human fetal membranes. However, the claim should be amended to recite the term in full, for example, “human fetal membranes (hFM),” upon its first occurrence so that the claim language is clear and self-contained. 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 19-27 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 19, the claim recites the limitation “contacting the sample with a reagent to a biomarker, to form a complex between the agent and the biomarker present in the sample” in lines 4-5. There is insufficient antecedent basis for this limitation in the claim. The recitation of “the agent” lacks antecedent basis. The claim previously introduces “a reagent,” but does not previously introduce “an agent.” It is therefore unclear from the claim language whether “the agent” is intended to refer to the previously recited reagent or to a separate component that has not otherwise been recited. For purposes of compact prosecution, the recitation of “the agent” will be interpreted as referring to the previously recited “reagent”, such that the claimed complex is interpreted as being formed between the reagent and the biomarker. Appropriate correction is required.
Claim 19 further recites, as separate initial steps, “obtaining peripheral leukocytes from said pregnant subject” and “obtaining a sample from a pregnant subject.” The first recitation refers back to the pregnant subject whose likelihood of delivery is being determined, whereas the second introduces “a pregnant subject” without stating whether this is the same pregnant subject or a different pregnant subject. Accordingly, it is unclear whether the peripheral leukocytes and the subsequently recited biomarker sample are required to originate from the same pregnant subject, and, if different pregnant subjects are contemplated, the claim does not recite any relationship between those subjects or explain how a sample obtained from one pregnant subject is relevant to determining the likelihood of delivery of the other pregnant subject. The specification likewise reproduces these two recitations in the combined embodiment without expressly resolving whether they refer to the same pregnant subject ([0028]–[0030]). For purposes of compact prosecution, “a pregnant subject” in the recitation “obtaining a sample from a pregnant subject” will be interpreted as referring to the same pregnant subject previously recited in claim 19, i.e., the subject whose likelihood of delivery is being determined and from whom the peripheral leukocytes are obtained. Thus, the claim will be interpreted as requiring both the peripheral leukocytes and the biomarker sample to be obtained from that same pregnant subject. Appropriate correction is required.
Claim 19 further recites “wherein an increased likelihood of delivery within about 7 days is indicated when said chemotactic activity of said leukocytes is at a level characteristic of a full term pregnancy.” However, “said chemotactic activity” lacks antecedent basis because no “chemotactic activity” has previously been introduced in claim 19 before this recitation. The claim previously recites obtaining peripheral leukocytes and performing a biomarker assay, but does not recite a step of determining or otherwise introducing a chemotactic activity before referring to “said chemotactic activity.” Although the claim subsequently recites “wherein determining said chemotactic activity comprises measuring migration of said leukocytes,” that subsequent language does not provide a clear antecedent for the earlier recitation of “said chemotactic activity.” For purposes of compact prosecution, the recitation of “said chemotactic activity” will be interpreted as referring to the chemotactic activity determined by the subsequently recited step of measuring migration of the leukocytes toward a chemoattractant. Appropriate correction is required.
Claim 19 further recites, in the final wherein clause, “wherein said chemoattractant is a factor present in a sample comprising hFM obtained from a full term pregnant subject.” This recitation introduces another “sample” in addition to the previously recited sample obtained from a pregnant subject for the biomarker assay. Although the specification indicates that “hFM” refers to human fetal membranes and describes human fetal membranes as releasing the chemoattractant used in the leukocyte migration assay ([001512]-[00153]), the claim itself does not clearly state the relationship between the previously recited biomarker sample and this subsequently recited hFM-containing sample.
In particular, it is unclear from claim 19 whether the hFM-containing sample is intended to be the same sample previously obtained from the pregnant subject, a separate sample obtained from the same pregnant subject, or a separate reference material obtained from another full-term pregnant subject. The ambiguity is heightened because the claim first requires “obtaining a sample from a pregnant subject” for formation and measurement of the biomarker complex, but later refers to “a sample comprising hFM obtained from a full term pregnant subject” as the source of the chemoattractant. The specification indicates that the latter hFM material serves as the source of the chemotactic stimulus in the migration assay; for example, Example 1 states that human fetal membranes (hFM) release a chemoattractant and describes leukocyte migration toward hFM chemoattractant ([001512]-[00153]). Thus, the specification suggests that the hFM-containing material performs a different assay function from the earlier biomarker sample, but that relationship is not distinctly recited in claim 19.
Nor does claim 19 expressly recite that the hFM-containing sample is itself a “control” sample or recite an express comparison of the test sample with that hFM sample. Rather, as presently written, the hFM-containing sample appears to provide the chemoattractant against which migration of the test subject’s leukocytes is measured, while the resulting chemotactic activity is then evaluated with respect to a “level characteristic of a full term pregnancy.” The claim should be amended to clearly identify the nature and function of the hFM-containing sample and its relationship, if any, to the previously recited biomarker sample and to the full-term comparator. For purposes of compact prosecution, “hFM” will be interpreted as “human fetal membranes,” and the “sample comprising hFM obtained from a full term pregnant subject” will be interpreted as a separate full-term human fetal-membrane material that provides the recited chemoattractant for measuring migration of the leukocytes obtained from the test subject. It will not be interpreted as the previously recited biomarker sample, nor will an unrecited control-comparison step be imported into the claim. Appropriate correction is required.
Claim 19 additionally contains an internal ambiguity regarding the relationship between the biomarker measurement and the determination of the likelihood of delivery. The claim requires obtaining a sample from a pregnant subject; contacting the sample with a reagent to a biomarker; forming a complex; and measuring the complex to determine the amount or concentration of the biomarker. The claim thereafter states that an increased likelihood of delivery within about seven days is indicated when the chemotactic activity of the leukocytes is at a level characteristic of a full-term pregnancy. The claim does not recite what role, if any, the measured amount or concentration of the biomarker has in determining the likelihood of delivery. Consequently, it is unclear whether: the biomarker amount or concentration is itself used in determining the likelihood of delivery; the chemotactic activity alone determines the likelihood of delivery; or the biomarker measurement and chemotactic activity must be considered together according to some unstated criterion. This ambiguity is particularly apparent because the specification describes a biomarker-based embodiment in which the measured biomarker itself is associated with the determination. For example, paragraph [00119] describes obtaining a sample, contacting the sample with a reagent to a biomarker, measuring the biomarker, and determining likelihood of term delivery based on a biomarker level characteristic of full-term pregnancy. The specification elsewhere separately describes determining likelihood based upon leukocyte chemotactic activity [0018]. However, those disclosed embodiments cannot be imported into claim 19 to resolve which relationship Applicant actually intends the claim to require. For purposes of compact prosecution, since claim 19 expressly requires both the biomarker-measurement steps and the chemotactic-activity determination, the claim will be interpreted as requiring both sets of steps to be performed. However, because claim 19 expressly states that the increased likelihood of delivery within about seven days is indicated when the leukocyte chemotactic activity is at a level characteristic of a full-term pregnancy, the likelihood determination will, for compact prosecution, be interpreted as being based on the recited chemotactic activity, while the biomarker measurement is treated as an additional required step for which claim 19 does not expressly recite a role in making that likelihood determination. Appropriate correction is required.
Claims 20—27 are rejected for the same reasons by virtue of their dependency from claim 19. 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 19-27 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to a judicial exception, specifically a law of nature, without additional elements that integrate the judicial exception into a practical application or amount to significantly more than the judicial exception.
This rejection is made in accordance with Patent Subject Matter Eligibility as set forth in MPEP §2106. Analysis of subject-matter eligibility under 35 U.S.C. §101 requires consideration under these steps as followed:
Step 1 – Statutory Category (Refer to MPEP §2106.03): Claims 19–27 are drawn to a process, which falls within a statutory category under 35 U.S.C. § 101.
Step 2A, Prong One – Recitation of a Judicial Exception (Refer to MPEP §2106.04): Regarding claim 19, the claim recites determining the likelihood that a pregnant subject will undergo delivery within about seven days and provides that an increased likelihood of such delivery is indicated when the chemotactic activity of the subject’s peripheral leukocytes is at a level characteristic of a full-term pregnancy. Under the interpretation set forth above for purposes of compact prosecution, the recitation of said chemotactic activity is interpreted as the chemotactic activity determined by the subsequently recited measurement of leukocyte migration toward the recited chemoattractant.
Claim 19 therefore recites a law of nature, namely, the naturally occurring relationship between the chemotactic responsiveness of maternal peripheral leukocytes associated with the physiological state characteristic of full-term pregnancy and the pregnant subject’s increased likelihood of undergoing delivery within about seven days. The migration behavior of the maternal leukocytes and the physiological progression toward delivery are naturally occurring biological phenomena of pregnancy and parturition. The claimed method does not create that relationship. Rather, the method measures the naturally occurring leukocyte response and relies upon the naturally occurring relationship between that response and proximity to delivery to provide the claimed likelihood determination. Claim 19 additionally requires obtaining peripheral leukocytes from the pregnant subject, obtaining another sample from the pregnant subject, contacting that sample with a reagent to a biomarker, forming a reagent-biomarker complex, measuring the complex to determine the amount or concentration of the biomarker, and measuring migration of the leukocytes toward a chemoattractant comprising a factor present in human fetal-membrane material obtained from a full-term pregnant subject. Under the compact-prosecution interpretation, the biomarker-measurement steps are required steps of claim 19, but claim 19 does not expressly assign the measured biomarker amount or concentration a role in determining the likelihood of delivery. Rather, the claim expressly states that the increased likelihood of delivery within about seven days is indicated by the recited chemotactic activity. Accordingly, the natural relationship relied upon by the claimed likelihood determination remains the relationship between maternal leukocyte chemotactic activity and proximity to delivery.
Claim 20 incorporates the law of nature recited in claim 19 and further specifies that the biomarker is selected from CXCR2, CXCR3, CXCR5, CCR1, CCR3, CCR5, CX3CR1 and/or CCR7. The additional identification of a particular chemokine-receptor biomarker does not alter the naturally occurring relationship between maternal leukocyte chemotactic activity and likelihood of delivery within about seven days. Claim 21 incorporates the law of nature recited in claim 19 and further specifies that the biomarker is PI3KCB, PI3KCD, Rac1, Vav1, Arp2 and/or Arp3. These intracellular biological molecules likewise constitute additional biological information obtained from the subject and do not alter the naturally occurring leukocyte-chemotaxis/proximity-to-delivery relationship recited in claim 19. Claim 22 incorporates the law of nature recited in claim 19 and merely specifies that the sample is a serum sample. The source or form of the biological sample does not change the naturally occurring relationship relied upon to make the claimed delivery-likelihood determination.
Claim 23 incorporates the law of nature recited in claim 19 and further limits the pregnant subject to one who is at least 35 weeks pregnant. Claim 24 instead limits the pregnant subject to one who is less than 35 weeks pregnant. These gestational-age limitations merely define the population in which the naturally occurring relationship is evaluated and do not change the relationship itself. Claim 25 incorporates the same law of nature and further limits the pregnant subject to one at risk of preterm delivery. Claim 26 further limits the pregnant subject to one having ruptured membranes. These limitations specify clinical characteristics of the pregnant subject but retain the same naturally occurring relationship between leukocyte chemotactic responsiveness and proximity to delivery.
Claim 27 incorporates the same law of nature and merely specifies that the subject is human. This field-of-use limitation likewise does not remove or alter the naturally occurring relationship recited in claim 19. Accordingly, claims 19–27 recite a judicial exception in the form of a law of nature.
Step 2A, Prong Two – Integration into a Practical Application (Refer to MPEP §2106.04 (d)): Regarding claim 19, the additional physical activity consists principally of collecting biological material and obtaining biological information used in connection with the naturally occurring relationship. The claim requires obtaining maternal peripheral leukocytes, obtaining a second sample, performing a biomarker-binding assay, and measuring leukocyte migration toward a chemoattractant derived from full-term human fetal-membrane material. These limitations do not recite an improvement to leukocyte-migration technology, an improved chemotaxis chamber, an improved flow-cytometry technique, an improved biomarker assay, a new reagent structure, or another technological improvement attributable to the claimed method. Rather, the migration assay supplies the biological information upon which the naturally occurring relationship operates. The biomarker assay similarly supplies additional biological information but, under the claim language as interpreted for compact prosecution, the measured biomarker amount or concentration is not expressly used to make the claimed likelihood determination. The claim therefore amounts to observing a naturally occurring biological characteristic of the pregnant subject and assigning predictive significance to that characteristic based on its naturally occurring association with proximity to delivery.
The claim also does not require, in response to the resulting likelihood determination, administering a therapeutic agent, altering medication, performing a medical procedure, hospitalizing the patient, changing obstetric management, initiating delivery, delaying delivery, administering corticosteroids, administering tocolytics, or otherwise applying the delivery-likelihood determination to produce a particular treatment or prophylactic result. In contrast to an eligible treatment claim in which a naturally occurring relationship is used to select and administer a particular treatment, claim 19 terminates at the diagnostic/prognostic determination itself. The use of a factor present in full-term human fetal-membrane material as the chemoattractant makes the measurement more specific but does not change the ultimate character of the claim. The fetal-membrane material is used to elicit and measure the biological leukocyte response that serves as the input to the naturally occurring correlation; the claim does not require any further technological or therapeutic application of the resulting prediction.
Claim 20’s recitation of specified chemokine-receptor biomarkers likewise merely narrows the biological information collected. It does not require that the measured receptor information be used to change treatment or otherwise produce a result beyond the claimed diagnostic assessment. Claim 21 similarly narrows the biomarker information to specified intracellular signaling/migration-associated molecules. The limitation provides another type of biological information for collection but does not impose any action upon the pregnant subject responsive to either that information or the resulting delivery prediction. Claim 22 merely specifies serum as the sample from which biological information is obtained. The limitation defines the source of the information but does not apply the judicial exception in a meaningful manner beyond the diagnostic field of use. Claims 23 and 24 restrict the gestational-age population in which the method is practiced. Those limitations merely define the patient population and do not impose a treatment, transformation, or technological operation responsive to the claimed delivery prediction. Claim 25’s limitation to pregnant subjects at risk of preterm delivery and claim 26’s limitation to subjects having ruptured membranes likewise define particular clinical populations. They do not require any treatment, prophylaxis, hospitalization decision, or other medical action resulting from the likelihood determination. Claim 27’s limitation to a human subject is similarly no more than a field-of-use limitation.
When claims 19–27 are considered as a whole, the additional elements therefore amount to obtaining biological specimens, measuring biological characteristics of those specimens, and using naturally occurring leukocyte chemotactic behavior to determine proximity to delivery. The claims do not recite a technological improvement or a subsequent treatment or other action that meaningfully applies the natural relationship. Accordingly, the judicial exception is not integrated into a practical application.
Step 2B, Inventive Concept (Refer to MPEP §2106.05): The additional elements are considered individually and as an ordered combination to determine whether they amount to significantly more than the judicial exception. One consideration is whether the additional elements merely constitute well-understood, routine, conventional activities previously engaged in within the relevant field. The evidence discussed below is relied upon only for this Step 2B determination, and not to establish the judicial exception itself.
Regarding claim 19’s collection and leukocyte-migration steps, Takeda demonstrates that the recited activities were established laboratory techniques in the pregnancy/parturition field. Takeda et al. (Pregnant Human Peripheral Leukocyte Migration during Several Late Pregnancy Clinical Conditions: A Cross-Sectional Observational Study. BMC Pregnancy and Childbirth. Vol. 17, No. 1, January 2017) teaches that peripheral blood samples were collected by venipuncture upon recruitment into the study and granting of consent using a standardized protocol for each subject in each of the groups and that leukocytes from maternal peripheral blood were isolated for the leukocyte migration assay (p. 2). Takeda further teaches that the procedure used was published with recent modifications to improve the assay performance and that modified boyden chemotaxis chambers were used in the assay (p. 3). Takeda further expressly states flow cytometry was used to quantify the number of leukocytes that migrated from the upper chamber down into the lower chamber through the polycarbonate membrane (p. 3). Takeda therefore demonstrates that obtaining maternal peripheral blood, isolating leukocytes, performing a Boyden-chamber chemotaxis assay, and quantifying migrated leukocytes by flow cytometry were not unconventional technical operations. Rather, Takeda itself characterizes the migration procedure as previously published and employs commercially identified Boyden-chamber and flow-cytometry equipment.
Takeda further demonstrates that applying such measurements to proximity-to-delivery assessment was already practiced. Takeda reports subjects in the pPROM group all delivered within 7 days of testing leukocyte migration and that the assay identified the cut-off point of delivery within 7 days at 37,082 leukocytes (p. 4; Fig. 3). Takeda further concludes that total leukocyte migration is an effective outcome measure for assessing proximity to delivery (p. 5). Thus, the recited migration measurement does not supply an unconventional technical mechanism beyond the natural correlation; the assay was already being used to obtain the same type of biological information concerning proximity to delivery.
Regarding claim 19’s separate biomarker-assay steps, Gomez-Lopez et al. (US 2014/0011205 A1 – IDS dated 07/30/2026) demonstrates that obtaining a sample from a pregnant subject, contacting it with a reagent to a biomarker, forming a complex, and quantitatively measuring the biomarker were established biomarker-assay activities. Gomez-Lopez expressly teaches obtaining a sample from a pregnant subject, contacting the sample with a reagent to a biomarker, to form a complex between the agent and the biomarker present in the sample; measuring the complex formed to determine the amount or concentration of said biomarker in the sample ([0023], p. 2). The use of the same sample/reagent/complex/measurement sequence in the prior art demonstrates that these additional laboratory operations, considered apart from the natural correlation, do not provide an unconventional inventive concept.
Regarding claim 20, the limitation specifying chemokine-receptor biomarkers likewise does not supply significantly more. Björkander et al. (Peripheral Monocyte Expression of the Chemokine Receptors CCR2, CCR5 and CXCR3 Is Altered at Parturition in Healthy Women and in Women with Systemic Lupus Erythematosus. Scandinavian Journal of Immunology. Vol. 77, No. 3, March 2013) demonstrates routine measurement of the very types of chemokine receptors encompassed by the claim in maternal peripheral immune cells. Björkander teaches that PBMCs were stained with antibodies including CCR5-APC (clone: 2D7/CCR5), CXCR3-APC (clone: 1C6/CXCR3) and that a minimum of 5000 monocyte events based on forward and side scatter properties were acquired using a BD FACSCalibur flow cytometer (p. 202). Björkander further states that the results were based on percentage of positive cells, and surface expression was defined as geometrical mean fluorescence intensity (p. 202). Björkander also reports that the percentages of CD16− CCR5+ and CD16− CXCR3+ monocytes were lower in pregnant women compared with non-pregnant women (p. 203; Fig. 1). Thus, specifying CCR5 or CXCR3 as the biomarker merely narrows claim 19 to chemokine-receptor measurements that were already being carried out on maternal peripheral immune cells using standard antibody staining and flow cytometry.
Regarding claim 21, Wójcik et al. (The Association of Leukocyte Phosphatidylinositol 3-Kinase Delta Overexpression with Gestational Diabetes Mellitus (GDM). Endokrynologia Polska. Vol. 65, No. 1, 2014) demonstrates that measuring PIK3CD expression in maternal leukocytes by quantitative PCR was likewise established. Wójcik teaches blood samples from women with normal glucose tolerance (NGT; n = 43) and GDM (n = 132) at 24–33 weeks of gestation were collected. After isolating leukocytes from the blood, quantitative real time PCR (qRT-PCR) was performed to determine PIK3CD gene expression in these cells (p. 17). Wójcik further teaches total RNA was extracted from leukocytes using a commercially available acid-phenol reagent according to the manufacturer’s instructions and that RT-PCR was performed using specific primers for PIK3CD (p. 19). Accordingly, claim 21’s restriction to PI3KCD does not convert the diagnostic method into an unconventional technical process. The claimed biomarker was already measurable in maternal leukocytes using commercially available reagents and conventional quantitative molecular-biological techniques. Fung-Leung et al. (Phosphoinositide 3-Kinase Delta (PI3Kδ) in Leukocyte Signaling and Function. Cellular Signalling. Vol. 23, No. 4, April 2011) further confirms that PI3Kδ-related leukocyte migration was an established biological subject rather than an unconventional technical implementation. Fung-Leung teaches the role of PI3K in leukocyte migration is at the stage of trans-endothelial migration and chemotaxis within tissues and PI3Kδ also participates in leukocyte chemotaxis (Fung-Leung, p. 605). Fung-Leung further reports neutrophil chemotaxis towards LTB4 in a transwell system is reduced in the absence of either PI3Kδ or PI3Kγ (p. 605). Thus, the PI3Kδ limitation adds biological specificity but no unconventional assay architecture or other technical feature.
Regarding claim 22, Gomez-Lopez further demonstrates that use of serum for biomarker measurement was an established specimen selection ([0233], p. 12). The reference expressly identifies serum as a biological sample and describes serum-based biomarker assays; therefore, limiting the sample to serum represents selection of a known biological specimen rather than an inventive technical feature. Regarding claims 23–27, Takeda demonstrates that application of leukocyte migration testing across the claimed pregnancy populations was already practiced. Takeda studied sTL (spontaneous normal labour delivered vaginally at term, 37–42 wk, n = 24), PTL (preterm in labour, 22–36 wk, n = 10), TPTL (threatened preterm labour as identified by uterine contractions or cervical dilation, 22–36 wk, n = 11), and pPROM (preterm with premature rupture of membranes but without contractions or dilated cervix, 22–36 wk, n = 8) (p. 2). Takeda additionally states pregnant women were recruited from the Royal Alexandra Hospital in Edmonton, Alberta (p. 2). Thus, limiting the method to subjects at or above 35 weeks, below 35 weeks, at risk for preterm delivery, having ruptured membranes, or being human merely restricts the patient population in which established biological measurements are performed. Those limitations do not provide an unconventional technological feature or otherwise supply an inventive concept.
Thus, when the additional elements of claim 19 are considered as an ordered combination rather than in isolation, the claim still amounts to obtaining maternal biological samples, performing established biomarker measurements, performing an established leukocyte chemotaxis assay, and using the resulting naturally occurring leukocyte-response information to reach the delivery-likelihood conclusion dictated by the claimed natural relationship. The ordered combination does not recite a new assay architecture, a new chemotaxis apparatus, a new measurement technology, a new reagent configuration, or a treatment step responsive to the determination. Rather, the known laboratory operations are used for their ordinary information-gathering functions in connection with the natural correlation. The additional limitations of claims 20–27 likewise only narrow the biomarker, specimen, gestational age, clinical status, membrane status, or subject population. Considered individually and in combination with claim 19, these limitations do not transform the naturally occurring relationship into patent-eligible subject matter. Accordingly, claims 19–27 do not recite additional elements that, individually or as an ordered combination, amount to significantly more than the judicial exception.
Therefore, claims 19–27 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to a law of nature without additional elements that integrate the law of nature into a practical application or provide an inventive concept sufficient to transform the judicial exception into patent-eligible subject matter.
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.
Claims 19 and 22-27 are rejected under 35 U.S.C. 103 as being unpatentable over Takeda et al. (Pregnant Human Peripheral Leukocyte Migration during Several Late Pregnancy Clinical Conditions: A Cross-Sectional Observational Study. BMC Pregnancy and Childbirth. Vol. 17, No. 1, January 2017) in view of Gomez-Lopez et al. (US 2014/0011205 A1 – IDS dated 07/30/2026) and Turhan et al. (Maternal Serum Interleukin 6 Levels in Preterm Labor: Prediction of Admission-to-Delivery Interval. Journal of Perinatal Medicine. Vol. 28, No. 2, January 2000).
Regarding claim 19, for a method of determining the likelihood of a pregnant subject undergoing delivery within about 7 days, Takeda teaches all preterm with premature rupture of membranes (pPROM) delivered within 7d and that receiver-operating-characteristic analysis identified the cut-off point of delivery within 7 days at 37,082 leukocytes with 78.1% sensitivity, 88.9% specificity, 91.4% positive predictive value, 72.7% negative predictive value, and an area under the curve of 0.83 (pp. 1, 4; Fig. 3). Takeda further teaches that its migration assay has the potential to distinguish subjects who will not deliver for several weeks from subjects experiencing symptoms who will deliver within a week (p. 4). Regarding obtaining peripheral leukocytes from said pregnant subject, Takeda teaches that peripheral blood samples were collected by venipuncture upon recruitment into the study and that leukocytes present in peripheral maternal blood samples were isolated and used in the leukocyte migration assay (p. 2). Takeda additionally teaches leukocytes (100,000) obtained by venipuncture were used in the assay (p. 1).
Regarding wherein an increased likelihood of delivery within about 7 days is indicated when said chemotactic activity of said leukocytes is at a level characteristic of a full term pregnancy, Takeda teaches that more spontaneous normal labour delivered vaginally at term (sTL) leukocytes migrated than preterm not in labour (PTNL) or elective caesarean section at term without labour (TNL) leukocytes, that leukocyte migration was similarly high in the sTL and preterm in labour (PTL) groups, and that there was no significant difference between the pPROM and PTL and sTL groups (p. 4; Fig. 2). Takeda further teaches that maternal human peripheral leukocytes increase their migration toward a term fetal membrane chemotactic signal when in labour at term or preterm or in the early stages of labour such as pPROM (p. 4).
Regarding wherein determining said chemotactic activity comprises measuring migration of said leukocytes towards a chemoattractant, Takeda teaches use of modified boyden chemotaxis chambers, placement of 100,000 leukocytes in the upper chamber, and chemoattractant extract in the lower chamber, followed by quantification of migrated leukocytes (p. 3; Fig. 1). Takeda expressly teaches that flow cytometry was used to quantify the number of leukocytes that migrated from the upper chamber down into the lower chamber through the polycarbonate membrane (p. 3). Regarding wherein said chemoattractant is a factor present in a sample comprising human fetal membrane (hFM) obtained from a full term pregnant subject, Takeda teaches chemotactic factor isolated from term labour fetal membranes (p. 1) and further teaches fetal membranes were collected from fifteen women who underwent term spontaneous labour without complications and processed to prepare the chemoattractant used in the migration assay (p. 2).
Takeda further provides an express reason to develop its migration assay using additional molecular or biochemical information. Takeda teaches that this principle has the potential to be improved to become a clinical test to predict delivery (pp. 1, 6), that further refinement and improvement may lead to an informative diagnostic test to predict preterm birth risk (p. 6), and that increased leukocyte responsiveness to the chemoattractant with labour onset may reflect more leukocyte receptors to the chemoattractant, better coupling of receptors with intracellular signal transduction mechanisms and/or an upregulation of the migration apparatus in the cells (p. 5).
However, Takeda does not teach obtaining a sample from the pregnant subject, contacting the sample with a reagent to a biomarker to form a reagent/agent-biomarker complex, and measuring the complex to determine the amount or concentration of the biomarker, as additionally required by claim 19.
Gomez-Lopez teaches these missing limitations. Regarding obtaining a sample from a pregnant subject; contacting the sample with a reagent to a biomarker; forming a complex between the agent and biomarker present in the sample; and measuring the complex to determine the amount or concentration of the biomarker, Gomez-Lopez teaches obtaining a sample from a pregnant subject, contacting the sample with a reagent to a biomarker, to form a complex between the agent and the biomarker present in the sample; measuring the complex formed to determine the amount or concentration of said biomarker in the sample ([0023], p. 2; [0129]–[0131], p. 7). Gomez-Lopez further teaches qualitatively or quantitatively determining, analyzing or measuring a biological sample from a subject for the presence or absence, or amount or concentration, of one or more biomarkers associated with the diagnosis and/or prognosis and/or therapeutic monitoring of pregnancy and/or a disorder associated with pregnancy ([0128], p. 7), and that the determination, analysis or measurement of the biomarker is correlated with normal term pregnancy, or a disorder associated with pregnancy ([0135], p. 7). Gomez-Lopez also provides a direct technical bridge between the biomarker and chemotaxis approaches because it separately teaches determining pregnancy-associated likelihood by measuring chemotaxis of leukocytes, obtained from a pregnant human female, towards a chemoattractant, and teaches that the degree of activation increases as delivery nears ([0124]–[0125], p. 6). Thus, Gomez-Lopez places quantitative biomarker measurement and leukocyte chemotaxis within the same pregnancy-prognosis field.
Turhan further strengthens the reason to incorporate quantitative maternal biomarker measurement into Takeda’s seven-day delivery-prediction method. Turhan teaches that maternal venous blood samples were obtained for IL-6, CRP and WBC count and IL-6 determination was performed chemiluminometrically by Immulite autoanalyzer (p. 134). Turhan further teaches maternal serum IL-6 levels were significantly higher in patients delivered within 2 and 7 days and that an IL-6 concentration of 8.3 pg/ml provided the best sensitivity and specificity for delivery within seven days (p. 135; Figs. 2–3). Following multivariate analysis, only maternal IL-6 was associated with a higher risk of delivering within 7 days (p. 136; Table II; Fig. 3). Turhan further concludes that elevated maternal serum IL-6 concentrations are associated with impending preterm delivery and that maternal IL-6 concentration was an independent variable of admission to delivery interval (p. 137).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Takeda’s method for predicting delivery within about seven days by additionally obtaining a biological sample from the pregnant subject and performing the quantitative reagent-biomarker-complex measurement taught by Gomez-Lopez. Takeda expressly identifies its leukocyte-migration principle as suitable for further development and improvement into a clinical delivery-prediction test; Gomez-Lopez teaches quantitative biomarker measurement in the same pregnancy-prognosis field and alongside leukocyte-chemotaxis methods; and Turhan independently demonstrates that quantitative measurement of a maternal biomarker is useful for the same delivery-within-seven-days endpoint addressed by Takeda. One of ordinary skill in the art would have had a reasonable expectation of success because Gomez-Lopez demonstrates established methods for quantitatively measuring pregnancy-associated biomarkers and Turhan demonstrates successful maternal biomarker measurement correlated with delivery within seven days. The modification therefore would predictably provide an additional biochemical measure associated with impending delivery while retaining Takeda’s chemotactic migration determination and its function in predicting delivery within seven days.
Regarding claim 22, wherein the sample is a serum sample, Gomez-Lopez expressly teaches that a biological sample includes plasma, serum and blood fractions or products including serum, plasma, platelets, red blood cells, white blood cells and the like ([0086], p. 4).Gomez-Lopez further teaches serum was isolated from the centrifuge tube and stored at -20°C. until assayed ([0233], p. 12) and performance of ELISAs in both serum and protein extracts of tissues ([0244], p. 13). Therefore, it would have been obvious to use serum as the sample in the method of Takeda as modified by Gomez-Lopez and Turhan because Gomez-Lopez expressly identifies serum as a suitable biological sample and demonstrates its use in biomarker assays. A skilled artisan would have had a reasonable expectation of success because Gomez-Lopez actually isolates and assays serum using established biomarker-detection techniques.
Regarding claim 23, wherein the pregnant subject is at least 35 weeks pregnant, Takeda expressly includes sTL (spontaneous normal labour delivered vaginally at term, 37–42 wk, n = 24) ( p. 2), and reports a mean gestational age at sampling of 39.2 ± 1.2 weeks for the sTL group (p. 4; Table 1).
Regarding claim 24, wherein the pregnant subject is less than 35 weeks pregnant, Takeda expressly studies PTL (preterm in labour, 22–36 wk), PTNL (normal women sampled preterm but not in labour, 22–36 wk), TPTL (threatened preterm labour as identified by uterine contractions or cervical dilation, 22–36 wk), and pPROM (preterm with premature rupture of membranes but without contractions or dilated cervix, 22–36 wk) (p. 2). Takeda reports mean gestational ages at sampling of 31.9 ± 3.8, 29.4 ± 4.0, 31.5 ± 2.6, and 31.8 ± 3.9 weeks, respectively (p. 4; Table 1).
Regarding claim 25, wherein the pregnant subject is at risk of preterm delivery, Takeda expressly studies PTL (preterm in labour, 22–36 wk), TPTL (threatened preterm labour as identified by uterine contractions or cervical dilation, 22–36 wk), and pPROM (preterm with premature rupture of membranes but without contractions or dilated cervix, 22–36 wk) (p. 2). Takeda further teaches that leukocyte migration has the potential to become a diagnostic test that would be valuable for identifying asymptomatic women who may be at risk for preterm birth (p. 6).
Regarding claim 26, wherein the pregnant subject has ruptured membranes, Takeda expressly includes a pPROM group comprising subjects preterm with premature rupture of membranes but without contractions or dilated cervix, 22–36 wk (p. 2). Takeda further reports subjects in the pPROM group all delivered within 7 days of testing leukocyte migration and that the pPROM group’s migration response was significantly greater than PTNL group and not significantly different from PTL and sTL groups (p. 4; Fig. 2c).
Regarding claim 27, wherein said subject is a human, Takeda is expressly directed to pregnant human peripheral leukocyte migration and teaches pregnant women were recruited from the Royal Alexandra Hospital in Edmonton, Alberta (p. 1–2).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Takeda et al., Gomez-Lopez et al., Turhan et al., as applied to claim 19 above, and further in view of Björkander et al. (Peripheral Monocyte Expression of the Chemokine Receptors CCR2, CCR5 and CXCR3 Is Altered at Parturition in Healthy Women and in Women with Systemic Lupus Erythematosus. Scandinavian Journal of Immunology. Vol. 77, No. 3, March 2013).
With respect to the teachings of Takeda et al, Gomez-Lopez et al., and Turhan et al., see the discussion above, which applies equally here. These references differ from the instant claim in failing to expressly teach or specify that the biomarker is CXCR2, CXCR3, CXCR5, CCR1, CCR3, CCR5, CX3CR1 and/or CCR7.
Björkander supplies the claimed receptor species. Björkander teaches chemokines and their receptors are involved in chemotaxis of leucocytes during homoeostatic and inflammatory conditions and specifically teaches that CCR5 and CXCR3 are chemokine receptors expressed on immune cells, including monocytes (p. 201). Björkander investigated chemokine receptor expression, migratory behaviour and responses to microbial stimulation of peripheral monocytes from pregnant women at parturition and demonstrated reduced percentages of CCR2+, CCR5+ and CXCR3+ monocytes in pregnant women (p. 200). Björkander further teaches staining PBMCs with CCR5-APC and CXCR3-APC antibodies and defining receptor surface expression by flow cytometry (p. 202), and reports that the percentages of CD16− CCR5+ and CD16− CXCR3+ monocytes were lower in pregnant women compared with non-pregnant women (p. 203; Fig. 1).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method of Takeda, as modified by Gomez-Lopez and Turhan, by selecting a leukocyte chemokine receptor such as CCR5 or CXCR3 as the biomarker, as taught by Björkander. Takeda expressly suggests that the increased leukocyte migratory responsiveness associated with labour may result from changes in leukocyte receptor abundance or receptor-associated signaling, thereby providing a direct reason to investigate leukocyte receptors underlying that migration phenotype, while Björkander teaches that CCR5 and CXCR3 are chemokine receptors involved in leukocyte chemotaxis and that their expression is measurably altered on peripheral monocytes from pregnant women at parturition. One of ordinary skill in the art therefore would have had a reasonable expectation of success in selecting and measuring CCR5 or CXCR3 as the biomarker because Björkander actually measured those receptors in peripheral monocytes from pregnant women using conventional antibody-based flow cytometry, and such modification would have predictably provided a molecular measure of the leukocyte receptor state associated with the chemotactic phenotype already relied upon in the Takeda-based delivery-prediction method.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Takeda et al., Gomez-Lopez et al., Turhan et al., as applied to claim 19 above, and further in view of Wójcik et al. (The Association of Leukocyte Phosphatidylinositol 3-Kinase Delta Overexpression with Gestational Diabetes Mellitus (GDM). Endokrynologia Polska. Vol. 65, No. 1, 2014) and Fung-Leung et al. (Phosphoinositide 3-Kinase Delta (PI3Kδ) in Leukocyte Signaling and Function. Cellular Signalling. Vol. 23, No. 4, April 2011)
With respect to the teachings of Takeda et al, Gomez-Lopez et al., and Turhan et al., see the discussion above, which applies equally here. These references differ from the instant claim in failing to expressly teach or specify that the biomarker is PI3KCB, PI3KCD, Rac1, Vav1, Arp2, and/or Arp3.
Regarding the claimed PI3KCD alternative, Wójcik teaches that the PI3-K catalytic isoforms are PI3-K alpha, PI3-K beta and PI3-K delta, and encoded by three separate genes, denoted PIK3CA, PIK3CB and PIK3CD respectively, and that PI3-Kdelta expression predominates in leukocytes (p. 18). Wójcik further teaches one hundred and thirty-two GDM and 43 NGT pregnant women between 24 and 33 weeks of gestation were recruited for this study and investigated changes in leukocyte PI3KCD mRNA expression (p. 18). Wójcik teaches that Total RNA was extracted from leukocytes and RT-PCR was performed using specific primers for PIK3CD (p. 19), and reports The changes in leukocyte PIK3CD gene expression in GDM (n = 132) v. NGT (n = 43) subjects were determined by RT-PCR, with a 1.98-fold up-regulation in the GDM group (p. 20; Fig. 1).
Fung-Leung provides the direct mechanistic link between PI3Kδ and the leukocyte migration/signaling phenomenon identified by Takeda. Fung-Leung teaches PI3Kδ is a lipid kinase of the PI3K class IA family involved in early signaling events of leukocytes responding to a wide variety of stimuli and PI3Kδ participates in the development, activation and migration of T cells and NK cells (p. 603). More specifically, Fung-Leung teaches the role of PI3K in leukocyte migration is at the stage of trans-endothelial migration and chemotaxis within tissues and PI3Kδ also participates in leukocyte chemotaxis (p. 605). Fung-Leung further reports that neutrophil chemotaxis towards LTB4 in a transwell system is reduced in the absence of either PI3Kδ or PI3Kγ (p. 605).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method of Takeda, as modified by Gomez-Lopez and Turhan, by selecting PI3Kδ/PIK3CD as the biomarker, as taught by Wójcik and Fung-Leung. Takeda expressly directs the skilled artisan toward intracellular signal-transduction mechanisms and the cellular migration apparatus as possible molecular bases for the increased leukocyte chemotactic responsiveness associated with impending delivery; Fung-Leung specifically identifies PI3Kδ as a leukocyte intracellular signaling component that participates in leukocyte migration and chemotaxis, thereby providing a direct reason to select PI3Kδ as a molecular marker relevant to Takeda’s migration phenotype; and Wójcik demonstrates that PIK3CD expression can actually be quantitatively determined in leukocytes obtained from pregnant women. One of ordinary skill in the art would therefore have had a reasonable expectation of success because the biological relevance of PI3Kδ to leukocyte chemotaxis was already established by Fung-Leung and Wójcik successfully measured PIK3CD expression in maternal leukocytes using conventional quantitative RT-PCR; accordingly, selecting and measuring PIK3CD as the biomarker would have predictably provided a measurable intracellular-signaling indicator associated with the leukocyte migration machinery identified by Takeda without altering the operation of Takeda’s chemotactic delivery-prediction assay.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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Claims 19 and 22-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4 and 6 of U.S. Patent No. 9880152 in view of Takeda et al., Gomez-Lopez et al. and Turhan et al.
Patent claim 4 recites determining the likelihood of preterm delivery by obtaining peripheral leukocytes from a pregnant subject and determining their chemotactic activity, wherein increased likelihood is indicated when the chemotactic activity of the leukocytes is at a level characteristic of a full-term pregnancy, by measuring leukocyte migration toward a chemoattractant including a full-thickness fetal membrane extract obtained from a full-term pregnancy subject. Instant claim 19 differs principally by specifying delivery within about 7 days and additionally requiring quantitative measurement of a biomarker. As discussed in the §103 rejection above, Takeda teaches use of leukocyte migration to predict delivery within 7 days, Gomez-Lopez teaches the claimed quantitative reagent-biomarker-complex measurement, and Turhan confirms the utility of quantitative maternal biomarker measurement for predicting delivery within seven days
It would have been obvious to specify the delivery-prediction interval of patented claim 4 as within about seven days, as taught by Takeda, because Takeda demonstrates that leukocyte migration is predictive over that clinically relevant interval, and to additionally perform the quantitative biomarker measurement taught by Gomez-Lopez and supported by Turhan to provide an additional biochemical indicator of impending delivery. The modifications would predictably provide complementary measures for determining impending delivery. Accordingly, claim 19 is not patentably distinct from patented claim 4.
Claims 22–26 likewise do not render the invention patentably distinct. Claim 22 specifies serum, which Gomez-Lopez teaches as a suitable biomarker sample. Claims 23 and 24 specify gestational-age populations demonstrated by Takeda. Claim 25 specifies a subject at risk of preterm delivery, the outcome already addressed by patented claim 4 and Takeda. Claim 26 specifies ruptured membranes, a pPROM population expressly evaluated by Takeda. It would have been obvious to apply the method as modified above to these known sample types and pregnancy populations because the references demonstrate their suitability for the same pregnancy/delivery-prediction purpose.
Regarding claim 27, patent claim 6 depends from claim 4 and expressly requires that said subject is a human, as likewise required by instant claim 27. Regarding the limitations inherited from instant claim 19, refer to the discussion above. Accordingly, for the reasons set forth above and in the §103 rejection, claim 27 is not patentably distinct from patented claim 6.
Claim 20 is rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 4 of U.S. Patent No. 9880152 in view of Takeda et al., Gomez-Lopez et al., Turhan et al., as applied to claim 19 above, and further in view of Björkander et al.
Regarding claim 19, refer to the discussion above. Claim 20 further specifies CXCR2, CXCR3, CXCR5, CCR1, CCR3, CCR5, CX3CR1 and/or CCR7 as the biomarker. As discussed in the §103 rejection, Björkander teaches measurable CCR5 and CXCR3 expression on peripheral monocytes from pregnant women and associates chemokine receptors with leukocyte chemotaxis. It would have been obvious to select CCR5 or CXCR3 as the biomarker because these receptors provide measurable molecular indicators associated with the leukocyte chemotactic phenotype underlying patented claim 4. Accordingly, claim 20 is not patentably distinct.
Claim 21 is rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 4 of U.S. Patent No. 9880152 in view of Takeda et al., Gomez-Lopez et al., Turhan et al., as applied to claim 19 above, and further in view of Wójcik et al. and Fung-Leung et al.
Regarding claim 19, refer to the discussion above. Claim 21 further specifies PI3KCB, PI3KCD, Rac1, Vav1, Arp2, and/or Arp3 as the biomarker. As discussed in the §103 rejection, Fung-Leung links PI3Kδ to leukocyte signaling, migration, and chemotaxis, while Wójcik demonstrates quantitative measurement of PIK3CD expression in leukocytes from pregnant women. It would have been obvious to select PI3KCD as the biomarker because PI3Kδ is involved in the leukocyte chemotactic machinery measured by patented claim 4 and its expression was known to be quantitatively measurable in maternal leukocytes. Accordingly, claim 21 is not patentably distinct.
Conclusion
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/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 September 1, 2026
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