DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to papers filed 03/26/2026.
Claims 59, 62, 64-67 and 69 have been amended.
Claim 63 has been newly canceled and claims 79-80 have been newly added.
Claims 59-62, and 64-80 are currently pending.
Claims 66-78 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/28/2025.
Claims 59-62, 64-65, and 79-80 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
The term “stabilization buffer” is defined by Applicant as referring to an aqueous buffer that maintains a substantial portion of cells in the stabilization buffer as intact, inviable (or nonproliferating) and substantially not expanding or contracting in size” (page 6 para 29).
The term “preservative” has been defined by Applicant as referring to an agent added to a composition comprising cells in order to prevent breakdown of biological components of the composition (page 6 para 30).
The term “inviable” is defined by Applicant as “nonproliferating” (page 6 para 29). This has been broadly interpreted as including dead, nonviable cells as well as cells rendered incapable of proliferating due to lack of nutrients or some other reason.
The term “associated” as recited in claim 62 has not been defined by Applicant and thus has been broadly interpreted as requiring some type of connection, direct or indirect, between at least a portion of the cells and the cellulosic device.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 59-62 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Fleming et al (WO 2013/192620-from IDS filed 04/13/2023) as evidenced by Storm et al (Journal of Histochemistry and Cytochemistry, 2016 -from IDS filed 04/13/2023).
Regarding claims 59-62, Fleming disclose a composition comprising a population of trophoblast and trophoblast-derived cells (abstract, pages 10-11, pages 30-31) in a stabilization buffer comprising a preservative and a cellulosic collection device (abstract, page 10, page 16, page 31, Fig. 33), wherein at least a subset of the population of cells is intact and inviable (non-proliferative cells such as syncytiotrophoblasts) as evidenced by Storm (page 769-770). The cells are collected in an absorbent medium that comprises a groove pre-filled with buffer and preservative, wherein the buffer and preservative would intrinsically stabilize the collected cells (stabilization buffer) (abstract; page 10, lines 27-28; page 16, lines 22-32; page 31, line 24; fig. 33). The cellulosic collection device comprising the absorbent medium, such as cellulose and cotton (cellulosic), is in the form of an interlabial pad, sanitary napkin, tampon or panty-liner (abstract; page 12, lines 30-31; page 17, lines 13-27). At least a subset of the population of cells are intact and inviable as they are used to analyze the genome of the fetus, thereby indicating intact cells during collection.
Fleming disclose wherein at least 50% of the population of cells are intact after 1 day in the stabilization buffer at room temperature (page 18 lines 15-16, page 30 lines 10-22).
Fleming disclose wherein the fetal trophoblast cells collected in the stabilization buffer are isolated from maternal cells using size-based separation of fetal trophoblast cells in flow cytometry, thereby indicating that the stabilization buffer maintains the size of the cells within a range of 0.5 to 1x of their actual size as compared with the size of the cells prior to contact with the stabilization buffer (page 18, lines 22-23; page 19, lines 13-17).
Therefore, the teaching of Fleming et al anticipates Applicant’s invention as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 59-62, 64-65, and 79-80 are rejected under 35 U.S.C. 103 as being unpatentable over Fleming et al (WO 2013/192620-from IDS filed 04/13/2023) as evidenced by Storm et al (Journal of Histochemistry and Cytochemistry, 2016 -from IDS filed 04/13/2023).
Regarding claims 58-62, 64, Fleming disclose a composition comprising a population of trophoblast and trophoblast-derived cells (abstract, pages 10-11, pages 30-31) in a stabilization buffer comprising a preservative and a cellulosic collection device (abstract, page 10, page 16, page 31, Fig. 33), wherein at least a subset of the population of cells is intact and inviable (non-proliferative cells such as syncytiotrophoblasts) as evidenced by Storm (page 769-770). The cells are collected in an absorbent medium that comprises a groove pre-filled with buffer and preservative, wherein the buffer and preservative would intrinsically stabilize the collected cells (stabilization buffer) (abstract; page 10, lines 27-28; page 16, lines 22-32; page 31, line 24; fig. 33). The cellulosic collection device comprising the absorbent medium, such as cellulose and cotton (cellulosic), is in the form of an interlabial pad, sanitary napkin, tampon or panty-liner (abstract; page 12, lines 30-31; page 17, lines 13-27). At least a subset of the population of cells are intact and inviable as they are used to analyze the genome of the fetus, thereby indicating intact cells during collection.
Fleming disclose wherein at least 50% of the population of cells are intact after 1 day in the stabilization buffer at room temperature (page 18 lines 15-16, page 30 lines 10-22).
Fleming disclose wherein the fetal trophoblast cells collected in the stabilization buffer are isolated from maternal cells using size-based separation of fetal trophoblast cells in flow cytometry, thereby indicating that the stabilization buffer maintains the size of the cells within a range of 0.5 to 1x of their actual size as compared with the size of the cells prior to contact with the stabilization buffer (page 18, lines 22-23; page 19, lines 13-17).
Since the cells of Fleming are selected based on size, the motivation to maintain the cell size within a range of +/- 20% after incubation with the stabilization buffer in order to maintain the same desired cell features is obvious and obtainable through routine optimization and experimentation with the buffer concentrations and ingredients as well as pore sizes of the cellulosic collection device.
Since Fleming disclose all the limitations of the claimed composition Fleming at least renders obvious the claims as the person of ordinary skill in the art would have been motivated to combine the different features with a reasonable expectation of success because Fleming teaches and suggests that the cell types, stabilization buffer, preservative, cellulosic collection device and other claimed limitations desirable and beneficial for use in their invention.
Regarding claim 65, Fleming do not specifically disclose wherein the population of cells comprises at least 100 cells. However, one of ordinary skill in the art would have been motivated with a reasonable expectation of success to optimize the composition to include as many of the desired cells as possible and at least enough cells for analysis.
With regard to the concentrations of cells in the composition, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
The selection of specific cell concentrations clearly would have been a routine matter of optimization and experimentation on the part of the artisan of ordinary skill, said artisan recognizing that the amount of the cells collected would need to be sufficient for the intended use of genetic analysis.
Regarding claim 79, Fleming disclose wherein their samples are collected beginning day 1 and up to 14 days, one sample each day (page 27 lines 30-33- page 28 lines 1-10) which suggests that maintaining the cells as intact and suitable for testing for at least 6 days would have been a desired beneficial feature of the stabilization buffer and thus an obvious modification to achieve through routine optimization and experimentation.
Regarding claim 80, Since the cells of Fleming are selected based on size, the motivation to maintain the cell size after incubation with the stabilization buffer for at least 1 day in order to maintain the same desired cell features is obvious and obtainable through routine optimization and experimentation with the buffer concentrations and ingredients as well as pore sizes of the cellulosic collection device.
Therefore, the teaching of Fleming renders obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 03/26/2026 have been fully considered but they are not persuasive.
Applicant argues that Fleming fails to describe all the limitations of the claim since syncytiotrophoblasts are non-proliferative once differentiated within the body (as evidenced by Storm) that contact with the stabilization buffer of Flemming would not render a population of these cells non-proliferative as they are already non-proliferative prior to contact with any buffer.
This is not found persuasive. Applicant’s definition of a stabilization buffer “refers to an aqueous buffer that maintains a substantial portion of cells in the stabilization buffer as intact, inviable (or nonproliferating) and substantially not expanding or contracting in size” (page 6 para 29). Applicant’s definition of a stabilization buffer, plus the fact that Applicant lists syncytiotrophoblasts as the type of trophoblast and trophoblast-derived cell to be included in their invention (see claim 60) indicates that the term “renders” is meant to broadly encompass delivering or providing a non-proliferative cell. In addition, Applicant’s original filed claims filed 01/05/2023 did not include the term “renders” nor does the Specification as filed. Therefore, if Applicant were to assert that “renders” were to be limited to a much narrower interpretation as specifically causing proliferative cells to be non-proliferative, then it would have to be determined that the later amendment to the claims on 08/03/2023 adding the term “renders” introduced new matter into the claims.
Applicant argues that Flemming is silent with regard to the percent of the cells that are intact following one day in the stabilization buffer at room temperature, let alone whether or not at least 50% of the population of cells are maintained as intact cells after one day in the stabilization buffer at room temperature.
This is not found persuasive. Fleming states that they are combining cells with their stabilization buffer for further analysis and testing and do not mention a loss of cells through breakage so the assumption is that 100% or close to 100% of the cells are intact (at least 50%) (abstract, page 18 lines 15-16, page 30 lines 10-22). In addition, the Figures 4 and 5 also show intact cells for analysis.
Applicant argues that, while Fleming describes a method where a measure of cell size can be obtained and fetal cells of a particular size can be isolated, Fleming is silent as to maintaining the size of a cell as compared to prior to contact with a buffer and thus does not teach this claim limitation.
This is not found persuasive. The cells are selected based on size and therefore maintaining cells of the necessary size is required for Fleming.
Applicant argues that the amendments to the claims have overcome the 102 rejection of the claims over Stelling as evidenced by Hologic and Storm.
This is found persuasive and this rejection has been withdrawn.
Applicant argues that a person of skill in the art would not have been motivated to modify the composition of Fleming to arrive at the claimed composition. Applicant argues that Fleming describes their collection devices while emphasizing the importance of maintaining the viability of the fetal cells collected and propagated and point to page 1 as evidence. Applicant asserts that Fleming’s emphasis on the compatibility of the methods therein for propagating isolated fetal cells would motivate a person of skill in the art to preserve the viability of the collected fetal cells consistent with Fleming’s stated purpose.
This is not found persuasive. The claims are drawn to a composition that comprises trophoblast and trophoblast derived cells combined with a stabilization buffer and a cellulosic collection device. While Fleming’s composition does mention viability in general they also describe isolating syncytiotrophoblasts for further use as well, which are a cell type well known to be nonproliferating as evidenced by Storm. So the maintenance of nonproliferating cells is not in contradiction with the compositions of Fleming.
Applicant argues that the claimed composition requires that contact with the stabilization buffer renders the population of trophoblast and trophoblast-derived cells non-proliferative and that this is contrast to Fleming which states that surprisingly it was determined that fetal cells remain viable in these devices and can be isolated and propagated following collection. Applicant asserts that a person skilled in the art would not have been motivated to alter the methods of Fleming to arrive at a composition with non-proliferative cells. Applicant asserts that a person skilled in the art would be motivated to use the buffers of Fleming to allow for isolation and propagation of the cells and maintain their proliferative state.
This is not found persuasive. Fleming is referring to viable cells as those that are not dead. Fleming requires syncytiotrophoblasts and thus also includes embodiments wherein their cells are nonproliferative.
Applicant argues that Storm does not remedy the deficiency of Fleming as Storm is merely cited for classifying syncytiotrophoblasts as non-proliferative. Applicant argues that Storm does not teach the claimed composition.
This is not found persuasive as Fleming is not deemed to be defective and Storm is only used as an evidence reference in the rejections above.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mueller et al., “Isolation of Fetal Cells from Maternal Blood to Enable Prenatal Diagnosis”, US 5,503,981, 1996, (discloses isolation of syncytiotrophoblasts for obtaining genetic information about the fetus -abstract and claim 1).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/ Primary Examiner, Art Unit 1631
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