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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/18/2026 has been entered.
No amendments to the claims have been provided. Amendments to the specification and drawing have been provided and will be addressed in the discussion of Applicant’s remarks.
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 51-65, as previously presented, remain rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more.
The claim(s) recite(s) “a population of mortal pluripotent stem cells”.
According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories of invention (i.e. process, machine, manufacture, or composition of matter). Claims 51-65 drawn to a composition of matter comprising a population of cells. Thus claims 51-65 meet the requirements for step 1 of the analysis.
Second, the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019PEG, “directed to” is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application”, requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application).
Regarding the first prong (1), claims 51-65 are expressly directed to “a population of mortal pluripotent stem cells (MSCP). The specification teaches a non-embryonic mammalian stem cell (e.g., a trophoblast stem cell) can be a source cell to make mortal pluripotent stem cells (MPSCs) disclosed herein. In some instances, the mammalian stem cells are isolated from amniotic fluid, amniotic membrane, Wharton's jelly, chorionic villi, or ectopic pregnancy, in a manner that is not disturbing nor destructive to an embryo ([0061]). Thus the claimed population of cells are found within blastocysts (trophoblast cells), amniotic fluid, amniotic membrane, Wharton’s jelly, and chorionic villi, which are all products of nature. Thus the claimed cells are also products of nature.
Regarding the second prong (2), the claimed product does not recite any limitations that would be considered integration into a practical application. Thus, claims 51-65 meet the requirement of step 2A as being directed to a judicial exception.
Third, if a judicial exception is present in the claim, it is further assessed to determine if the claim recites any additional elements or steps that are sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. Claim 51 recite the population of cells with the additional elements of having the functional characteristics of being “mortal”, “pluripotent” and the functional/structural characteristics of expressing markers HLA-G and HSP90, with at least 80% having HLA markers A, B, and C. The claims also recite the additional functional limitations at least 89 population doubling times within about 90 days from a start of culturing the MSPCs. All of these element solely describe structural/functional inherent to the cell and not any particular modification to the cell. As such, the claimed cell population encompasses one that is present in its source cell or isolated therefrom. Therefore, the claimed population of cell is not marked different in any way from its natural counterpart.
Regarding dependent claims 53-65, all of these claims further specify marker expression and chromosomal quality that are inherent to the cell present within the natural counterpart. As such, these claims also do not markedly distinguish the population of cells from their natural counterpart.
As such, claims 51-65 do not meet the requirements of step 2B of the 2019PEG because the cell population is not markedly different from its natural counterpart.
In conclusion, claims 51-65 do not meet all the requirements of the 2019PEG and therefore are deemed patent ineligible.
Response to Arguments
Applicant's arguments filed 3/18/2026 have been fully considered but they are not persuasive in overcoming the rejection of record.
Amendments to the Specification:
Applicant submits an amended specification stating that the amendment rectify typographical errors and add inadvertently left out text from the parent application PCT/US2021/30686. In response, a review of the amendment to the specification and drawing are as Applicant submits and no new matter has been introduced. As such, the amendments to the specification will be entered.
Amendments to Drawings:
Applicant submits all Figures from Replacement Sheets 1-12 comprising FIGS. 1, 2A-2D, 3, 4, 5A-5D, and 6A-6G are herein amended such that the text and drawings of prior Sheets 1-7 are enlarged and resolution enhanced for clarity in compliance with 37 C.F.R. 1.84. No changes have been made to the data and no new matter is believed to have been added.
In accordance with MPEP §608.01(p) and 37 CFR §1.57(b), Applicant further encloses Replacement Sheets 13-21 comprising drawings from the parent PCT application (PCT/US2021/030686) as filed May 4, 2021 that were unintentionally excluded during the filing of instant US Application No.17/964,399 filed October 12, 2022. Applicant respectfully requests that the corresponding figures of record be replaced with the Replacement Sheets filed herewith. No new matter is believed to have been added by amendment.
In response, Examiner agrees with Applicant’s remarks, particularly no new matter has been introduced and the replacement drawings are accepted.
Claim Rejections under 35 U.S.C 101:
Applicant continues to traverse with rejection. Applicant submits that the claims “pass” the machine or transformation test as outlined in Bilski v Kappos. Examples 1,3, and 9 describes MPSCs are in “a different state or thing” as evidenced by the four-marker difference. Applicant submits that in paragraph [00061] the source of trophoblast stem cells simply refer to the source cells and MPSCs are not source cells themselves, but rather, MPSCs are the result of manipulation by precise culture conditions. The designed culture techniques conferred divergent marker signatures and characteristics different from those found in Gregori disclosing naturally occurring trophoblast stem cells. Applicant submit that example 1 identifies the seeding cell density needed and Example 7 discloses the framework used for culturing an evaluating the different MPSC cell lines. Examples 3 and 8 show divergent marker signatures resulting from the culture conditions of example 1 and 7. Example 3 shows specific makers whose statuses are different from the naturally occurring cells in cited references such as Gregori. Example 8 demonstrates opposite marker status with those of naturally occurring cells occurring cited references such as Gregori.
In response, the machine or transformation test as outlined in Bilski v Kappos (2010) procedure by which patent eligible subject matter is determined but rather the 2019 PEG which requires further evaluation. Further, Applicant is reminded claims are not to an MPSC culture or MSCP culture conditions but rather a population of MPSCs themselves. Example 1 states in [0077] of the PreGrant publication, “Lowering seeding density improved the number of population doublings for MPSC”. As such, Example 1 demonstrates that the population doubling achieved is a product of the culture conditions themselves and subject to change is conditions of the culture are changed. As such this particular characteristic as described by the specification occurs because of the culture conditions in which the naturally occurring MSCPs are placed and not a demonstration of a transformed MSCP cell with uniquely function property that occurs independent of the culture conditions. Figure 1 also shows that culturing conditions of differential media results in differential growth curves overtime. Again showing that characteristics of growth and PD are media dependent and not inherent unchanging properties associated with a cell transformation. Examples show marker expression are all only demonstrated under one culture condition and therefore the markers expressed by the MSCPs cannot be evaluated outside of this culture condition. Further, as described by Gregori in vivo a population of MSCPs of the same origin as the claimed cells also express HLA-G and HSP90 as claimed.
Applicant disagrees with Examiner interpretation of Gregori demonstrating that the EVT of Gregori express HLA-G. Applicant refers to the prior art of Loke to clarify that the EVT cells described by Gregori prior to and after differentiation are classical HLA Class I (A, B, and C) negative and that the instant MSCPs are positive for the classical HLA Class I A, B, C and non-classical HLA-G and HSP90. Thus the cells of the claims are different because their expression patterns are different.
In response, Applicant is not considering the breadth of the claims and furtherer is not considering fully considering the marked distinction requirement step 2B. It is again pointed out that the EVT cells are established MSCPs but in vivo of the same origin as the MSCPs of the claims. The difference between them is that one is in vitro culture conditions and one is in vivo culture conditions. Gregori does teach a population of EVTs that are HLA-G and HSP90 positive and is silent as to the expression of HLA-A, B, and C. Silent as to the expression of HLA-A, B, C does not mean negative. Applicant’s reference to Loke teaches that in vivo none of these markers are expressed in vivo but is silent as to which markers are expressed. Reciting the cell population is one that is MSCPs means that the cells have to have the functional characteristic known for MSCPs in vivo. So the structure of claimed cell population is one that has the same MSCP properties as the in vivo naturally occurring cell type. The distinction in questions is that the marker expression pattern are different from the naturally occurring cell that rises to a transformative level to consider the MSCP with these differential expression patterns are in fact a different cell. The claimed cell and the naturally occurring product ultimately both function as MSCP and Gregori shows that the MSCP in nature in their natural environment have conditions in which they do express HLA-G and HSP90. Even if the cells claimed express HLA-A, B, and C not seen in same cell when it is in vivo, this would not amount to a marked or transformative distinction because ultimately the cell is still structurally identified as a MSCP with the same stem cell properties unaffected by the expressed of HLA-A, B, C, and G, as well as HSP90.
Examiner further points how that as many as 20% of the population of MSCP can be negative for all of the recited markers which therefore means that the part of the claimed cell population is indistinguishable from the natural product. Regardless, the HLA markers and HSP90 do not appear to have any connect to the stemness of the MSCPs and does appears to arrive as a result of culture conditions that have a ability to change. As such, the distinction does not amount to a marked distinct as required under step 2B of the analysis.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632