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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/09/2026 has been entered.
Claim Status
In the submission filed 06/09/2026, claims 9 and 12 have been amended, claim 18 has been new added. Accordingly, claims 9-18 are pending and under current examination.
Priority
The instant application is a national stage entry of PCT application PCT/JP2021/014365, filed 09/30/2022 under 35 USC 371. Acknowledgment is made of applicant's claim for foreign priority based on applications JP2020-067038 (filed in Japan on 04/02/2020) and JP2020-199458 (filed in Japan on 12/01/2020).
Status of Prior rejections / Response to Arguments
The rejection to claims 9-17 under 35 U.S.C.112(a) New matter is maintained:
In the submission filed 06/09/2026, Applicant has acknowledged that the specification as filed discloses that the CD133- positive, SSEA-3-positive, and CD34-negative pluripotent stem cells are present in the embryo- derived cells at a level of approximately 2.0%, not 50% or more (Remarks, p6). However, Applicant has asserted that it is common technical knowledge for one of ordinary skill in the art to concentrate or proliferate isolated pluripotent stem cells to over 50% (Remarks, p6), in the way such as FACS and MACS (Remarks, p8). Therefore, even if only 2.0% of the cells disclosed in the specification were clearly CD133-positive, SSEA-3-positive, and CD34-negative pluripotent stem cells, the specification further describes separation by FACS in the Examples, and it was common technical knowledge that highly efficient purification could be achieved using standard techniques such as those discussed above (Remarks, p8).
In response, the Examiner respectfully submits that as stated in Office Action mailed 04/20/2026, Applicant is reminded that new matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP 608.04(a). In instant case, as Applicant acknowledges, the specification originally discloses that there are only 2% of CD133-positive, SSEA-3 positive, and CD-34 negative pluripotent stem cells in bone marrow-derived Muse cells (which are isolated from embryonic tissue), but not as high as 50% or more as claimed. Applicant asserts this percentage can be achieved by concentration or proliferation. However, firstly, instant claims do not limit that this percentage (50% or more) is achieved by concentration or proliferation. Secondly, it is not disclosed in the specification that the concentration or proliferation of the cells would achieve this specific percentage. Without the support, the introducing of this specific percentage is a new matter. Furthermore, MPEP 2163.07 states “[A]mendments to an application which are supported in the original description are NOT new matter: rephrasing; (correct an) obvious errors; inherent function, theory, or advantage; incorporation by reference”. In instant case, the amendment to the claims adding a new specific percentage is not under any of these situations. Therefore, the limitation that the cell population isolated from embryonic tissue includes 50% or more of CD133-positive, SSEA-3-positive and CD-34 negative cells is considered as a new matter. The rejection is maintained in modified form to address amended limitations.
Moreover, a new ground of rejection under 35 U.S.C. 101 is set forth since the cell population is obtained by isolating the cell population with specific cell markers (CD133-positive, SSEA-3-positive and CD-34 negative) from an extraembryonic tissue or embryonic tissue, it is a nature-based product. The enrichment of the cell population (i.e., by FACS and MACS) does not transform the nature-based mixture into a patent-eligible application.
New/Modified Rejections
Modified Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 9-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This new matter rejection is modified as necessitated by Applicant’s amendment.
In the submission, Applicant’s amendment to the independent claim 9 limits the pluripotent stem cells isolated from an extraembryonic tissue or embryonic tissue are CD133- positive, SSEA-3 positive, and CD-34 negative, and includes 50 % or more of CD133-positive cells in the pluripotent stem cells. The Specification discloses the human amnion-derived SSEA-3-positive cells (cell population isolated from an extraembryonic tissue), the double positivity of SSEA-3 and CD133 was 71.5% (p39, L4-6). Besides, the specification teaches CD34 was not expressed in the human amnion-derived MSCs and human amnion-derived SSEA-3-positive cells, as in the bone marrow-derived MSCs and Muse cells (p39, L8-9). These teachings disclose a cell population (human amnion-derived SSEA-3-positive cells) comprising >50% (i.e., 71.5%) of the pluripotent stem cells are CD133- positive, SSEA-3 positive, and CD-34 negative. However, there is no support about a cell population isolated from embryonic tissue comprising 50% or more of the pluripotent stem cells having CD133- positive, SSEA-3 positive, and CD-34 negative. The specification teaches bone marrow-derived MSCs and Muse cells do not express CD34 (p39, L8-9), but only 2.0% of the SSEA-3-positive cells in the bone marrow-derived Muse cell was CD133-positive. The specification does not specifically teach the cell surface markers of other embryonic tissue such as peripheral blood, fat, and skin. Therefore instant disclosure does not have support for the cell population isolated from an embryonic tissue comprising 50% or more of the CD133- positive, SSEA-3 positive, and CD-34 negative pluripotent stem cells.
New Claim Objections
Claim 18 is objected to because of the following informalities: Claim 18 recites “the pluripotent stem cell is enriched by flow cytometry” needs to be “the pluripotent stem cells are enriched by flow cytometry”. Appropriate correction is required.
New 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.
Claim 18 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 18 recites “the pluripotent stem cell is enriched by flow cytometry using a CD133 antibody” renders instant claim indefinite. It is not clear whether the claim limits that the pluripotent stem cells isolated from an extraembryonic tissue or embryonic tissue are enriched by flow cytometry using a CD133 antibody to the percentage of 50% of CD133-positive, SSEA-3- positive, and CD-34 negative cells in the cell population, or further enrich the pluripotent stem cells which include 50 % or more of CD133-positive cells to a higher percentage. The scope of the claim is therefore indefinite.
New 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 9-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (a product of nature) without reciting additional elements that amount to significantly more than the exception.
The claim 1 is directed to a composition of matter (a cell population comprising pluripotent stem cells that are CD133-positive, SSEA-3- positive, and CD-34 negative, wherein the cell population has been isolated from an extraembryonic tissue or embryonic tissue, and includes 50 % or more of CD133-positive cells in the pluripotent stem cells). As such, the claim falls within a statutory category (Step 1: YES). However, the claimed composition recites only nature-based components, namely pluripotent stem cells that are CD133-positive, SSEA-3- positive, and CD-34 negative which are isolated from an extraembryonic tissue or embryonic tissue. Therefore the composition is a nature-based product that must be analyzed to determine whether it is “markedly different” from its naturally occurring counterparts under the markedly different characteristics analysis set forth in MPEP 2106.04(c) and related guidance.
Under Step 2A, Prong 1, the claim recites a nature-based product limitation, namely pluripotent stem cells that are CD133-positive, SSEA-3- positive, and CD-34 negative which been isolated from an extraembryonic tissue or embryonic tissue. Under Step 2A, Prong 2, the pluripotent stem cells that are CD133-positive, SSEA-3- positive, and CD-34 negative which been isolated from an extraembryonic tissue or embryonic tissue is compared to its closest natural counterparts, which are CD133-positive, SSEA-3- positive, and CD-34 negative pluripotent stem cells in an extraembryonic tissue or embryonic tissue by itself. The claim does not positively recite any structural, functional, or other property of the mixture that is different from, or improved over, the properties of CD133-positive, SSEA-3- positive, and CD-34 negative pluripotent stem cells in an extraembryonic tissue or embryonic tissue as they occur in nature. The CD133-positive, SSEA-3- positive, and CD-34 negative pluripotent stem cells in the cell population as claimed remain as pluripotent stem cells, there is no indication in the claim of a change in structure (e.g., fractionation, chemical modification, or formation of a new substance) or of a new functional characteristic (e.g., have the ability to differentiate to other cell types in addition of triploblastic-lineage cells) that is markedly different from the natural products themselves. Merely isolating and collecting natural products, even at a non-naturally occurring ratio (i.e., herein 50%or more), does not by itself confer markedly different characteristics when the components retain their natural properties, as explained in USPTO examples and case law applying the product-of-nature exception. Accordingly, the claimed composition is directed to a product-of-nature judicial exception (Step 2A: YES).
Under Step 2B, the claim is evaluated to determine whether any additional elements, individually or in combination, amount to significantly more than the product-of-nature exception. The only elements in the claim are the nature-based product components (CD133-positive, SSEA-3- positive, and CD-34 negative pluripotent stem cells isolated from an extraembryonic tissue or embryonic tissue) and the percentage of CD133-positive cells (50% or more) in the pluripotent stem cells. The specified percentage of CD133-positive cells in the pluripotent stem cells merely reflects routine optimization or selection of concentrations for a known purpose (i.e., enrichment of certain type of cells) and does not add a meaningful limitation that transforms the nature-based mixture into a patent-eligible application. The claim as a whole therefore does not include any additional features that integrate the product-of-nature exception into a practical application, nor does it add an inventive concept sufficient to amount to significantly more than the judicial exception itself.
Moreover, the depending claims are further limiting the source of the CD133-positive, SSEA-3- positive, and CD-34 negative pluripotent stem cells (claims 10-13) and the characteristics of the population of cells (claims 14-16). Dependent claim 17 teach a regenerative medicine comprising the cell population, but with no additional components beyond this nature-based product components (CD133-positive, SSEA-3- positive, and CD-34 negative pluripotent stem cells isolated from an extraembryonic tissue or embryonic tissue). Dependent claim 18 is directed to an enrichment of the pluripotent stem cells by flow cytometry. For these reasons stated above, claim 9 and the dependent claims 10-18 are rejected under 35 U.S.C. 101 as being directed to a judicial exception (a product of nature) without reciting additional elements that amount to significantly more than the exception.
Related Prior arts
As stated in the office action mailed 01/09/2026, instant claims are directed to a cell population comprising pluripotent stem cells that are CD133-positive, SSEA-3 positive, and CD-34-negative, wherein the cell population has been isolated from an extraembryonic tissue or embryonic tissue, and includes 50 % or more of CD133-positive cells in the pluripotent stem cells. Ramuta et al. (Cell Transplant. 2018 Jan;27(1):77-92) and Pavon et al. (Oncotarget. 2016 Jun 28;7(26):40546-40557) are considered as two closet prior arts. Ramuta et al. teach human amniotic membrane (hAM) and amniotic membrane–derived cells (including human amniotic epithelial cells [hAECs] and human amniotic mesenchymal stromal cells [hAMSCs]) (Abstract and p77, left column). The hAMSC layer consists of a mixture of amniotic mesenchymal stromal cells (CD34+) and the mature mesenchymal stromal fibroblasts (CD34-). A minor fraction (less than 10%) of the mature mesenchymal stromal fibroblasts (CD34-) express CD117, CD133, CD146, CD201, SSEA-1, SSEA-3, and Globo H as well (p78, right column). However, the CD34- mature mesenchymal stromal fibroblasts are not pluripotent stem cells, and only less than 10% of the CD34- mature mesenchymal stromal fibroblasts express CD133 and SSEA-3. Pavon et al. teach highly purified, neurosphere-forming CD133+ cells, obtained from human glioblastomas, express the cell marker profile characteristics of MSCs and the pluripotency markers, SSEA-1, Mush-1 and Nanog (p40547, right column). Pavon et al. teach flow cytometry analyses showed that the CD133+ cells highly expressed CD44 (94.0%) and CD90 (94.4%) (Figure 1D, 1E). In addition, a percentage of these cells also co-expressed CD44 and SSEA-3 (99.8%), as well as Mush-1 and Nanog (96.7%) (parag 40547, right column), the CD133+ cells did not express high levels of either HLA-DR or the hematopoietic and vascular cell markers CD14, CD31, CD34, CD45 and CD106 (parag 40547, right column). However, though the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells (see Abstract), they are not pluripotent stem cells which can form any cell type in the body. Therefore the claimed CD133-positive, SSEA-3 positive, and CD-34-negative pluripotent stem cells in instant claims are considered novel and art free.
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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