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 .
Claim Status
Claims 1-9 are pending in the instant Application.
Applicant’s election of the invention of group I drawn to a trophoblast stem cell-like cell (claims 1-5) in the reply filed on 05 December, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 6-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1-5 are pending and under examination in the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2020/027766, filed 17 July, 2020.
The earliest possible priority for the instant application is 17 July, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 13 January, 2023, 28 March, 2024, 03 September, 2024, and 24 February, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The Drawings submitted on 13 January, 2023 are accepted by the Examiner.
Claim Objections
Claims 1-5 are objected to because of the following informalities: Abbreviations/acronyms need to be spelled out upon their first encounter in the claims (for example: SALL4, MYC). Appropriate correction is required.
Claim Interpretation
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The second clause of claim 1, “which is induced from a trophoblast cell derived from a placenta of or after the second trimester of pregnancy”, is product-by-process language. There is no indication in the claims or the instant specification of what structures distinguish a trophoblast cell derived from a first trimester placenta from an identically-named cell derived from a second or third trimester cell. Thus, for the purpose of applying prior art, a trophoblast cell from a placenta of the first trimester is interpreted as being identical to a trophoblast cell from a placenta of the second or third trimester.
Claim Rejections - 35 USC § 112
Claims 1-5 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.
Claim 1 recites “a trophoblast cell derived from a placenta”. The metes and bounds of this recitation are unclear because it is unclear what steps must be taken for a trophoblast cell to be derived from a placenta. This rejection could be overcome by replacing “derived from” with “isolated from”. Claims 2-5 are further rejected for their dependency on a rejected base claim.
Claim 3 recites two alternative properties of the cell of claim 1 without reciting a corresponding structure responsible for said properties. Consequently, claim 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: an exogenous gene functionally linked to a second exogenous inducible promoter, wherein the exogenous gene is at least one selected from the group consisting of an exogenous p53 dominant negative gene and an exogenous MYC gene” as recited in claim 4.
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 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Okae, Hiroaki, et al., Cell stem cell 22.1 (2018): 50-63, hereinafter “Okae”, Of Record on the IDS submitted 13 January, 2023 in view of US2019/0112575, published 18 April, 2019 (hereinafter “Takahashi”), Zhang et al., Nature cell biology 8.10 (2006): 1114-1123, hereinafter “Zhang”, Of Record, Miller, et al., Development 143.17 (2016): 3074-3084, hereinafter “Miller”, and US20140342369 (hereinafter “Elling”).
Regarding claim 1, Okae teaches the differentiation of cytotrophoblast cells into trophoblast stem cells (Okae, page 50, fourth paragraph). Okae teaches that the human placenta is comprised of cytotrophoblast cells, extravillous cytotrophoblast cells, and syncytiotrophoblast cells (Okae, page 50, first paragraph). Okae also teaches the differentiation of the trophoblast stem cells into syncytiotrophoblast cells and extravillous trophoblast cells (Okae, Figure 2). Thus, Okae teaches trophoblast stem cells having potential to differentiate into a placenta-constituting cell. Regarding the product-by-process language in claim 1, Okae teaches first trimester trophoblast cells as the starting cells (Okae, page e3, “Isolation of trophoblast and stromal cells”). Trophoblast stem cells induced from a trophoblast cell derived from a placenta of or after the second trimester of pregnancy are interpreted as being substantially identical to the trophoblast stem cells derived from a trophoblast cell of a first trimester placenta as in Okae (See claim interpretation above).
Okae does not teach a trophoblast stem cell comprising a SALL4 gene functionally linked to a first exogenous inducible promoter.
Miller teaches embryonic stem cells comprising a SALL4 gene functionally linked to an inducible promoter (Miller, Figure 2). Miller also teaches that the dosage of SALL4 within cells is very important because too little might inappropriately activate genes while too much could interfere with expression of lineage-specific genes (Miller, page 17, first partial paragraph).
Zhang teaches that reducing SALL4 activates transcription of Pou5f1 which encodes Oct4 and is important for early cell fate decisions (Zhang, Abstract). Zhang also teaches that reduction in SALL4 leads to specification of embryonic stem cells into trophoblast cells (Zhang, page 1, third paragraph). Zhang also teaches that SALL4 is required to appropriately regulate Oct4 levels to maintain pluripotent cells (Zhang, page 8, fourth paragraph).
Elling teaches that trophoblast stem cells can be converted into ES-like pluripotent stem cells when overexpressing Oct4 (Elling, [0055]).
Thus, a person having ordinary skill in the art would have known from the teachings of Elling, Zhang, and Miller that (1) trophoblast stem cells and ES cells are related pluripotent stem cells which are connected through Oct4 activity, (2) SALL4 is required to appropriately regulate Oct4 levels to maintain pluripotency, and (3) SALL4 can be functionally linked to an inducible promoter to control the dosage of SALL4 within cells which is very important because too little might inappropriately activate genes while too much could interfere with expression of lineage-specific genes.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have used an inducible promoter to express SALL4 as taught by Miller in the trophoblast stem cells of Okae and to have arrived at the invention in claim 1 with a reasonable expectation of success because they would have been motivated to do so to control the dosage of SALL4 in order to appropriately regulate Oct4 levels in the cells to maintain pluripotency as taught by Zhang and Elling. There would have been a reasonable expectation of success in doing so insofar as a person having ordinary skill in the art would have reasonably expected an inducible SALL4 gene to allow for the regulation of Oct4 in trophoblast stem cells just as it does in ES cells because Elling teaches that trophoblast stem cells are related to ES cells through Oct4 activity.
Regarding claim 2, the SALL4 of Zhang is an exogenous SALL4 (Zhang, page 8, “Plasmid construction”).
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Okae, Hiroaki, et al., Cell stem cell 22.1 (2018): 50-63, hereinafter “Okae”, Of Record on the IDS submitted 13 January, 2023, Zhang et al., Nature cell biology 8.10 (2006): 1114-1123, hereinafter “Zhang”, Of Record, Miller, et al., Development 143.17 (2016): 3074-3084, hereinafter “Miller”, and US20140342369 (hereinafter “Elling”) as applied to claims 1-2 above, and further in view of US2019/0112575, published 18 April, 2019 (hereinafter “Takahashi”).
As discussed above, Okae, Miller, Zhang, and Elling render prima facie obvious the invention of claims 1.
Regarding claims 3-5, neither Okae, Miller, Elling, nor Zhang teaches the activity of p53 is suppressed or the expression of a MYC gene is promoted, or wherein the trophoblast stem cell further comprises an exogenous p53 dominant negative gene or an exogenous MYC gene.
Takahashi teaches an assortment of reprogramming factors that have been used in the art to induce somatic cells into pluripotent stem cells (Takahashi, [0033]). Takahashi specifically teaches SALL4, dominant-negative form p53, and Myc as several reprogramming factors that have been used in the art to induce somatic cells into pluripotent stem cells (Takahashi, [0033]). Takahashi teaches the production of induced pluripotent cells by introducing MYC and a dominant-negative form of p53 (Takahashi, [0149]). Takahashi teaches that dominant-negative form p53 is an inhibitor of p53 (Takahashi, [0034]). Thus, Takahashi suggests to a person having ordinary skill in the art to express dominant-negative form p53 or MYC alongside SALL4 to induce a somatic cell into a pluripotent cell.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have expressed p53 or MYC alongside SALL4 in the trophoblast stem cells of Okae, Miller, Elling, and Zhang and to have arrived at the invention claimed in instant claims 3-5 with a reasonable expectation of success because Takahashi suggests such a combination and such reprogramming factors would be reasonably expected to induce pluripotency.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MARIA G LEAVITT can be reached at 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA MARVICH/Primary Examiner, Art Unit 1634