DETAILED ACTION
This action is in reply to papers filed 3/24/2026. Claims 1-2,6,9,12-15,17-19,21,24,26-27, 29 and 32 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240041010A1, Published 2/8/2024.
Withdrawn Rejection(s)
The 35 USC U.S.C. 102(a) (2) rejection of claims 1, 2, 6-7, 9, 12, 13, 17, 18, 19, 21, 27 as being anticipated by University of Tokyo (WO2017175745A1, Published 10/12/2017, Ref. 7 in IDS filed 5/4/2023) is withdrawn in view of amendments made to independent claims 1 and 24.
The 103 (a) rejection of claims 4, 14-15, 22, and 24 as being unpatentable over University of Tokyo (WO2017175745A1, Published 10/12/2017, Ref. 7 in IDS filed 5/4/2023) as applied to claims 1, 2, 6-7, 9, 12, 13, 17, 18, 19, 21, 27 and further in view of Ideta et al. (PgPub US20180116191A1, Published 5/3/2018) and Newman et al. (PgPub US20030079240A1, Published 4/24/2003) is withdrawn in view of amendments made to independent claims 1 and 24.
Maintained Rejection(s)
The 35 USC U.S.C. 102(a) (2) rejection of claims 26,29 and 32 as being anticipated by University of Tokyo (WO2017175745A1, Published 10/12/2017, Ref. 7 in IDS filed 5/4/2023) is maintained. Applicant’s arguments will be addressed following maintained rejection.
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)(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.
Prior Art Rejection 1
Claim(s) 26, 29 and 32 remain rejected under 35 U.S.C. 102(a) (2) as being anticipated by University of Tokyo (WO2017175745A1, Published 10/12/2017, Ref. 7 in IDS filed 5/4/2023). Although maintained, the rejection has been updated to only reflect claims that are still rejected.
Regarding claim 26 and claim 32, Univ Tokyo discloses a method for producing a non-human chimeric embryo (Pg. 11, second paragraph from bottom of page) with donor-derived germ cells, the method comprising: providing a host embryo comprising the inactivated primordial germ cell (PGC) specification gene and complementing the host embryo (Pg. 6/14, three paragraphs from bottom) with a donor ES cells pluripotent (Pg. 5/14, para. 3) cells to the chimeric embryo, wherein the germ cells of the chimeric embryo are exclusively derived from the donor (Pg. 3/14, para. 3). Univ Tokyo discloses a chimeric animal produced from said method (Pg. 4/14, para. 3+). Regarding claim 29, Univ Tokyo discloses the animal is a mouse, pig or cattle (Pg. 6/14, last paragraph).
Accordingly, Univ Tokyo discloses anticipates the claimed invention.
Applicant’s Arguments /Response to Arguments
Applicant argues: In an effort to expedite prosecution, and without acquiescing to the Examiner's rejection, claim 1 has been amended to recite in pertinent part, "complementing the host embryo at the 4- cell stage to 7-cell stage with a blastomere from a donor 2-cell stage to morula stage embryo to yield the chimeric embryo". Claim 24 has also been amended similarly.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Note that claim 26 has not been amended in the same manner as claim 1 or claim 24. See below
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Accordingly, the claims remain rejected.
Rejection(s) Necessitated by Amendments
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 2, 6 and 24 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 2 is copied below.
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However, claim 1 is drawn to the following:
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The metes and bounds of claim 2 are unclear because the inactivated PGC specification gene was limited to one of PRDM14, PRDM1 or NANOG in claim 1. Thus, the purpose of the inactivated PGC specification gene in claim 2 is wholly unclear.
Claim 6 refers to “the donor cells”. There is a lack of antecedent basis for this limitation as the phrase “donor cells” has been canceled in claim 1. See above.
Claim 24 is copied below.
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Note that at lines 3-4, claim 24 claims the guide RNA targets the PRDM14 gene or the PRDM1 gene. However, the claim has now been amended to recite the inactivated PGC specification gene is PRDM14, PRDM1 or NANOG. The inclusion of this new limitation is wholly confusing. First, there is no antecedent basis for an inactivated PGC specification gene in the claim. Note that there is no step of inactivating a PGC gene, let alone, any gene in the claim. Accordingly, the metes and bounds of the claim are wholly unclear.
Clarification is requested.
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.
Prior Art Rejection 2
Claims 1, 6, 9, 12-15, 17-19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over University of Tokyo (WO2017175745A1, Published 10/12/2017; previously cited) in view of Gleicher, N. (PgPub US20040123337A1, Published 6/24/2004) and Hai et al. (Cell Research volume 24, pages372–375 (2014)).
Regarding claim 1 (in-part) and claim 17, Univ Tokyo teaches a method for producing a non-human chimeric embryo (Pg. 11, second paragraph from bottom of page) with donor-derived germ cells, the method comprising: providing a host embryo comprising the inactivated primordial germ cell (PGC) specification gene and complementing the host embryo (Pg. 6/14, three paragraphs from bottom) with a donor ES cells pluripotent (as in claim 6) (Pg. 5/14, para. 3) cells to the chimeric embryo, wherein the germ cells of the chimeric embryo are exclusively derived from the donor (Pg. 3/14, para. 3). Univ Tokyo teaches a chimeric animal produced from said method (Pg. 4/14, para. 3+). With further regards to claim 1, Univ Tokyo teaches the inactivated PGC specification gene is PRDM14 (Pg. 3/14, last paragraph). Regarding claim 9, Univ Tokyo teaches the animal is a mouse, pig or cattle (Pg. 6/14, last paragraph). Regarding claim 12,Univ Tokyo teaches the inactivation of the PGC specification gene is accomplished by gene editing (Pg. 5/14, para. 34). Regarding claim 13, Univ Tokyo teaches the gene editing comprises use of a RNA-guided CRISPR-Cas (Pg. 8/14, para. 1-2). Regarding claim 18, Univ Tokyo teaches transferring the chimeric embryo into a recipient female animal; and allowing the transferred chimeric embryo to develop to term as a chimeric animal (Pg. 4/14, para. 3+). Regarding claim 19, Univ Tokyo teaches breeding the chimeric animal with a second animal to produce one or more progeny animals (Pg. 4/14, para. 3+). Regarding claim 21, Univ Tokyo teaches wherein the breeding comprises natural mating (Pg. 4/14, para. 2+).
And although Univ Tokyo does not explicitly teach the donor cells are from an elite animal, Univ Tokyo does teach the donor cells are from an animal "having a desired genetic modification" (Pg. 3/14, para. 3) which is reasonably interpreted to mean an elite animal. Thus, use of donor cells from an elite animal would have been prima facie obvious (as in claim 15).
However, Univ Tokyo does not teach a host 4-cell to 7-cell stage embryo and a blastomere from a donor 2-cell stage to morula stage embryo(as further in claim 1).
Before the effective filing date of the claimed invention, Gleicher taught a method for creating chimeric embryos, wherein blastomeres from a donor embryo at an early stage is removed and introduced into a recipient embryo at an early stage. The recipient embryo is then grown to a later stage of development. Approximately one to three blastomeres are removed from the donor embryo at Day 3 of development and introduced into a recipient embryo at Day 3 (Abstract). Gleicher teaches Day 3 to be 4-10 cell stage (Pg. 2, para. 36) (as further in claim 1).
And although Univ Tokyo teaches the inactivation of the PGC specification gene is accomplished by CRISPR, Univ Tokyo fails to teach injecting a zygote with a Cas protein and a guide RNA that targets the PGC specification gene (as in claim 14).
Before the effective filing date of the claimed invention, Hai et al. report the efficient generation of biallelic knockout pigs in one step by direct cytoplasmic injection of Cas9 mRNA and sgRNA into zygotes (as in claim 14) (Pg. 372, Col. 1, para. 2).
It would have been obvious to one of ordinary skill in the art that the pluripotent stem cells in the method of Univ Tokyo could comprise a blastomere of a 4-cell stage donor embryo according to Gleicher and that blastomore could be injected into a host embryo at a 4-cell cleavage stage because Gleicher achieved success with this protocol.
Prior Art Rejection 3
Claim 27 is rejected under 35 U.S.C. 102(a) (2) as being unpatentable over University of Tokyo (WO2017175745A1, Published 10/12/2017, Ref. 7 in IDS filed 5/4/2023; previously cited) as applied to claims 26, 29 and 32 and further in view of Chen et al. (Stem Cell Reports. 2014 Oct 11;3(5):892–904).
The teachings of Univ Tokyo are relied upon as detailed above. However, Univ Tokyo fails to teach the inactivated PGC specification gene is DAZL (as in claim 27).
Before the effective filing date of the claimed invention, Chen et al. taught that in the mouse, germline specification begins around E6.25, when the expression of PR domain proteins (PRDM1 and PRDM14) mediates the transcriptional suppression of the somatic differentiation program in the nascent primordial germ cells (PGCs). Shortly after the specification period, the importance of posttranscriptional regulation in germ cell maintenance becomes evident. For example, in mice lacking DND1 or NANOS3, both of which are germ cell-specific RNA binding proteins, PGCs are gradually lost by apoptosis starting at E8.5, when PGCs start to migrate toward the future gonads. Upon arrival in the gonad, DAZL (Deleted in azoospermia-like), a germ cell-specific RNA-binding protein, is essential for developing PGCs (Pg. 892, Col. 1). Chen notes that given the importance of DAZ family proteins in germ cells, much effort has been invested in elucidating the molecular mechanisms of Dazl function (Pg. 892, Col. 2). Towards this end, Chen demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation (Abstract).
When taking with the teachings of Univ Tokyo, wherein Univ Tokyo teaches a method comprising introducing pluripotent cells that possess the target genetic modification both in a paternal chromosome and a maternal chromosome into an animal embryo that loses its own reproductive cells in a developmental stage, one of ordinary skill in the art would have found it prima facie obvious to substitute the PRDM14 gene of Univ Tokyo with DAZl gene of Chen. The skilled artisan would have found it prima facie obvious to do so in order to further elucidate the role of DAZL gene in germ cells, an objective considered in Chen. A reasonable expectation was present in view of Chen’s identification of DAZL and PRDM14 as PGC markers during in vitro germ cell development.
Thus, the combination of Univ of Tokyo in view of Chen would have been prima facie obvious.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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 extension fee 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 date of this final action.
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632