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 .
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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/15/26 has been entered.
Claim Status
Applicant’s arguments and amendments dated 9/15/26 have been received and entered in the application.
Claims 1-2, 5-8, 11-12, 15, 20, 24, 27, 34, 38-40, 42-45 are currently pending and examined on the merits.
Claims 1, 6, 20, 34, 45 are currently amended.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
Claim Rejections - 35 USC § 103
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 6-8, 38-40, 42-45 is/are rejected under 35 U.S.C. 103 as being obvious over Rho et al., (1998) Cellular composition and viability of demi- and quarter-embryos made from bisected bovine morulae and blastocysts produced in vitro. Theriogenology, 50: pp. 885-895 (hereinafter Rho) in view of Silvestri, G. (2017) Novel approaches of generating and selecting high genetic merit in vitro produced pig and cattle embryos. Thesis, University of Kent (hereinafter Silvestri).
Regarding claims 6-7, 38-39, 45, Rho compares methods of bovine embryo splitting, including serial splitting (Abstract). Rho discloses mechanically bisecting a blastocyst with a microsurgical blade (Bisection and quality classification of embryos). In some embodiments, following 24 hours of culture, the demi-embryos are bisected a second time to produce quarter-embryos (Bisection and quality classification of embryos). Rho explains that serial bisection produced a similar quantity of transferable embryos to embryos bisected a single time (Discussion).
Regarding claim 40, embryos are cultured in M199 media containing Earle’s salts supplemented with sodium pyruvate, glutamine, antibiotics, and polyvinyl alcohol (Media).
Regarding claim 42, Rho discloses producing bovine morulae and blastocytes by in vitro fertilization (Embryo preparation).
Regarding claims 6, 45, Rho does not disclose disrupting the zona pellucida using non-mechanical means. Regarding claim 8, Rho does not disclose that the embryos are serially split at least two times. Regarding claim 43, Rho does not disclose that the embryos are selected based on genetic criteria.
Silvestri compares methods for splitting embryos to increase offspring (Abstract). Silvestri discloses that embryos may be serially split; an embryo may be split from an embryo derived from a previous split (1.4.2.9). Silvestri discloses serial splitting bovine embryos using three different strategies. In the first strategy, eight-cell stage embryos are split into two 4/8 splits (2.2.3.4, 4.4.6, 4.4.6.1, Fig. 2.5). Embryos that progress to form a blastocyst are split a second time via bisectioning (2.2.3.4, 4.4.6,4.4.6.1, Fig. 2.5). For the second strategy, two-cell stage embryos are split via disaggregation (2.2.3.5, 4.4.6). Embryos that demonstrate cleavage are disaggregated a second time (2.2.3.5, 4.4.6, 4.4.6.2). For the third strategy, embryos are disaggregated a third time to form third serial splits (2.2.3.5, 4.4.6, 4.4.6.2). Silvestri explains that triple embryo splitting results in a decrease in blastulation rate of the splits, but produces an increase in the net output of blastocysts (4.5.5).
Silvestri discloses that the embryos are subjected to enzymatic digestion or mechanical removal of the zona pelucida (ZP) followed by separation of the blastomere (1.4.2.1, Fig. 1.17). Silvestri explains that splitting at the cleavage stage embryo is that it can lead to the formation of a number of embryos equal to the number of blastomeres recovered (1.4.2.1). Alternatively, a blastocyst may be bisectioned by passing a fine bore pipette through an embryo to produce two demi-embryos (1.4.2.2, Fig. 1.18).
Silvestri further discloses that embryos may be biopsied for preimplantation genetic diagnosis, genetic screening, or genomic selection prior to splitting (1.6, 1.7, 1.9, Fig. 1.22).
As both Silvestri and Rho are directed to methods of splitting embryos, in particularly serial splitting, it would be obvious to one of ordinary skill in the art that the references could be combined. Regarding claims 6, 45, a skilled artisan would understand that the non-mechanical means could be used to disrupt the zona pellucida as Silvestri teaches that mechanical removal and enzymatic digestion are art recognized alternatives. Regarding claim 8, a skilled artisan would be motivated to combine the references for the successful production of multiple, optimized monozygotic embryos as taught by Rho. Regarding claim 43, a skilled artisan would be motivated to select embryos based on genetic criteria as application of a known technique to improve a similar method in the same way.
Response to Arguments
Applicant’s arguments and amendments dated 9/15/26 have been fully considered but are moot in part and not persuasive in part due to the new grounds of rejection necessitated by applicant’s amendments, and in view of applicant’s arguments. To the extent that the arguments are pertinent to the current grounds of rejection they are responded to below.
Claims 6-8, 38-40, 42-45 is/are rejected under 35 U.S.C. 103 as being obvious over Rho in view of Silvestri.
Applicant argues that the teachings of Silvestri that one of ordinary skill in the art would be motivated to use non-mechanical means, nor would there be a reasonable expectation of success (Response p11). Applicant argues that strategy A of Silvestri requires enzymatic disaggregation of an 8-cell stage embryo followed by mechanical bisection (Response p11-12). Applicant argues that Silvestri teaches that strategy A is not successful such that a skilled artisan would not be motivated to try enzymatic disruption at the more disruption resistant 16-cell stage (Response p12-13).
In response, Silvestri discloses multiple strategies for embryo splitting; Silvestri discloses each of bisectioning (2.2.3), serial splitting with disaggregation and bisectioning (2.2.3.4, i.e., Strategy A), and serial splitting with serial disaggregation (2.2.3.5, 4.4.6, i.e., Strategy B and C). Silvestri explains that both strategy B and C successfully produce higher numbers of blastocyst stage embryos as compared to single splitting strategies. Therefore, applicant’s assertions that Silvestri does not disclose enzymatic disruption alone, and that a skilled artisan would have no expectation of success, are considered without merit.
Allowable Subject Matter
Claims 1-2, 5, 11-12, 15, 20, 24, 27, 34 are allowed.
Conclusion
Claims 1-2, 5, 11-12, 15, 20, 24, 27, 34 are allowed. Claims 6-8, 38-40, 42-45 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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, Peter Paras can be reached at (571) 272-4517. 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.
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
