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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to applicant’s amendment and response filed 06/24/2026.
Claims 7, 10, 13-14, 16-17, 19 and 20 are currently pending in the application. Claim 7 is amended, no new claims are added and no claims are canceled as set forth in the claim set filed 06/24/2026.
Claims 13 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/10/2022.
Therefore, claims 7, 10, 16, 17, and 19-20 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2018/067811, filed July 02, 2018.
Applicant’s claim for the benefit of a prior-filed foreign patent EP17305841.3 filed June 30, 2017 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is June 30, 2017.
Response to arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(a)
The rejection of claims 7, 10, 13-14, 16-17, 19 and 20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn.
Applicant’s arguments and amendments filed 06/24/2026 have been considered and are persuasive. Particularly, Applicant’s amendments narrow the scope of the invention to only small interfering molecules and a nonproteasome-degradable Geminin protein with a specific sequence.
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claims 7, 16 and 17 remain rejected under 35 U.S.C. 103 as being unpatentable over Chandrasekaran (MOLECULAR AND CELLULAR BIOLOGY, Nov. 2011, Vol 31, No. 22, p. 4405–4416) in view of Xouri ( The EMBO Journal (2007) 26, 1303–1314)
Regarding claim 7, 16, and 17, Chandrasekaran teaches contacting a small interfering molecule inhibiting Cdt1 (i.e. siRNA) with HeLa cells (i.e. somatic diploid cells) which are synchronized in early S phase to control the stability and activity of cdt1 (p. 4405, 2nd column; p. 4406, 1st column; p. 4408, Fig 3C). Chandrasekaran additionally teaches HCT-116 cells (i.e. somatic cell) which are contacted with siRNA targeting cdt1 (Fig 7A). HCT-116 cells are known in the art to be readily synchronized in G1 phase, and for a different study involving p38 and JNK in the same paper are synchronized in G1 phase (p. 4412, 1st column; 4413, 1st column).
However, Chandrasekaran does not explicitly teach siRNA for cdt1 contacted with synchronized G1 cells in the G1 phase.
Xouri teaches Cdt1 has dynamic interactions with geminin and chromatin during G1 phase (Abstract). Licensing is temporally limited to only G1 phase and that overexpression of cdt1 alone in mammals is enough to induce re-replication (p. 1303, 2nd column). Xouri further teaches that Geminin inhibits Cdt1 activity and expression of geminin during G1 phase could sequester cdt1 from chromatin (p. 1304, 1st column). The cells in Xouri’s study of cdt1 in G1 phase with its inhibitor Geminin are synchronized in mitosis and are released into a synchronous cell cycle with data taken as the cells progressed into G1 (p. 1306, 1st column; Figure 1 description).
It would have been obvious to one of ordinary skill in the art to contact the siRNA for cdt1 as taught by Chandrasekaran with synchronized G1 cells as taught by Xouri instead of S phase synchronized cells. An artisan would have been motivated to contact the siRNA for Cdt1 in G1 phase as it is known in the art that licensing is temporally limited to only G1 phase and that overexpression of cdt1 alone in mammals is enough to induce re-replication (Xouri; p. 1303, 2nd column). This highlights how important Cdt1 is in G1 phase and therefore, an artisan would be motivated to study synchronized cells in G1 phase. Moreover, Xouri teaches studies involving inhibitors of cdt1 such as geminin contacting somatic cells in G1 phase from a synchronized mitosis are known in the art (Figure 1 description; p. 1306, 1st column). Therefore, applying another inhibitor of the activity of cdt1 such as siRNA to Cdt1 in G1 phase would be obvious.
Regarding the intended use limitation in the preamble, “producing in vitro mammalian somatic haploid cells from mammalian somatic diploid cells” in Claim 7, and the limitation of being capable of mitosis in Claim 16, Chandrasekaran and Xouri do not explicitly state that the method is for producing haploid cells. However, each and every method step has been described by Chandrasekaran and Xouri, therefore the result of producing haploid cells in vitro has a predictable expectation of success from the method itself and the characteristic recited in Claim 16 is an inherent characteristic to the haploid cells produced.
Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims."
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claim 10 remains rejected under 35 U.S.C. 103 as being unpatentable over Chandrasekaran (supra) in view of Xouri (supra) as applied to claims 7, 16 and 17, and in further view of Li (Cell Stem Cell 14, 404–414; previously cited).
The combined teachings of Chandrasekaran and Xouri make obvious a method of producing haploid cells through contacting a G1 synchronized somatic diploid cell population with siRNA for Cdt1 as discussed above and incorporated here in its entirety.
However, regarding claim 10, Chandrasekaran and Xouri do not teach that the cells produced are made into an isolated haploid cell line.
Li teaches that haploid cells contain only one set of allelic genes of the normal diploid cells, and they therefore have the advantage for fast functional gene identification and have been used for genetic screening in yeast and human KBM-7 leukemia cells (p. 404, bridging paragraph).
Based on such teachings, it would have been obvious to one of ordinary skill in the art to take the cells of Chandrasekaran and Xouri which inherently are haploid based on the method described and create a cell line from said haploid cells as taught by Li with a reasonable expectation of success. An artisan would have been motivated to do so as Li teaches haploid cells have the advantage for fast function gene identification (p. 404, 1st column).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
In response to Applicant’s arguments and amendments regarding the 103 rejections filed 06/24/2026,
Applicant’s arguments and amendments filed 06/24/2026 have been considered, however they are not persuasive.
Applicant argues that Chandrasekaran is distinguishable from the claimed method. Applicant reiterates various facts of Chandrasekaran about Cdt1 protein and then states “Chandrasekaran therefore proposes a model in which the activity of p38/JNK kinases during the G2 phase of the cell cycle allows Cdtl to accumulate in a stable but low-activity form. This mechanism allows the cell to accumulate Cdtl in preparation for the next cell cycle, while preventing it from prematurely initiating a new round of DNA replication, thereby preserving genomic integrity. In summary, Chandrasekaran demonstrates a sophisticated regulatory mechanism for Cdtl, in which phosphorylation by stress kinases renders it stable but inactive, and uses siRNAs in human somatic cells to achieve this.” Moreover, “Chandrasekaran does not disclose the use of siRNA targeting the Cdtl protein in the context of cells synchronized in the G1 phase.”
Examiner agrees that the primary reference does not disclose contacting the synchronized cells in G1 phase. As discussed in the above 103 rejection, Xouri is utilized to provide teaching, suggestion and motivation for that limitation which in combination would provide a reasonable expectation of success to an artisan. Moreover, Chandrasekaran teaches that the cells they utilize are readily synchronized in G1 phase. The rejection is based on the combination of references as discussed below.
Applicant reiterates various components of Xouri and the aim of the study in examining the behavior of Cdt1 protein in specifically G1 phase of the cell cycle to demonstrate that Xouri does not cure the deficiency of Chandrasekaran. Moreover, Applicant states “Xouri does not indicate in any way that the cell cycle continues after total inhibition of Cdtl by geminin in G1 phase. Xouri describes the interaction of CDT1 with chromatin with or without geminin. The impact of Geminin or CDT1 dysregulation on cell cycle progression has not been studied at all. In fact, CDT1 activity is not inhibited at any point. These experiments, therefore, cannot predict that mitosis could occur in the absence of replication. This is the key point of the presently claimed method.”
First, Examiner states the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Xouri provides teaching, suggestion and motivation to contact siRNA for Cdt1 in a G1 phase. This is a modification of the primary reference which already contacts the siRNA with cells in S phase. Xouri as discussed by Applicant, demonstrates that G1 phase is a critical part of Cdt1 activity. Therefore, as discussed in the above 103 rejection, an artisan would have been motivated to contact the siRNA for Cdt1 in G1 phase as it is known in the art that licensing is temporally limited to only G1 phase and that overexpression of cdt1 alone in mammals is enough to induce re-replication (Xouri; p. 1303, 2nd column). This highlights how important Cdt1 is in G1 phase and therefore, an artisan would be motivated to study synchronized cells in G1 phase. Moreover, Xouri teaches studies involving inhibitors of cdt1 such as geminin contacting somatic cells in G1 phase from a synchronized mitosis are known in the art (Figure 1 description; p. 1306, 1st column). Therefore, applying another inhibitor of the activity of cdt1 such as siRNA to Cdt1 in G1 phase would be obvious. While Applicant argues that Xouri “cannot predict that mitosis could occur in the absence of replication. This is the key point of the presently claimed method”, this is an intended outcome of the steps made obvious by the combination of references. Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) provides "that since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims." While the outcome may or may not be predictable, the method steps have a reasonable expectation of success within the claimed method and through the combination of references.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
Claims 19 and 20 recite SEQ ID NO: 9 and 10 which are free of the prior art as previously indicated in the Final Rejection filed 09/10/2025.
Conclusion
Claims 7, 10, 16 and 17 are rejected.
Claims 19 and 20 are objected to.
No claims are 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA CONNORS whose telephone number is (571)272-7010. The examiner can normally be reached Monday - Friday (9AM-5PM).
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 LEAVITT can be reached on (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.
/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
Prosecution Insights