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 .
Claims 1-8 are pending in the application. Claims 1-7 are withdrawn. Claim 8 is currently under examination.
This office action is in response to the amendment filed on 8/3/2025.
All previous rejection not reiterated in this office action are withdrawn.
Response to Amendment
The amendment to the claims filed on 8/3/2025 does not comply with the requirements of 37 CFR 1.121(c) because claims 1-7 do not have correct status identifier. As indicated in the previous office action, claims 1-7 are withdrawn from consideration, which should be identified with “withdrawn” or “withdrawn-currently amended.” Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
Since the reply filed on 8/3/2025 appears to be bona fide, applicant is given a time period same as the response period for replying to the present office action. For purpose of compact examination, the claim amendment filed on 8/3/2025 is examined for merits (for the elected invention claim 8).
Election/Restrictions
Applicant argues that claim 8 was included in the restriction groups in the parent application that was divided because Group I (claims 1-4, 6 and 7) includes synthetic chromosomes and cells comprising the synthetic chromosomes.
This argument is not persuasive because applicant elected Group I for examination in parent application 16/120,638. Even if claim 8 is in consonance with claim 4 of the parent application, there is no division between the subject matter of claim 8 of present application and elected invention of Group I in the ‘638 application. As such, the non-statuary double patenting rejections prohibition under 35 U.S.C. 121 does not apply.
Claim Rejections - 35 USC § 112
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.
Claim 8 is 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 is a new matter rejection.
Claim 8 is amended to recite that the isolated animal cell comprising a non-integrated synthetic chromosome acting as a multifunctional biosensor that comprises amplified ribosomal DNA. Applicant asserts that support for this amendment is found throughout the specification specially in paragraphs [0007]-[0008], [0039]-[0043], [0049] and [0054-[0057]). A reviewed of the cited paragraphs does not support the notion that the newly amended claim 8 is supported by the cited paragraphs. Specially, paragraphs [0007] and [0008] describes synthetic chromosomes that comprises different type of promoters, and do not mention amplified ribosomal DNA. Paragraphs [0039]-[0043] describes potential ways to use said synthetic chromosome to define status of a single cell, such as transferring the synthetic chromosome into human iPSC, differentiate said cells, and exposing the cell to different signals, which does not mention amplified ribosomal DNA. Paragraph [0049] describes a fourth approach for production of synthetic chromosomes that involves de novo chromosome generation by targeted amplification of specific chromosomal segments, which triggers large scale amplification of pericentromeric/ribosomal DNA region situated on acrocentric chromosomes. Paragraph [0054]-[0057] describes the lineage reporter synthetic chromosomes is transferred into human iPSCs, and uses fluorescent markers suitable for the in vitro analysis; specially, transferring lineage reporter synthetic chromosome into DG44 cells and detecting the GFP positive cell suing PCR and FISH following transfer; differentiation of the transfected iPSC to EBs; and the benefit of developing said iPSC and EB. The most relevant paragraph to the “amplified ribosomal DNA” is paragraph [0049], however, there is no additional teaching that the claimed cell is produced using said method. Paragraph [0053] simply states a BAC backbone vector was constructed using IN-Fusion cloning to contain blasticidin drug resistance and attB sits necessary for λINTR recombination. While paragraph [0049] states that “the amplification is triggered by co-transfection of excess DNA specific to the pericentric region of chromosomes, such as ribosomal RNA, along with DNA sequences that allow for site specific integration of target DNA sequences and also a drug selectable marker which integrates into the pericentric regions of the chromosomes,” there is no teaching in the present specification that the lineage reporter synthetic chromosome is mad by this method that may include amplified ribosomal DNA. Moreover, paragraph [0046] states the synthetic chromosomes of the present invention may be produced by any currently employed methods of synthetic chromosome production, give examples of “top down,” “bottom up,” and induced de novo chromosome generation method used in the art. Since paragraph [0049] is only one of the method may be used in producing the lineage reporter synthetic chromosome, and there is no record showing the lineage reporter synthetic chromosome is produced with the 4th method, the teaching from the present specification does not support an isolated animal cell comprising a synthetic chromosome that comprises amplified ribosomal DNA. Therefore, such amendment introduces new matter.
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.
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.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Suzuki et al (PLOS ONE, 2014, Vol.9, issue 10, pages 1-9), in view of Csonka et al (Journal of Cell Science, 2000, vol.113, pages 3207-3216). This rejection is necessitated by claim amendment.
Suzuki et al. teach a novel system for simultaneous or sequential integration of multiple gene loading vectors (GLV) into a defined site of a human artificial chromosome (title). Suzuki et al. teach integration of three GLVs comprising recombination sequences and reporters into human artificial chromosomes (HAC), which result in HAC that comprises loxp, Bxb1 attR, and φC31 attR, and expresses Venus, TdTomato and EGFP reporters in CHO cells (Figure 2 and legend). Suzuki further teaches that multiple applications of the technology for constructing HACs. Suzuki teaches “it could also be applicable to load multiple fluorescent gene cassettes under control of different lineage specific promoters to trace differentiation status by multi-color live imaging (page 5, 2nd col., 5-7, and Figure 6 and legend).
The difference between Suzuki et al. and the claimed invention is that Suzuki does not amplified ribosomal DNA in the synthetic chromosome.
Csonka teaches a method of making human satellite DNA-based artificial chromosomes in mammalian cells (title). Csonka demonstrates generating of a prototype human satellite DNA based artificial chromosome via amplification dependent de novo chromosome formation induced by integration of exogenous DNA sequences into the centrometric/rDNA region of human acrocentric chromosomes (abstract, and page 3211, 2nd col., 2nd paragraph). Csonka teaches coamplified rDNA sequences may provide a suitable chromatin environment for the expression of the integrated foreign genes (page 3214, 2nd col., 12-14).
It would have been obvious to an ordinary skilled in the art to integrating different reporters operably linked to different lineage specific promoters for monitoring cellular differentiation into human artificial chromosome as taught by Suzuki et al. The ordinary skilled in the art would have reasonable expectation of success because Suzuki teaches how to make HAC with different promoters (PGK, EF1 and CAG promoter driven EGFP, TdTomato, and Venus expression units, page 6, bridging paragraph) operably linked to different fluorescent reporters. Integrating different promoter into an existing HAC does not matter how the HAC is made based on the teaching from Suzuki. The ordinary skilled in the art may use the method taught by Csonka et al. to make a HAC prior to the integration of multiple promoter as taught by Suzuki. The ordinary skilled in the art would be motivated to use the method taught by Csonka et al. because Csonka teaches said method comprises coamplified rDNA sequences may provide a suitable chromatin environment for the expression of the integrated foreign gene. Therefore, the claimed invention would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11851719 in view of Csonka. This rejection has been rewritten to address the amendment.
The claimed eukaryotic synthetic chromosome of claim 1 of the ‘719 patent meets almost all limitation of the synthetic chromosome claimed in claim 8 of the present application except that it does not recite an amplified ribosomal DNA region.
The teaching from Csonka has been discussed above.
It would have been obvious to an ordinary skilled in the art to use the method taught by Csonka et al. to make the eukaryotic synthetic chromosome before integrating different promoter constructs into said HAC. The ordinary skilled in the art would be motivated to use the method taught by Csonka et al. because Csonka teaches said method comprises coamplified rDNA sequences may provide a suitable chromatin environment for the expression of the integrated foreign gene. Therefore, the claimed invention of claim 8 would not have been patentably distinct from claim 1 of ‘719 patent.
Conclusion
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 CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637