DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 10/27/2025 in response to the Non-Final Rejection mailed on 06/26/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 5, 11-14 and 17 are cancelled.
4. Claims 1-4, 6-10, 15-16, and 18 are pending.
5. Applicant’s remarks filed on 10/27/2025 in response to the Non-Final Rejection mailed on 06/26/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Nucleotide and/or Amino Acid Sequence Disclosures
6. The objection to the drawings and specification under 37 CFR 1.821-1.825 is withdrawn in view of applicants’ updated sequence listing, replacement drawings and amendment to the specification filed on 10/27/2025 to include appropriate sequence identifiers.
Specification
7. The objection to the specification for embedded hyperlinks is withdrawn in view of applicants’ amendment to the specification to remove said hyperlinks.
Claim Rejections - 35 USC § 112(b)
8. The rejection of claims 5 and 17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for indefiniteness is withdrawn in view of applicants’ amendment to the claims to cancel claims 5 and 17.
9. Claims 1-4, 6-10, 15-16, and 18 are newly 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. This new grounds of rejection is necessitated by applicants’ amendment to the claims.
Regarding claim 1 (claims 2-4, 6-10, 15-16, and 18), there is insufficient antecedent basis for the limitation “the unmodified cell” in the claim. It is suggested that applicants clarify the meaning of the claims.
Claim Rejections - 35 USC § 112(a)
10. The written description rejection of claims 1-11 and 15-18 under 35 U.S.C. 112(a) is withdrawn in view of applicants’ amendment to claim 1 to recite “one or more DNA repair genes in the cells selected from XRCC6, ATM, PRKDC, RAD1, TP53, FANCM, MDM2, PTTG1, WRN, and UVSSA or reverting a silencing of one or more DNA repair genes in the cell selected from MCM7, PPP2R5A, PIAS4, PBRM1, and PARP2” and amendment to cancel claims 5, 11 and 17.
11. The scope of enablement rejection of claims 1-11 and 15-18 under 35 U.S.C. 112(a) is withdrawn in view of applicants’ amendment to claim 1 to recite “one or more DNA repair genes in the cells selected from XRCC6, ATM, PRKDC, RAD1, TP53, FANCM, MDM2, PTTG1, WRN, and UVSSA or reverting a silencing of one or more DNA repair genes in the cell selected from MCM7, PPP2R5A, PIAS4, PBRM1, and PARP2” and amendment to cancel claims 5, 11 and 17.
Claim Rejections - 35 USC § 102
12. The rejection of claims 5 and 17 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lee et al. (US 2019/0300859 A1, priority to 04/02/2018; cited on IDS filed on 09/06/2022) is withdrawn in view of applicants’ amendment to the claims to cancel claims 5 and 17.
13. The rejection of claims 1-4, 6-10, 15, and 18 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lee et al. (US 2019/0300859 A1, priority to 04/02/2018; cited on IDS filed on 09/06/2022) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims.
14. As amended, claims 1-4, 6-10, 15, and 18 are drawn to a method of preparing a cell for expression of a gene of interest into a recombinant protein, comprising modifying the cell by reverting a mutation of one or more DNA repair gene in the cell selected from XRCC6, ATM, PRKDC, RAD1, TP53, FANCM, MDM2, PTTG1, WRN, and UVSSA or reverting a silencing of one or more DNA repair genes in the cell selected from MCM7, PPP2R5A, PIAS4, PBRM1, and PARP2, wherein the cell is a CHO cell and the cell with a reverted mutation has an improved double strand break repair and/or genome stability, compared to the expression in the unmodified cell.
15. With respect to claim 1, Lee et al. teach a method of preparing a CHO cell for expression of a gene of interest, comprising heterologous expression of a double stranded DNA repair protein from a Chinese hamster cell by transforming into a CHO cell containing a mutation in said DNA repair gene (interpreted as reverting a mutation), wherein the one or more DNA repair gene targeted by reverting mutation are XRCC6, LIG4, PALB2, PARP1 and PARI, wherein the cell has improved double strand break repair and/or genome stability [see Abstract; paragraphs 0004-0007; 0009-0010; 0066-0067].
With respect to claim 2, Lee et al. teach the method wherein the gene of interest has an increased expression level as compared to the expression in the unmodified cell [see Abstract].
With respect to claim 3, Lee et al. teach the method wherein the cell has improved double strand break repair and/or genome stability [see Abstract; paragraphs 0004-0007; 0009-0010; 0066-0067].
With respect to claim 4, Lee et al. teach the method wherein the cell has improved protein product titer [see Abstract; paragraphs 0004-0007; 0009-0010; 0066-0067].
With respect to claim 6, Lee et al. teach the method wherein the one or more DNA repair gene is selected from XRCC6 [see paragraph 0010].
With respect to claim 7, Lee et al. teach the method wherein the one or more DNA repair gene is target for reversing a silencing [see Abstract; paragraphs 0004-0007; 0009-0010; 0066-0067].
With respect to claim 8, Lee et al. teach the method wherein the mutation includes XRCC6 Q606H (result of a SNP) [see Table 3].
With respect to claim 9, Lee et al. teach the method wherein CHO cells are deficient in DSB repair caused by mutation in DSB repair genes as compared to native Chinese hamster cells [see paragraph 0007].
With respect to claim 10, Lee et al. teach the method wherein the one or more DNA repair gene is one gene [see paragraph 0010].
With respect to claim 15, Lee et al. teach the method wherein the mutation is XRCC6 (Q606H) [see Table 3].
With respect to claims 17 and 18, Lee et al. teach the method wherein the CHO cell is CHO-K1 [see paragraph 0075].
Claim Rejections - 35 USC § 103
16. The rejection of claim 16 under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2019/0300859 A1, priority to 04/02/2018; cited on IDS filed on 09/06/2022) in view of Beck et al. (Experimental Cell Research, 2014; cited on PTO-892 mailed on 06/26/2025). The rejection has been modified in order to address applicants’ amendment to the claims.
17. The relevant teachings of Lee et al. as applied to claims 1-4, 6-10, 15, and 18 are set forth above.
With respect to claim 16, Lee et al. teach a method of preparing a CHO cell for expression of a gene of interest, comprising heterologous expression of a double stranded DNA repair protein from a Chinese hamster cell by transforming into a CHO cell containing a mutation in said DNA repair gene (interpreted as reverting a mutation), and wherein the one or more DNA repair gene targeted by reverting mutation are XRCC6, LIG4, PALB2, PARP1 and PARI [see Abstract; paragraphs 0004-0007; 0009-0010; 0066-0067].
However, Lee et al. does not teach the method wherein the one or more DNA repair gene is selected from MCM7, PPP2R5A, PIAS4, PBRM1, and/or PARP2.
Beck et al. teach that PARP1 and PARP2 play a key contribution in the DNA damage response network via the resolution of single strand breaks and also contribute to resolution double-strand breaks [see Abstract].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Lee et al. and Beck et al. according to the teachings of Beck et al. to heterologously express PARP2 in the methods of Lee et al. because Lee et al. teach the rescue of DSB deficient CHO cells through heterologous expression of PARP1. Beck et al. teach that both PARP1 and PARP2 play a role in the resolution of single strand and double stranded breaks in response to DNA damage. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Lee et al. and Beck et al. because Beck et al. acknowledges that both PARP1 and PARP2 play a role in the resolution of single strand and double stranded breaks in response to DNA damage. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Remarks Regarding Prior Art Rejections
18. Beginning on p. 10 of applicants’ remarks, applicants in summary contend that the Office’s interpretation of the limitation “reverting a mutation” is unreasonably stretched to include overexpression of transgenes as purportedly taught by Lee et al. and Beck et al. Applicants contend that it is clear from the instant specification that “reverting a mutation” and “reverting a silencing” of a DNA repair gene encompasses genetic modification of the cellular genome.
These arguments are found to be not persuasive for the reasons set forth above and the reasons set forth below. The examiner agrees that “reverting a mutation” and “reverting a silencing” encompasses genetic modification of the cellular genome; however, encompassing a species within a genus does not limit the interpretation to that one specific modification. MPEP 2145.VI also states “[a]lthough the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993)”. The examiner is of the position that “reverting a mutation” or “reverting a silencing” can reasonably be interpreted as also the expression of XRCC6 as taught by Lee et al. and PARP1 and PARP2 by Beck et al. can reasonably be interpreted as reverting a mutation or reverting a silencing as expression of these genes in CHO cells reverts the effects of the mutation or effects of silencing of said genes to increase double strand repair and genomic stability as taught by Lee et al. and Beck et al.
Conclusion
19. Status of the claims:
Claims 1-4, 6-10, 15-16, and 18 are pending.
Claims 1-4, 6-10, 15-16, and 18 are rejected.
No claims are in condition for an allowance.
THIS ACTION IS MADE FINAL. 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 PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 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, Manjunath Rao can be reached at 571-272-0939. 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.
/PAUL J HOLLAND/Primary Examiner, Art Unit 1656