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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/28/2026 has been entered.
Applicant's amendment of claims 1, 20, 22, 24, in the paper of 3/17/2026, is acknowledged. Applicants' arguments filed on 3/17/2026, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1, 20, 22, 24, 46, 52, 56, 66, 68, 73, 77, 91 and 94 are still at issue and are present for examination.
Applicants attention is directed to the proper method of amending the claims as per MPEP 714, 37 CFR 1.121 Manner of making amendments in application. Applicants attention is directed to the currently amended claim 52 which appears to be amended from that of previous claim 52, as it existed in the paper of 12/15/2025. Applicants amendment should properly have a status identifier “(Currently amended)” and should also show with proper markings (i.e. strike-through, underlining, etc…) for the amended text.
Please use proper markings in all future amendments. This is required to clarify the record and prosecution and avoid issues that result from a lack of clarity of the record and prosecution.
Election/Restrictions
Applicant's election without traverse of the invention of Group 1, claims 1, 16, 19-24, 39, 42, 46, 52, 56, 66, 68, 101-104), to an engineered E. coli strain host cell, in the paper of 8/18/2025, is acknowledged. Applicant's election without traverse of the invention of following species: Species Group 1: SbcC, Species Group 2: SEQ ID NO: 39 and Species Group 4: inverted repeat sequence, in the paper of 8/18/2025, is acknowledged.
Claims 73, 77, 91, 94 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Objections
Claim 1, 66, 68 are objected to because of the following informalities:
Claim 1 recites “D5Ha” which should be “DH5a”.
Claims 66 and 68 depende from rejected claim 56.
Appropriate correction is required.
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.
The rejection of claim 1 (claims 16, 19-24, 39, 42, 46, 52, 56, 66, 68, 101-105 dependent on) as being indefinite in the recitation “engineered viability- or yield-reducing mutations in any of the sbcB, recB, recD, and recJ genes” is withdrawn based upon applicants arguments presented in the paper of 12/15/2025.
Claim 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 24 is indefinite in the recitation “wherein the temperature-sensitive lambda repressor is a phage cp80 attachment site chromosomally integrated copy of an arabinose inducible CITs857 gene” in that it is unclear and confusing as what applicants are claiming on the basis that it is unclear how a “temperature-sensitive lambda repressor” which is a protein can be a “phage cp80 attachment site chromosomally integrated copy of an arabinose inducible CITs857 gene”. How can a repressor protein also be a gene?
Claim 24 is further indefinite in the recitation “wherein the temperature-sensitive lambda repressor is a phage cp80 attachment site chromosomally integrated copy of an arabinose inducible CITs857 gene” in that it is unclear and confusing as to what a phage cp80 is.
Appropriate correction and/or comment is required.
Claim Rejections - 35 USC § 112
The rejection of claim(s) 16 and 22 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention, is withdrawn based upon applicants amendment of the claims in the paper of 12/15/2025.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Darmon et al. (J. of Bacteriology, Vol 189, No. 18, pp 6686-6694, Sept. 2007) is withdrawn based upon applicants amendment of the claims in the paper of 12/15/2025. It is noted that while applicants did not specifically traverse the rejection, the strain taught by Darmon et al. is not isogenic to the strain from which it is derived, the strain from which it is derived being selected from D5Ha, DH1, JM107, JM108, JM109, MG1644, and XL1Blue (see also above rejection under 35 U.S.C. 112(b)).
The rejection of claim(s) 1, 16, 19, 20, 24, 39, 42, 46, 52, 56, 101-03, is/are under 35 U.S.C. 102(a)(1) as being anticipated by Williams (US 2015/0191735) is withdrawn based upon applicants amendment of the claims and arguments presented in the paper of 12/15/2025. Specifically the GT115 strain taught by Williams comprises a Delta (mrr-hsdRMS-mcrBC).
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.
Claim(s) 1, 20, 46, 52, 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Williams (US 2015/0191735) and Darmon et al. (J. of Bacteriology, Vol 189, No. 18, pp 6686-6694, Sept. 2007).
Williams (US 2015/0191735) teaches methods of improving yield of plasmid vectors having a replication origin such as R6K by introducing the nucleotide sequence encoding the Rep protein into the genome of GT115, the E. coli strain in which the SbcC, SbcD and dcm genes were knocked out further using the E. coli strain containing a temperature sensitive lambda repressor for temperature expression of the Rep protein (see Examples and supporting text)(claims . Williams is silent with regard to the sbcB, recB, recD and recJ genes, which by virtue that they exist in the wild-type E. coli strains are considered to have no engineered viability- or yield-reducing mutations. Williams is silent with regard to the uvrC gene, which by virtue that they exist in the wild-type E. coli strains are considered to have no engineered viability- or yield-reducing mutations (claims 1, 16, 19, 20, 24, 39).
Williams (US 2015/0191735) teaches methods of improving yield of plasmid vectors having a replication origin such as R6K by introducing the nucleotide sequence encoding the Rep protein into the genome of GT115, a E. coli strain in which the SbcC, SbcD and dcm genes were knocked out further using the E. coli strain containing a temperature sensitive lambda repressor (cITs857) for temperature expression of the Rep protein (see Examples and supporting text)(claims). Williams is silent with regard to the sbcB, recB, recD and recJ genes, which by virtue that they exist in the wild-type E. coli strains are considered to have no engineered viability- or yield-reducing mutations. Williams is silent with regard to the uvrC gene, which by virtue that they exist in the wild-type E. coli strains are considered to have no engineered viability- or yield-reducing mutations (claims 1, 16, 19, 20, 24, 39). Williams further teach that the pINT pR pL R6K Rep plasmids can be integrated into alternative E. coli strains to create production hosts. Williams teach that any strain that is acceptable for plasmid production, such as JM108, BL21, DH5, DH1, DH5.alpha., GT115, GT116, DH10B, EC100, can be converted to a high yield temperature inducible R6K plasmid production host by integration of a pINT pR pL R6K Rep plasmid into the genome. The pR pL R6K Rep expression cassette may alternatively be removed from the pINT vector backbone and directly integrated into the chromosome.
Williams teach the above engineered E. coli strains comprising a genomic nucleic acid sequence encoding a Rep protein having 100% sequence identity to instant SEQ ID NO:34 (see SEQ ID NO:15 of Williams). Williams teachand evidence the above engineered E. coli strains comprising a genomic nucleic acid sequence encoding a sbcB gene comprising instant SEQ ID NO:11, a recB gene comprising instant SEQ ID NO:12, a recD gene comprising instant SEQ ID NO:13 and a recJ gene comprising instant SEQ ID NO:65 as each of these genes are found in the wild-type E. coli (claim 42). Williams teach the above engineered E. coli strains comprising a plasmid vector comprising a nucleic acid having a direct repeat (claim 46) (see claim 23 and supporting text paragraph [0080]) or a mRNA vector (claim 28 and supporting text). Williams teach the above engineered E. coli strains comprising a knockout of the dcm gene (claim 103) (see Example 1 and supporting text).
Darmon teaches an engineered Escherichia coli (E. coli) host cell, wherein the engineered E. coli host cell comprises a gene knockout of at least one gene selected from the group consisting of SbcC and SbcD, and wherein the engineered E. coli host cell does not include an engineered viability or yield-reducing mutation in any of sbcB, recB, recD, and recJ (p. 6686, col 2, para 7 "The E. coli MG1655 [delta)(Plac-lacZY) [delta]sbcDC PsbcDC-lacZ-aph reporter strain (DL 1649; Fig. 1A) was constructed by replacement of the sbcDC operon with a DNA fragment containing the lacZ gene and the kanamycin resistance gene aph"; p. 6687, col 2, para 1 top. 6688, col 1, para 1 "Correct excision of the sbcDC operon"; p. 6688, col 1, Fig. 1 "the cassette containing the lacZ and the kanamycin resistance genes was placed under the control of the sbcDC promoter region and fused to the beginning of the sbcD gene. sbcD', 3' truncated sbcD gene; Kanr, kanamycin resistance gene"; note, there is no mention in the full publication of any modifications to any other sbc or rec genes).
One of skill in the art before the effective filing date would have been motivated to practice methods of improving yield of plasmid vectors having a replication origin such as R6K by introducing the nucleotide sequence encoding the Rep protein into the genome of GT115, a E. coli strain in which the SbcC, SbcD and dcm genes were knocked out further using the E. coli strain containing a temperature sensitive lambda repressor for temperature expression of the Rep protein as taught by Williams (US 2015/0191735) substituting the MG1655 strain taught by Darmon for the GT115 strain used by Williams. The motivation for such comes from Williams who teach that any strain that is acceptable for plasmid production, such as JM108, BL21, DH5, DH1, DH5.alpha., GT115, GT116, DH10B, EC100, can be converted to a high yield temperature inducible R6K plasmid production host by integration of a pINT pR pL R6K Rep plasmid into the genome. Further motivation comes from the fact that both strain used by Wiliams, GT115 and the MG1655 strain taught by Darmon both comprise a knockout of the sbcDC operon. The expectation of success is high as the level of expertise in bacterial genetic engineering is high and all the tools, constructs and methods needed are taught by both Williams et al. and Darmon
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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, Robert Mondesi can be reached at (408) 918-7584. 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.
rgh
5/19/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
Prosecution Insights