DETAILED CORRESPONDENCE
Status of the Application
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 and 2 are pending in the application and are being examined on the merits.
Applicant’s amendment to the claims, filed October 31, 2025, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed October 31, 2025 in response to the non-final rejection mailed July 31, 2025 are acknowledged and have been fully considered.
Claim Objections
The objections to claims 1 and 2 are withdrawn in view of applicant’s amendments to claims 1 and 2.
Claim 1 is newly objected to in the recitation of “deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.” In the interest of improving claim form, it is suggested that the noted phrase be amended to recite “deleting the asparaginase B (ansB) gene in Escherichia coli strain deposited with Korean Federation of Culture Collection under accession number KFCC11660P or Escherichia coli strain deposited with Korean Culture Center of Microorganisms under accession number KCCM10016.”
Claim Rejections - 35 USC § 112(a)
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.
Claims 1 and 2 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This new rejection is necessitated by applicant’s amendment to claim 1 to recite “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.”
As amended, the claims recite an Escherichia coli strain deposited under accession number KFCC11660P or KCCM10016. Since the recited Escherichia coli strain deposited under accession number KFCC11660P or KCCM10016 is essential to the claimed invention, it must be obtainable by a repeatable method set forth in the specification or otherwise be readily available to the public. In this case, the specification does not disclose a repeatable process to obtain the recited Escherichia coli strain deposited under accession number KFCC11660P or KCCM10016 and it is not apparent if the recited Escherichia coli strain deposited under accession number KFCC11660P or KCCM10016 is readily available to the public. Accordingly, it is deemed that a deposit of this bacterium should have been made in accordance with 37 CFR 1.801-1.809 and the enablement requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the recited Escherichia coli strain deposited under accession number KFCC11660P or KCCM10016 is readily available to the public.
If the strain has been deposited and accepted under the terms of the Budapest Treaty, then an affidavit or declaration by applicant, or a statement by an attorney of record over his or her signature and registration number, stating that the specific strain has been deposited and accepted under the Budapest Treaty and that the strain will be irrevocably and without restriction or condition released to the public upon the issuance of the patent, would satisfy the deposit requirement made herein.
If the strain has been deposited, but not under the terms of the Budapest treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809, applicant may provide assurance or compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, including:
A statement that a deposit of the material has been made in a depository affording permanence of the deposit and ready accessibility thereto by the public if a patent is granted. The depository is to be identified by name and address.
A statement of the name and address of the depositor.
A statement of the date of deposit.
A statement that the deposited material has been accorded a specific (recited) accession number given by the depository.
A viability statement in accordance with 37 CFR 1.807(a) including the date of the viability test, the procedures used to obtain a sample if the test is not done by the depository, and a statement that the deposit is capable of reproduction.
A statement that all restrictions upon the availability to the public of the material so deposited will be irrevocably removed upon the granting of a patent.
A statement that the material has been deposited under conditions that access to the material will be available during the pendency of the patent application to one determined by the Commissioner to be entitled thereto under 37 CFR 1.14 and 35 U.S.C § 122.
A statement that the deposited material will be maintained with all the care necessary to keep it viable and uncontaminated for a period of at least five years after the most recent request for the furnishing of a sample of the deposited microorganism, and in any case, for a period of at least thirty (30) years after the date of deposit for the enforceable life of the patent, whichever period is longer.
That he/she declares further that all statements made therein of his/her own knowledge are true and that all statements made on information and belief are believed to be true, and further that these statements were made with knowledge that willful false statements and the like so made are punishable by fine or imprisonment, or both, under section 1001 of Title 18 of the United States Code and that such willful false statements may jeopardize the validity of the instant patent application or any patent issuing thereon.
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 rejection of claim 1 under 35 U.S.C. 103 as being unpatentable over Chen et al. (Appl. Microbiol. Biotechnol. 101:559-568, 2017; cited on the IDS filed on October 19, 2023; hereafter “Chen”) in view of Derst et al. (Protein Science 9:2009-2017, 2000; cited on the IDS filed on October 19, 2023; hereafter “Derst”), Pickens et al. (Annu. Rev. Chem. Biomol. Eng. 2:211-236, 2011; cited on the IDS filed on October 19, 2023; hereafter “Pickens”), and Abribat et al. (WO 2011/003886 A1; cited on the IDS filed on October 19, 2023; hereafter “Abribat”), and
the rejection of claim 2 under 35 U.S.C. 103 as being unpatentable over Chen in view of Derst, Pickens, and Abribat as applied to claim 1 above, and further in view of GenBank Database Accession Number CP047127 (January 2020, 2 pages; cited on the IDS filed on October 19, 2023; hereafter “GenBank”)
are withdrawn in view of applicant’s amendment to claim 1 to recite “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.” The combination of cited prior art does not teach or suggest the noted limitation.
The following new rejections are raised in the interest of compact prosecution in the event that Escherichia coli strain deposited under accession number KFCC11660P is readily available to the public. These rejections are necessitated by applicant’s amendment to claim 1 to recite “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.”
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Chen in view of Derst, Pickens, Abribat, and Lee et al. (KR 10-1830002 B1; cited on the IDS filed October 19, 2023; hereafter “Lee”; reference is made to applicant’s machine translation of Lee).
As amended, claim 1 is drawn to a method for producing L-tryptophan or L-phenylalanine, comprising:
constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain;
culturing the mutant strain in a medium; and
recovering L-tryptophan or L-phenylalanine from the cultured mutant strain and the medium.
Chen teaches rational design and metabolic analysis of E. coli for effective production of L-tryptophan at high concentration (title). Chen teaches biosynthesis of L-tryptophan in E. coli requires the precursor L-glutamine (p. 560, column 1, bottom), yet the intracellular concentration of L-glutamine during tryptophan production stayed at a relatively low level throughout fermentation (p. 559, column 1, bottom) and suggests that a bottleneck for tryptophan production is the insufficient supply of L-glutamine (p. 566, column 2, top). Chen teaches methods for culturing Escherichia coli for production of tryptophan (pp. 560-562).
Chen does not teach deleting an asparaginase B (ansB) gene and does not teach Escherichia coli KFCC11660P strain as a parent strain.
Regarding deletion of an asparaginase B (ansB) gene, Derst teaches that Escherichia coli asparaginase B has a significant glutaminase side activity (p. 2009, abstract), which converts L-glutamine to L-glutamate.
Pickens teaches the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria (pp. 215 and 218).
Abribat teaches a method for deleting an ansB gene encoding the E. coli L-asparaginase B by homologous recombination and teaches an E. coli BL21 strain with a deleted ansB gene (paragraph [0100]).
In view of the combined teachings of Chen, Derst, Pickens, and Abribat, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify an E. coli used in a tryptophan production method by deleting the ansB gene. Given that Chen taught that intracellular concentration of L-glutamine during tryptophan production stayed at a relatively low level throughout fermentation, Derst taught that E. coli asparaginase B has a glutaminase side activity (converting L-glutamine to L-glutamate), and Pickens taught the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria, one would have been motivated to delete the ansB gene of a tryptophan-producing E. coli in order to remove the glutaminase side activity of asparaginase B and increase the supply of the precursor L-glutamine for tryptophan production. One would have expected success to do this because Abribat taught deleting an ansB gene encoding the E. coli asparaginase B.
Regarding Escherichia coli KFCC11660P strain as a parent strain, similar to Chen, Lee acknowledges that a sufficient supply of glutamine is considered to be an important parameter for improving productivity of tryptophan and suggests developing tryptophan-producing strains (machine translation at p. 2, top). Lee teaches Escherichia coli strain W0G is a wild-type parent strain having accession number KFCC11660P (machine translation at p. 4, top). Lee teaches genetically modifying the W0G strain to enhance tryptophan production (machine translation at Example 1 beginning at p. 4).
In view of the combined teachings of Chen, Derst, Pickens, Abribat, and Lee, it would have been obvious to one of ordinary skill in the art before the effective filing date for Escherichia coli strain W0G having accession number KFCC11660P to be the parent strain modified to delete the ansB gene. One would have been motivated and expected success for W0G to be the parent strain modified to delete the ansB gene because Lee teaches W0G as a parental strain that can be genetically modified to enhance production of L-tryptophan.
Therefore, the method of claim 1 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Chen in view of Derst, Pickens, Abribat, and Lee as applied to claim 1 above, and further in view of GenBank.
Claim 2 is drawn to the method of claim 1, wherein the ansB gene consists of the nucleotide sequence of SEQ ID NO: 1.
The relevant teachings of Chen, Derst, Pickens, Abribat, and Lee as applied to claim 1 are set forth above. The combination of Chen, Derst, Pickens, Abribat, and Lee does not teach or suggest the nucleotide sequence of SEQ ID NO: 1.
GenBank teaches the sequence of an Escherichia coli genome, including the sequence of an ansB gene encoding asparaginase B (relevant portion of GenBank is pasted below).
PNG
media_image1.png
238
550
media_image1.png
Greyscale
The ansB gene sequence of GenBank is identical to SEQ ID NO: 1 of this application (see Appendix at p. 22 of the Office action mailed on December 2, 2024).
It would have been obvious to one of ordinary skill in the art before the effective filing date to combine Chen, Derst, Pickens, Abribat, Lee, and GenBank for the deleted ansB gene to have the sequence of GenBank Accession Number CP047127. One would have recognized that the deleted ansB gene has the sequence of GenBank because GenBank teaches the ansB gene of Escherichia coli. One would have expected success for the deleted ansB gene to have the sequence of GenBank because GenBank teaches the ansB gene of Escherichia coli. Therefore, the method of claim 2 would have been obvious to one of ordinary skill in the art before the effective filing date.
RESPONSE TO REMARKS: Applicant argues the cited references do not teach or suggest the parent strain having accession number KFCC11660P or KCCM10016 and do not teach or suggest the recited mutant strain has enhanced productivity of L-tryptophan or L-phenylalanine.
Applicant’s argument is not found persuasive. As stated above, Lee acknowledges that a sufficient supply of glutamine is considered to be an important parameter for improving productivity of tryptophan and suggests developing tryptophan-producing strains (machine translation at p. 2, top); Lee teaches Escherichia coli strain W0G is a wild-type parent strain having accession number KFCC11660P (machine translation at p. 4, top); and Lee teaches genetically modifying the W0G strain to enhance tryptophan production (machine translation at Example 1 beginning at p. 4). Since E. coli asparaginase B has glutaminase activity, which consumes L-glutamine, one would have reasonably expected that deleting the asparaginase B (ansB) gene of Lee’s KFCC11660P would have had the effect of removing glutaminase activity of asparaginase B with a corresponding increase in L-glutamine and improved productivity of tryptophan.
For these reasons, it is the examiner’s position that the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claim Rejections - 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.
The provisional rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 5 of U.S. application no. 17/418,072 (reference application) in view of Chen, Derst, Pickens, and Abribat, and
the provisional rejection of claim 2 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 5 of U.S. application no. 17/418,072 (reference application) in view of Chen, Derst, Pickens, and Abribat as applied to claim 1 above, and further in view of GenBank
are withdrawn in view of applicant’s amendment to claim 1 to recite “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain” and the abandonment of the reference application. The claims of the reference application do not recite and the combination of cited prior art does not teach or suggest “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.”
The provisional rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,704 (reference application) in view of Chen, Derst, Pickens, and Abribat,
the provisional rejection of claim 2 on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,704 (reference application) in view of Chen, Derst, Pickens, and Abribat as applied to claim 1 above, and further in view of GenBank,
the provisional rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,706 (reference application) in view of Chen, Derst, Pickens, and Abribat,
the provisional rejection of claim 2 on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,706 (reference application) in view of Chen, Derst, Pickens, and Abribat as applied to claim 1 above, and further in view of GenBank,
the provisional rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 11, and 12 of U.S. application no. 18/838,721 (reference application) in view of Chen, Derst, Pickens, and Abribat,
the provisional rejection of claim 2 on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 11, and 12 of U.S. application no. 18/838,721 (reference application) in view of Chen, Derst, Pickens, and Abribat as applied to claim 1 above, and further in view of GenBank
the provisional rejection of claim 1 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-8 of U.S. application no. 19/238,915 (reference application) in view of Chen, Derst, Pickens, and Abribat, and
the provisional rejection of claim 2 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-8 of U.S. application no. 19/238,915 (reference application) in view of Chen, Derst, Pickens, and Abribat as applied to claim 1 above, and further in view of GenBank
are withdrawn in view of applicant’s amendment to claim 1 to recite “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.” The claims of the reference application do not recite and the combination of cited prior art does not teach or suggest the noted limitation.
The following new provisional rejections are raised in the interest of compact prosecution in the event that Escherichia coli strain deposited under accession number KFCC11660P is readily available to the public. These provisional rejections are necessitated by applicant’s amendment to claim 1 to recite “constructing an Escherichia coli mutant strain by deleting the asparaginase B (ansB) gene in KFCC11660P or KCCM10016 as a parent strain.”
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,704 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee.
Claim 6 of the reference application recites a method for producing an L-aromatic amino acid, comprising steps of:
culturing the transformant of claim 3 in a medium; and
recovering an L-aromatic amino acid from the transformant or the medium in which the transformant has been cultured,
claim 3 of the reference application recites a transformant comprising A zinc-binding dehydrogenase variant consisting of the amino acid sequence of SEQ ID NO: 1 in which glycine at position 102 in the amino acid sequence of SEQ ID NO: 3 is substituted with arginine,
claim 4 of the reference application recites the transformant of claim 3, which is an Escherichia sp. strain, and
claim 7 of the reference application recites the method of claim 6, wherein the L-aromatic amino acid is at least one selected from the group consisting of L-tryptophan, L-phenylalanine, and L-tyrosine.
The claims of the reference application do not recite deleting an asparaginase B (ansB) gene and do not recite Escherichia coli KFCC11660P strain as a parent strain.
Regarding deletion of an asparaginase B (ansB) gene, Chen teaches rational design and metabolic analysis of E. coli for effective production of L-tryptophan at high concentration (title). Chen discloses that the biosynthesis of L-tryptophan in E. coli requires the precursor L-glutamine (p. 560, column 1, bottom), yet the intracellular concentration of L-glutamine during tryptophan production stayed at a relatively low level throughout fermentation (p. 559, column 1, bottom) and suggests that a bottleneck for tryptophan production is the insufficient supply of L-glutamine (p. 566, column 2, top). Chen teaches methods for culturing E. coli for production of tryptophan (pp. 560-562).
Derst teaches that E. coli asparaginase II has a significant glutaminase side activity (p. 2009, abstract), which converts L-glutamine to L-glutamate.
Pickens teaches the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria (pp. 215 and 218).
Abribat teaches a method for deleting an ansB gene encoding the E. coli L-asparaginase II by homologous recombination (paragraph [0100]).
In view of the teachings of Chen, Derst, Pickens, and Abribat, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the transformant of the claims of the reference application to delete the ansB gene. Since the claims of the reference application encompass a method for producing L-tryptophan using an Escherichia and given that Chen taught that intracellular concentration of L-glutamine during tryptophan production by E. coli stayed at a relatively low level throughout fermentation, Derst taught that E. coli asparaginase B has a glutaminase side activity (converting L-glutamine to L-glutamate), and Pickens taught the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria, one would have been motivated to delete the ansB gene of the transformant of the claims of the reference application in order to remove the glutaminase side activity of asparaginase B and increase the supply of the precursor L-glutamine for tryptophan production. One would have had a reasonable expectation of success to do this because Abribat taught deleting an ansB gene encoding the E. coli L-asparaginase B by homologous recombination.
Regarding Escherichia coli KFCC11660P strain as a parent strain, similar to Chen, Lee acknowledges that a sufficient supply of glutamine is considered to be an important parameter for improving productivity of tryptophan and suggests developing tryptophan-producing strains (machine translation at p. 2, top). Lee teaches Escherichia coli strain W0G is a wild-type parent strain having accession number KFCC11660P (machine translation at p. 4, top). Lee teaches genetically modifying the W0G strain to enhance tryptophan production (machine translation at Example 1 beginning at p. 4).
In view of the combined teachings of Chen, Derst, Pickens, Abribat, and Lee, it would have been obvious to one of ordinary skill in the art before the effective filing date for Escherichia coli strain W0G having accession number KFCC11660P to be the parent strain of the transformant of the claims of the reference application. One would have been motivated and expected success for W0G to be the parent strain of the transformant of the claims of the reference application because the claims of the reference application recite an E. coli transformant that produces L-tryptophan and Lee teaches W0G as a parental strain that can be genetically modified to enhance production of L-tryptophan.
Therefore, claim 1 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, and Lee. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,704 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee as applied to claim 1 above, and further in view of GenBank.
The claims of the reference application do not recite the nucleotide sequence of SEQ ID NO: 1.
GenBank teaches the sequence of an E. coli genome, including the sequence of an ansB gene encoding asparaginase B (relevant portion of GenBank Accession Number CP047127 is pasted below).
PNG
media_image1.png
238
550
media_image1.png
Greyscale
The ansB gene sequence of GenBank is identical to SEQ ID NO: 1 of this application (see Appendix at p. 22 of the Office action mailed on December 2, 2024).
In view of the teachings of Chen, Derst, Pickens, Abribat, Lee, and GenBank, it would have been obvious to one of ordinary skill in the art for the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application to have the sequence of GenBank. One would have recognized that the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application has the sequence of GenBank because the claims recite an Escherichia transformant, and GenBank teaches the ansB gene of E. coli. One would have had a reasonable expectation of success for the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application to have the sequence of GenBank because the claims recite an Escherichia transformant, and GenBank teaches the ansB gene of E. coli. Therefore, claim 2 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, Lee, and GenBank.
Therefore, claim 2 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, Lee, and GenBank. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,706 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee.
Claim 6 of the reference application recites a method for producing an L-aromatic amino acid, comprising steps of:
culturing the transformant of claim 3 in a medium; and
recovering an L-aromatic amino acid from the transformant or the medium in which the transformant has been cultured,
claim 3 of the reference application recites a transformant comprising an ATP synthase variant composed of the amino acid sequence of SEQ ID NO: 1 in which glycine at position 235 in the amino acid sequence of SEQ ID NO: 3 is substituted with serine,
claim 4 of the reference application recites the transformant of claim 3, which is an Escherichia sp. strain, and
claim 7 of the reference application recites the method of claim 6, wherein the L-aromatic amino acid is at least one selected from the group consisting of L-tryptophan, L-phenylalanine, and L-tyrosine.
The claims of the reference application do not recite deleting an asparaginase B (ansB) gene and do not recite Escherichia coli KFCC11660P strain as a parent strain.
Regarding deletion of an asparaginase B (ansB) gene, Chen teaches rational design and metabolic analysis of E. coli for effective production of L-tryptophan at high concentration (title). Chen discloses that the biosynthesis of L-tryptophan in E. coli requires the precursor L-glutamine (p. 560, column 1, bottom), yet the intracellular concentration of L-glutamine during tryptophan production stayed at a relatively low level throughout fermentation (p. 559, column 1, bottom) and suggests that a bottleneck for tryptophan production is the insufficient supply of L-glutamine (p. 566, column 2, top). Chen teaches methods for culturing E. coli for production of tryptophan (pp. 560-562).
Derst teaches that E. coli asparaginase II has a significant glutaminase side activity (p. 2009, abstract), which converts L-glutamine to L-glutamate.
Pickens teaches the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria (pp. 215 and 218).
Abribat teaches a method for deleting an ansB gene encoding the E. coli L-asparaginase II by homologous recombination (paragraph [0100]).
In view of the teachings of Chen, Derst, Pickens, and Abribat, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the transformant of the claims of the reference application to delete the ansB gene. Since the claims of the reference application encompass a method for producing L-tryptophan using an Escherichia and given that Chen taught that intracellular concentration of L-glutamine during tryptophan production by E. coli stayed at a relatively low level throughout fermentation, Derst taught that E. coli asparaginase B has a glutaminase side activity (converting L-glutamine to L-glutamate), and Pickens taught the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria, one would have been motivated to delete the ansB gene of the transformant of the claims of the reference application in order to remove the glutaminase side activity of asparaginase B and increase the supply of the precursor L-glutamine for tryptophan production. One would have had a reasonable expectation of success to do this because Abribat taught deleting an ansB gene encoding the E. coli L-asparaginase B by homologous recombination.
Regarding Escherichia coli KFCC11660P strain as a parent strain, similar to Chen, Lee acknowledges that a sufficient supply of glutamine is considered to be an important parameter for improving productivity of tryptophan and suggests developing tryptophan-producing strains (machine translation at p. 2, top). Lee teaches Escherichia coli strain W0G is a wild-type parent strain having accession number KFCC11660P (machine translation at p. 4, top). Lee teaches genetically modifying the W0G strain to enhance tryptophan production (machine translation at Example 1 beginning at p. 4).
In view of the combined teachings of Chen, Derst, Pickens, Abribat, and Lee, it would have been obvious to one of ordinary skill in the art before the effective filing date for Escherichia coli strain W0G having accession number KFCC11660P to be the parent strain of the transformant of the claims of the reference application. One would have been motivated and expected success for W0G to be the parent strain of the transformant of the claims of the reference application because the claims of the reference application recite an E. coli transformant that produces L-tryptophan and Lee teaches W0G as a parental strain that can be genetically modified to enhance production of L-tryptophan.
Therefore, claim 1 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, and Lee. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 4, 6, and 7 of U.S. application no. 18/838,706 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee as applied to claim 1 above, and further in view of GenBank.
The claims of the reference application do not recite the nucleotide sequence of SEQ ID NO: 1.
GenBank teaches the sequence of an E. coli genome, including the sequence of an ansB gene encoding asparaginase B (relevant portion of GenBank Accession Number CP047127 is pasted below).
PNG
media_image1.png
238
550
media_image1.png
Greyscale
The ansB gene sequence of GenBank is identical to SEQ ID NO: 1 of this application (see Appendix at p. 22 of the Office action mailed on December 2, 2024).
In view of the teachings of Chen, Derst, Pickens, Abribat, Lee, and GenBank, it would have been obvious to one of ordinary skill in the art for the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application to have the sequence of GenBank. One would have recognized that the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application has the sequence of GenBank because the claims recite an Escherichia transformant, and GenBank teaches the ansB gene of E. coli. One would have had a reasonable expectation of success for the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application to have the sequence of GenBank because the claims recite an Escherichia transformant, and GenBank teaches the ansB gene of E. coli. Therefore, claim 2 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, Lee, and GenBank.
Therefore, claim 2 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, Lee, and GenBank. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 11, and 12 of U.S. application no. 18/838,721 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee.
Claim 11 of the reference application recites a method for producing an L-aromatic amino acid, comprising steps of:
culturing the transformant of claim 8 in a medium; and
recovering an L-aromatic amino acid from the transformant or the medium in which the transformant has been cultured,
claim 8 of the reference application recites a transformant comprising a polynucleotide encoding a variant selected from among:
a glutathione reductase variant consisting of the amino acid sequence of SEQ ID NO: 1 in which threonine at position 74 in the amino acid sequence of SEQ ID NO: 3 is substituted with isoleucine; and
a stress protein B variant consisting of the amino acid sequence of SEQ ID NO: 5 in which glutamine at position 42 in the amino acid sequence of SEQ ID NO: 7 is substituted with a stop codon,
claim 9 of the reference application recites the transformant of claim 8, which is an Escherichia sp. strain, and
claim 12 of the reference application recites the method of claim 11, wherein the L-aromatic amino acid is at least one selected from the group consisting of L-tryptophan, L-phenylalanine, and L-tyrosine.
The claims of the reference application do not recite deleting an asparaginase B (ansB) gene and do not recite Escherichia coli KFCC11660P strain as a parent strain.
Regarding deletion of an asparaginase B (ansB) gene, Chen teaches rational design and metabolic analysis of E. coli for effective production of L-tryptophan at high concentration (title). Chen discloses that the biosynthesis of L-tryptophan in E. coli requires the precursor L-glutamine (p. 560, column 1, bottom), yet the intracellular concentration of L-glutamine during tryptophan production stayed at a relatively low level throughout fermentation (p. 559, column 1, bottom) and suggests that a bottleneck for tryptophan production is the insufficient supply of L-glutamine (p. 566, column 2, top). Chen teaches methods for culturing E. coli for production of tryptophan (pp. 560-562).
Derst teaches that E. coli asparaginase II has a significant glutaminase side activity (p. 2009, abstract), which converts L-glutamine to L-glutamate.
Pickens teaches the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria (pp. 215 and 218).
Abribat teaches a method for deleting an ansB gene encoding the E. coli L-asparaginase II by homologous recombination (paragraph [0100]).
In view of the teachings of Chen, Derst, Pickens, and Abribat, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the transformant of the claims of the reference application to delete the ansB gene. Since the claims of the reference application encompass a method for producing L-tryptophan using an Escherichia and given that Chen taught that intracellular concentration of L-glutamine during tryptophan production by E. coli stayed at a relatively low level throughout fermentation, Derst taught that E. coli asparaginase B has a glutaminase side activity (converting L-glutamine to L-glutamate), and Pickens taught the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria, one would have been motivated to delete the ansB gene of the transformant of the claims of the reference application in order to remove the glutaminase side activity of asparaginase B and increase the supply of the precursor L-glutamine for tryptophan production. One would have had a reasonable expectation of success to do this because Abribat taught deleting an ansB gene encoding the E. coli L-asparaginase B by homologous recombination.
Regarding Escherichia coli KFCC11660P strain as a parent strain, similar to Chen, Lee acknowledges that a sufficient supply of glutamine is considered to be an important parameter for improving productivity of tryptophan and suggests developing tryptophan-producing strains (machine translation at p. 2, top). Lee teaches Escherichia coli strain W0G is a wild-type parent strain having accession number KFCC11660P (machine translation at p. 4, top). Lee teaches genetically modifying the W0G strain to enhance tryptophan production (machine translation at Example 1 beginning at p. 4).
In view of the combined teachings of Chen, Derst, Pickens, Abribat, and Lee, it would have been obvious to one of ordinary skill in the art before the effective filing date for Escherichia coli strain W0G having accession number KFCC11660P to be the parent strain of the transformant of the claims of the reference application. One would have been motivated and expected success for W0G to be the parent strain of the transformant of the claims of the reference application because the claims of the reference application recite an E. coli transformant that produces L-tryptophan and Lee teaches W0G as a parental strain that can be genetically modified to enhance production of L-tryptophan.
Therefore, claim 1 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, and Lee. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 9, 11, and 12 of U.S. application no. 18/838,721 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee as applied to claim 1 above, and further in view of GenBank.
The claims of the reference application do not recite the nucleotide sequence of SEQ ID NO: 1.
GenBank teaches the sequence of an E. coli genome, including the sequence of an ansB gene encoding asparaginase B (relevant portion of GenBank Accession Number CP047127 is pasted below).
PNG
media_image1.png
238
550
media_image1.png
Greyscale
The ansB gene sequence of GenBank is identical to SEQ ID NO: 1 of this application (see Appendix at p. 22 of the Office action mailed on December 2, 2024).
In view of the teachings of Chen, Derst, Pickens, Abribat, Lee, and GenBank, it would have been obvious to one of ordinary skill in the art for the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application to have the sequence of GenBank. One would have recognized that the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application has the sequence of GenBank because the claims recite an Escherichia transformant, and GenBank teaches the ansB gene of E. coli. One would have had a reasonable expectation of success for the ansB gene deleted in the tryptophan-producing transformant of the claims of the reference application to have the sequence of GenBank because the claims recite an Escherichia transformant, and GenBank teaches the ansB gene of E. coli. Therefore, claim 2 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, Lee, and GenBank.
Therefore, claim 2 of this application is unpatentable over the claims of the reference application in view of Chen, Derst, Pickens, Abribat, Lee, and GenBank. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-8 of U.S. application no. 19/238,915 (reference application) in view of Chen, Derst, Pickens, Abribat, and Lee.
Claim 7 of the reference application recites a method for producing an aromatic amino acid, comprising steps of:
culturing the mutant strain of claim 1 in a medium; and
recovering an aromatic amino acid from the cultured mutant strain and the medium,
claim 1 of the reference application recites a mutant strain having improved aromatic amino acid production capability due to inactivation or weakening of activity of glutaminase which is expressed by glutaminase B (glsB) gene,
claim 6 of the reference application recites wherein the strain of the genus Escherichia is Escherichia coli, and
claim 8 of the reference application recites wherein the aromatic amino acid is at least one of L-tryptophan and L-phenylalanine.
The claims of the reference application do not recite deleting an asparaginase B (ansB) gene and do not recite Escherichia coli KFCC11660P strain as a parent strain.
Regarding deletion of an asparaginase B (ansB) gene, Chen teaches rational design and metabolic analysis of E. coli for effective production of L-tryptophan at high concentration (title). Chen discloses that the biosynthesis of L-tryptophan in E. coli requires the precursor L-glutamine (p. 560, column 1, bottom), yet the intracellular concentration of L-glutamine during tryptophan production stayed at a relatively low level throughout fermentation (p. 559, column 1, bottom) and suggests that a bottleneck for tryptophan production is the insufficient supply of L-glutamine (p. 566, column 2, top). Chen teaches methods for culturing E. coli for production of tryptophan (pp. 560-562).
Derst teaches that E. coli asparaginase II has a significant glutaminase side activity (p. 2009, abstract), which converts L-glutamine to L-glutamate.
Pickens teaches the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria (pp. 215 and 218).
Abribat teaches a method for deleting an ansB gene encoding the E. coli L-asparaginase II by homologous recombination (paragraph [0100]).
In view of the teachings of Chen, Derst, Pickens, and Abribat, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the transformant of the claims of the reference application to delete the ansB gene. Since the claims of the reference application encompass a method for producing L-tryptophan using an Escherichia and given that Chen taught that intracellular concentration of L-glutamine during tryptophan production by E. coli stayed at a relatively low level throughout fermentation, Derst taught that E. coli asparaginase B has a glutaminase side activity (converting L-glutamine to L-glutamate), and Pickens taught the concept of eliminating pathways that degrade precursors and using gene inactivation to increase precursor supply for production of natural products using bacteria, one would have been motivated to delete the ansB gene of the transformant of the claims of the reference application in order to remove the glutaminase side activity of asparaginase B and increase the supply of the precursor L-glutamine for tryptophan production. One would have had a reasonable expectation of success to do this because Abribat taught deleting an ansB gene encoding the E. coli L-asparaginase B by homologous recombination.
Regarding Escherichia coli KFCC11660P strain as a parent strain, similar to Chen, Lee acknowledges that a sufficient supply of glutamine is considered to be an important parameter for improving productivity of tryptophan and suggests developing tryptophan-producing strains (machine translation at p. 2, top). Lee teaches Escherichia coli strain W0G is a wild-type parent strain having accession number KFCC11660P (machine translation at p. 4, top). Lee teaches genetically modifying the W0G strain to enhance tryptophan production (machine translation at Example 1 beginning at p. 4).
In view of the combined teachings of Chen, Derst, Pickens, Abribat, and Lee, it would have been obvious to one of ordinary skill in the art before the effective filing date for Escherichia coli strain W0G having accession number KFCC11660P to be the parent strain of the transformant of the claims of the reference application. One would have been motivated and expected su