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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/09/2026 has been entered.
Priority
This application claims benefit of priority to Republic of Korea Application No. KR10-2020-0156903 filed on 11/20/2020. This application is also a 371 of PCT/KR2021/017074 filed on 11/19/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, an English translation of the foreign patent documents was not provided. Therefore, for the purposes of applying prior art, the effective filing date of the claimed invention is the filing date of the PCT, 11/19/2021.
Information Disclosure Statement
The Information Disclosure Statement filed 07/01/2026 has been acknowledged and considered.
Amendment and Claim Status
In the reply filed 09/09/2026, Applicant amended claims 6 and 12 and added new claims 23-26. Claim 8 is cancelled.
Claims 6-7 and 9-26 are currently pending and under examination.
Claim Objections
Claim 15 is objected to because of the following informalities: Corynebacterium glutamicum in line 2 is not italicized. Appropriate correction is required.
Claim 25 is objected to because of the following informalities: the claim does not recite “wherein” after the preamble. Appropriate correction is required.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 6-7, 9-24 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Eikmanns et al. (US 20020065403 A1, 05/30/2002) (Of Record) and Nakamura et al. (US 20040152175 A1, 08/05/2004).
Regarding claims 6, 10-12, 15-24 and 26, Eikmanns et al. disclose a process for the fermentative preparation of L-amino acids utilizing Coryneform bacteria, which already produce L-amino acids, wherein the nucleotide sequence which codes for the pck (phosphoenolpyruvate carboxykinase) gene is attenuated and therefore expressed at a low level (See entire document, Paragraph [0033]). More specifically, Eikmanns et al. claim:
A process for the fermentative preparation of L-amino acids, wherein bacteria in which
a) the polynucleotide as claimed in claim 1 is attenuated or the activity of the polypeptide for which the polynucleotide mentioned codes is reduced;
b) the desired product is concentrated in the medium or in the cells of the bacteria and;
c) the product is isolated (Claim 11 of Eikmanns et al.).
The polynucleotide of claim 1 is a polynucleotide coding for a polypeptide which comprises the amino acid sequence of SEQ ID NO: 2 (Claim 1 of Eikmanns et al.) wherein SEQ ID NO: 2 is a specific pck gene from C. glutamicum (Paragraph [0067]). SEQ ID NO. 2 of Eikmanns et al. shares 100% sequence identity to instant SEQ ID NO. 1. A Sequence alignment is provided below wherein Qy is instant SEQ ID NO: 1 and Db is SEQ ID NO: 2 of Eikmanns et al.
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Eikmanns et al. further disclose it is advantageous for the production of L-amino acids to over-express one or more enzymes of the particular biosynthesis route in addition to the attenuation of the pck gene (Paragraph [0078]).
It is noted, as discussed above, Eikmanns et al. disclose Coryneform bacteria naturally produce L-amino acids (Paragraph [0033]). It is further noted the instant Specification indicates Corynebacterium glutamicum ATCC13032 is a wild type strain (Page 28, Example 2, First Paragraph) and goes on to disclose strain ATCC13032, with no changes, produced 0.89 g/L of L-glutamine (Page 30, Table 30). Therefore, it appears, absent evidence to the contrary, Corynebacterium glutamicum naturally produces at least some L-glutamine. It is further noted Eikmanns et al. also teach this specific strain, C. glutamicum ATCC13032, for the production of L-amino acids (Paragraphs [0035]-[0036]).
Additionally, Nakamura et al. disclose an L-glutamine producing Coryneform bacteria (See entire document, Paragraph [0002]). There are various techniques for increasing L-amino acid production using recombinant DNA techniques, including enhancing activities of enzymes involved in L-amino acid biosynthesis and reducing activities of enzymes involved in the degradation of L-amino acids (Paragraph [0004]). Glutaminase is a known enzyme that degrades L-glutamine by hydrolysis (Paragraph [0006]), reading on a protein involved in L-glutamine degradation. Glutamine synthetase is known to be involved in glutamine biosynthesis (Paragraph [0004]). Nakamura et al. disclose L-glutamine producing ability is far superior in a strain with reduced glutaminase activity as compared to a strain where glutaminase activity was similar to that of the wild-type strain (Paragraph [0009]). Furthermore, the L-glutamine producing ability can be further improved by also enhancing glutamine synthetase activity (Paragraph [0009]). Nakamura et al. create a strain with the glutaminase gene attenuated and a strain with the glutaminase gene attenuated and the glutamine synthetase gene enhanced (Table 7 of Nakamura et al.). The wild-type strain produced 13.4 g/L L-glutamine, the strain with just the glutaminase gene attenuated produced 18.8 g/L L-glutamine while the strain with the glutaminase gene attenuated and the glutamine synthetase gene enhanced produced 24.4 g/L L-glutamine (Table 7 of Nakamura et al.).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have enhanced activity of a glutamine synthetase in the bacteria of Eikmanns et al. because Eikmanns et al. specifically state it is advantageous to over-express an enzyme of the particular L-amino acid biosynthesis route in addition to attenuating the pck gene and glutamine synthetase is an enzyme known to be part of the L-glutamine biosynthesis pathway as taught by Nakamura et al. Therefore, it would have been obvious to overexpress glutamine synthetase in the bacteria of Eikmanns et al. because it is a known and effective means of increasing L-glutamine production in Coryneform bacteria and Eikmanns et al. is drawn to producing L-amino acids in Coryneform bacteria.
Regarding the limitation of the production or production ability being increased by 5% compared to a wild-type strain present in claims 12, 23 and 26, as discussed above, Nakamura et al. disclose the strain with glutamine synthetase enhanced produces 24.4 g/L L-glutamine while the wild-type strain only produced 13.4 g/L L-glutamine (Table 7 of Nakamura et al.). The increase from 13.4 g/L L-glutamine to 24.4 g/L L-glutamine is more than a 5% increase in L-glutamine production. Thus, it would be expected that the L-glutamine production increasing by at least 5% would naturally flow from combining the teachings of Eikmanns et al. and Nakamura et al. to create a recombinant C. glutamicum strain with an attenuated pck gene and enhanced activity of glutamine synthetase.
Regarding claims 7 and 13, as discussed above, the product, being L-amino acids, are isolated (Claim 11 of Eikmanns et al.). Isolated means separated out of its natural environment (Paragraph [0029]). Thus, separating the L-amino acids from their natural environment, in this case being the bacteria or culture medium, reads on recovering L-glutamine from the medium or microorganism.
Regarding claims 9 and 14, as the gene is from C. glutamicum and the bacterial cell used is C. glutamicum, the pck gene represented by SEQ ID NO. 2 of Eikmanns et al. reads on an intrinsic protein.
Claims 6-7 and 9-26 are rejected under 35 U.S.C. 103 as being unpatentable over Eikmanns et al. (US 20020065403 A1, 05/30/2002) (Of Record), Nakamura et al. (US 20040152175 A1, 08/05/2004) and Choi et al. (US 20220396815 A1, 12/15/2022, with priority to the filing date of 03/04/2021).
Regarding claim 25, neither Eikmanns et al. nor Nakamura et al. disclose the microorganism comprises a glutamine synthetase comprising the sequence of SEQ ID NO: 11.
However, Choi et al. disclose a polypeptide having glutamine synthetase activity (Claim 1 of Choi et al.) wherein the polypeptide consists of an amino acid sequence set forth in SEQ ID NO: 2 (Claim 6 of Choi et al.) and a method of producing L-glutamine comprising culturing C. glutamicum comprising the polypeptide with glutamine synthetase activity (Claim 12 of Choi et al.). SEQ ID NO: 2 of Choi et al. shares 100% sequence identity to instant SEQ ID NO: 11. An alignment is provided below wherein Qy is instant SEQ ID NO: 11 and Db is SEQ ID NO: 2 of Choi et al.
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Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the glutamine synthetase of Choi et al. in the bacteria of Eikmanns et al. because it was a known and effective glutamine synthetase useful for producing L-glutamine in C. glutamicum as taught by Choi et al. and Nakamura et al. disclose the enhancement of glutamine synthetase in C. glutamicum increases the production of L-glutamine and Eikmanns et al. is drawn to increasing the production of L-amino acids in C. glutamicum.
Claims 6-7 and 9-26 are rejected under 35 U.S.C. 103 as being unpatentable over Eikmanns et al. (US 20020065403 A1, 05/30/2002) (Of Record), Nakamura et al. (US 20040152175 A1, 08/05/2004), Pompejus et al. (US 20050260707 A1, 11/24/2005) and French et al. (Journal of Molecular Evolution, 1983).
Regarding claim 25, neither Eikmanns et al. nor Nakamura et al. disclose the microorganism comprises a glutamine synthetase comprising the sequence of SEQ ID NO: 11.
However, Pompejus et al. disclose metabolic pathway (MP) proteins from C. glutamicum (See entire document, Paragraph [0003]). The MP proteins can be used to modulate the production of fine chemical from a microorganism, for example, improve yield or production of a fine chemical from a Corynebacterium species (Paragraph [0004]). The fine chemical is an amino acid (Claim 32 of Pompejus et al.) wherein the amino acid can be glutamine (Claim 33 of Pompejus et al.). Pompejus et al. disclose SEQ ID NO: 98, a specific glutamine synthetase (Table 1 of Pompejus et al.). SEQ ID NO: 98 disclosed by Pompejus et al. shares 99.8% sequence identity to instant SEQ ID NO: 11. It is noted there is only one amino acid difference between the sequences, being SEQ ID NO: 98 disclosed by Pompejus et al. having an aspartic acid (D) at position 401 and instant SEQ ID NO: 11 having an asparagine (N) at position 401. An alignment is provided below wherein Qy is instant SEQ ID NO: 11 and Db is SEQ ID NO: 98 of Pompejus et al.
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Pompejus et al. go on to disclose there are naturally-occurring variants of the MP sequences and changes that can be introduced into the MP sequences (Paragraph [0070]). Nucleotide substitutions leading to amino acid substitutions at non-essential residues can be made without altering the function of the MP (Paragraph [0070]). Preferably, conservative amino acid substitutions are made at predicted non-essential amino acid residues (Paragraph [0073]). A conservative amino acid substitution is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain (Paragraph [0073]).
Additionally, French et al. teach a substitution of one amino acid residue for another has a far greater chance of being accepted if the two residues are similar in properties (Page 171, Left Column, “Summary”). French et al. disclose amino acids can be classified into five groups, one group being hydrophilic amino acids which includes both asparagine and aspartic acid (Page 172, Left Column, Paragraph 2).
Thus, as disclosed above, it would have been obvious to utilize a glutamine synthetase in the bacteria of Eikmanns et al. because overexpressing glutamine synthetase results in an increase in L-glutamine production as taught by Nakamura et al. Therefore, it would have been obvious to utilize the glutamine synthetase disclosed by Pompejus et al. in the bacteria of Eikmanns et al. because it was a known and effective glutamine synthetase usable in Corynebacterium for the production of L-amino acids, such a L-glutamine, as taught by Pompejus et al. It would have been further obvious to one of ordinary skill in the art to make a conservative amino acid substitution at any non-essential position, including position 401, within the glutamine synthetase of Pompejus et al., including an aspartic acid to asparagine substitution, because Pompejus et al. disclose the MP proteins can have conservative substitutions and still retain their functions and French et al. teach asparagine and aspartic acid are both hydrophilic amino acids. One of ordinary skill in the art would be motivated to make the aspartic acid to asparagine substitution to ensure the protein maintained its function and aspartic acid and asparagine are both hydrophilic amino acids that would constitute a conservative substitution.
Response to Arguments
Applicant's arguments filed 09/09/2026 have been fully considered but they are not persuasive.
Applicant argued L-glutamine is produced from L-glutamate through a pathway different from the oxaloacetate-derived amino-acid derived pathways studied in Eikmanns and therefore there is no reason to select an L-glutamine specific pathway modification and combine it with PEPCK weakening, nor is there a reasonable expectation of success (Page 5, Last Paragraph).
The Examiner respectfully disagrees. Eikmanns is broadly directed to the production of L-amino acids. The modified rejection set forth above addresses the newly presented limitations and the arguments regarding there being no reason to select an L-glutamine specific pathway modification and combine it with PEPCK weakening and no reasonable expectation of success.
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.
Claims 6-7 and 9-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12270061 B2 in view of Eikmanns et al.
Claims 1-7 of ‘061 are drawn to a polypeptide, or polynucleotide, having glutamine synthetase activity with claim 6 specifically claiming SEQ ID NO: 2. SEQ ID NO: 2 of ‘061 shares 100% sequence identity to instant SEQ ID NO: 11. Claims 8-11 of ‘061 are drawn to a microorganism comprising the polypeptide or polynucleotide wherein the microorganism has L-glutamine producing ability and the microorganism is specifically Corynebacterium glutamicum. Claims 12-15 of ‘061 are drawn to a method of producing L-glutamine comprising culturing a microorganism, specifically C. glutamicum, comprising the polypeptide of claim 1 and recovering the L-glutamine from the medium.
‘061 does not disclose having phosphoenolpyruvate carboxykinase activity weakened.
However, as discussed above, Eikmanns et al. teach a process for the fermentative preparation of L-amino acids utilizing Coryneform bacteria, which already produce L-amino acids, wherein the nucleotide sequence which codes for the pck (phosphoenolpyruvate carboxykinase) gene is attenuated, and therefore expressed at a low level (See entire document, Paragraph [0033]).
Thus, it would have been obvious to weaken the phosphoenolpyruvate activity in the microorganism of ‘061 because it was a known and effective means of increasing L-amino acid production in Coryneform bacteria as taught by Eikmanns et al.
Therefore, the claims of ‘061 are obvious over the instant claims in view of Eikmanns et al.
Conclusion
Claims 6-7 and 9-26 are rejected.
No claims are allowed.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
