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 .
DETAILED ACTION
Claims 1-11 are pending and under examination.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-11 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.
Claims 1 and 10 require the limitation of a microorganism having enhanced NADH:quinone oxidoreductase activity. It is unclear what degree or level of oxidoreductase activity is required by the relative term “enhanced” in the instant claims. It is unclear if the claim means that the oxidoreductase gene is modified so that the encoded protein has increased enzyme activity, or if the claim means that the genes encoding the enzyme complex are overexpressed. Therefore, the claim is considered indefinite as one of ordinary skill in the art would not know what structural features the microorganism requires to have enhanced enzyme activity.
Claims 2-9 are also rejected as they depend from claim 1. Claim 11 is also rejected as it depends from claim 10.
Claim 2 recites: wherein the enhancement…is achieved by an increase in the expression of nuo operon. However, it is unclear if the claim means that the microorganism contains an enhancer that increases transcription of the operon, if the claim means that a constitutive promoter replaces the native operon promoter, if the claim means that the native promoter is modified to allow for increased expression of the operon, etc. Therefore, the scope of the claim is unclear as one of ordinary skill in the art would not know what structural features the microorganism requires.
Claim 3 recites: wherein the enhancement of the NADH:quinone oxidoreductase activity comprises a gene expression regulatory sequence with enhanced activity. It is unclear if the claim means that the microorganism comprises an enhancer that increases transcription of the genes encoding the enzyme, if the claim means that a constitutive promoter replaces the native promoter, if the claim means that the native promoter is modified to allow for increased expression of the genes it controls, etc. Therefore, the scope of the claim is unclear and one of ordinary skill in the art would not know what structural features the microorganism requires.
Claim 4 recites: wherein the upstream of the gene encoding the NADH:quinone oxidoreductase is the upstream of nuoA gene. It is unclear what the claim means as the entire nuo operon, including nuoA, encodes for the 14 subunit complex that makes up the NADH:quinone oxidoreductase. Therefore, it is unclear if the claim means that nuoA is the most upstream gene of the operon, or if the claim means something else.
Claim 5 recites the limitation "the activity of phosphoserine phosphatase is further weakened". There is insufficient antecedent basis for this limitation in the claim. Moreover, independent claim 1 does not recite a weakened phosphoserine phosphatase, therefore it is unclear how the activity is further weakened. It is also unclear what is meant by “weakened”, i.e., it is unclear if the gene encoding the enzyme is modified so that the enzyme activity is decreased, or if the gene encoding the enzyme exhibits decreased expression, etc.
Claim 6 recites the limitation "the activity of O-phosphoserine export protein is further enhanced". There is insufficient antecedent basis for this limitation in the claim. Moreover, claim 1 does not recite enhanced O-phosphoserine export activity, therefore it is unclear how the activity is further enhanced. It is also unclear what is meant by “enhanced”, i.e., it is unclear if the individual export proteins are modified so as to export more O-phosphoserine, or if the genes encoding the export proteins are overexpressed leading to increased O-phosphoserine export, etc.
Claim 10 recites: culturing an O-phosphoserine-producing microorganism in a medium to produce O-phosphoserine or a medium containing the same. It is unclear what the phrase “or a medium containing the same” means, i.e., it is unclear what components the medium contains. Claim 10 also recites: reacting O-phosphoserine produced in step a) or a medium containing the same with a sulfide in the presence of O-phosphoserine sulfhydrylase or a microorganism expressing the same. It is unclear what the phrase “a medium containing the same” means, i.e., it is unclear what components the medium contains. It is unclear if “a microorganism containing expressing the same” means a microorganism expressing an O-phosphoserine sulfhydrylase or if the claim means something else.
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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Spehr et al., (Overexpression of the Escherichia coli nuo-operon and isolation of the overproduced NADH:ubiquinone oxidoreductase (complex I). Biochemistry. 1999 Dec 7;38(49):16261-7, cited in the IDS filed 12/21/2023) in view of Kim et al., (EP3348567 B1, cited in the IDS filed 02/24/2025).
Regarding claim 1, Spehr teaches a recombinant Escherichia coli microorganism in which the genes encoding NADH:ubiquinone oxidoreductase, i.e., complex I, is overexpressed (Abstract). Therefore, the microorganism of Spehr has enhanced NADH:quinone oxidoreductase activity.
Spher does not teach that the microorganism has O-phosphoserine producing ability.
However, Kim teaches an O-phosphoserine-producing microorganism (para. [0001]).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to engineer the recombinant microorganism of Spehr to produce O-phosphoserine, as taught by Kim. One of ordinary skill in the art would have been motivated to do so because Kim teaches that O-phosphoserine may be used to produce L-cysteine, which is an amino acid with an important role in sulfur metabolism in all living organisms (para. [0002]- [0003]). One of ordinary skill in the art would have had a reasonable expectation of success because Spehr and Kim are in the same field of endeavor of recombinant microorganism development.
Regarding claim 2, Spehr teaches that the nuo-operon is overexpressed (Abstract).
Regarding claim 3, Spehr teaches that overexpression of the nuo-operon was achieved by replacing its 5’-promoter region, i.e., the region upstream of the operon, with the phage-T7 RNA polymerase promoter and by expressing the genes with the T7 RNA polymerase coded on an inducible plasmid (Abstract). The system of Spehr is considered to meet the limitation of a gene regulatory sequence with enhanced activity.
Regarding claim 4, it is interpreted that the claim requires that the nuoA gene is upstream of all other genes of the operon. Because nuoA is canonically the first gene in the operon, it is considered that nuoA of Spehr is upstream of all other genes of the operon.
Regarding claim 5, Kim teaches that, in the O-phosphoserine-producing microorganism, the activity of phosphoserine phosphatase (SerB) may be further weakened compared to its endogenous activity (para. [0034]). One of ordinary skill in the art would have been motivated to do so because Kim teaches that a microorganism with reduced SerB activity has the property of accumulating O-phosphoserine and therefore is useful for the production of O-phosphoserine (para. [0035]).
Regarding claim 6, Kim teaches that the O-phosphoserine-producing microorganism expresses a polypeptide with O-phosphoserine export activity (para. [0001]) and teaches that the polypeptide may be a YhhS major facilitatory superfamily transporter variant with improved activity compared to that of wild type YhhS (para. [0016]). One of ordinary skill in the art would have been motivated to do so because Kim teaches that the variant can effectively export O-phosphoserine from an O-phosphoserine-producing microorganism (para. [0005]).
Regarding claim 7, Spehr teaches that the recombinant microorganism is Escherichia coli (Abstract). Kim teaches that the microorganism may be Escherichia coli (para. [0027]).
Regarding claim 8, Kim teaches a method for producing O-phosphoserine comprising culturing the microorganism that produces it (para. [0001]; para. [0009]). Kim teaches that the culture process may be performed according to the appropriate medium and conditions for culture known in the art (para. [0064]).
Regarding claim 9, Kim teaches that the O-phosphoserine may be recovered from the culture (para. [0068]).
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al., (EP3348567 B1, cited in the IDS filed 02/24/2025) in view of Spehr et al., (Overexpression of the Escherichia coli nuo-operon and isolation of the overproduced NADH:ubiquinone oxidoreductase (complex I). Biochemistry. 1999 Dec 7;38(49):16261-7, cited in the IDS filed 12/21/2023).
Regarding claim 10, Kim teaches a method for producing cysteine or a derivative thereof, comprising culturing an O-phosphoserine-producing microorganism in a medium to produce O-phosphoserine; and reacting the O-phosphoserine with a sulfide in the presence of O-phosphoserine sulfhydrylase (OPSS) or a microorganism expressing the OPSS (para. [0069]).
Kim does not teach that the microorganism has enhanced NADH:quinone oxioreductase activity.
However, Spehr teaches a recombinant Escherichia coli microorganism in which the genes encoding NADH:ubiquinone oxidoreductase, i.e., complex I, is overexpressed (Abstract). Therefore it is considered that the microorganism of Spehr has enhanced NADH:quinone oxidoreductase activity.
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to modify the O-phosphoserine-producing microorganism to overexpress the genes encoding NADH:ubiquinone oxidoreductase, as taught by Spehr, in the method of producing cysteine as taught by Kim. NADH:ubiquinone oxidoreductase, i.e., complex I, couples the transfer for electrons from NADH to ubiquinone with the translocation of protons across the membrane (Spehr, p. 16261, col. 1), which drives ATP synthesis. Therefore, one of ordinary skill in the art would be motivated to overexpress the nuo operon to generate a recombinant microorganism that generates more energy and in turn can produce higher levels of a desired product, such as cysteine. One of ordinary skill in the art would have had a reasonable expectation of success because Spehr and Kim are in the same field of endeavor of recombinant microorganism development.
Regarding claim 11, Kim teaches that the sulfide may be Na2S, NaSH, (NH4)2S, or Na2S2O3 (para. [0073]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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, Louise Humphrey can be reached at (571) 272-5543. 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.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657