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 1-12 are pending and under examination.
Priority
This application, filed on 9/20/2024, is a 371 of PCT/KR2022/011047 filed on 7/27/2022, which claims priority to REPUBLIC OF KOREA 10-2022-0036257 filed on 3/23/2022. The effective filing date of the current application for prior art purposes is July 27, 2022.
Information Disclosure Statement
The information disclosure statements filed on 9/20/2024 and 9/24/2025 all comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. All references were considered.
Specification
The abstract of the disclosure is objected to because there are two abstracts dated 9/20/2024 with different content, and it is not clear which abstract should be considered. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 1, 4, 8 and 10-12 are objected to because of the following informalities:
Claim 1 recites “genus Yarrowia” in line 1 and “Dunaliella salina-derived” in line 2, which does not follow the traditional designation of using italics to denote each genera and species. It is suggested that the claim be amended to recite “genus Yarrowia” and “Dunaliella salina-derived”.
Claim 4 recites “Yarrowia” in line 1 and “Yarrowia lipolytica” in line 2, which does not follow the traditional designation of using italics to denote each genera and species. It is suggested that the claim be amended to recite “Yarrowia” and “Yarrowia lipolytica”.
Claims 8 and 10-12 recite “genus Yarrowia”, which does not follow the traditional designation of using italics to denote each genera and species. It is suggested that the claims be amended to recite “Yarrowia”.
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 1, 4-10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (“Removal of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica”. Nature Communications, 31 January 2022, Vol. 13, Article No. 572; 11 pages) in view of Xu et al. (“Relationship between β-carotene accumulation and geranylgeranyl pyrophosphate synthase in different species of Dunaliella”, 2022, Plants, Vol. 11, article 27, 14 pages; published December 22, 2021) and GenBank (accession no. APW83740, deposited on January 28, 2017. The rejection of claims 5, 7 and 11 is further evidenced by Olson (“Provitamin A Function of Carotenoids: The Conversion of β-carotene into Vitamin A”, The Journal of Nutrition, 1989, Vol. 119, No. 1, pp.105-108).
Regarding claims 1 and 4, Ma teaches carotenoid biosynthesis in Yarrowia lipolytica (abstract). Ma teaches establishing a geranylgeranyl pyrophosphate synthase-mediated flux flow restrictor results in high levels of near-exclusive β-carotene production (abstract). Ma teaches the geranylgeranyl pyrophosphate synthase (GGPPS) expression in Y. lipolytica (p. 5, Fig. 3 legend). Ma does not teach Dunaliella salina-derived geranylgeranyl pyrophosphate synthase.
Xu teaches a relationship between β-carotene accumulation and geranylgeranyl pyrophosphate synthase (GGPS) in different species of Dunaliella (title). Xu teaches that GGPS enzyme activity has a positive linear relationship with the β-carotene synthesis content (abstract). Xu further teaches that Dunaliella salina is often used as a model algal species (p.1, Introduction 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the geranylgeranyl pyrophosphate synthase taught by Ma with the geranylgeranyl pyrophosphate synthase from Dunaliella salina taught by Xu, because Xu teaches that GGPS enzyme activity has a positive linear relationship with β-carotene synthesis content and that Dunaliella salina is often used as a model algal species, and it was known in the art at the time of invention that increased geranylgeranyl pyrophosphate synthase activity resulted in increased β-carotene synthesis content.
Regarding claims 5 and 7, β-carotene is a precursor for producing retinal, retinol and Vitamin A, as evidenced by Olson (p.106, Figure 1).
Regarding claim 6, Ma teaches strains that result in high levels of near-exclusive β-carotene production (abstract).
Regarding claims 8 and 9, Ma teaches that a GGPPS-mediate metabolic flow restrictor can vary the amount of flux through the carotenoid synthesis pathway, thus regulating lycopene formation rates. Ma further teaches the flux flow restrictor affects the production of squalene, by regulating the flow towards the carotenoid synthesis pathway (Fig. 3A).
Regarding claims 10 and 12, Ma teaches single colonies of recombinant strains were picked from a plate, inoculated into 2mL YPD media, and cultivated overnight at 30°C and 230 rpm, then transferred into a 50mL shake flask containing 10mL YPD media and cultivated at 30°C with shaking at 230 rpm for 3-5 days (p.9, 1st column – shake flask fermentations). Ma teaches carotenoid extraction from the culture (p.9, 2nd column – extraction of carotenoids).
Claims 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (Nature Communications, 31 January 2022, Vol. 13, Article No. 572; 11 pages) in view of Xu et al. (Plants 2022, Vol. 11, article 27, 14 pages; December 22, 2021) as applied to claim 1 above, and further in view of GenBank (accession number APW83740, deposited on January 28, 2017).
Regarding claims 2 and 3, Ma does not teach the amino acid sequence of instant SEQ ID NO:91 (claim 2) or a polynucleotide consisting of a nucleotide sequence of instant SEQ ID NO:1 (claim 3).
However, GenBank accession number APW83740 is a sequence of geranylgeranyl diphosphate synthase from the organism Dunaliella salina (title), which has 100% identity to the amino acid sequence of instant SEQ ID NO:91, as shown in the alignment below. The nucleotide sequence of instant SEQ ID NO:1 translated into amino acids also has 100% identity to instant SEQ ID NO:91.
PNG
media_image1.png
526
801
media_image1.png
Greyscale
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the geranylgeranyl pyrophosphate synthase taught by Ma with the sequence taught by GenBank, which is the geranylgeranyl pyrophosphate synthase from Dunaliella salina as suggested by Xu, because it would amount to a simple substitution of one known geranylgeranyl pyrophosphate synthase for another, and the amino acid sequence and nucleotide sequence of geranylgeranyl pyrophosphate synthase from Dunaliella salina were known in the art at the time of invention.
Claims 1, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kildegaard et al. (“Engineering of Yarrowia lipolytica for production of astaxanthin”, Synthetic and Systems Biotechnology, 2017, Vol. 2, Issue 4, pp.287-294) in view of Xu et al. (“Relationship between β-carotene accumulation and geranylgeranyl pyrophosphate synthase in different species of Dunaliella”, 2022, Plants, Vol. 11, article 27, 14 pages; published December 22, 2021).
Regarding claims 1, 10 and 11, Kildegaard teaches engineering Y. lipolytica produces β-carotene (abstract). Kildegaard teaches optimizing the geranylgeranyl diphosphate synthase in the best producing strain to obtain 453.9 ± 20.2 mg/L β-carotene (abstract). Kildegaard further teaches introducing β-carotene ketolase and hydroxylase to convert β-carotene into astaxanthin (abstract).
Kildegaard does not teach the microorganism expressing Dunaliella salina derived geranylgeranyl pyrophosphate synthase.
However, Xu teaches a relationship between β-carotene accumulation and geranylgeranyl pyrophosphate synthase (GGPS) in different species of Dunaliella (title). Xu teaches that GGPS enzyme activity has a positive linear relationship with the β-carotene synthesis content (abstract). Xu further teaches that Dunaliella salina is often used as a model algal species (p.1, Introduction 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the geranylgeranyl pyrophosphate synthase taught by Kildegaard with the geranylgeranyl pyrophosphate synthase from Dunaliella salina taught by Xu, because Xu teaches that GGPS enzyme activity has a positive linear relationship with β-carotene synthesis content. One of ordinary skill in the art would have found it beneficial to substitute the geranylgeranyl pyrophosphate synthase from Dunaliella salina because Xu teaches Dunaliella salina is often used as a model algal species, and it was known in the art at the time of invention that increased geranylgeranyl pyrophosphate synthase activity resulted in increased β-carotene synthesis content.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEEPA MISHRA whose telephone number is (571) 272-6464. The examiner can normally be reached Monday - Friday 9:30am - 3:30pm 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 W. 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.
/DEEPA MISHRA/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
Prosecution Insights