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 .
Claims
Claims 1-20 are pending and are examined in this Office Action.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The priority document was received on Dec. 18, 2024 (Taiwan 112151485, filed on Dec. 29, 2023), however no translation was provided. If the Examiner finds intervening art, publicly available between Dec. 29, 2023, and the instant filing date, Dec. 10, 2024, then this art will be applied and a translation will be required to disqualify the intervening document as prior art.
Information Disclosure Statement
The information disclosure statement (IDS) filed Mar. 6, 2025, fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the document listed as citation No. 2 is not in English and Applicant did not provide an English translation, and English abstract, or an English summary and statement of relevance. It has been placed in the application file, but the information referred to in citation No. 2 has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
For the IDS received on Dec. 10, 2024, multiple documents were foreign documents that were not in English, and Applicant has provided an English abstract for these documents and checked the “T” box on the IDS. The Examiner considered the English abstracts only for these documents.
Specification
The disclosure is objected to because the title of the invention is not descriptive enough of the claimed invention. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: - - MICROORGANISM PRODUCING BLACK DYES BY RECOMBINANTLY EXPRESSING A PED-GENE-CLUSTER-ENCODED ABC TRANSPORTER AND A TYROSINASE - - .
Appropriate correction is requested.
Claim Objections
Claims 1-3, 5-18, and 20 are objected to because of the following informalities:
Claims 1 and 12 are missing an article before “ped gene cluster”; applicant is advised to insert - - a - - between “for” and “ped”.
In addition “ped” is an acronym which should be defined in the first claim in which it is recited. Applicant is advised to recite - - pediocin (ped) - - .
Claims 1, 8, 12, and 17 are each missing an article before “tyrosinase”; applicant is advised to insert - - a - - between “encoding” and “tyrosinase”.
Claims 2 and 13 each recite “wherein a source microorganism … … comprises a bacterium, an actinomycete, a yeast or a mold” and “wherein the bacterium comprises” followed by a list of bacteria species and “the yeast comprises” followed by a list of yeast species. This is objected to because it is technically incorrect. The organism does not “comprise” one of the listed choices, instead the organism IS one of those choices. Applicant is advised to replace “comprises” with - - is - - . The same replacement should be made immediately before the list of bacteria species and the list of yeast species.
Claims 3 and 12 are each is missing an article before “pedA1 gene”; applicant is advised to insert - - a - - between “comprises” and “pedA1 gene”.
Claims 3, 5-7, 9, and 15-17 each recite “SEQ ID NO.” however the preferred presentation for this is - - SEQ ID NO: - - with a colon instead of a period. This is because claims are only supposed to have one period at the very end of the claim.
Claim 10 has an issue with subject/verb agreement because it recites “the first expression vector and the second expression vector independently comprises…”; applicant is advised to replace “comprises” with - - comprise - - .
Claims 11 and 20 each recite “Escherichia coli of which the deposit number is BCRC 940700”, and this is awkward. Applicant is advised to insert - - , a sample of cells of said strain having been deposited under accession number BCRC 940700 - - .
Appropriate correction is requested.
Claim Rejections - 35 USC § 112
Indefiniteness
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 1-20 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. All dependent claims are included in these rejections unless they include a limitation that overcomes the deficiencies of the parent claim.
Claims 1 and 12 each recite “ped gene cluster” and it is unclear what is required for this. It is understood that the “ped gene cluster” is a collection of genes at the pediocin locus, however, it is unclear if all of the genes are required to be the recited “cluster” or if only a subset are required. See, for example, Wehrmann et al ((2019) Frontiers in Microbiology; Vol. 10; pp. 1-14) who teach that the “ped” gene cluster comprises 14 different “ped” genes and three non-ped genes (Wehrmann 7, Figure 5). It is unclear how many of the genes from this cluster are required by the current claim language.
Claims 1 and 12 each recite “a genetically modified microorganism producing black dyes”, and it is unclear if this is intended to exclude a microorganism comprising the required first and second nucleic acid but not actively producing black dyes because either the nucleic acids aren’t being actively expressed or the cells lack the required precursors and co-factors for producing a black dye. It is also unclear if the claim excludes a microorganism that produces only one kind of black dye. Essentially it is unclear if the production of black dye must be actively happening, or if the microorganism is merely required to be capable of producing a black dye if given the necessary precursor(s) and cofactor(s).
Claims 4 and 15 each specify what organism the “ped gene cluster” is “derived from” and claims 8 and 17 each specify what organism the tyrosinase is “derived from”. It is unclear how one would determine if any particular nucleic acid is “derived from” the required organism. This is similar to a product-by-process limitation because the required claim element is produced by starting with the designated organism and deriving the required sequence. It is unclear how many nucleotides can be altered and still be considered “derived from” the designation organism. If any given sequence has a nucleotide sequence that is not a 100% match to any particular organism, how would one know which endogenous genome the sequence was “derived from”?
Lack of Enablement
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a microorganism producing black dyes and comprising a nucleic acid encoding a ped gene cluster and a nucleic acid encoding a tyrosinase wherein each nucleic acid is operably linked to a promoter that is functional in said microorganism, does not reasonably provide enablement for a microorganism producing black dyes and comprising two coding sequences without any promoter to initiate transcription. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
All dependent claims are included in these rejections unless they include a limitation that overcomes the deficiencies of the parent claim.
The claims are directed to a genetically modified microorganism producing black dyes comprising two exogenous nucleic acids which are both coding sequences. None of the claims require a operably linked promoter. It is known in the art that an exogenous nucleic acid will not express without a promoter to initiate transcription. If the nucleic acid encoding the tyrosinase is not expressed, then there will be no tyrosinase enzyme and no black dye will be produced.
Furthermore, tyrosinase is known to require copper for its enzymatic function, and it requires tyrosine or L-DOPA as a substrate to cause production of melanin (black dye) (Pavan et al. (2020) Applied Microbiology and Biotechnology; Vol. 104; pp. 13-57; p. 1359, left column and p. 1360, Figure 2). For this reason, a microorganism comprising a nucleic acid encoding tyrosinase with an operably linked promoter could make the microorganism capable of producing black dye, but for the organism to actively produce black dye, it would require media with copper and sufficient amounts of endogenous tyrosine.
For claims 11 and 20 in particular, these claims are not enabled because the depository used for the Escherichia coli strain is not an approved International Depository Authority that is recognized by the USPTO. In addition, Applicant has not provided the street address of the depository, nor has the applicant disclosed if the deposit was accepted under the Budapest Treaty, nor has the Applicant provided a statement that all restrictions to public availability will be irrevocably withdrawn upon issuance of a patent.
(a) If a deposit is made and accepted under the terms of the Budapest Treaty, then the specification must include the street address of the depository and Applicant must provide a statement, affidavit or declaration by Applicants, or a statement by an attorney of record over their signature and registration number, or someone empowered to make such a statement, stating that the instant invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
(b) If a deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, Applicant may provide assurance of compliance by statement, affidavit or declaration, or by someone empowered to make the same, or by a statement by an attorney of record over his or her signature and registration number showing that:
(i) during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
(ii) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent in accordance with 37 CFR § 1.808(a)(2);
(iii) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer, and the specification will include the street address of the depository;
(iv) a test of the viability of the biological material at the time of deposit (see 37 CFR § 1.807); and,
(v) the deposit will be replaced if it should ever become inviable.
Lastly, claim 12 is not enabled for a method that utilizes all potential ped gene clusters with all possible rare earth elements. Applicant’s own work shows that the only rare earth element that had a measurable effect on bacterial growth with the Pseudomonas putida ped gene cluster was Lanthanide (Figure 4). Given the unpredictability demonstrated by the Applicant’s own work, it would require undue experimentation to engage in mix and match trials with different ped clusters and different rare earth elements to find the ones that would actually enhance the bacterial growth and thus the yield of the black dye.
Inadequate Written Description
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. All dependent claims are included in these rejections unless they include a limitation that overcomes the deficiencies of the parent claim.
The claims are broadly drawn to a genetically modified microorganism producing black dyes and comprising two exogenous nucleic acids which are both coding sequences; one encoding an ABC transporter and comprising a ped gene cluster, the other encoding a tyrosinase.
Applicants describe Escherichia coli capable of producing black dye and comprising a pedA1 gene, a pedA2 gene, a pedB gene, and a pedC gene from the ped gene cluster of Pseudomonas putida strain KT2440. The gene sequences of these genes is described as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4, respectively (Spec 24). Applicants describe the sequence for all four genes put together as SEQ ID NO: 5 (Id. 25). Applicants describe the nucleic acid encoding tyrosinase as SEQ ID NO: 6 (Id.). Applicants describe inserting these sequences into a microbial expression vector comprising a T7 promoter to initiate transcription of the operably linked coding sequence (Figs. 1A and 1B). Applicants describe a medium formula for the bacteria as Luria Bertani broth (LB) (Id. 27). Applicants describe growing the cultures with added lanthanum ions at different concentrations (Id. 29). Applicant describes growing the cultures with cerium ions and erbium ions as well (Id. 30; and Figure 4). Applicant describes Lanthanum uptake as improved in the bacterial strain expressing the ped gene cluster compared with the parent bacterial strain lacking the ped gene cluster (Id. 31, Figure 5). Applicant describe a strain referred to as ITRI-RB3 which comprises both plasmids thereby expressing both the ped gene cluster and the tyrosinase, and they describe depositing this strain with the Bioresource Collection and Research Centre under deposit number BCRC 940700 (Id. 33).
Applicants do not describe any host microorganism other than Escherichia coli. Applicants do not describe an effect from any rare earth metal or ion other than Lanthanum ions. Applicants do not describe any ped gene cluster other than the ped gene cluster from Pseudomonas putida.
Applicants own data show that the other two rare earth metal ions that were tested did not produce any effect, and Applicant did not test any other ped gene cluster for effectiveness with other rare earth ions. This shows that only one embodiment within the genus being claimed was reduced to practice. Applicant was not in possession of the broad genus of microorganisms, ped gene clusters, and rare earth metal ions encompassed by the instant claims. For this reason, Applicant has not provided an adequate written description for the broad genus encompassed by the claims.
Close Prior Art
The prior art has numerous examples of expressing recombinant tyrosinase to make melanin (black dye), see, for example, Pavan (cited above) and Martinez et al. ((2019) Frontiers in Bioengineering and Biotechnology; Vol. 10; pp. 1-14).
The prior art also has numerous examples of expressing recombinant ped gene clusters in microorganisms, see, for example Wenhua et al. ((2003) Biological Trace Element Research; Vol. 94; pp. 167-177).
The prior art of record does not include any examples of these being co-expressed, and the Examiner is not aware of any publications providing a rationale, logic, or motivation to do this co-expression.
Summary
No claim is allowed.
Examiner’s Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHY KINGDON whose telephone number is (571)272-8784. The examiner can normally be reached M-F 9:00 - 5:30 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, Amjad A Abraham can be reached at (571) 270-7058. 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.
CATHY KINGDON
Primary Examiner
Art Unit 1663
/CATHY KINGDON/Primary Examiner, Art Unit 1663
Prosecution Insights