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 .
Election/Restrictions
Applicant’s election of Group II, claims 9-12 in the reply filed on 11/17/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-8 and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-13 are pending. Claims 9-12 (claim set filed 02/06/2024) are examined on the merits herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) based on application REPUBLIC OF KOREA 10-2022-0102333 filed 08/16/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/30/2023 and 07/19/2024 comply with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 10 is objected to because of the following informalities: claims 10 recites: “E. coli”. Applicant is suggested to replace recitation with: “Escherichia coli” since the unabbreviated form is not recited in the elected claims prior to claim 10.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 10 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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.
Claim 10 is directed to the transformant, i.e. E. coli W3310 ∆xylAB pTRCHIS2A-yahK deposited under the accession number KCTC15024BP at Korean Collection for Type Cultures (KCTC) of Korea Research Institute of Biotechnology and Bioscience on 07/01/2022. It is apparent that microorganism KCTC15024BP is required to practice the claimed invention. As such the biological material must be readily available or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112, first paragraph, may be satisfied by a deposit of the strain.
The process disclosed in the specification does not appear to be repeatable, it is not clear that the invention will work with commonly available material and it is not apparent if the biological materials considered necessary to make and use the invention is both known and readily available to the public. The prior art of Cirino (Cirino et al. Biotechnol. Bioeng., 2006, 95, 1167-1176) teaches strains of Escherichia coli W3110 transformed with the plasmids carrying genes encoding xylose reductase from different microorganisms, e.g. Candida biodinii, and producing xylitol from xylose (Abstract, p. 1168, Table 1). However the transformant of Cirino teaching does not carry yanK gene or other endogenous E. coli genes for conversion of xylose to xylitol. Thus, a person skilled in the art could not make or use the invention defined without access to the specific biological material.
It is noted that the novel strain was deposited on 07/01/2022 in Korean Collection for Type Cultures (KCTC) of Korea Research Institute of Biotechnology and Bioscience under accession number KCTK15024BP (specification, paragraphs 0082-0084 and Receipt in the case of an original deposit under Budapest Treaty filed 08/16/2023). The depositary information filed 08/16/2023 is acknowledged, however, there is no indication as to public availability statement and viability statement.
If the deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicants, or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit, 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.
If the deposit is a non-Budapest Treaty deposit, then in order to certify that the deposit meets the requirements set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, a statement, affidavit or declaration Applicant, by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit would satisfy the requirements herein by stating and providing that:
(a) During the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) All restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) The deposit will be maintained in a public depositary for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer; and
(d) Provide evidence of the test of the viability of the biological material at the time of deposit (see 37 CFR 1.807).
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 9-12 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.
Claim 9 recites stage 1 in parenthesis in line 2, then stage 1 without parenthesis and stage 2 in parenthesis in line 3. It is not clear whether stage 1 and stage 2 in parenthesis are limiting to the claim or optional. The scope and boundaries of claim 9 are not certain making claim 9 indefinite.
Claims 10-12, dependent on claim 9, do not resolve the issue mentioned above and are rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Akinterinwa (Akinterinwa and Cirino, Metab. Engin., 2009, 11, 48-55) in view of Parajo (Parajo et al. Bioresource Technology, 1998, 65, 191-201) and Pick (Pick et al. Appl. Microbiol. Biotechnol., 2013, 97, 5815-5824) as evidenced by Cirino (Cirino et al. Biotechnol. Bioeng., 2006, 95, 1167-1176).
Regarding claim 9, Akinterinwa teaches production of xylitol by culturing engineered Escherichia coli on the substrate containing xylose (Abstract). Akinterinwa discloses that xylitol is naturally produced from xylose by metabolizing yeast by the action of NAD(P)H-dependent xylose reductase (p. 48, left column, 1st paragraph, p. 48, Fig. 1). The xylose reductase in yeast is also called aldose or aldehyde reductase as evidenced by Cirino (p. 1167, right column, 2nd paragraph). In E.coli xylose is converted to xylulose by xylose isomerase (p. 48, Fig. 1). Akinterinwa describes the E.coli transformed with the expression vector for heterologous expression of NAD(P)H-dependent xylose reductase from Candida boidinii (p. 48, left column, 2nd paragraph).
Akinterinwa does not teach transformant transformed with expression vector comprising gene encoding YahK enzyme.
Parajo teaches that although most of bacteria possess xylose isomerase converting xylose to xylulose, bacterial strains such as Corynebacterium and Enterobacter were shown to produce xylitol. Parajo discusses that these bacteria can possess an enzymatic oxido-reductive system allowing reduction of xylose into xylitol (p. 193, left column, last paragraph, right column, 1st paragraph).
Pick teaches identification of YahK and YjgB aldehyde reductases in E. coli (Abstract). Pick describes the search for enzymes in E. coli responsible for the major NADPH-dependent aldehyde reductase activity (p. 5818, left column, 2nd paragraph). Pick discloses identification of two enzymes, YahK and YjgB, and their characterization along with already known aldehyde reductase, YqhD. YahK and YjgB were shown to have broad substrate specificity, strong preference to aldehyde compounds and were dependent on NADPH, substitution of which with NADH resulted in loosing of >99% activity (Abstract, p. 5819, right column). Pick mentions that the broad substrate range of YahK and YjgB implies a more universal function (p. 5822, right column, 1st paragraph). The comparative analysis of the structures of YahK and YjgB revealed more spacious active site for YahK allowing to bind substrates with diverse structure (p. 5821, right column, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Parajo teaching and look for endogenous aldehyde reductase in E. coli capable to convert xylose to xylitol. One would have been motivated to do that since Parajo teaches that several bacteria were shown to convert xylose to xylitol and the same reaction in yeast is catalyzed by xylose or aldehyde reductases as taught by Akinterinwa and Cirino. A skilled artisan would have reasonably expected success in this combination since Akinterinwa and Parajo discuss production of xylitol from xylose by microorganisms.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to try substitution of yeast xylose/aldehyde reductase in Akinterinwa method of xylitol production with aldehyde reductase identified by Pick in E. coli and elect YahK aldehyde reductase. One would have been motivated to do that since Pick teaches that YahK is an aldehyde reductase, is NADPH-dependent, has broad substrate specificity, allows binding of more diverse substrates in comparison with YjgB aldehyde reductase and may have more universal function and YahK aldehyde reductase is similar to yeast xylose/aldehyde reductase which is also NADPH-dependent and catalyze the same reaction type. Besides, Parajo indicated possibility of the presence of enzymes converting xylose to xylitol in bacteria. A skilled artisan would have reasonably expected success in that because Akinterinwa teaches method of production of xylitol in engineered E. coli by yeast xylose/aldehyde reductase, Parajo points to the presence of similar to yeast aldehyde reductase in E. coli and Pick identifies endogenous aldehyde reductases in E.coli. Thus, teachings of Akinterinwa, Parajo and Pick as evidenced by Cirino render claim 9 obvious.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Akinterinwa (Akinterinwa and Cirino, Metab. Engin., 2009, 11, 48-55) in view of Parajo (Parajo et al. Bioresource Technology, 1998, 65, 191-201) and Pick (Pick et al. Appl. Microbiol. Biotechnol., 2013, 97, 5815-5824) as evidenced by Cirino (Cirino et al. Biotechnol. Bioeng., 2006, 95, 1167-1176) as applied to claim 9 above, and further in view of Cabulong (Cabulong et al. Enzyme and Microbiol. Technol., 2017, 97, 11-20 on record in IDS).
The teachings of Akinterinwa, Parajo and Pick have been set forth above.
Akinterinwa teaches E. coli W3110 cells for preparation of transformant (p. 50, Table 1) and discloses that deletion of xylA gene encoding xylose isomerase and xylB gene encoding xylulokinase results in significant elevation of xylitol production (p. 48, right column, 1st paragraph, p. 49, left column, 2nd paragraph). However, Akinterinwa, Parajo and Pick do not teach transformant E. coli W3310 ∆xylAB pTRCHIS2A-yahK with the accession number KCTC15024BP.
Cabulong teaches production of ethylene glycol from D-xylose (Abstract). Cabulong describes preparing transformant based on E. coli W3110 ∆xylAB cells that have deletion mutation of xylAB genes to block metabolizing xylose in xylose isomerase pathway (p. 12, left column, 1st paragraph, p. 13, Table 1). Cabulong discloses testing YahK, YjgB and YqhD NADPH-dependent aldehyde reductases to improve production of ethylene glycol (p. 15-17, section 3.2). The corresponding plasmid for expression of YahK is pTRCHIS2A-yahK (p. 13, Table 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare transformant based on Cabulong teaching using W3110 ∆xylAB cells transformed with pTRCHIS2A-yahK plasmid resulting in E. coli W3310 ∆xylAB pTRCHIS2A-yahK transformant and use it for method of production of xylitol based on Akinterinwa, Parajo and Pick teachings. One would have been motivated to do that since the W3110 ∆xylAB cells have deletion of xylAB genes that according to Akinterinwa will result in significant elevation of xylitol production and plasmid pTRCHIS2A-yahK provides expression of YahK aldehyde reductase which Pick teaches to be a NADPH-dependent aldehyde reductase with broad substrate specificity similar to yeast xylose/aldehyde reductase as described above and which can be tested to catalyze the same reaction of conversion of xylose to xylitol. A skilled artisan would have reasonably expected success in this combination since Akinterinwa teaches method of production of xylitol in engineered E. coli by yeast xylose/aldehyde reductase, Parajo points to the presence of similar to yeast aldehyde reductase in E. coli, Pick identifies endogenous aldehyde reductases, YahK, in E.coli and Cabulong provides the cells and vector expressing YahK for transformation.
Cabulong does not teach the instant strain with accession number KCTC15024BP, however it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the transformant E. coli W3310 ∆xylAB pTRCHIS2A-yahK prepared based on Cabulong teaching is an obvious variant of instant strain. One would have been motivated to assume so with reasonably expected success since the transformant has the same structure as KCTC15024BP strain unless shown to the contrary and the same properties of expression of YahK and blocking expression of xylAB and hence and will necessarily produce xylitol from xylose. MPEP 2112.01: “Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” Therefore, absent evidence to the contrary, if the strain is not the same, the use of an obvious variant of E. coli W3310 ∆xylAB pTRCHIS2A-yahK with the same function and for the same purpose is obvious. Thus, teachings of Akinterinwa, Parajo, Pick and Cabulong as evidenced by Cirino render claim 10 obvious.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Akinterinwa (Akinterinwa and Cirino, Metab. Engin., 2009, 11, 48-55) in view of Parajo (Parajo et al. Bioresource Technology, 1998, 65, 191-201) and Pick (Pick et al. Appl. Microbiol. Biotechnol., 2013, 97, 5815-5824) as evidenced by Cirino (Cirino et al. Biotechnol. Bioeng., 2006, 95, 1167-1176) as applied to claim 9 above, and further in view of Ko (Ko et al. Appl. Environ. Microbiol., 2006, 72, 4207-4213).
The teachings of Akinterinwa, Parajo and Pick have been set forth above.
Akinterinwa, Parajo and Pick do not teach the substrate to contain glycerol.
Regarding claim 11, Ko teaches production of xylitol from D-xylose by genetically engineered Candida tropicalis. Ko describes that xylitol production was evaluated in xylose medium with glucose as a cosubstrate. Since glucose was found to be insufficient cosubstrate, various carbon sources were screened. Glycerol was found to be the best cosubstrate (Abstract). In the presence of 1% glycerol 100% of xylose was converted into xylitol (p. 4211, Table 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Ko teaching and add glycerol as a cosubstrate to the xylose containing medium during production of xylitol based on Akinterinwa, Parajo and Pick teachings. One would have been motivated to do that since Ko showed that glycerol was the best cosubstrate providing 100% conversion of xylose to xylitol during xylitol production by C. tropicalis. A skilled artisan would have reasonably expected success in this combination since Akinterinwa, Parajo and Ko teach production of xylitol from xylose by microorganisms. Thus, teachings of Akinterinwa, Parajo, Pick and Ko as evidenced by Cirino render claim 11 obvious.
Regarding claim 12, Ko teaches glycerol at concentration 1% (p. 4211, Table 3) that is close to 0.8% in instant limitation.
Pursuant to MPEP 2144.05(I), a prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the glycerol concentration used as a cosubstrate in the production of xylitol. One would have been motivated to do that to reach the highest production level. A skilled artisan would have reasonably expected success in that since it is within the skills of the artisan in the field to optimize concentration of substrates in the fermentation medium. Thus, teachings of Akinterinwa, Parajo, Pick and Ko as evidenced by Cirino render claim 12 obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653